Genes associate with progression and response in chronic myeloid leukemia and uses thereof

This application includes a Sequence Listing submitted on compact disc, recorded on two compact discs, including one duplicate, containing Filename seqlisting 9301-253-999 as filed.txt, of size 10,385,215 bytes, created Dec. 8, 2006. The Sequence Listing on the compact discs is incorporated by reference herein in its entirety.

1. FIELD OF THE INVENTION

The invention relates to molecular markers that are associated with the progression of chronic myeloid leukemia (CML). The invention also relates to methods and computer systems tor evaluating the progression of CML based on these molecular markers. The present invention also relates to methods and compositions for treating CML patients by modulating the expression or activity of certain genes involved in CML progression and/or their encoded proteins. The invention further relates to methods and compositions for determining the responsiveness of a CML patient to imatinib mesylate (Gleevec™).

2. BACKGROUND OF THE INVENTION

Chronic myeloid leukemia (CML) is a hematopoetic stem cell disease with distinct biological and clinical features. In humans, a majority of CML (about 95%) has been found to be associated with a chromosomal abnormality that involves a t(9;22)(q34;q11) translocation, which results in the expression of the BCR/ABL fusion gene (Philadelphia Chromosome or Ph). The rest is associated with either a cryptic translocation that is invisible on G-banded chromosome preparations or a variant translocation involving another chromosome or chromosomes as well as chromosomes 9 and 22. CML usually presents in the so-called chronic phase, in which the clonal expansion of mature myeloid cells leads to an elevated white blood cell (WBC) count. Without curative intervention chronic phase CML will invariably transform through a phase of “acceleration,” often heralded by the appearance of increased immature myeloid cells in the bone marrow and peripheral blood, as well as new cytogenetic changes in addition to the Ph chromosome. Progression then proceeds quickly to blast crisis, with immature blast cells overwhelming the production of normal hematopoetic elements. Blast crisis is highly resistant to treatment, with death generally occurring from infection and bleeding complications secondary to the absence of normal granulocytes and platelets. The median time from diagnosis of chronic phase CML to progression blast crisis is approximately 3-4 years but the range of timing is quite broad, encompassing from 0.5-15 years (Faderl et al., 1999, Ann Intern Med 131:207).

There is a broad range of treatment options for CML. All treatments work far better on chronic phase disease than on accelerated or blast phase. The only known curative therapy for CML is stem cell transplantation, a complex and potentially toxic modality that carries a high potential for morbidity and mortality (Radich et al., 2003, Blood 102:31). Non-transplant therapy includes alpha interferon, which can produce a major reduction in the proportion of Ph positive cells and extend the natural history of the disease in approximately 10-20% of cases (Kantarjian et al., 1999, J Clin Oncol 17:284). The tyrosine kinase inhibitor, imatinib mesylate, suppresses the Ph to the point where it is undetectable by cytogenetic evaluation (“complete cytogenetic remission”) in >70% of newly diagnosed chronic phase CML cases (Druker et al., 2001, N Engl J Med 344:1031). The duration of such responses is unknown, as is potential for cure with imatinib. Resistance to imatinib occurs (especially in advanced phase disease) often accompanied by point mutations in the active area of imatinib binding in the abl gene (Shah et al., 2002, Cancer Cell 2:117). The natural history of such relapses is unknown, though some appear to have a speedy entry into advanced disease (Branford et al., 2003, Blood 102:276).

U.S. Patent Application Publication No. 2003/0104426 A1 discloses genetic markers whose expression correlates with progression of CML. Specifically, the patent application discloses sets of markers whose expression patterns can be used to differentiate chronic phase individuals from those in blast crisis, and methods of using these markers to distinguish these conditions. The patent application also discloses kits containing ready-to-use microarrays and computer data analysis software for carrying out the disclosed methods.

PRAME (Preferentially Expressed Antigen of Melanoma) was identified as a tumor antigen recognized by cytotoxic T-cells against a melanoma surface antigen (Matsushita et al., 2001, Br J Haematol 112:916, 2001; van Baren et al., 1998, Br J Haematol 102:1376). PRAME has been found to be overexpressed in over 25% of leukemia, and has been found to be induced by Bcr-Abl in CML cell lines (Watari et al., 2000, FEBS Lett 466:367). PRAME over-expression has been described as one of the few features that characterize the transient myeloproliferative syndrome of Down's syndrome from the progressive acute megakaryoblastic leukemia found in that disorder (McElwaine et al., 2004, Br J Haematol 125:729).

The genetic events that cause the progression of chronic phase to blast crisis CML are unknown (Calabretta et al., 2004, Blood 103:4010; Shet et al., 2002, Leukemia 16:1402). Numerous genetic abnormalities have been demonstrated, including chromosomal changes including a multiplication of the Ph, the disruption of TP53, the deletion of the p15/p16 tumor suppressor genes (the latter only in lymphoid blast crisis). However, none of these changes are particularly common. Genetic instability is apparent in the additional chromosomal changes that occur with progression, though standard assays of instability, such as alterations in minisatellite repeats, is relatively uncommon (Wada et al., 1994, Blood 83:3449; Mori et al., 1997, Leukemia 11:151). Unfortunately, clinical and molecular tests cannot predict where on the “clock” of progression an individual lies at the time of the initial diagnosis, and this makes it impossible to tailor therapy to the degree of risk that faces an individual CML patient. It is also not possible to identify the subset of patients who will benefit most from the variety of therapy options, such as interferon, imatinib, or transplantation. Thus, presently tailoring therapy to individual risk is difficult. There is therefore a need to identify genes whose levels of expression change during the evolution of the chronic phase to blast crisis. There is a need for methods that utilize measured expression levels of such genes to determine the phase and/or progression of CML in a patient. There is also a need for methods of treating CML by targeting such genes.

Discussion or citation of a reference herein shall not be construed as an admission that such reference is prior art to the present invention.

3. SUMMARY OF THE INVENTION

The invention provides a method for determining the progression of chronic myeloid leukemia (CML) in a patient, comprising (a) classifying a marker profile comprising measurements of a plurality of gene products in a cell sample taken from said patient as a chronic phase (CP-CML) profile or as an advanced phase (ADV-CML) profile, wherein said gene products are respectively products of at least 5 of the genes listed in Table 1a and/or Table 1b or respective functional equivalents thereof, wherein at least one of said 5 genes is from Table 1a; and (b) determining said patient as in a chronic phase if said marker profile is classified as a CP-CML profile, or determining said patient as in an advanced phase if said 10 marker profile is classified as an ADV-CML profile. In one embodiment, said plurality of gene products are of at least 5, 10, 20, 50, 70 or 100 of the genes listed in Table 1a. In one embodiment, said cell sample is a bone marrow sample or a peripheral blood sample.

In one embodiment, the method further comprises obtaining said marker profile by a method comprising measuring said plurality of gene products in a cell sample taken from said patient.

In preferred embodiments, said gene products are products of at least 10, at least 20, at least 40, at least 70, at least 100, or at least 500 of the genes, respectively, listed in Table 1a and/or 1b.

In another preferred embodiment, said gene products are products of at least 10, at 20 least 20, at least 40, at least 70, at least 100, or at least 200 of the genes, respectively, listed in Table 2a.

In still another preferred embodiment, said gene products are products of at least 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 or all of the genes, respectively, corresponding to the markers listed in Table 3. In one embodiment, said gene products are products of at least 5, 6, 7, 8, 9 or all of the genes, respectively, corresponding to the up-regulated markers listed in Table 3, or are products of at least 5, 6, 7, 8, 9 or all of the genes, respectively, corresponding to the down-regulated markers listed in Table 3.

In one embodiment, each of said gene products is a gene transcript.

In one embodiment, measurement of each said gene transcript is obtained by a method comprising contacting a positionally-addressable microarray with nucleic acids from said cell sample or nucleic acids derived therefrom under hybridization conditions, and detecting the amount of hybridization that occurs, said microarray comprising one or more polynucleotide probes complementary to a hybridizable sequence of each said gene transcript.

In another embodiment, measurement of each said gene transcript is obtained by quantitative reverse transcriptase PCR (qRT-PCT).

In another embodiment, each of said plurality of gene products is a protein.

In a preferred embodiment, said classifying is carried out using a progression classifier, which receives an input comprising said marker profile and provides an output comprising data indicating whether said marker profile is a CP-CML profile or an ADV-CML profile.

In one embodiment, said progression classifier is trained with training data from a plurality of training CML patients, wherein said training data comprise for each of said plurality of training CML patients (i) a training maker profile comprising measurements of said plurality of gene products in a cell sample taken from said training patient; and (ii) data indicating whether said training patient is in CP-CML or ADV-CML.

In a preferred embodiment, said progression classifier comprises a CP-CML template comprising measurements of said plurality of gene products representative of measurements of said plurality of genes products in a plurality of patients having CP-CML and/or an ADV-CML template comprising measurements of said plurality of gene products representative of measurements of said plurality of genes products in a plurality of patients having ADV-CML, and said step of classifying is carried out by a method comprising (i) comparing said marker profile with said CP-CML template and/or said ADV-CML template; and (ii) classifying said marker profile as a CP-CML profile if said marker profile has a high similarity to said CP-CML template and/or has a low similarity to said ADV-CML template, or classifying said marker profile as a ADV-CML profile if said marker profile has a high similarity to said ADV-CML template and/or has a low similarity to said CP-CML template, wherein a high similarity corresponds to a degree of similarity above a predetermined threshold, and wherein a low similarity corresponds to a degree of similarity no greater than said predetermined threshold.

In a specific embodiment, said step of classifying is carried out by a method comprising (i) comparing said marker profile with said CP-CML template or said ADV-CML template; and (ii) classifying said marker profile as a CP-CML profile if said marker profile has a high similarity to said CP-CML template or has a low similarity to said ADV-CML template, or classifying said marker profile as a ADV-CML profile if said marker profile has a high similarity to said ADV-CML template or has a low similarity to said CP-CML template, wherein a high similarity corresponds to a degree of similarity above a predetermined threshold, and wherein a low similarity corresponds to a degree of similarity no greater than said predetermined threshold.

In another specific embodiment, said step of classifying is carried out by a method comprising (i) comparing said marker profile with said CP-CML template and said ADV-CML template; and (ii) classifying said marker profile as a CP-CML profile if said marker profile has a higher similarity to said CP-CML template than to said ADV-CML template, or classifying said marker profile as a ADV-CML profile if said marker profile has a higher similarity to said ADV-CML template than to said CP-CML template.

In one embodiment, said similarity to said CP-CML template is represented by a correlation coefficient between said marker profile and said CP-CML template, wherein said similarity to said ADV-CML template is represented by a correlation coefficient between said marker profile and said ADV-CML template. In one embodiment, said correlation coefficients between said marker profile and said CP-CML template and said ADV-CML template are respectively calculated according to the equation

P_i=({right arrow over (z)}_i•{right arrow over (y)})/(∥{right arrow over (z)}_i∥·∥{right arrow over (y)}∥)

where i=1 and 2, wherein {right arrow over (y)} represents said marker profile, {right arrow over (z)}₁represents said CP-CML template, and {right arrow over (z)}₂represents said ADV-CML template, P₁represents said correlation coefficient between said marker profile and said CP-CML template, and P₂represents said correlation coefficient between said marker profile and said ADV-CML template.

In one embodiment, the measurement of each gene product in said CP-CML template or said ADV-CML template is an average of the measurements of said gene product in a plurality of CP-CML patients or in a plurality of ADV-CML patients, respectively.

In one embodiment, said measurement of each gene product in said marker profile is a relative level of said gene product in said cell sample taken from the patient versus level of said gene product in a reference pool, represented as a log ratio; the respective measurement of each gene product in said CP-CML template is a relative level of said gene product representative of level of said gene product in a plurality of CP-CML patients versus level of said gene product in a reference pool, represented as a log ratio; and the respective measurement of each gene product in said ADV-CML template is a relative level of said gene product representative of level of said gene product in a plurality of ADV-CML patients versus level of said gene product in a reference pool, represented as a log ratio.

In one embodiment, the respective log ratio for each gene product in said CP-CML template or said ADV-CML template is an average of the log ratios for said gene product in a plurality of CP-CML patients or in a plurality of ADV-CML patients, respectively.

In another preferred embodiment, said progression classifier is an artificial neural network (ANN) or a support vector machine (SVM).

The invention also provides a method for assigning a therapeutic regimen for a CML patient, comprising (a) determining the progression of said patient using any of the above described methods; and (b) assigning said patient a therapeutic regimen according to the status of progression determined in step (a). In one embodiment, said patient is determined to be in ADV-CML, and said therapeutic regimen assigned to said patient comprises bone marrow transplant.

The invention also provides a method for enrolling CML patients for a clinical trial of an agent for treating CML, comprising (a) determining the progression of said patient using any of the above described methods; and (b) assigning each patient having a CP-CML to one patient group and each patient having an ADV-CML to another patient group, at least one of said patient group being enrolled in said clinical trial.

The invention also provides a method for determining the responsiveness of a chronic myeloid leukemia (CML) patient to imatinib mesylate (IM), comprising (a) determining the progression of said patient using any of the above described methods; and (b) determining said patient as responsive to IM treatment if said marker profile is classified as a CP-CML profile, or determining said patient as resistant to IM treatment if said marker profile is classified as an ADV-CML profile.

In another aspect, the invention provides a method for determining the responsiveness of a chronic myeloid leukemia (CML) patient to imatinib mesylate (IM), comprising (a) classifying a marker profile comprising measurements of a plurality of gene products in a cell sample taken from said patient as an IM-sensitive profile or an IM-resistant profile, wherein said gene products are respectively products of at least 5 of the genes listed in Table 4 or respective functional equivalents thereof, and (b) determining said patient as responsive to IM treatment if said marker profile is classified as an IM-sensitive profile, or determining said patient as resistant to IM treatment if said marker profile is classified as an IM-resistant profile. In one embodiment, said plurality of gene products are of at least 5 of the genes listed in Table 4. In one embodiment, said cell sample is a bone marrow sample or a peripheral blood sample.

In one embodiment, the method further comprises obtaining said marker profile by a method comprising measuring said plurality of gene products in a cell sample taken from said patient.

In preferred embodiments, said gene products are products of at least 10, at least 20, at least 40, at least 70, at least 100, or at least 200 of the genes, respectively, listed in Table 4.

In one embodiment, each of said gene products is a gene transcript.

In another embodiment, each of said plurality of gene products is a protein.

In a preferred embodiment, said classifying is carried out by a method comprising using a progression classifier, wherein said progression classifier receives an input comprising said marker profile and provides an output comprising data indicating whether said marker profile is an IM-sensitive profile or an IM-resistant profile.

In one embodiment, said progression classifier is trained with training data from a plurality of tranining CML patients, wherein said training data comprise for each of said plurality of training CML patients (i) a training maker profile comprising measurements of said plurality of gene products in a cell sample taken from said training patient; and (ii) data indicating whether said training patient is sensitive or resistant to imatinib mesylate.

In one embodiment, said progression classifier comprises an IM-sensitive template comprising measurements of said plurality of gene products representative of measurements of said plurality of genes products in a plurality of patients responsive to IM treatment and/or an IM-resistant template comprising measurements of said plurality of gene products representative of measurements of said plurality of genes products in a plurality of patients resistant to IM treatment, and said step of classifying is carried out by a method comprising (a1) comparing said marker profile with said IM-sensitive template and/or said IM-resistant template; and (a2) classifying said marker profile as a IM-sensitive profile if said marker profile has a high similarity to said IM-sensitive template and/or has a low similarity to said IM-resistant template, or classifying said marker profile as a IM-resistant profile if said marker profile has a high similarity to said IM-resistant template and/or has a low similarity to said IM-sensitive template, wherein a high similarity corresponds to a degree of similarity above a predetermined threshold, and wherein a low similarity corresponds to a degree of similarity no greater than said predetermined threshold.

In a specific embodiment, said step of classifying is carried out by a method comprising (a1) comparing said marker profile with said IM-sensitive template or said IM-resistant template; and (a2) classifying said marker profile as an IM-sensitive profile if said marker profile has a high similarity to said IM-sensitive template or has a low similarity to said IM-resistant template, or classifying said marker profile as a IM-resistant profile if said marker profile has a high similarity to said IM-resistant template or has a low similarity to said IM-sensitive template, wherein a high similarity corresponds to a degree of similarity above a predetermined threshold, and wherein a low similarity corresponds to a degree of similarity no greater than said predetermined threshold.

In another specific embodiment, said step of classifying is carried out by a method comprising (a1) comparing said marker profile with said IM-sensitive template and said IM-resistant template; and (a2) classifying said marker profile as an IM-sensitive profile if said marker profile has a higher similarity to said IM-sensitive template than to said IM-resistant template, or classifying said marker profile as a IM-resistant profile if said marker profile has a higher similarity to said IM-resistant template than to said IM-sensitive template.

In one embodiment, said similarity to said IM-sensitive template is represented by a correlation coefficient between said marker profile and said IM-sensitive template, and said similarity to said IM-resistant template is represented by a correlation coefficient between said marker profile and said IM-resistant template.

In one embodiment, said correlation coefficients between said marker profile and said IM-sensitive template and said IM-sensitive template are respectively calculated according to the equation

P_i=({right arrow over (z)}_i•{right arrow over (y)})/(∥{right arrow over (z)}_i∥·∥{right arrow over (y)}∥)

where i=1 and 2, wherein {right arrow over (y)} represents said marker profile, {right arrow over (z)}₁represents said IM-sensitive template, and {right arrow over (z)}₂represents said IM-resistant template, P₁represents said correlation coefficient between said marker profile and said IM-sensitive template, and P₂represents said correlation coefficient between said marker profile and said IM-resistant template.

In one embodiment, the measurement of each gene product in said IM-sensitive template or said IM-resistant template is an average of the measurements of said gene product in a plurality of patients responsive to IM treatment or in a plurality of patients resistant to IM treatment, respectively.

In one embodiment, said measurement of each gene product in said marker profile is a relative level of said gene product in said cell sample taken from the patient versus level of said gene product in a reference pool, represented as a log ratio; the respective measurement of each gene product in said IM-sensitive template is a relative level of said gene product representative of level of said gene product in a plurality of patients responsive to IM treatment versus level of said gene product in a reference pool, represented as a log ratio; and the respective measurement of each gene product in said IM-resistant template is a relative level of said gene product representative of level of said gene product in a plurality of patients resistant to IM treatment versus level of said gene product in a reference pool, represented as a log ratio.

In one embodiment, the respective log ratio for each gene product in said IM-sensitive template or said IM-resistant template is an average of the log ratios for said gene product in a plurality of patients responsive to IM treatment or in a plurality of ADV-CML patients, respectively.

In another preferred embodiment, said progression classifier is an artificial neural network (ANN) or a support vector machine (SVM).

The invention also provides a method for assigning a treatment regimen for a CML patient, comprising (i) determining whether said patient is responsive or resistant to imatinib mesylate using a method as described above; and (ii) assigning said patient a treatment regimen comprising bone marrow transplant if said patient is determined to be resistant to imatinib mesylate.

The invention also provides a method for enrolling CML patients for a clinical trial of a treatment modality for treating CML, comprising (i) determining whether said patient is responsive or resistant to imatinib mesylate using a method as described above; and (ii) assigning each patient who is predicted to be resistant to imatinib mesylate to one patient group and each patient who is predicted to be responsive to imatinib mesylate to another patient group, at least one of said patient group being enrolled in said clinical trial.

In still another aspect, the invention provides a method for treating a patient having chronic myeloid leukemia (CML), comprising administering to said patient a treatment regimen, said treatment regimen comprising one or more agents that modulate the expression and/or activity of one or more different genes listed in one or more of Tables 2a, 2b, 5a and 5b and/or their encoded proteins, wherein said patient exhibits aberrant regulation of said one or more genes.

In one embodiment, said one or more different genes are selected from the different genes listed in one or more of Tables 2a and 5a.

In another embodiment, said one or more different genes are selected from the genes listed in both Tables 2a and 5a, i.e., genes common in Tables 2a and 5a.

In still another embodiment, said one or more different genes are selected from the genes listed in Table 3.

In one embodiment, said one or more different genes are selected from the up-regulated genes listed in Table 3, and said treatment regimen comprises a substance selected from the group consisting of siRNA, antisense nucleic acid, ribozyme, and triple helix forming nucleic acid, each reducing the expression of one or more of said one or more different genes in said patient.

In another embodiment, said one or more different genes are selected from the up-regulated genes listed in Table 3, and said treatment regimen comprises a substance selected from the group consisting of antibody, peptide, and small molecule, each reducing the activity of one or more of proteins encoded by said one or more different genes in said patient.

In a preferred embodiment, said treatment regimen comprises an siRNA targeting said one or more different genes.

In preferred embodiment, said one or more different genes consisting of 2, 3, 4, 5, 6, or 10 different genes.

In another embodiment, said one or more different genes are selected from the down-regulated genes listed in Table 3, and said treatment regimen comprises subjecting said patient to gene therapy, said gene therapy enhancing the expression of said one or more different genes in said patient.

In one embodiment, the methods of the invention further comprises determining a transcript level of each of said one or more different genes, and said patient is determined to exhibit aberrant regulation of said different gene if said transcript level deviated from a predetermined threshold level. In some embodiments, said transcript level deviates from said predetermined threshold level by at least 1.5-fold, 2-fold or 3-fold.

In one embodiment, each said transcript level is determined by a method comprising measuring the transcript level of said different gene using one or more polynucleotide probes, each of said one or more polynucleotide probes comprising a nucleotide sequence complementary to a hybridizable sequence in said transcript of said different gene. In one embodiment, said one or more polynucleotide probes are polynucleotide probes on a microarray.

In another embodiment, each said transcript level is determined by a method comprising measuring the transcript level of said different gene using quantitative reverse transcriptase PCT (qRT-PCR).

In still another aspect, the invention provides a method for treating a patient having chronic myeloid leukemia (CML), comprising administering to said patient a treatment regimen, said treatment regimen comprising (i) an effective amount of imatinib mesylate (IM), and (ii) an agent other than IM, wherein said agent modulates the expression and/or activity of 1, 2, 3, 4, 5, 10 or more of the genes listed in Table 4 and/or their encoded proteins, and wherein said patient exhibits aberrant regulation of said one or more genes.

In one embodiment, said one or more genes are selected from the group consisting of the up-regulated genes listed in Table 4, and said agent comprises a substance selected from the group consisting of siRNA, antisense nucleic acid, ribozyme, and triple helix forming nucleic acid, each reducing the expression of one or more of said one or more genes in said patient.

In another embodiment, said one or more genes are selected from the group consisting of the up-regulated genes listed in Table 4, and said agent comprises a substance selected from the group consisting of antibody, peptide, and small molecule, each reducing the activity of one or more of proteins encoded by said one or more genes in said patient.

In one embodiment, said treatment regimen comprises an siRNA targeting said one or more target genes.

In some embodiments, said one or more genes consists of at least 2, 3, 4, 5, 6, or 10 target genes.

In one embodiment, said one or more genes are selected from the group consisting of the down-regulated genes listed in Table 4, and said agent comprises subject said patient to gene therapy, said gene therapy enhancing the expression of said one or more genes in said patient.

The methods can further comprises determining a transcript level of each said gene, and said patient is determined to exhibit aberrant regulation of said gene if said transcript level deviated from a predetermined threshold level. In some embodiment, said transcript level deviates from said predetermined threshold level by at least 1.5-fold, 2-fold or 3-fold.

In one embodiment, each said transcript level is determined by a method comprising measuring the transcript level of said gene using one or more polynucleotide probes, each of said one or more polynucleotide probes comprising a nucleotide sequence complementary to a hybridizable sequence in said transcript of said different gene.

In one embodiment, said one or more polynucleotide probes are polynucleotide probes on a microarray.

In another embodiment, each said transcript level is determined by a method comprising measuring the transcript level of said CML target gene using quantitative reverse transcriptase PCT (qRT-PCR).

In still another aspect, the invention provides a method for diagnosing whether a patient has advanced phase chronic myeloid leukemia (CML), comprising (a) contacting cells a cell sample from said patient with an antibody conjugate, said antibody conjugate comprising an antibody that binds a PRAME protein, said antibody being conjugated with a label; and (b) detecting said label on said cells, wherein detection of said label above a predetermined threshold indicates that said patient has advanced phase CML. The cell sample can be a bone marrow sample or a peripheral blood sample.

In one embodiment, said antibody is a monoclonal antibody.

In another embodiment, said label is fluorescence label, and said detecting is carried out using a fluorescence activated cell sorter.

In still another aspect, the invention provides a method for treating a patient having chronic myeloid leukemia (CML), comprising administering to said patient a therapeutically sufficient amount of an antibody, wherein said antibody binds a PRAME protein, and wherein said patient expresses PRAME protein on hematopoetic stem cells and/or immature myeloid cells. The invention also provides a method for treating a patient having chronic myeloid leukemia (CML), comprising administering to said patient a therapeutically sufficient amount of an antibody conjugate comprising an antibody that binds a PRAME protein, said antibody being conjugated with a therapeutic molecule, wherein said patient expresses PRAME protein on hematopoetic stem cells and/or immature myeloid cells.

In one embodiment, said antibody is a monoclonal antibody.

The invention also provides a method for ex vivo depletion of advanced phase hematopoetic stem cells and/or immature myeloid cells from a bone marrow or peripheral blood sample of a patient, comprising (a) incubating said bone marrow or peripheral blood sample with an antibody that binds a PRAME protein; and (b) removing cells having said antibody attached. The invention also provides a method for treating a patient having chronic myeloid leukemia (CML), comprising (i) depleting advanced phase hematopoetic stem cells and/or immature myeloid cells from a bone marrow or peripheral blood sample of said patient using the method described above; and (ii) transplanting the sample obtained in step (i) to said patient.

In still another aspect, the invention provides a method for identifying a set of genes that are associated with progression of chronic myeloid leukemia (CML), comprising: (a) subtracting from each of a plurality of CML expression profiles a CD34+ expression profile to obtain a plurality of CD34+(−) CML expression profiles, each said CML expression profile comprising levels of expression of a plurality of genes in cells of one of a plurality of chronic myeloid leukemia (CML) patients, said CD34+ expression profile comprising levels of expression of said plurality of genes in non cancerous immature CD34+ cells, said plurality of CML patients comprising patients of different phases of CML; (b) comparing said plurality of CD34+(−) CML expression profiles; and (c) identifying one or more genes that exhibit significant differences in levels of expression between different phases of CML across said plurality of CD34+(−) CML expression profiles.

In one embodiment, said comparing is carried out by ANOVA and said identifying is carried out by identifying one or more genes one or more genes whose p-value corresponds to a predetermined significance level. In one embodiment, said predetermined significance level is p<10₋₈.

The method can further comprise: (d) comparing levels of expression of said identified genes between cells of CML blast crisis and normal immature CD34+ cells; and (e) selecting those genes that exhibit significant differences in expression.

In another embodiment, said comparing is carried out by ANOVA and said selecting is carried out by selecting one or more genes whose p-value corresponds to a predetermined significance level. In one embodiment, said predetermined significance level is p-value<0.01%.

The invention also provides a computer system comprising a processor, and a memory coupled to said processor and encoding one or more programs,

wherein said one or more programs cause the processor to carry out any one of the methods of the invention.

The invention also provides a computer program product for use in conjunction with a computer having a processor and a memory connected to the processor, said computer program product comprising a computer readable storage medium having a computer program mechanism encoded thereon, wherein said computer program mechanism may be loaded into the memory of said computer and cause said computer to carry out any one of the methods of the invention.

In still anther aspect, the invention provides a microarray comprising for each of a plurality of genes, said genes being at least 5 of the genes selected from the group consisting of the genes as identified respectively by SEQ ID NOS: 1-3968, wherein at least one of said 5 genes is not a gene selected from the group consisting of genes as identified respectively by SEQ ID NOS: 56, 65, 70, 177, 190, 199, 1758, 1773, 1774, 1776, 1786, 1815, 1823, 3925, 3933, 3947, 3956, and 3961, one or more polynucleotide probes complementary and hybridizable to a sequence in said gene, wherein polynucleotide probes complementary and hybridizable to said genes constitute at least 50%, 70%, 80%, 90% or 98% of the probes on said microarray.

In one embodiment, said plurality of genes is at least 10, 20, 40, 70, 100, or 200 genes.

In another embodiment, said plurality of genes is selected from the group consisting of the genes listed in Tables 1a and/or 1b.

In still another embodiment, said plurality of genes is selected from the group consisting of the genes listed in Tables 2a and/or 2b.

In still another embodiment, said plurality of genes is at least 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 or all 20 of the genes listed in Table 3.

In still another embodiment, said plurality of genes are selected from the group consisting of the genes listed in Table 4.

In still another embodiment, said plurality of genes is selected from the group consisting of the genes listed in Tables 5a and/or 5b.

4. BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1. Genes associated with CML progression. Samples of CML cases in chronic phase, accelerated by cytogenetic criteria only, accelerated phase, blast crisis, and blast crisis “in remission” were compared to a pool of chronic phase RNA. Approximately 3,000 genes were significantly associated with progressive disease at a significance level of p<10₋₁₁. Each row represents one sample, and each column represents one gene. A darker color indicates over-expression relative to the control pool, and a lighter color indicates low-expression.

FIG. 2. 2a: Genes differentially expressed in blast crisis CML compared to normal CD34+ stem cells. CML blast crisis samples with >70% blasts were compared to normal CD34+ bone marrow stem cells. 2b: Approximately 400 genes were significantly differentially expressed between CML blasts and their immature CD34+ normal counterparts (ANOVA P<0.1%). 2c: Phase genes corrected for normal CD34+ gene expression (ANOVA P<1×10₋₈). The gene expression of normal CD34+ cells was subtracted from each disease sample. The resulting pattern reflects genes associated with progression independent of normal blast biology.

FIG. 3. Genes expression signature of genes associated with specific promoter sequences. Genes with specific promoter sequences were tested for their differential enrichment across different phases of CML (see Methods). FIG. 3a shows genes bearing a MZF promoter; FIG. 3b shows expression of genes under putative control of delta EF1.

FIG. 4. Gene expression in Imatinib failure cases. 4a: All CML eases including cases of imatinib failure; gene expression is based on the previously obtained ˜3,000 phase reporter set. 4b: Cases are ranked and sorted by the correlation of summed gene expression, with cases representing the most “cp-like” and most “bc-like” forming the boundries of gene expression patterns. Cases of imatinib failures are shown. 3c: Genes differentially expressed in imatinib resistant cases that are not associated with progression gene set. The boxed areas represent genes differentially expressed in the imatinib resistant cases compared to blast crisis cases.

FIG. 5. Comparison of gene expression in accelerated phase versus blast phase CML. The graph shows the scatter plot of log(ratio) of all 25K genes in blast crisis and accelerated phase cases. Each blue dot represents a gene. Thus, genes in the upper left hand box are up in accelerated phase, but down in blast crisis. Genes in the upper right box are up both in accelerated and blast crisis. The gene expression levels are very highly correlated between accelerated and blast crisis (r=0.81).

FIG. 6. Phase reporter genes after removal of normal CD34+ signature. The gene expression signature of normal CD34+ cells was subtracted from the data of CML cases. The genes shown are the genes differentially expressed across disease phases after genome wide removal of CD34+ signatures (p-value of <10₋₄).

FIG. 7. Comparison of gene expression between bone marrow and peripheral blood. In three cases of blast crisis samples were simultaneously drawn from marrow and blood. The figures show a high correlation of gene expression for these three cases.

FIG. 8 illustrates an exemplary embodiment of a computer system for implementing the methods of this invention.

5. DETAILED DESCRIPTION OF THE INVENTION

The invention provides molecular markers, i.e., genes, the expression levels of which can be used for evaluating the progression of chronic myeloid leukemia (CML) from chronic phase to advanced phase. The identities of these markers and the measurements of their respective gene products, e.g., measurements of levels (abundances) of their encoded mRNAs or proteins, can be used by application of a pattern recognition algorithm to develop a progression classifier that discriminates between different phases of CML based on measurements of such gene products in a sample from a patient. As used herein, the term “gene product” includes mRNA transcribed from the gene and protein encoded by the gene.

Chronic myelogenous leukemia (CML) is characterized by high peripheral white blood cell (WBC) counts with granulocyte predominance and extramedullary hematopoiesis. CML typically evolves through 3 clinically distinct stages or phases: chronic phase (CP-CML or CP), accelerated phase (AP-CML or AP), and blast phase (BP-CML or BP), which is also called acute phase or blast crisis (BC-CML or BC). The chronic phase lasts several years and is characterized by accumulation of myeloid precursors and mature cells in bone marrow, peripheral blood, and extramedullary sites. During the chronic phase, patients typically have fewer than 10% blasts (or 20% blasts and promyelocytes combined) in blood or bone marrow samples. These patients usually have relatively mild symptoms and usually respond to standard treatments. The chronic phase progresses into the accelerated phase, which lasts about 4 to 6 months. During the accelerated phase, patients typically have more than 10% blasts (or 20% blasts and promyelocytes combined) but less than 30% blasts and promyelocytes in their bone marrow or blood samples. These patients often have fever, poor appetite, and weight loss. Symptoms and blood counts of an AP-CML patient are not as responsive to treatments as they are during the chronic phase. The leukemia cells often have developed new chromosomal changes, in addition to the Philadelphia chromosome. The accelerated phase progresses to the blast phase, which lasts for a few months. During the blast phase, patients typically have more than 30% blasts and promyelocytes in their bone marrow and/or blood samples. The blast cells often spread to tissues and organs beyond the bone marrow. The accelerated phase and the blast phase are often grouped together into an advanced phase of CML (ADV-CML or ADV). The molecular markers of the invention are particular useful for evaluating the progression of a CML patient from the chronic phase to the advanced phase.

The invention provides a list of genes that are differentially expressed across different phases of CML (Tables 1a and 1b, infra). This set of genes is called the phase reporter geneset. Measurements of gene products of these molecular markers, as well as of their functional equivalents, can be used for staging a CML patient. A functional equivalent with respect to a gene, designated as gene A, refers to a gene that encodes a protein or mRNA that at least partially overlaps in physiological function in the cell to that of the protein or mRNA encoded by gene A. In particular, CML staging in a patient is carried out by a method comprising determining whether the patient is in a chronic phase or an advanced phase (accelerated phase or blast phase) based on a profile of measurements (e.g., of the levels) of gene products of (i.e., encoded by) at least 5, 10, 20, 30, 40, 50, 60, 70, 80, 100, 200, 500 or all of the genes in Tables 1a and/or 1b; or of at least 2%, 5%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, or 90% of the genes in Tables 1a and/or 1b, or functional equivalents of such genes, in an appropriate cell sample from the patient, e.g., a bone marrow or blood sample obtained from the patient, wherein at least 1, 2, 3, 5, or 10 genes as appropriate are from Table 1a. Such a profile of measurements is also referred to herein as an “expression profile” or a “marker profile.” In a specific embodiment, the evaluation of CML progression in a patient is carried out using measurements (e.g., of the levels) of gene products of (i.e., encoded by) at least 5, 10, 20, 30, 40, 50, 60, 70, 80, 100, 200, 500 or all of the genes in Tables 1a; or of at least 2%, 5%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, or 90% of the genes in Tables 1a, or functional equivalents of such genes. In another specific embodiment, the evaluation of CML progression in a patient is carried out using measurements of gene products of less than 30, 40, 50, 70, 100, 200, 300, 400, or 500 total genes, in which all or at least 20%, 30%, 40%, 50%, 60%, 70%, 80%, or 90% of the genes are from Tables 1a and/or 1b or their functional equivalents, or at least 5, 10, 20, 30, 40, 50, 60, 70, 80, or 100 of the genes are from Tables 1a and/or 1b or their functional equivalents. In one embodiment, if the patient expression profile is classified as a CP-CML profile, the patient is determined as in chronic phase, whereas if the patient expression profile is classified as a ADV-CML profile, the patient is determined as in an advanced phase (accelarated phase or blast crisis).

The invention also provides a list of genes that are associated with CML progression (Tables 2a and 2b, infra). These genes are also termed “progression genes” in the application. This set of genes is called the progression geneset. Measurements of gene products of these molecular markers, as well as of their finctional equivalents, can be used for staging a CML patient. Since these genes are associated with CML progression, they are also targets for therapeutic intervention of CML. For example, a CML patient exhibiting aberrant regulation of such genes can be treated by therapies targeting such genes. Thus, measurements of gene products of these molecular markers, as well as of their functional equivalents, can also be used for determining an appropriated treatment regimen for a CML patient.

Different subcombination of CML progression genes can also be used. Thus, in various embodiments, the markers that are the genes listed in Tables 2a-2b or 3 are used. Measurements of gene products of these molecular markers and/or their functional equivalents can be used for evaluating the progression of CML. in a patient. The evaluation of CML progression in a patient is carried out by a method comprising determining whether the patient is in a chronic phase or an advanced phase (accelerated phase or blast phase) based on a profile of measurements (e.g., of the levels) of gene products of (i.e., encoded by) at least 5, 10, 20, 30, 40, 50, 60, 70, 80, 100, 200 or all of the genes in Tables 2a and/or 2b, or at least 5, 10, 15 or all of the genes in Table 3; or of at least 2%, 5%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, or 90% of the genes in Tables 2a and/or 2b or in Table 3, or functional equivalents of such genes, in an appropriate cell sample from the patient, e.g., a bone marrow or peripheral blood sample obtained from the patient, wherein at least 1, 2, 3, 5, or 10 genes as appropriate are from Table 2a. In a specific embodiment, the evaluation of CML progression in a patient is carried out using measurements (e.g., of the levels) of gene products of (i.e., encoded by) at least 5, 10, 20, 30, 40, 50, 60, 70, 80, 100, 200, 300 or all of the genes in Tables 2a; or of at least 2%, 5%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, or 90% of the genes in Tables 2a, or functional equivalents of such genes. In one embodiment, if the patient expression profile is classified as a CP-CML profile, the patient is determined as in chronic phase, whereas if the patient expression profile is classified as a ADV-CML profile, the patient is determined as in an advanced phase (accelarated phase or blast crisis).

The invention also provides a list of genes that are associated with resistence to imatinib mesylate (Table 4, infra). These genes are also termed “imatinib resistence genes” in the application. This set of genes is called the imatinib resistence geneset. Measurements of gene products of these molecular markers, as well as of their functional equivalents, can be used for evaluating the responsiveness of a CML patient to imatinib treatment. The evaluation of responsiveness of a patient to imatinib is carried out by a method comprising determining whether the patient is likely to be responsive to imatinib treatment based on a profile of measurements (e.g., of the levels) of gene products of (i.e., encoded by) at least 5, 10, 20, 30, 40, 50, 60, 70, 80, 100, 200 or all of the genes in Table 4; or of at least 2%, 5%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, or 90% of the genes in Table 4, or functional equivalents of such genes, in an appropriate cell sample from the patient, e.g., a bone marrow or peripheral blood sample obtained from the patient. In one embodiment, if the patient expression profile is classified as a IM-resistence profile, the patient is determined as likely to be resistent to imatinib treatment, whereas if the patient expression profile is classified as a IM-sensitive profile, the patient is determined as likely to be responsive to imatinib treatment. In a specific embodiment, a CML patient in the chronic phase is evaluated for responsiveness to imatinib treatment based on an expression profile of such imatinib resistence genes. If the patient's expression profile indicates that the patient is likely to be resistent to imatinib treatment, bone marrow transplantation and/or other investigative treatment regimens may be assigned to the patient.

In another embodiment, the responsiveness of a CML patient to imatinib treatment can also be evaluated based on expression of phase reporters or progression genes. In this embodiment, the patient expression profile comprising measurements of phase reporter genes (Table 1a and/or 1b) or progression genes (Table 2a and/or 2b) is evaluated using a method described above. If the patient expression profile is classified as a ADV-CML profile, the patient is determined as likely to be resistent to imatinib treatment.

The measurements in the profiles of the gene products that are used can be any suitable measured values representative of the expression levels of the respective genes. The measurement of the expression level of a gene can be direct or indirect, e.g., directly of abundance levels of RNAs or proteins or indirectly, by measuring abundance levels of cDNAs, amplified RNAs or DNAs, proteins, or activity levels of RNAs or proteins, or other molecules (e.g., a metabolite) that are indicative of the foregoing. In one embodiment, the profile comprises measurements of abundances of the transcripts of the marker genes. The measurement of abundance can be a measurement of the absolute abundance of a gene product. The measurement of abundance can also be a value representative of the absolute abundance, e.g., a normalized abundance value (e.g., an abundance normalized against the abundance of a reference gene product) or an averaged abundance value (e.g., average of abundances obtained at different time points or from different tumor cell samples from the patients, or average of abundances obtained using different probes, etc.), or a combination of both. As an example, the measurement of abundance of a gene transcript can be a value obtained using an Affymetrix® GeneChip® to measure hybridization to the transcript.

In another embodiment, the expression profile is a differential expression profile comprising differential measurements of a plurality of transcripts in a sample derived from the patient versus measurements of the plurality of transcripts in a reference sample, e.g., a cell sample of normal cells. Each differential measurement in the profile can be but is not limited to an arithmetic difference, a ratio, or a log(ratio). As an example, the measurement of abundance of a gene transcript can be a value for the transcript obtained using an ink-jet array or a cDNA array in a two-color measurement. In a preferred embodiment, the reference sample comprise target polynucleotide molecules from normal cell samples (i.e., cell sample, e.g., bone marrow or peripheral blood, from those not afflicted with CML). In another preferred embodiment, the reference sample comprise target polynucleotide molecules from cell samples, e.g., bone marrow or peripheral blood, from chronic phase CML patients.

The invention also provides methods and computer systems for evaluating the progression of CML in a patient based on a measured marker profile comprising measurements of the markers of the present invention, e.g., an expression profile comprising measurements of transcripts of at least some of the genes listed in Tables 1a and/or 1b, e.g., at least 5, 10, 20, 30, 40, 50, 60, 70, 80, or 100 in Tables 1a and/or 1b or funtional equivalents of such genes, wherein at least 1, 2, 3, 5 or 10 genes are from Table 1a. The methods and systems of the invention use a progression classifier for evaluating the progression of CML. The progression classifier can be based on any appropriate pattern recognition method (such as those described in Section 5.2) that receives an input comprising a marker profile and provides an output comprising data indicating which phase the patient belongs, i.e., chronic phase or advanced phase. The progression classifier can be constructed with training data from a plurality of CML patients for whom marker profiles and progression status are known. The plurality of patients used for training the progression classifier is also referred to herein as the training population. The training data comprise for each patient in the training population (a) a marker profile comprising measurements of gene products of a plurality of genes, respectively, in an appropriate cell sample, e.g., a bone marror or peripheral blood sample, taken from the patient; and (b) progression status information (e.g., the CML phase of the patient). Various progression classifiers that can be used in conjunction with the present invention are described in Section 5.2., infra. In some embodiments, additional patients having known marker profiles and progression status can be used to test the accuracy of the progression classifier obtained using the training population. Such additional patients are also called “the testing population.”

The markers in the marker sets are selected based on their ability to discriminate patients having different CML phases in a plurality of CML patients for whom the progression status are known. Various methods can be used to evaluate the correlation between marker levels and CML progression. For example, genes whose expression levels are significantly different across patients in different CML phases can be identified using an appropriate statistical method, e.g., ANOVA.

The invention also provides methods and compositions for treating a patient having CML by modulating, e.g., enhancing or reducing, the expression and/or activities of one or more CML progression genes and/or target genes and/or their gene products. The invention also provides methods and compositions for treating a patient having CML by modulating, e.g., enhancing or reducing, certain CML pathways that involve in CML progression and response. The CML progression genes include those genes listed in Tables 2a and 2b. The CML target genes include those genes listed in Tables 5a and 5b. The CML pathways include FLT3; Rras2; beta-catenin; and SOCS2. The invention also provides methods and compositions for treating a patient having CML by modulating, e.g., enhancing or reducing, certain proteosomes and chaperone proteins. The invention also provides methods and compositions for treating a patient having CML by modulating genes controlled by a promoter selected from the group consisting of the following MZF, delta EF1, SPI-B, Yin Yang, and Ahr-ARNT. The invention also provides methods and compositions for treating a patient having CML by modulating, e.g., reducing, the expression and/or activity of CD47. The invention also provides methods and compositions for treating a patient having CML by targeting PRAME. The invention is based, at least in part, on the identification of aberrant regulation of these genes and pathways in CML.

Thus, the invention provides methods and compositions for treating CML by modulating the expression and/or activity of CML progression genes and/or CML target genes and/or their gene products, and/or by modulating interactions of the CML progression genes and/or target genes and/or their gene products with other proteins or molecules, e.g., substrates. The methods and compositions can be used for treating CML patient who exhibit aberrant regulation in such CML progression/target genes. Thus, such methods and compositions can be used in conjunction with imatinib mesylate. In one embodiment, the expression of one or more of the CML progression/target genes is modulated, e.g., reduced or enhanced, to treat a CML patient exhibiting aberrant regulation of these CML progression/target genes. Such modulation can be achieved by, e.g., using siRNA, antisense nucleic acid, ribozyme, and/or triple helix forming nucleic acid that target the CML progression/target genes. In another embodiment, the activity of one or more CML progression/target proteins is modulated, e.g., reduced or enhanced, to enhance the effects of chemotherapy agents. Such modulation can be achieved by, e.g., using antibodies, peptide molecules, and/or small molecules that target a CML progression/target protein.

The invention also provides methods and compositions for treating CML by modulating the expression and/or activity of imatinib mesylate resistance genes and/or their gene products, and/or by modulating interactions of the IM-resistance genes and/or their gene products with other proteins or molecules, e.g., substrates, in combination of imatinib mesylate. In one embodiment, the expression of one or more of the IM-resistance genes is modulated, e.g., reduced or enhanced, to treat a CML patient undergoing imatinib mesylate treatment. Such modulation can be achieved by, e.g., using siRNA, antisense nucleic acid, ribozyme, and/or triple helix forming nucleic acid that target the imatinib mesylate genes. In another embodiment, the activity of one or more imatinib mesylate proteins is modulated, e.g., reduced or enhanced, to enhance the effects of chemotherapy agents. Such modulation can be achieved by, e.g., using antibodies, peptide molecules, and/or small molecules that target imatinib mesylate proteins.

The invention also provides methods and compositions for utilizing CML progression/target genes or IM-resistance genes, and/or their products for screening for agents that modulate their expression and/or activity and/or modulating their interactions with other proteins or molecules. Agents that modulate expression and/or activity of CML progression/target genes can be used for treating CML patient exhibiting aberrant regulation of one or more CML progression/target genes. Agents that modulate expression and/or activity of IM-resistance genes can be used in combination with IM for treating CML patient exhibiting resistance to IM treatment. Thus, the invention provides methods and compositions for utilizing CML progression/target genes and gene products for screening for agents that are useful in modulating expression and/or activity of CML progression/target genes or IM resistance genes and/or their products and/or modulating their interactions with other proteins or molecules in a CML patient exhibiting aberrant regulation of one or more CML progression/target genes or IM resistance genes. The compositions of the invention include but not limited to siRNA, antisense nucleic acid, ribozyme, triple helix forming nucleic acid, antibody, peptide or polypeptide molecules, and small organic or inorganic molecules.

The present invention also provides methods and compositions for identifying other extra- or intra-cellular molecules, e.g., genes and proteins, which interacts with the CML progression/target genes or IM resistance genes, and/or their gene products, and/or CML progression pathways. The present invention also provides methods and compositions for treating CML by modulating such cellular constituents and/or pathways.

As used herein, a patient is an animal having CML. The patient can be but is not limited to a human, or, in a veterinary context, from non-human animals such as ruminants, horses, swine or sheep, or from domestic companion animals such as felines and canines. In a preferred embodiment, the patient is a human patient. Suitable samples that can be used in conjunction with the present invention include but are not limited to bone marrow samples and peripheral blood samples.

5.1. Genes Associated with CML Progression and Response

The invention provides molecular marker sets (of genes) that can be used for evaluating progression and/or imatinib resistance in a CML patient based on a profile of the markers in the marker set (containing measurements of marker gene products).

Tables 1a and 1b list genes that are differentially expressed across different phases of CML. This set of genes is called the phase reporter geneset. The phase reporter genes are identified by their SEQ ID NOs in Tables 1a and 1b. Tables 1a and 1b also listed for each gene the log ratio of expression level of the gene in samples from patients of a particular phase (e.g., CP, AP, or BC) versus expression level of the gene in a pool of CML bone marrow samples from chronic phase patients. Each log ratio column thus contains expression levels of markers for a particular phase. Information for these genes is presented in Table 8. In Table 8, the following information is presented for each gene: gene identifier (column 1), gene name (column 2), the SEQ ID NO of the sequence of the gene (column 3), and the SEQ ID NO of the probe sequence used in the present application (column 4). The first column of Table 8 shows the identifiers of genes disclosed in the application. The term “SUBS” is shorthand for substance identifier. For those genes listed in Table 8 that have a GenBank® accession number, the GenBank® accession number is listed. For those genes in Table 8 that do not have a GenBank® Accession No, the Contig ID numbers of the transcript sequences in the Phil Green assembly (Nat Genet 2000 Jun;25(2):232-4) is listed. Phil Green's group at the University of Washington assembled ESTs from the Washington University-Merck Human EST Project and CGAP archives. Analysis of expressed sequence tags indicates 35,000 human genes (Nat Genet 2000 Jun;25(2):232-4). This assembly, dated Mar. 17, 2000, resulted in 62,064 contigs representing 795,000 ESTs (see web address: www.phrap.org/est_assembly/human/gene_number_methods.html; and www.phrap.org/est_assembly/human/gene_number_methods.html). These contigs have the word “contig” included in their identifiers. Table 1a lists phase reporters that were not disclosed in U.S. Patent Application Publication 2003/01044026 A1, dated Jun. 5, 2003. Table 1b lists phase reporters that were also identified in U.S. Patent Application Publication 2003/01044026 A1, dated Jun. 5, 2003.

TABLE 1aphase reporter genesSEQ IDlog(ratio)NOCPlog(ratio) APlog(ratio) BC1−0.004060.1965630.3316312−0.0130360.3311910.136193−0.01517−0.1969−0.519974−0.012260.2347030.5063175−0.01055−0.11513−0.2523960.023330.22340.38529470.001109−0.04225−0.3892280.0221780.3204910.3626869−0.01332−0.22505−0.26552100.0024910.1075140.4024811−0.03342−0.12983−0.3485612−0.02396−0.1739−0.56037130.004316−0.16534−0.1595414−0.002250.4643570.63715515−0.06413−0.10146−0.58794160.0091280.2358740.469511170.0202361.1236030.742981180.0162140.1596370.39282919−0.04723−0.47509−1.3626421−0.010950.2322210.294685220.0121720.4277070.72902723−0.01999−0.21291−0.3614924−0.00972−0.14706−0.4052250.004981−0.21328−0.3713526−0.02611−0.30231−0.45226270.0105140.3388240.43401929−0.02088−0.283−0.4598730−0.00198−0.11265−0.28724310.0235770.7707370.690215320.008671−0.0801−0.28421330.012103−0.15124−0.15019340.010651−0.14341−0.51535−0.001260.0104890.264385360.0273480.347740.624742370.0337620.2130530.520588380.003765−0.14306−0.39624390.0330250.2812920.40656540−0.06315−0.28017−1.14257410.0077480.095810.33590342−0.01732−0.09377−0.68791430.018086−0.22492−0.285440.014232−0.27373−0.31289450.0361970.1422950.46693746−0.010220.2997370.425197470.0068220.1992140.443601480.0216020.1863920.3367549−0.03649−0.26722−0.49009520.0082480.5029710.507442530.0401870.6875020.56468854−0.00051−0.10576−0.4070955−0.01352−0.22612−0.4912857−0.052650.4336480.40219580.0192390.1871270.325353590.006451−0.22186−0.18506600.0102010.6151171.017473610.013254−0.23449−0.26153620.012036−0.20146−0.36216630.0186560.2628290.53086864−0.01623−0.1428−0.5084166−0.00346−0.1026−0.30257670.0098410.3352990.527591680.0096650.971430.99069269−0.035170.365880.442864710.005961−0.17466−0.2080373−0.00646−0.25708−0.2174974−0.0186210.110352−0.54136275−0.00408−0.21342−0.26897760.0092070.7694530.850508780.01230.1678050.337085790.00674−0.17218−0.2541480−0.00232−0.13768−0.2596281−0.04268−0.09565−0.7612382−0.00889−0.18131−0.3448830.009640.1394170.32827484−0.034770.147022−0.6705285−0.0546−0.22956−1.3298886−0.01987−0.41057−0.6381487−0.00053−0.16512−0.19246890.0291340.1667040.39906690−0.00832−0.13645−0.3186920.0371550.2841530.6453294−0.01142−0.13881−0.3608950.011250.109550.227757960.0125270.2292950.293851980.0602570.9525320.999368100−0.0643−0.33585−0.590981010.0093630.1843720.293381102−0.0128−0.2329−0.544221030.0197990.4728630.545631040.0394490.4157330.5766711060.010496−0.12076−0.186661070.011423−0.16555−0.23653108−0.084431.1788850.8020821090.0139940.2643280.4019941100.044380.406530.5803661110.0271080.2659550.6042121120.003332−0.25986−0.29846113−0.01029−0.26712−0.2846114−0.05586−0.21334−0.822931150.0095940.0179810.208686117−0.010230.4529980.673941118−0.006590.4904570.517515119−0.022540.7442890.818592120−0.01441−0.29009−0.5309121−0.01153−0.19616−0.337881220.0286020.4053150.525104123−0.005640.3557020.574731240.0056640.1946530.2308881250.0297940.4542780.726423126−0.01071−0.33686−0.439681270.0377020.5419840.729726128−0.007530.1399320.2468751290.0244291.3750491.029358130−0.01338−0.13678−0.287291310.0141080.4322320.7715131320.0269760.4255440.616671330.0246330.1461290.39073135−0.00713−0.09868−0.64744136−0.03239−0.08145−0.37526137−0.04003−0.24301−0.62499138−0.003080.5028290.7238241390.0064950.7313820.8639951400.001806−0.20936−0.37679141−0.03144−0.20901−0.556341430.007968−0.15803−0.23468144−0.03705−0.14512−0.623851450.0277580.1447930.533543146−0.01241−0.08289−0.713421470.024977−0.11774−0.37273148−0.03021−0.24989−0.41756149−0.07893−0.2035−1.03931510.0009920.4893960.562018152−0.03269−0.19994−0.50103153−0.01351−0.07093−0.351611540.0201010.1324170.359255156−0.02182−0.18751−0.492041570.00543−0.2313−0.38327159−0.02675−0.26775−0.37637160−0.10326−0.41976−1.24875161−0.06485−0.23089−1.088971620.010219−0.24712−0.311221630.006220.1758040.3341461640.0080230.2755260.371384165−0.0136−0.18292−0.50396166−0.04425−0.16366−0.880141670.0124610.4064840.521279168−0.00562−0.17893−0.63614169−0.00540.1658720.354167170−0.02256−0.17498−0.389891720.0116770.2612140.3401981730.0202320.3078230.4289411750.0130730.3005560.4633541760.0032760.3472930.312461780.0098240.2327760.381628179−0.02289−0.25739−0.33021800.0095750.3901540.6200311810.0066260.4662490.4268521820.006874−0.17448−0.30214183−0.04255−0.18274−0.567521850.0229860.2769360.4097731860.0356380.3965990.57451187−0.030480.291510.4989251880.0183370.1507710.4332591890.0191290.2146690.445425192−0.00127−0.15435−0.149011930.027950.1989280.2889371940.007888−0.17921−0.215341960.0350640.1241820.42622197−0.007830.3411370.350515198−0.01383−0.24055−0.43808200−0.0088−0.19251−0.408812010.0153690.1249610.3668432020.0121270.2152120.262119203−0.017820.4395680.95044205−0.009240.2682110.43449206−0.016890.2474570.4070072070.009984−0.20509−0.242772080.001180.2675590.335573209−0.06306−0.26661−0.33283210−0.0089−0.26158−0.69113211−0.02429−0.21795−0.69236212−0.002920.2010490.501509213−0.010960.5498830.588095214−0.00632−0.05677−0.384032150.0138080.2163260.45018216−0.020670.9938310.8572422170.0305040.2375090.318043218−0.01132−0.3714−0.322072190.0243790.1050730.271123220−0.04224−0.24384−0.679242210.007430.245240.402431222−0.004560.3773280.497584223−0.002270.2904120.6120272240.000149−0.22094−0.27218225−0.00048−0.21954−0.270352260.0200370.2440550.2634232270.005396−0.1374−0.20983228−0.02345−0.26901−0.57294229−0.002220.3263810.351552230−0.008050.5639870.7643542310.005230.5063450.8080132320.0350610.2197850.405612330.013849−0.15255−0.43366234−0.00462−0.22522−0.25117235−0.00656−0.33242−0.94825236−0.02885−0.00068−0.322162370.0326260.079410.332713238−0.05042−0.25277−1.18988239−0.05805−0.33763−0.85786240−0.03475−0.31239−0.42272241−0.00172−0.13603−0.180372420.0144590.275390.475543244−0.00314−0.1324−0.31292450.0154450.2157090.389195247−0.001290.0450090.2719152480.0227730.7558320.762127249−0.004370.630180.8752632500.0281680.4107530.722373251−0.005660.0437140.278866252−0.011159−0.181168−0.3380222530.0031490.3809090.533681255−0.0062−0.31339−0.361572560.036950.2595420.377038257−0.01933−0.28626−0.26047258−0.037880.6862620.9058162590.0300020.2204850.3718932600.0366630.5181390.7569592610.002136−0.0139390.252784262−0.00929−0.3146−0.331852630.002577−0.2136−0.268032640.0251240.1838560.3510432650.017567−0.1399−0.1726266−0.02625−0.19264−0.32146268−0.00566−0.26083−0.47188270−0.00065−0.21267−0.22762271−0.03035−0.20616−1.268872720.011657−0.02278−0.48484273−0.015940.063149−0.5003274−0.03779−0.29016−0.73186276−0.00502−0.10018−0.26137277−0.038−0.40089−1.25651278−0.06888−0.20805−1.09992790.012839−0.17955−0.37213280−0.00925−0.14564−0.23232810.001026−0.09417−0.426912820.0371450.5372810.683985284−0.12422−0.39967−0.73152285−0.001670.1734090.6358982860.0213590.5108420.8760092870.0040450.040739−0.320672880.0221730.1850170.362062289−0.013630.2950390.4636152900.0036110.303090.5595362910.0045750.5168750.753323293−0.08872−0.344−0.578332940.001582−0.08399−0.4561295−0.02727−0.08523−0.573372960.017609−0.10028−0.13923297−0.001560.2058130.568643298−0.05053−0.21837−0.42199299−0.00722−0.073710.267236300−0.00720.0813840.2614283010.0115860.3167030.6030773020.0466240.1489240.379405303−0.01548−0.27466−0.390793040.0135240.2569520.367345305−0.00086−0.14331−0.770613060.0042580.4197880.507983070.0061420.2055770.3413273080.0237890.2076320.4177473100.0079160.3691390.409188311−0.01836−0.20108−0.71669312−0.006268−0.169392−0.415121313−0.00495−0.13587−0.78354314−0.00110.087840.463253150.0228410.0880060.320199316−0.02455−0.02247−0.591533170.0066730.2166860.3620713180.0042820.2129880.3622943190.009590.257890.4452023200.0044010.3234330.4268673210.0172930.2640730.3518153220.0050.3560680.595108323−0.001550.251120.276408324−0.00324−0.13033−0.722843250.00840.1767450.433833326−0.02092−0.09038−0.49155327−0.019830.5708320.8911893280.0074030.2183080.3281823290.002464−0.29977−0.4368330−0.004060.3220860.397844331−0.000960.2931210.435914332−0.03766−0.12709−0.795533330.0077460.1794490.3559483340.0011460.2019230.364199335−0.0092−0.11216−0.248133360.0025380.2553320.328868338−0.013780.5808610.677954339−0.010990.4376240.71671340−0.04397−0.28419−0.474513410.0021150.3500310.5624313440.0110130.3593110.387564345−0.0544−0.40219−0.964253460.00386−0.16004−0.210883470.008691−0.12593−0.29733480.0310930.3293180.780388349−0.024750.264980.691058350−0.004040.3114880.516583351−0.009270.6074150.9328393520.0226150.3107210.4076423530.0293530.2842480.4648043540.0276510.205460.357579355−0.02613−0.20506−0.37711356−0.000830.3148840.564315357−0.03262−0.16231−0.512773580.0099310.4247440.4454653590.000838−0.18535−0.36657360−0.003940.3444070.3244673610.013027−0.22952−0.452543620.0125040.5054960.8814253630.004492−0.184−0.355983640.0184330.1042710.2819783660.0236310.1795260.4510273670.0116270.4340040.7168563680.0029490.5165010.6703023690.015105−0.30705−0.467622373−0.026520.2879020.4719743740.006262−0.12699−0.20681375−0.03478−0.32675−0.650353760.0232130.376580.4481673780.003855−0.20696−0.308333790.0119720.1531750.2872323800.038180.448120.568722381−0.01575−0.33744−0.321453820.0095251.0556491.229694383−0.016450.3774290.5851753840.003458−0.13346−0.32546385−0.026480.3914550.3763563870.0117920.1773230.2383693880.0025070.2667790.4014033890.0208360.2181510.367914391−0.00888−0.17832−0.229693920.009940.782010.698796394−0.022040.379830.574414395−0.015270.5246320.73152396−0.021830.1995210.4585253970.010494−0.18981−0.235333980.035990.6514680.7839083990.0276440.1662530.382499400−0.004780.1841650.341955401−0.04717−0.30622−0.912064020.0086950.1364210.3158814030.0011630.0376980.202135404−0.00339−0.18226−0.2593405−0.002280.3105560.465954407−0.02149−0.34683−0.42713408−0.004040.0334050.2626414090.0078760.0874870.304334100.012271−0.18684−0.358754110.0200910.3223110.477211412−0.00568−0.1428−0.3547413−0.02569−0.24238−0.87728414−0.01495−0.31741−0.285734150.0022450.2779850.577752416−0.01237−0.3593−0.27374417−0.0330.5714360.4975394180.0078540.2493270.425654190.019821−0.26045−0.390064200.033080.2475330.4077834210.0209480.4891590.557808422−0.006470.417340.4515844230.0190160.1870740.2793174240.0564750.4011030.5325014250.005889−0.26002−0.364264270.009398−0.16823−0.18166428−0.02152−0.13742−0.3652429−0.00502−0.17865−0.51519430−0.02829−0.23927−0.267314310.006892−0.15152−0.23519432−0.010940.2647260.2394724330.003070.2625160.4358944340.0068670.1131440.1641294350.0086690.1689660.366591436−0.02165−0.24157−0.27957437−0.02808−0.17851−0.47493438−0.01511−0.24775−0.25327439−0.00157−0.1947−0.268534400.0047160.2034040.422278441−0.00177−0.14061−0.2414430.0355310.5005520.7625784450.001111−0.22997−0.20668446−0.009660.2625470.5322994470.022051−0.17196−0.173584480.02208−0.20758−0.544534490.003789−0.26541−0.420684500.008518−0.27104−0.36638451−0.004550.2563730.3446554520.0133630.2013990.489434530.006363−0.42802−0.575714540.0178160.4637590.5590274550.0294970.9233930.8743854570.0092850.2708460.4330794580.0029750.2851860.5594864600.004206−0.25199−0.257374610.0362780.3098370.480654620.003674−0.24833−0.33834463−0.009220.1354920.3274924640.018334−0.16889−0.203054650.0106830.4545980.6912974660.0107240.6895230.82927467−0.04167−0.0735−0.57092468−0.0225−0.36378−0.972194700.0186210.3507420.523891471−0.0407−0.25963−0.753114720.019640.3892190.7234584730.0214690.5081210.605512474−0.01762−0.15235−0.59443475−0.000140.0562880.3512474760.0121520.6096580.7803554770.0012360.316290.53508478−0.01143−0.18139−0.260734790.002234−0.16979−0.23309481−0.02373−0.30404−0.58894482−0.03178−0.32713−0.492624830.002809−0.10396−0.43271484−0.06435−0.19262−0.801054850.0004780.194850.514866486−0.08957−0.12042−0.676564870.013939−0.24216−0.280644880.0126440.1297770.534351489−0.00390.4525680.7639854900.0322250.6972530.4734384910.006365−0.13366−0.26424492−0.02582−0.14697−0.40098493−0.013290.3474130.799548496−0.12522−0.40255−1.290414970.01042−0.2418−0.351144980.0043990.2510070.451326499−0.01108−0.24741−0.339245000.006845−0.13731−0.219625010.0098690.4866070.629945020.001451−0.16634−0.222455040.0033540.4289440.6383445050.0091450.5417830.6404685060.0022220.2444180.413136507−0.02701−0.27514−0.50565080.0186130.2230.514935509−0.00241−0.23143−0.26272510−0.00802−0.16617−0.43514511−0.002350.2579710.4530025120.0400320.4214330.627533513−0.03045−0.21394−0.69964514−0.06115−0.27077−0.83265515−0.01716−0.35696−0.63809516−0.05133−0.29445−0.522835170.009223−0.14528−0.197225180.0243060.2916880.612915519−0.0176−0.22202−0.316985200.0345550.4878550.723822521−0.24116−0.1809−1.51236523−0.0280.3505680.474606524−0.01417−0.35675−0.315065250.0056520.018971−0.43584526−0.00638−0.23708−0.606355270.0248281.0660961.01296528−0.01588−0.2259−0.702485290.0058630.2547030.2544735300.006005−0.11549−0.19425532−0.03536−0.32282−0.705785330.003023−0.19447−0.22887534−0.008870.3009120.41484535−0.02229−0.31605−0.62805536−0.01746−0.2479−0.37075370.0078450.6527930.694802538−0.0181930.1502840.2709795390.002643−0.21014−0.22848540−0.10813−0.23606−1.12333541−0.0173−0.21271−0.32485420.019658−0.04887−0.191645430.0052120.6984491.0619875440.0497010.30530.632118545−0.01576−0.26269−0.43173546−0.00177−0.16459−0.350645470.0044990.2860520.541283548−0.000360.2741030.3010375490.007366−0.13753−0.38447550−0.04882−0.32016−0.84231551−0.01520.3055260.3174552−0.02703−0.32147−0.99173553−0.05272−0.13234−0.518015540.018185−0.12473−0.179485550.0177480.4661240.7779135560.008038−0.17631−0.198375570.000468−0.22168−0.30063558−0.11451−0.38803−0.78032559−0.00090.072870.2680415600.0281920.2127340.313642561−0.12161−0.59358−1.61579562−0.007465−0.085295−0.4514085630.002504−0.08158−0.577745640.0248540.2341570.699992565−0.0133770.1899350.3583985660.0061480.82830.9881525670.001478−0.20409−0.292345690.0135130.2597740.3895545700.002998−0.14785−0.19082572−0.04096−0.21747−0.545855730.0277670.167470.3784485740.0195770.366250.620855750.00827−0.18984−0.214045770.0416650.4792580.630781578−0.01208−0.22961−0.570365790.0202340.4417290.519404580−0.01711−0.32502−0.33935581−0.057250.4226320.81318582−0.0174−0.16658−0.50015830.0213270.4566220.9927075840.0155260.4819360.6452185850.0256480.3130610.522952586−0.001250.1396150.4597495870.003988−0.14491−0.25971588−0.14462−0.51176−0.64378589−0.000820.015573−0.566755900.02049−0.04531−0.53244591−0.000390.5342620.755197592−0.04775−0.24053−0.50456593−0.02065−0.27304−0.27685940.0188190.3311820.288672595−0.00063−0.17735−0.18189596−0.027369−0.300983−0.6767285970.004781−0.26501−0.26476598−0.00272−0.36897−0.48838599−0.01164−0.27727−0.44042601−0.00966−0.10751−0.27903602−0.029470.1526020.288592603−0.00852−0.25099−0.300676040.012565−0.18969−0.12342606−0.04446−0.08468−0.764586070.0052950.1407450.3053856080.0484040.3928270.678865609−0.00583−0.2845−0.225766100.008709−0.12867−0.191836110.0147510.1522970.272206612−0.045630.157375−0.631296130.0012080.5451430.478695614−0.01227−0.34599−0.30686160.0083030.3101160.3344076170.0215720.2349660.409616618−0.02922−0.28728−0.30017619−0.0576−0.28502−0.754276200.0364860.2639990.326197621−0.01196−0.15869−0.388766230.0193760.2766590.32361624−0.00797−0.19147−0.34348625−0.05054−0.19751−0.74917626−0.0001−0.16253−0.575766270.014376−0.11856−0.195356290.0044730.2217210.4151946300.02181−0.17889−0.25501631−0.01378−0.18604−0.36808632−0.03351−0.11657−1.071366330.0209920.000039−0.313136340.052280.3560450.555225635−0.01133−0.35665−0.46195636−0.0052−0.22931−0.262846370.0340090.161140.5374736380.013030.5574820.950396390.0002690.2619430.4537196400.0078240.5143750.4454896410.004039−0.28474−0.69362642−0.02654−0.19434−0.283616430.0042150.2592260.4543286440.011035−0.188829−0.2361916450.006618−0.23616−0.189586460.005768−0.1888−0.183726470.000143−0.204−0.231156480.0290860.7951720.9203156490.011574−0.26945−0.424276500.0560190.8502010.9898026510.01505−0.04939−0.358716520.013020.0692930.3105826530.034272−0.31715−0.52764654−0.0085−0.16306−0.330496550.0276660.2017080.4301756560.0219610.3981410.3882526570.0108630.2322440.382436580.0021580.4418870.807217660−0.02496−0.23046−0.53717661−0.02486−0.27484−0.882626660.0060070.4294140.417403667−0.05507−0.22247−0.847666680.002160.1181850.2609376690.0388540.3918180.596807671−0.0359−0.25121−1.337946720.0317140.1283190.274932673−0.00491−0.32528−0.27831674−0.01249−0.29579−0.934496770.031550.286690.43691678−0.00818−0.23129−0.44976679−0.00242−0.23058−0.268576800.0497570.2692090.3666836810.0016020.047578−0.524066820.0228650.5448860.684953683−0.000051−0.16042−0.34528684−0.0076−0.28875−0.37374685−0.10296−0.46829−1.011846860.0035420.6230741.0078036870.0139240.2750940.562663688−0.00395−0.06428−0.45396890.009220.8713871.1834146900.0065710.4184030.5013886910.018275−0.11329−0.334056920.005479−0.20021−0.568066930.0160650.078890.5094616940.0352460.5205460.908218695−0.009930.0964730.324842696−0.04241−0.25184−0.463696970.0474590.3874420.5884066980.0313690.9493670.7794156990.002836−0.136336−0.204499700−0.0035730.1866630.111998702−0.0047950.436930.231795703−0.06028−0.31369−1.027267040.0036210.3197290.650712705−0.01483−0.20685−0.215787060.0142290.224220.5250727070.001577−0.09783−0.40964708−0.04664−0.34529−1.271097100.00051−0.260385−0.3252567110.002346−0.21907−0.20731712−0.02008−0.28454−0.838167130.0123030.3179330.3254427140.002157−0.15149−0.20467715−0.01341−0.28726−0.512497160.0175090.473790.6964017170.0083810.1816490.3552267180.0438770.671051.033417190.000274−0.20319−0.2538720−0.02417−0.10504−0.966117210.008385−0.16697−0.178117230.0039950.1659780.3371617240.0313180.2629310.5306977250.002671−0.22388−0.24884726−0.017410.975950.7972317270.0263510.2255210.5139687290.020650.1656210.3975377300.007214−0.100867−0.390067731−0.0053−0.24753−0.237657320.016166−0.23723−0.26246733−0.01548−0.23219−0.50029734−0.02537−0.18612−0.578157350.0112890.6260920.824474736−0.039680.3938520.572199737−0.01477−0.37806−0.769527380.014599−0.14944−0.159437390.0216060.40660.648213740−0.02684−0.1602−0.6932742−0.00331−0.21531−0.28527430.0415620.6101250.7147227440.010195−0.23868−0.522727460.0075150.9637170.900577470.0227990.0479650.2664297480.018810.3979860.4729187490.000816−0.18066−0.626837500.011577−0.18089−0.269157510.0159590.232930.296034752−0.00275−0.35468−0.25756753−0.00158−0.31664−0.350177540.0149540.1037770.342093755−0.00071−0.19677−0.195497560.013480.385430.649152757−0.01417−0.20752−0.450137580.0054480.5864970.766039760−0.06324−0.39472−0.96545761−0.04803−0.38169−0.822867620.004229−0.13539−0.229937630.020979−0.11787−0.47577764−0.014080.3062510.459896765−0.00132−0.15961−0.17249767−0.02884−0.17041−0.496417690.000097−0.14405−0.31241770−0.01516−0.36294−0.301477710.011930.2887310.5770957720.0124680.1320630.4724297730.0363770.1756910.4211567740.0209380.2920110.4146097750.0018040.2152510.408338776−0.01539−0.23391−0.326517770.008326−0.15574−0.151617780.021720.1794770.451299779−0.00330.1204090.6423827800.0197320.333450.690417810.0494640.6613730.6214147820.012342−0.18948−0.33074783−0.0155−0.21106−0.277217840.0240830.2739310.378123786−0.008690.2005540.342694787−0.039450.040775−0.7592789−0.0111350.0730250.220549791−0.036370.9593341.221178792−0.02054−0.35395−0.60127793−0.04991−0.27242−0.57387794−0.00593−0.34796−0.3923795−0.010290.2584790.340795797−0.04052−0.23779−0.615417980.0457750.4038040.8134927990.008074−0.16841−0.31739800−0.007060.2409220.3343878010.0163040.1425570.4099498020.0099120.0627220.253013803−0.00912−0.14396−0.214328040.0224450.3685060.476569805−0.04348−0.04699−0.733878060.04220.4037040.844882807−0.003760.7598290.986519808−0.00610.4148940.6509498100.0256450.2241210.479134811−0.06415−0.26997−1.46272812−0.04969−0.36744−1.108898130.0199760.4372940.712531814−0.002640.3637770.646788815−0.00046−0.19979−0.249878160.0092950.2735220.4912668170.0050980.3326140.5022818−0.02468−0.31556−0.42146819−0.009730.353170.3335128200.0139070.1820630.3667428210.036670.1760630.3126058220.016225−0.17943−0.28798823−0.05108−0.24513−0.919638240.00525−0.18863−0.231818250.0224760.3149850.518725826−0.001530.4131110.5656268270.006651−0.26096−0.451558280.0118970.5183420.800249829−0.00438−0.15288−0.512548300.001568−0.15148−0.55304831−0.00465−0.15151−0.234878320.008715−0.16021−0.23078330.010857−0.27968−0.6406834−0.002360.1027480.46468350.0147480.2382510.268061836−0.01 0680.3365030.498429837−0.01263−0.1071−0.45097838−0.01939−0.22991−0.52394839−0.00016−0.09603−0.22419842−0.02570.1802380.5346298440.007381−0.22632−0.296858460.026896−0.25572−0.44026848−0.01661−0.39972−0.97718849−0.01307−0.06095−0.441418500.010372−0.02883−0.412238510.0108840.4815560.677496852−0.0097770.0619730.2174138530.005281−0.20109−0.26239854−0.00896−0.14598−0.39826855−0.02612−0.10349−0.34689857−0.00174−0.01196−0.369498580.0359830.3633920.460554859−0.01618−0.19735−0.43419860−0.02435−0.07585−0.533628610.0031440.3271130.4797298620.0036770.3140810.5704068620.0125120.1011030.3469598630.0074510.2748640.258577864−0.02988−0.30442−0.610038650.0278810.2290760.4537848660.0165540.3348820.523243867−0.00904−0.22622−0.35397868−0.00683−0.14427−0.193888690.0074470.4561830.5789138700.014298−0.1555−0.37831871−0.01855−0.376−0.72345872−0.02113−0.05347−0.524874−0.10276−0.17356−0.647918750.0506310.3715670.5832428760.006277−0.17522−0.181628770.026906−0.16371−0.222328780.03110.4980370.731472879−0.06188−0.17245−0.70482881−0.003170.2519980.4731318820.0137990.1845410.4774548830.003912−0.20012−0.227648850.007449−0.15174−0.482118860.0283210.1957590.414775887−0.02561−0.25312−0.785148880.0206670.1010940.2791328890.0392510.8345831.008713890−0.01837−0.1427−0.381158910.0009750.2888750.7758538920.0443880.4427430.6394318930.0341740.6637340.752687895−0.0313−0.22239−0.45958960.0019950.3215560.3875788970.0020440.2349510.3494038980.0381210.4426560.544638990.0059280.120060.2543969010.036664−0.30177−0.355459020.0111750.3711030.6146969030.0162070.6196330.9179779040.0039980.1684210.202759905−0.08003−0.36991−0.747149060.0091530.1066280.432846907−0.004660.6006550.532454909−0.0164−0.38781−0.332559100.011684−0.28883−0.44642911−0.035790.5490780.508632912−0.04968−0.34888−0.82801913−0.00198−0.17084−0.19839140.0406610.3905450.4991579160.024181.1761810.7939729180.0398660.2816550.5789459190.0215580.6182840.670695920−0.001830.1095120.3040219210.0517820.418220.704089922−0.00581−0.29828−0.28228923−0.07327−0.1579−0.892489250.0190410.3650250.8628749260.0274570.2152970.3661489270.0033690.1103520.5047869280.000941−0.16168−0.17619929−0.01183−0.17313−0.25897930−0.04618−0.24458−0.820889310.0174210.7286060.6792569320.003436−0.16538−0.15426933−0.02288−0.07943−0.60235934−0.0015150.494370.3491629350.0431920.1554670.415401936−0.013320.2390280.4306349370.006872−0.15327−0.175869380.005084−0.09074−0.320859390.0142720.1795760.438968940−0.03475−0.29724−0.571189410.0205240.3324540.6848499420.0314810.3063970.4381969430.0156660.3011350.654813944−0.00517−0.32082−0.246019450.0171040.2837830.6068059460.0215710.2453720.496499470.028340.4341940.686041948−0.04565−0.14863−0.460359490.002425−0.27508−0.5014950−0.01103−0.35658−0.308759510.0172440.5726190.667183952−0.04401−0.3078−1.29359530.021905−0.21672−0.183739540.0143260.3073430.497944955−0.01014−0.28982−0.28704956−0.04652−0.28568−0.64755957−0.005990.0096690.356692958−0.001380.131550.339588959−0.05625−0.17665−0.57717961−0.02031−0.16875−0.39111963−0.024440.1609980.5266019640.0215770.1143270.3619679650.0101290.1843280.3551739660.0434470.4762250.800959670.0118530.3802020.54573968−0.02322−0.29491−0.396749690.005774−0.20359−0.31987970−0.036690.020952−0.785049710.0721520.4399440.9701339720.007861−0.16402−0.20729740.0229860.1913530.3668819750.0314310.3099870.6219389760.011977−0.20413−0.180179780.03035−0.08794−0.261329790.0240460.3800120.527625981−0.02969−0.39102−0.646589820.042540.2650780.600318983−0.009189−0.179037−0.279808984−0.09009−0.15535−1.52231985−0.01148−0.18115−0.30972986−0.00499−0.24362−0.38006987−0.00309−0.16729−0.18861988−0.00048−0.20341−0.219829890.032610.2987250.6001479900.0068070.3128970.452625991−0.04519−0.23−0.67622992−0.02925−0.26477−0.67592993−0.00823−0.07657−0.550879940.007742−0.18516−0.372689950.0182820.1354550.283378996−0.0016−0.17755−0.220219970.0051160.3210960.3188559980.014517−0.20872−0.188419990.008411−0.25078−0.1784810010.0141140.2798410.48707410020.006213−0.20625−0.191381003−0.01909−0.06829−0.6008210040.0004040.6816580.7639171005−0.0042060.2646130.4069121006−0.02649−0.15549−1.281211007−0.001170.4084470.5849521009−0.05018−0.36597−0.487781010−0.000530.255520.5536251011−0.02185−0.15114−0.3387710130.010628−0.19019−0.190311014−0.0270320.2184310.36987410150.0186760.2799770.4112381016−0.03486−0.21403−0.661751017−0.00635−0.1185−0.269011018−0.1021−0.35522−0.928781019−0.0324−0.05782−0.434521020−0.004020.3525910.5894091021−0.02319−0.24806−0.23611022−0.002070.2304910.4950731024−0.11797−0.46245−1.0021025−0.014310.3365620.38284910260.0186030.2207770.3273281027−0.110230.028131−0.649831028−0.04121−0.34023−1.1637610290.0000380.0731280.35682210300.011849−0.24586−0.3510310310.016593−0.15782−0.2024910320.0330090.2029370.39680910330.0003990.3491910.4116581034−0.01282−0.19304−0.697361035−0.04048−0.28852−0.5842610360.0184570.1501210.2820321039−0.00901−0.22817−0.287911040−0.02948−0.28206−0.281261041−0.00327−0.10615−0.3823410420.0303210.199160.3089771043−0.03145−0.24414−0.9741910440.0195750.0623650.38815610450.0102580.1737010.3318311046−0.02510.1498570.3332231047−0.003750.2501170.45455210480.0349810.2492280.4875581049−0.04425−0.33632−0.80631050−0.00768−0.17663−0.3434510530.062610.781430.86841810550.0194690.1780760.5244381056−0.06308−0.26881−0.417210570.006551−0.42887−0.5387410580.0235350.500370.59971610600.0045920.3807190.65633510610.0219650.2087960.52357410620.0250670.3579620.5318181063−0.008340.5635540.85916610640.0124270.3557330.55398510650.0173770.3573650.56284910660.0073020.4349510.81262810680.0176370.4016770.4255261069−0.02752−0.31181−0.916881070−0.02093−0.18417−0.363021071−0.00263−0.14252−0.279971072−0.05215−0.06966−1.076661073−0.02875−0.12441−0.664410740.004721−0.03479−0.3326410750.0128180.1005040.2932131076−0.047660.5808870.6674471077−0.01309−0.17865−0.2416110780.0119270.0654310.30547910790.0167930.5108370.67080410800.0244050.3419920.6294131081−0.00395−0.03511−0.413531082−0.020.3118050.35733410830.0171460.2253440.44143210840.0244640.1318990.30300410850.021970.4163740.73414510860.010730.1129160.4538481087−0.01838−0.15669−0.5449810880.0183140.5471870.4608081089−0.0569210.2653450.48813810900.0236260.0857680.54973710910.0103880.2782950.44966910920.0311640.7413990.65044310930.0290090.3669460.3508241094−0.057850.0682340.38378910960.005542−0.21656−0.2677810970.0006931.0271830.81762410980.0034620.5705490.63617510990.037640.1543190.3211771100−0.026376−0.1074880.12057911010.012177−0.14239−0.1790811020.0250670.2907260.47470111030.0020980.5724340.4969891104−0.038080.5781970.6075711050.0355171.3479170.84326811060.0132750.0531450.2848041107−0.031820.059138−0.614861108−0.02981−0.17465−0.9300311090.0166060.2309110.31563711100.0330770.2706560.44420911110.0166240.316070.5683111130.011372−0.22076−0.188231114−0.01167−0.16839−0.5638911150.0252860.332270.59299911160.0089120.0444170.2555181117−0.033080.3168850.450631118−0.07635−0.42718−1.1791119−0.00971−0.20014−0.442611120−0.0004−0.09832−0.245811121−0.027830.01481−0.5206511220.0349770.9036760.7529221123−0.03938−0.12671−0.895781125−0.03756−0.25992−0.321281126−0.022630.4380010.5410051127−0.02351−0.21881−0.337821128−0.042530.3704190.51178211290.0152410.4275150.72910611300.01660.321080.4797251131−0.01176−0.25284−0.617881133−0.03665−0.32606−0.9890111340.0065420.3356450.4173381135−0.01257−0.26131−0.431661136−0.00908−0.04902−0.424291137−0.03391−0.14525−0.419311390.0025030.2122910.32694911410.026550.4115720.48752411420.018869−0.08067−0.3310211440.0008810.204460.3561941145−0.003373−0.121256−0.28882311460.0120570.5030470.76683211470.017324−0.15498−0.1286611480.0146540.5801630.56995911490.005960.2263720.53238211500.0141930.4003760.6025911151−0.04481−0.36921−0.5934611520.0026550.2138230.316251153−0.000940.6383680.9733221154−0.03225−0.28277−0.454941155−0.01660.1989750.3318511560.0153010.2423370.41974911590.0275060.3537940.6513151161−0.036419−0.112814−0.2899791162−0.01107−0.20437−0.2525711630.0191380.2325560.31560311640.0069380.2938180.32869211660.006071−0.17796−0.256461167−0.015230.3663070.56985311680.0250430.1357940.32997611690.009461−0.11973−0.220211710.0022630.1222440.29659611720.0093290.2537370.41723311740.0408780.6786480.87816911750.0151550.3633920.53024711760.0081890.196670.21630711770.01844−0.06651−0.1804711780.0061440.3609870.47389111790.008132−0.18457−0.266721180−0.0030150.1494850.24315211810.0123960.3807190.56032411820.0245930.385965−0.454461184−0.00575−0.18627−0.1445611850.017383−0.19347−0.434811860.0127560.2064340.4283431187−0.01855−0.24637−0.279991189−0.02801−0.19253−0.506741191−0.05399−0.00446−0.7711911920.0214750.2863490.45967311930.005136−0.2011−0.288281194−0.01826−0.21315−0.4936511950.0103770.498890.62969411960.01497−0.12611−0.2381811980.010758−0.09252−0.776591199−0.021051.1212810.79346212000.012658−0.11724−0.146721201−0.08507−0.26107−0.917861203−0.00142−0.12588−0.384741204−0.03462−0.12201−0.862821205−0.010140.213710.38201112060.0091310.2187450.42402812070.004704−0.012450.59383312080.024320.3208490.40232112090.0164720.4427690.43245412100.0529410.3944560.65763712110.0033050.3180150.65400312120.0111720.3570950.58877212130.0199490.2013690.5027112140.0180470.3542270.6540531216−0.00689−0.18258−0.1883212170.0198840.4031710.56908812180.004345−0.222−0.5830512200.0431710.7431220.8184231221−0.01673−0.29039−0.9141112220.0178480.2994270.4022361225−0.005810.0241240.28178112260.022046−0.13504−0.25921227−0.00376−0.2512−0.320981228−0.00739−0.2564−0.333081229−0.018390.5112720.7179461230−0.007110.3055140.53305112310.0374690.6134470.56635912320.0096660.1364010.266441233−0.006550.5034640.56358912340.003295−0.168464−0.2339291235−0.01657−0.23722−0.4469612360.0032710.2989490.53939912370.0258430.1138910.5274521238−0.003580.9263680.7585911239−0.014050.3822830.7586991240−0.00226−0.18271−0.256261241−0.02257−0.30133−0.8553312420.0128980.1957080.35228912430.004795−0.20695−0.38291244−0.053490.4534190.5086431245−0.06682−0.191−0.7739212460.0295240.1969780.46264712480.0341580.3536520.50256412500.0292490.3390360.45208312510.003557−0.23636−0.436712520.010304−0.10733−0.118731253−0.00495−0.24998−0.2313412550.0342830.3595010.45337812560.0294140.540190.7220061257−0.013210.5976740.6779031258−0.02966−0.28207−0.347312590.0378580.6313980.88066412600.0124790.158260.2519381261−0.04607−0.35607−0.8752312620.0321080.4006890.74031112630.0260030.1719050.3040261264−0.00432−0.14192−0.2899812650.0453580.2655580.42142912660.004985−0.24648−0.4558612680.019584−0.17999−0.1874412690.014640.1996960.3754171270−0.04419−0.09453−0.901111271−0.0335−0.24235−0.4104812720.0226580.2159620.33683712730.0136570.3220770.3618421274−0.005280.4529850.48414312750.0270950.1251920.30954612760.0227060.345970.5686712770.0572210.2287460.52240412780.0222880.2166960.40435812790.0115030.2214810.29556712800.0264460.3143270.4465941281−0.02678−0.28869−0.431941282−0.03664−0.23212−0.535212830.0042790.2918870.37716112840.0005880.1305530.4288641285−0.06086−0.27789−0.978131286−0.01709−0.07024−0.464011287−0.09316−0.29114−1.168491288−0.0251780.3935850.5663521289−0.007010.1591810.49926312900.0195820.3534490.48909812910.0334490.3342950.54318312920.0177640.5767650.825811293−0.00263−0.32052−0.7943112940.0135730.4451780.58802612950.0093770.3235220.47399812960.0111370.5873710.667521297−0.04222−0.11578−0.599891298−0.01041−0.17175−0.3499812990.0052810.7433110.7411941301−0.005380.2354710.38888813020.0201690.1196380.3510791303−0.02888−0.11932−0.4852513040.0208140.1995390.67755313050.0086890.3435360.40699413070.0073560.4284070.466051308−0.051939−0.225136−1.14209413090.0053950.3421720.44303313100.0003160.5185690.5852381312−0.01431−0.18005−0.4983713130.0304940.1674020.47294513140.0201660.3133460.41452313150.0547480.4519250.83038613160.0046130.2926230.38857713170.00910.0208120.34078613180.0146140.4024440.50314413190.028630.4747090.73885213200.0304760.7560530.98261513210.001629−0.29821−0.2985513220.005325−0.2292−0.423131324−0.005260.364230.42437613260.033310.1947190.4257813270.02320.291620.33075113280.016117−0.125314−0.19333413300.0167890.1826360.34649113320.0059760.2545640.3568741333−0.005040.7683391.0026211334−0.0031940.078374−0.58541113350.0008350.2229680.34234713370.00182−0.19066−0.2349913380.0323850.1610680.47724413390.0146180.7513560.94454213400.0321220.4669010.64857613410.0219170.2080590.30777613420.0187340.5423540.8224061343−0.00563−0.19206−0.2352813440.0186210.2927520.26911313450.0101440.330470.612511346−0.02857−0.28307−1.0343813470.030260.3679450.52837213480.0150110.1926410.501741349−0.00353−0.14764−0.2033713500.0323190.0142090.510813510.0183540.3805670.5936331352−0.013243−0.259131−0.72449513530.035392−0.05243−0.377381354−0.02446−0.22995−0.659221355−0.01664−0.19935−0.274681356−0.03214−0.02532−0.8128713570.008521−0.34216−0.4273313580.0154620.278660.64527213590.0239890.1218330.38351313600.010781−0.18127−0.152913610.0260420.3531570.62305413620.003863−0.23455−0.33011363−0.03543−0.25903−1.167371364−0.00654−0.19963−0.604031365−0.02165−0.12628−0.3323813660.013687−0.15116−0.234551368−0.01815−0.18952−0.691391369−0.060130.032736−0.9465113700.0280470.2806690.4863313710.0092330.2569920.4018491372−0.00438−0.25873−0.5833913730.0203130.6095720.91253813740.00521−0.18885−0.2724513750.003456−0.07589−0.4719113760.0252570.3367020.3424213770.0449330.3687290.37433413780.0159940.2201070.5625713800.019559−0.18793−0.2435713810.015070.7386920.6958331382−0.00849−0.1489−0.241621383−0.04272−0.27617−0.997651384−0.03381−0.33113−0.896081385−0.06548−0.40109−1.306471386−0.006090.1468010.47984613870.0136370.1284140.5621113880.0176220.0290030.28613413900.0045080.3729770.67264713910.003613−0.23198−0.3148613920.0177670.2718950.43257113930.0331740.6333480.8532921394−0.022210.6210030.79364413950.0001570.5188130.5504431396−0.008610.2132810.42290713970.0142660.1639620.19648513980.0217450.4525570.5304161399−0.001010.2621920.6673071400−0.034692−0.392913−0.8553721401−0.038280.4511750.6850841402−0.09483−0.42459−1.1625714030.0169890.4797430.6349461404−0.03076−0.18561−0.7535814050.0132860.3136710.491614060.0154570.2340710.3754411407−0.00814−0.17416−0.631021408−0.02704−0.28184−0.9923114120.0242520.2243210.5197181413−0.04924−0.18212−0.4786214140.0159230.456820.58442214170.0069980.4871010.5378851418−0.0141−0.27303−0.259221419−0.01389−0.31268−0.498681420−0.01003−0.08542−0.524781421−0.03398−0.29302−1.5129414220.0175880.3423590.58305614230.014237−0.10384−0.4690714240.008310.1399540.48563214250.019320.284380.3854481426−0.12693−0.40622−1.137421427−0.004580.1234410.4386351428−0.01252−0.30184−0.494211429−0.008990.0617330.42107414300.0319130.4414980.7632281431−0.020150.3160710.3178731432−0.00569−0.28524−0.21661433−0.0028−0.0174−0.558414340.0128350.0794220.40563814360.007760.1414420.47522914370.0153110.3798260.4828441438−0.0554−0.17035−0.6633414390.0279060.3654610.3479871441−0.01263−0.13879−0.33761442−0.024660.005115−0.5441814430.0249480.1501950.41899214440.0043660.6533990.5959641445−0.02−0.18717−0.3857414470.0125920.1482410.3275861448−0.000610.1844860.31518714500.0119630.3805940.48526114510.0004310.3456940.4251811453−0.00975−0.2067−0.36331454−0.014980.1452030.36210914550.0335460.2460960.41341814570.0014520.8064690.88004914580.0023330.3644290.57383514590.0069210.1997190.26947514600.0156690.40890.47751714610.0220910.8192770.7776431462−0.003510.3055030.4269731463−0.02995−0.25237−0.479161465−0.02790.6001830.5107331466−0.011950.2503780.3791881467−0.0752−0.22959−0.952481468−0.05201−0.24888−0.915631469−0.01809−0.24602−0.2663214700.0107160.2217320.5728321471−0.025160.2568860.56667514730.007390.7209570.6539031474−0.01891−0.35534−0.6996514750.006673−0.26152−0.474311476−0.06571−0.13156−0.7506214770.0250570.2525850.41563214790.0022650.0956330.3619841480−0.00258−0.31055−0.7275914810.0008070.166790.3764151483−0.02429−0.27549−0.412114840.009480.220980.58743814850.0314230.1613230.37289714860.0255270.5037570.6000761487−0.02211−0.04469−0.4148114880.0266680.3896110.4585411489−0.0058250.1713990.19889114900.012848−0.13059−0.2789814910.0095650.2782490.41131514920.0213420.5068820.62482614930.0157180.1819330.4792914960.0135990.4290260.49577514970.0245940.4411410.6095811498−0.02213−0.09246−0.483391499−0.00567−0.17376−0.270311501−0.00667−0.18173−0.302211503−0.0108460.339610.3443461504−0.06109−0.27532−0.999291505−0.018090.2006740.36434415060.0230440.1131550.36889615070.0260590.2630470.47170415080.0335350.2565860.320191509−0.0239−0.03673−0.3574315100.033680.343750.51075815110.0105370.2774340.4329171512−0.009690.10480.43368115130.0017540.1230490.16759515140.0304310.2038570.3187611515−0.005090.1258180.32676815160.0173550.2701160.49917415170.0171650.3370020.58363315180.0036250.4648030.52503515190.0229470.4222690.51384715200.0243720.0865030.3367291521−0.00251−0.32015−0.612721523−0.02740.2032630.44166415240.0173890.2018760.29855215250.0088770.3232430.4645021528−0.03814−0.28518−0.6455815290.0403590.2911330.44043715300.0132530.2175640.3729461531−0.022130.363120.4247091533−0.006950.3221660.39489315350.010588−0.22576−0.256351536−0.0106−0.25536−0.2361537−0.0322−0.27265−0.3965915380.0118850.2046770.43159915390.0080230.4885430.6498841540−0.02315−0.16887−0.4398415410.009146−0.14302−0.3194715420.0154910.3868820.6304615430.019390.2354710.4385621544−0.00477−0.05625−0.3976815450.01744−0.11171−0.1547115460.0171380.1592880.28080315470.0084540.2047830.37350815480.0069460.1171290.37003115500.006569−0.17032−0.2104715510.010456−0.16989−0.2171615520.0302110.1852620.28009215530.0271680.5240540.55233615540.0253220.4442690.54777715550.0074270.0981150.32385315560.0074210.2212840.29020615570.0262520.2611430.4957661558−0.04298−0.28254−1.010181559−0.057110.7327320.78174715600.005559−0.19059−0.293481561−0.02338−0.13568−0.4096615620.0252810.6041430.6845831563−0.032430.4833880.5078091564−0.006860.1212160.4649411565−0.01559−0.34333−0.3852415670.0279370.3920110.69466515680.0039470.3066490.25287115690.01190.0505540.347031570−0.016130.2917680.4335491571−0.03333−0.03399−0.542511572−0.028710.3089570.46184715730.008427−0.19856−0.178341574−0.009660.061794−0.505231575−0.04733−0.23751−0.3421515760.0307220.3090890.5796011577−0.04503−0.32515−1.4751315780.0131080.1735410.32589815790.0395730.4557840.59310815800.014880.1673810.33744815810.015780.9660150.74721315820.021767−0.06571−0.222011583−0.033770.9577430.95213915840.0001020.3751680.42744415850.0122210.3647570.4980081586−0.059680.1312140.2319791587−0.001290.2568180.3543981588−0.020640.2517690.4482261589−0.00735−0.29792−0.4653415900.000483−0.24237−0.5602815920.0059321.0512921.0738115930.023196−0.1622−0.448211594−0.00259−0.26185−0.4220215950.0163220.2450380.4012391596−0.0122670.3150770.46298215970.0138690.6267530.56970715980.016480.443010.7022871599−0.00148−0.17565−0.3006516000.0216850.2735280.47167516010.0115570.1340170.3006551602−0.03634−0.1835−0.374051603−0.05299−0.10304−0.7616040.0277670.4645550.6357431605−0.01022−0.11629−0.7045916060.0163580.1573950.27513916070.0257920.3975090.6721541609−0.01086−0.01430.3809831610−0.03769−0.15816−1.1458116110.0265360.6110730.63777316120.009768−0.17633−0.2021916130.0186720.6398350.6861311614−0.00595−0.17151−0.412251615−0.03355−0.29946−0.406161616−0.005050.1074020.156991617−0.04052−0.29872−0.683891618−0.006681.1118671.05392116190.015573−0.03576−0.2132316200.0206090.2864740.3932241621−0.00870.3239350.33901616220.0222520.2652310.49929816230.03090.4981980.6571981624−0.003494−0.128858−0.4162831625−0.05632−0.39999−0.438861626−0.01350.3148840.64904816270.0287720.4886790.75976116280.004670.4274850.58806316290.0021550.7649250.73209416300.0254180.225080.314061631−0.010460.2091150.3869831632−0.010490.8780230.77556616330.0255320.3425070.50273816340.0154810.5602520.5384291635−0.043530.2597420.65924916360.0202750.0933390.36106316370.0072080.1574070.254871638−0.04262−0.28323−0.8757916390.0514210.4919450.6531171640−0.010180.3472680.5880211641−0.04504−0.35082−0.898881642−0.02474−0.25739−0.476191644−0.01609−0.09535−0.59321645−0.03235−0.16356−0.3966516460.0289680.322580.52016616470.0321730.5900620.8112581648−0.02776−0.13951−0.50181649−0.002720.1633070.25352416500.0192660.4387980.49908916510.005638−0.13247−0.313811653−0.000210.0905480.2953771654−0.005−0.24979−0.536881655−0.073590.053071−0.9151116560.0076970.4690610.57056316580.02950.192960.35948416590.0102310.9023530.8040321660−0.00649−0.15261−0.177316610.0122190.6139120.5499351662−0.06415−0.43774−0.434721663−0.0078−0.18865−0.1695616640.0164520.1225480.3182951665−0.09894−0.44748−1.1883516660.0071630.4506310.6578416670.020618−0.152906−0.0735141668−0.01219−0.23803−0.2491816690.0299240.4525120.7804916700.008377−0.24035−0.390031672−0.02109−0.04326−0.96141673−0.0073−0.28445−0.269116740.0010520.2303890.3655511675−0.002280.2354540.5553811676−0.035230.2795160.55600516770.0144960.7000220.7725681678−0.00423−0.26803−0.594741679−0.017490.0642390.39328316800.014303−0.15699−0.5294916810.0036970.1318170.3177341682−0.00306−0.17935−0.309641683−0.00440.1527420.3568691684−0.07893−0.43101−0.575061685−0.026−0.35847−0.5081416860.016683−0.18902−0.18421687−0.01704−0.2493−0.2375916880.008536−0.19671−0.1661216900.0342810.1684940.2979681691−0.04203−0.24984−0.5865716920.0405460.20540.4099341693−0.009290.1136010.33014116940.0225390.3512810.47096316950.0298920.2677050.4866441696−0.00019−0.22543−0.492381697−0.01354−0.06666−0.5442516980.005153−0.16834−0.2409116990.019570.2163290.3994871700−0.038220.049127−0.796411701−0.020740.3579890.537941702−0.013780.1909930.4245591703−0.05184−0.19677−0.7863217040.0255770.2108630.32397617050.027740.3054470.72429217060.0177410.352520.6400831707−0.10203−0.508005−0.43394817090.0034480.2501310.2652641710−0.021080.1350590.62951713−0.0000330.2271190.2932111714−0.004180.2633710.40627217150.021060.3368230.53312117160.000778−0.28099−0.3459117170.0674550.3406270.534871718−0.00514−0.18407−0.4494317190.0251750.1994870.34382917200.0103430.2824490.4768961721−0.06784−0.30027−0.866351722−0.029540.3725420.46487217230.0141270.378860.6006331725−0.03063−0.15378−0.6685217260.005904−0.22601−0.3931217270.0165040.3197580.474731729−0.038970.8060081.0673721730−0.0123−0.28524−0.296917320.018434−0.15661−0.142471733−0.02347−0.17755−0.5709317340.0184220.1896450.38217117350.0239110.1652440.3913111736−0.01529−0.19416−0.420517370.009313−0.12753−0.231841738−0.05497−0.17588−0.457261739−0.00577−0.13309−0.6185417400.0001290.0826480.20270617410.0036930.2258270.34568917420.0316050.0893720.31214217430.0103640.3489080.3679081744−0.02434−0.091440.1561561745−0.02231−0.20802−0.226451746−0.04199−0.25892−1.004361747−0.01659−0.1995−0.301641748−0.03118−0.26385−0.3996317490.001133−0.16781−0.228771750−0.0074−0.24548−0.529617510.0308460.507710.5647821752−0.00230.5572870.44755417530.044274−0.18457−0.1741817540.0054580.2586690.43850717550.0267090.2659360.4331341756−0.07289−0.28387−0.8740517590.0175640.2315650.5888961760−0.00904−0.20562−0.229717610.0344790.1437450.28147817630.0020590.4226890.66130717640.0159310.3810830.6018511765−0.0696080.229406−0.9428881766−0.011090.233710.47414717680.045070.2297230.3454611769−0.076270.1561280.25049617700.011440.3469820.4909841771−0.02162−0.28795−0.2780717720.0192250.2361770.44134117750.0229180.1837740.30186617770.0109110.1186110.2091981778−0.05232−0.2939−1.1819117790.0114740.2671020.35354817800.0327060.2339020.4808011782−0.00163−0.14093−0.2697317830.0301670.1803560.29933717840.0154010.5949290.8620541785−0.002640.2918940.365071787−0.01282−0.21492−0.3430617880.009731−0.13302−0.116451789−0.00598−0.0331−0.2812517900.008607−0.16296−0.2006217910.0024380.3887320.32992217920.0019590.0238720.20833417930.0100730.4048280.4267441794−0.03895−0.21887−0.58351795−0.0592−0.09279−0.447371796−0.0262−0.25466−0.216551797−0.12257−0.31528−1.522317980.0068630.1256180.17983318010.002794−0.12806−0.337441802−0.006187−0.271892−0.5472141803−0.02679−0.23885−0.4607918040.007217−0.21745−0.208091805−0.11509−0.38375−0.602231806−0.02318−0.33783−1.072631807−0.00505−0.2652−0.3581318080.0047540.1697660.3458441809−0.01864−0.17631−0.302831810−0.01537−0.11929−0.498321811−0.02414−0.22298−0.563071812−0.05789−0.46577−0.6711618130.0049290.074195−0.389021814−0.12994−0.5422−0.6739418160.000462−0.29172−0.786291817−0.05267−0.08425−0.5620918180.0219280.1039570.6121971819−0.04001−0.08007−0.6215218210.0123660.6082220.81180218220.0087090.0585350.17278718240.0559011.0192951.141661825−0.01941−0.32585−0.3533818260.0248150.3591430.5862031827−0.01719−0.20544−0.218551829−0.03510.3823620.46307418300.012246−0.22063−0.174541831−0.01595−0.15761−0.4007318320.0189620.220870.56699418330.0296530.0340920.2533651834−0.01445−0.24365−0.303841835−0.02682−0.22033−0.325681836−0.09901−0.30331−1.4741418370.0302380.2396520.47062818380.002423−0.19623−0.57611841−0.03342−0.13149−0.6676318420.0293580.3371170.45963918430.001903−0.21172−0.374061844−0.03995−0.30379−0.417431845−0.00479−0.13037−0.307561846−0.00041−0.34946−0.659831847−0.00414−0.14024−0.317721848−0.01386−0.22644−0.3293118500.010790.2119820.3264171851−0.02231−0.2043−1.1904618520.0151810.1110860.2519671853−0.01527−0.28004−0.4771518540.000932−0.24516−0.2845418550.0335970.1848150.2655541856−0.03302−0.34634−0.7655418570.005193−0.22844−0.627291858−0.05483−0.30502−0.8293518590.001499−0.10385−0.3232918600.0131050.2104620.24899318610.0086750.4965610.92709118620.010826−0.21583−0.308591863−0.02181−0.43456−0.942641864−0.01059−0.24026−0.506071865−0.013820.3745210.5552371866−0.12558−0.46355−1.2184818670.016134−0.25351−0.5705218680.0015770.3725090.346091869−0.14247−0.50568−1.114691871−0.03321−0.44414−1.207418720.0227550.2373580.52671218740.0158510.3986750.46173118750.0281640.2909710.405341876−0.003630.3304910.4724811877−0.01271−0.28482−0.412471878−0.05324−0.21202−0.974941879−0.012310.2721850.5014518800.009419−0.16361−0.2856818810.0240080.3854280.5105051882−0.01343−0.30202−0.2511718830.0199950.2306820.2738891884−0.02340.359630.44484418850.0261380.2130970.3838051886−0.008910.004522−0.568891887−0.00744−0.28972−0.5569118880.0167430.3033480.42923518890.0014910.1454510.3606231890−0.00739−0.14358−0.515511891−0.01196−0.17613−0.298651892−0.04341−0.18291−1.3293718940.0363740.3088750.3470831895−0.01486−0.35427−0.7527218960.020399−0.17097−0.2899618970.00121−0.17923−0.196331899−0.02719−0.20241−0.704061900−0.00544−0.1899−0.314521901−0.02757−0.18302−1.1428119020.002335−0.21384−0.3012419030.0220390.2365330.4518281904−0.02356−0.35422−0.5989319050.0121930.1494760.3247081906−0.018987−0.066969−0.2678319070.0060330.1100370.28489519080.001763−0.19256−0.249061909−0.03746−0.27994−0.989121910−0.014553−0.104128−0.2026991911−0.00195−0.19606−0.260831912−0.00425−0.25347−0.325481913−0.09292−0.0302−0.945191914−0.01006−0.17543−0.7241719150.016217−0.11786−0.335241916−0.23712−0.79448−1.1798719170.020851−0.31695−0.307971918−0.00017−0.20379−0.4229519190.0037610.0797210.314221920−0.01211−0.21388−0.235051921−0.23852−0.78111−1.157031922−0.01943−0.36905−0.847021923−0.11396−0.29114−1.283131924−0.02134−0.19369−0.8797219250.019202−0.23042−0.3161919270.0161890.022638−0.2101031928−0.11288−0.43825−1.018881929−0.15456−0.55089−1.753871930−0.04421−0.41059−1.080441931−0.02591−0.15838−0.647111932−0.03919−0.38915−1.4027619330.0174220.399760.609261934−0.09323−0.42485−1.399821935−0.00778−0.23173−0.650591936−0.04034−0.37519−0.849271937−0.001280.2219310.2606651938−0.02216−0.35136−0.766241939−0.04121−0.30657−0.738421940−0.00255−0.03829−0.6088319410.001721−0.28062−0.726851942−0.0357−0.30908−0.9994619430.0017240.2585810.2406671945−0.02465−0.27186−0.860811946−0.08093−0.47696−1.432261947−0.03385−0.32059−0.328619500.002196−0.17359−0.1967219510.006991−0.20072−0.253291952−0.00608−0.40942−0.7357819530.005028−0.15884−0.169451954−0.01496−0.38759−0.806251955−0.00401−0.23755−0.26861956−0.0131−0.35273−0.478461957−0.33149−0.64113−1.6735619580.0117060.1585740.30792419600.0018430.6201710.79109219610.0072720.2093980.4070651962−0.03168−0.28618−0.393731963−0.03105−0.33984−1.103171964−0.02235−0.19517−0.603351966−0.01351−0.15096−0.501091967−0.0447−0.30407−0.7766619680.0188180.6328141.0067891969−0.02596−0.08579−0.55931970−0.00539−0.12713−0.514891971−0.00231−0.27674−0.5318319720.011694−0.16092−0.1715119730.0252220.269645−0.25499919740.005887−0.23322−0.310219750.0102730.1586690.37597119760.011640.0694510.3027219770.0031530.0201070.29116119780.0102750.0353430.2909661979−0.007260.2901230.4127219800.0272740.1144470.3176921981−0.00299−0.18464−0.1865519820.003371−0.20588−0.275551983−0.02234−0.24084−0.255631984−0.01421−0.27928−0.473621985−0.01976−0.32802−0.5023719860.0075110.1406530.3812451987−0.07456−0.17753−1.535761988−0.11518−0.48269−0.62961989−0.02835−0.34393−0.5148319920.0252320.103730.2127541993−0.010010.4950770.43126519940.0115640.1993550.295281995−0.08513−0.34241−0.7585819960.009808−0.08644−0.667231997−0.00362−0.24336−0.585731998−0.027543−0.140155−0.69991419990.0106020.3818860.46686920000.0052320.0904120.3037922001−0.04158−0.10036−0.7571620020.00709−0.25448−0.4286220030.0203280.3490020.5400232004−0.10392−0.26626−1.145522005−0.00395−0.14092−0.8125320060.0189240.162050.30164320080.017035−0.18494−0.324942009−0.0108−0.2725−0.6025720100.0627150.8583991.0707112011−0.00319−0.23151−0.4070720130.0164260.5851050.73507220140.015113−0.07451−0.2561520150.0157060.2270530.4340432016−0.01066−0.06296−0.2656420170.0297940.2960550.35155920180.0296920.4372820.89888720190.0214970.0436230.28706820200.012762−0.000580.24970620210.0191740.2981940.5396252022−0.009530.157470.37858320240.0027460.0216350.2403662025−0.018670.1482420.39305520260.0124090.297720.5377532027−0.10141−0.42795−0.960112028−0.04498−0.43649−1.457092029−0.006980.0842080.2267752030−0.01906−0.07943−0.373620310.0373430.1351450.34501820340.0162880.264750.3644920350.006041−0.39239−0.277920360.005805−0.16315−0.1876620370.008439−0.20905−0.208922038−0.04899−0.25655−0.6555920390.008925−0.17251−0.1647120410.0252590.4726690.60244720420.003359−0.068862−0.1308222043−0.02582−0.14361−0.6628820440.0090580.2719750.40151520450.0033750.4812130.5819920460.0302470.2024170.3606152047−0.01954−0.24101−0.5226520480.020790.1229790.28702720490.018410.1286830.2971372050−0.07838−0.3133−0.8183920510.0356550.120480.32555820520.0195670.2086630.30519220530.006616−0.14349−0.2510920540.012830.7637071.30496320550.0111990.1458670.39172320560.017212−0.089889−0.16057620570.020607−0.18267−0.208392058−0.010110.2345980.453920590.0284850.9753271.0389842060−0.00122−0.11435−0.2634220610.007696−0.15684−0.413572062−0.10026−0.36029−1.44282063−0.0135−0.27765−0.7330620650.0139470.0891980.208722066−0.00563−0.28159−0.252682067−0.034481−0.314757−0.57100520680.0148920.2344830.34153320690.013673−0.24452−0.317462070−0.03035−0.24676−0.3361120710.0167160.0699540.2749272072−0.00023−0.14279−0.1887520740.0201030.3979080.35805420750.000883−0.16172−0.2755520760.0048590.171270.33249320770.01037−0.21565−0.188882078−0.01703−0.29207−0.335320790.004482−0.13823−0.19882080−0.004230.2649120.5389552083−0.01884−0.22222−0.5498320840.0024290.1917390.2869462086−0.11171−0.3468−1.662022089−0.00222−0.2653−0.229052090−0.00873−0.25551−0.3928820910.0178630.39950.5633142092−0.02737−0.29124−0.5479220930.0014380.3933120.6450132094−0.001610.3291790.5994672095−0.04662−0.4555−1.3934520960.00868−0.14575−0.160842097−0.010690.4383070.53055820980.005224−0.1524−0.571372099−0.00512−0.23121−0.2058121000.01594−0.11251−0.153432102−0.03821−0.13991−0.373792103−0.0791−0.56806−0.769432105−0.00320.1849210.61302221070.0282120.4768910.55763221080.016664−0.18764−0.1998321090.0243440.2707970.43436821100.0169460.260320.4065672111−0.03403−0.18774−0.476932112−0.03586−0.18075−0.819042113−0.03026−0.30742−0.7197721140.0475531.2603441.1565522115−0.01266−0.26929−0.31552116−0.09454−0.21809−1.425352117−0.12163−0.41838−1.705652118−0.03225−0.24102−0.43282119−0.0277−0.23099−0.7640321200.00625−0.06197−0.479912121−0.01834−0.27363−0.9041421220.0117650.2535160.39882521230.00067−0.1136−0.4814721240.017464−0.20661−0.223462125−0.0182−0.13711−0.282222127−0.0426660.6897940.24863721280.002977−0.20398−0.244832129−0.051430.8036660.88710121300.00574−0.21235−0.293822131−0.00303−0.18488−0.881682132−0.0015350.1408870.1968822133−0.00393−0.06911−0.363932134−0.037220.5132880.8152222135−0.01418−0.07171−0.471542136−0.0166790.50140.1587512137−0.03413−0.34893−1.1412321380.0215450.1637290.28043121390.001657−0.20288−0.320992140−0.04362−0.26001−0.887142141−0.0604−0.3014−1.241321420.014533−0.1873−0.28032143−0.1554−0.1203−1.281432144−0.06871−0.3596−1.31712146−0.035320.8615530.96092147−0.08402−0.07325−1.1769421480.007504−0.089503−0.4244512149−0.01090.39890.46238221500.0171220.2490820.42117521520.000207−0.21526−0.622052153−0.0968−0.31175−1.5018121540.0276420.219520.3233572155−0.12683−0.4516−1.825521560.010058−0.11429−0.2426221570.00001−0.29205−0.3592721580.02961−0.09941−0.510432159−0.008060.6523610.83123321600.001866−0.1929−0.583272162−0.018781−0.151041−0.2568121630.0062280.0643270.2977622164−0.05889−0.38329−1.4363621650.0165160.6193340.8051912166−0.04869−0.23011−0.8392321670.003504−0.18951−0.1922168−0.02315−0.07567−0.89442169−0.03608−0.27598−1.164092170−0.02692−0.43046−1.3902521710.002668−0.37727−0.5285621730.0121660.2381580.4574932175−0.01559−0.12915−0.272421760.025237−0.09022−0.199882177−0.03027−0.22427−1.292092179−0.0000170.118178−0.5189521800.0169510.1038970.3330142182−0.01191−0.17284−0.303442184−0.03966−0.14011−0.493952185−0.01437−0.17107−0.6214921860.017920.0583240.38545121870.0143170.5710450.97928421880.010466−0.25055−0.4223721900.0185410.3279890.4173222191−0.0577−0.35017−0.724942192−0.0357−0.26097−0.3425921930.006228−0.2797−0.7332821940.0150710.3593110.47745821950.005636−0.20457−0.2251821960.001252−0.045446−0.14524121970.0190990.1615040.4779821980.013844−0.2143−0.370912201−0.02295−0.15527−0.343642202−0.05247−0.1837−1.0253222030.0136740.1405930.2498992204−0.0042−0.15621−0.882492205−0.03294−0.48168−1.480882208−0.0036−0.14616−0.2464422090.0071250.1994270.31104922100.0024710.2033270.3743232211−0.02716−0.35947−0.7465422130.0220130.2360320.4276542214−0.0196−0.21397−0.726372215−0.00274−0.14692−0.254592216−0.00131−0.17937−0.193942217−0.02213−0.13748−0.350952218−0.0019940.1322730.1029832219−0.01994−0.35781−0.3997522200.000037−0.30384−0.358712221−0.05789−0.22934−0.5087822220.0089790.5386230.7359422223−0.01819−0.49118−0.437622250.003237−0.23548−0.308382226−0.0949−0.38963−1.441712227−0.007250.2486860.39554222290.0092710.1145220.37651222300.008480.2060590.40104322310.003439−0.20575−0.196782232−0.02501−0.18181−0.5566122330.000061−0.20966−0.2577722340.012291−0.1024−0.1962322350.012667−0.11775−0.148312236−0.04859−0.21001−0.442392237−0.01381−0.12472−0.4814222380.031630.5932490.94671122390.0120680.316050.5173752240−0.00959−0.37927−0.94352241−0.00071−0.20447−0.1628122420.0212620.3232190.6301792243−0.0233−0.27218−0.271462245−0.029480.4356080.6489832246−0.01451−0.11772−0.400972247−0.01953−0.32074−0.895512248−0.0126640.3248010.4859212249−0.11577−0.70415−1.8816722500.012475−0.08448−0.5259822510.0194590.0824970.3066362254−0.014640.40150.60771622550.008703−0.03485−0.24592256−0.00734−0.24854−0.358872257−0.1667−0.29214−1.5741622580.0255760.2844060.3280532259−0.04541−0.3858−1.5625822600.0013920.2508030.37440622610.009299−0.21002−0.1930722620.0183020.2511870.3473442263−0.02879−0.29245−0.451052264−0.014690.1424280.4000882265−0.05956−0.10194−1.1485722670.0183650.2861510.44826222680.0183010.0886420.35118422700.0163180.1845840.43790922710.00117−0.17535−0.183572272−0.00670.1459260.46550922730.0283170.2605720.40793222740.0039240.1001850.39410822750.001144−0.016170.2379652276−0.00554−0.27487−0.46122277−0.05148−0.1106−1.3790722780.0002590.2179950.3699692279−0.00916−0.136−0.2766322800.0066310.1974810.57374222810.0253660.076441−0.4198922820.003573−0.28411−0.29689322830.0112970.428490.7420612284−0.01898−0.2316−0.655332286−0.00426−0.361198−0.34230222870.0047290.1371320.32894222880.0181710.2415460.3597322290−0.01784−0.18518−0.202552291−0.01003−0.11266−0.2941922930.010189−0.1935−0.726322294−0.03967−0.08272−0.377492295−0.01802−0.14871−0.633212296−0.01662−0.15705−0.5308622970.0281140.1181320.192962298−0.0099−0.20647−0.376352299−0.06665−0.49226−0.7625223000.0030240.1855320.32979223010.003459−0.09165−0.1722423020.008627−0.135924−0.18481323030.001354−0.20444−0.387612305−0.02601−0.27937−0.936222306−0.032−0.17657−0.407312307−0.02362−0.24769−0.489452308−0.01428−0.1252−0.5625323090.004879−0.016260.1770992310−0.001488−0.154965−0.1516112311−0.0355−0.06494−0.8152723140.0000470.1732990.3308423150.014775−0.21485−0.262342316−0.0855−0.4418−1.054372317−0.1403−0.11166−1.3030323180.0196650.3222360.46146923190.00727−0.17689−0.1748223210.029903−0.18599−0.17372322−0.01996−0.20753−0.4711923230.0195250.4995320.7067262324−0.00226−0.09615−0.2692223250.002831−0.12896−0.407152326−0.03027−0.29217−0.527452327−0.03554−0.15001−0.4424323280.0273050.1070610.40479323300.0027610.0781520.23214123310.014591−0.20659−0.245912332−0.01237−0.3604−0.9626223330.003339−0.13529−0.3005823340.0202320.1786170.40509123350.0100950.1520310.29926923360.0188810.0982890.23341123370.014850.1090050.28436623380.0143680.1882750.32700423390.0154090.1342880.18534623400.003810.0832880.2284862341−0.008680.1745260.20540223420.0027690.1676360.26099123430.0232920.0824310.20782523440.0099220.1745440.38932523450.0283080.2994210.3638842346−0.05802−0.49477−0.5397623470.006781−0.16619−0.502522348−0.00471−0.24265−0.406322349−0.00289−0.26804−0.244492350−0.00163−0.26011−0.67222351−0.01717−0.49896−0.457492352−0.03309−0.1127−0.786672353−0.01112−0.18403−0.676582355−0.05419−0.28594−1.000552357−0.00326−0.2309−0.3035323580.001835−0.08573−0.213322359−0.01645−0.1167−0.286132360−0.01825−0.20883−0.3422423610.005704−0.11607−0.174992362−0.010470.2319990.35717923630.0107470.2750060.3413282364−0.00207−0.18193−0.155262365−0.0054−0.20264−0.32122366−0.003650.3459830.58518323670.003710.3481810.5742412368−0.00047−0.39854−0.2704523690.004161−0.11105−0.2549923700.009182−0.2079−0.2117123710.005776−0.16574−0.176862373−0.07101−0.19618−1.275072374−0.05482−0.24994−1.20832375−0.08589−0.36391−1.3988423760.0127390.2060790.35945223770.011456−0.12574−0.4245123780.0114570.2523120.4956952379−0.00327−0.2122−0.379552380−0.01316−0.25034−0.606062381−0.01115−0.19235−0.403412382−0.12207−0.52644−1.560032383−0.06705−0.47182−1.6149523840.0061980.2052570.1929642385−0.01366−0.28913−0.3019723860.003211−0.20733−0.227572388−0.0575990.2409090.47552389−0.01387−0.23521−0.409672390−0.00202−0.24353−0.6169723910.009540.3132850.5400152392−0.00821−0.28209−0.345092393−0.01174−0.24409−0.301222394−0.0009−0.23828−0.283052395−0.00185−0.15898−0.182662396−0.02047−0.18068−0.392592397−0.01208−0.20406−0.254782398−0.01655−0.06001−0.570222399−0.02925−0.1465−0.591472400−0.0331−0.10996−0.635712401−0.064940.3420790.4659852402−0.04543−0.21281−0.3491124030.010530.1494840.28812824040.008288−0.20655−0.464112405−0.004890.1338010.3129152407−0.02636−0.26027−0.3462424080.0191850.1301160.2717824090.0202640.019220.33709224100.0315270.4195810.58672424110.0147960.1864490.31202824120.0141630.1104520.25491124130.0205380.2011870.4254624140.010840.145810.2727062415−0.015830.3317770.3924342416−0.026−0.20967−0.7812124170.0096030.1346980.34487424180.001308−0.26017−0.4148424190.0130340.1472380.2343682420−0.00937−0.22861−0.3710824210.0279950.5006710.7127132422−0.004560.060910.3067792423−0.01058−0.10054−0.3111124240.019249−0.14345−0.147362425−0.00553−0.21816−0.2309524260.018803−0.12179−0.1699224280.0290880.151820.393382429−0.02133−0.10692−0.593332430−0.00858−0.14883−0.3940424310.000421−0.20582−0.2689124320.0105770.0806470.32373124330.0102720.1584070.25343624340.0183040.0911540.2387372435−0.013270.2153670.6431052436−0.008980.3968560.48094124380.023180.1438160.48214324390.0128430.1002850.33732224400.003224−0.22144−0.380042441−0.17071−0.64477−1.706732443−0.039060.097856−0.738322444−0.03501−0.31146−0.564812445−0.08669−0.23792−1.0646524460.0051750.0271880.2178522447−0.02276−0.37514−0.73382448−0.03247−0.26674−0.667522450−0.0089−0.1816−0.417212451−0.009−0.18197−0.2577224520.0111270.141730.59452524530.0104070.1470580.4935812455−0.03877−0.35242−0.7206924560.0169550.2247890.29562224570.0142590.2305410.4576362458−0.010360.977510.847872459−0.00972−0.22179−0.277122460−0.010030.2822590.2493752461−0.00813−0.26674−0.383862462−0.04743−0.42331−1.048922463−0.01118−0.17632−0.381272464−0.014960.256090.53037324650.0151670.2723070.48653124660.0076070.0910230.2422324670.001203−0.17614−0.211442468−0.0495−0.20539−1.0330224700.011666−0.01179−0.3951524710.0078390.0152930.1796792472−0.0675−0.2604−0.7718924730.0424540.3569550.5259924740.0247980.4245260.62247624750.0171850.1189850.2729972476−0.00151−0.20843−0.263592477−0.03325−0.19374−0.7053824780.0007720.2009760.2368624790.009625−0.032207−0.20655324800.0347590.2254370.48701924810.0226640.6109160.66769624820.0058430.0879910.2675742483−0.0108−0.23961−0.278672484−0.0489−0.49706−0.747652485−0.00739−0.22778−0.265882486−0.02303−0.19453−0.907442487−0.0127−0.19671−0.2710224880.001240.3346350.4099772489−0.033470.3269860.485732490−0.00637−0.16367−0.294632491−0.04518−0.3492−1.2980524930.0537451.126420.948452494−0.03874−0.31269−0.9346324950.023159−0.11675−0.1038012496−0.04042−0.18134−0.327962497−0.00968−0.17688−0.315442498−0.00646−0.13239−0.2754924990.020456−0.11915−0.208172500−0.000240.1500110.28185325010.002305−0.19−0.162912502−0.00389−0.26393−0.5136325030.0070550.2268360.6504372504−0.02326−0.21997−0.2039125060.003697−0.17838−0.1641225070.0148560.2117120.66225825080.0049920.2062530.3221372509−0.013350.3872160.6441125100.003760.1762150.17501325110.0211210.2503970.4757912512−0.01114−0.14474−0.292322513−0.00899−0.26498−0.329292514−0.0094−0.33164−0.342525150.009736−0.12433−0.2429225160.014748−0.14755−0.363362517−0.02821−0.14399−0.9672425180.016951−0.22681−0.284925190.0138790.045590.23897225200.0080050.1209570.27153725210.0193150.191780.3596792522−0.01642−0.25679−0.655125230.0008140.147210.28161825240.0034310.1085770.2931282526−0.007560.3815120.49993625270.0173970.164360.3804042528−0.00472−0.14086−0.279492529−0.04997−0.30686−1.0305225300.0203470.4258120.6999232532−0.02576−0.1743−0.4007525330.011399−0.11366−0.5332525340.008381−0.17413−0.381272535−0.038430.324440.39874525360.0190720.111280.26576825370.0116580.0866940.32589825380.0093530.0959960.30113725390.0141660.2457340.54744225400.0066220.02503−0.5041825410.014146−0.23165−0.298472542−0.00111−0.13198−0.2020825430.0245460.1568420.41341325440.010614−0.2345−0.2590425460.0225780.3521060.34375425470.0147810.1843970.34854925480.011386−0.1538−0.278432549−0.000980.3372690.3607112550−0.05955−0.38445−0.652422551−0.01004−0.23455−0.494842552−0.00126−0.1658−0.458612555−0.02678−0.35264−0.747332556−0.07595−0.25382−1.1874825570.00079−0.15267−0.1772225580.0176020.4830660.5690612559−0.10296−0.5151−1.333112560−0.012130.6524330.81457425610.0425920.9048331.18507625620.0196060.5583420.63305825630.008532−0.26733−0.218592566−0.05012−0.11162−0.8531625670.0187740.4815160.61725125690.0112410.1589750.35330425700.0221750.2377880.39676925710.0052270.2710520.4590742572−0.05856−0.07066−0.6702525730.000905−0.23692−0.207792574−0.00505−0.27258−0.4015525750.0361130.9506091.14816625760.0161980.2989180.27131525770.0133610.5139110.7191172578−0.02544−0.03916−0.672425790.004507−0.02659−0.3480725800.0362640.3306480.38171325810.0015920.1327320.51943525830.008092−0.22414−0.248332584−0.10180.3102740.4974632585−0.00552−0.23275−0.197692586−0.0004−0.26457−0.7030525870.0070710.1089240.2943352588−0.01101−0.26872−0.2431225890.013947−0.18537−0.359692590−0.0019−0.15674−0.175272591−0.0143770.0165830.17092525920.012950.1536620.38201325930.002620.158530.2675672594−0.0291−0.1754−0.340282595−0.03633−0.1049−0.8239225960.0126580.1851740.3115612597−0.09052−0.0452−0.728762598−0.029080.328830.62374325990.00495−0.09515−0.375732601−0.02013−0.22364−0.62052602−0.18084−0.4668−1.753426030.001916−0.23833−0.3244626040.0239430.1863420.3004426050.0086120.066150.2462282606−0.00227−0.0397−0.331252607−0.00624−0.32819−0.2653626080.014148−0.24843−0.766952609−0.00987−0.34001−0.734792610−0.01228−0.31508−1.2294326110.031850.2533840.4045182612−0.01704−0.22853−0.9080526130.0062490.3511380.79323226140.002701−0.14953−0.1867926160.0070450.2064710.2787932617−0.02856−0.17137−0.6937326190.0239460.1662490.41560826200.0046850.1483480.2970142621−0.02346−0.27184−0.36632622−0.09931−0.49581−0.6431926230.0245830.1861440.2426912624−0.06684−0.27099−0.653926250.0253260.1549760.3172662626−0.02775−0.27761−0.507052627−0.03352−0.39158−0.764812628−0.02107−0.1802−0.858782630−0.01450.4459040.606022631−0.091338−0.170022−1.0151372634−0.046390.107567−0.698592635−0.01869−0.18888−0.320526360.0243580.0319290.2279662637−0.01386−0.33834−0.753962638−0.01211−0.17702−0.234932639−0.029160.3285870.41399926400.0186570.6695850.52016826410.0169610.2205980.3002942642−0.005150.1762720.47542426430.019320.2598280.568532644−0.017920.2189630.50168626450.011227−0.21091−0.2587426460.019195−0.10398−0.456492647−0.0711−0.32248−0.616652648−0.02232−0.1408−1.049532650−0.00213−0.15863−0.215382651−0.17163−0.67147−1.851842654−0.018035−0.080645−0.3801952655−0.04895−0.36896−0.83152656−0.001180.1477770.34912326570.0206220.5575760.5834672659−0.059060.2705060.4022152661−0.05978−0.38606−1.0225326620.014390.124260.34124726630.01138−0.25562−0.208672664−0.03397−0.32905−0.581592667−0.03061−0.21083−0.386912668−0.001830.0901120.3072482669−0.025950.2248070.29846826710.003312−0.18156−0.5544926720.0002280.0796830.2782162673−0.04497−0.28606−0.6429926740.0185080.2875350.3838352675−0.04517−0.10085−0.6747126760.0130430.1422840.31590426770.018862−0.11512−0.156322678−0.00649−0.24672−0.1873626790.0131450.0765210.173632680−0.02291−0.26992−0.355452681−0.0172−0.1704−0.4260326820.0129190.3003040.5271162683−0.0369−0.31319−0.656332684−0.000780.0324480.216226850.0132140.2852260.37424526870.0251240.8646090.89398826880.0227060.2315440.44047426890.00576−0.18355−0.161932690−0.007580.1237960.403872691−0.056170.002515−0.6060326920.0310660.1890180.24641526930.002933−0.23438−0.438726940.0274550.1061660.3182912695−0.01234−0.15248−0.6743426960.0616990.2956730.6241812698−0.00845−0.11741−0.2326426990.021373−0.029099−0.14344427000.0038990.2023640.3250232701−0.06426−0.22383−0.9470427020.027532−0.22419−0.246662703−0.09451−0.3224−0.4828627040.0003120.2765390.3137762705−0.00553−0.17665−0.7849627060.0122380.1411660.3984362707−0.03874−0.38717−1.352692708−0.05333−0.23516−1.428022709−0.05484−0.22256−0.965162710−0.06505−0.20362−1.450882711−0.025910.385230.61311727120.02510.3024370.4941242713−0.0261−0.41054−0.884892714−0.02071−0.19565−0.3492327150.0290050.2222920.47824427160.010292−0.22227−0.28427170.005257−0.12139−0.200792718−0.03409−0.2738−0.5622927190.0093880.1236030.4191332720−0.00948−0.14352−0.2374127210.0166310.2116590.3584812722−0.05307−0.09342−0.6551127230.0043260.2604340.30774527240.0194−0.15387−0.1521927250.0262710.1685120.3727612726−0.02547−0.1861−0.3548927270.0168730.1072480.264312728−0.002010.1824890.3299762729−0.00645−0.12001−0.370527300.0143740.1012140.2213222731−0.03619−0.15552−0.406492732−0.00689−0.24428−0.190662733−0.003790.3411420.6509922735−0.00090.4494560.4113882736−0.00403−0.25021−0.3031827370.014266−0.09848−0.523332738−0.008110.1044950.2969982740−0.0598−0.33464−0.830892741−0.00346−0.2422−0.2170827420.0200070.1978740.4877642743−0.04421−0.29753−0.397842744−0.05582−0.27547−1.4161527450.0088730.2502210.30360127460.009041−0.1964−0.191652747−0.04114−0.21991−0.4680127480.0028160.2494590.41575827490.0231710.2099570.42797527500.007282−0.224306−0.3356652751−0.00413−0.26488−0.6003427520.00973−0.12429−0.191832753−0.04282−0.27188−0.628682754−0.02887−0.12252−0.937952755−0.00187−0.1844−0.225412757−0.004−0.26216−0.3948727580.0091760.1892470.3159722759−0.00615−0.12202−0.272572760−0.0351−0.19813−0.4228327610.000833−0.08427−0.392872762−0.01219−0.19936−0.259542763−0.16163−0.53089−1.3278127640.0131240.2618920.44638427650.0201370.2204690.3233652767−0.01952−0.20113−0.2732127680.00059−0.35561−0.505062769−0.04199−0.22403−1.0832727700.0031480.2963140.51270327710.019729−0.14299−0.255482772−0.00232−0.29066−0.318362773−0.01355−0.29771−0.305827740.012705−0.1251−0.4065927750.029410.1431350.3197842776−0.00825−0.32347−0.4141727780.0035680.2441880.43480627790.016160.3075860.3107842781−0.04576−0.29594−0.604852782−0.06077−0.54338−1.4201327830.0106780.3383060.3943512784−0.02934−0.20385−0.405112785−0.07145−0.36143−0.9785327860.0188980.2062240.3636632787−0.00883−0.18902−0.367092789−0.00572−0.13531−0.348732790−0.0735−0.23269−1.511432791−0.05897−0.30025−1.621662792−0.03988−0.11644−0.4274127930.0266390.3762110.4168322794−0.01133−0.14615−0.677072795−0.025130.0302910.42463927960.013267−0.13917−0.2217527970.0105930.0917770.26114527980.0004030.3254070.68484827990.003311−0.10639−0.21312800−0.011140.3847060.5240912801−0.01057−0.16236−0.874682803−0.01069−0.168−0.213512804−0.03986−0.33729−1.210882805−0.16102−0.43208−1.592622806−0.03892−0.26461−0.6148328080.0063580.0598240.3745452809−0.01802−0.32733−1.10682810−0.04049−0.36347−0.782292811−0.0034−0.20011−0.270792812−0.00165−0.28443−0.4085728130.0033360.2026590.1917142814−0.06861−0.23165−0.6589928150.0063030.0923940.15083628160.0267990.2489920.36512817−0.02931−0.20321−0.522128180.006975−0.20782−0.316322819−0.0002−0.26998−0.260632820−0.0174−0.26042−0.2340528210.0006570.1522480.270112822−0.00262−0.35167−0.6941428230.0147540.148470.377052824−0.03396−0.07618−0.820522826−0.05703−0.25432−0.5669128270.0123010.3125660.5761782829−0.00672−0.19801−0.277162831−0.000880.1897130.3245262832−0.00508−0.20367−0.3312328330.0035180.4890110.75823728340.0153030.2395280.37649728350.010979−0.2097−0.2658628360.0126160.3508840.40843528370.007863−0.11288−0.3488428380.0230010.2936050.48305628390.0154170.0643530.22822840−0.01948−0.13793−0.412472841−0.00974−0.17467−0.7517428430.00165−0.12552−0.3949928450.002541−0.18358−0.287728460.0108960.2831790.418052847−0.06383−0.40518−0.5005628480.0193750.6288861.04291928490.0229030.333190.621622850−0.00501−0.13298−0.323582851−0.02006−0.1888−0.228472852−0.008160.5706710.6050132853−0.01898−0.16103−0.472122854−0.02199−0.19576−0.459822855−0.06362−0.30184−0.5382228560.004923−0.15456−0.467972857−0.0198−0.21892−0.594692858−0.0124−0.19867−0.3108328590.0046540.2013060.3532822860−0.08969−0.45642−1.765722861−0.00546−0.12932−0.335152864−0.033760.3133270.57291328650.002638−0.150304−0.2654392866−0.00529−0.19319−0.296928670.017267−0.1494−0.3995328680.0126070.2585030.5055242869−0.01303−0.34736−0.30712870−0.0758−0.006670.4074642871−0.02757−0.18451−0.3620428720.003653−0.3916−1.175672873−0.07463−0.61553−1.832442874−0.01321−0.14784−0.238182875−0.03974−0.16305−0.6383828760.0122210.1040160.4466252877−0.01922−0.22468−0.388072878−0.07287−0.52202−0.589428800.021490.0571750.31727528810.0051670.2390140.44373328820.012339−0.16847−0.212842883−0.01227−0.24525−0.2944828840.0176660.0640750.2961622885−0.0284−0.02721−0.3386628860.0022420.3961690.435952887−0.04032−0.1874−0.63422888−0.00529−0.24167−0.507712889−0.03780.3297270.5815042890−0.039−0.01533−0.807692891−0.005430.4242070.3041932892−0.04168−0.21264−0.424872893−0.006350.3756730.53512928950.009807−0.19318−0.2220528970.0092730.2537540.33445328980.0302190.1530760.5580652899−0.02054−0.14638−0.511452901−0.01498−0.36242−0.447722902−0.06741−0.31666−0.6579529030.0105070.4513630.44766229040.0131150.2327740.4468622905−0.00359−0.22495−0.361852906−0.00018−0.26065−0.199212907−0.02028−0.24598−0.4281829080.003810.1255320.30701729090.0059150.1768430.459162910−0.005690.229650.40517429110.0163550.1637110.3693212912−0.00538−0.19107−0.2392229130.0130080.2540140.51320329140.017230.4963810.6465892915−0.03446−0.34402−1.054612916−0.004610.5810740.69535129170.011926−0.12652−0.3461229180.0104330.2079890.30837629190.0288630.4357130.55244229200.007439−0.18482−0.160522922−0.01718−0.19775−0.658732923−0.05394−0.35788−0.8870329240.007022−0.22385−0.1879529250.0293360.1687390.25530629260.0312020.3302270.3724512927−0.011840.1838680.2871342929−0.009980.2060450.36151429300.0328510.360530.5902929310.035760.4225640.58401329320.0131860.2928280.3546842933−0.00303−0.16442−0.3349929340.0203980.2271650.38077429350.0121850.2672160.26017329360.024484−0.182182−0.1123462937−0.00041−0.14593−0.1665829380.01805−0.289863−0.2732442939−0.000081−0.14541−0.190032940−0.0187−0.15705−0.601622941−0.013980.6555210.6474362943−0.00569−0.16623−0.2574529440.0120970.2862650.5625722945−0.07967−0.44647−1.6445629460.000761−0.27061−0.329132947−0.02328−0.22028−0.397932948−0.004530.1821180.34215929490.0293010.2064660.3641792950−0.0834−0.04703−0.956562951−0.01477−0.39573−0.665052952−0.005590.3590040.53503129540.0479320.4589510.62991729550.0151370.1082640.3379852956−0.00029−0.20181−0.651272957−0.01247−0.38495−0.661392958−0.00978−0.09718−0.511052959−0.003420.3341660.4332252960−0.01243−0.20204−0.370042961−0.09822−0.34643−1.47072962−0.00298−0.24026−0.4010929630.0190650.3207160.42233429640.019559−0.127505−0.38553429650.005619−0.12517−0.286332966−0.12764−0.3992−1.465732968−0.01383−0.19388−0.179132969−0.035380.3800630.71385729700.0216430.1476230.31146629710.0036220.1646050.2657532972−0.013410.3240550.3990542973−0.063970.8200250.6999942974−0.026480.0159750.3362952975−0.023560.009007−0.349842976−0.11295−0.04438−1.363052978−0.01266−0.08436−0.530582979−0.008−0.24206−0.434452981−0.018057−0.15181−0.33547229820.004258−0.09973−0.271672983−0.01474−0.37219−0.7175729850.009237−0.11864−0.133532986−0.00048−0.30194−0.2692929870.008786−0.20533−0.1964729880.006482−0.06617−0.1694929900.033576−0.02725−0.3369629910.0032320.1795890.4386392992−0.01259−0.20203−0.3448329930.003781−0.21029−0.295862995−0.0014−0.27584−0.527232996−0.02464−0.17473−0.456462997−0.03992−0.14858−0.387032998−0.00727−0.36316−0.786712999−0.03383−0.18387−0.4842130000.003352−0.26397−0.2632130010.0173490.7773880.86538630020.000544−0.20052−0.327163004−0.0045860.0549520.21318830050.0186770.1908540.3013043006−0.040940.2295190.3655233007−0.025330.3026810.3639683008−0.06654−0.2406−1.3029830090.005668−0.19868−0.291530100.0153440.1736430.27498230110.0180290.2824020.40446830120.0141160.1431820.23979330130.010910.143190.2755573014−0.00079−0.21327−0.3186630160.0099720.3298680.4070733017−0.006580.0900070.36342330180.0206460.2395360.42370430210.013140.2322750.42754930220.015475−0.112142−0.2085323023−0.04766−0.1538−0.5142530240.021520.2960870.35864330250.0032950.5586970.57362230260.0082920.2345950.36120830280.0192620.2681670.27596530300.018755−0.16557−0.516973031−0.03294−0.15371−0.371083032−0.00015−0.0984−0.375153033−0.008540.1929890.7441943034−0.00319−0.1583−0.2183930350.0094870.2657060.4327923036−0.03611−0.19937−0.4744530370.0014150.0545280.28851130380.0197250.3190220.50597830390.0167020.2961820.4017873041−0.13197−0.47988−0.617563042−0.00948−0.13928−0.3539130430.0140270.0883530.35242630440.012480.0510550.23662830450.0103760.428960.482513046−0.00696−0.15996−0.520273049−0.03367−0.12396−0.576313050−0.02681−0.20596−0.405643052−0.003590.4744850.83555630530.003314−0.27792−0.498453054−0.03475−0.38399−0.69930550.0069030.0202610.34715730560.0047460.1044260.17126930570.003378−0.17245−0.2443630580.0304410.2187770.3578330590.0250410.3591760.43372830600.0180980.1839120.3658283061−0.0000340.1581420.41303230620.0430790.3330020.4866743063−0.020760.2811960.5430213064−0.011830.3658790.40726130650.013810.5155950.84088930660.0392710.2510360.3728933067−0.005890.341180.52763068−0.04032−0.327−1.0099630690.003072−0.25928−0.2488830700.0105170.0929180.22907830710.0143340.3310220.4010463072−0.01646−0.3282−0.5315730730.003834−0.22565−0.236593074−0.014160.3780920.5080693076−0.05507−0.23452−0.944493077−0.00817−0.25111−0.4676830780.0303420.077990.272793079−0.04798−0.33419−0.7040730800.0164570.2034790.44890830810.0138040.0978690.25165430820.010480.3451720.50264230830.022320.4450020.4892763084−0.000910.1631350.294763085−0.007467−0.154645−0.2635353086−0.01528−0.25361−0.457273087−0.05711−0.09675−0.6469930880.002833−0.28011−0.602363089−0.05295−0.27133−0.544523090−0.02010.3500370.5270043091−0.00468−0.15449−0.1910230920.0203520.0842010.3438453094−0.01318−0.14226−0.563883096−0.05777−0.30537−0.7318730980.0085370.356880.5016013099−0.02475−0.0732−0.5723531000.01775−0.18804−0.18293101−0.025670.2811010.42756431020.0048680.4958210.5961343104−0.01012−0.12775−0.3244131050.0192481.058391.0400933106−0.005961.3141360.79098731070.0134090.0971760.2664563108−0.04616−0.28704−1.183593109−0.014720.2598790.48880631100.0272940.2303580.28222931110.0061230.2259820.3870853112−0.02267−0.18104−0.637943113−0.06425−0.26503−1.076913114−0.0948−0.36956−1.233353115−0.04583−0.49382−1.207273116−0.028180.051385−0.871593117−0.0115−0.1814−0.9153431180.001685−0.25086−0.3917931190.0272020.6557980.7338793120−0.05247−0.08431−1.5229431210.0136770.5371470.80307331220.014001−0.12847−0.157253123−0.00239−0.08607−0.2308331240.017320.2956970.3777153125−0.03826−0.21146−0.7515931260.008702−0.15491−0.1371831270.0127020.2256010.23366131280.0139010.2665710.4029743129−0.04573−0.37916−0.447473130−0.00287−0.27159−0.3330131310.0005510.045020.30779431320.010392−0.20774−0.498393133−0.013230.2738430.45895831340.020184−0.16107−0.2960231350.0310840.3984810.6271753137−0.01305−0.21173−0.2473331380.018786−0.18142−0.3137431390.0187−0.14742−0.203543140−0.05516−0.25108−0.549023141−0.0048−0.15275−0.227723142−0.02270.2791960.570743143−0.002540.0868090.31254431440.0488190.7394250.99959231460.0176880.0275960.25884531470.01390.1659540.38852531480.006463−0.34808−0.5532331500.0014220.1532640.2738453151−0.06787−0.47637−0.9597431520.0074790.2371460.5328393153−0.07307−0.36885−1.3419631540.0107490.2292790.47129731550.010019−0.20671−0.213133156−0.13663−0.04778−0.9022931570.0116990.2965880.4374113158−0.018120.319050.7095413159−0.03859−0.42023−0.8213731600.007129−0.24125−0.256083161−0.00211−0.17613−0.2548231620.0133970.3271070.446913163−0.02918−0.24804−0.3286331640.007546−0.13599−0.3061331650.0076480.1501290.3202593166−0.009250.3150410.3703531670.008692−0.18589−0.135233168−0.01645−0.17733−0.3233331690.0053290.355990.50198931700.00096−0.13687−0.2780731710.0251620.2535050.43225231730.008033−0.20975−0.202043174−0.006670.2235810.43282231750.012684−0.23036−0.375113176−0.0022−0.12761−0.241513177−0.00613−0.21416−0.823533179−0.02798−0.09902−0.373253180−0.06937−0.35675−0.453653182−0.00878−0.19553−0.4347531840.0141230.1537140.279163185−0.0116620.3241660.47681131860.0039250.2186410.4162953187−0.0217−0.21766−0.3545531880.009443−0.17399−0.3021331890.0133930.2462280.32973631900.0093920.1166170.2261143192−0.00689−0.1435−0.3855831930.0231310.187650.36303531940.0218320.287940.6024363195−0.00808−0.17928−0.3228931970.000099−0.25158−0.428643198−0.00178−0.09534−0.362523199−0.0045−0.23936−0.2482732000.021765−0.14444−0.326093201−0.00066−0.14665−0.2380932020.01394−0.19605−0.171163203−0.06709−0.12779−1.072132040.0097070.3200080.3537953205−0.00024−0.10284−0.4764132060.0086180.1264780.2161983207−0.01478−0.17977−0.38263208−0.05194−0.28887−0.39463209−0.00240.1991060.3062453210−0.01425−0.2533−0.2516332110.0306760.5772090.82704832120.0376960.3367720.4281383213−0.07147−0.0399−0.7575332140.0166210.2401820.55081532150.00353−0.064073−0.1677933216−0.001670.2304870.3794683217−0.028270.3990710.414232180.01687−0.15702−0.1588532190.0009070.4828550.585263220−0.00058−0.24158−0.5786932210.0395530.3177840.4259083223−0.004480.2008520.3550453224−0.03101−0.10041−0.405243225−0.00451−0.09154−0.540893226−0.00489−0.22115−0.269133227−0.12484−0.54845−1.513363228−0.00735−0.29045−0.360983229−0.01115−0.23759−0.3646532300.004136−0.10636−0.268283231−0.01215−0.35269−0.326223232−0.07169−0.26568−1.359963233−0.05571−0.36337−0.8135932350.0104250.3372720.56539832360.001723−0.25054−0.3766432370.0214060.3082150.5604283238−0.002910.1624780.277613242−0.0207−0.41811−0.8866432430.0234590.2749220.42878432440.0148250.2632940.4243093245−0.039738−0.344767−0.51240932460.0432420.1828420.2963093247−0.03455−0.25575−1.180193248−0.03044−0.28089−0.445473249−0.07284−0.3393−0.76143250−0.0067−0.19891−0.6283232510.0080650.0473970.27035332520.0345530.1931190.2261083253−0.01395−0.18672−0.2582132550.0024760.3919980.5374253256−0.026520.1947280.3772243257−0.005650.2862850.43089332580.0348620.132890.2299983259−0.00161−0.12845−0.281143260−0.00019−0.13256−0.195063261−0.001650.4144380.57645132620.0002750.1199380.38023332640.0159440.1714960.3736353265−0.106020.065469−0.9625632660.007249−0.15939−0.1505132680.0350570.1355110.3508043269−0.00071−0.21354−0.3200632700.009556−0.08782−0.2077732710.0379120.3829120.60660432730.0300810.0920240.241763274−0.03181−0.19188−0.653113275−0.02899−0.26298−0.52523276−0.00612−0.239−0.257233277−0.03396−0.36011−0.9790232780.005417−0.22054−0.2798832790.004210.2415440.3373833280−0.04008−0.24002−0.4935232810.011397−0.05727−0.211393282−0.003070.4382220.64515732830.015044−0.17112−0.179763285−0.023590.1203690.3688063286−0.01503−0.14384−0.3367732870.030360.1695110.31801932880.000511−0.27843−0.258263289−0.03333−0.14182−0.531663290−0.01495−0.15518−0.429823291−0.004310.2761520.45538932920.0292580.1546120.3118693293−0.02497−0.3162−0.6324132940.0088260.1937750.32727232950.011080.2906890.4695143296−0.01098−0.19785−0.2974632970.0025530.1565260.38402632980.0025430.5170460.53524632990.021292−0.25826−0.4640133000.056170.7868710.88387233010.0073090.3425970.38771533020.0214370.0580260.3036933030.0269650.1535040.31251233040.0307940.4658120.6655463305−0.00064−0.24084−0.390233060.0142180.3233980.5079243307−0.00603−0.16018−0.2557833080.0273360.1429090.41794833090.0212530.3596490.53426533100.015830.2145670.35270933110.0046630.2468440.43379833130.0122630.097740.2591473314−0.01847−0.18197−0.30453315−0.01891−0.12996−0.5113833160.012776−0.09152−0.122423318−0.01352−0.20692−0.498243319−0.01725−0.13233−0.341433200.0053160.2050020.3217623321−0.02382−0.28781−0.3871333220.019935−0.03942−0.121993323−0.03422−0.20408−1.17433250.010350.2089770.25919133260.0099190.4873120.79847433270.0323580.3514120.5396553328−0.0015450.0725950.20773329−0.010330.2980930.3697773330−0.01145−0.26775−0.3068333310.021030.2938520.5146893332−0.01512−0.052840.20933933330.0075940.1496510.2108033335−0.01696−0.25564−0.3154933360.0038740.19670.30917133370.0026920.2392370.2247743338−0.05145−0.42643−1.101983340−0.019220.3120480.5194113341−0.01633−0.29083−0.7171533430.0149050.1932050.3036073344−0.04371−0.17744−0.576943345−0.01708−0.17088−0.3292733460.005582−0.18765−0.1200433470.0061030.3064870.48147833480.0112070.2467710.4734693349−0.055960.053807−0.8277433500.003028−0.26366−0.2548733510.0002150.4201670.7023443352−0.00142−0.2055−0.2016733530.035970.3193690.4067333540.0190530.293340.6464683355−0.032850.1402380.2824993356−0.02039−0.31003−0.403743357−0.00365−0.26832−0.345393358−0.00683−0.1512−0.1602633590.002591−0.19241−0.2171233610.002381−0.16775−0.384883362−0.027980.001446−0.7358833630.0020060.0735070.24569833650.012282−0.08127−0.289523366−0.013160.4914640.5377133670.0229130.2432050.33540833680.0210860.2160260.3766843369−0.016970.6190620.9124893371−0.04089−0.35226−0.8170333720.002305−0.13597−0.283323374−0.000850.3551650.50989433750.0156070.2641970.38696233760.001514−0.16232−0.34833770.0105340.3267940.4866833790.0015190.2233360.4621283380−0.012204−0.399725−0.45496933810.0030040.2068570.5184793382−0.04527−0.47572−0.797673383−0.00646−0.09346−0.3370733840.0107450.1919020.70744233850.0031270.6699570.7776013386−0.0023−0.36617−0.4644433870.0075180.0626120.327263388−0.01240.3435690.49018133900.0185990.5285330.8891393391−0.03171−0.31391−1.2135133920.0190310.6152190.7585013393−0.04515−0.24606−0.8508333940.0141150.3036570.4227433395−0.006382−0.249059−0.20136533970.0145660.4031640.50239533990.0060080.2844520.43042534010.0131820.2482620.4639443402−0.0848960.0549380.4637163403−0.02621−0.10465−0.367934040.0307460.8937670.89601634050.020912−0.17105−0.1681234060.0111060.1481780.43610434070.000072−0.19676−0.1347934080.0117660.1250370.38457834090.0034890.4676130.5917213410−0.01813−0.21229−0.583834110.0184020.1662560.3194183412−0.0302−0.11487−0.694434130.0085290.2327170.2666493414−0.03538−0.37811−0.825783415−0.04675−0.1464−0.873923416−0.04048−0.14832−0.36463417−0.04323−0.2426−0.6564134180.0163380.368360.5067373419−0.03218−0.19306−0.628743420−0.02344−0.31573−0.633953420−0.000395−0.09677−0.2063534210.0016990.1528190.3610653422−0.02327−0.30397−0.5828434230.0180630.1684560.3674234240.0014170.464570.54431234250.0171970.0840690.2367743426−0.0143−0.415−0.490233427−0.008260.0116920.39720434290.011585−0.21061−0.191353430−0.003890.255290.41748634310.0180410.1163790.70120134320.0010960.2439690.34906234340.0100970.1070820.28080534350.000005−0.20201−0.3331234360.0038030.2385080.33067934370.0180840.3890010.45915234380.0268420.2938590.57882234390.000424−0.28683−0.3350634400.0240020.3067650.39931134410.0280820.0488870.27470434420.0208090.3009730.4449483443−0.00612−0.26467−0.2143934440.0059340.2219960.3929873445−0.026−0.24664−0.403733446−0.01545−0.1622−0.532413447−0.019160.6313211.04690434480.004799−0.026190.2615093449−0.002560.2716470.6106463450−0.00687−0.23718−0.836763451−0.04042−0.2342−0.498593452−0.006950.6371480.90421834530.0120650.2718770.40886834540.0131560.3168840.46769434550.0020330.385490.5238723457−0.23356−0.34986−1.4876534580.0042190.238960.4164523459−0.00864−0.25095−0.4965834600.0199510.1798620.2920423461−0.05881−0.35086−0.543573463−0.002040.2014640.23850834640.0247330.1650910.28992834650.0029460.3826870.5477263466−0.03176−0.33056−0.317743467−0.007560.0069830.30740934680.0231280.588330.5439473469−0.00921−0.47814−0.389534700.0215080.3179460.74335534710.014745−0.23137−0.21373472−0.07754−0.54498−0.5884834730.0102560.2010120.5032333474−0.01069−0.31679−1.2415434750.004935−0.18108−0.243283477−0.007804−0.0120070.18018334780.007381−0.1484−0.1546934800.0081990.2057830.3354613481−0.004220.1225690.42097734830.0272510.0851330.26787934840.0063080.1094440.3158383485−0.00387−0.13886−0.2069634860.014010.2108190.38599234870.0308190.2427690.50303334880.0294450.1421190.27982334890.0278980.1961720.3318493490−0.0195−0.19389−0.5575334910.0113530.1383510.23779734920.0074250.2204270.3721783493−0.03338−0.2384−0.513513494−0.02411−0.01836−0.4978634950.0136760.2276140.4063013496−0.0789140.888380.61924434970.0048640.2552840.42708534980.0100620.1533470.34581434990.0052490.2859960.50230335000.0289840.2131530.33103935010.0152770.0511250.2622623502−0.00541−0.23659−0.4190635030.0055180.2538840.2765583504−0.01431−0.24218−0.4397635050.0065670.1305840.3319843506−0.000840.0578020.24598335070.0186680.0978330.19446835080.0164480.1150950.22768835090.0137630.1200720.23093510−0.001760.1721360.39266135110.0331540.4228280.50253335120.0190040.2608740.60565635130.004740.1237860.27224535150.0037640.258540.3541735160.006238−0.19753−0.192935170.006540.0310320.21113935180.0077110.0253930.33729735190.0210360.1272580.3165293520−0.01732−0.17969−1.058163521−0.03832−0.14892−0.6481635220.0026990.3360470.75543235230.02720.0630650.32633935240.007645−0.13807−0.119013525−0.00460.1145680.2171533526−0.00152−0.26116−0.283213527−0.02135−0.26583−0.5797135280.0252880.3479450.4593993529−0.06764−0.29288−0.8187235300.0212770.1549930.3241063531−0.0000320.2134660.3161823532−0.023070.3830060.43059835340.0060690.2484460.3678673535−0.01309−0.25375−0.6869335360.0145690.2353390.39080235370.0083940.365690.44189935390.0296540.1905360.22344735400.0226590.2878140.4609053541−0.00210.1703090.2894843542−0.01138−0.18146−0.325783543−0.01974−0.2489−0.2721435440.0270740.4247130.6756143545−0.07683−0.51183−1.3691235470.0000210.0940570.22326835480.0119550.289190.48546535490.0239040.4281220.6807763550−0.03893−0.19043−0.685423551−0.07238−0.3147−1.4600435520.0155690.2827940.3473643553−0.006880.2728230.32535835560.046650.3386270.45755435570.0149130.2019380.414135580.0324990.0746780.25315335590.0080880.3018920.45392335600.0045160.2191960.3856533561−0.00872−0.14402−0.301535620.0112290.194810.27076535630.0022520.1970590.46789835640.004196−0.17839−0.3581235650.0059190.4334960.70471135660.0141410.2598420.62566435670.002687−0.07275−0.1686535680.0193860.1807560.32082635690.0080550.2364480.4633643570−0.00885−0.19005−0.189433571−0.01066−0.2524−0.3128135720.0035860.1752940.3366835730.003077−0.16699−0.267935740.010204−0.24174−0.210233575−0.01722−0.23788−0.52733576−0.00986−0.15833−0.3500635770.0024170.1159330.27538935780.019310.1282650.2574423579−0.00892−0.21633−0.263413580−0.00471−0.23215−0.484835810.020012−0.19936−0.174563582−0.03815−0.31028−0.8340535830.050287−0.019540.2209943584−0.00585−0.12787−0.30863585−0.008770.2850350.31392535860.0239510.4619680.5222363587−0.03648−0.06649−0.966443588−0.0798−0.35864−0.6144.43589−0.01895−0.18531−0.597843590−0.00434−0.0927−0.574523591−0.01872−0.15803−0.3998335920.0349910.4435660.69783935930.003399−0.19622−0.337793594−0.00647−0.26511−0.2823135950.024670.2067960.4453733596−0.05031−0.1575−0.4858735970.01621−0.09026−0.1580235980.012908−0.04883−0.17073599−0.00487−0.18513−0.319873600−0.00359−0.15119−0.290523601−0.0151−0.13785−0.444863602−0.0169−0.22645−0.4229736030.005186−0.17402−0.168653604−0.051880.3155350.63268736050.0239420.830180.8816636060.0252620.2457620.34236436070.011981−0.24067−0.4590736080.006730.188530.4150953609−0.01799−0.22257−0.340493610−0.01097−0.04613−0.417433612−0.01484−0.1804−0.459636130.0009390.2637930.67854936140.006779−0.2545−0.2985736150.0157330.1994860.34885736160.0271230.2546580.407393617−0.02985−0.1815−0.39093618−0.05222−0.31387−0.668636190.0120110.0938530.4369183621−0.03416−0.08213−0.765936220.012578−0.13075−0.238293623−0.0000070.2386390.5147363624−0.01407−0.01854−0.636136250.039310.3569070.46302336260.0189080.1553170.3682183627−0.018961−0.122255−0.45528636280.0147160.2067840.4342243629−0.07553−0.33141−0.978736300.0151570.2739840.2471173631−0.000330.2009360.4169336330.0076650.2428670.36827836340.0095170.7491210.7307163635−0.00042−0.03395−0.2798236360.0148690.1772990.3855493637−0.000890.3433970.5234063638−0.01318−0.24177−0.2602636390.0152990.1664540.3123263641−0.02405−0.22617−0.364823643−0.01067−0.22275−0.3083736440.0156240.2724950.4281136450.026790.1396020.30464236470.016106−0.23904−0.349713648−0.007850.4151340.5762153649−0.03814−0.24153−0.627283651−0.001680.1789460.29666336520.0054170.2012310.29337336530.0209920.0984990.32356336540.0098970.1718460.3043853655−0.009543−0.0303720.28024536560.0050390.1090440.43707736570.009618−0.13852−0.3465236580.010488−0.100563−0.31682236590.0221090.003490.2542053660−0.029240.2480240.3493433661−0.01618−0.25316−0.59363662−0.00179−0.29298−0.401636630.0106920.1952570.2592743664−0.02055−0.16417−0.6388136650.006512−0.20855−0.2249736660.0147620.1306350.2731636670.005038−0.15002−0.30113668−0.00370.1611250.4403173669−0.014880.171730.37703636700.0046620.2044470.40500336710.0313630.2250540.3916843672−0.017160.3639380.4549983673−0.02599−0.26151−0.8585236740.0077810.2403230.61729636750.0171880.3810030.5845453676−0.01941−0.18262−0.524353678−0.07755−0.25462−1.2145736790.0295030.265280.5457583680−0.01146−0.05606−0.5783936810.029160.2847170.39918136820.0313110.8864421.0434373684−0.05039−0.22784−0.6753636870.0251340.0777780.2336853688−0.03452−0.2365−0.659136890.0209590.1354350.4420653690−0.00061−0.22418−0.2169636910.0306150.3688670.46378936930.0082420.135380.23898836940.0221640.244850.36978736950.0083480.3454150.44549136970.0270440.2752820.42306636980.0082220.3500650.7409093699−0.00952−0.19156−0.226173700−0.00774−0.16099−0.199233701−0.05313−0.33669−0.523537020.0038560.2099350.35896137030.007194−0.37491−0.3140937040.0011220.27610.3712093705−0.007090.3573320.48983737060.0409310.4629460.600493707−0.005160.2710880.29442937080.007970.3059480.3722613709−0.01333−0.34526−0.325653710−0.008420.7438930.60355537120.005041−0.17492−0.297023713−0.0289−0.19531−0.4022837140.0111650.1550110.2791363715−0.001330.3906660.77364937160.0212920.2177230.53207437170.0297640.1331390.3635093719−0.005690.2722220.39559937200.0069750.316981−0.5546673721−0.007180.1741980.2130693722−0.01824−0.14028−0.5581937230.0014490.4338770.7508063724−0.06438−0.34026−0.9063137260.0167830.0745320.329373727−0.023638−0.142935−0.65174737280.0053530.1855610.37424837290.0153330.4667160.3387653730−0.11273−0.34033−0.743043731−0.052−0.44987−1.0060237320.0015210.0871230.2192623733−0.007740.2970370.41174437340.007834−0.27308−0.27953735−0.00030.14270.2844453736−0.003040.2479810.4190583737−0.05269−0.14303−0.969137380.0587990.237470.502693739−0.02901−0.34538−0.6056537400.0084980.1004320.2807813741−0.00080.2582630.4559683742−0.045840.0665030.3752833743−0.033490.2889050.5025983744−0.04514−0.31129−1.3161237450.0086070.2365020.37907737470.0250510.6546140.6733973748−0.00402−0.23433−0.602353749−0.035591.0654481.0238983750−0.024190.2137750.6398563751−0.03336−0.27007−0.764183752−0.04430.3398350.4988223753−0.016580.105430.22612137540.0094930.2755590.6231793755−0.0219190.1954420.37917537560.0071380.2183290.3573653757−0.00525−0.21511−0.3272837580.0124730.2011750.3625963759−0.01279−0.2507−0.5384237600.0250250.1510790.28612637610.0138490.1499880.3055573762−0.02366−0.28636−0.819373764−0.01564−0.19303−0.260923766−0.00780.337880.5590233767−0.14766−0.58681−0.83033768−0.02365−0.02657−0.404233769−0.07505−0.45329−0.8136437700.0142560.2529520.79168637710.0007620.4143310.4737453772−0.04075−0.10969−0.8733937730.009132−0.19384−0.2635437740.0067820.3088860.58672237750.016697−0.13758−0.224653776−0.00641−0.09848−0.321793777−0.01008−0.30175−0.748483778−0.18892−0.16936−0.9609337790.0151980.4606930.9201113780−0.003430.309790.44349837810.007713−0.22269−0.191073782−0.00516−0.21752−0.4303137830.008031−0.275−0.2695937840.0015440.1527550.2291137860.0339830.3144540.4671673787−0.00797−0.17558−0.347563788−0.010130.2528030.45176337890.011368−0.17659−0.276073790−0.011870.5592250.86539237910.007796−0.11536−0.758043794−0.02133−0.24973−0.6010437950.006022−0.33209−0.2686237960.0106230.3702660.3869437970.014382−0.13074−0.18623798−0.00565−0.31968−0.721643799−0.00825−0.25969−0.457543801−0.00696−0.08637−0.2504338020.0171050.2459650.52408438030.012106−0.10429−0.3984738050.0003560.4132560.47810638060.0109340.296350.38620238070.000112−0.09254−0.201723808−0.029−0.27661−0.4961438090.0109570.1439250.42727638100.0136060.2883170.38497938110.00107−0.14349−0.2386238130.0157570.0499630.32291638140.0127750.2687040.4898823815−0.00178−0.24858−0.5553938160.0204780.3285180.36349638170.0244180.1918810.3395023818−0.01942−0.29161−0.2815738190.0001030.2702940.3254213820−0.011430.4886761.06763821−0.009520.4030540.42265138220.009236−0.18298−0.286023823−0.00386−0.02828−0.2322238240.0141090.2222560.35242138250.020320.2652150.45912338260.0335850.2526230.4387133827−0.03236−0.26125−0.5184638280.0345940.1562090.28587838290.0202270.2486770.34679538300.0149780.0911810.2091853831−0.00336−0.26565−0.320133832−0.01958−0.3121−0.4292738330.0261130.3820080.53230138340.023708−0.1401−0.3033138350.0053440.2322290.3373138370.0159780.1486980.335043838−0.06039−0.39414−1.080793839−0.05249−0.43012−0.9703938400.0353520.4204280.63436538410.0147260.0659690.29602738420.0149310.3377950.4807138430.0006320.0842080.3639033846−0.12428−0.61888−1.1486838470.0240940.2428980.53295138480.014222−0.20545−0.187443850−0.0071−0.39614−1.3129138510.0126840.0707520.27474538520.023720.1723960.34236138530.00189−0.145487−0.2291473854−0.00101−0.21912−0.7296138550.007222−0.15336−0.2696538560.007543−0.15408−0.1518738580.018762−0.28212−0.401153859−0.08983−0.08099−0.9619138600.0041340.119890.7752353861−0.004760.7997690.7754643862−0.020690.6193470.55240438630.0238250.1989660.28891438640.002065−0.18112−0.362738650.0237990.3738230.5027923866−0.07514−0.16355−1.155873867−0.023570.4268810.7680053868−0.06742−0.22372−1.4836238690.007952−0.20656−0.181473870−0.00995−0.18825−0.325613871−0.09391−0.49811−0.671553872−0.01577−0.30748−0.3646938730.00135−0.177−0.2657438740.01437−0.27493−0.6499238750.0086010.1754170.36872538770.02150.2395520.54396838780.007867−0.14612−0.2193879−0.02127−0.13431−0.52143881−0.01449−0.22729−0.386593882−0.008−0.28045−0.350333883−0.00282−0.22456−0.32463884−0.010060.1253350.4374323885−0.0341−0.33793−0.649813886−0.02831−0.22518−0.448433887−0.00342−0.15249−0.4628938880.0143930.4845540.49593138890.0017760.2620780.38302838900.011023−0.01062−0.4416438920.004332−0.00059−0.3824238930.001464−0.14286−0.181263894−0.01231−0.2316−0.3200538950.0181860.0892570.21046638960.0075−0.17357−0.274993897−0.00568−0.14148−0.3782938980.002511−0.14907−0.152973899−0.0092−0.1654−0.4146639000.017440.1081670.3035293902−0.21525−0.62727−0.8826439030.0122940.1017540.42233939040.007328−0.12993−0.1764739060.0325470.22370.37484239070.0208240.4552490.66673239080.001958−0.08941−0.209013909−0.03403−0.28041−0.6676139100.0051240.3733030.45639639110.0075270.4367130.6352863912−0.01004−0.18805−0.19453913−0.138410.130768−0.7861239140.005593−0.24982−0.4592139160.0078710.2945610.47205639170.0004560.3504530.5120853918−0.00721−0.20685−0.3078239190.002490.45530.46741839200.0034330.2341060.34774339210.021590.2676660.2724913922−0.01034−0.23596−0.403163923−0.0218−0.17331−0.315033924−0.01052−0.2608−0.4525839260.005481−0.19415−0.388623927−0.00198−0.15223−0.263783928−0.00481−0.19212−0.600113929−0.02907−0.31237−0.6711539300.0189320.5024990.63077939310.0078230.3301780.3748283932−0.00625−0.19177−0.361883934−0.01138−0.16719−0.6232739360.013418−0.12059−0.219943937−0.00602−0.17249−0.198863938−0.00093−0.18338−0.216213940−0.00630.322370.4472773941−0.031230.7535251.0286173942−0.03893−0.15886−1.0369339430.0161770.3188780.50070839440.029472−0.14649−0.373173945−0.15185−0.49868−0.6073946−0.09644−0.46037−0.5759639480.0101570.2792470.4887239490.002141−0.34666−0.26613950−0.03206−0.28804−0.3691139510.0062730.1221160.4146853952−0.040240.1769530.38337739530.0072−0.23691−0.3425339540.012744−0.16741−0.246553955−0.019735−0.159647−0.330033957−0.001720.0660090.29068339580.0000070.2586180.3664263959−0.07307−0.35372−0.425843960−0.005−0.29445−0.897363962−0.00971−0.14007−0.771283963−0.0012−0.19036−0.181343964−0.00871−0.31654−0.7335139650.007545−0.19764−0.311173967−0.09077−0.42429−0.5019239680.002684−0.24249−0.27393

TABLE 1b

phase reporter genes

SEQ ID NO
log(ratio) CP
log(ratio) AP
log(ratio) BC

56
−0.01844
−0.2843
−0.52572

65
−0.043
−0.27935
−0.61442

70
−0.02677
0.321263
0.479287

177
−0.02343
−0.25951
−0.53988

190
−0.04631
−0.22027
−0.61104

199
−0.19435
−0.66091
−1.74771

1758
−0.0427
−0.06237
−0.68566

1773
0.032164
0.295407
0.487261

1774
0.02296
0.304684
0.561645

1786
0.014041
0.225619
0.584752

1815
0.035253
0.254518
0.53063

1823
0.014591
0.300107
0.456781

3925
−0.04398
−0.3128
−0.99975

3933
−0.0347
−0.12523
−0.74375

3947
−0.04231
−0.53589
−1.45253

3956
−0.00856
−0.16684
−0.95119

Tables 2a and 2b list a set of 386 progression genes identified by searching for phase reporter genes after removing CD34 content (p<10₋₈) (the “progression geneset”). The CD34 content is removed by subtracting the expression level of each gene in a sample of CD34+ cells from the expression level of the gene in a tumor sample from a CML patient. The progression genes are identified by their SEQ ID NOs in Tables 2a and 2b. Information for these genes is presented in Table 8. Table 2a lists progression genes that were not disclosed in U.S. Patent Application Publication 2003/01044026 A1, dated Jun. 5, 2003. Table 2b lists progression genes that were also identified in U.S. Patent Application Publication 2003/01044026 A1, dated Jun. 5, 2003. Tables 2a and 2b also listed for each gene the log ratio of CD34+(−) expression level of the gene (i.e., the expression level of the gene in a tumor sample from a CML patient minus the expression level of the gene in a sample of CD34+ cells) in samples from patients of a particular phase (e.g., CP, AP, or BC) versus CD34+(−) expression level of the gene in a pool of CML bone marrow samples from chronic phase patients. Each log ratio column thus contains expression levels of markers for a particular phase.

TABLE 2aprogression genesSEQ ID NOlog(ratio) CPlog(ratio) APlog(ratio) BC2−0.0130360.3311910.1361922−0.0276250.251240.29716844−0.008283−0.175784−0.3517674−0.0186210.110352−0.541362750.012898−0.15485−0.08157898−0.00650.2261990.3845761180.02350.4137950.572899120−0.068801−0.238346−0.788486123−0.0147760.1538840.3153371270.0143610.27320.196317146−0.062898−0.026859−0.467529166−0.008117−0.02223−0.588809192−0.03375−0.376045−0.824014201−0.0460380.7454510.938831252−0.011159−0.181168−0.338022260−0.0149830.1693810.3782072610.002136−0.0139390.252784277−0.0590710.153895−0.707755282−0.0112920.2468310.217263300−0.0155530.2646160.213715312−0.006268−0.169392−0.4151213210.0172930.2640730.3518153290.015519−0.110525−0.1324423480.0033770.2928660.3850253590.011735−0.238758−0.1591333610.0199−0.29195−0.3081273690.015105−0.30705−0.4676223790.0119720.1531750.287232382−0.0346130.5398560.385649392−0.0180910.2117410.1513593970.001911−0.204817−0.142157398−0.0552560.4547740.4635634010.010902−0.0223−0.4350774070.022957−0.146156−0.1441784080.0005870.0426330.171636413−0.004104−0.021944−0.541188432−0.0211050.3182340.369384530.000187−0.016503−0.2337944620.015733−0.049378−0.203749464−0.007901−0.242419−0.192786468−0.0698180.055712−0.7928614830.0220870.013675−0.264371487−0.044506−0.226859−0.7302554900.0322250.6972530.4734384930.0053650.1176150.2798245060.0022220.2444180.413136508−0.0010480.1498480.252886513−0.0259420.105185−0.5892675320.013898−0.091144−0.105794535−0.029730.31094−0.640132549−0.024057−0.192808−0.507538562−0.007465−0.085295−0.4514085640.0107060.161590.377863565−0.0133770.1899350.358398596−0.027369−0.300983−0.676728602−0.029470.1526020.288592607−0.032080.1636790.433561629−0.0171350.1647540.393246631−0.0059190.0297020.1828956380.0059950.1581710.295784641−0.0023510.141381−0.3713986440.011035−0.188829−0.236191648−0.0003050.093990.156447671−0.0526860.224817−0.778464678−0.011662−0.03032−0.483853686−0.0441460.3934480.3525196870.0041280.0141880.147004688−0.0071120.135577−0.3842386920.01078−0.193913−0.3392496940.0269030.2387280.1989846990.002836−0.136336−0.204499700−0.0035730.1866630.111998702−0.0047950.436930.2317957040.0086520.4485270.6238117080.035423−0.072534−0.2435777100.00051−0.260385−0.325256715−0.031368−0.034762−0.281797250.018721−0.110491−0.076317270.0117010.3524840.5996637300.007214−0.100867−0.390067739−0.0215490.3133990.2305567580.0060660.1972320.154028774−0.0114280.2979060.4607587810.0494640.6613730.621414789−0.0111350.0730250.2205497940.00587−0.124811−0.092198852−0.0097770.0619130.2174138620.0125120.1011030.346959878−0.0071590.6246760.3425398790.0152920.310113−0.6195469020.010570.1085170.2828899060.0091530.1066280.432846912−0.03355−0.086456−0.556116913−0.002153−0.162393−0.176945934−0.0015150.494370.349162949−0.009006−0.003959−0.2606659690.009521−0.194416−0.088755983−0.009189−0.179037−0.2798089840.0037830.428077−0.3045779950.0181940.1155360.4530151005−0.0042060.2646130.40691210060.0137150.253173−0.481711014−0.0270320.2184310.3698741027−0.0978020.14838−0.40913810300.012193−0.156904−0.12991810360.0184570.1501210.28203210420.0164060.123990.2541551047−0.0109560.1603880.2937041053−0.0035970.1682340.18855410650.0413370.3568080.45742810860.0121670.1265560.3088081089−0.0569210.2653450.48813810920.0311640.7413990.6504431093−0.0194580.2652620.2815981100−0.026376−0.1074880.12057911050.0004020.2416750.37454711060.0132750.0531450.28480411110.0066950.3901090.46703311130.00931−0.151037−0.0942381145−0.003373−0.121256−0.2888231161−0.036419−0.112814−0.28997911690.004364−0.149179−0.1377031180−0.0030150.1494850.2431521181−0.0065520.3547430.2737381182−0.0639250.133911−0.7967331201−0.0246310.061529−0.4625341211−0.01310.425410.38921912270.003709−0.172158−0.1199821228−0.001968−0.182794−0.1598812340.003295−0.168464−0.23392912640.007382−0.120962−0.2280591288−0.0251780.3935850.56635212940.0045450.1267080.2836471308−0.051939−0.225136−1.14209413240.0008020.1952160.36847613270.02320.291620.33075113280.016117−0.125314−0.1933341333−0.0016150.1571040.1609181334−0.0031940.078374−0.5854111352−0.013243−0.259131−0.72449513640.020286−0.059623−0.366691394−0.0380310.5694990.2810121400−0.034692−0.392913−0.85537214080.0126130.202286−0.41050914210.0158030.301704−0.28057114340.0234410.248490.40488514650.0113011.1197580.38081714750.002495−0.174538−0.1447461489−0.0058250.1713990.1988911503−0.0108460.339610.34434615380.0087740.2504970.3807361544−0.001566−0.118486−0.22561215650.003841−0.24087−0.1880871586−0.059680.1312140.2319791596−0.0122670.3150770.4629821598−0.0403360.4051190.29597716000.0164730.1719370.48030916130.0186720.6398350.68613116150.003796−0.155045−0.12378716210.0007430.1822620.220261622−0.014220.1085040.4411131624−0.003494−0.128858−0.4162831631−0.0662380.081560.3551716440.0127510.004567−0.2564951653−0.0510370.5759030.6598911666−0.0050180.3044180.39177316670.020618−0.152906−0.07351416740.0010520.2303890.3655511707−0.10203−0.508005−0.4339481713−0.0000330.2271190.2932111723−0.008555−0.0131570.31174217260.01878−0.134004−0.11454417290.0178530.1228850.40371917400.0001290.0826480.2027061744−0.0081650.0289020.1576051754−0.033290.249690.2763911756−0.006572−0.090777−0.1872991764−0.0232920.0619190.4393671765−0.0696080.229406−0.94288817690.0047350.1118160.3802031772−0.0532310.9143640.70312517840.0116650.2661760.26210217980.0068630.1256180.1798331802−0.006187−0.271892−0.54721418130.0049290.074195−0.3890218220.0087090.0585350.1727871851−0.0387060.176417−0.58555718540.011347−0.148867−0.0875918560.023502−0.039695−0.26037818570.001175−0.00306−0.2609831864−0.023131−0.110894−0.59576419020.011275−0.14224−0.0839231906−0.018987−0.066969−0.267831910−0.014553−0.104128−0.20269919270.0161890.022638−0.2101031936−0.008747−0.190402−0.1708719660.009815−0.207021−0.10994919730.0252220.269645−0.25499919970.000408−0.206852−0.0936921998−0.027543−0.140155−0.69991420240.0027460.0216350.2403662041−0.0065460.1621010.39062220420.003359−0.068862−0.13082220540.0032870.1882190.31128320560.017212−0.089889−0.1605762059−0.0201811.1173760.5932132067−0.034481−0.314757−0.57100520690.020052−0.126164−0.0925282084−0.0300240.355370.65156121160.013573−0.038963−0.250632121−0.0710150.041386−0.8509152127−0.0426660.6897940.2486372132−0.0015350.1408870.1968822136−0.0166790.50140.15875121480.007504−0.089503−0.4244512162−0.018781−0.151041−0.2568121960.001252−0.045446−0.14524121970.0119390.0828140.42180322110.016656−0.118424−0.178142218−0.0019940.1322730.1029832222−0.0800430.1290910.18753822470.014934−0.139989−0.1209122248−0.0126640.3248010.48592122590.0091350.109045−0.39041722760.010096−0.162022−0.12012922770.0133340.571954−0.22775622820.003573−0.28411−0.2968932286−0.00426−0.361198−0.3423022298−0.042053−0.27671−0.58916923020.008627−0.135924−0.1848132310−0.001488−0.154965−0.15161123340.0227820.1187420.1550212344−0.046131−0.0435560.35468623730.0136980.020747−0.3003192388−0.0575990.2409090.475523920.007643−0.159192−0.1268312398−0.042170.124478−0.49021924140.0062470.0392790.2313442458−0.047592−0.0211810.6226524640.0094920.4970280.5501052465−0.0617320.8447780.7466452474−0.0105350.3171390.3263824790.009625−0.032207−0.20655324820.0077130.1343650.2281624860.008277−0.165135−0.5053592494−0.008876−0.013903−0.34578824950.023159−0.11675−0.10380125010.024313−0.133841−0.1031725170.010041−0.026346−0.28451825410.001637−0.123709−0.16506125550.009862−0.295888−0.19527125610.0034410.1432970.3936232563−0.001684−0.157035−0.18093525670.0187740.4815160.61725125800.0017170.0720930.4498712584−0.1085110.2372850.3589452591−0.0143770.0165830.1709252599−0.0043140.138559−0.44988626030.011638−0.148946−0.1411572606−0.008722−0.002843−0.26365226120.006823−0.083968−0.18177426270.033377−0.002066−0.3075582631−0.091338−0.170022−1.01513726370.000709−0.02223−0.366862654−0.018035−0.080645−0.38019526590.0229760.5370170.8162122664−0.002476−0.035144−0.35438726960.0616990.2956730.6241812698−0.008783−0.162188−0.31909626990.021373−0.029099−0.14344427000.0041120.2787440.20427127070.014731−0.005959−0.19209427500.007282−0.224306−0.3356652769−0.0853570.275787−0.77208427720.017216−0.120145−0.3432862775−0.0116730.7692120.45189628100.004075−0.190069−0.24061928110.009903−0.176453−0.08596828130.0033360.2026590.19171428150.0063030.0923940.15083628240.00192−0.131874−0.16637128350.020297−0.126422−0.20697128560.006157−0.130875−0.2875152864−0.0125840.1129570.20256928650.002638−0.150304−0.2654392868−0.0023540.0255940.2768772873−0.003375−0.040933−0.55943328910.0129680.266850.2126122897−0.0042670.323080.4630932905−0.045096−0.397135−0.8599172926−0.0052350.0983920.20083629310.0249670.1932280.41026829360.024484−0.182182−0.11234629380.01805−0.289863−0.27324429460.005996−0.125692−0.08421429640.019559−0.127505−0.38553429650.007544−0.131222−0.157632972−0.0620890.0823590.19947229730.0031450.1460620.41322629760.0077410.072786−0.2994742981−0.018057−0.15181−0.33547229950.012536−0.169059−0.0902523004−0.0045860.0549520.21318830140.005466−0.153481−0.20364130220.015475−0.112142−0.2085323059−0.0148590.2699370.2417673079−0.011007−0.20423−0.5163563085−0.007467−0.154645−0.26353530940.009534−0.137767−0.1464231050.0232820.3251010.25434631200.03070.350781−0.24119831300.009997−0.13136−0.14397631320.011847−0.085343−0.25160531610.008344−0.156984−0.1873693185−0.0116620.3241660.47681131940.0020830.140880.28490432110.0041570.2062720.38662832140.0254590.1027410.24095732150.00353−0.064073−0.16779332280.017223−0.161965−0.072632370.002668−0.0092350.219073245−0.039738−0.344767−0.5124093269−0.033522−0.404287−0.5882283279−0.0597440.2642620.3893713288−0.001709−0.176379−0.3801423328−0.0015450.0725950.207733370.013590.2447760.2081253338−0.020347−0.138845−0.5065523341−0.049209−0.011969−0.41913933560.023516−0.13485−0.11047633570.000456−0.135074−0.0918563380−0.012204−0.399725−0.45496933870.0082670.3306650.1910953390−0.0020490.2483030.327033395−0.006382−0.249059−0.2013653402−0.0848960.0549380.4637163416−0.039529−0.201668−0.5784393420−0.000395−0.09677−0.2063534230.0125580.0878820.24239434260.011070.146821−0.4329863443−0.015748−0.058532−0.4008993444−0.0178380.1123610.2170734700.012350.2026630.42568634730.0077910.2227270.4869923477−0.007804−0.0120070.1801833496−0.0789140.888380.6192443516−0.03045−0.252169−0.48505135220.0142470.2556930.38797535490.0121221.0723680.65204135600.0104520.0671710.16782535690.0080550.2364480.46336435710.012994−0.148049−0.08774435790.004924−0.17069−0.1222343585−0.0014110.2039540.12442435940.022686−0.159764−0.11360535950.008890.7782680.7245423627−0.018961−0.122255−0.4552863649−0.00753−0.075377−0.2459853655−0.009543−0.0303720.28024536580.010488−0.100563−0.3168223662−0.021261−0.177479−0.1649253678−0.018901−0.069804−0.4040536890.0081790.1116660.21224337150.0005970.194480.23731537200.0069750.316981−0.5546673724−0.0067560.02331−0.3927423727−0.023638−0.142935−0.65174737490.010030.0439790.21577637510.029168−0.073576−0.14018237540.0014960.1071860.1659133755−0.0219190.1954420.37917537740.0086010.0818420.1894293781−0.027603−0.124679−0.3892113795−0.009508−0.235417−0.34075638480.008156−0.137025−0.09142538530.00189−0.145487−0.2291473854−0.009932−0.323309−0.6279163865−0.0067820.0818350.09988738690.026028−0.164373−0.0895238740.0029770.004837−0.3541823878−0.00536−0.135863−0.29369839080.01371−0.080601−0.14001939380.005563−0.114606−0.09846939410.0180120.1776390.0904443955−0.019735−0.159647−0.33003

TABLE 2b

progression genes

SEQ ID NO
log(ratio) CP
log(ratio) AP
log(ratio) BC

3925
0.003797
−0.153433
−0.114664

Table 3 lists the “top ten” genes that are associated with progression and response, independent of normal CD34+ expression, based on log 10 ratio of expression compared to the chronic phase pool. These genes are identified by their SEQ ID NOs in Table 3. Information for these genes is presented in Table 8.

TABLE 3“top ten” genesSEQID NOlog(ratio) CPlog(ratio) APlog(ratio) BCREGULATION902000.599663up98400−0.77846down133400−0.94289down175600−0.78849down181300−0.85091down197300−0.79673down205600−1.01514down221100−0.82401down2561000.686131up281000−0.85992down2813000.652041up2815000.816212up282400−1.14209down2864000.651561up2973000.746645up308500−0.85537down3211000.617251up3477000.619244up3749000.703125up3941000.659891up

Table 4 lists a set of 228 genes associated with imatinib resistance (the “imatinib resistance genes”). The imatinib resistance genes are identified by their SEQ ID NOs in Table 4. Information for these genes is presented in Table 8. Table 4 also listed for each gene the log ratio of expression level of the gene in samples from patients of a particular phase (e.g., CP, AP, or BC) or IM resistance (IM) versus expression level of the gene in a pool of CML bone marrow samples from chronic phase patients. Each log ratio column thus contains expression levels of markers for a particular phase or IM resistence.

TABLE 4genes associated with imatinib resistanceSEQ ID NOlog(ratio) CPlog(ratio) APlog(ratio) BClog(ratio) IM2000−0.387090.2638872800−0.019120.26512450000.049670.3837037200−0.031840.2486687700−0.10970.2309799100−0.213630.30213593000.0128720.24898997000.0840150.441542124000.2308880.53546213400−0.037030.17900615000−0.06930.17206815500−0.136790.157108171000.1969590.633551195000.021230.207227243000.111120.69570725400−0.081120.26940126900−0.035730.29894927500−0.152510.21230528300−0.035960.21647292000.206140.549719342000.2081940.67779337100−0.060270.44978637200−0.021060.35123437700−0.169010.16143838600−0.075310.18077640600−0.067670.37169942600−0.050360.28157644200−0.144730.19871845600−0.054280.21539445900−0.032020.34577146900−0.189030.227286480000.0382170.68465553100−0.171950.41487956800−0.064140.09845262200−0.407980.83349766200−0.008840.21749666300−0.094380.10719867000−0.172450.1338709000.1874560.55381872200−0.110730.16212476800−0.101150.42413785000.2195110.69075879600−0.126560.14598185600−0.019240.40057588000−0.102360.27847589400−0.027320.20698491700−0.255610.212912924000.2242690.70807797300−0.012750.73076597700−0.103170.40081898000−0.17850.286644100800−0.109280.1081721014000.1482440.8650651023000.0983350.878985103700−0.334760.837053103800−0.206270.621468105200−0.20690.2368611059000.1480360.402311107400−0.332640.2398421089000.1742840.9854521095000.3046560.927005112400−0.070930.616113114300−0.181750.201291115700−0.181740.21747117000−0.083770.431166117300−0.095150.560044118200−0.454460.1425461190000.0410070.359776121500−0.067810.83596121900−0.072240.165806122400−0.057760.205308124700−0.086940.1854211249000.2635150.6057481267000.2634641.063745132300−0.22060.10102132900−0.005370.436924133100−0.014090.755256133600−0.156670.34331136700−0.32070.489696137900−0.170260.2052011389000.0799370.3592091435000.0921790.722108144900−0.4670.1719561451000.4251810.859676147800−0.1520.1220731482000.1119520.395553149400−0.167520.177726152600−0.155690.1660921534000.100570.802351154900−0.019580.262207156600−0.072280.3140481591000.2531250.761339165700−0.027030.334287167100−0.135320.128801170800−0.039560.2063511709000.2652640.510844173100−0.160890.119466178900−0.281250.246382182000−0.428720.604742183900−0.019850.6524891840000.0572410.774482189800−0.394670.3785271948000.0827450.793455194900−0.182080.868135195900−0.224550.344545196500−0.265220.569866201200−0.352470.314792033000.0400060.3453422073000.0392770.877752208100−0.055390.149592208700−0.295160.404949208800−0.025810.326797210600−0.235920.332507212600−0.024390.515267214500−0.25590.725553215100−0.011350.414351217200−0.081990.39351217800−0.266190.102312218100−0.060550.1581352183000.2236050.9779492189000.2169361.068883219900−0.277140.840265220700−0.296810.440807222800−0.056890.930733224400−0.373350.576383226900−0.174820.171115228500−0.053230.923962228600−0.111880.142335228900−0.317470.3542292292000.4373190.959855235400−0.061860.222863238700−0.605220.324344238800−0.117860.7254992408000.271780.449011242700−0.08120.1741952437000.0278951.0828112449000.0120280.297163247900−0.225820.179989249200−0.250090.3491562531000.072760.6623122545000.0216030.945236255300−0.012760.395767256400−0.283450.250146256800−0.109770.196162582000.2530150.6341722615000.1288641.013705261800−0.29050.559533262900−0.062430.410775263300−0.416920.3928932652000.2050310.647252265300−0.003960.377357266000−0.534330.3936172665000.0625540.6864412666000.0172310.2766122686000.0740550.3529622697000.1428790.7226472756000.0338830.281303278000−0.431990.4572222802000.0320770.2489532807000.0888180.8654092828000.3758050.936957284400−0.101820.193285287900−0.110630.376181289600−0.126020.4338512942000.0383290.2616382955000.3379850.6164132977000.0063180.640784298000−0.062560.752042298400−0.08390.535325298900−0.047670.23291299400−0.124130.24541300400−0.222210.402371301500−0.384680.767185304000−0.158740.553807305100−0.160140.258388309500−0.234490.4533993145000.0467090.349592314900−0.074790.13184317200−0.092160.235379317800−0.160510.189495318100−0.181230.657828318300−0.085630.644291323400−0.093190.622993323900−0.152250.543178326300−0.098850.51508326700−0.08020.247087327200−0.065190.20193328400−0.399280.5646773317000.0422570.663222332400−0.03870.202691333400−0.142180.4021623342000.0943680.377785336000−0.181530.352019337000−0.072910.1546293373000.2662081.011433378000.1548220.4717373389000.0962150.2923963402000.1662220.929501343300−0.089580.164089347600−0.026120.185903347900−0.238060.3072063482000.0173780.2675813546000.0716370.321201355400−0.108650.21563362000−0.181830.2307873632000.048040.247622367700−0.144730.2013143683000.003010.2633368600−0.038520.375431369200−0.593340.407906371100−0.076970.1336372500−0.11570.688963374600−0.096860.406243376500−0.384590.568063378500−0.027610.586677379300−0.016820.4329563800000.0939780.6930843804000.1493440.9638173812000.0788750.7190193836000.2457250.62927387600−0.103770.2457473891000.0567430.30804390500−0.189470.77305393500−0.18370.688495393900−0.132030.177443394600−0.575960.119957396600−0.148540.290791

Tables 5a and 5b list 386 target genes, which are differentially expressed between CML blast crisis and normal immature CD34+ cells (p<0.1%) (the “target geneset”). The target genes are identified by their SEQ ID NOs in Tables 5a and 5b. Information for these genes is presented in Table 8. Table 5a lists target genes that that were not disclosed in U.S. Patent Application Publication 2003/01044026 A1, dated Jun. 5, 2003. Table 5b lists target genes that were also identified in U.S. Patent Application Publication 2003/01044026 A1, dated Jun. 5, 2003.

TABLE 5aCML target genesSEQ ID NO2851748899105109116142146158174184185191204246252261267298309312321337343359365370379390393432444483490493494495503506522562564565571576596600602605607615628629631638644659664665675676688700701727728730741745759766781788790809813843840841845847873878884900902906908915934960962983100010121014102010271036105110541067108910931106111211321138114011451158116011611164116511831188119712021223124512541288130013061308131113251331133413461352138014001409141014111415141614401441144614521456146414721489149515001502150315221527153215341575159616081614164316521674168917111712171317241728175617571762176717721781178517981799180018021803181318281849187018731893191019261927194419901991199820072011202320322040204220562064208220852101210421362161216221742188220022062211221222132218222422482252225322662279230423102312231323202329235623722388240624422454246224692479250525252534255425612563256525672591260026312632264926542658266426652670267626962699272127262734273927662775277727882810282428252830284228622863286428922894290029032921292829382953296429672981300330193020302730293047304830673075308530933094309731033136318531913194319632153222323832403241324532483254327933123329333933483361336433733380339533963398340034023428345634623470350035143533353835553569358235833611362836403642364636503655365836853689369637183755376337923844384538493857388039013915393739403955

TABLE 5b

CML target genes

SEQ ID NO
log(ratio) BC

1776
0

3961
0

Genes that are not listed in Table 1a or 1b but which are functional equivalents of any gene listed in Table 1a or 1b can also be used with or in place of the gene listed in the table. A functional equivalent of a gene A refers to a gene that encodes a protein or mRNA that at least partially overlaps in physiological function in the cell to that of the protein or mRNA of gene A.

In various specific embodiments, different numbers and subcombinations of the genes listed in Tables 1a and/or 1b are selected as the marker set, whose profile is used in the methods of the invention, as described in Section 5.2., infra. In various embodiments, all or a subset of those genes listed in each of Tables 2a and/or 2b or Table 3, supra, or their respective functional equivalents are used.

In one embodiment, one or more genes that cluster together with one or more genes listed in a table can be selected to represent the cluster such that the marker set contains genes representing a plurality of different clusters.

In a specific embodiment, measurements of gene products of the genes, respectively, shown in Tables 2a and/or 2b, or their respective functional equivalents, are used for CML progression evaluation. In a particular embodiment, measurements of gene products of all or at least 5, 10, 15, 20, 25, 30, 40, 50, 60, 70, 80, 90, 100 or 200 of the genes listed in Tables 2a and/or 2b are used.

In another embodiment, measurements of the gene products of the set of 20 genes shown in Table 3 (which is a subset of the genes listed in Table 2a and Table 5a) or their respective functional equivalents are used CML progression evaluation. In a particular embodiment, measurements of gene products of all or at least 5, 10, 15 or 20 of the genes listed in Table 3 are used.

In another embodiment, measurements of the gene products of the set of 10 up-regulated genes shown in Table 3 or their respective functional equivalents are used CML progression evaluation. In a particular embodiment, measurements of gene products of all or at least 5, 6, 7, 8, 9 or all 10 of the up-regulated genes listed in Table 3 are used.

In another embodiment, measurements of the gene products of the set of 10 down-regulated genes shown in Table 3 or their respective functional equivalents are used CML progression evaluation. In a particular embodiment, measurements of gene products of all or at least 5, 6, 7, 8, 9 or all 10 of the down-regulated genes listed in Table 3 are used.

In still another embodiment, measurements of the genes, respectively, shown in Table 4 or their respective functional equivalents are used for determining imatinib resistence in a patient. In a particular embodiment, measurements of gene products of all or at least 5, 10, 15, 20, 25, 30, 40, 50, 60, 70, 80, 90, 100 or 200 of the genes listed in Table 4 are used. In a specific embodiment, imatinib resistance is determined according to the measurements of gene products of all or at least 5, 6, 7, or 8 of the genes selected from the group consisting of serine threonine kinases CTRL, MAP21K14, CLK3, MAP kinase MKNK2, the tyrosine kinase oncogene FYN, TCF7 (a putatively T cell specific transcription factor), guanine nucleotide binding proteins GNAZ and GNG11, and the MAF.

The invention also provides sets of promoter controlled genes, measurements of which can be used for evaluating the progression of CML in a patient. In one embodiment, measurements of the gene products of genes that are controlled by one or more of the promoters shown in Table 6 or their respective functional equivalents are used for evaluating CML progression. In a particular embodiment, measurements of gene products controlled by a promoter selected from the group consisting of set of promoters shown in Table 6 or their respective functional equivalents are used.

TABLE 6Promoters associated with CML progressionPROMOTERP-VALUEEXPECTATIONSOURCESPECIESMZF_1-400Genes with common promoter sitesHomosapiensS81.22E−127.69E−11Genes with common promoter sitesHomosapiensdeltaEF15.87E−113.70E−09Genes with common promoter sitesHomosapiensSPI-B1.48E−109.35E−09Genes with common promoter sitesHomosapiensYin-Yang1.48E−099.30E−08Genes with common promoter sitesHomosapiensAhr-ARNT1.60E−091.01E−07Genes with common promoter sitesHomosapiensMZF_5-131.26E−067.96E−05Genes with common promoter sitesHomosapiensc-MYB_15.10E−060.000321Genes with common promoter sitesHomo

The invention provides methods for identifying a set of genes for evaluating stage/progression of CML. The methods make use of measured expression profiles of a plurality of genes (e.g., measurements of abundance levels of the corresponding gene products) in bone marrow or blood samples from a plurality of patients whose CML stage/progression status are known. As used herein, a patient is animal inflicted with CML. The patient can be but is not limited to a human, or, in a veterinary context, from non-human animals such as ruminants, horses, swine or sheep, or from domestic companion animals such as felines and canines. In one embodiment, for each of the plurality of genes a metric of correlation between expression level of the gene and survival outcome in the plurality of CML patients is determined. One or more genes are then selected based on their metrics of correlation.

Progression markers can be obtained by identifying genes whose expression levels are significantly different across CML patients of different phases of CML. In preferred embodiments, genes whose expression levels exhibit differences across different phrase groups to at least a predetermined level are selected as the genes whose expression levels correlate with CML phases. In one embodiment, the expression level differences among patients of different CML phases are evaluated using ANOVA. In one embodiment, a gene is selected if the p-value of the gene corresponds to a predetermined significance level, e.g., a p-value less than 10₋₁₁.

The invention also provides a computer system comprising a processor, and a memory coupled to said processor and encoding one or more programs, wherein said one or more programs cause the processor to carry out a method described above.

5.2. Methods of Evaluating CML Progression and Responses The invention provides methods for determining the stage or progression status in a CML patient using a measured marker profile comprising measurements of the gene products of genes, e.g., the sets of genes described in Section 5.1., supra.
5.2.1. Methods for Evaluating Progression Based On Expression Profiles

In preferred embodiments, the methods of the invention use a progression classifier, also called a classifier, for predicting CML progression and/or responsiveness to imatinib mesylate in a patient. The progression classifier can be based on any appropriate pattern recognition method that receives an input comprising a marker profile and provides an output comprising data indicating which phase the patient belongs. The progression classifier can be trained with training data from a training population of CML patients. Typically, the training data comprise for each of the CML patients in the training population a training marker profile comprising measurements of respective gene products of a plurality of genes in a suitable sample taken from the patient and CML progression information. In a preferred embodiment, the training population comprises patients from each of the different stages of CML, i.e., CP-CML, ADV-CML, or AP-CML and BC-CML. In another preferred embodiment, the training population comprises patients from each of the different IM response groups, i.e., IM resistant and IM responsive.

In preferred embodiments, the progression classifier can be based on a classification (pattern recognition) method described below, e.g., profile similarity (Section 5.2.1.1., infra); artificial neural network (Section 5.2.1.2., infra); support vector machine (SVM, Section 5.2.1.3., infra); logic regression (Section 5.2.1.4., infra), linear or quadratic discriminant analysis (Section 5.2.1.5., infra), decision trees (Section 5.2.1.6., infra), clustering (Section 5.2.1.7., infra), principal component analysis (Section 5.2.1.8., infra), nearest neighbor classifer analysis (Section 5.2.1.9., infra). Such progression classifiers can be trained with the training population using methods described in the relevant sections, infra.

The marker profile can be obtained by measuring the plurality of gene products in a CML cell sample from the patient using a method known in the art, e.g., a method described in Section 5.2.4-5.2.5., infra.

Various known statistical pattern recognition methods can be used in conjunction with the present invention. A progression classifier based on any of such methods can be constructed using the marker profiles and progression data of training patients. Such a progression classifier can then be used to evaluate the progression status of a CML patient based on the patient's marker profile. The methods can also be used to identify markers that discriminate between different progression status and/or imatinib resistance using a marker profile and progression and/or imatinib resistance data of training patients. For simplicity, the methods are often discussed with respect to evaluation of the progression status. It will be understood by a person skilled in the art that the methods are equally applicable to evaluation of IM responsiveness.

5.2.1.1. Profile Matching

A patient's CML stage or progression status can be evaluated by comparing a marker profile obtained in a suitable sample from the patient with a marker profile that is representative of a particular CML phase. Such a marker profile is also termed a “template profile” or a “template.” The degree of similarity to such a template profile provides an evaluation of the patient's CML stage or progression status. If the degree of similarity of the patient marker profile and a template profile is above a predetermined threshold, the patient is assigned a CML phase or progression status represented by the template. For example, a patient's CML stage or progression status can be evaluated by comparing a marker profile of the patient to a predetermined template profile corresponding to a certain CML stage or progression status, e.g., an ADV-CML template comprising measurements of the plurality of markers which are representative of levels of the markers in a plurality of advanced phase patients or a CP-CML template comprising measurements of the plurality of markers which are representative of levels of the markers in a plurality of chronic phase patients.

In one embodiment, the similarity is represented by a correlation coefficient between the patient's profile and the template. In one embodiment, a correlation coefficient above a correlation threshold indicates a high similarity, whereas a correlation coefficient below the threshold indicates a low similarity.

In a specific embodiment, P_imeasures the similarity between the patient's profile {right arrow over (y)} and a template profile, e.g., a template profile comprising measurements of marker gene products representative of measurements of marker gene products of a level of progression of CML, e.g., the CP-CML template {right arrow over (z)}_CPor the ADV-CML template {right arrow over (z)}_ADV. Such a coefficient, P_i, can be calculated using the following equation:

P_i=({right arrow over (z)}_i•{right arrow over (y)})/(∥{right arrow over (z)}_i∥·∥{right arrow over (y)}∥)

where i designates the ith template. For example, i is CP for CP-CML template. Thus, in one embodiment, {right arrow over (y)} is classified as a CP-CML profile if P_CPis greater than a selected correlation threshold. In another embodiment, {right arrow over (y)} is classified as an ADV-CML profile if P_ADVis greater than a selected correlation threshold. In preferred embodiments, the correlation threshold is set as 0.3, 0.4, 0.5 or 0.6. In another embodiment, {right arrow over (y)} is classified as a CP-CML profile if P_CPis greater than P_ADV, whereas {right arrow over (y)} is classified as a ADV-CML profile if P_CPis less than P_ADV.

In another embodiment, the correlation coefficient is a weighted dot product of the patient's profile {right arrow over (y)} and a template profile, in which measurements of each different marker is assigned a weight.

In another embodiment, similarity between a patient's profile and a template is represented by a distance between the patient's profile and the template. In one embodiment, a distance below a given value indicates high similarity, whereas a distance equal to or greater than the given value indicates low similarity.

In one embodiment, the Euclidian distance according to the formula

D_i=∥{right arrow over (y)}−{right arrow over (z)}_i∥

is used, where D_imeasures the distance between the patient's profile {right arrow over (y)} and a template proflie comprising measurements of marker gene products representative of measurements of marker gene products of a level of progression of CML, e.g., the CP-CML template {right arrow over (z)}_CP, the ADV-CML template {right arrow over (Z)}_ADVor the AP-CML template {right arrow over (Z)}_APor BC-CML template {right arrow over (Z)}_BC. In other embodiments, the Euclidian distance is squared to place progressively greater weight on cellular constituents that are further apart. In alternative embodiments, the distance measure D_iis the Manhattan distance provide by
$D_{i} = \sum_{n} \langle y (n) - z_{i} (n) \rangle$

where y(n) and z_i(n) are respectively measurements of the nth marker gene product in the patient's profile {right arrow over (y)} and a template profile.

In another embodiment, the distance is defined as D_i=1−P_i, where P_iis the correlation coefficient or normalized dot product as described above.

In still other embodiments, the distance measure may be the Chebychev distance, the power distance, and percent disagreement, all of which are well known in the art.

A distance based similarity measure is particularly useful for classifying advanced phase CML patients as either AP-CML or BC-CML since the marker profiles of AP-CML and BC-CML differ from each other in a quantitative rather than qualitative manner. Thus, in one embodiment, the invention provides a method for classifying an advanced phase CML patient as either AP-CML or BC-CML by comparing the distances between a marker profile of the patient with an AP-CML template and a BC-CML template, and classifying the patient as either AP-CML or BC-CML if the distance to the corresponding template is smaller.

A person skilled in the art would understand that the above described methods can be applied to expression profiles of IM resistance genes for evaluation of IM responsiveness. For example, the methods can be used to compare a patient expression profile to IM resistance template and IM responsive template by calculating a P_imeasuring the similarity between the patient's profile {right arrow over (y)} and the IM resistance template comprising measurements of marker gene products representative of measurements of marker gene products in IM resistant patients, {right arrow over (z)}_resist, and/or IM responsive template comprising measurements of marker gene products representative of measurements of marker gene products in IM responsive patients, {right arrow over (z)}_resp. Such a coefficient, P_i, can be calculated using the equation described above.

5.2.1.2. Artificial Neutal Network

In some embodiments, a neural network is used to classify a patient marker profile. The neural network takes the patient marker profile as an input and generates an output comprising the progression status and/or IM responsiveness. A neural network can be constructed for a selected set of molecular markers of the invention. A neural network is a two-stage regression or classification model. A neural network has a layered structure that includes a layer of input units (and the bias) connected by a layer of weights to a layer of output units. For regression, the layer of output units typically includes just one output unit. However, neural networks can handle multiple quantitative responses in a seamless fashion.

In multilayer neural networks, there are input units (input layer), hidden units (hidden layer), and output units (output layer). There is, furthermore, a single bias unit that is connected to each unit other than the input units. Neural networks are described in Duda et al., 2001, Pattern Classification, Second Edition, John Wiley & Sons, Inc., New York; and Hastie et al., 2001, The Elements of Statistical Learning, Springer-Verlag, New York.

The basic approach to the use of neural networks is to start with an untrained network, present a training pattern, e.g., marker profiles from training patients, to the input layer, and to pass signals through the net and determine the output, e.g., the status of progression and/or the status of imatinib resistance in the training patients, at the output layer. These outputs are then compared to the target values; any difference corresponds to an error. This error or criterion function is some scalar finction of the weights and is minimized when the network outputs match the desired outputs. Thus, the weights are adjusted to reduce this measure of error. For regression, this error can be sum-of-squared errors. For classification, this error can be either squared error or cross-entropy (deviation). See, e.g., Hastie et al., 2001, The Elements of Statistical Learning, Springer-Verlag, New York.

Three commonly used training protocols are stochastic, batch, and on-line. In stochastic training, patterns are chosen randomly from the training set and the network weights are updated for each pattern presentation. Multilayer nonlinear networks trained by gradient descent methods such as stochastic back-propagation perform a maximum-likelihood estimation of the weight values in the model defined by the network topology. In batch training, all patterns are presented to the network before learning takes place. Typically, in batch training, several passes are made through the training data. In online training, each pattern is presented once and only once to the net.

In some embodiments, consideration is given to starting values for weights. If the weights are near zero, then the operative part of the sigmoid commonly used in the hidden layer of a neural network (see, e.g., Hastie et al., 2001, The Elements of Statistical Learning, Springer-Verlag, New York) is roughly linear, and hence the neural network collapses into an approximately linear model. In some embodiments, starting values for weights are chosen to be random values near zero. Hence the model starts out nearly linear, and becomes nonlinear as the weights increase. Individual units localize to directions and introduce nonlinearities where needed. Use of exact zero weights leads to zero derivatives and perfect symmetry, and the algorithm never moves. Alternatively, starting with large weights often leads to poor solutions.

Since the scaling of inputs determines the effective scaling of weights in the bottom layer, it can have a large effect on the quality of the final solution. Thus, in some embodiments, at the outset all expression values are standardized to have mean zero and a standard deviation of one. This ensures all inputs are treated equally in the regularization process, and allows one to choose a meaningful range for the random starting weights. With standardization inputs, it is typical to take random uniform weights over the range [−0.7, +0.7].

A recurrent problem in the use of networks having a hidden layer is the optimal number of hidden units to use in the network. The number of inputs and outputs of a network are determined by the problem to be solved. In the present invention, the number of inputs for a given neural network can be the number of molecular markers in the selected set of molecular markers of the invention. The number of output for the neural network will typically be just one. However, in some embodiment more than one output is used so that more than just two states can be defined by the network. If too many hidden units are used in a neural network, the network will have too many degrees of freedom and is trained too long, there is a danger that the network will overfit the data. If there are too few hidden units, the training set cannot be learned. Generally speaking, however, it is better to have too many hidden units than too few. With too few hidden units, the model might not have enough flexibility to capture the nonlinearities in the data; with too many hidden units, the extra weight can be shrunk towards zero if appropriate regularization or pruning, as described below, is used. In typical embodiments, the number of hidden units is somewhere in the range of 5 to 100, with the number increasing with the number of inputs and number of training cases.

One general approach to determining the number of hidden units to use is to apply a regularization approach. In the regularization approach, a new criterion function is constructed that depends not only on the classical training error, but also on classifier complexity. Specifically, the new criterion function penalizes highly complex models; searching for the minimum in this criterion is to balance error on the training set with error on the training set plus a regularization term, which expresses constraints or desirable properties of solutions:

J=J_pat+λJ_reg.

The parameter λ is adjusted to impose the regularization more or less strongly. In other words, larger values for λ will tend to shrink weights towards zero: typically cross-validation with a validation set is used to estimate λ. This validation set can be obtained by setting aside a random subset of the training population. Other forms of penalty can also be used, for example the weight elimination penalty (see, e.g., Hastie et al., 2001, The Elements of Statistical Learning, Springer-Verlag, New York).

Another approach to determine the number of hidden units to use is to eliminate—prune—weights that are least needed. In one approach, the weights with the smallest magnitude are eliminated (set to zero). Such magnitude-based pruning can work, but is nonoptimal; sometimes weights with small magnitudes are important for learning and training data. In some embodiments, rather than using a magnitude-based pruning approach, Wald statistics are computed. The fundamental idea in Wald Statistics is that they can be used to estimate the importance of a hidden unit (weight) in a model. Then, hidden units having the least importance are eliminated (by setting their input and output weights to zero). Two algorithms in this regard are the Optimal Brain Damage (OBD) and the Optimal Brain Surgeon (OBS) algorithms that use second-order approximation to predict how the training error depends upon a weight, and eliminate the weight that leads to the smallest increase in training error.

Optimal Brain Damage and Optimal Brain Surgeon share the same basic approach of training a network to local minimum error at weight w, and then pruning a weight that leads to the smallest increase in the training error. The predicted functional increase in the error for a change in full weight vector δw is:
$δ J = {(\frac{\partial J}{\partial w})}^{t} \cdot δ w + \frac{1}{2} δ w^{t} \cdot \frac{\partial^{2} J}{\partial w^{2}} \cdot δ w + O ({ δ w }^{3})$

where
$\frac{\partial^{2} J}{\partial w^{2}}$

is the Hessian matrix. The first term vanishes because we are at a local minimum in error; third and higher order terms are ignored. The general solution for minimizing this function given the constraint of deleting one weight is:
$δ w = - \frac{w_{q}}{{[H^{- 1}]}_{qq}} H^{- 1} \cdot u_{q} and L_{q} = \frac{1}{2} - \frac{w_{q}^{2}}{{[H^{- 1}]}_{qq}}$

Here, u_qis the unit vector along the qth direction in weight space and L_qis approximation to the saliency of the weight q—the increase in training error if weight q is pruned and the other weights updated δw. These equations require the inverse of H. One method to calculate this inverse matrix is to start with a small value, H₀₋₁=α₋₁I, where α is a small parameter—effectively a weight constant. Next the matrix is updated with each pattern according to
$H_{m + 1}^{- 1} = H_{m}^{- 1} - \frac{H_{m}^{- 1} X_{m + 1} X_{m + 1}^{T} H_{m}^{- 1}}{\frac{n}{a_{m}} + X_{m + 1}^{T} H_{m}^{- 1} X_{m + 1}}$

where the subscripts correspond to the pattern being presented and α_mdecreases with m. After the full training set has been presented, the inverse Hessian matrix is given by H₋=H_n₋₁. In algorithmic form, the Optimal Brain Surgeon method is:

- begin initialize n_H, w, θ
  - train a reasonably large network to minimum error
  - do compute H₋₁by Eqn. 1
    $q^{*} \leftarrow \arg \min_{q} w_{q}^{2} / ({2 [H^{- 1}]}_{qq}) (saliency L_{q})$ $w \leftarrow w - \frac{w_{q^{*}}}{{[H^{- 1}]}_{q^{*} q^{*}}} H^{- 1} e_{q^{*}} (saliency L_{q})$
  - until J(w)>θ
- return w
- end

The Optimal Brain Damage method is computationally simpler because the calculation of the inverse Hessian matrix in line 3 is particularly simple for a diagonal matrix. The above algorithm terminates when the error is greater than a criterion initialized to be θ. Another approach is to change line 6 to terminate when the change in J(w) due to elimination of a weight is greater than some criterion value.

In some embodiments, a back-propagation neural network (see, for example Abdi, 1994, “A neural network primer”, J. Biol System. 2, 247-283) containing a single hidden layer of ten neurons (ten hidden units) found in EasyNN-Plus version 4.0 g software package (Neural Planner Software Inc.) is used. In a specific example, parameter values within the EasyNN-Plus program are set as follows: a learning rate of 0.05, and a momentum of 0.2. In some embodiments in which the EasyNN-Plus version 4.0 g software package is used, “outlier” samples are identified by performing twenty independently-seeded trials involving 20,000 learning cycles each.

5.2.1.3. Support Vector Machine

In some embodiments of the present invention, support vector machines (SVMs) are used to classify subjects using expression profiles of marker genes described in the present invention. The SVM takes the patient marker profile as an input and generates an output comprising the progression status and/or IM responsiveness. General description of SVM can be found in, for example, Cristianini and Shawe-Taylor, 2000, An Introduction to Support Vector Machines, Cambridge University Press, Cambridge, Boser et al., 1992, “A training algorithm for optimal margin classifiers, in Proceedings of the 5^thAnnual ACM Workshop on Computational Learning Theory, ACM Press, Pittsburgh, Pa., pp. 142-152; Vapnik, 1998, Statistical Learning Theory, Wiley, N.Y.; Duda, Pattern Classification, Second Edition, 2001, John Wiley & Sons, Inc.; Hastie, 2001, The Elements of Statistical Learning, Springer, N.Y.; and Furey et al., 2000, Bioinformatics 16, 906-914. Applications of SVM in biological applications are described in Jaakkola et al., Proceedings of the 7^thInternational Conference on Intelligent Systems for Molecular Biology, AAAI Press, Menlo Park, Calif. (1999); Brown et al., Proc. Natl. Acad. Sci. 97(1):262-67 (2000); Zien et al., Bioinformatics, 16(9):799-807 (2000); Furey et al., Bioinformatics, 16(10):906-914 (2000)

In one approach, when a SVM is used, the gene expression data is standardized to have mean zero and unit variance and the members of a training population are randomly divided into a training set and a test set. For example, in one embodiment, two thirds of the members of the training population are placed in the training set and one third of the members of the training population are placed in the test set. The expression values for a selected set of genes of the present invention is used to train the SVM. Then the ability for the trained SVM to correctly classify members in the test set is determined. In some embodiments, this computation is performed several times for a given selected set of molecular markers. In each iteration of the computation, the members of the training population are randomly assigned to the training set and the test set. Then, the quality of the combination of molecular markers is taken as the average of each such iteration of the SVM computation.

Support vector machines map a given set of binary labeled training data to a high-dimensional feature space and separate the two classes of data with a maximum margin hyperplane. In general, this hyperplane corresponds to a nonlinear decision boundary in the input space. Let X └ R₀⊂ custom character ⁿbe the input vectors, y ∈ {−1,+1} be the labels, and φ: R₀→F be the mapping from input space to feature space. Then the SVM learning algorithm finds a hyperplane (w,b) such that the quantity
$γ = \min_{i} y_{i} {〈 w, ϕ (X_{i}) 〉 - b}$

is maximized, where the vector w has the same dimensionality as F, b is a real number, and γ is called the margin. The corresponding decision function is then

ƒ(X)=sign(<w,φ(X)>−b)

This minimum occurs when
$w = \sum_{i} α_{i} y_{i} ϕ (X_{i})$

where {α_i} are positive real numbers that maximize
$\sum_{i} α_{i} - \sum_{ij} α_{i} α_{j} y_{i} y_{j} 〈 ϕ (X_{i}), ϕ (X_{j}) 〉$ $subject to$ $\sum_{i} α_{i} y_{i} = 0, α_{i} > 0$

The decision function can equivalently be expressed as
$f (X) = sign (\sum_{i} α_{i} y_{i} 〈 ϕ (X_{i}, ϕ (X) 〉 - b)$

From this equation it can be seen that the α_iassociated with the training point X_iexpresses the strength with which that point is embedded in the final decision function. A remarkable property of this alternative representation is that only a subset of the points will be associated with a non-zero α_i. These points are called support vectors and are the points that lie closest to the separating hyperplane. The sparseness of the α vector has several computational and learning theoretic consequences. It is important to note that neither the learning algorithm nor the decision function needs to represent explicitly the image of points in the feature space, φ(X_i), since both use only the dot products between such images, <φ(X_i),φ(X_j)>. Hence, if one were given a function K(X, Y)=<φ(X),φ(X)>, one could learn and use the maximum margin hyperplane in the feature space without ever explicitly performing the mapping. For each continuous positive definite function K(X, Y) there exists a mapping φ such that K(X, Y)=<φ(X),φ(X)> for all X, Y∈R₀(Mercer's Theorem). The function K(X, Y) is called the kernel function. The use of a kernel function allows the support vector machine to operate efficiently in a nonlinear high-dimensional feature spaces without being adversely affected by the dimensionality of that space. Indeed, it is possible to work with feature spaces of infinite dimension. Moreover, Mercer's theorem makes it possible to learn in the feature space without even knowing φ and F. The matrix K_ij=<φ(X_i),φ(X_i)> is called the kernel matrix. Finally, note that the learning algorithm is a quadratic optimization problem that has only a global optimum. The absence of local minima is a significant difference from standard pattern recognition techniques such as neural networks. For moderate sample sizes, the optimization problem can be solved with simple gradient descent techniques. In the presence of noise, the standard maximum margin algorithm described above can be subject to overfitting, and more sophisticated techniques should be used. This problem arises because the maximum margin algorithm always finds a perfectly consistent hypothesis and does not tolerate training error. Sometimes, however, it is necessary to trade some training accuracy for better predictive power. The need for tolerating training error has led to the development the soft-margin and the margin-distribution classifiers. One of these techniques replaces the kernel matrix in the training phase as follows:

K←K+λI

while still using the standard kernel finction in the decision phase. By tuning λ, one can control the training error, and it is possible to prove that the risk of misclassifying unseen points can be decreased with a suitable choice of λ.

If instead of controlling the overall training error one wants to control the trade-off between false positives and false negatives, it is possible to modify K as follows:

K←K+λD

where D is a diagonal matrix whose entries are either d⁺or d⁻, in locations corresponding to positive and negative examples. It is possible to prove that this technique is equivalent to controlling the size of the α_iin a way that depends on the size of the class, introducing a bias for larger α_iin the class with smaller d. This in turn corresponds to an asymmetric margin; i.e., the class with smaller d will be kept further away from the decision boundary. In some cases, the extreme imbalance of the two classes, along with the presence of noise, creates a situation in which points from the minority class can be easily mistaken for mislabelled points. Enforcing a strong bias against training errors in the minority class provides protection agaist such errors and forces the SVM to make the positive examples support vectors. Thus, choosing
$d^{+} = \frac{1}{n^{+}} and d^{-} = \frac{1}{n^{-}}$

provides a heuristic way to automatically adjust the relative importance of the two classes, based on their respective cardinalities. This technique effectively controls the trade-off between sensitivity and specificity.

In the present invention, a linear kernel can be used. The similarity between two marker profiles X and Y can be the dot product X·Y. In one embodiment, the kernel is

K(X, Y)=X·Y+1

In another embodiment, a kernel of degree d is used

- K(X, Y)=(X·Y+1)^d, where d can be either 2, 3, . . .

In still another embodiment, a Gaussian kernel is used
$K (X, Y) = \exp (\frac{- {\langle X - Y \rangle}^{2}}{2 σ^{2}})$

where σ is the width of the Gaussian.

5.2.1.4. Logistic Regression

In some embodiments, the progression classifier is based on a regression model, preferably a logistic regression model. Such a regression model includes a coefficient for each of the molecular markers in a selected set of molecular markers of the invention. In such embodiments, the coefficients for the regression model are computed using, for example, a maximum likelihood approach. In particular embodiments, molecular marker data from two different clinical groups, e.g., chronic phase and advanced phase or imatinib resistant and imatinib sensitive, is used and the dependent variable is the clinical status of the patient for which molecular marker characteristic data are from.

Some embodiments of the present invention provide generalizations of the logistic regression model that handle multicategory (polychotomous) responses. Such embodiments can be used to discriminate an organism into one or three or more clinical groups, e.g., chronic phase, accelerated phase, and blast phase. Such regression models use multicategory logit models that simultaneously refer to all pairs of categories, and describe the odds of response in one category instead of another. Once the model specifies logits for a certain (J-1) pairs of categories, the rest are redundant. See, for example, Agresti, An Introduction to Categorical Data Analysis, John Wiley & Sons, Inc., 1996, New York, Chapter 8, which is hereby incorporated by reference.

5.2.1.5. Discriminant Analysis

Linear discriminant analysis (LDA) attempts to classify a subject into one of two categories based on certain object properties. In other words, LDA tests whether object attributes measured in an experiment predict categorization of the objects. LDA typically requires continuous independent variables and a dichotomous categorical dependent variable. In the present invention, the expression values for the selected set of molecular markers of the invention across a subset of the training population serve as the requisite continuous independent variables. The clinical group classification of each of the members of the training population serves as the dichotomous categorical dependent variable.

LDA seeks the linear combination of variables that maximizes the ratio of between-group variance and within-group variance by using the grouping information. Implicitly, the linear weights used by LDA depend on how the expression of a molecular marker across the training set separates in the two groups (e.g., a group that has CP-CML and a group that have ADV-CMP) and how this gene expression correlates with the expression of other genes. In some embodiments, LDA is applied to the data matrix of the N members in the training sample by K genes in a combination of genes described in the present invention. Then, the linear discriminant of each member of the training population is plotted. Ideally, those members of the training population representing a first subgroup (e.g. those subjects that have CP-CML) will cluster into one range of linear discriminant values (e.g., negative) and those member of the training population representing a second subgroup (e.g. those subjects that have ADV-CML) will cluster into a second range of linear discriminant values (e.g., positive). The LDA is considered more successful when the separation between the clusters of discriminant values is larger. For more information on linear discriminant analysis, see Duda, Pattern Classification, Second Edition, 2001, John Wiley & Sons, Inc; and Hastie, 2001, The Elements of Statistical Learning, Springer, N.Y.; Venables & Ripley, 1997, Modern Applied Statistics with s-plus, Springer, N.Y.

Quadratic discriminant analysis (QDA) takes the same input parameters and returns the same results as LDA. QDA uses quadratic equations, rather than linear equations, to produce results. LDA and QDA are interchangeable, and which to use is a matter of preference and/or availability of software to support the analysis. Logistic regression takes the same input parameters and returns the same results as LDA and QDA.

5.2.1.6. Decision Trees

In some embodiments of the present invention, decision trees are used to classify patients using expression data for a selected set of molecular markers of the invention. Decision tree algorithms belong to the class of supervised learning algorithms. The aim of a decision tree is to induce a classifier (a tree) from real-world example data. This tree can be used to classify unseen examples which have not been used to derive the decision tree.

A decision tree is derived from training data. An example contains values for the different attributes and what class the example belongs. In one embodiment, the training data is expression data for a combination of genes described in the present invention across the training population.

The following algorithm describes a decision tree derivation:

Tree(Examples,Class,Attributes)

Create a root node

If all Examples have the same Class value, give the root this label

Else if Attributes is empty label the root according to the most common value

Else begin

- Calculate the information gain for each attribute
- Select the attribute A with highest information gain and make this the root attribute
- For each possible value, v, of this attribute
  - Add a new branch below the root, corresponding to A=v
  - Let Examples(v) be those examples with A=v
  - If Examples(v) is empty, make the new branch a leaf node labeled with the most common value among Examples
  - Else let the new branch be the tree created by
    - Tree(Examples(v),Class,Attributes—{A}) end
      
      A more detailed description of the calculation of information gain is shown in the following. If the possible classes v_i; of the examples have probabilities P(v_i) then the information content I of the actual answer is given by:
      $I (P (v_{1}), \dots, P (v_{n})) = \sum_{i = 1}^{n} - P (v_{i}) \log_{2} P (v_{i})$
      
      The I-value shows how much information we need in order to be able to describe the outcome of a classification for the specific dataset used. Supposing that the dataset contains p positive (e.g. has ADV-CML) and n negative (e.g. has CP-CML) examples (e.g. individuals), the information contained in a correct answer is:
      $I (\frac{p}{p + n}, \frac{n}{p + n}) = - \frac{p}{p + n} \log_{2} \frac{p}{p + n} - \frac{n}{p + n} \log_{2} \frac{n}{p + n}$
      
      where log₂is the logarithm using base two. By testing single attributes the amount of information needed to make a correct classification can be reduced. The remainder for a specific attribute A (e.g. a gene) shows how much the information that is needed can be reduced.
      $Remainder (A) = \sum_{i = 1}^{v} \frac{p_{i} + n_{i}}{p + n} I (\frac{p_{i}}{p_{i} + n_{i}}, \frac{n_{i}}{p_{i} + n_{i}})$
      
      “v” is the number of unique attribute values for attribute A in a certain dataset, “i” is a certain attribute value, “p_i” is the number of examples for attribute A where the classification is positive (e.g. cancer), “n_i” is the number of examples for attribute A where the classification is negative (e.g. healthy).

The information gain of a specific attribute A is calculated as the difference between the information content for the classes and the remainder of attribute A:
$Gain (A) = I (\frac{p}{p + n}, \frac{n}{p + n}) - Remainder (A)$

The information gain is used to evaluate how important the different attributes are for the classification (how well they split up the examples), and the attribute with the highest information.

In general there are a number of different decision tree algorithms, many of which are described in Duda, Pattern Classification, Second Edition, 2001, John Wiley & Sons, Inc. Decision tree algorithms often require consideration of feature processing, impurity measure, stopping criterion, and pruning. Specific decision tree algorithms include, cut are not limited to classification and regression trees (CART), multivariate decision trees, ID3, and C4.5.

In one approach, when an exemplary embodiment of a decision tree is used, the gene expression data for a selected set of molecular markers of the invention across a training population is standardized to have mean zero and unit variance. The members of the training population are randomly divided into a training set and a test set. For example, in one embodiment, two thirds of the members of the training population are placed in the training set and one third of the members of the training population are placed in the test set. The expression values for a select combination of genes described in the present invention is used to construct the decision tree. Then, the ability for the decision tree to correctly classify members in the test set is determined. In some embodiments, this computation is performed several times for a given combination of molecular markers. In each iteration of the computation, the members of the training population are randomly assigned to the training set and the test set. Then, the quality of the combination of molecular markers is taken as the average of each such iteration of the decision tree computation.

5.2.1.7. Clustering

In some embodiments, the expression values for a selected set of molecular markers of the invention are used to cluster a training set. For example, consider the case in which ten genes described in the present invention are used. Each member m of the training population will have expression values for each of the ten genes. Such values from a member m in the training population define the vector:

X_1mX_2mX_3mX_4mX_5mX_6mX_7mX_8mX_9mX_10m

where X_imis the expression level of the i^thgene in organism m. If there are m organisms in the training set, selection of i genes will define m vectors. Note that the methods of the present invention do not require that each the expression value of every single gene used in the vectors be represented in every single vector m. In other words, data from a subject in which one of the i^thgenes is not found can still be used for clustering. In such instances, the missing expression value is assigned either a “zero” or some other normalized value. In some embodiments, prior to clustering, the gene expression values are normalized to have a mean value of zero and unit variance.

Those members of the training population that exhibit similar expression patterns across the training group will tend to cluster together. A particular combination of genes of the present invention is considered to be a good classifier in this aspect of the invention when the vectors cluster into the trait groups found in the training population. For instance, if the training population includes patients with chronic phase and advanced phase CML, a clustering classifier will cluster the population into two groups, with each group uniquely representing either chronic phase or advanced phase.

Clustering is described on pages 211-256 of Duda and Hart, Pattern Classification and Scene Analysis, 1973, John Wiley & Sons, Inc., New York. As described in Section 6.7 of Duda, the clustering problem is described as one of finding natural groupings in a dataset. To identify natural groupings, two issues are addressed. First, a way to measure similarity (or dissimilarity) between two samples is determined. This metric (similarity measure) is used to ensure that the samples in one cluster are more like one another than they are to samples in other clusters. Second, a mechanism for partitioning the data into clusters using the similarity measure is determined.

Similarity measures are discussed in Section 6.7 of Duda, where it is stated that one way to begin a clustering investigation is to define a distance function and to compute the matrix of distances between all pairs of samples in a dataset. If distance is a good measure of similarity, then the distance between samples in the same cluster will be significantly less than the distance between samples in different clusters. However, as stated on page 215 of Duda, clustering does not require the use of a distance metric. For example, a nonmetric similarity ftmction s(x, x′) can be used to compare two vectors x and x′. Conventionally, s(x, x′) is a symmetric function whose value is large when x and x′ are somehow “similar”. An example of a nonmetric similarity function s(x, x′) is provided on page 216 of Duda.

Once a method for measuring “similarity” or “dissimilarity” between points in a dataset has been selected, clustering requires a criterion function that measures the clustering quality of any partition of the data. Partitions of the data set that extremize the criterion function are used to cluster the data. See page 217 of Duda. Criterion functions are discussed in Section 6.8 of Duda.

More recently, Duda et al., Pattern Classification, 2^ndedition, John Wiley & Sons, Inc. New York, has been published. Pages 537-563 describe clustering in detail. More information on clustering techniques can be found in Kaufman and Rousseeuw, 1990, Finding Groups in Data: An Introduction to Cluster Analysis, Wiley, New York, N.Y.; Everitt, 1993, Cluster analysis (3d ed.), Wiley, New York, N.Y.; and Backer, 1995, Computer-Assisted Reasoning in Cluster Analysis, Prentice Hall, Upper Saddle River, N.J. Particular exemplary clustering techniques that can be used in the present invention include, but are not limited to, hierarchical clustering (agglomerative clustering using nearest-neighbor algorithm, farthest-neighbor algorithm, the average linkage algorithm, the centroid algorithm, or the sum-of-squares algorithm), k-means clustering, fuzzy k-means clustering algorithm, and Jarvis-Patrick clustering.

5.2.1.8. Principal Component Analysis

Principal component analysis (PCA) has been proposed to analyze gene expression data. Principal component analysis is a classical technique to reduce the dimensionality of a data set by transforming the data to a new set of variable (principal components) that summarize the features of the data. See, for example, Jolliffe, 1986, Principal Component Analysis, Springer, N.Y. Principal components (PCs) are uncorrelate and are ordered such that the k^thPC has the kth largest variance among PCs. The k^thPC can be interpreted as the direction that maximizes the variation of the projections of the data points such that it is orthogonal to the first k−1 PCs. The first few PCs capture most of the variation in the data set. In contrast, the last few PCs are often assumed to capture only the residual ‘noise’ in the data.

PCA can also be used to create a progression classifier in accordance with the present invention. In such an approach, vectors for a selected set of molecular markers of the invention can be constructed in the same manner described for clustering above. In fact, the set of vectors, where each vector represents the expression values for the select genes from a particular member of the training population, can be considered a matrix. In some embodiments, this matrix is represented in a Free-Wilson method of qualitative binary description of monomers (Kubinyi, 1990, 3D QSAR in drug design theory methods and applications, Pergamon Press, Oxford, pp 589-638), and distributed in a maximally compressed space using PCA so that the first principal component (PC) captures the largest amount of variance information possible, the second principal component (PC) captures the second largest amount of all variance information, and so forth until all variance information in the matrix has been accounted for.

Then, each of the vectors (where each vector represents a member of the training population) is plotted. Many different types of plots are possible. In some embodiments, a one-dimensional plot is made. In this one-dimensional plot, the value for the first principal component from each of the members of the training population is plotted. In this form of plot, the expectation is that members of a first group (e.g. chronic phase patients) will cluster in one range of first principal component values and members of a second group (e.g., advance phase patients) will cluster in a second range of first principal component values.

In one example, the training population comprises two groups: chronic phase patients and advanced phase patients or imatinib resistant and imatinib sensitive. The first principal component is computed using the molecular marker expression values for the select genes of the present invention across the entire training population data set. Then, each member of the training set is plotted as a function of the value for the first principal component. In this example, those members of the training population in which the first principal component is positive are the chronic phase (or imatinib sensitive) patients and those members of the training population in which the first principal component is negative are advanced phase (or imatinib resistant) patients.

In some embodiments, the members of the training population are plotted against more than one principal component. For example, in some embodiments, the members of the training population are plotted on a two-dimensional plot in which the first dimension is the first principal component and the second dimension is the second principal component. In such a two-dimensional plot, the expectation is that members of each subgroup represented in the training population will cluster into discrete groups. For example, a first cluster of members in the two-dimensional plot will represent subjects with CP-CML, a second cluster of members in the two-dimensional plot will represent subjects with ADV-CML, and so forth.

In some embodiments, the members of the training population are plotted against more than two principal components and a determination is made as to whether the members of the training population are clustering into groups that each uniquely represents a subgroup found in the training population. In some embodiments, principal component analysis is performed by using the R mva package (Anderson, 1973, Cluster Analysis for applications, Academic Press, New York 1973; Gordon, Classification, Second Edition, Chapman and Hall, CRC, 1999.). Principal component analysis is further described in Duda, Pattern Classification, Second Edition, 2001, John Wiley & Sons, Inc.

5.2.1.9. Nearest Neighbor Classifier Analysis

Nearest neighbor classifiers are memory-based and require no model to be fit. Given a query point x₀, the k training points x_(r), r, . . . , k closest in distance to x₀are identified and then the point x₀is classified using the k nearest neighbors. Ties can be broken at random. In some embodiments, Euclidean distance in feature space is used to determine distance as:

d_(i)=∥x_(i)−x₀∥·

Typically, when the nearest neighbor algorithm is used, the expression data used to compute the linear discriminant is standardized to have mean zero and variance 1. In the present invention, the members of the training population are randomly divided into a training set and a test set. For example, in one embodiment, two thirds of the members of the training population are placed in the training set and one third of the members of the training population are placed in the test set. Profiles of a selected set of molecular markers of the invention represents the feature space into which members of the test set are plotted. Next, the ability of the training set to correctly characterize the members of the test set is computed. In some embodiments, nearest neighbor computation is performed several times for a given combination of genes of the present invention. In each iteration of the computation, the members of the training population are randomly assigned to the training set and the test set. Then, the quality of the combination of genes is taken as the average of each such iteration of the nearest neighbor computation.

The nearest neighbor rule can be refined to deal with issues of unequal class priors, differential misclassification costs, and feature selection. Many of these refinements involve some form of weighted voting for the neighbors. For more information on nearest neighbor analysis, see Duda, Pattern Classification, Second Edition, 2001, John Wiley & Sons, Inc; and Hastie, 2001, The Elements of Statistical Learning, Springer, N.Y.

5.2.1.10. Evolutionary Methods

Inspired by the process of biological evolution, evolutionary methods of classifier design employ a stochastic search for an optimal classifier. In broad overview, such methods create several classifiers—a population—from measurements of gene products of the present invention. Each classifier varies somewhat from the other. Next, the classifiers are scored on expression data across the training population. In keeping with the analogy with biological evolution, the resulting (scalar) score is sometimes called the fitness. The classifiers are ranked according to their score and the best classifiers are retained (some portion of the total population of classifiers). Again, in keeping with biological terminology, this is called survival of the fittest. The classifiers are stochastically altered in the next generation—the children or offspring. Some offspring classifiers will have higher scores than their parent in the previous generation, some will have lower scores. The overall process is then repeated for the subsequent generation: The classifiers are scored and the best ones are retained, randomly altered to give yet another generation, and so on. In part, because of the ranking, each generation has, on average, a slightly higher score than the previous one. The process is halted when the single best classifier in a generation has a score that exceeds a desired criterion value. More information on evolutionary methods is found in, for example, Duda, Pattern Classification, Second Edition, 2001, John Wiley & Sons, Inc.

5.2.1.11. Bagging, Boosting and the Random Subspace Method

Bagging, boosting and the random subspace method are combining techniques that can be used to improve weak classifiers. These techniques are designed for, and usually applied to, decision trees. In addition, Skurichina and Duin provide evidence to suggest that such techniques can also be useful in linear discriminant analysis.

In bagging, one samples the training set, generating random independent bootstrap replicates, constructs the classifier on each of these, and aggregates them by a simple majority vote in the final decision rule. See, for example, Breiman, 1996, Machine Learning 24, 123-140; and Efron & Tibshirani, An Introduction to Bootstrap, Chapman & Hall, New York, 1993.

In boosting, classifiers are constructed on weighted versions of the training set, which are dependent on previous classification results. Initially, all objects have equal weights, and the first classifier is constructed on this data set. Then, weights are changed according to the performance of the classifier. Erroneously classified objects (molecular markers in the data set) get larger weights, and the next classifier is boosted on the reweighted training set. In this way, a sequence of training sets and classifiers is obtained, which is then combined by simple majority voting or by weighted majority voting in the final decision. See, for example, Freund & Schapire, “Experiments with a new boosting algorithm,” Proceedings 13^thInternational Conference on Machine Learning, 1996, 148-156.

To illustrate boosting, consider the case where there are two phenotypic groups exhibited by the population under study, phenotype 1 (e.g., advanced phase patients), and phenotype 2 (e.g., chronic phase patients). Given a vector of molecular markers X, a classifier G(X) produces a prediction taking one of the type values in the two value set: {phenotype 1, phenotype 2}. The error rate on the training sample is
$\overline{err} = \frac{1}{N} \sum_{i = 1}^{N} I (y_{i} \neq G (x_{i}))$

where N is the number of subjects in the training set (the sum total of the subjects that have either phenotype 1 or phenotype 2).

A weak classifier is one whose error rate is only slightly better than random guessing. In the boosting algorithm, the weak classification algorithm is repeatedly applied to modified versions of the data, thereby producing a sequence of weak classifiers G_m(x), m,=1, 2, . . . , M. The predictions from all of the classifiers in this sequence are then combined through a weighted majority vote to produce the final prediction:
$G (x) = sign (\sum_{m = 1}^{M} α_{m} G_{m} (x))$

Here α₁, α₂, . . . , α_Mare computed by the boosting algorithm and their purpose is to weigh the contribution of each respective G_m(x). Their effect is to give higher influence to the more accurate classifiers in the sequence.

The data modifications at each boosting step consist of applying weights w₁, w₂, . . . , w_nto each of the training observations (x_i, y_i), i=1, 2, . . . , N. Initially all the weights are set to w_i=1/N, so that the first step simply trains the classifier on the data in the usual manner. For each successive iteration m=2, 3, . . . , M the observation weights are individually modified and the classification algorithm is reapplied to the weighted observations. At stem m, those observations that were misclassified by the classifier G_m−1(x) induced at the previous step have their weights increased, whereas the weights are decreased for those that were classified correctly. Thus as iterations proceed, observations that are difficult to correctly classify receive ever-increasing influence. Each successive classifier is thereby forced to concentrate on those training observations that are missed by previous ones in the sequence.

The exemplary boosting algorithm is summarized as follows:

1. Initialize the observation weights w_i=1/N, i=1, 2, . . . , N.

2. For m=1 to M:

- (a) Fit a classifier G_m(x) to the training set using weights w_i.
- (b) Compute
  ${err}_{m} = \frac{\sum_{i = 1}^{N} w_{i} I (y_{i} \neq G_{m} (x_{i}))}{\sum_{i = 1}^{N} w_{i}}$

(d) Set w_i←w_i·exp[α_m·I(y_i≠G_m(x_i))],i=1, 2, . . . , N.

3. Output G(x)=sign └Σ_m=1^Mα_mG_m(x)┘

In the algorithm, the current classifier G_m(x) is induced on the weighted observations at line 2a. The resulting weighted error rate is computed at line 2b. Line 2c calculates the weight α_mgiven to G_m(x) in producing the final classifier G(x) (line 3). The individual weights of each of the observations are updated for the next iteration at line 2d. Observations misclassified by G_m(x) have their weights scaled by a factor exp(α_m), increasing their relative influence for inducing the next classifier G_m+1(x) in the sequence. In some embodiments, modifications of the Freund and Schapire, 1997, Journal of Computer and System Sciences 55, pp. 119-139, boosting method are used. See, for example, Hasti et al., The Elements of Statistical Learning, 2001, Springer, N.Y., Chapter 10. In some embodiments, boosting or adaptive boosting methods are used.

In some embodiments, modifications of Freund and Schapire, 1997, Journal of Computer and System Sciences 55, pp. 119-139, are used. For example, in some embodiments, feature preselection is performed using a technique such as the nonparametric scoring methods of Park et al., 2002, Pac. Symp. Biocomput. 6, 52-63. Feature preselection is a form of dimensionality reduction in which the genes that discriminate between classifications the best are selected for use in the classifier. Then, the LogitBoost procedure introduced by Friedman et al., 2000, Ann Stat 28, 337-407 is used rather than the boosting procedure of Freund and Schapire. In some embodiments, the boosting and other classification methods of Ben-Dor et al., 2000, Journal of Computational Biology 7, 559-583 are used in the present invention. In some embodiments, the boosting and other classification methods of Freund and Schapire, 1997, Journal of Computer and System Sciences 55, 119-139, are used.

In the random subspace method, classifiers are constructed in random subspaces of the data feature space. These classifiers are usually combined by simple majority voting in the final decision rule. See, for example, Ho, “The Random subspace method for constructing decision forests,” IEEE Trans Pattern Analysis and Machine Intelligence, 1998; 20(8): 832-844.

5.2.1.12. Other Algorithms

The pattern classification and statistical techniques described above are merely examples of the types of models that can be used to construct a model for classification. Moreover, combinations of the techniques described above can be used. Some combinations, such as the use of the combination of decision trees and boosting, have been described. However, many other combinations are possible. In addition, in other techniques in the art such as Projection Pursuit and Weighted Voting can be used to construct a progression classifier.

5.2.2. Methods of Determining Aberrant Regulation of CML Target Genes

The invention also provides methods and compositions for determining aberrant regulation in CML target genes and/or their encoded proteins. Such information can be used to determine a treatment regimen for a patient. For example, patients who have a defective regulation of a CML target gene can be identified. A treatment regimen including a therapy to regulate the gene can be prescribed to the patient. Thus, the invention provides methods and composition for assigning treatment regimen for a cancer patient. The invention also provides methods and composition for monitoring treatment progress for a CML patient based on the status of one or more of the CML target proteins.

A variety of methods can be employed for the diagnostic and prognostic evaluation of patients for their status of CML target genes or proteins. In one embodiment, measurements of expression level of one or more of the CML target genes listed in Tables 5a and 5b, and/or abundance or activity level the encoded proteins are used. One or more of these genes or proteins having a level of expression or activity deviated from a respective predetermined threshold indicate aberrant regulation of the genes or proteins.

In one embodiment, the method comprises determining an expression level of a CML target gene (a gene listed in Table 5a or 5b) in the sample of a patient, and determining whether the expression level is deviated (above or below) a predetermined threshold, and the expression level deviated from a predetermined threshold level indicates aberrant regulation of the gene in the patient. Preferably, the predetermined threshold level is at least 2-fold, 4-fold, 8-fold, or 10-fold of the normal expression level of an aberrantly up-regulated CML target gene or less than 50%, 25%, 10% or 1% of the nomal level of an aberrantly down-regulated CML target gene. In another embodiment, the method comprises determining a level of abundance of a CML target protein, i.e., a protein encoded by a CML target gene, in a sample from a patient, and determining whether the level of abundance is deviated a predetermined threshold, and a level of abundance of the protein deviated from a predetermined threshold level indicates aberrant regulation of the protein in the patient. In still another embodiment, the method comprises determining a level of activity of a protein encoded by the CML target gene in a sample of a patient, and determining whether the level of activity is devaited a predetermined threshold, and an activity level deviated from a predetermined threshold level indicates aberrant regulation of the protein in the patient. A reduced activity may be a result of mutation of the CML target gene. Thus, the invention also provides a method for evaluating the status of CML target in a patient, comprising determining a mutation in a CML target gene or a protein encoded by the CML target gene in a sample from the patient, and the detection of a mutation causing the activity of the CML target protein to deviate from a predetermined threshold level indicates aberrant regulation of the protein in the patient. Preferably, the predetermined threshold level of abundance or activity is at least 2-fold, 4-fold, 8-fold, or 10-fold above the normal level of abundance or activity of an aberrantly up-regulated CML target protein or less than 50%, 25%, 10% or 1% of the nomal level of an aberrantly down-regulated CML target protein. In the foregoing embodiments, and the embodiments described below, the sample can be an ex vivo cell sample, e.g., cells in a cell culture, or in vivo cells.

In a specific embodiment, the method comprises determining an expression level of a CML target gene selected from the group consisting of the up-regulated genes listed in Table 3 (which is a subset of the genes listed in Table 5a) in the sample of a patient, and determining whether the expression level is above a predetermined threshold, and an expression level above a predetermined threshold level indicates aberrant regulation of the gene in the patient. Preferably, the predetermined threshold level is at least 2-fold, 4-fold, 8-fold, or 10-fold of the normal expression level of the gene. In another embodiment, the method comprises determining a level of abundance of a protein encoded by a gene selected from the group consisting of the up-regulated genes listed in Table 3 in a sample from a patient, and determining whether the level is above a predetermined threshold, and a level of abundance of the protein above a predetermined threshold level indicates aberrant regulation of the protein in the patient.

In another specific embodiment, the method comprises determining an expression level of a CML target gene selected from the group consisting of the down-regulated genes listed in Table 3 in the sample of a patient, and determining whether the expression level is below a predetermined threshold, and an expression level below a predetermined threshold level indicates aberrant regulation of the gene in the patient. Preferably, the predetermined threshold level is a level less than 50%, 25%, 10% or 1% of the normal expression level of the gene. In another embodiment, the method comprises determining a level of abundance of a protein encoded by a gene selected from the group consisting of the down-regulated genes listed in Table 3 in a sample from a patient, and determining whether the level is below a predetermined threshold, and a level of abundance of the protein below a predetermined threshold level indicates aberrant regulation of the protein in the patient.

In one embodiment, the method comprises determining an expression level of an imatinib resistance gene (a gene listed in Table 4) in the sample of a patient, and determining whether the expression level is deviated (above or below) a predetermined threshold, and an expression level deviated from a predetermined threshold level indicates that the patient is resistant to imatinib treatment. Preferably, the predetermined threshold level is at least 2-fold, 4-fold, 8-fold, or 10-fold of the normal expression level of an aberrantly up-regulated imatinib resistance gene or less than 50%, 25%, 10% or 1% of the normal level of an aberrantly down-regulated imatinib resistance gene. In another embodiment, the method comprises determining a level of abundance of an imatinib resistance protein, i.e., a protein encoded by an imatinib resistance gene, in a sample from a patient, and determining whether the level is deviated (above or below) a predetermined threshold, and a level of abundance of the protein deviated from a predetermined threshold level indicates that the patient is resistant to imatinib treatment. In still another embodiment, the method comprises determining a level of activity of a protein encoded by an imatinib resistance gene in a sample of a patient, and determining whether the level is deviated (above or below) a predetermined threshold, and an activity level deviated from a predetermined threshold level indicates that the patient is resistant to imatinib treatment. Such reduce activity may be a result of mutation of the imatinib resistance gene. Thus, the invention also provides a method for evaluating imatinib resistance in a patient, comprising determining a mutation in an imatinib resistance gene or a protein encoded by the imatinib resistance gene in a sample from the patient, and the detection of a mutation causing the activity of the imatinib resistance protein to deviate from a predetermined threshold level indicates the patient is resistant to imatinib treatment. Preferably, the predetermined threshold level of abundance or activity is at least 2-fold, 4-fold, 8-fold, or 10-fold above the normal level of abundance or activity of an aberrantly up-regulated imatinib resistance protein or less than 50%, 25%, 10% or 1% of the nomal level of an aberrantly down-regulated imatinib resistance protein.

In a specific embodiment, imatinib resistance is determined according to the expression levels of one or more genes selected from the group consisting of serine threonine kinases CTRL, MAP21K14, CLK3, MAP kinase MKNK2, the tyrosine kinase oncogene FYN, TCF7 (a putatively T cell specific transcription factor), guanine nucleotide binding proteins GNAZ and GNG11, and the MAF.

Such methods may, for example, utilize reagents such as nucleotide sequences and antibodies, e.g., the CML progression nucleotide sequences, and antibodies directed against CML progression proteins, including peptide fragments thereof. Specifically, such reagents may be used, for example, for: (1) the detection of the presence of mutations in a CML progression gene, or the detection of either over- or under-expression of a CML progression gene relative to the normal expression level; and (2) the detection of either an over- or an under-abundance of a CML progression protein relative to the normal CML progression protein level. These methods are also applicable to imatinib resistance genes and/or proteins.

The methods described herein may be performed, for example, by utilizing pre-packaged diagnostic kits comprising nucleic acid of at least one specific CML progression gene or an antibody that binds a CML progression/target protein or an IM resistance protein described herein, which may be conveniently used, e.g., in clinical settings, to diagnose patients exhibiting CML progression/target protein related disorder or abnormalities or exhibiting IM resistance.

For the detection of mutations in a CML progression/target gene or an IM resistance gene, any nucleated cell can be used as a starting source for genomic nucleic acid, e.g., bone marrow or peripheral blood. For the detection of expression of a CML progression/target gene or an IM resistance gene or CML progression/target gene or IM resistance gene products, any cell type or tissue in which the CML progression/target gene or the IM resistance gene is expressed may be utilized.

Nucleic acid-based detection techniques and peptide detection techniques are described in Section 5.3., infra. In one embodiment, the expression levels of one or more marker genes are measured using qRT-PCR.

5.2.3. Methods of Detecting CML Cells

The invention also provides diagnostic methods for the detection of CML cells, e.g., advanced phase CML hematopoetic stem cells and/or immature myeloid cells, by detecting a cell surface expressed CML progression protein (e.g., PRAME or CD47) or conserved variants or peptide fragments thereof, using, for example, immunoassays wherein the CML progression protein or conserved variants or peptide fragments are detected by their interaction with an anti-CML progression protein antibody.

For example, antibodies, or fragments of antibodies, such as those described in the present invention may be used to quantitatively or qualitatively detect advanced phase CML hematopoetic stem cells and/or immature myeloid cells by the presence of a CML progression protein or conserved variants or peptide fragments thereof on their surfaces. This can be accomplished, for example, by immunofluorescence techniques employing a fluorescently labeled antibody (see below, this Section) coupled with light microscopic, flow cytometric, or fluorimetric detection.

The antibodies (or fragments thereof) useful in the present invention may, additionally, be employed histologically, as in immunofluorescence or immunoelectron microscopy, for in situ detection of a CML progression protein or conserved variants or peptide fragments thereof. In situ detection may be accomplished by removing a histological specimen from a patient, e.g., bone marrow, and applying thereto a labeled antibody of the present invention. The antibody (or fragment) is preferably applied by overlaying the labeled antibody (or fragment) onto a biological sample. Through the use of such a procedure, it is possible to determine not only the presence of the CML progression protein, or conserved variants or peptide fragments, but also its distribution in the examined tissue. Using the present invention, those of ordinary skill will readily perceive that any of a wide variety of histological methods (such as staining procedures) can be modified in order to achieve such in situ detection.

Immunoassays for a CML progression protein or conserved variants or peptide fragments thereof will typically comprise incubating a sample, such as a biological fluid, a tissue extract, freshly harvested cells, or lysates of cells which have been incubated in cell culture, in the presence of a detectably labeled antibody capable of identifying A CML progression protein or conserved variants or peptide fragments thereof, and detecting the bound antibody by any of a number of techniques well-known in the art.

The biological sample may be brought in contact with and immobilized onto a solid phase support or carrier such as nitrocellulose, or other solid support which is capable of immobilizing cells, cell particles or soluble proteins. The support may then be washed with suitable buffers followed by treatment with the detectably labeled antibody specific for a CML progression protein. The solid phase support may then be washed with the buffer a second time to remove unbound antibody. The amount of bound label on solid support may then be detected by conventional means.

By “solid phase support or carrier” is intended any support capable of binding an antigen or an antibody. Well-known supports or carriers include glass, polystyrene, polypropylene, polyethylene, dextran, nylon, amylases, natural and modified celluloses, polyacrylamides, gabbros, and magnetite. The nature of the carrier can be either soluble to some extent or insoluble for the purposes of the present invention. The support material may have virtually any possible structural configuration so long as the coupled molecule is capable of binding to an antigen or antibody. Thus, the support configuration may be spherical, as in a bead, or cylindrical, as in the inside surface of a test tub, or the external surface of a rod. Alternatively, the surface may be flat such as a sheet, test strip, etc. Preferred supports include polystyrene beads. Those skilled in the art will know many other suitable carriers for binding antibody or antigen, or will be able to ascertain the same by use of routine experimentation.

The binding activity of a given lot of an antibody may be determined according to well known methods. Those skilled in the art will be able to determine operative and optimal assay conditions for each determination by employing routine experimentation.

One of the ways in which the antibody specific to a CML progression protein can be detectably labeled is by linking the same to an enzyme and use in an enzyme immunoassay (EIA) (Voller, A., “The Enzyme Linked Immunosorbent Assay (ELISA)”, 1978, Diagnostic Horizons 2:1-7, Microbiological Associates Quarterly Publication, Walkersville, Md.); Voller, A. et al., 1978, J. Clin. Pathol. 31:507-520; Butler, J. E., 1981, Meth. Enzymol. 73:482-523; Maggio, E. (ed.), 1980, Enzyme Immunoassay, CRC Press, Boca Raton, Fla.,; Ishikawa, E. et al., (eds.), 1981, Enzyme Immunoassay, Kgaku Shoin, Tokyo). The enzyme which is bound to the antibody will react with an appropriate substrate, preferably a chromogenic substrate, in such a manner as to produce a chemical moiety which can be detected, for example, by spectrophotometric, fluorimetric or by visual means. Enzymes which can be used to detectably label the antibody include, but are not limited to, malate dehydrogenase, staphylococcal nuclease, delta-5-steroid isomerase, yeast alcohol dehydrogenase, alpha-glycerophosphate, dehydrogenase, triose phosphate isomerase, horseradish peroxidase, alkaline phosphatase, asparaginase, glucose oxidase, beta-galactosidase, ribonuclease, urease, catalase, glucose-6-phosphate dehydrogenase, glucoamylase and acetylcholinesterase. The detection can be accomplished by colorimetric methods which employ a chromogenic substrate for the enzyme. Detection may also be accomplished by visual comparison of the extent of enzymatic reaction of a substrate in comparison with similarly prepared standards.

Detection may also be accomplished using any of a variety of other immunoassays. For example, by radioactively labeling the antibodies or antibody fragments, it is possible to detect a CML progression protein through the use of a radioimmunoassay (RIA) (see, for example, Weintraub, B., Principles of Radioimmunoassays, Seventh Training Course on Radioligand Assay Techniques, The Endocrine Society, March, 1986, which is incorporated by reference herein). The radioactive isotope can be detected by such means as the use of a gamma counter or a scintillation counter or by autoradiography.

It is also possible to label the antibody with a fluorescent compound. When the fluorescently labeled antibody is exposed to light of the proper wave length, its presence can then be detected due to fluorescence. Among the most commonly used fluorescent labeling compounds are fluorescein isothiocyanate, rhodamine, phycoerythrin, phycocyanin, allophycocyanin, o-phthaldehyde and fluorescamine.

The antibody can also be detectably labeled using fluorescence emitting metals such as ¹⁵²Eu, or others of the lanthanide series. These metals can be attached to the antibody using such metal chelating groups as diethylenetriaminepentacetic acid (DTPA) or ethylenediaminetetraacetic acid (EDTA).

The antibody also can be detectably labeled by coupling it to a chemiluminescent compound. The presence of the chemiluminescent-tagged antibody is then determined by detecting the presence of luminescence that arises during the course of a chemical reaction. Examples of particularly useful chemiluminescent labeling compounds are luminol, isoluminol, theromatic acridinium ester, imidazole, acridinium salt and oxalate ester.

Likewise, a bioluminescent compound may be used to label the antibody of the present invention. Bioluminescence is a type of chemiluminescence found in biological systems in, which a catalytic protein increases the efficiency of the chemiluminescent reaction. The presence of a bioluminescent protein is determined by detecting the presence of luminescence. Important bioluminescent compounds for purposes of labeling are luciferin, luciferase and aequorin.

An antibody that is specific to a CML progression protein conjugated to detectable substances can be utilized to sort advanced phase CML cells from normal cells by methods known to those of skill in the art. In one embodiment, the advanced phase CML cells are sorted using a fluorescence activated cell sorter (FACS). Fluorescence activated cell sorting (FACS) is a well-known method for separating particles, including cells, based on the fluorescent properties of the particles (Kamarch, 1987, Methods Enzymol, 151:150-165). Laser excitation of fluorescent moieties in the individual particles results in a small electrical charge allowing electromagnetic separation of positive and negative particles from a mixture.

In one embodiment, cells, e.g, cells in bone marrow or peripheral blood, obtained from a patient, e.g., a human, are incubated with fluorescently labeled antibody specific for the CML progression protein for a time sufficient to allow the labeled antibodies to bind to the cells. In an alternative embodiment, such cells are incubated with the antibody, the cells are washed, and the cells are incubated with a second labeled antibody that recognizes the CML progression protein-specific antibody. In accordance with these embodiments, the cells are washed and processed through the cell sorter, allowing separation of cells that bind both antibodies to be separated from hybrid cells that do not bind both antibodies. FACS sorted particles may be directly deposited into individual wells of 96-well or 384-well plates to facilitate separation and further characterization.

5.2.4. Sample Collection

In the present invention, gene products, such as target polynucleotide molecules or proteins, are extracted from a sample taken from a CML patient. The sample may be collected in any clinically acceptable manner, but must be collected such that marker-derived polynucleotides (i.e., RNA) are preserved (if gene expression is to be measured) or proteins are preserved (if encoded proteins are to be measured). In one embodiment, bone marrow samples are used. In another embodiment, peripheral blood samples are used. In one embodiment, the pre-treatment bone marrow or peripheral blood sample from a patient is used. In another embodiment, the treatment bone marrow or peripheral blood sample from a patient after and/or during treatment is used. In one embodiment, the unsorted bone marrow or peripheral blood sample from a patient is used. In one embodiment, the unsorted bone marrow or peripheral blood sample from a clinical chronic phase patient is used. In another embodiment, the sorted bone marrow or peripheral blood sample from a patient after and/or during treatment is used. Other suitable samples may comprise any clinically relevant tissue sample, such as a tumor biopsy or fine needle aspirate, or a sample of body fluid, such as blood, plasma, serum, lymph, ascitic fluid, cystic fluid, or urine. The sample may be taken from a human, or, in a veterinary context, from non-human animals such as ruminants, horses, swine or sheep, or from domestic companion animals such as felines and canines.

In a specific embodiment, MRNA or nucleic acids derived therefrom (i.e., cDNA or amplified RNA or amplied DNA) are preferably labeled distinguishably from polynucleotide molecules of a reference sample, and both are simultaneously or independently hybridized to a microarray comprising some or all of the markers or marker sets or subsets described above. Alternatively, mRNA or nucleic acids derived therefrom may be labeled with the same label as the reference polynucleotide molecules, wherein the intensity of hybridization of each at a particular probe is compared.

Methods for preparing total and poly(A)+ RNA are well known and are described generally in Sambrook et al., MOLECULAR CLONING—A LABORATORY MANUAL (2ND ED.), Vols. 1-3, Cold Spring Harbor Laboratory, Cold Spring Harbor, N.Y. (1989)) and Ausubel et al., CURRENT PROTOCOLS IN MOLECULAR BIOLOGY, vol. 2, Current Protocols Publishing, New York (1994)). Preferably, total RNA, or total mRNA (poly(A)+ RNA) is meausured in the methods of the invention directly or indirectly (e.g., via measuring cDNA or cRNA).

RNA may be isolated from eukaryotic cells by procedures that involve lysis of the cells and denaturation of the proteins contained therein. Cells of interest include wild-type cells (i.e., non-cancerous), drug-exposed wild-type cells, tumor- or tumor-derived cells, modified cells, normal or tumor cell line cells, and drug-exposed modified cells. Preferably, the cells are breast cancer tumor cells.

Additional steps may be employed to remove DNA. Cell lysis may be accomplished with a nonionic detergent, followed by microcentrifugation to remove the nuclei and hence the bulk of the cellular DNA. In one embodiment, RNA is extracted from cells of the various types of interest using guanidinium thiocyanate lysis followed by CsCl centrifugation to separate the RNA from DNA (Chirgwin et al., Biochemistry 18:5294-5299 (1979)). Poly(A)+ RNA is selected by selection with oligo-dT cellulose (see Sambrook et al., MOLECULAR CLONING—A LABORATORY MANUAL (2ND ED.), Vols. 1-3, Cold Spring Harbor Laboratory, Cold Spring Harbor, N.Y. (1989). Alternatively, separation of RNA from DNA can be accomplished by organic extraction, for example, with hot phenol or phenol/chloroform/isoamyl alcohol.

If desired, RNase inhibitors may be added to the lysis buffer. Likewise, for certain cell types, it may be desirable to add a protein denaturation/digestion step to the protocol.

For many applications, it is desirable to preferentially enrich mRNA with respect to other cellular RNAs, such as transfer RNA (tRNA) and ribosomal RNA (rRNA). Most mRNAs contain a poly(A) tail at their 3′ end. This allows them to be enriched by affinity chromatography, for example, using oligo(dT) or poly(U) coupled to a solid support, such as cellulose or Sephadex™ (see Ausubel et al., CURRENT PROTOCOLS IN MOLECULAR BIOLOGY, vol. 2, Current Protocols Publishing, New York (1994). Once bound, poly(A)+ mRNA is eluted from the affinity column using 2 mM EDTA/0.1% SDS.

In a specific embodiment, total RNA or total mRNA from cells is used in the methods of the invention. The source of the RNA can be cells of an animal, e.g., human, mammal, primate, non-human animal, dog, cat, mouse, rat, bird, etc. In specific embodiments, the method of the invention is used with a sample containing total mRNA or total RNA from 1×10⁶cells or less. In another embodiment, proteins can be isolated from the foregoing sources, by methods known in the art, for use in expression analysis at the protein level.

Probes to the homologs of the marker sequences disclosed herein can be employed preferably when non-human nucleic acid is being assayed.

5.2.5. Determination of Abundance Levels of Gene Products

The abundance levels of the gene products of the genes in a sample may be determined by any means known in the art. The levels may be determined by isolating and determining the level (i.e., amount) of nucleic acid transcribed from each marker gene. Alternatively, or additionally, the level of specific proteins encoded by a marker gene may be determined.

The levels of transcripts of specific marker genes can be accomplished by determining the amount of mRNA, or polynucleotides derived therefrom, present in a sample. Any method for determining RNA levels can be used. For example, RNA is isolated from a sample and separated on an agarose gel. The separated RNA is then transferred to a solid support, such as a filter. Nucleic acid probes representing one or more markers are then hybridized to the filter by northern hybridization, and the amount of marker-derived RNA is determined. Such determination can be visual, or machine-aided, for example, by use of a densitometer. Another method of determining RNA levels is by use of a dot-blot or a slot-blot. In this method, RNA, or nucleic acid derived therefrom, from a sample is labeled. The RNA or nucleic acid derived therefrom is then hybridized to a filter containing oligonucleotides derived from one or more marker genes, wherein the oligonucleotides are placed upon the filter at discrete, easily-identifiable locations. Hybridization, or lack thereof, of the labeled RNA to the filter-bound oligonucleotides is determined visually or by densitometer. Polynucleotides can be labeled using a radiolabel or a fluorescent (i.e., visible) label.

The levels of transcripts of particular marker genes may also be assessed by determining the level of the specific protein expressed from the marker genes. This can be accomplished, for example, by separation of proteins from a sample on a polyacrylamide gel, followed by identification of specific marker-derived proteins using antibodies in a western blot. Alternatively, proteins can be separated by two-dimensional gel electrophoresis systems. Two-dimensional gel electrophoresis is well-known in the art and typically involves isoelectric focusing along a first dimension followed by SDS-PAGE electrophoresis along a second dimension. See, e.g., Hames et al, 1990, GEL ELECTROPHORESIS OF PROTEINS: A PRACTICAL APPROACH, IRL Press, New York; Shevchenko et al., Proc. Nat'l Acad. Sci. USA 93:1440-1445 (1996); Sagliocco et al., Yeast 12:1519-1533 (1996); Lander, Science 274:536-539 (1996). The resulting electropherograms can be analyzed by numerous techniques, including mass spectrometric techniques, western blotting and immunoblot analysis using polyclonal and monoclonal antibodies.

Alternatively, marker-derived protein levels can be determined by constructing an antibody microarray in which binding sites comprise immobilized, preferably monoclonal, antibodies specific to a plurality of protein species encoded by the cell genome. Preferably, antibodies are present for a substantial fraction of the marker-derived proteins of interest. Methods for making monoclonal antibodies are well known (see, e.g., Harlow and Lane, 1988, ANTIBODIES: A LABORATORY MANUAL, Cold Spring Harbor, N.Y., which is incorporated in its entirety for all purposes). In one embodiment, monoclonal antibodies are raised against synthetic peptide fragments designed based on genomic sequence of the cell. With such an antibody array, proteins from the cell are contacted to the array, and their binding is assayed with assays known in the art. Generally, the expression, and the level of expression, of proteins of diagnostic or prognostic interest can be detected through immunohistochemical staining of tissue slices or sections.

Finally, levels of transcripts of marker genes in a number of tissue specimens may be characterized using a “tissue array” (Kononen et al., Nat. Med 4(7):844-7 (1998)). In a tissue array, multiple tissue samples are assessed on the same microarray. The arrays allow in situ detection of RNA and protein levels; consecutive sections allow the analysis of multiple samples simultaneously.

5.2.5.1. Microarrays

In preferred embodiments, polynucleotide microarrays are used to measure expression so that the expression status of each of the markers above is assessed simultaneously. Generally, microarrays according to the invention comprise a plurality of markers informative for clinical category determination, for a particular disease or condition.

The invention also provides a microarray comprising for each of a plurality of genes, said genes being all or at least 5, 10, 20, 30, 40, 50, 70, 100 or 200 of the genes listed in Tables 1a and/or 1b or any of Tables 2a-2b, 4 and 5a-5b, or all or at least 5, 10, or 15 of the genes listed in Table 3, one or more polynucleotide probes complementary and hybridizable to a sequence in said gene, wherein polynucleotide probes complementary and hybridizable to said genes constitute at least 50%, 60%, 70%, 80%, 90%, 95%, or 98% of the probes on said microarray. In a particular embodiment, the invention provides such a microarray wherein the plurality of genes comprises the 20 genes listed in Table 3 or the 228 genes listed in Table 4 or the 368 genes listed in Tables 5a and 5b. The microarray can be in a sealed container.

The microarrays preferably comprise at least 2, 3, 4, 5, 7, 10, 15, 20, 25, 30, 35, 40, 45, 50, 75, 100, 150, 200 or more of markers, or all of the markers, or any combination of markers, identified as informative for CML progression and/or imatinib resistance, e.g., within Tables 1a and 1b or any of Tables 2a-2b, 3, 4, and 5a-5b. The actual number of informative markers the microarray comprises will vary depending upon the particular condition of interest.

In other embodiments, the invention provides polynucleotide arrays in which the CML progression markers comprise at least 50%, 60%, 70%, 80%, 85%, 90%, 95% or 98% of the probes on the array. In another specific embodiment, the microarray comprises a plurality of probes, wherein said plurality of probes comprise probes complementary and hybridizable to at least 75% of the CML progression markers.

General methods pertaining to the construction of microarrays comprising the marker sets and/or subsets above are described in the following sections.

5.2.5.2. Construction of Microarrays

Microarrays are prepared by selecting probes which comprise a polynucleotide sequence, and then immobilizing such probes to a solid support or surface. For example, the probes may comprise DNA sequences, RNA sequences, or copolymer sequences of DNA and RNA. The polynucleotide sequences of the probes may also comprise DNA and/or RNA analogues, or combinations thereof. For example, the polynucleotide sequences of the probes may be full or partial fragments of genomic DNA. The polynucleotide sequences of the probes may also be synthesized nucleotide sequences, such as synthetic oligonucleotide sequences. The probe sequences can be synthesized either enzymatically in vivo, enzymatically in vitro (e.g., by PCR), or non-enzymatically in vitro.

The probe or probes used in the methods of the invention are preferably immobilized to a solid support which may be either porous or non-porous. For example, the probes may be polynucleotide sequences which are attached to a nitrocellulose or nylon membrane or filter covalently at either the 3′ or the 5′ end of the polynucleotide. Such hybridization probes are well known in the art (see, e.g., Sambrook et al., MOLECULAR CLONING—A LABORATORY MANUAL (2ND ED.), Vols. 1-3, Cold Spring Harbor Laboratory, Cold Spring Harbor, N,Y. (1989). Alternatively, the solid support or surface may be a glass or plastic surface. In a particularly preferred embodiment, hybridization levels are measured to microarrays of probes consisting of a solid phase on the surface of which are immobilized a population of polynucleotides, such as a population of DNA or DNA mimics, or, alternatively, a population of RNA or RNA mimics. The solid phase may be a nonporous or, optionally, a porous material such as a gel.

In preferred embodiments, a microarray comprises a support or surface with an ordered array of binding (e.g., hybridization) sites or “probes” each representing one of the markers described herein. Preferably the microarrays are addressable arrays, and more preferably positionally addressable arrays. More specifically, each probe of the array is preferably located at a known, predetermined position on the solid support such that the identity (i.e., the sequence) of each probe can be determined from its position in the array (i.e., on the support or surface). In preferred embodiments, each probe is covalently attached to the solid support at a single site.

Microarrays can be made in a number of ways, of which several are described below. However produced, microarrays share certain characteristics. The arrays are reproducible, allowing multiple copies of a given array to be produced and easily compared with each other. Preferably, microarrays are made from materials that are stable under binding (e.g., nucleic acid hybridization) conditions. The microarrays are preferably small, e.g., between 1 cm²and 25 cm², between 12 cm²and 13 cm², or 3 cm². However, larger arrays are also contemplated and may be preferable, e.g., for use in screening arrays. Preferably, a given binding site or unique set of binding sites in the microarray will specifically bind (e.g., hybridize) to the product of a single gene in a cell (e.g., to a specific mRNA, or to a specific cDNA derived therefrom). However, in general, other related or similar sequences will cross hybridize to a given binding site.

The microarrays of the present invention include one or more test probes, each of which has a polynucleotide sequence that is complementary to a subsequence of RNA or DNA to be detected. Preferably, the position of each probe on the solid surface is known. Indeed, the microarrays are preferably positionally addressable arrays. Specifically, each probe of the array is preferably located at a known, predetermined position on the solid support such that the identity (i.e., the sequence) of each probe can be determined from its position on the array (i.e., on the support or surface).

According to the invention, the microarray is an array (i.e., a matrix) in which each position represents one of the markers described herein. For example, each position can contain a DNA or DNA analogue based on genomic DNA to which a particular RNA or cDNA transcribed from that genetic marker can specifically hybridize. The DNA or DNA analogue can be, e.g., a synthetic oligomer or a gene fragment. In one embodiment, probes representing each of the markers are present on the array. In a preferred embodiment, the array comprises probes for each of the markers listed in Tables 1a and/or 1b or any one of Tables 2a-2b, 3, 4, and 5a-5b.

5.2.5.3. Preparing Probes for Microarrays

As noted above, the “probe” to which a particular polynucleotide molecule specifically hybridizes according to the invention contains a complementary genomic polynucleotide sequence. The probes of the microarray preferably consist of nucleotide sequences of no more than 1,000 nucleotides. In some embodiments, the probes of the array consist of nucleotide sequences of 10 to 1,000 nucleotides. In a preferred embodiment, the nucleotide sequences of the probes are in the range of 10-200 nucleotides in length and are genomic sequences of a species of organism, such that a plurality of different probes is present, with sequences complementary and thus capable of hybridizing to the genome of such a species of organism, sequentially tiled across all or a portion of such genome. In other specific embodiments, the probes are in the range of 10-30 nucleotides in length, in the range of 10-40 nucleotides in length, in the range of 20-50 nucleotides in length, in the range of 40-80 nucleotides in length, in the range of 50-150 nucleotides in length, in the range of 80-120 nucleotides in length, and most preferably are 60 nucleotides in length.

The probes may comprise DNA or DNA “mimics” (e.g., derivatives and analogues) corresponding to a portion of an organism's genome. In another embodiment, the probes of the microarray are complementary RNA or RNA mimics. DNA mimics are polymers composed of subunits capable of specific, Watson-Crick-like hybridization with DNA, or of specific hybridization with RNA. The nucleic acids can be modified at the base moiety, at the sugar moiety, or at the phosphate backbone. Exemplary DNA mimics include, e.g., phosphorothioates.

DNA can be obtained, e.g., by polymerase chain reaction (PCR) amplification of genomic DNA or cloned sequences. PCR primers are preferably chosen based on a known sequence of the genome that will result in amplification of specific fragments of genomic DNA. Computer programs that are well known in the art are useful in the design of primers with the required specificity and optimal amplification properties, such as Oligo version 5.0 (National Biosciences). Typically each probe on the microarray will be between 10 bases and 50,000 bases, usually between 300 bases and 1,000 bases in length. PCR methods are well known in the art, and are described, for example, in Innis et al., eds., PCR PROTOCOLS: A GUIDE TO METHODS AND APPLICATIONS, Academic Press Inc., San Diego, Calif. (1990). It will be apparent to one skilled in the art that controlled robotic systems are useful for isolating and amplifying nucleic acids.

An alternative, preferred means for generating the polynucleotide probes of the microarray is by synthesis of synthetic polynucleotides or oligonucleotides, e.g., using N-phosphonate or phosphoramidite chemistries (Froehler et al., Nucleic Acid Res. 14:5399-5407 (1986); McBride et al., Tetrahedron Lett. 24:246-248 (1983)). Synthetic sequences are typically between about 10 and about 500 bases in length, more typically between about 20 and about 100 bases, and most preferably between about 40 and about 70 bases in length. In some embodiments, synthetic nucleic acids include non-natural bases, such as, but by no means limited to, inosine. As noted above, nucleic acid analogues may be used as binding sites for hybridization. An example of a suitable nucleic acid analogue is peptide nucleic acid (see, e.g., Egholm et al., Nature 363:566-568 (1993); U.S. Pat. No. 5,539,083).

Probes are preferably selected using an algorithm that takes into account binding energies, base composition, sequence complexity, cross-hybridization binding energies, and secondary structure. See Friend et al., International Patent Publication WO 01/05935, published Jan. 25, 2001; Hughes et al., Nat. Biotech. 19:342-7 (2001).

A skilled artisan will also appreciate that positive control probes, e.g., probes known to be complementary and hybridizable to sequences in the target polynucleotide molecules, and negative control probes, e.g., probes known to not be complementary and hybridizable to sequences in the target polynucleotide molecules, should be included on the array. In one embodiment, positive controls are synthesized along the perimeter of the array. In another embodiment, positive controls are synthesized in diagonal stripes across the array. In still another embodiment, the reverse complement for each probe is synthesized next to the position of ilie probe to serve as a negative control. In yet another emboodiment, sequences from other species of organism are used as negative controls or as “spike-in” controls.

5.2.5.4. Attaching Probes to the Solid Surface

The probes are attached to a solid support or surface, which may be made, e.g., from glass, plastic (e.g., polypropylene, nylon), polyacrylamide, nitrocellulose, gel, or other porous or nonporous material. A preferred method for attaching the nucleic acids to a surface is by printing on glass plates, as is described generally by Schena et al, Science 270:467-470 (1995). This method is especially useful for preparing microarrays of cDNA (See also, DeRisi et al, Nature Genetics 14:457-460 (1996); Shalon et al., Genome Res. 6 :639-645 (1996); and Schena et al., Proc. Natl. Acad. Sci. U.S.A. 93:10539-11286 (1995)).

A second preferred method for making microarrays is by making high-density oligonucleotide arrays. Techniques are known for producing arrays containing thousands of oligonucleotides complementary to defined sequences, at defined locations on a surface using photolithographic techniques for synthesis in situ (see, Fodor et al., 1991, Science 251:767-773; Pease et al., 1994, Proc. Natl. Acad. Sci. U.S.A. 91:5022-5026; Lockhart et al., 1996, Nature Biotechnology 14:1675; U.S. Pat. Nos. 5,578,832; 5,556,752; and 5,510,270) or other methods for rapid synthesis and deposition of defined oligonucleotides (Blanchard et al., Biosensors & Bioelectronics 11:687-690). When these methods are used, oligonucleotides (e.g., 60-mers) of known sequence are synthesized directly on a surface such as a derivatized glass slide. Usually, the array produced is redundant, with several oligonucleotide molecules per RNA.

Other methods for making microarrays, e.g., by masking (Maskos and Southern, 1992, Nuc. Acids. Res. 20:1679-1684), may also be used. In principle, and as noted supra, any type of array, for example, dot blots on a nylon hybridization membrane (see Sambrook et al., MOLECULAR CLONING—A LABORATORY MANUAL (2ND ED.), Vols. 1-3, Cold Spring Harbor Laboratory, Cold Spring Harbor, N.Y. (1989)) could be used. However, as will be recognized by those skilled in the art, very small arrays will frequently be preferred because hybridization volumes will be smaller.

In one embodiment, the arrays of the present invention are prepared by synthesizing polynucleotide probes on a support. In such an embodiment, polynucleotide probes are attached to the support covalently at either the 3′ or the 5′ end of the polynucleotide.

In a particularly preferred embodiment, microarrays are manufactured by means of an ink jet printing device for oligonucleotide synthesis, e.g., using the methods and systems described by Blanchard in U.S. Pat. No. 6,028,189; Blanchard et al., 1996, Biosensors and Bioelectronics 11:687-690; Blanchard, 1998, in Synthetic DNA Arrays in Genetic Engineering, Vol. 20, J. K. Setlow, Ed., Plenum Press, New York at pages 111-123. Specifically, the oligonucleotide probes in such microarrays are preferably synthesized in arrays, e.g., on a glass slide, by serially depositing individual nucleotide bases in “microdroplets” of a high surface tension solvent such as propylene carbonate. The microdroplets have small volumes (e.g., 100 pL or less, more preferably 50 pL or less) and are separated from each other on the microarray (e.g., by hydrophobic domains) to form circular surface tension wells which define the locations of the array elements (i.e., the different probes). Microarrays manufactured by this ink-jet method are typically of high density, preferably having a density of at least about 2,500 different probes per 1 cm². The polynucleotide probes are attached to the support covalently at either the 3′ or the 5′ end of the polynucleotide.

5.2.5.5. Target Labeling and Hybridization to Microarrays

The polynucleotide molecules which may be analyzed by the present invention (the “target polynucleotide molecules”) may be from any clinically relevant source, but are expressed RNA or a nucleic acid derived therefrom (e.g, cDNA or amplified RNA derived from cDNA that incorporates an RNA polymerase promoter), including naturally occurring nucleic acid molecules, as well as synthetic nucleic acid molecules. In one embodiment, the target polynucleotide molecules comprise RNA, including, but by no means limited to, total cellular RNA, poly(A)⁺messenger RNA (mRNA) or fraction thereof, cytoplasmic mRNA, or RNA transcribed from cDNA (i.e., cRNA; see, e.g., Linsley & Schelter, U.S. patent application No. 09/411,074, filed Oct. 4, 1999, or U.S. Pat. Nos. 5,545,522, 5,891,636, or 5,716,785). Methods for preparing total and poly(A)⁺RNA are well known in the art, and are described generally, e.g., in Sambrook et al., MOLECULAR CLONING—A LABORATORY MANUAL (2ND ED.), Vols. 1-3, Cold Spring Harbor Laboratory, Cold Spring Harbor, N.Y. (1989). In one embodiment, RNA is extracted from cells of the various types of interest in this invention using guanidinium thiocyanate lysis followed by CsCl centrifugation (Chirgwin et al., 1979, Biochemistry 18:5294-5299). In another embodiment, total RNA is extracted using a silica gel-based column, commercially available examples of which include RNeasy (Qiagen, Valencia, Calif.) and StrataPrep (Stratagene, La Jolla, Calif.). In an alternative embodiment, which is preferred for S. cerevisiae, RNA is extracted from cells using phenol and chloroform, as described in Ausubel et al., eds., 1989, CURRENT PROTOCOLS IN MOLECULAR BIOLOGY, Vol. III, Green Publishing Associates, Inc., John Wiley & Sons, Inc., New York, at pp. 13.12.1-13.12.5). Poly(A)⁺RNA can be selected, e.g., by selection with oligo-dT cellulose or, alternatively, by oligo-dT primed reverse transcription of total cellular RNA. In one embodiment, RNA can be fragmented by methods known in the art, e.g., by incubation with ZnCI₂, to generate fragments of RNA. In another embodiment, the polynucleotide molecules analyzed by the invention comprise cDNA, or PCR products of amplified RNA or cDNA.

In one embodiment, total RNA, mRNA, or nucleic acids derived therefrom, is isolated from a sample taken from a CML patient. Target polynucleotide molecules that are poorly expressed in particular cells may be enriched using normalization techniques (Bonaldo et al., 1996, Genome Res. 6:791-806).

As described above, the target polynucleotides are detectably labeled at one or more nucleotides. Any method known in the art may be used to detectably label the target polynucleotides. Preferably, this labeling incorporates the label uniformly along the length of the RNA, and more preferably, the labeling is carried out at a high degree of efficiency. One embodiment for this labeling uses oligo-dT primed reverse transcription to incorporate the label; however, conventional methods of this method are biased toward generating 3′ end fragments. Thus, in a preferred embodiment, random primers (e.g., 9-mers) are used in reverse transcription to uniformly incorporate labeled nucleotides over the full length of the target polynucleotides. Alternatively, random primers may be used in conjunction with PCR methods or T7 promoter-based in vitro transcription methods in order to amplify the target polynucleotides.

In a preferred embodiment, the detectable label is a luminescent label. For example, fluorescent labels, bioluminescent labels, chemiluminescent labels, and colorimetric labels may be used in the present invention. In a highly preferred embodiment, the label is a fluorescent label, such as a fluorescein, a phosphor, a rhodamine, or a polymethine dye derivative. Examples of commercially available fluorescent labels include, for example, fluorescent phosphoramidites such as FluorePrime (Amersham Pharmacia, Piscataway, N.J.), Fluoredite (Miilipore, Bedford, Mass.), FAM (ABI, Foster City, Calif.), and Cy3 or Cy5 (Amersham Pharmacia, Piscataway, N.J.). In another embodiment, the detectable label is a radiolabeled nucleotide.

In a further preferred embodiment, target polynucleotide molecules from a patient sample are labeled differentially from target polynucleotide molecules of a reference sample. The reference can comprise target polynucleotide molecules from normal cell samples (i.e., cell sample, e.g., bone marrow or peripheral blood, from those not afflicted with CML) or from cell samples, e.g., bone marrow or peripheral blood, from chronic phase CML patients.

Nucleic acid hybridization and wash conditions are chosen so that the target polynucleotide molecules specifically bind or specifically hybridize to the complementary polynucleotide sequences of the array, preferably to a specific array site, wherein its complementary DNA is located.

Arrays containing double-stranded probe DNA situated thereon are preferably subjected to denaturing conditions to render the DNA single-stranded prior to contacting with the target polynucleotide molecules. Arrays containing single-stranded probe DNA (e.g., synthetic oligodeoxyribonucleic acids) may need to be denatured prior to contacting with the target polynucleotide molecules, e.g., to remove hairpins or dimers which form due to self complementary sequences.

Optimal hybridization conditions will depend on the length (e.g., oligomer versus polynucleotide greater than 200 bases) and type (e.g., RNA, or DNA) of probe and target nucleic acids. One of skill in the art will appreciate that as the oligonucleotides become shorter, it may become necessary to adjust their length to achieve a relatively uniform melting temperature for satisfactory hybridization results. General parameters for specific (i.e., stringent) hybridization conditions for nucleic acids are described in Sambrook et al., MOLECULAR CLONING—A LABORATORY MANUAL (2ND ED.), Vols. 1-3, Cold Spring Harbor Laboratory, Cold Spring Harbor, N.Y. (1989), and in Ausubel et al., CURRENT PROTOCOLS IN MOLECULAR BIOLOGY, vol. 2, Current Protocols Publishing, New York (1994). Typical hybridization conditions for the cDNA microarrays of Schena et al. are hybridization in 5×SSC plus 0.2% SDS at 65° C. for four hours, followed by washes at 25° C. in low stringency wash buffer (1×SSC plus 0.2% SDS), followed by 10 minutes at 25° C. in higher stringency wash buffer (0.1×SSC plus 0.2% SDS) (Schena et al., Proc. Natl. Acad. Sci. U.S.A. 93:10614 (1993)). Useful hybridization conditions are aiso provided in, e.g., Tijessen, 1993, HYBRIDIZATION WITH NUCLEIC ACID PROBES, Elsevier Science Publishers B.V.; and Kricka, 1992, NONISOTOPIC DNA PROBE TECHNIQUES, Academic Press, San Diego, Calif.

Particularly preferred hybridization conditions include hybridization at a temperature at or near the mean melting temperature of the probes (e.g., within 51° C., more preferably within 21° C.) in 1 M NaCl, 50 mM MES buffer (pH 6.5), 0.5% sodium sarcosine and 30% formamide.

5.2.5.6. Signal Detection and Data Analysis

When fluorescently labeled gene products are used, the fluorescence emissions at each site of a microarray may be, preferably, detected by scanning confocal laser microscopy. In one embodiment, a separate scan, using the appropriate excitation line, is carried out for each of the two fluorophores used. Alternatively, a laser may be used that allows simultaneous specimen illumination at wavelengths specific to the two fluorophores and emissions from the two fluorophores can be analyzed simultaneously (see Shalon et al., 1996, “A DNA microarray system for analyzing complex DNA samples using two-color fluorescent probe hybridization,” Genome Research 6:639-645, which is incorporated by reference in its entirety for all purposes). In a preferred embodiment, the arrays are scanned with a laser fluorescent scanner with a computer controlled X-Y stage and a microscope objective. Sequential excitation of the two fluorophores is achieved with a multi-line, mixed gas laser and the emitted light is split by wavelength and detected with two photomultiplier tubes. Fluorescence laser scanning devices are described in Schena et al., Genome Res. 6:639-645 (1996), and in other references cited herein. Alternatively, the fiber-optic bundle described by Ferguson et al., Nature Biotech. 14:1681-1684 (1996), may be used to monitor mRNA abundance levels at a large number of sites simultaneously.

5.2.5.7. Other Assays for Detecting and Quantifying RNA

In addition to microarrays such as those described above any technique known to one of skill for detecting and measuring RNA can be used in accordance with the methods of the invention. Non-limiting examples of techniques include Northern blotting, nuclease protection assays, RNA fingerprinting, polymerase chain reaction, ligase chain reaction, Qbeta replicase, isothermal amplification method, strand displacement amplification, transcription based amplification systems, nuclease protection (SI nuclease or RNAse protection assays), SAGE as well as methods disclosed in International Publication Nos. WO 88/10315 and WO 89/06700, and International Applications Nos. PCT/US87/00880 and PCT/US89/01025.

A standard Northern blot assay can be used to ascertain an RNA transcript size, identify alternatively spliced RNA transcripts, and the relative amounts of mRNA in a sample, in accordance with conventional Northern hybridization techniques known to those persons of ordinary skill in the art. In Northern blots, RNA samples are first separated by size via electrophoresis in an agarose gel under denaturing conditions. The RNA is then transferred to a membrane, crosslinked and hybridized with a labeled probe. Nonisotopic or high specific activity radiolabeled probes can be used including random-primed, nick-translated, or PCR-generated DNA probes, in vitro transcribed RNA probes, and oligonucleotides. Additionally, sequences with only partial homology (e.g., cDNA from a different species or genomic DNA fragments that might contain an exon) may be used as probes. The labeled probe, e.g., a radiolabelled cDNA, either containing the full-length, single stranded DNA or a fragment of that DNA sequence may be at least 20, at least 30, at least 50, or at least 100 consecutive nucleotides in length. The probe can be labeled by any of the many different methods known to those skilled in this art. The labels most commonly employed for these studies are radioactive elements, enzymes, chemicals that fluoresce when exposed to ultraviolet light, and others. A number of fluorescent materials are known and can be utilized as labels. These include, but are not limited to, fluorescein, rhodamine, auramine, Texas Red, AMCA blue and Lucifer Yellow. A particular detecting material is anti-rabbit antibody prepared in goats and conjugated with fluorescein through an isothiocyanate. Proteins can also be labeled with a radioactive element or with an enzyme. The radioactive label can be detected by any of the currently available counting procedures. Non-limiting examples of isotopes include ³H, ¹⁴C, ³²P, ³⁵S, ³⁶Cl, ³⁵Cr, ⁵⁷Co, ⁵⁸Co, ⁵⁹Fe, ⁹⁰Y, ¹²⁵I,¹³¹I, and ¹⁸⁶Re. Enzyme labels are likewise useful, and can be detected by any of the presently utilized colorimetric, spectrophotometric, fluorospectrophotometric, amperometric or gasometric techniques. The enzyme is conjugated to the selected particle by reaction with bridging molecules such as carbodiimides, diisocyanates, glutaraldehyde and the like. Any enzymes known to one of skill in the art can be utilized. Examples of such enzymes include, but are not limited to, peroxidase, beta-D-galactosidase, urease, glucose oxidase plus peroxidase and alkaline phosphatase. U.S. Pat. Nos. 3,654,090, 3,850,752, and 4,016,043 are referred to by way of example for their disclosure of alternate labeling material and methods.

Nuclease protection assays (including both ribonuclease protection assays and SI nuclease assays) can be used to detect and quantitate specific mRNAs. In nuclease protection assays, an antisense probe (labeled with, e.g., radiolabeled or nonisotopic) hybridizes in solution to an RNA sample. Following hybridization, single-stranded, unhybridized probe and RNA are degraded by nucleases. An acrylamide gel is used to separate the remaining protected fragments. Typically, solution hybridization is more efficient than membrane-based hybridization, and it can accommodate up to 100 μg of sample RNA, compared with the 20-30 μg maximum of blot hybridizations.

The ribonuclease protection assay, which is the most common type of nuclease protection assay, requires the use of RNA probes. Oligonucleotides and other single-stranded DNA probes can only be used in assays containing SI nuclease. The single-stranded, antisense probe must typically be completely homologous to target RNA to prevent cleavage of the probe:target hybrid by nuclease.

Serial Analysis Gene Expression (SAGE), which is described in e.g., Velculescu et al., 1995, Science 270:484-7; Carulli, et al., 1998, Journal of Cellular Biochemistry Supplements 30/31:286-96, can also be used to determine RNA abundances in a cell sample.

Quantitative reverse transcriptase PCR (qRT-PCR) can also be used to determine the expression profiles of marker genes (see, e.g., U.S. Patent Application Publication No. 2005/0048542A1). The first step in gene expression profiling by RT-PCR is the reverse transcription of the RNA template into cDNA, followed by its exponential amplification in a PCR reaction. The two most commonly used reverse transcriptases are avilo myeloblastosis virus reverse transcriptase (AMV-RT) and Moloney murine leukemia virus reverse transcriptase (MLV-RT). The reverse transcription step is typically primed using specific primers, random hexamers, or oligo-dT primers, depending on the circumstances and the goal of expression profiling. For example, extracted RNA can be reverse-transcribed using a GeneAmp RNA PCR kit (Perkin Elmer, Calif., USA), following the manufacturer's instructions. The derived cDNA can then be used as a template in the subsequent PCR reaction.

Although the PCR step can use a variety of thermostable DNA-dependent DNA polymerases, it typically employs the Taq DNA polymerase, which has a 5′-3′ nuclease activity but lacks a 3′-5′ proofreading endonuclease activity. Thus, TaqMan® PCR typically utilizes the 5′-nuclease activity of Taq or Tth polymerase to hydrolyze a hybridization probe bound to its target amplicon, but any enzyme with equivalent 5′ nuclease activity can be used. Two oligonucleotide primers are used to generate an amplicon typical of a PCR reaction. A third oligonucleotide, or probe, is designed to detect nucleotide sequence located between the two PCR primers. The probe is non-extendible by Taq DNA polymerase enzyme, and is labeled with a reporter fluorescent dye and a quencher fluorescent dye. Any laser-induced emission from the reporter dye is quenched by the quenching dye when the two dyes are located close together as they are on the probe. During the amplification reaction, the Taq DNA polymerase enzyme cleaves the probe in a template-dependent manner. The resultant probe fragments disassociate in solution, and signal from the released reporter dye is free from the quenching effect of the second fluorophore. One molecule of reporter dye is liberated for each new molecule synthesized, and detection of the unquenched reporter dye provides the basis for quantitative interpretation of the data.

TaqMan® RT-PCR can be performed using commercially available equipment, such as, for example, ABI PRISM 7700™. Sequence Detection System™ (Perkin-Elmer-Applied Biosystems, Foster City, Calif., USA), or Lightcycler (Roche Molecular Biochemicals, Mannheim, Germany). In a preferred embodiment, the 5′ nuclease procedure is run on a real-time quantitative PCR device such as the ABI PRISM 7700™ Sequence Detection SysteM™. The system consists of a thermocycler, laser, charge-coupled device (CCD), camera and computer. The system includes software for running the instrument and for analyzing the data. 5′-Nuclease assay data are initially expressed as Ct, or the threshold cycle. Fluorescence values are recorded during every cycle and represent the amount of product amplified to that point in the amplification reaction. The point when the fluorescent signal is first recorded as statistically significant is the threshold cycle (Ct).

To minimize errors and the effect of sample-to-sample variation, RT-PCR is usually performed using an internal standard. The ideal internal standard is expressed at a constant level among different tissues, and is unaffected by the experimental treatment. RNAs most frequently used to normalize patterns of gene expression are mRNAs for the housekeeping genes glyceraldehyde-3-phosphate-dehydrogenase (GAPDH) and β-actin.

A more recent variation of the RT-PCR technique is the real time quantitative PCR, which measures PCR product accumulation through a dual-labeled fluorigenic probe (i.e., TaqMan® probe). Real time PCR is compatible both with quantitative competitive PCR, where internal competitor for each target sequence is used for normalization, and with quantitative comparative PCR using a normalization gene contained within the sample, or a housekeeping gene for RT-PCR. For further details see, e.g. Held et al., Genome Research 6:986-994 (1996).

5.2.5.8. Detection and Quantification of Protein

Measurement of the translational state may be performed according to several methods. For example, whole genome monitoring of protein (e.g., the “proteome,”) can be carried out by constructing a microarray in which binding sites comprise immobilized, preferably monoclonal, antibodies specific to a plurality of protein species encoded by the cell genome. Preferably, antibodies are present for a substantial fraction of the encoded proteins, or at least for those proteins relevant to the action of a drug of interest. Methods for making monoclonal antibodies are well known (see, e.g., Harlow and Lane, 1988, Antibodies: A Laboratory Manual, Cold Spring Harbor, N.Y., which is incorporated in its entirety for all purposes). In one embodiment, monoclonal antibodies are raised against synthetic peptide fragments designed based on genomic sequence of the cell. With such an antibody array, proteins from the cell are contacted to the array and their binding is assayed with assays known in the art.

Immunoassays known to one of skill in the art can be used to detect and quantify protein levels. For example, ELISAs can be used to detect and quantify protein levels. ELISAs comprise preparing antigen, coating the well of a 96 well microtiter plate with the antigen, adding the antibody of interest conjugated to a detectable compound such as an enzymatic substrate (e.g., horseradish peroxidase or alkaline phosphatase) to the well and incubating for a period of time, and detecting the presence of the antigen. In ELISAs the antibody of interest does not have to be conjugated to a detectable compound; instead, a second antibody (which recognizes the antibody of interest) conjugated to a detectable compound may be added to the well. Further, instead of coating the well with the antigen, the antibody may be coated to the well. In this case, a second antibody conjugated to a detectable compound may be added following the addition of the antigen of interest to the coated well. One of skill in the art would be knowledgeable as to the parameters that can be modified to increase the signal detected as well as other variations of ELISAs known in the art. In a preferred embodiment, an ELISA may be performed by coating a high binding 96-well microtiter plate (Costar) with 2 μg/ml of rhu-IL-9 in PBS overnight. Following three washes with PBS, the plate is incubated with three-fold serial dilutions of Fab at 25° C. for 1 hour. Following another three washes of PBS, 1 μg/ml anti-human kappa-alkaline phosphatase-conjugate is added and the plate is incubated for 1 hour at 25° C. Following three washes with PBST, the alkaline phosphatase activity is determined in 50 μl/AMP/PPMP substrate. The reactions are stopped and the absorbance at 560 nm is determined with a VMAX microplate reader. For further discussion regarding ELISAs see, e.g., Ausubel et al, eds, 1994, Current Protocols in Molecular Biology, Vol. 1, John Wiley & Sons, Inc., New York at 11.2.1.

Protein levels may be determined by Western blot analysis. Further, protein levels as well as the phosphorylation of proteins can be determined by immunoprecitation followed by Western blot analysis. Immunoprecipitation protocols generally comprise lysing a population of cells in a lysis buffer such as RIPA buffer (1% NP-40 or Triton X-100, 1% sodium deoxycholate, 0.1% SDS, 0.15 M NaCl, 0.01 M sodium phosphate at pH 7.2, 1% Trasylol) supplemented with protein phosphatase and/or protease inhibitors (e.g., EDTA, PMSF, aprotinin, sodium vanadate), adding the antibody of interest to the cell lysate, incubating for a period of time (e.g., 1 to 4 hours) at 40° C., adding protein A and/or protein G sepharose beads to the cell lysate, incubating for about an hour or more at 40° C., washing the beads in lysis buffer and resuspending the beads in SDS/sample buffer. The ability of the antibody of interest to immunoprecipitate a particular antigen can be assessed by, e.g., western blot analysis. One of skill in the art would be knowledgeable as to the parameters that can be modified to increase the binding of the antibody to an antigen and decrease the background (e.g., pre-clearing the cell lysate with sepharose beads). For further discussion regarding immunoprecipitation protocols see, e.g., Ausubel et al, eds, 1994, Current Protocols in Molecular Biology, Vol. 1, John Wiley & Sons, Inc., New York at 10.16.1.

Western blot analysis generally comprises preparing protein samples, electrophoresis of the protein samples in a polyacrylamide gel (e.g., 8%-20% SDS-PAGE depending on the molecular weight of the antigen), transferring the protein sample from the polyacrylamide gel to a membrane such as nitrocellulose, PVDF or nylon, incubating the membrane in blocking solution (e.g., PBS with 3% BSA or non-fat milk), washing the membrane in washing buffer (e.g., PBS-Tween 20), incubating the membrane with primary antibody (the antibody of interest) diluted in blocking buffer, washing the membrane in washing buffer, incubating the membrane with a secondary antibody (which recognizes the primary antibody, e.g., an anti-human antibody) conjugated to an enzymatic substrate (e.g., horseradish peroxidase or alkaline phosphatase) or radioactive molecule (e.g., ³²P or ¹²⁵I) diluted in blocking buffer, washing the membrane in wash buffer, and detecting the presence of the antigen. One of skill in the art would be knowledgeable as to the parameters that can be modified to increase the signal detected and to reduce the background noise. For further discussion regarding western blot protocols see, e.g., Ausubel et al, eds, 1994, Current Protocols in Molecular Biology, Vol. 1, John Wiley & Sons, Inc., New York at 10.8.1.

Protein expression levels can also be separated by two-dimensional gel electrophoresis systems. Two-dimensional gel electrophoresis is well-known in the art and typically involves iso-electric focusing along a first dimension followed by SDS-PAGE electrophoresis along a second dimension. See, e.g., Hames et al., 1990, Gel Electrophoresis ofproteins: A Practical Approach, IRL Press, New York; Shevchenko et al., 1996, Proc. Natl. Acad. Sci. USA 93:1440-1445; Sagliocco et al., 1996, Yeast 12:1519-1533; Lander, 1996, Science 274:536-539. The resulting electropherograms can be analyzed by numerous techniques, including mass spectrometric techniques, Western blotting and immunoblot analysis using polyclonal and monoclonal antibodies, and internal and N-terminal micro-sequencing.

5.3. Treating CML by Modulating Expression and/or Activity of CML Progression Genes and/or Their Products

The invention provides methods and compositions for utilizing CML target genes listed in Table 3 or 5a or 5b and or imatinib resistance genes listed in Table 4 in treating CML. The methods and compositions are used for treating CML patient exhibiting aberrant regulation of one or more CML target/progression genes or IM resistance genes by modulating the expression and/or activity of such genes and/or the encoded proteins. The methods and composition can be used in conjunction with other CML treatment, e.g., imatinib mesylate. The compositions (e.g., agents that modulate expression and/or activity of the CML target gene or gene product) of the invention are preferably purified. In the following, for simplicity reasons, the methods are often described with reference to CML target gene(s). It will be understood that the methods are equally applicable to CML progression genes and IM resistance genes.

In one embodiment, the invention provides methods and compositions for treating a CML patient exhibiting an aberrant up-regulation of a CML target gene by reducing the expression and/or activity of the gene, and/or its encoded protein by at least 2 fold, 3 fold, 4 fold, 6 fold, 8 fold or 9 fold.

In a specific embodiment, the invention provides methods and compositions for treating a CML patient exhibiting an aberrant up-regulation of a CML target gene as listed in Table 5a or 5b by reducing the expression and/or activity of the gene, and/or its encoded protein.

In another embodiment, the invention provides methods and compositions for treating a CML patient exhibiting an aberrant down-regulation of a CML target gene by enhancing the expression and/or activity of the gene, and/or its encoded protein by at least 2 fold, 3 fold, 4 fold, 6 fold, 8 fold or 9 fold.

In a specific embodiment, the invention provides methods and compositions for treating a CML patient exhibiting an aberrant down-regulation of a CML target gene as listed in Table 5a or 5b by enhancing the expression and/or activity of the gene, and/or its encoded protein.

In a specific embodiment, the invention provides a method for treating CML by administering to a patient (i) an agent that modulates the expression and/or activity of an imatinib resistance gene and/or the encoded protein, and (ii) a therapeutically sufficient amount of imatinib mesylate.

In another embodiment, the invention provides methods and compositions for treating a CML patient exhibiting aberrant regulation of a plurality of different CML target gene as listed in Tables 5a and 5b by modulating the expression and/or activity of the plurality of genes, and/or its encoded proteins. In one embodiment, a CML patient exhibiting aberrant up-regulation of a plurality of CML progression gene listed in Tables 5a and 5b, e.g. 2, 3, 4, 5, 10 or more different CML target genes, is treated by administering to the patient one or more agents that reduce the expression and/or activities of these genes, and/or their encoded proteins.

A variety of therapeutic approaches may be used in accordance with the invention to modulate expression of a CML target gene or imatinib resistance gene and/or its encoded protein in vivo. For example, siRNA molecules may be engineered and used to silence a CML target gene in vivo. Antisense DNA molecules may also be engineered and used to block translation of a CML target mRNA in vivo. Alternatively, ribozyme molecules may be designed to cleave and destroy the mRNAs of a CML target gene in vivo. In another alternative, oligonucleotides designed to hybridize to the 5′ region of the CML target gene (including the region upstream of the coding sequence) and form triple helix structures may be used to block or reduce transcription of the CML target gene. The expression and/or activity of a CML target protein can be modulated using antibody, peptide or polypeptide molecules, and small organic or inorganic molecules. In the following, for simplicity, methods are described in reference to a CML target gene or protein. These methods are equally applicable to imatinib resistance genes.

In a preferred embodiment, RNAi is used to knock down the expression of a CML target gene. In one embodiment, double-stranded RNA molecules of 21-23 nucleotides which hybridize to a homologous region of mRNAs transcribed from the CML target gene are used to degrade the mRNAs, thereby “silence” the expression of the CML target gene. The method can be used to reduce expression levels of aberrantly up-regulated CML target genes. Preferably, the dsRNAs have a hybridizing region, e.g., a 19-nucleotide double-stranded region, which is complementary to a sequence of the coding sequence of the CML target gene. Any siRNA that targets an appropriate coding sequence of a CML target gene and exhibit a sufficient level of silencing can be used in the invention. As exemplary embodiments, 21-nucleotide double-stranded siRNAs targeting the coding regions of a CML target gene are designed according to selection rules known in the art (see, e.g., Elbashir et al., 2002, Methods 26:199-213; International Application No. PCT/US04/35636, filed Oct. 27, 2004, each of which is incorporated herein by reference in its entirety). In a preferred embodiment, the siRNA or siRNAs specifically inhibit the translation or transcription of a CML target protein without substantially affecting the translation or transcription of genes encoding other protein kinases in the same kinase family. In a specific embodiment, siRNAs targeting an up-regulated gene listed in Table 4 are used to silence the respective CML target genes.

The invention also provides methods and compositions for treating a CML patient exhibiting aberrant up-regulation of a plurality of CML target genes as listed in Tables 5a and 5b by reducing the expression and/or activities of these genes, and/or their encoded proteins. In one embodiment, a CML patient exhibiting aberrant up-regulation of a plurality of CML target gene listed in Tables 5a and 5b, e.g. 2, 3, 4, 5, 10 or more different CML target genes, is treated by administering to the patient one or more agents that reduce the expression and/or activities of these genes, and/or their encoded proteins. In a preferred embodiment, an siRNA is used to silence the plurality of different CML target genes. The sequence of the siRNA is chosen such that the transcript of each of the genes comprises a nucleotide sequence that is identical to a central contiguous nucleotide sequence of at least 11 nucleotides of the sense strand or the antisense strand of the siRNA, and/or comprises a nucleotide sequence that is identical to a contiguous nucleotide sequence of at least 9 nucleotides at the 3′ end of the sense strand or the antisense strand of the siRNA. Thus, when administrated to the patient, the siRNA silences all of the plurality of genes in cells of the patient. In preferred embodiments, the central contiguous nucleotide sequence of the siRNA that is identical to one or more CML target genes is 11-15, 14-15, 11, 12, or 13 nucleotides in length. In other preferred embodiments, the 3′ contiguous nucleotide sequence of the siRNA that is identical to one or more CML target genes is 9-15, 9-12, 11, 10, or 9 nucleotides in length. The length and nucleotide base sequence of the target sequence of each different target gene, i.e., the sequence of the gene that is identical to an appropriate sense or antisense sequence of the siRNA, can be different from gene to gene. For example, gene A may have a sequence of 11 nucleotides identical to the nucleotide sequence 3-13 of the sense strand of the siRNA, while gene B may have a sequence of 12 nucleotides identical to the nucleotide sequence 4-15 of the sense strand of the siRNA. Thus, a single siRNA may be designed to silence a large number of CML target genes in cells.

RNAi can be carried out using any standard method for introducing nucleic acids into cells. In one embodiment, gene silencing is induced by presenting the cell with one or more siRNAs targeting the CML target gene (see, e.g., Elbashir et al., 2001, Nature 411, 494-498; Elbashir et al., 2001, Genes Dev. 15, 188-200, all of which are incorporated by reference herein in their entirety). The siRNAs can be chemically synthesized, or derived from cleavage of double-stranded RNA by recombinant Dicer. Another method to introduce a double stranded DNA (dsRNA) for silencing of the CML target gene is shRNA, for short hairpin RNA (see, e.g., Paddison et al., 2002, Genes Dev. 16, 948-958; Brummelkamp et al., 2002, Science 296, 550-553; Sui, G. et al. 2002, Proc. Natl. Acad. Sci. USA 99, 5515-5520, all of which are incorporated by reference herein in their entirety). In this method, a siRNA targeting a CML target gene is expressed from a plasmid (or virus) as an inverted repeat with an intervening loop sequence to form a hairpin structure. The resulting RNA transcript containing the hairpin is subsequently processed by Dicer to produce siRNAs for silencing. Plasmid- or virus-based shRNAs can be expressed stably in cells, allowing long-term gene silencing in cells both in vitro and in vivo (see, McCaffrey et al. 2002, Nature 418, 38-39; Xia et al., 2002, Nat. Biotech. 20, 1006-1010; Lewis et al., 2002, Nat. Genetics 32, 107-108; Rubinson et al., 2003, Nat. Genetics 33, 401-406; Tiscornia et al., 2003, Proc. Natl. Acad. Sci. USA 100, 1844-1848, all of which are incorporated by reference herein in their entirety). Such plamid- or virus-based shRNAs can be delivered using a gene therapy approach. SiRNAs targeting the CML target gene can also be delivered to an organ or tissue in a mammal, such a human, in vivo (see, e.g., Song et al. 2003, Nat. Medicine 9, 347-351; Sorensen et al., 2003, J Mol. Biol. 327, 761-766; Lewis et al., 2002, Nat. Genetics 32, 107-108, all of which are incorporated by reference herein in their entirety). In this method, a solution of siRNA is injected intravenously into the mammal. The siRNA can then reach an organ or tissue of interest and effectively reduce the expression of the target gene in the organ or tissue of the mammal.

In preferred embodiments, an siRNA pool (mixture) containing at least k (k=2, 3, 4, 5, 6 or 10) different siRNAs targeting a CML target gene at different sequence regions is used to silence the gene. In a preferred embodiment, the total siRNA concentration of the pool is about the same as the concentration of a single siRNA when used individually. As used herein, the word “about” with reference to concentration means within 20%. Preferably, the total concentration of the pool of siRNAs is an optimal concentration for silencing the intended target gene. An optimal concentration is a concentration further increase of which does not increase the level of silencing substantially. In one embodiment, the optimal concentration is a concentration further increase of which does not increase the level of silencing by more than 5%, 10% or 20%. In a preferred embodiment, the composition of the pool, including the number of different siRNAs in the pool and the concentration of each different siRNA, is chosen such that the pool of siRNAs causes less than 30%, 20%, 10% or 5%, 1%, 0.1% or 0.01% of silencing of any off-target genes (e.g., as determined by standard nucleic acid assay, e.g., PCR). In another preferred embodiment, the concentration of each different siRNA in the pool of different siRNAs is about the same. In still another preferred embodiment, the respective concentrations of different siRNAs in the pool are different from each other by less than 5%, 10%, 20% or 50% of the concentration of any one siRNA or said total siRNA concentration of said different siRNAs. In still another preferred embodiment, at least one siRNA in the pool of different siRNAs constitutes more than 90%, 80%, 70%, 50%, or 20% of the total siRNA concentration in the pool. In still another preferred embodiment, none of the siRNAs in the pool of different siRNAs constitutes more than 90%, 80%, 70%, 50%, or 20% of the total siRNA concentration in the pool. In other embodiments, each siRNA in the pool has a concentration that is lower than the optimal concentration when used individually. In a preferred embodiment, each different siRNA in the pool has an concentration that is lower than the concentration of the siRNA that is effective to achieve at least 30%, 50%, 75%, 80%, 85%, 90% or 95% silencing when used in the absence of other siRNAs or in the absence of other siRNAs designed to silence the gene. In another preferred embodiment, each different siRNA in the pool has a concentration that causes less than 30%, 20%, 10% or 5% of silencing of the gene when used in the absence of other siRNAs or in the absence of other siRNAs designed to silence the gene. In a preferred embodiment, each siRNA has a concentration that causes less than 30%, 20%, 10% or 5% of silencing of the target gene when used alone, while the plurality of siRNAs causes at least 80% or 90% of silencing of the target gene. In specific embodiments, a pool containing the 3 different is used for targeting a CML target gene. More detailed descriptions of techniques for carrying out RNAi are also presented in Section 5.6.

In other embodiments, antisense, ribozyme, and triple helix forming nucleic acid are designed to inhibit the translation or transcription of a CML target protein or gene with minimal effects on the expression of other genes that may share one or more sequence motif with the CML target gene. To accomplish this, the oligonucleotides used should be designed on the basis of relevant sequences unique to a CML target gene. In one embodiment, the oligonucleotide used specifically inhibits the translation or transcription of a CML target protein or gene without substantially affecting the translation or transcription of other proteins in the same protein family.

For example, and not by way of limitation, the oligonucleotides should not fall within those regions where the nucleotide sequence of a CML target gene is most homologous to that of other genes. In the case of antisense molecules, it is preferred that the sequence be at least 18 nucleotides in length in order to achieve sufficiently strong annealing to the target mRNA sequence to prevent translation of the sequence. Izant et al., 1984, Cell, 36:1007-1015; Rosenberg et al., 1985, Nature, 313:703-706.

Ribozymes are RNA molecules which possess highly specific endoribonuclease activity. Hammerhead ribozymes comprise a hybridizing region which is complementary in nucleotide sequence to at least part of the target RNA, and a catalytic region which is adapted to cleave the target RNA. The hybridizing region contains nine (9) or more nucleotides. Therefore, the hammerhead ribozymes useful for targeting a CML target gene having a hybridizing region which is complementary to the sequences of the target gene and is at least nine nucleotides in length. The construction and production of such ribozymes is well known in the art and is described more fully in Haseloffet al., 1988, Nature, 334:585-591.

The ribozymes of the present invention also include RNA endoribonucleases (hereinafter “Cech-type ribozymes”) such as the one which occurs naturally in Tetrahymena Thermophila (known as the IVS, or L-19 IVS RNA) and which has been extensively described by Thomas Cech and collaborators (Zaug, et al., 1984, Science, 224:574-578; Zaug and Cech, 1986, Science, 231:470-475; Zaug, et al., 1986, Nature, 324:429-433; published International patent application No. WO 88/04300 by University Patents Inc.; Been et al., 1986, Cell, 47:207-216). The Cech endoribonucleases have an eight base pair active site which hybridizes to a target RNA sequence whereafter cleavage of the target RNA takes place.

In the case of oligonucleotides that hybridize to and form triple helix structures at the 5′ terminus of a CML target gene and can be used to block transcription, it is preferred that they be complementary to those sequences in the 5′ terminus of a CML target gene which are not present in other related genes. It is also preferred that the sequences not include those regions of the promoter of a CML target gene which are even slightly homologous to that of other related genes.

The foregoing compounds can be administered by a variety of methods which are known in the art including, but not limited to the use of liposomes as a delivery vehicle. Naked DNA or RNA molecules may also be used where they are in a form which is resistant to degradation such as by modification of the ends, by the formation of circular molecules, or by the use of alternate bonds including phosphothionate and thiophosphoryl modified bonds. In addition, the delivery of nucleic acid may be by facilitated transport where the nucleic acid molecules are conjugated to poly-lysine or transferrin. Nucleic acid may also be transported into cells by any of the various viral carriers, including but not limited to, retrovirus, vaccinia, AAV, and adenovirus.

Alternatively, a recombinant nucleic acid molecule which encodes, or is, such antisense nucleic acid, ribozyme, triple helix forming nucleic acid, or nucleic acid molecule of a CML target gene can be constructed. This nucleic acid molecule may be either RNA or DNA. If the nucleic acid encodes an RNA, it is preferred that the sequence be operatively attached to a regulatory element so that sufficient copies of the desired RNA product are produced. The regulatory element may permit either constitutive or regulated transcription of the sequence. In vivo, that is, within the cells or cells of an organism, a transfer vector such as a bacterial plasmid or viral RNA or DNA, encoding one or more of the RNAs, may be transfected into cells e.g. (Llewellyn et al., 1987, J. Mol. Biol., 195:115-123; Hanahan et al. 1983, J. Mol. Biol., 166:557-580). Once inside the cell, the transfer vector may replicate, and be transcribed by cellular polymerases to produce the RNA or it may be integrated into the genome of the host cell. Alternatively, a transfer vector containing sequences encoding one or more of the RNAs may be transfected into cells or introduced into cells by way of micromanipulation techniques such as microinjection, such that the transfer vector or a part thereof becomes integrated into the genome of the host cell.

The activity of a CML target protein can be modulated by modulating the interaction of a CML target protein with its binding partners. In one embodiment, agents, e.g., antibodies, peptides, aptamers, small organic or inorganic molecules, can be used to inhibit binding of a CML target protein binding partner to treat CML. In another embodiment, agents, e.g., antibodies, aptamers, small organic or inorganic molecules, can be used to inhibit the activity of a CML target protein to treat CML.

In other embodiments, when the CML target protein is a kinase, the invention provides small molecule inhibitors of the CML target protein. A small molecule inhibitor is a low molecular weight phosphorylation inhibitor. As used herein, a small molecule refers to an organic or inorganic molecule having a molecular weight is under 1000 Daltons, preferably in the range between 300 to 700 Daltons, which is not a nucleic acid molecule or a peptide molecule. The small molecule can be naturally occurring, e.g., extracted from plant or microorganisms, or non-naturally occurring, e.g., generated de novo by synthesis. A small molecule that is an inhibitor can be used to block a cellular process that dependent on a CML target protein. In one embodiment, the inhibitors are substrate Mimics. In a preferred embodiment, the inhibitor of the CML target proteins is an ATP mimic. In one embodiment, such ATP mimics possess at least two aromatic rings. In a preferred embodiment, the ATP mimic comprises a moiety that forms extensive contacts with residues lining the ATP binding cleft of the CML target protein and/or peptide segments just outside the cleft, thereby selectively blocking the ATP binding site of the CML target protein. Minor structural differences from ATP can be introduced into the ATP mimic based on the peptide segments just outside the cleft. Such differences can lead to specific hydrogen bonding and hydrophobic interactions with the peptide segments just outside the cleft.

In still other embodiments, antibodies that specifically bind the CML target protein are used. In a preferred embodiment, the invention provides antibodies that specifically bind the extracellular domain of a CML target protein that is a receptor. Antibodies that specifically bind a target can be obtained using standard method known in the art, e.g., a method described in Section 5.8.

In one embodiment, an antibody-drug conjugate comprising an antibody that specifically binds a CML target protein is used. The efficacy of the antibodies that targets specific molecules expressed by advanced phase immature myeloid cells can be increased by attaching toxins to them. Existing immunotoxins are based on bacterial toxins like pseudomonas exotoxin, plant exotoxin like ricin or radio-nucleotides. The toxins are chemically conjugated to a specific ligand such as the variable domain of the heavy or light chain of the monoclonal antibody. Normal cells lacking the cancer specific antigens are not targeted by the targeted antibody. In a preferred embodiment, the CML target protein target is PRAME.

In other embodiments, a peptide and peptidomimetic that interferes with the interaction of a CML target protein with its interaction partner is used. A peptide preferably has a size of at least 5, 10, 15, 20 or 30 amino acids. Such a peptide or peptidomimetic can be designed by a person skilled in the art based on the sequence and structure of a CML target protein. In one embodiment, a peptide or peptidomimetic that interferes with substrate binding of a CML target protein is used. In another embodiment, peptide or peptidomimetic that interferes with the binding of a signal molecule to a CML target protein is used. In some embodiments of the invention, a fragment or polypeptide of at least 5, 10, 20, 50, 100 amino acids in length of a CML target protein are used. In a specific embodiment, a peptide or peptidomimetic that interferes with the interaction with PRAME is used. The peptide can be prepared by standard method known in the art.

In another embodiment, a dominant negative mutant of a CML target protein is used to reduce activity of a CML target protein. Such a dominant negative mutant can be designed by a person skilled in the art based on the sequence and structure of a CML target protein. In one embodiment, a dominant negative mutant that interferes with substrate binding of a CML target protein is used. In another embodiment, a dominant negative mutant that interferes with the binding of a signal molecule to a CML target protein is used. In a preferred embodiment, the invention provides a dominant negative mutant that comprises the C-terminal region of a CML target protein. In another embodiment, the invention provides a dominant negative mutant that comprises the N-terminal region of the CML target protein.

Gene therapy can be used for delivering any of the above described nucleic acid and protein/peptide therapeutics into target cells. Gene therapy is particularly useful for enhancing aberrantly down-regulated genes. Exemplary methods for carrying out gene therapy are described below. For general reviews of the methods of gene therapy, see Goldspiel et al., 1993, Clinical Pharmacy 12:488-505; Wu and Wu, 1991, Biotherapy 3:87-95; Tolstoshev, 1993, Ann. Rev. Pharmacol. Toxicol. 32:573-596; Mulligan, 1993, Science 260:926-932; and Morgan and Anderson, 1993, Ann. Rev. Biochem. 62:191-217; May, 1993, TIBTECH 11 (5):155-215). Methods commonly known in the art of recombinant DNA technology which can be used are described in Ausubel et al. (eds.), 1993, Current Protocols in Molecular Biology, John Wiley & Sons, New York; and Kriegler, 1990, Gene Transfer and Expression, A Laboratory Manual, Stockton Press, New York.

In a preferred embodiment, the therapeutic comprises a nucleic acid that is part of an expression vector that expresses a the therapeutic nucleic acid or peptide/polypeptide in a suitable host. In particular, such a nucleic acid has a promoter operably linked to the coding region, said promoter being inducible or constitutive, and, optionally, tissue-specific. In another particular embodiment, a nucleic acid molecule is used in which the coding sequences and any other desired sequences are flanked by regions that promote homologous recombination at a desired site in the genome, thus providing for intrachromosomal expression of the CML target nucleic acid (see e.g., Koller and Smithies, 1989, Proc. Natl. Acad. Sci. U.S.A. 86:8932-8935; Zijlstra et al., 1989, Nature 342:435-438).

Delivery of the nucleic acid into a patient may be either direct, in which case the patient is directly exposed to the nucleic acid or nucleic acid-carrying vector, or indirect, in which case, cells are first transformed with the nucleic acid in vitro, then transplanted into the patient. These two approaches are known, respectively, as in vivo or ex vivo gene therapy.

In a specific embodiment, the nucleic acid is directly administered in vivo, where it is expressed to produce the encoded product. This can be accomplished by any of numerous methods known in the art, e.g., by constructing it as part of an appropriate nucleic acid expression vector and administering it so that it becomes intracellular, e.g., by infection using a defective or attenuated retroviral or other viral vector (see U.S. Pat. No. 4,980,286), or by direct injection of naked DNA, or by use of microparticle bombardment (e.g., a gene gun; Biolistic, Dupont), or coating with lipids or cell-surface receptors or transfecting agents, encapsulation in liposomes, microparticles, or microcapsules, or by administering it in linkage to a peptide which is known to enter the nucleus, by administering it in linkage to a ligand subject to receptor-mediated endocytosis (see e.g., Wu and Wu, 1987, J. Biol. Chem. 262:4429-4432) (which can be used to target cell types specifically expressing the receptors), etc. In another embodiment, a nucleic acid-ligand complex can be formed in which the ligand comprises a fusogenic viral peptide to disrupt endosomes, allowing the nucleic acid to avoid lysosomal degradation. In yet another embodiment, the nucleic acid can be targeted in vivo for cell specific uptake and expression, by targeting a specific receptor (see, e.g., PCT Publications WO 92/06180 dated Apr. 16, 1992 (Wu et al.); WO 92/22635 dated Dec. 23, 1992 (Wilson et al.); WO92/20316 dated Nov. 26, 1992 (Findeis et al.); WO93/14188 dated Jul. 22, 1993 (Clarke et al.), WO 93/20221 dated Oct. 14, 1993 (Young)). Alternatively, the nucleic acid can be introduced intracellularly and incorporated within host cell DNA for expression, by homologous recombination (Koller and Smithies, 1989, Proc. Natl. Acad. Sci. U.S.A. 86:8932-8935; Zijlstra et al., 1989, Nature 342:435-438).

In a specific embodiment, a viral vector that contains the nucleic acid of a CML target gene is used. For example, a retroviral vector can be used (see Miller et al., 1993, Meth. Enzymol. 217:581-599). These retroviral vectors have been modified to delete retroviral sequences that are not necessary for packaging of the viral genome and integration into host cell DNA. The CML target nucleic acid to be used in gene therapy is cloned into the vector, which facilitates delivery of the gene into a patient. More detail about retroviral vectors can be found in Boesen et al., 1994, Biotherapy 6:291-302, which describes the use of a retroviral vector to deliver the mdrl gene to hematopoietic stem cells in order to make the stem cells more resistant to chemotherapy. Other references illustrating the use of retroviral vectors in gene therapy are: Clowes et al., 1994, J. Clin. Invest. 93:644-651; Kiem et al., 1994, Blood 83:1467-1473; Salmons and Gunzberg, 1993, Human Gene Therapy 4:129-141; and Grossman and Wilson, 1993, Curr. Opin. Genet. and Devel. 3:110-114.

Adenoviruses are other viral vectors that can be used in gene therapy. Adenoviruses are especially attractive vehicles for delivering genes to respiratory epithelia. Adenoviruses naturally infect respiratory epithelia where they cause a mild disease. Other targets for adenovirus-based delivery systems are liver, the central nervous system, endothelial cells, and muscle. Adenoviruses have the advantage of being capable of infecting non-dividing cells. Kozarsky and Wilson (1993, Current Opinion in Genetics and Development 3:499-503) present a review of adenovirus-based gene therapy. Bout et al. (1994, Human Gene Therapy 5:3-10) demonstrated the use of adenovirus vectors to transfer genes to the respiratory epithelia of rhesus monkeys. Other instances of the use of adenoviruses in gene therapy can be found in Rosenfeld et al., 1991, Science 252:431-434; Rosenfeld et al., 1992, Cell 68:143-155; and Mastrangeli et al., 1993, J. Clin. Invest. 91:225-234.

Adeno-associated virus (AAV) has also been proposed for use in gene therapy (Walsh et al., 1993, Proc. Soc. Exp. Biol. Med. 204:289-300).

Another approach to gene therapy involves transferring a gene to cells in tissue culture by such methods as electroporation, lipofection, calcium phosphate mediated transfection, or viral infection. Usually, the method of transfer includes the transfer of a selectable marker to the cells. The cells are then placed under selection to isolate those cells that have taken up and are expressing the transferred gene. Those cells are then delivered to a patient.

In this embodiment, the nucleic acid is introduced into a cell prior to administration in vivo of the resulting recombinant cell. Such introduction can be carried out by any method known in the art, including but not limited to transfection, electroporation, microinjection, infection with a viral or bacteriophage vector containing the nucleic acid sequences, cell fusion, chromosome-mediated gene transfer, microcell-mediated gene transfer, spheroplast fusion, etc. Numerous techniques are known in the art for the introduction of foreign genes into cells (see e.g., Loeffler and Behr, 1993, Meth. Enzymol. 217:599-618; Cohen et al., 1993, Meth. Enzymol. 217:618-644; Cline, 1985, Pharmac. Ther. 29:69-92) and may be used in accordance with the present invention, provided that the necessary developmental and physiological functions of the recipient cells are not disrupted. The technique should provide for the stable transfer of the nucleic acid to the cell, so that the nucleic acid is expressible by the cell and preferably heritable and expressible by its cell progeny.

The resulting recombinant cells can be delivered to a patient by various methods known in the art. In a preferred embodiment, epithelial cells are injected, e.g., subcutaneously. In another embodiment, recombinant skin cells may be applied as a skin graft onto the patient. Recombinant blood cells (e.g., hematopoietic stem or progenitor cells) are preferably administered intravenously. The amount of cells envisioned for use depends on the desired effect, patient state, etc., and can be determined by one skilled person in the art.

Cells into which a nucleic acid can be introduced for purposes of gene therapy encompass any desired, available cell type, and include but are not limited to epithelial cells, endothelial cells, keratinocytes, fibroblasts, muscle cells, hepatocytes; blood cells such as T lymphocytes, B lymphocytes, monocytes, macrophages, neutrophils, eosinophils, megakaryocytes, granulocytes; various stem or progenitor cells, in particular hematopoietic stem or progenitor cells, e.g., as obtained from bone marrow, umbilical cord blood, peripheral blood, fetal liver, etc.

In a preferred embodiment, the cell used for gene therapy is autologous to the patient.

In an embodiment in which recombinant cells are used in gene therapy, a nucleic acid is introduced into the cells such that it is expressible by the cells or their progeny, and the recombinant cells are then administered in vivo for therapeutic effect. In a specific embodiment, stem or progenitor cells are used. Such stem cells can be hematopoietic stem cells (HSC).

Any technique which provides for the isolation, propagation, and maintenance in vitro of HSC can be used in this embodiment of the invention. Techniques by which this may be accomplished include (a) the isolation and establishment of HSC cultures from bone marrow cells isolated from the future host, or a donor, or (b) the use of previously established long-term HSC cultures, which may be allogeneic or xenogeneic. Non-autologous HSC are used preferably in conjunction with a method of suppressing transplantation immune reactions of the future host/patient. In a particular embodiment of the present invention, human bone marrow cells can be obtained from the posterior iliac crest by needle aspiration (see e.g., Kodo et al., 1984, J. Clin. Invest. 73:1377-1384). The HSCs can be made highly enriched or in substantially pure form. This enrichment can be accomplished before, during, or after long-term culturing, and can be done by any techniques known in the art. Long-term cultures of bone marrow cells can be established and maintained by using, for example, modified Dexter cell culture techniques (Dexter et al., 1977, J. Cell Physiol. 91:335) or Witlock-Witte culture techniques (Witlock and Witte, 1982, Proc. Natl. Acad. Sci. U.S.A. 79:3608-3612).

In a specific embodiment, the nucleic acid to be introduced for purposes of gene therapy comprises an inducible promoter operably linked to the coding region, such that expression of the nucleic acid is controllable by controlling the presence or absence of the appropriate inducer of transcription. The methods and/or compositions described above for modulating the expression and/or activity of a CML target gene or CML target protein may be used to treat patients in conjunction with a chemotherapeutic agent, e.g., Gleevec™.

The effects or benefits of administration of the compositions of the invention alone or in conjunction with a chemotherapeutic agent can be evaluated by any methods known in the art, e.g., by methods that are based on measuring the survival rate, side effects, dosage requirement of the chemotherapeutic agent, or any combinations thereof. If the administration of the compositions of the invention achieves any one or more benefits in a patient, such as increasing the survival rate, decreasing side effects, lowing the dosage requirement for the chemotherapeutic agent, the compositions of the invention are said to have augmented a chemotherapy, and the method is said to have efficacy.

5.4. Diagnosis and Treatment of CML by Targeting Cell Surface Expressed PRAME

The present invention provides methods and compositions for diagnosis and treatment of CML by targeting PRAME (GenBank® accession no. NM_—006115) on cell surfaces of advanced phase hematopoetic stem cells and immature myeloid cells. PRAME is known to be expressed in testis and to expressed at a low level in endometrium, adrenals and ovaries, and is not expressed in other normal tissues. The inventors have found that PRAME is significantly overexpressed in advanced phase CML cells as compared to chronic phase CML cells. Thus, methods and compositions that target PRAME can be used for detecting advanced phase CML cells and for treating CML by selectively targeting advanced phase CML cells.

5.4.1. Methods of Detecting Advanced Phase CML

Antibodies or labeled antibodies directed against a PRAME (Preferentially Expressed Antigen of Melanoma) can be used for evaluating CML progression, e.g., by detecting the presence of PRAME protein on cell surface of hematopoetic stem cells and immature myeloid cells. Such diagnostic/prognostic methods are particularly useful for detecting CML progression in unsorted samples.

The tissue or cell type to be analyzed may include those which are known to relate to CML, e.g., bone marrow or peripheral blood. The protein isolation methods employed herein may, for example, be such as those described in Harlow and Lane (Harlow, E. and Lane, D., 1988, “Antibodies: A Laboratory Manual”, Cold Spring Harbor Laboratory Press, Cold Spring Harbor, N.Y.), which is incorporated herein by reference in its entirety. The isolated cells can be derived from cell culture or from a patient. The analysis of cells taken from culture may be a necessary step in the assessment of cells to be used as part of a cell-based gene therapy technique or, alternatively, to test the effect of compounds for CML treatment.

In one embodiment, the invention provides a method for diagnosing whether a patient has advanced phase chronic myeloid leukemia (CML), comprising (a) contacting a cell sample from said patient with an antibody conjugate, said antibody conjugate comprising an antibody that binds a PRAME protein conjugated with a label; and (b) detecting said label in said sample, wherein detection of said label above a predetermined threshold indicating said patient has advanced phase CML. Detection of the labeled antibody can be performed using a method described in Section 5.2.5, supra.

5.4.2. Methods of Treating CML by Targeting PRAME

The invention provides methods and compositions for treating CML by targeting PRAME expressed on the cell surface.

In one embodiment, the present invention provides methods of using anti-PRAME antibodies for treatment of a CML patient. In the methods of the invention, one or more anti-PRAME antibodies are administered to the patient. The anti-PRAME antibodies bind to PRAME on the surface of advanced phase CML hematopoetic stem cells and/or immature myeloid cells. The binding of arti-PRAME antibodies to PRAME blocks the function mediated by PRAME, thereby preventing the proliferation of advanced phase hematopoetic stem cells.

In another embodiment, the present invention provides a method for treatment of CML using an anti-PRAME antibody that belongs to an isotype that is capable of mediating lysis of cells to which the anti-PRAME antibody is bound. In a preferred embodiment, the anti-PRAME antibody belongs to an isotype that binds a growth factor receptor and activates serum complement and/or mediates antibody dependent cellular cytotoxicity (ADCC) by activating effector cells, e.g., macrophages. In another preferred embodiment, the isotype is IgG1, IgG2a, IgG3 or IgM.

In still another embodiment, the anti-PRAME antibodies are used in conjunction with one or more other chemotherapeutic drugs. In such combined therapies, the anti-PRAME antibodies can be administered in a manner such as described in Section 5.10.5.

The dosage of the anti-PRAME antibodies can be determined by routine experiments that are familiar to one skilled in the art. The effects or benefits of administration of the anti-PRAME antibodies can be evaluated by any method known in the art.

In another embodiment, an antibody-drug conjugate comprising an antibody that specifically binds PRAME and a chemotherapeutic drug is used to selectively deliver the chemotherapeutic drug to advanced phase CML hematopoetic stem cells and/or immature myeloid cells. Chemotherapeutic drugs normally spread throughout the body, reaching not only the intended target but also healthy cells/organs such as the intestines and healthy bone marrow, where they kill off normal dividing cells. A drug conjugated to PRAME should be able to selectively target the advance phase CML hematopoetic stem cells and/or immature myeloid cells, thus increasing the sensitivity and specificity of the drug. For example, an anti-PRAME antibody may be conjugated to a therapeutic moiety such as a cytotoxin, e.g., a cytostatic or cytocidal agent, or a radioactive metal ion (see, e.g., Section 5.8). Any suitable antibody-drug conjugate, e.g., those described in Section 5.8.3 can be used. Normal hematopoetic stem cells and/or myeloid cells lack PRAME and are not targeted by the antibody.

In still another embodiment, a peptide or a peptidomimetic that interferes with the interaction of PRAME with its interaction partner is used. A peptide preferably has a size of at least 5, 10, 15, 20 or 30 amino acids. Such a peptide or peptidomimetic can be designed by a person skilled in the art based on the sequence and structure of PRAME. In some embodiments of the invention, a PRAME fragment of at least 5, 10, 20, 50, 100 amino acids in length is used. In a specific embodiment, a peptide or peptidomimetic that interferes with the interaction with PRAME is used. The peptide can be prepared by a standard method known in the art (see, e.g., Section 5.8.4).

The invention also provides methods for treating CML using fragments of a PRAME protein as vaccines to elicit an immunotherapeutic response in a patient, e.g., an antibody response and/or a cell mediated immune response. Antibody responses involve the production of antibodies, which are proteins called immunoglobulins. The antibodies circulate in the bloodstream and permeate the other body fluids, where they bind specifically to the foreign antigen that elicited them. Binding by antibody inactivates advanced phase CML hematopoetic stem cells and/or immature myeloid cells by blocking their functions facilitated by PRAME. Antibody binding also marks advanced phase CML hematopoetic stem cells and/or immature myeloid cells, either by making it easier for a phagocytic cell to ingest them or by activating a system of blood proteins, collectively called complement, which kills the marked target cells.

Cell-mediated immune responses to PRAME involve the production of specialized cells that react with PRAME antigen on the surface of advanced phase CML cells. T lymphocytes, which develop in the thymus, are responsible for cell-mediated immunity. The majority of T lymphocytes, called helper T cells and suppressor T cells, play a regulatory role in immunity, acting either to enhance or suppress the responses of other white blood cells. Other T lymphocytes, called cytotoxic T cells (CTLs), kill virus-infected cells, parasites, and cancer cells. The surface of T cells contains transmembrane proteins called T cell receptors that recognize the PRAME antigen on the surface of PRAME presenting advanced phase CML cells. T cell receptors are antibody-like proteins. The antigen must be presented to the T cell by a particular membrane protein, one encoded by a complex of genes called the major histocompatibility complex (MHC). Histocompatibility molecules are expressed on the cells of all higher vertebrates. There are two principal classes of MHC molecules, class I MHC and class II MHC. Cytotoxic T lymphocytes (CTLs) recognize foreign antigens in association with class I MHC glycoproteins on the surface of an antigen-presenting cell, whereas helper T cells recognize foreign antigens in association with class II MHC glycoproteins on the surface of an antigen-presenting cell. A cytotoxic T lymphocyte will kill an antigen-presenting cell when it recognizes antigen bound to class I MHC molecules on the surface of the antigen-presenting cell. In one embodiment, a PRAME vaccine is used to elicit production of CTLs.

The PRAME protein fragment or polypeptide can be prepared by a standard method known in the art. In a specific embodiment, the fragment is a human PRAME protein fragment, or its murine homolog. In another embodiment, the vaccine comprises a peptide sequence that is at least 30%, 50%, 70%, 90%, or 95% homologous (e.g., over an equal size) to such fragments of a PRAME protein, e.g., as determined by a BLAST algorithm. In some embodiments, the PRAME protein fragments or polypeptides are at least 5, 10, 20, 50, 100 amino acids in length.

A peptide or polypeptide which is functionally equivalent to any PRAME fragment described above can also be used. Such an equivalent PRAME fragment may contain deletions, additions or substitutions of amino acid residues within the amino acid sequence encoded by the PRAME gene sequence but which result in a silent change, thus producing a functionally equivalent PRAME protein fragment. Amino acid substitutions may be made on the basis of similarity in polarity, charge, solubility, hydrophobicity, hydrophilicity, and/or the amphipathic nature of the residues involved. Conservative substitutions may be made from among amino acids of the same polarity. For example, nonpolar (hydrophobic) amino acids include alanine, leucine, isoleucine, valine, proline, phenylalanine, tryptophan, and methionine; polar neutral amino acids include glycine, serine, threonine, cysteine, tyrosine, asparagine, and glutamine; positively charged (basic) amino acids include arginine, lysine, and histidine; and negatively charged (acidic) amino acids include aspartic acid and glutamic acid. “Functionally equivalent”, as utilized herein, refers to a protein fragment capable of exhibiting a substantially similar in vivo activity as the endogenous PRAME protein fragment.

The PRAME peptide fragments may be produced by recombinant DNA technology using techniques well known in the art (see, e.g., Section 5.8.4).

The PRAME peptide can be used in combination with a suitable carrier and/or adjuvant, such as Freund's complete or incomplete adjuvant, or a similar immunostimulatory agent. An oil/surfactant based adjuvant comprising one or more surfactants combined with one or more non-metabolizable mineral oil or metabolizable oil, such as the Incomplete Seppic Adjuvant (Seppic, Paris, France), may be used. An Incomplete Seppic Adjuvant has a comparable effect as Incomplete Freund's Adjuvant for antibody production, but induces a lower inflammatory response.

A fragment of a PRAME gene can also be used as a DNA or RNA vaccine. In a specific embodiment, the fragment of a PRAME gene is a fragment of a human PRAME gene, or its murine homolog. The invention also provides any sequence that is at least 30%, 50%, 70%, 90%, or 95% homologous (e.g., over an equal size) to such fragments of a PRAME gene. In some embodiments of the invention, the fragment of a PRAME gene is at least 20, 25, 40, 60, 80, 100, 500, 1000 bases in length. Such sequences may be useful for production of PRAME peptides.

In another embodiment, the present invention provides a naked DNA or RNA vaccine comprising a fragment of a PRAME gene, and uses thereof. The PRAME DNA fragment can be administered as a vaccine to elicit anti-PRAME antibodies. The DNA can be converted to RNA for example by subcloning the DNA into a transcriptional vector, such as pGEM family of plasmid vectors, or under control of a transcriptional promoter of a virus such as vaccinia, and the RNA used as a naked RNA vaccine. The naked DNA or RNA vaccine can be injected alone, or combined with one or more DNA or RNA vaccines directed to PRAME.

The naked DNA or RNA vaccine of the present invention can be administered for example intramuscularly, or alternatively, can be used in nose drops. The DNA or RNA fragment or a portion thereof can be injected as naked DNA or RNA, as DNA or RNA encapsulated in liposomes, as DNA or RNA entrapped in proteoliposomes containing viral envelope receptor proteins (Nicolau, C. et al. Proc. Natl. Acad. Sci. U.S.A. 1983, 80, 1068; Kanoda, Y., et al. Science 1989, 243, 375; Mannino, R. J. et al. Biotechniques 1988, 6, 682). Alternatively, the DNA can be injected along with a carrier. A carrier can be a protein or such as a cytokine, for example interleukin 2, or a polylysine-glycoprotein carrier (Wu, G. Y. and Wu, C. H. J. Biol. Chem. 1988, 263, 14621), or a nonreplicating vector, for example expression vectors containing either the Rous sarcoma virus or cytomegalovirus promoters. Such carrier proteins and vectors and methods for using same are known to a person in the art (See for example, Acsadi, G. et al. Nature 1991, 352, 815-818). In addition, the DNA or RNA could be coated onto tiny gold beads and the beads introduced into the skin with, for example, a gene gun (Cohen, J. Science 1993, 259, 1691-1692; Ulmer, J. B. et al. Science 1993, 259, 1745-1749).

5.4.3. Depletion of Advanced Phase CML Hematopoetic Stem Cells and/or Immature Myeloid Cells In Vitro

The invention provides methods of depleting advanced phase CML hematopoetic stem cells and/or immature myeloid cells from bone marrow or blood in vitro (or ex vivo). In particular, the invention provides for methods of depleting advanced phase CML hematopoetic stem cells and/or immature myeloid cells by killing them or by separating them from bone marrow or blood. In one embodiment, anti-PRAME antibodies are combined, e.g., incubated, in vitro with bone marrow or blood from a patient, e.g., a human. In one embodiment, a column containing an anti-PRAME antibody bound to a solid matrix is used to remove advanced phase hematopoetic stem cells and/or immature myeloid cells from a bone marrow or blood sample.

The anti-PRAME antibodies used in the in vitro depletion of advanced phase CML hematopoetic stem cells and/or immature myeloid cells from samples can be conjugated to detectable labels (e.g., various enzymes, fluorescent materials, luminescent materials, bioluminescent materials, and radioactive materials) or therapeutic agents (e.g., cytostatic and cytocidal agents), which are disclosed in section 5.8.3.

Anti-PRAME antibodies conjugated to detectable substances can be utilized to sort advanced phase hematopoetic stem cells and/or immature myeloid cells from bone marrow or peripheral blood samples by methods known to those of skill in the art. In one embodiment, advanced phase hematopoetic stem cells and/or immature myeloid cells are sorted using a fluorescence activated cell sorter (FACS). Fluorescence activated cell sorting (FACS) is a well-known method for separating particles, including cells, based on the fluorescent properties of the particles (Kamarch, 1987, Methods Enzymol, 151:150-165). Laser excitation of fluorescent moieties in the individual particles results in a small electrical charge allowing electromagnetic separation of positive and negative particles from a mixture.

In one embodiment, bone marrow or peripheral blood samples, obtained from a patient, e.g., a human, are incubated with fluorescently labeled PRAME specific antibodies for a time sufficient to allow the labeled antibodies to bind to the cells. In an alternative embodiment, such cells are incubated with PRAME specific antibodies, the cells are washed, and the cells are incubated with a second labeled antibody that recognizes the PRAME specific antibodies. In accordance with these embodiments, the cells are washed and processed through the cell sorter, allowing separation of cells that bind both antibodies to be separated from hybrid cells that do not bind both antibodies. FACS sorted particles may be directly deposited into individual wells of 96-well or 384-well plates to facilitate separation.

In another embodiment, magnetic beads can be used to separate advanced phase immature myeloid cells from bone marrow or peripheral blood samples. Advanced phase immature myeloid cells may be sorted using a magnetic activated cell sorting (MACS) technique, a method for separating particles based on their ability to bind magnetic beads (0.5-100 nm diameter) (Dynal, 1995). A variety of useful modifications can be performed on the magnetic microspheres, including covalent addition of antibody which immunospecifically recognizes PRAME. A magnetic field is then applied, to physically manipulate the selected beads. The beads are then mixed with the cells to allow binding. Cells are then passed through a magnetic field to separate out advanced phase CML hematopoetic stem cells and/or immature myeloid cells.

Bone marrow or peripheral blood sample from a patient that is depleted of advanced phase CML hematopoetic stem cells and/or immature myeloid cells can be used for autologous transplant treatment of the patient. Healthy bone marrow or peripheral blood cells from a sample depleted of advanced phase CML hematopoetic stem cells and/or immature myeloid cells can be collected. These cells can then be administered to the patient to replace the abnormal cells in the patient's bone marrow. Healthy bone marrow or peripheral blood cells can also be stored, e.g., frozen, for transplant at a later time.

5.5. Methods for Screening Agents That Modulate CML PROGRESSION/TARGET OR IM RESISTANCE PROTEINS

Agents that modulate the expression or activity of a CML progression/target gene or encoded protein (or imatinib resistance gene or encoded protein), or modulate interaction of a CML progression/target protein (or imatinib resistance protein) with other proteins or molecules can be identified using a method described in this section. Such agents are useful in treating CML patients who exhibit aberrant regulation of these genes. In the following, for simplicity, methods directed to CML progression/target gene are described. These methods are equally applicable to imatinib resistance genes.

5.5.1. Screening Assays

The following assays are designed to identify compounds that bind to a CML progression gene or its products, bind to other cellular proteins that interact with a CML progression protein, bind to cellular constituents, e.g., proteins, that are affected by a CML progression protein, or bind to compounds that interfere with the interaction of the CML progression gene or its product with other cellular proteins and to compounds which modulate the expression or activity of a CML progression gene (i.e., modulate the expression level of the CML progression gene and/or modulate the activity level of the CML progression protein). Assays may additionally be utilized which identify compounds which bind to CML progression protein regulatory sequences (e.g., promoter sequences), see e.g., Platt, K. A., 1994, J. Biol. Chem. 269:28558-28562, which is incorporated herein by reference in its entirety, which may modulate the level of CML progression gene expression. Compounds may include, but are not limited to, small organic molecules which are able to affect expression of the CML progression gene or some other gene involved in the CML progression protein pathways, or other cellular proteins. Further, among these compounds are compounds which affect the level of CML progression gene expression and/or CML progression protein activity and which can be used in the regulation of sensitivity to the effect of a chemotherapy agent.

Compounds may include, but are not limited to, peptides such as, for example, soluble peptides, including but not limited to, Ig-tailed fusion peptides, and members of random peptide libraries (see, e.g., Lam, K. S. et al., 1991, Nature 354:82-84; Houghten, R. et al., 1991, Nature 354:84-86), and combinatorial chemistry-derived molecular library made of D- and/or L-configuration amino acids, phosphopeptides (including, but not limited to members of random or partially degenerate, directed phosphopeptide libraries; see, e.g., Songyang, Z. et al., 1993, Cell 72:767-778), antibodies (including, but not limited to, polyclonal, monoclonal, humanized, anti-idiotypic, chimeric or single chain antibodies, and Fab, F(ab′)₂and Fab expression library fragments, and epitope-binding fragments thereof), and small organic or inorganic molecules.

Compounds identified via assays such as those described herein may be useful, for example, in modulating the biological function of the CML progression protein.

In vitro systems may be designed to identifv compounds capable of binding a CML progression protein. Compounds identified may be useful, for example, in modulating the activity of wild type and/or mutant CML progression protein, may be useful in elaborating the biological function of the CML progression protein, may be utilized in screens for identifying compounds that disrupt normal CML progression protein interactions, or may in themselves disrupt such interactions.

The principle of the assays used to identify compounds that bind to the CML progression protein involves preparing a reaction mixture of the CML progression protein and the test compound under conditions and for a time sufficient to allow the two components to interact and bind, thus forming a complex which can be removed and/or detected in the reaction mixture. These assays can be conducted in a variety of ways. For example, one method to conduct such an assay would involve anchoring CML progression protein or the test substance onto a solid phase and detecting CML progression protein/test compound complexes anchored on the solid phase at the end of the reaction. In one embodiment of such a method, the CML progression protein may be anchored onto a solid surface, and the test compound, which is not anchored, may be labeled, either directly or indirectly.

In practice, microtiter plates may conveniently be utilized as the solid phase. The anchored component may be immobilized by non-covalent or covalent attachments. Non-covalent attachment may be accomplished by simply coating the solid surface with a solution of the protein and drying. Alternatively, an immobilized antibody, preferably a monoclonal antibody, specific for the protein to be immobilized may be used to anchor the protein to the solid surface. The surfaces may be prepared in advance and stored.

In order to conduct the assay, the nonimmobilized component is added to the coated surface containing the anchored component. After the reaction is complete, unreacted components are removed (e.g., by washing) under conditions such that any complexes formed will remain immobilized on the solid surface. The detection of complexes anchored on the solid surface can be accomplished in a number of ways. Where the previously nonimmobilized component is pre-labeled, the detection of label immobilized on the surface indicates that complexes were formed. Where the previously nonimmobilized component is not pre-labeled, an indirect label can be used to detect complexes anchored on the surface; e.g., using a labeled antibody specific for the previously nonimmobilized component (the antibody, in turn, may be directly labeled or indirectly labeled with a labeled anti-Ig antibody).

Alternatively, a reaction can be conducted in a liquid phase, the reaction products separated from unreacted components, and complexes detected; e.g., using an immobilized antibody specific for a CML progression protein or the test compound to anchor any complexes formed in solution, and a labeled antibody specific for the other component of the possible complex to detect anchored complexes.

The CML progression gene or CML progression protein may interact in vivo with one or more intracellular or extracellular molecules, such as proteins. For purposes of this discussion, such molecules are referred to herein as “binding partners”. Compounds that disrupt CML progression protein binding may be useful in modulating the activity of the CML progression protein. Compounds that disrupt CML progression gene binding may be useful in modulating the expression of the CML progression gene, such as by modulating the binding of a regulator of CML progression gene. Such compounds may include, but are not limited to molecules such as peptides which would be capable of gaining access to the CML progression protein.

The basic principle of the assay systems used to identify compounds that interfere with the interaction between the CML progression protein and its intracellular or extracellular binding partner or partners involves preparing a reaction mixture containing the CML progression protein, and the binding partner under conditions and for a time sufficient to allow the two to interact and bind, thus forming a complex. In order to test a compound for inhibitory activity, the reaction mixture is prepared in the presence and absence of the test compound. The test compound may be initially included in the reaction mixture, or may be added at a time subsequent to the addition of a CML progression protein and its binding partner. Control reaction mixtures are incubated without the test compound or with a placebo. The formation of any complexes between the CML progression protein and the binding partner is then detected. The formation of a complex in the control reaction, but not in the reaction mixture containing the test compound, indicates that the compound interferes with the interaction of the CML progression protein and the interactive binding partner. Additionally, complex formation within reaction mixtures containing the test compound and a normal CML progression protein may also be compared to complex formation within reaction mixtures containing the test compound and a mutant CML progression protein. This comparison may be important in those cases where it is desirable to identify compounds that disrupt interactions of mutant but not the normal CML progression protein.

The assay for compounds that interfere with the interaction of the CML progression proteins and binding partners can be conducted in a heterogeneous or homogeneous format. Heterogeneous assays involve anchoring either the CML progression protein or the binding partner onto a solid phase and detecting complexes anchored on the solid phase at the end of the reaction. In homogeneous assays, the entire reaction is carried out in a liquid phase. In either approach, the order of addition of reactants can be varied to obtain different information about the compounds being tested. For example, test compounds that interfere with the interaction between the CML progression proteins and the binding partners, e.g., by competition, can be identified by conducting the reaction in the presence of the test substance; i.e., by adding the test substance to the reaction mixture prior to or simultaneously with the CML progression protein and interactive binding partner. Alternatively, test compounds that disrupt preformed complexes, e.g. compounds with higher binding constants that displace one of the components from the complex, can be tested by adding the test compound to the reaction mixture after complexes have been formed. The various formats are described briefly below.

In a heterogeneous assay system, either the CML progression protein or its interactive binding partner, is anchored onto a solid surface, while the non-anchored species is labeled, either directly or indirectly. In practice, microtiter plates are conveniently utilized. The anchored species may be immobilized by non-covalent or covalent attachments. Non-covalent attachment may be accomplished simply by coating the solid surface with a solution of the CML progression protein or binding partner and drying. Alternatively, an immobilized antibody specific for the species to be anchored may be used to anchor the species to the solid surface. The surfaces may be prepared in advance and stored.

In order to conduct the assay, the partner of the immobilized species is exposed to the coated surface with or without the test compound. After the reaction is complete, unreacted components are removed (e.g., by washing) and any complexes formed will remain immobilized on the solid surface. The detection of complexes anchored on the solid surface can be accomplished in a number of ways. Where the non-immobilized species is pre-labeled, the detection of label immobilized on the surface indicates that complexes were formed. Where the non-immobilized species is not pre-labeled, an indirect label can be used to detect complexes anchored on the surface; e.g., using a labeled antibody specific for the initially non-immobilized species (the antibody, in turn, may be directly labeled or indirectly labeled with a labeled anti-Ig antibody). Depending upon the order of addition of reaction components, test compounds which inhibit complex formation or which disrupt preformed complexes can be detected.

Alternatively, the reaction can be conducted in a liquid phase in the presence or absence of the test compound, the reaction products separated from unreacted components, and complexes detected; e.g., using an immobilized antibody specific for one of the binding components to anchor any complexes formed in solution, and a labeled antibody specific for the other partner to detect anchored complexes. Again, depending upon the order of addition of reactants to the liquid phase, test compounds which inhibit complex or which disrupt preformed complexes can be identified.

In an alternative embodiment of the invention, a homogeneous assay can be used. In this approach, a preformed complex of the CML progression protein and the interactive binding partner is prepared in which either the CML progression protein or its binding partners is labeled, but the signal generated by the label is quenched due to complex formation (see, e.g., U.S. Pat. No. 4,109,496 which utilizes this approach for immunoassays). The addition of a test substance that competes with and displaces one of the species from the preformed complex will result in the generation of a signal above background. In this way, test substances which disrupt CML progression protein/binding partner interaction can be identified.

In a particular embodiment, the CML progression protein can be prepared for immobilization using recombinant DNA techniques. For example, the coding region of CML progression gene can be fused to a glutathione-S-transferase (GST) gene using a fusion vector, such as pGEX-5X-1, in such a manner that its binding activity is maintained in the resulting fusion protein. The interactive binding partner can be purified and used to raise a monoclonal antibody, using methods routinely practiced in the art. This antibody can be labeled with the radioactive isotope ¹²⁵I, for example, by methods routinely practiced in the art. In a heterogeneous assay, e.g., the GST-CML progression protein fusion protein can be anchored to glutathione-agarose beads. The interactive binding partner can then be added in the presence or absence of the test compound in a manner that allows interaction and binding to occur. At the end of the reaction-period, unbound material can be washed away, and the labeled monoclonal antibody can be added to the system and allowed to bind to the complexed components. The interaction between the CML progression protein and the interactive binding partner can be detected by measuring the amount of radioactivity that remains associated with the glutathione-agarose beads. A successful inhibition of the interaction by the test compound will result in a decrease in measured radioactivity.

Alternatively, the GST-CML progression protein fusion protein and the interactive binding partner can be mixed together in liquid in the absence of the solid glutathione-agarose beads. The test compound can be added either during or after the species are allowed to interact. This mixture can then be added to the glutathione-agarose beads and unbound material is washed away. Again the extent of inhibition of the CML progression protein/binding partner interaction can be detected by adding the labeled antibody and measuring the radioactivity associated with the beads.

In another embodiment of the invention, these same techniques can be employed using peptide fragments that correspond to the binding domains of the CML progression protein and/or the interactive binding partner (in cases where the binding partner is a protein), in place of one or both of the full length proteins. Any number of methods routinely practiced in the art can be used to identify and isolate the binding sites. These methods include, but are not limited to, mutagenesis of the gene encoding one of the proteins and screening for disruption of binding in a co-immunoprecipitation assay. Compensating mutations in the gene encoding the second species in the complex can then be selected. Sequence analysis of the genes encoding the respective proteins will reveal the mutations that correspond to the region of the protein involved in interactive binding. Alternatively, one protein can be anchored to a solid surface using methods described in this section above, and allowed to interact with and bind to its labeled binding partner, which has been treated with a proteolytic enzyme, such as trypsin. After washing, a short, labeled peptide comprising the binding domain may remain associated with the solid material, which can be isolated and identified by amino acid sequencing. Also, once the gene coding for the binding partner is obtained, short gene segments can be engineered to express peptide fragments of the protein, which can then be tested for binding activity and purified or synthesized.

For example, and not by way of limitation, a CML progression protein can be anchored to a solid material as described in this section, above, by making a GST-CML progression protein fusion protien and allowing it to bind to glutathione agarose beads. The interactive binding partner can be labeled with a radioactive isotope, such as ³⁵S, and cleaved with a proteolytic enzyme such as trypsin. Cleavage products can then be added to the anchored GST-CML progression protein fusion protein and allowed to bind. After washing away unbound peptides, labeled bound material, representing the binding partner binding domain, can be eluted, purified, and analyzed for amino acid sequence by well-known methods. Peptides so identified can be produced synthetically or fused to appropriate facilitative proteins using recombinant DNA technology.

Some CML progression proteins are kinases. Kinase activity of a CML progression protein can be assayed in vitro using a synthetic peptide substrate of a CML progression protein of interest, e.g., a GSK-derived biotinylated peptide substrate. The phosphopeptide product is quantitated using a Homogenous Time-Resolved Fluorescence (HTRF) assay system (Park et al., 1999, Anal. Biochem. 269:94-104). The reaction mixture contains suitable amounts of ATP, peptide substrate, and the CML progression protein. The peptide substrate has a suitable amino acid sequence and is biotinylated at the N-terminus. The kinase reaction is incubated, and then terminated with Stop/Detection Buffer and GSK3α anti-phosphoserine antibody (e.g., Cell Signaling Technologies, Beverly, Mass.; Cat# 9338) labeled with europium-chelate (e.g., from Perkin Elmer, Boston, Mass.). The reaction is allowed to equilibrate, and relative fluorescent units are determined. Inhibitor compounds are assayed in the reaction described above, to determine compound IC50s. A particular compound is added to in a half-log dilution series covering a suitable range of concentrations, e.g., from 1 nM to 100 μM. Relative phospho substrate formation, read as HTRF fluorescence units, is measured over the range of compound concentrations and a titration curve generated using a four parameter sigmoidal fit. Specific compounds having IC₅₀below a predetermined threshold value, e.g., ≦50 μM against a substrate, can be identified.

The extent of peptide phosphorylation can be determined by Homogeneous Time Resolved Fluorescence (HTRF) using a lanthanide chelate (Lance)-coupled monoclonal antibody specific for the phosphopeptide in combination with a streptavidin-linked allophycocyanin (SA-APC) fluorophore which binds to the biotin moiety on the peptide. When the Lance and APC are in proximity (i.e. bound to the same phosphopeptide molecule), a non-radiative energy transfer takes place from the Lance to the APC, followed by emission of light from APC at 665 nm. The assay can be run using various assay format, e.g., streptavidin flash plate assay, streptavidin filter plate assay.

A standard PKA assay can be used to assay the activity of protein kinase A (PKA). A standard PKC assay can be used to assay the activity of protein kinase C (PKC). The most common methods for assaying PKA or PKC activity involves measuring the transfer of ³²P-labeled phosphate to a protein or peptide substrate that can be captured on phosphocellulose filters via weak electrostatic interactions.

Kinase inhibitors can be identified using fluorescence polarization to monitor kinase activity. This assay utilizes GST-CML progression protein, peptide substrate, peptide substrate tracer, an anti-phospho monoclonal IgG, and the inhibitor compound. Reactions are incubated for a period of time and then terminated. Stopped reactions are incubated and fluorescence polarization values determined.

In a specific embodiment, a standard SPA Filtration Assay and FlashPlate® Kinase Assay can be used to measure the activity of a CML progression protein. In these assays, GST-CML progression protein, biotinylated peptide substrate, ATP, and ³³P-γ-ATP are allowed to react. After a suitable period of incubation, the reactions are terminated. In a SPA Filtration Assay, peptide substrate is allowed to bind Scintilation proximity assay (SPA) beads (Amersham Biosciences), followed by filtration on a Packard GF/B Unifilter plate and washed with phosphate buffered saline. Dried plates are sealed and the amount of ³³P incorporated into the peptide substrate is determined. In a FlashPlate® Kinase Assay, a suitable amount of the reaction is transferred to streptavidin-coated FlashPlates® (NEN) and incubated. Plates are washed, dried, sealed and the amount of ³³P incorporated into the peptide substrate is determined.

A standard DELFIA® Kinase Assay can also be used. In a DELFIA® Kinase Assay, GST-CML progression protein, peptide substrate, and ATP are allowed to react. After the reactions are terminated, the biotin-peptide substrates are captured in the stopped reactions. Wells are washed and reacted with anti-phospho polyclonal antibody and europium labeled anti-rabbit-IgG. Wells are washed and europium released from the bound antibody is detected.

Other assays, such as those described in WO 04/080973, WO 02/070494, and WO 03/101444, may also be utilized to determine biological activity of the instant compounds.

5.5.2. Screening Compounds That Modulate Expression or Activity of a Gene and/or Its Products

For CML progression genes that are kinases, inhibitor compounds can be assayed for their ability to inhibit a CML progression protein in hematopoetic stem cells and/or immature myeloid cells by monitoring the phosphorylation or autophosphorylation in response to the compound. Cells are grown in culture medium. Cells are pooled, counted, seeded into 6 well dishes at 200,000 cells per well in 2 ml media, and incubated. Serial dilution series of compounds or control are added to each well and incubated. Following the incubation period, each well is washed and Protease Inhibitor Cocktail Complete is added to each well. Lysates are then transferred to microcentrifuge tubes and frozen at −80° C. Lysates are thawed on ice and cleared by centrifugation and the supernatants are transferred to clean tubes. Samples are electorphoresed and proteins are transferred onto PVDF. Blots are then blocked and probed using an antibody against phospho-serine or phospho threonine. Bound antibody is visualized using a horseradish peroxidase conjugated secondary antibody and enhanced chemiluminescence. After stripping of the first antibody set, blots are re-probed for total CML progression protein, using a monoclonal antibody specific for the CML progression protein. The CML progression protein monoclonal is detected using a sheep anti-mouse IgG coupled to horseradish peroxidase and enhanced chemiluminescence. ECL exposed films are scanned and the intensity of specific bands is quantitated. Titrations are evaluated for level of phosphor-Ser signal normalized to total CML progression protein and IC50 values are calculated.

Detection of phosphonucleolin in cell lysates can be carried out using biotinylated anti-nucleolin antibody and ruthenylated goat anti-mouse antibody. To each well of a 96-well plate is added biotynylated anti-nucleolin antibody and streptavidin coated paramagnetic beads, along with a suitable cell lysate. The antibodies and lysate are incubated. Next, another anti-phosphonucleolin antibody are added to each well of the lysate mix and incubated. Lastly, the ruthenylated goat anti-mouse antibody in antibody buffer is added to each well and incubated. The lysate antibody mixtures are read and EC50s for compound dependent increases in phosphor-nucleolin are determined.

The compounds identified in the screen include compounds that demonstrate the ability to selectively modulate the expression or activity of a CML progression gene or its encoded protein. These compounds include but are not limited to siRNA, antisense nucleic acid, ribozyme, triple helix forming nucleic acid, antibody, and polypeptide molecules, aptamrs, and small organic or inorganic molecules.

5.6. Methods of Performing RNA Interference

Any method known in the art for gene silencing can be used in the present invention (see, e.g., Guo et al., 1995, Cell 81:611-620; Fire et al., 1998, Nature 391:806-811;Grant, 1999, Cell 96:303-306; Tabara et al., 1999, Cell 99:123-132; Zamore et al., 2000, Cell 101:25-33; Bass, 2000, Cell 101:235-238; Petcherski et al., 2000, Nature 405:364-368; Elbashir et al., Nature 411:494-498; Paddison et al., Proc. Natl. Acad. Sci. USA 99:1443-1448). The siRNAs targeting a gene can be designed according to methods known in the art (see, e.g., International Application Publication No. WO 2005/018534, published on Mar. 3, 2005, and Elbashir et al., 2002, Methods 26:199-213, each of which is incorporated herein by reference in its entirety).

An siRNA having only partial sequence homology to a target gene can also be used (see, e.g., International Application Publication No. WO 2005/018534, published on Mar. 3, 2005, which is incorporated herein by reference in its entirety). In one embodiment, an siRNA that comprises a sense strand contiguous nucleotide sequence of 11-18 nucleotides that is identical to a sequence of a transcript of a gene but the siRNA does not have full length homology to any sequences in the transcript is used to silence the gene. Preferably, the contiguous nucleotide sequence is in the central region of the siRNA molecules. A contiguous nucleotide sequence in the central region of an siRNA can be any continuous stretch of nucleotide sequence in the siRNA which does not begin at the 3′ end. For example, a contiguous nucleotide sequence of 11 nucleotides can be the nucleotide sequence 2-12, 3-13, 4-14, 5-15, 6-16, 7-17, 8-18, or 9-19. In preferred embodiments, the contiguous nucleotide sequence is 11-16, 11-15, 14-15, 11, 12, or 13 nucleotides in length.

In another embodiment, an siRNA that comprises a 3′ sense strand contiguous nucleotide sequence of 9-18 nucleotides which is identical to a sequence of a transcript of a gene but which siRNA does not have full length sequence identity to any contiguous sequences in the transcript is used to silence the gene. In this application, a 3′ 9-18 nucleotide sequence is a continuous stretch of nucleotides that begins at the first paired base, i.e., it does not comprise the two base 3′ overhang. Thus, when it is stated that a particular nucleotide sequence is at the 3′ end of the siRNA, the 2 base overhang is not considered. In preferred embodiments, the contiguous nucleotide sequence is 9-16, 9-15, 9-12, 11, 10, or 9 nucleotides in length.

An siRNA having only paitial sequence homology to its target genes is especially useful for silencing a plurality of different genes in a cell. In one embodiment, an siRNA is used to silence a plurality of different genes, the transcript of each of the genes comprises a nucleotide sequence that is identical to a central contiguous nucleotide sequence of at least 11 nucleotides of the sense strand or the antisense strand of the siRNA, and/or comprises a nucleotide sequence that is identical to a contiguous nucleotide sequence of at least 9 nucleotides at the 3′ end of the sense strand or the antisense strand of the siRNA. In preferred embodiments, the central contiguous nucleotide sequence is 11-15, 14-15, 11, 12, or 13 nucleotides in length. In other preferred embodiments, the 3′ contiguous nucleotide sequence is 9-15, 9-12, 11, 10, or 9 nucleotides in length.

In one embodiment, in vitro siRNA transfection is carried out as follows: one day prior to transfection, 100 microliters of chosen cells, e.g., cervical cancer HeLa cells (ATCC, Cat. No. CCL-2), grown in DMEM/10% fetal bovine serum (Invitrogen, Carlsbad, Calif.) to approximately 90% confluency are seeded in a 96-well tissue culture plate (Corning, Corning, N.Y.) at 1500 cells/well. For each transfection 85 microliters of OptiMEM (Invitrogen) is mixed with 5 microliter of serially diluted siRNA (Dharna on, Denver) from a 20 micro molar stock. For each transfection 5 microliter OptiMEM is mixed with 5 microliter Oligofectamine reagent (Invitrogen) and incubated 5 minutes at room temperature. The 10 microliter OptiMEM/Oligofectamine mixture is dispensed into each tube with the OptiMEM/siRNA mixture, mixed and incubated 15-20 minutes at room temperature. 10 microliter of the transfection mixture is aliquoted into each well of the 96-well plate and incubated for 4 hours at 37° C. and 5% CO₂.

In preferred embodiments, an siRNA pool containing at least k (k=2, 3, 4, 5, 6 or 10) different siRNAs targeting the secondary target gene at different sequence regions is used to transfect the cells. In another preferred embodiment, an siRNA pool containing at least k (k=2, 3, 4, 5, 6 or 10) different siRNAs targeting two or more different target genes is used to transfect the cells.

In a preferred embodiment, the total siRNA concentration of the pool is about the same as the concentration of a single siRNA when used individually, e.g., 100 nM. Preferably, the total concentration of the pool of siRNAs is an optimal concentration for silencing the intended target gene. An optimal concentration is a concentration further increase of which does not increase the level of silencing substantially. In one embodiment, the optimal concentration is a concentration further increase of which does not increase the level of silencing by more than 5%, 10% or 20%. In a preferred embodiment, the composition of the pool, including the number of different siRNAs in the pool and the concentration of each different siRNA, is chosen such that the pool of siRNAs causes less than 30%, 20%, 10% or 5%, 1%, 0.1% or 0.01% of silencing of any off-target genes (e.g., as determined by standard nucleic acid assay, e.g., PCR). In another preferred embodiment, the concentration of each different siRNA in the pool of different siRNAs is about the same. In still another preferred embodiment, the respective concentrations of different siRNAs in the pool are different from each other by less than 5%, 10%, 20% or 50% of the concentration of any one siRNA or said total siRNA concentration of said different siRNAs. In still another preferred embodiment, at least one siRNA in the pool of different siRNAs constitutes more than 90%, 80%, 70%, 50%, or 20% of the total siRNA concentration in the pool. In still another preferred embodiment, none of the siRNAs in the pool of different siRNAs constitutes more than 90%, 80%, 70%, 50%, or 20% of the total siRNA concentration in the pool. In other embodiments, each siRNA in the pool has an concentration that is lower than the optimal concentration when used individually. In a preferred embodiment, each different siRNA in the pool has an concentration that is lower than the concentration of the siRNA that is effective to achieve at least 30%, 50%, 75%, 80%, 85%, 90% or 95% silencing when used in the absence of other siRNAs or in the absence of other siRNAs designed to silence the gene. In another preferred embodiment, each different siRNA in the pool has a concentration that causes less than 30%, 20%, 10% or 5% of silencing of the gene when used in the absence of other siRNAs or in the absence of other siRNAs designed to silence the gene. In a preferred embodiment, each siRNA has a concentration that causes less than 30%, 20%, 10% or 5% of silencing of the target gene when used alone, while the plurality of siRNAs causes at least 80% or 90% of silencing of the target gene.

Another method for gene silencing is to introduce an shRNA, for short hairpin RNA (see, e.g., Paddison et al., 2002, Genes Dev. 16, 948-958; Brummelkamp et al., 2002, Science 296, 550-553; Sui, G. et al. 2002, Proc. Natl. Acad. Sci. USA 99, 5515-5520, all of which are incorporated by reference herein in their entirety), which can be processed in the cells into siRNA. In this method, a desired siRNA sequence is expressed from a plasmid (or virus) as an inverted repeat with an intervening loop sequence to form a hairpin structure. The resulting RNA transcript containing the hairpin is subsequently processed by Dicer to produce siRNAs for silencing. Plasmid-based shRNAs can be expressed stably in cells, allowing long-term gene silencing in cells both in vitro and in vivo, e.g., in animals (see, McCaffrey et al. 2002, Nature 418, 38-39; Xia et al., 2002, Nat. Biotech. 20, 1006-1010; Lewis et al., 2002, Nat. Genetics 32, 107-108; Rubinson et al., 2003, Nat. Genetics 33, 401-406; Tiscornia et al., 2003, Proc. Natl. Acad. Sci. USA 100, 1844-1848, all of which are incorporated by reference herein in their entirety). Thus, in one embodiment, a plasmid-based shRNA is used.

In a preferred embodiment, shRNAs are expressed from recombinant vectors introduced either transiently or stably integrated into the genome (see, e.g., Paddison et al., 2002, Genes Dev 16:948-958; Sui et al., 2002, Proc Natl Acad Sci USA 99:5515-5520; Yu et al., 2002, Proc Natl Acad Sci U S A 99:6047-6052; Miyagishi et al., 2002, Nat Biotechnol 20:497-500; Paul et al., 2002, Nat Biotechnol 20:505-508; Kwak et al., 2003, J Pharmacol Sci 93:214-217; Brummelkamp et al., 2002, Science 296:550-553; Boden et al., 2003, Nucleic Acids Res 31:5033-5038; Kawasaki et al., 2003, Nucleic Acids Res 31:700-707). The siRNA that disrupts the target gene can be expressed (via an shRNA) by any suitable vector which encodes the shRNA. The vector can also encode a marker which can be used for selecting clones in which the vector or a sufficient portion thereof is integrated in the host genome such that the shRNA is expressed. Any standard method known in the art can be used to deliver the vector into the cells. In one embodiment, cells expressing the shRNA are generated by transfecting suitable cells with a plasmid containing the vector. Cells can then be selected by the appropriate marker. Clones are then picked, and tested for knockdown. In a preferred embodiment, the expression of the shRNA is under the control of an inducible promoter such that the silencing of its target gene can be turned on when desired. Inducible expression of an siRNA is particularly useful for targeting essential genes.

In one embodiment, the expression of the shRNA is under the control of a regulated promoter that allows tuning of the silencing level of the target gene. This allows screening against cells in which the target gene is partially knocked out. As used herein, a “regulated promoter” refers to a promoter that can be activated when an appropriate inducing agent is present. An “inducing agent” can be any molecule that can be used to activate transcription by activating the regulated promoter. An inducing agent can be, but is not limited to, a peptide or polypeptide, a hormone, or an organic small molecule. An analogue of an inducing agent, i.e., a molecule that activates the regulated promoter as the inducing agent does, can also be used. The level of activity of the regulated promoter induced by different analogues may be different, thus allowing more flexibility in tuning the activity level of the regulated promoter. The regulated promoter in the vector can be any mammalian transcription regulation system known in the art (see, e.g., Gossen et al, 1995, Science 268:1766-1769; Lucas et al, 1992, Annu. Rev. Biochem. 61:1131; Li et al., 1996, Cell 85:319-329; Saez et al., 2000, Proc. Natl. Acad. Sci. USA 97:14512-14517; and Pollock et al., 2000, Proc. Nati. Acad. Sci. USA 97:13221-13226). In preferred embodiments, the regulated promoter is regulated in a dosage and/or analogue dependent manner. In one embodiment, the level of activity of the regulated promoter is tuned to a desired level by a method comprising adjusting the concentration of the inducing agent to which the regulated promoter is responsive. The desired level of activity of the regulated promoter, as obtained by applying a particular concentration of the inducing agent, can be determined based on the desired silencing level of the target gene.

In one embodiment, a tetracycline regulated gene expression system is used (see, e.g., Gossen et al, 1995, Science 268:1766-1769; U.S. Pat. No. 6,004,941). A tet regulated system utilizes components of the tet repressor/operator/inducer system of prokaryotes to regulate gene expression in eukaryotic cells. Thus, the invention provides methods for using the tet regulatory system for regulating the expression of an shRNA linked to one or more tet operator sequences. The methods involve introducing into a cell a vector encoding a fusion protein that activates transcription. The fusion protein comprises a first polypeptide that binds to a tet operator sequence in the presence of tetracycline or a tetracycline analogue operatively linked to a second polypeptide that activates transcription in cells. By modulating the concentration of a tetracycline, or a tetracycline analogue, expression of the tet operator-linked shRNA is regulated.

In other embodiments, an ecdyson regulated gene expression system (see, e.g., Saez et al., 2000, Proc. Natl. Acad. Sci. USA 97:14512-14517), or an MMTV glucocorticoid response element regulated gene expression system (see, e.g., Lucas et al, 1992, Annu. Rev. Biochem. 61:1131) may be used to regulate the expression of the shRNA.

In one embodiment, the pRETRO-SUPER (pRS) vector which encodes a puromycin-resistance marker and drives shRNA expression from an HI (RNA Pol III) promoter is used. The pRS-shRNA plasmid can be generated by any standard method known in the art. In one embodiment, the pRS-shRNA is deconvoluted from the library plasmid pool for a chosen gene by transforming bacteria with the pool and looking for clones containing only the plasmid of interest. Preferably, a 19mer siRNA sequence is used along with suitable forward and reverse primers for sequence specific PCR. Plasmids are identified by sequence specific PCR, and confirmed by sequencing. Cells expressing the shRNA are generated by transfecting suitable cells with the pRS-shRNA plasmid. Cells are selected by the appropriate marker, e.g., puromycin, and maintained until colonies are evident. Clones are then picked, and tested for knockdown. In another embodiment, an shRNA is expressed by a plasmid, e.g., a pRS-shRNA. The knockdown by the pRS-shRNA plasmid, can be achieved by transfecting cells using Lipofectarnine 2000 (Invitrogen).

In yet another method, siRNAs can be delivered to an organ or tissue in an animal, such a human, in vivo (see, e.g., Song et al. 2003, Nat. Medicine 9, 347-351; Sorensen et al., 2003, J Mol. Biol. 327, 761-766; Lewis et al., 2002, Nat. Genetics 32, 107-108, all of which are incorporated by reference herein in their entirety). In this method, a solution of siRNA is injected intravenously into the animal. The siRNA can then reach an organ or tissue of interest and effectively reduce the expression of the target gene in the organ or tissue of the animal.

5.7. Production of CML Progression/Target or IM Resistance PROTEINS AND PEPTIDES

CML progression proteins, or peptide fragments thereof, can be prepared for uses according to the present invention. For example, CML progression proteins, or peptide fragments thereof, can be used for the generation of antibodies, in diagnostic assays, for screening of inhibitors, or for the identification of other cellular gene products involved in the regulation of expression and/or activity of a CML progression gene.

The CML progression proteins or peptide fragments thereof, may be produced by recombinant DNA technology using techniques well known in the art. The amino acid sequences of the CML progression proteins are well-known and can be obtained from, e.g., GenBank®. Methods which are well known to those skilled in the art can be used to construct expression vectors containing CML progression protein coding sequences and appropriate transcriptional and translational control signals. These methods include, for example, in vitro recombinant DNA techniques, synthetic techniques, and in vivo genetic recombination. See, for example, the techniques described in Sambrook et al., 1989, supra, and Ausubel et al., 1989, supra. Alternatively, RNA capable of encoding CML progression protein sequences may be chemically synthesized using, for example, synthesizers. See, for example, the techniques described in “Oligonucleotide Synthesis”, 1984, Gait, M. J. ed., IRL Press, Oxford, which is incorporated herein by reference in its entirety.

A variety of host-expression vector systems may be utilized to express the CML progression gene coding sequences. Such host-expression systems represent vehicles by which the coding sequences of interest may be produced and subsequently purified, but also represent cells which may, when transformed or transfected with the appropriate nucleotide coding sequences, exhibit the CML progression protein in situ. These include but are not limited to microorganisms such as bacteria (e.g., E. coli, B. subtilis) transformed with recombinant bacteriophage DNA, plasmid DNA or cosmid DNA expression vectors containing CML progression protein coding sequences; yeast (e.g., Saccharomyces, Pichia) transformed with recombinant yeast expression vectors containing the CML progression protein coding sequences; insect cell systems infected with recombinant virus expression vectors (e.g., baculovirus) containing the CML progression protein coding sequences; plant cell systems infected with recombinant virus expression vectors (e.g., cauliflower mosaic virus, CaMV; tobacco mosaic virus, ™V) or transformed with recombinant plasmid expression vectors (e.g., Ti plasmid) containing CML progression protein coding sequences; or mammalian cell systems (e.g., COS, CHO, BHK, 293, 3T3, N2a) harboring recombinant expression constructs containing promoters derived from the genome of mammalian cells (e.g., metallothionein promoter) or from mammalian viruses (e.g., the adenovirus late promoter; the vaccinia virus 7.5K promoter).

In bacterial systems, a number of expression vectors may be advantageously selected depending upon the use intended for the CML progression protein being expressed. For example, when a large quantity of such a protein is to be produced, for the generation of pharmaceutical compositions of CML progression protein protein or for raising antibodies to CML progression protein protein, for example, vectors which direct the expression of high levels of fusion protein products that are readily purified may be desirable. Such vectors include, but are not limited, to the E. coli expression vector pUR278 (Ruther et al., 1983, EMBO J. 2:1791), in which the CML progression protein coding sequence may be ligated individually into the vector in frame with the lac Z coding region so that a fusion protein is produced; pIN vectors (Inouye & Inouye, 1985, Nucleic Acids Res. 13:3101-3109; Van Heeke & Schuster, 1989, J. Biol. Chem. 264:5503-5509); and the like. pGEX vectors may also be used to express foreign polypeptides as fusion proteins with glutathione S-transferase (GST). In general, such fusion proteins are soluble and can easily be purified from lysed cells by adsorption to glutathione-agarose beads followed by elution in the presence of free glutathione. The pGEX vectors are designed to include thrombin or factor Xa protease cleavage sites so that the cloned target gene product can be released from the GST moiety.

In an insect system, Autographa californica nuclear polyhedrosis virus (AcNPV) is used as a vector to express foreign genes. The virus grows in Spodoptera frugiperda cells. The CML progression gene coding sequence may be cloned individually into non-essential regions (for example the polyhedrin gene) of the virus and placed under control of an AcNPV promoter (for example the polyhedrin promoter). Successful insertion of CML progression gene coding sequence will result in inactivation of the polyhedrin gene and production of non-occluded recombinant virus (i.e., virus lacking the proteinaceous coat coded for by the polyhedrin gene). These recombinant viruses are then used to infect Spodoptera frugiperda cells in which the inserted gene is expressed. (E.g., see Smith et al., 1983, J. Virol. 46: 584; Smith, U.S. Pat. No. 4,215,051).

In mammalian host cells, a number of viral-based expression systems may be utilized. In cases where an adenovirus is used as an expression vector, the CML progression gene coding sequence of interest may be ligated to an adenovirus transcription/translation control complex, e.g., the late promoter and tripartite leader sequence. This chimeric gene may then be inserted in the adenovirus genome by in vitro or in vivo recombination. Insertion in a non-essential region of the viral genome (e.g., region E1 or E3) will result in a recombinant virus that is viable and capable of expressing CML progression protein in infected hosts. (E.g., See Logan & Shenk, 1984, Proc. Natl. Acad. Sci. USA 81:3655-3659). Specific initiation signals may also be required for efficient translation of inserted CML progression protein coding sequences. These signals include the ATG initiation codon and adjacent sequences. In cases where an entire CML progression gene, including its own initiation codon and adjacent sequences, is inserted into the appropriate expression vector, no additional translational control signals may be needed. However, in cases where only a portion of the CML progression gene coding sequence is inserted, exogenous translational control signals, including, perhaps, the ATG initiation codon, must be provided. Furthermore, the initiation codon must be in phase with the reading frame of the desired coding sequence to ensure translation of the entire insert. These exogenous translational control signals and initiation codons can be of a variety of origins, both natural and synthetic. The efficiency of expression may be enhanced by the inclusion of appropriate transcription enhancer elements, transcription terminators, etc. (see Bittner et al., 1987, Methods in Enzymol. 153:516-544).

In addition, a host cell strain may be chosen which modulates the expression of the inserted sequences, or modifies and processes the gene product in the specific fashion desired. Such modifications (e.g., glycosylation) and processing (e.g., cleavage) of protein products may be important for the function of the protein. Different host cells have characteristic and specific mechanisms for the post-translational processing and modification of proteins and gene products. Appropriate cell lines or host systems can be chosen to ensure the correct modification and processing of the foreign protein expressed. To this end, eukaryotic host cells which possess the cellular machinery for proper processing of the primary transcript, glycosylation, and phosphorylation of the gene product may be used. Such mammalian host cells include but are not limited to CHO, VERO, BHK, HeLa, COS, MDCK, 293, 3T3, W138.

For long-term, high-yield production of recombinant proteins, stable expression is preferred. For example, cell lines which stably express the CML progression protein may be engineered. Rather than using expression vectors which contain viral origins of replication, host cells can be transformed with DNA controlled by appropriate expression control elements (e.g., promoter, enhancer, sequences, transcription terminators, polyadenylation sites, etc.), and a selectable marker. Following the introduction of the foreign DNA, engineered cells may be allowed to grow for 1-2 days in an enriched media, and then are switched to a selective media. The selectable marker in the recombinant plasmid confers resistance to the selection and allows cells to stably integrate the plasmid into their chromosomes and grow to form foci which in turn can be cloned and expanded into cell lines. This method may advantageously be used to engineer cell lines which express the CML progression protein. Such engineered cell lines may be particularly useful in screening and evaluation of compounds that affect the endogenous activity of the CML progression protein.

In another embodiment, the expression characteristics of an endogenous gene (e.g., a CML progression gene) within a cell, cell line or microorganism may be modified by inserting a DNA regulatory element heterologous to the endogenous gene of interest into the genome of a cell, stable cell line or cloned microorganism such that the inserted regulatory element is operatively linked with the endogenous gene (e.g., a CML progression gene) and controls, modulates, activates, or inhibits the endogenous gene. For example, endogenous CML progression genes which are normally “transcriptionally silent”, i.e., a CML progression gene which is normally not expressed, or is expressed only at very low levels in a cell line or microorganism, may be activated by inserting a regulatory element which is capable of promoting the expression of the gene product in that cell line or microorganism. Alternatively, transcriptionally silent, endogenous CML progression genes may be activated by insertion of a promiscuous regulatory element that works across cell types.

A heterologous regulatory element may be inserted into a stable cell line or cloned microorganism, such that it is operatively linked with and activates or inhibits expression of endogenous CML progression genes, using techniques, such as targeted homologous recombination, which are well known to those of skill in the art, and described e.g., in Chappel, U.S. Pat. No. 5,272,071; PCT Publication No. WO 91/06667 published May 16, 1991; Skoultchi, U.S. Pat. No. 5,981,214; and Treco et al U.S. Pat. No. 5,968,502 and PCT Publication No. WO 94/12650 published Jun. 9, 1994. Alternatively, non-targeted, e.g. non-homologous recombination techniques may be used which are well-known to those of skill in the art and described, e.g., in PCT Publication No. WO 99/15650 published Apr. 1, 1999.

CML progression gene activation (or inactivation) may also be accomplished using designer transcription factors using techniques well known in the art. Briefly, a designer zinc finger protein transcription factor (ZFP-TF) is made which is specific for a regulatory region of the CML progression gene to be activated or inactivated. A construct encoding this designer ZFP-TF is then provided to a host cell in which the CML progression gene is to be controlled. The construct directs the expression of the designer ZFP-TF protein, which in turn specifically modulates the expression of the endogenous CML progression gene. The following references relate to various aspects of this approach in further detail: Wang & Pabo, 1999, Proc. Natl. Acad. Sci. USA 96, 9568; Berg, 1997, Nature Biotechnol. 15, 323; Greisman & Pabo, 1997, Science 275, 657; Berg & Shi, 1996, Science 271, 1081; Rebar & Pabo, 1994, Science 263, 671; Rhodes & Klug, 1993, Scientific American 269, 56; Pavletich & Pabo, 1991, Science 252, 809; Liu et al., 2001, J. Biol. Chem. 276, 11323; Zhang et al., 2000, J. Biol. Chem. 275, 33850; Beerli et al., 2000, Proc. Natl. Acad. Sci. USA 97, 1495; Kang et al., 2000, J. Biol. Chem. 275, 8742; Beerli et al., 1998, Proc. Natl. Acad. Sci. USA 95, 14628; Kim & Pabo, 1998, Proc. Natl. Acad. Sci. USA 95, 2812; Choo et al., 1997, J. Mol. Biol. 273, 525; Kim & Pabo, 1997, J. Biol. Chem. 272, 29795; Liu et al, 1997, Proc. Natl. Acad. Sci. USA 94, 5525; Kim et al, 1997, Proc. Natl. Acad. Sci. USA 94, 3616; Kikyo et al., 2000, Science 289, 2360; Robertson & Wolffe, 2000, Nature Reviews 1, 11; and Gregory, 2001, Curr. Opin. Genet. Devt. 11, 142.

A number of selection systems may be used, including but not limited to the herpes simplex virus thymidine kinase (Wigler, et al., 1977, Cell 11:223), hypoxanthine-guanine phosphoribosyltransferase (Szybalska & Szybalski, 1962, Proc. Natl. Acad. Sci. USA 48:2026), and adenine phosphoribosyltransferase (Lowy, et al., 1980, Cell 22:817) genes can be employed in tk⁻, hgprt⁻ or aprt⁻ cells, respectively. Also, antimetabolite resistance can be used as the basis of selection for the following genes: dhfr, which confers resistance to methotrexate (Wigler, et al., 1980, Natl. Acad. Sci. USA 77:3567; O'Hare, et al., 1981, Proc. Natl. Acad. Sci. USA 78:1527); gpt, which confers resistance to mycophenolic acid (Mulligan & Berg, 1981, Proc. Natl. Acad. Sci. USA 78:2072); neo, which confers resistance to the aminoglycoside G-418 (Colberre-Garapin, et al., 1981, J. Mol. Biol. 150:1); and hygro, which confers resistance to hygromycin (Santerre, et al., 1984, Gene 30:147).

Alternatively, any fusion protein may be readily purified by utilizing an antibody specific for the fusion protein being expressed. For example, a system described by Janknecht et al. allows for the ready purification of non-denatured fusion proteins expressed in human cell lines (Janknecht, et al., 1991, Proc. Natl. Acad. Sci. USA 88: 8972-8976). In this system, the gene of interest is subcloned into a vaccinia recombination plasmid such that the gene's open reading frame is translationally fused to an amino-terminal tag consisting of six histidine residues. Extracts from cells infected with recombinant vaccinia virus are loaded onto Ni²⁺·nitriloacetic acid-agarose columns and histidine-tagged proteins are selectively eluted with imidazole-containing buffers.

In a specific embodiment, recombinant human CML progression proteins can be expressed as a fusion protein with glutathione S-transferase at the amino-terminus (GST-CML progression protein) using standard baculovirus vectors and a (Bac-to-Bac®) insect cell expression system purchased from GIBCO™ Invitrogen. Recombinant protein expressed in insect cells can be purified using glutathione sepharose (Amersham Biotech) using standard procedures described by the manufacturer.

5.8. Production of Antibodies that Bind a CML Progression/Target or IM Resistance Protein

CML progression protein or a fragment thereof can be used to raise antibodies which bind CML progression protein. Such antibodies include but are not limited to polyclonal, monoclonal, chimeric, single chain, Fab fragments, and an Fab expression library. In a preferred embodiment, anti CML progression protein C-terminal antibodies are raised using an appropriate C-terminal fragment of a CML progression protein, e.g., the kinase domain. Such antibodies bind the kinase domain of the CML progression protein. In another preferred embodiment, anti CML progression protein N-terminal antibodies are raised using an appropriate N-terminal fragment of a CML progression protein. The N-terminal domain of a CML progression protein are less homologous to other kinases, and therefore offered a more specific target for a particular CML progression protein.

5.8.1. Production of Monoclonal Antibidies Specific for a CML Progression/Target of IM Resistance Protein

Antibodies can be prepared by immunizing a suitable subject with a CML progression protein or a fragment thereof as an immunogen. The antibody titer in the immunized subject can be monitored over time by standard techniques, such as with an enzyme linked immunosorbent assay (ELISA) using immobilized polypeptide. If desired, the antibody molecules can be isolated from the mammal (e.g., from the blood) and further purified by well-known techniques, such as protein A chromatography to obtain the IgG fraction.

At an appropriate time after immunization, e.g., when the specific antibody titers are highest, antibody-producing cells can be obtained from the subject and used to prepare monoclonal antibodies by standard techniques, such as the hybridoma technique originally described by Kohler and Milstein (1975, Nature 256:495-497), the human B cell hybridoma technique by Kozbor et al. (1983, Immunol. Today 4:72), the EBV-hybridoma technique by Cole et al. (1985, Monoclonal Antibodies and Cancer Therapy, Alan R. Liss, Inc., pp. 77-96) or trioma techniques. The technology for producing hybridomas is well known (see Current Protocols in Immunology, 1994, John Wiley & Sons, Inc., New York, N.Y.). Hybridoma cells producing a monoclonal antibody are detected by screening the hybridoma culture supernatants for antibodies that bind the polypeptide of interest, e.g., using a standard ELISA assay.

Monoclonal antibodies are obtained from a population of substantially homogeneous antibodies, i.e., the individual antibodies comprising the population are identical except for possible naturally occurring mutations that may be present in minor amounts. Thus, the modifier “monoclonal” indicates the character of the antibody as not being a mixture of discrete antibodies. For example, the monoclonal antibodies may be made using the hybridoma method first described by Kohler et al., 1975, Nature, 256:495, or may be made by recombinant DNA methods (U.S. Pat. No. 4,816,567). The term “monoclonal antibody” as used herein also indicates that the antibody is an immunoglobulin.

In the hybridoma method of generating monoclonal antibodies, a mouse or other appropriate host animal, such as a hamster, is immunized as hereinabove described to elicit lymphocytes that produce or are capable of producing antibodies that will specifically bind to the protein used for immunization (see, e.g., U.S. Pat. No. 5,914,112, which is incorporated herein by reference in its entirety).

Alternatively, lymphocytes may be immunized in vitro. Lymphocytes then are fused with myeloma cells using a suitable fusing agent, such as polyethylene glycol, to form a hybridoma cell (Goding, Monoclonal Antibodies: Principles and Practice, pp. 59-103 (Academic Press, 1986)). The hybridoma cells thus prepared are seeded and grown in a suitable culture medium that preferably contains one or more substances that inhibit the growth or survival of the unfused, parental myeloma cells. For example, if the parental myeloma cells lack the enzyme hypoxanthine guanine phosphoribosyl transferase (HGPRT or HPRT), the culture medium for the hybridomas typically will include hypoxanthine, aminopterin, and thymidine (HAT medium), which substances prevent the growth of HGPRT-deficient cells.

Preferred myeloma cells are those that fuse efficiently, support stable high-level production of antibody by the selected antibody-producing cells, and are sensitive to a medium such as HAT medium. Among these, preferred myeloma cell lines are murine myeloma lines, such as those derived from MOPC-21 and MPC-11 mouse tumors available from the Salk Institute Cell Distribution Center, San Diego, Calif. USA, and SP-2 cells available from the American Type Culture Collection, Rockville, Md. USA.

Human myeloma and mouse-human heteromyeloma cell lines also have been described for the production of human monoclonal antibodies (Kozbor, 1984, J. Immunol., 133:3001; Brodeur et al., Monoclonal Antibody Production Techniques and Applications, pp. 51-63 (Marcel Dekker, Inc., New York, 1987)). Culture medium in which hybridoma cells are growing is assayed for production of monoclonal antibodies directed against the antigen. Preferably, the binding specificity of monoclonal antibodies produced by hybridoma cells is determined by immunoprecipitation or by an in vitro binding assay, such as radioimmunoassay (RIA) or enzyme-linked immuno-absorbent assay (ELISA). The binding affinity of the monoclonal antibody can, for example, be determined by the Scatchard analysis of Munson et al., 1980, Anal. Biochem., 107:220.

After hybridoma cells are identified that produce antibodies of the desired specificity, affinity, and/or activity, the clones may be subcloned by limiting dilution procedures and grown by standard methods (Goding, Monoclonal Antibodies: Principles and Practice, pp. 59-103, Academic Press, 1986). Suitable culture media for this purpose include, for example, D-MEM or RPMI-1640 medium. In addition, the hybridoma cells may be grown in vivo as ascites tumors in an animal. The monoclonal antibodies secreted by the subclones are suitably separated from the culture medium, ascites fluid, or serum by conventional immunoglobulin purification procedures such as, for example, protein A-Sepharose, hydroxylapatite chromatography, gel electrophoresis, dialysis, or affinity chromatography.

Alternative to preparing monoclonal antibody-secreting hybridomas, a monoclonal antibody directed against a CML progression protein or a fragment thereof can be identified and isolated by screening a recombinant combinatorial immunoglobulin library (e.g., an antibody phage display library) with the CML progression protein or the fragment. Kits for generating and screening phage display libraries are commercially available (e.g., Pharmacia Recombinant Phage Antibody System, Catalog No. 27-9400-01; and the Stratagene antigen SurfZAP™ Phage Display Kit, Catalog No. 240612). Additionally, examples of methods and reagents particularly amenable for use in generating and screening antibody display library can be found in, for example, U.S. Pat. Nos. 5,223,409 and 5,514,548; PCT Publication No. WO 92/18619; PCT Publication No. WO 91/17271; PCT Publication No. WO 92/20791; PCT Publication No. WO 92/15679; PCT Publication No. WO 93/01288; PCT Publication No. WO 92/01047; PCT Publication No. WO 92/09690; PCT Publication No. WO 90/02809; Fuchs et al., 1991, Bio/Technology 9:1370-1372; Hay et al., 1992, Hum. Antibod. Hybridomas 3:81-85; Huse et al., 1989, Science 246:1275-1281; Griffiths et al., 1993, EMBO J. 12:725-734.

In addition, techniques developed for the production of “chimeric antibodies” (Morrison, et al., 1984, Proc. Natl. Acad. Sci., 81, 6851-6855; Neuberger, et al., 1984, Nature 312, 604-608; Takeda, et al., 1985, Nature, 314, 452-454) by splicing the genes from a mouse antibody molecule of appropriate antigen specificity together with genes from a human antibody molecule of appropriate biological activity can be used. A chimeric antibody is a molecule in which different portions are derived from different animal species, such as those having a variable region derived from a murine mAb and a human immunoglobulin constant region. (See, e.g., Cabilly et al., U.S. Pat. No. 4,816,567; and Boss et al., U.S. Pat. No. 4,816,397, which are incorporated herein by reference in their entirety.)

Humanized antibodies are antibody molecules from non-human species having one or more complementarity determining regions (CDRs) from the non-human species and a framework region from a human immunoglobulin molecule. (see e.g., U.S. Pat. No. 5,585,089, which is incorporated herein by reference in its entirety.) Such chimeric and humanized monoclonal antibodies can be produced by recombinant DNA techniques known in the art, for example using methods described in PCT Publication No. WO 87/02671; European Patent Application 184,187; European Patent Application 171,496; European Patent Application 173,494; PCT Publication No. WO 86/01533; U.S. Pat. No. 4,816,567 and 5,225,539; European Patent Application 125,023; Better et al., 1988, Science 240:1041-1043; Liu et al., 1987, Proc. Natl. Acad. Sci. USA 84:3439-3443; Liu et al., 1987, J. Immunol. 139:3521-3526; Sun et al., 1987, Proc. Natl. Acad. Sci. USA 84:214-218; Nishimura et al., 1987, Canc. Res. 47:999-1005; Wood et al., 1985, Nature 314:446-449; Shaw et al., 1988, J. Natl. Cancer Inst. 80:1553-1559; Morrison 1985, Science 229:1202-1207; Oi et al., 1986, Bio/Techniques 4:214; Jones et al., 1986, Nature 321:552-525; Verhoeyan et al., 1988, Science 239:1534; and Beidler et al., 1988, J. Immunol. 141:4053-4060.

Complementarity determining region (CDR) grafting is another method of humanizing antibodies. It involves reshaping murine antibodies in order to transfer full antigen specificity and binding affinity to a human framework (Winter et al. U.S. Pat. No. 5,225,539). CDR-grafted antibodies have been successfully constructed against various antigens, for example, antibodies against IL-2 receptor as described in Queen et al., 1989 (Proc. Natl. Acad. Sci. USA 86:10029); antibodies against cell surface receptors-CAMPATH as described in Riechmann et al. (1988, Nature, 332:323; antibodies against hepatitis B in Cole et al. (1991, Proc. Natl. Acad. Sci. USA 88:2869); as well as against viral antigens-respiratory syncitial virus in Tempest et al. (1991, Bio-Technology 9:267). CDR-grafted antibodies are generated in which the CDRs of the murine monoclonal antibody are grafted into a human antibody. Following grafting, most antibodies benefit from additional amino acid changes in the framework region to maintain affinity, presumably because framework residues are necessary to maintain CDR conformation, and some framework residues have been demonstrated to be part of the antigen binding site. However, in order to preserve the framework region so as not to introduce any antigenic site, the sequence is compared with established germline sequences followed by computer modeling.

Completely human antibodies are particularly desirable for therapeutic treatment of human patients. Such antibodies can be produced using transgenic mice which are incapable of expressing endogenous immunoglobulin heavy and light chain genes, but which can express human heavy and light chain genes. The transgenic mice are immunized in the normal fashion with a CML progression protein.

Monoclonal antibodies directed against a CML progression protein can be obtained using conventional hybridoma technology. The human immunoglobulin transgenes harbored by the transgenic mice rearrange during B cell differentiation, and subsequently undergo class switching and somatic mutation. Thus, using such a technique, it is possible to produce therapeutically useful IgG, IgA and IgE antibodies. For an overview of this technology for producing human antibodies, see Lonberg and Huszar (1995, Int. Rev. Immunol. 13:65-93). For a detailed discussion of this technology for producing human antibodies and human monoclonal antibodies and protocols for producing such antibodies, see e.g., U.S. Pat. No. 5,625,126; U.S. Pat. No. 5,633,425; U.S. Pat. No. 5,569,825; U.S. Pat. No. 5,661,016; and U.S. Pat. No. 5,545,806. In addition, companies such as Abgenix, Inc. (Freemont, Calif., see, for example, U.S. Pat. No. 5,985,615) and Medarex, Inc. (Princeton, N.J.), can be engaged to provide human antibodies directed against a CML progression protein or a fragment thtereof using technology similar to that described above.

Completely human antibodies which recognize and bind a selected epitope can be generated using a technique referred to as “guided selection.” In this approach a selected non-human monoclonal antibody, e.g., a mouse antibody, is used to guide the selection of a completely human antibody recognizing the same epitope (Jespers et al., 1994, Bio/technology 12:899-903).

A pre-existing anti-CML progression protein antibody can be used to isolate additional antigens of the CML progression protein by standard techniques, such as affinity chromatography or immunoprecipitation for use as immunogens. Moreover, such an antibody can be used to detect the protein (e.g., in a cellular lysate or cell supernatant) in order to evaluate the abundance and pattern of expression of CML progression protein. Detection can be facilitated by coupling the antibody to a detectable substance. Examples of detectable substances include various enzymes, prosthetic groups, fluorescent materials, luminescent materials, bioluminescent materials, and radioactive materials. Examples of suitable enzymes include horseradish peroxidase, alkaline phosphatase, beta-galactosidase, or acetylcholinesterase; examples of suitable prosthetic group complexes include streptavidin/biotin and avidin/biotin; examples of suitable fluorescent materials include umbelliferone, fluorescein, fluorescein isothiocyanate, rhodamine, dichlorotriazinylamine fluorescein, dansyl chloride or phycoerythrin; an example of a luminescent material includes luminol; examples of bioluminescent materials include luciferase, luciferin, and aequorin, and examples of suitable radioactive material include 125I, 131I, 35S or 3H.

5.8.2. Production of Polyclonal anti-CML Progression/Target or IM Resistance Protein Antibodies

The anti-CML progression protein antibodies can be produced by immunization of a suitable animal, such as but are not limited to mouse, rabbit, and horse.

An immunogenic preparation comprising a CML progression protein or a fragment thereof can be used to prepare antibodies by immunizing a suitable subject (e.g., rabbit, goat, mouse or other mammal). An appropriate immunogenic preparation can contain, for example, recombinantly expressed or chemically synthesized CML progression protein peptide or polypeptide. The preparation can further include an adjuvant, such as Freund's complete or incomplete adjuvant, or similar immunostimulatory agent.

A fragment of a CML progression protein suitable for use as an immunogen comprises at least a portion of the CML progression protein that is 8 amino acids, more preferably 10 amino acids and more preferably still, 15 amino acids long.

The invention also provides chimeric or fusion CML progression protein polypeptides for use as immunogens. As used herein, a “chimeric” or “fusion” CML progression protein polypeptide comprises all or part of a CML progression protein polypeptide operably linked to a heterologous polypeptide. Within the fusion CML progression protein polypeptide, the term “operably linked” is intended to indicate that the CML progression protein polypeptide and the heterologous polypeptide are fused in-frame to each other. The heterologous polypeptide can be fused to the N-terminus or C-terminus of the CML progression protein polypeptide.

One useful fusion CML progression protein polypeptide is a GST fusion CML progression protein polypeptide in which the CML progression protein polypeptide is fused to the C-terminus of GST sequences. Such fusion CML progression protein polypeptides can facilitate the purification of a recombinant CML progression protein polypeptide.

In another embodiment, the fusion CML progression protein polypeptide contains a heterologous signal sequence at its N-terminus so that the CML progression protein polypeptide can be secreted and purified to high homogeneity in order to produce high affinity antibodies. For example, the native signal sequence of an immunogen can be removed and replaced with a signal sequence from another protein. For example, the gp67 secretory sequence of the baculovirus envelope protein can be used as a heterologous signal sequence (Current Protocols in Molecular Biology, Ausubel et al., eds., John Wiley & Sons, 1992). Other examples of eukaryotic heterologous signal sequences include the secretory sequences of melittin and human placental alkaline phosphatase (Stratagene; La Jolla, Calif.). In yet another example, useful prokaryotic heterologous signal sequences include the phoA secretory signal and the protein A secretory signal (Pharmacia Biotech; Piscataway, N.J.).

In yet another embodiment, the fusion CML progression protein polypeptide is an immunoglobulin fusion protein in which all or part of a CML progression protein polypetide is fused to sequences derived from a member of the immunoglobulin protein family. The immunoglobulin fusion proteins can be used as immunogens to produce antibodies directed against the CML progression protein polypetide in a subject.

Chimeric and fusion CML progression protein polypeptide can be produced by standard recombinant DNA techniques. In one embodiment, the fusion gene can be synthesized by conventional techniques including automated DNA synthesizers. Alternatively, PCR amplification of gene fragments can be carried out using anchor primers which give rise to complementary overhangs between two consecutive gene fragments which can subsequently be annealed and reamplified to generate a chimeric gene sequence (e.g., Ausubel et al., supra). Moreover, many expression vectors are commercially available that already encode a fusion domain (e.g., a GST polypeptide). A nucleic acid encoding an immunogen can be cloned into such an expression vector such that the fusion domain is linked in-frame to the polypeptide.

The CML progression protein immunogenic preparation is then used to immunize a suitable animal. Preferably, the animal is a specialized transgenic animal that can secret human antibody. Non-limiting examples include transgenic mouse strains which can be used to produce a polyclonal population of antibodies directed to a specific pathogen (Fishwild et al., 1996, Nature Biotechnology 14:845-851; Mendez et al., 1997, Nature Genetics 15:146-156). In one embodiment of the invention, transgenic mice that harbor the unrearranged human immunoglobulin genes are immunized with the target immunogens. After a vigorous immune response against the immunogenic preparation has been elicited in the mice, the blood of the mice are collected and a purified preparation of human IgG molecules can be produced from the plasma or serum. Any method known in the art can be used to obtain the purified preparation of human IgG molecules, including but is not limited to affinity column chromatography using anti-human IgG antibodies bound to a suitable column matrix. Anti-human IgG antibodies can be obtained from any sources known in the art, e.g., from commercial sources such as Dako Corporation and ICN. The preparation of IgG molecules produced comprises a polyclonal population of IgG molecules that bind to the immunogen or immunogens at different degree of affinity. Preferably, a substantial fraction of the preparation contains IgG molecules specific to the immunogen or immunogens. Although polyclonal preparations of IgG molecules are described, it is understood that polyclonal preparations comprising any one type or any combination of different types of immunoglobulin molecules are also envisioned and are intended to be within the scope of the present invention.

A population of antibodies directed to a CML progression protein can be produced from a phage display library. Polyclonal antibodies can be obtained by affinity screening of a phage display library having a sufficiently large and diverse population of specificities with a CML progression protein or a fragment thereof. Examples of methods and reagents particularly amenable for use in generating and screening antibody display library can be found in, for example, U.S. Pat. Nos. 5,223,409 and 5,514,548; PCT Publication No. WO 92/18619; PCT Publication No. WO 91/17271; PCT Publication No. WO 92/20791; PCT Publication No. WO 92/15679; PCT Publication No. WO 93/01288; PCT Publication No. WO 92/01047; PCT Publication No. WO 92/09690; PCT Publication No. WO 90/02809; Fuchs et al., 1991, Bio/Technology 9:1370-1372; Hay et al., 1992, Hum. Antibod. Hybridomas 3:81-85; Huse et al., 1989, Science 246:1275-1281; Griffiths et al., 1993, EMBO J. 12:725-734. A phage display library permits selection of desired antibody or antibodies from a very large population of specificities. An additional advantage of a phage display library is that the nucleic acids encoding the selected antibodies can be obtained conveniently, thereby facilitating subsequent construction of expression vectors.

In other preferred embodiments, the population of antibodies directed to a CML progression protein or a fragment thereof is produced by a method using the whole collection of selected displayed antibodies without clonal isolation of individual members as described in U.S. Pat. No. 6,057,098, which is incorporated by reference herein in its entirety. Polyclonal antibodies are obtained by affinity screening of a phage display library having a sufficiently large repertoire of specificities with, e.g., an antigenic molecule having multiple epitopes, preferably after enrichment of displayed library members that display multiple antibodies. The nucleic acids encoding the selected display antibodies are excised and amplified using suitable PCR primers. The nucleic acids can be purified by gel electrophoresis such that the full length nucleic acids are isolated. Each of the nucleic acids is then inserted into a suitable expression vector such that a population of expression vectors having different inserts is obtained. The population of expression vectors is then expressed in a suitable host.

5.8.3 Production of Antibody-Drug Conjugates Targeting a CML Progression/Target of IM Resistance Protein

Cancer cells can be targeted and killed using anti-CML progression protein antibody-drug conjugates that target an advanced phase CML hematopoetic stem cell and/or immature myeloid cell expressing a CML progression protein on its surface, e.g., PRAME. For example, an antibody specific for a CML progression protein may be conjugated to a therapeutic moiety such as a cytotoxin, e.g., a cytostatic or cytocidal agent, or a radioactive metal ion. Antibody-drug conjugates can be prepared by method known in the art (see, e.g., Immunoconjugates, Vogel, ed. 1987; Targeted Drugs, Goldberg, ed. 1983; Antibody Mediated Delivery Systems, Rodwell, ed. 1988). Therapeutic drugs, such as but are not limited to, paclitaxol, cytochalasin B, gramicidin D, ethidium bromide, emetine, mitomycin, etoposide, tenoposide, vincristine, vinblastine, colchicin, doxorubicin, daunorubicin, dihydroxy anthracin dione, mitoxantrone, mithramycin, actinomycin D, 1-dehydrotestosterone, glucocorticoids, procaine, tetracaine, lidocaine, propranolol, and puromycin and analogs or homologs thereof, can be conjugated to anti-CML progression protein antibodies. Other therapeutic agents that can be conjugated to anti-CML progression protein antibodies include, but are not limited to, antimetabolites, e.g., methotrexate, 6-mercaptopurine, 6-thioguanine, cytarabine, 5-fluorouracil decarbazine; alkylating agents, e.g., mechlorethamine, thioepa chlorambucil, melphalan, carmustine (BSNU) and lomustine (CCNU), cyclothosphamide, busulfan, dibromomannitol, streptozotocin, mitomycin C, and cis-dichlorodiamine platinum (II) (DDP) cisplatin; anthracyclines, e.g., daunorubicin (daunomycin) and doxorubicin; antibiotics, e.g., dactinomycin (actinomycin), bleomycin, mithramycin, anthramycin (AMC); and anti-mitotic agents, e.g., vincristine and vinblastine. The therapeutic agents that can be conjugated to anti-CML progression protein antibodies may also be a protein or polypeptide possessing a desired biological activity. Other chemotherapeutic agents known in the art, such as those described in Section 5.8.5, infra, can also be conjugated with such an anti-CML progression protein antibody. Such proteins may include, for example, a toxin such as abrin, ricin A, pseudomonas exotoxin, or diphtheria toxin.

The drug molecules can be linked to the anti-CML progression protein antibody via a linker. Any suitable linker can be used for the preparation of such conjugates. In some embodiments, the linker can be a linker that allows the drug molecules to be released from the conjugates in unmodified form at the target site.

The antibodies can also be used diagnostically to, for example, monitor the presence of cancer cells as part of a clinical testing procedure to, e.g., determine the efficacy of a given treatment regimen. Detection can be facilitated by coupling the antibody to a detectable substance. Examples of detectable substances include various enzymes, prosthetic groups, fluorescent materials, luminescent materials, bioluminescent materials, radioactive materials, positron emitting metals using various positron emission tomographies, and nonradioactive paramagnetic metal ions. See generally U.S. Pat. No. 4,741,900 for metal ions which can be conjugated to antibodies for use as diagnostics according to the present invention. Examples of suitable enzymes include horseradish peroxidase, alkaline phosphatase, beta-galactosidase, or acetylcholinesterase; examples of suitable prosthetic group complexes include streptavidin/biotin and avidin/biotin; examples of suitable fluorescent materials include fluorescent proteins, e.g., green fluorescent protein (GFP), umbelliferone, fluorescein, fluorescein isothiocyanate, rhodamine, dichlorotriazinylamine fluorescein, dansyl chloride or phycoerythrin; an example of a luminescent material includes luminol; examples of bioluminescent materials include luciferase, luciferin, and aequorin, and examples of suitable radioactive material include ¹²⁵I, ¹³¹I, ¹¹¹In, ¹⁷⁷Lu, ⁹⁰Y or ⁹⁹Tc.

Techniques for conjugating therapeutic moieties to antibodies are well known, see, e.g., Arnon et al., “Monoclonal Antibodies For Immunotargeting Of Drugs In Cancer Therapy”, in Monoclonal Antibodies And Cancer Therapy, Reisfeld et al. (eds.), pp. 243-56 (Alan R. Liss, Inc. 1985); Hellstrom et al., “Antibodies For Drug Delivery”, in Controlled Drug Delivery (2nd Ed.), Robinson et al. (eds.), pp. 623-53 (Marcel Dekker, Inc. 1987); Thorpe, “Antibody Carriers Of Cytotoxic Agents In Cancer Therapy: A Review”, in Monoclonal Antibodies '84: Biological And Clinical Applications, Pinchera et al. (eds.), pp. 475-506 (1985); “Analysis, Results, And Future Prospective Of The Therapeutic Use Of Radiolabeled Antibody In Cancer Therapy”, in Monoclonal Antibodies For Cancer Detection And Therapy, Baldwin et al. (eds.), pp. 303-16 (Academic Press 1985), and Thorpe et al., “The Preparation And Cytotoxic Properties Of Antibody-Toxin Conjugates”, Immunol. Rev., 62:119-58 (1982); each of which is incorporated herein by reference.

Alternatively, an antibody can be conjugated to a second antibody to form an antibody heteroconjugate as described by Segal in U.S. Pat. No. 4,676,980, which is incorporated herein by reference.

5.8.4 Production of Peptides

A CML progression protein-binding peptide or polypeptide or peptide or polypeptide of a CML progression protein may be produced by recombinant DNA technology using techniques well known in the art. Thus; the polypeptide or peptide can be produced by expressing nucleic acid containing sequences encoding the polypeptide or peptide. Methods which are well known to those skilled in the art can be used to construct expression vectors containing coding sequences and appropriate transcriptional and translational control signals. These methods include, for example, in vitro recombinant DNA techniques, synthetic techniques, and in vivo genetic recombination. See, for example, the techniques described in Sambrook et al., 1989, supra, and Ausubel et al., 1989, supra. Alternatively, RNA capable of encoding CML progression protein polypeptide sequences may be chemically synthesized using, for example, synthesizers. See, for example, the techniques described in “Oligonucleotide Synthesis”, 1984, Gait, M. J. ed., IRL Press, Oxford, which is incorporated herein by reference in its entirety.

5.8.5 Chemotherapeutic Drugs

The invention can be practiced with any known chemotherapeutic drugs, including but not limited to DNA damaging agents, anti-metabolites, anti-mitotic agents, or a combination of two or more of such known anti-cancer agents.

DNA damage agents cause chemical damage to DNA and/or RNA. DNA damage agents can disrupt DNA replication or cause the generation of nonsense DNA or RNA. DNA damaging agents include but are not limited to topoisomerase inhibitor, DNA binding agent, and ionizing radiation. A topoisomerase inhibitor that can be used in conjunction with the invention can be a topoisomerase I (Topo I) inhibitor, a topoisomerase II (Topo II) inhibitor, or a dual topoisomerase I and II inhibitor. A topo I inhibitor can be for example from any of the following classes of compounds: camptothecin analogue (e.g., karenitecin, aminocamptothecin, lurtotecan, topotecan, irinotecan, BAY 56-3722, rubitecan, GI14721, exatecan mesylate), rebeccamycin analogue, PNU 166148, rebeccamycin, TAS-103, camptothecin (e.g., camptothecin polyglutamate, camptothecin sodium), intoplicine, ecteinascidin 743, J-107088, pibenzimol. Examples of preferred topo I inhibitors include but are not limited to camptothecin, topotecan (hycaptamine), irinotecan (irinotecan hydrochloride), belotecan, or an analogue or derivative of any of the foregoing.

A topo II inhibitor that can be used in conjunction with the invention can be for example from any of the following classes of compounds: anthracycline antibiotics (e.g., carubicin, pirarubicin, daunorubicin citrate liposomal, daunomycin, 4-iodo-4-doxydoxorubicin, doxorubicin, n,n-dibenzyl daunomycin, morpholinodoxorubicin. aclacinomycin antibiotics, duborimycin, menogaril, nogalamycin, zorubicin, epirubicin, marcellomycin, detorubicin, annamycin, 7-cyanoquinocarcinol, deoxydoxorubicin, idarubicin, GPX-100, MEN-10755, valrubicin, KRN5500), epipodophyllotoxin compound (e.g., podophyllin, teniposide, etoposide, GL331, 2-ethylhydrazide), anthraquinone compound (e.g., ametantrone, bisantrene, mitoxantrone, anthraquinone), ciprofloxacin, acridine carboxamide, amonafide, anthrapyrazole antibiotics (e.g., teloxantrone, sedoxantrone trihydrochloride, piroxantrone, anthrapyrazole, losoxantrone), TAS-103, fostriecin, razoxane, XK469R, XK469, chloroquinoxaline sulfonamide, merbarone, intoplicine, elsamitrucin, CI-921, pyrazoloacridine, elliptinium, amsacrine. Examples of preferred topo II inhibitors include but are not limited to doxorubicin (Adriamycin), etoposide phosphate (etopofos), teniposide, sobuzoxane, or an analogue or derivative of any of the foregoing.

DNA binding agents that can be used in conjunction with the invention include but are not limited to a DNA groove binding agent, e.g., DNA minor groove binding agent; DNA crosslinking agent; intercalating agent; and DNA adduct forming agent. A DNA minor groove binding agent can be an anthracycline antibiotic, mitomycin antibiotic (e.g., porfiromycin, KW-2149, mitomycin B, mitomycin A, mitomycin C), chromomycin A3, carzelesin, actinomycin antibiotic (e.g., cactinomycin, dactinomycin, actinomycin F1), brostallicin, echinomycin, bizelesin, duocarmycin antibiotic (e.g., KW 2189), adozelesin, olivomycin antibiotic, plicamycin, zinostatin, distamycin, MS-247, ecteinascidin 743, amsacrine, anthramycin, and pibenzimol, or an analogue or derivative of any of the foregoing.

DNA crosslinking agents include but are not limited to antineoplastic alkylating agent, methoxsalen, mitomycin antibiotic, psoralen. An antineoplastic alkylating agent can be a nitrosourea compound (e.g., cystemustine, tauromustine, semustine, PCNU, streptozocin, SarCNU, CGP-6809, carmustine, fotemustine, methylnitrosourea, nimustine, ranimustine, ethylnitrosourea, lomustine, chlorozotocin), mustard agent (e.g., nitrogen mustard compound, such as spiromustine, trofosfamide, chlorambucil, estramustine, 2,2,2-trichlorotriethylamine, prednimustine, novembichin, phenamet, glufosfamide, peptichemio, ifosfamide, defosfamide, nitrogen mustard, phenesterin, mannomustine, cyclophosphamide, melphalan, perfosfamide, mechlorethamine oxide hydrochloride, uracil mustard, bestrabucil, DHEA mustard, tallimustine, mafosfamide, aniline mustard, chlornaphazine; sulfur mustard compound, such as bischloroethylsulfide; mustard prodrug, such as TLK286 and ZD2767), ethylenimine compound (e.g., mitomycin antibiotic, ethylenimine, uredepa, thiotepa, diaziquone, hexamethylene bisacetamide, pentamethylmelamine, altretamine, carzinophilin, triaziquone, meturedepa, benzodepa, carboquone), alkylsulfonate compound (e.g., dimethylbusulfan, Yoshi-864, improsulfan, piposulfan, treosulfan, busulfan, hepsulfam), epoxide compound (e.g., anaxirone, mitolactol, dianhydrogalactitol, teroxirone), miscellaneous alkylating agent (e.g., ipomeanol, carzelesin, methylene dimethane sulfonate, mitobronitol, bizelesin, adozelesin, piperazinedione, VNP40101M, asaley, 6-hydroxymethylacylfulvene, EO9, etoglucid, ecteinascidin 743, pipobroman), platinum compound (e.g., ZD0473, liposomal-cisplatin analogue, satraplatin, BBR 3464, spiroplatin, ormaplatin, cisplatin, oxaliplatin, carboplatin, lobaplatin, zeniplatin, iproplatin), triazene compound (e.g., imidazole mustard, CB10-277, mitozolomide, temozolomide, procarbazine, dacarbazine), picoline compound (e.g., penclomedine), or an analogue or derivative of any of the foregoing. Examples of preferred alkylating agents include but are not limited to cisplatin, dibromodulcitol, fotemustine, ifosfamide (ifosfamid), ranimustine (ranomustine), nedaplatin (latoplatin), bendamustine (bendamustine hydrochloride), eptaplatin, temozolomide (methazolastone), carboplatin, altretamine (hexamethylmelamine), prednimustine, oxaliplatin (oxalaplatinum), carmustine, thiotepa, leusulfon (busulfan), lobaplatin, cyclophosphamide, bisulfan, melphalan, and chlorambucil, or an analogue or derivative of any of the foregoing.

Intercalating agents can be an anthraquinone compound, bleomycin antibiotic, rebeccamycin analogue, acridine, acridine carboxamide, amonafide, rebeccamycin, anthrapyrazole antibiotic, echinomycin, psoralen, LU 79553, BW A773U, crisnatol mesylate, benzo(a)pyrene-7,8-diol-9,10-epoxide, acodazole, elliptinium, pixantrone, or an analogue or derivative of any of the foregoing.

DNA adduct forming agents include but are not limited to enediyne antitumor antibiotic (e.g., dynemicin A, esperamicin A1, zinostatin, dynemicin, calicheamicin gamma II), platinum compound, carmustine, tamoxifen (e.g., 4-hydroxy-tamoxifen), psoralen, pyrazine diazohydroxide, benzo(a)pyrene-7,8-diol-9,10-epoxide, or an analogue or derivative of any of the foregoing.

Anti-metabolites block the synthesis of nucleotides or deoxyribonucleotides, which are necessary for making DN, thereby preventing cells from replicating. Anti-metabolites include but are not limited to cytosine, arabinoside, floxuridine, 5-fluorouracil (5-FU), mercaptopurine, gemcitabine, hydroxyurea (HU), and methotrexate (MTX).

Anti-mitotic agents disrupt the the development of the mitotic spindle thereby interfering with tumor cell proliferation. Anti-mitotic agents include but are not limited to Vinblastine, Vincristine, and Pacitaxel (Taxol). Anti-mitotic agents also includes agents that target the enzymes that regulate mitosis, e.g., agents that target kinesin spindle protein (KSP), e.g., L-001000962-000Y.

5.9. Kits

The invention provides kits that are useful in determining the stage of CML in a patient. The kits of the present invention comprise one or more probes and/or primers for each of at least 5, 10, 20, 30, 40, 50, 60, 70, 80, or 100 gene products that are encoded by the respectively marker genes listed in Tables 1a and/or 1b or funtional equivalents of such genes, wherein the probes and/or primers are at least 50%, 75%, 80%, 85%, 90%, 95%, 97%, 98%, 99% or 100% of the total probes and/or primers in the kit. The probes of marker genes may be part of an array, or the biomarker(s) may be packaged separately and/or individually.

The invention provides kits that are useful in determining the progression of CML in a patient. The kits of the present invention comprise one or more probes and/or primers for each of at least 5, 10, 20, 30, 40, 50, 60, 70, 80, or 100 gene products that are encoded by the respectively marker genes listed in Tables 2a and/or 2b or functional equivalents of such genes, wherein the probes and/or primers are at least 50%, 75%, 80%, 85%, 90%, 95%, 97%, 98%, 99% or 100% of the total probes and/or primers in the kit. In a preferred embodiment, the kits comprise one or more probes and/or primers for each of at least 5, 10, 20, 30, 40, 50, 60, 70, 80, or 100 gene products that are encoded by the respectively marker genes listed in Table 4 or funtional equivalents of such genes, wherein the probes and/or primers are at least 50%, 75%, 80%, 85%, 90%, 95%, 97%, 98%, 99% or 100% of the total probes and/or primers in the kit. The probes of marker genes may be part of an array, or the biomarker(s) may be packaged separately and/or individually.

In one embodiment, the invention provides kits comprising probes that are immobilized at an addressable position on a substrate, e.g., in a microarray. In a particular embodiment, the invention provides such a microarray.

The kits of the present invention may also contain probes that can be used to detect protein products of the marker genes of the invention. In a specific embodiment, the invention provides a kit comprises a plurality of antibodies that specifically bind a plurality of at least 5, 10, 20, 30, 40, 50, 60, 70, 80, or 100 protens that are encoded by the respectively marker genes listed in Tables 1a and/or 1b or any one of Tables 2a and/or 2b and 5a and/or 5b or funtional equivalents of such genes, wherein the antibodies are at least 50%, 75%, 80%, 85%, 90%, 95%, 97%, 98%, 99% or 100% of the total antibodies in the kit. In accordance with this embodiment, the kit may comprise a set of antibodies or functional fragments or derivatives thereof (e.g., Fab, F(ab′)₂, Fv, or scFv fragments). In accordance with this embodiment, the kit may include antibodies, fragments or derivatives thereof (e.g., Fab, F(ab′)₂, Fv, or scFv fragments) that are specific for these proteins. In one embodiment, the antibodies may be detectably labeled.

The kits of the present invention may also include reagents such as buffers, or other reagents that can be used in obtaining the marker profile. Prevention of the action of microorganisms can be ensured by the inclusion of various antibacterial and antifungal agents, for example, paraben, chlorobutanol, phenol sorbic acid, and the like. It may also be desirable to include isotonic agents such as sugars, sodium chloride, and the like.

In some embodiments of the invention, the kits of the present invention comprise a microarray. The microarray can be any of the microarrays described above, e.g., in Section 5.6.1, optionally in a sealed container. In one embodiment this microarray comprises a plurality of probe spots, wherein at least 20%, 40%, 60%, 80%, or 90% of the probe spots in the plurality of probe spots correspond to marker genes listed in Tables 1a and/or 1b or any one of Tables 2a and/or 2b and 4.

In still other embodiments, the kits of the invention may further comprise a computer program product for use in conjunction with a computer system, wherein the computer program product comprises a computer readable storage medium and a computer program mechanism embedded therein. In such kits, the computer program mechanism comprises instructions for prediction of prognosis using a marker profile obtained with the reagents of the kits.

In still other embodiments, the kits of the present invention comprise a computer having a central processing unit and a memory coupled to the central processing unit. The memory stores instructions for for prediction of prognosis using a marker profile obtained with the reagents of the kits.

5.10. Pharmaceutical Formulations and Routes of Administration

The compounds that can be used to modulate the expression of the CML progression genes or the activity of their gene products can be administered to a patient at therapeutically effective doses. A therapeutically effective dose refers to that amount of the compound sufficient to result in normal expression or activity level.

5.10.1. Effective Dose

Toxicity and therapeutic efficacy of such compounds can be determined by standard pharmaceutical procedures in cell cultures or experimental animals, e.g., for determining the LD₅₀(the dose lethal to 50% of the population) and the ED₅₀(the dose therapeutically effective in 50% of the population). The dose ratio between toxic and therapeutic effects is the therapeutic index and it can be expressed as the ratio LD₅₀/ED₅₀. Compounds which exhibit large therapeutic indices are preferred. While compounds that exhibit toxic side effects may be used, care should be taken to design a delivery system that targets such compounds to the site of affected tissue in order to minimize potential damage to uninfected cells and, thereby, reduce side effects.

The data obtained from the cell culture assays and animal studies can be used in formulating a range of dosage for use in humans. The dosage of such compounds lies preferably within a range of circulating concentrations that include the ED₅₀with little or no toxicity. The dosage may vary within this range depending upon the dosage form employed and the route of administration utilized. For any compound used in the method of the invention, the therapeutically effective dose can be estimated initially from cell culture assays. A dose may be formulated in animal models to achieve a circulating plasma concentration range that includes the IC₅₀(i.e., the concentration of the test compound which achieves a half-maximal inhibition of symptoms) as determined in cell culture. Such information can be used to more accurately determine useful doses in humans. Levels in plasma may be measured, for example, by high performance liquid chromatography.

5.10.2. Formulations and Use

Pharmaceutical compositions for use in accordance with the present invention may be formulated in conventional manner using one or more pharmaceutically acceptable carriers or excipients.

Thus, the compounds and their pharmaceutically acceptable salts and solvates may be formulated for administration by inhalation or insufflation (either through the mouth or the nose) or oral, buccal, parenteral or rectal administration.

For oral administration, the pharmaceutical compositions may take the form of, for example, tablets or capsules prepared by conventional means with pharmaceutically acceptable excipients such as binding agents (e.g., pregelatinised maize starch, polyvinylpyrrolidone or hydroxypropyl methylcellulose); fillers (e.g., lactose, microcrystalline cellulose or calcium hydrogen phosphate); lubricants (e.g., magnesium stearate, talc or silica); disintegrants (e.g., potato starch or sodium starch glycolate); or wetting agents (e.g., sodium lauryl sulphate). The tablets may be coated by methods well known in the art. Liquid preparations for oral administration may take the form of, for example, solutions, syrups or suspensions, or they may be presented as a dry product for constitution with water or other suitable vehicle before use. Such liquid preparations may be prepared by conventional means with pharmaceutically acceptable additives such as suspending agents (e.g., sorbitol syrup, cellulose derivatives or hydrogenated edible fats); emulsifying agents (e.g., lecithin or acacia); non-aqueous vehicles (e.g., almond oil, oily esters, ethyl alcohol or fractionated vegetable oils); and preservatives (e.g., methyl or propyl-p-hydroxybenzoates or sorbic acid). The preparations may also contain buffer salts, flavoring, coloring and sweetening agents as appropriate.

Preparations for oral administration may be suitably formulated to give controlled release of the active compound.

For buccal administration the compositions may take the form of tablets or lozenges formulated in conventional manner.

For administration by inhalation, the compounds for use according to the present invention are conveniently delivered in the form of an aerosol spray presentation from pressurized packs or a nebuliser, with the use of a suitable propellant, e.g., dichlorodifluoromethane, trichlorofluoromethane, dichlorotetrafluoroethane, carbon dioxide or other suitable gas. In the case of a pressurized aerosol the dosage unit may be determined by providing a valve to deliver a metered amount. Capsules and cartridges of e.g. gelatin for use in an inhaler or insufflator may be formulated containing a powder mix of the compound and a suitable powder base such as lactose or starch.

The compounds may be formulated for parenteral administration by injection, e.g., by bolus injection or continuous infusion. Formulations for injection may be presented in unit dosage form, e.g., in ampoules or in multi-dose containers, with an added preservative. The compositions may take such forms as suspensions, solutions or emulsions in oily or aqueous vehicles, and may contain formulatory agents such as suspending, stabilizing and/or dispersing agents. Alternatively, the active ingredient may be in powder form for constitution with a suitable vehicle, e.g., sterile pyrogen-free water, before use.

The compounds may also be formulated in rectal compositions such as suppositories or retention enemas, e.g., containing conventional suppository bases such as cocoa butter or other glycerides.

In addition to the formulations described previously, the compounds may also be formulated as a depot preparation. Such long acting formulations may be administered by implantation (for example subcutaneously or intramuscularly) or by intramuscular injection. Thus, for example, the compounds may be formulated with suitable polymeric or hydrophobic materials (for example as an emulsion in an acceptable oil) or ion exchange resins, or as sparingly soluble derivatives, for example, as a sparingly soluble salt.

5.10.3. Routes of Administration

Suitable routes of administration may, for example, include oral, rectal, transmucosal, transdermal, or intestinal administration; parenteral delivery, including intramuscular, subcutaneous, intramedullary injections, as well as intrathecal, direct intraventricular, intravenous, intraperitoneal, intranasal, or intraocular injections.

Alternately, one may administer the compound in a local rather than systemic manner, for example, via injection of the compound directly into an affected area, often in a depot or sustained release formulation.

Furthermore, one may administer the drug in a targeted drug delivery system, for example, in a liposome coated with an antibody specific for affected cells. The liposomes will be targeted to and taken up selectively by the cells.

5.10.4. Packaging

The compositions may, if desired, be presented in a pack or dispenser device which may contain one or more unit dosage forms containing the active ingredient. The pack may for example comprise metal or plastic foil, such as a blister pack. The pack or dispenser device may be accompanied by instructions for administration. Compositions comprising a compound formulated in a compatible pharmaceutical carrier may also be prepared, placed in an appropriate container, and labeled for treatment of an indicated condition. Suitable conditions indicated on the label may include treatment of a disease such as one characterized by aberrant or excessive expression or activity of a CML progression protein.

5.10.5. Combination Therapy

In a combination therapy, one or more compositions of the present invention can be administered before, at the same time as, or after the administration of a chemotherapeutic agent. In one embodiment, the compositions of the invention are administered before the administration of an chemotherapeutic agent (i.e., the agent that modulates expression or activity of a CML progression gene or imatinib mesylate resistance gene and/or encoded protein is for sequential or concurrent use with one or more chemotherapeutic agents). In one embodiment, the composition of the invention and a chemotherapeutic agent are administered in a sequence and within a time interval such that the composition of the invention and a chemotherapeutic agent can act together to provide an increased benefit than if they were administered alone. In another embodiment, the composition of the invention and a chemotherapeutic agent are administered sufficiently close in time so as to provide the desired therapeutic outcome. The time intervals between the administration of the compositions of the invention and a chemotherapeutic agent can be determined by routine experiments that are familiar to one skilled person in the art. In one embodiment, a chemotherapeutic agent is given to the patient after the level of the CML progression gene or imatinib mesylate resistance gene and/or encoded protein reaches a desirable threshold. The level of a CML progression gene or imatinib mesylate resistance gene and/or encoded protein can be determined by using any techniques known in the art such as those described in Section 5.3., infra.

The composition of the invention and a chemotherapeutic agent can be administered simultaneously or separately, in any appropriate form and by any suitable route. In one embodiment, the composition of the invention and the chemotherapeutic agent are administered by different routes of administration. In an alternate embodiment, each is administered by the same route of administration. The composition of the invention and the chemotherapeutic agent can be administered at the same or different sites, e.g. arm and leg.

In various embodiments, such as those described above, the composition of the invention and a chemotherapeutic agent are administered less than 1 hour apart, at about I hour apart, 1 hour to 2 hours apart, 2 hours to 3 hours apart, 3 hours to 4 hours apart, 4 hours to 5 hours apart, 5 hours to 6 hours apart, 6 hours to 7 hours apart, 7 hours to 8 hours apart, 8 hours to 9 hours apart, 9 hours to 10 hours apart, 10 hours to 1 1 hours apart, 11 hours to 12 hours apart, no more than 24 hours apart or no more than 48 hours apart, or no more than 1 week or 2 weeks or 1 month or 3 months apart. As used herein, the word about means within 10%. In other embodiments, the composition of the invention and a chemotherapeutic agent are administered 2 to 4 days apart, 4 to 6 days apart, 1 week apart, 1 to 2 weeks apart, 2 to 4 weeks apart, one month apart, 1 to 2 months apart, or 2 or more months apart. In preferred embodiments, the composition of the invention and a chemotherapeutic agent are administered in a time frame where both are still active. One skilled in the art would be able to determine such a time frame by determining the half life of each administered component. In separate or in the foregoing embodiments, the composition of the invention and a chemotherapeutic agent are administered less than 2 weeks, one month, six months, 1 year or 5 years apart.

In another embodiment, the compositions of the invention are administered at the same time or at the same patient visit, as the chemotherapeutic agent.

In still another embodiment, one or more of the compositions of the invention are administered both before and after the administration of a chemotherapeutic agent. Such administration can be beneficial especially when the chemotherapeutic agent has a longer half life than that of the one or more of the composition of the invention used in the treatment.

In one embodiment, the chemotherapeutic agent is administered daily and the composition of the invention is administered once a week for the first 4 weeks, and then once every other week thereafter. In one embodiment, the chemotherapeutic agent is administered daily and the composition of the invention is administered once a week for the first 8 weeks, and then once every other week thereafter.

In certain embodiments, the composition of the invention and the chemotherapeutic agent are cyclically administered to a subject. Cycling therapy involves the administration of the composition of the invention for a period of time, followed by the administration of a chemotherapeutic agent for a period of time and repeating this sequential administration. Cycling therapy can reduce the development of resistance to one or more of the therapies, avoid or reduce the side effects of one of the therapies, and/or improve the efficacy of the treatment. In such embodiments, the invention contemplates the alternating administration of the composition of the invention followed by the administration of a chemotherapeutic agent 4 to 6 days later, preferable 2 to 4 days, later, more preferably 1 to 2 days later, wherein such a cycle may be repeated as many times as desired.

In certain embodiments, the composition of the invention and a chemotherapeutic agent are alternately administered in a cycle of less than 3 weeks, once every two weeks, once every 10 days or once every week. In a specific embodiment of the invention, one cycle can comprise the administration of a chemotherapeutic agent by infusion over 90 minutes every cycle, 1 hour every cycle, or 45 minutes every cycle. Each cycle can comprise at least 1 week of rest, at least 2 weeks of rest, at least 3 weeks of rest. In an embodiment, the number of cycles administered is from 1 to 12 cycles, more typically from 2 to 10 cycles, and more typically from 2 to 8 cycles.

It will be apparent to one skilled person in the art that any combination of different timing of the administration of the compositions of the invention and a chemotherapeutic agent can be used. For example, when the chemotherapeutic agent has a longer half life than that of the composition of the invention, it is preferable to administer the compositions of the invention before and after the administration of the chemotherapeutic agent.

The frequency or intervals of administration of the compositions of the invention depends on the desired level of the CML progression gene or imatinib mesylate resistance gene and/or encoded protein, which can be determined by any of the techniques known in the art, e.g., those techniques described infra. The administration frequency of the compositions of the invention can be increased or decreased when the level of the CML progression gene or imatinib mesylate resistance gene and/or encoded protein changes either higher or lower from the desired level.

5.11. Implementation Systems and Methods

The analytical methods of the present invention can preferably be implemented using a computer system, such as the computer system described in this section, according to the following programs and methods. Such a computer system can also preferably store and manipulate measured signals obtained in various experiments that can be used by a computer system implemented with the analytical methods of this invention. Accordingly, such computer systems are also considered part of the present invention.

An exemplary computer system suitable from implementing the analytic methods of this invention is illustrated in FIG. 8. Computer system 801 is illustrated here as comprising internal components and as being linked to external components. The internal components of this computer system include one or more processor elements 802 interconnected with a main memory 803. For example, computer system 801 can be an Intel Pentium IV®-based processor of 2 GHZ or greater clock rate and with 256 MB or more main memory. In a preferred embodiment, computer system 801 is a cluster of a plurality of computers comprising a head “node” and eight sibling “nodes,” with each node having a central processing unit (“CPU”). In addition, the cluster also comprises at least 128 MB of random access memory (“RAM”) on the head node and at least 256 MB of RAM on each of the eight sibling nodes. Therefore, the computer systems of the present invention are not limited to those consisting of a single memory unit or a single processor unit.

The external components can include a mass storage 804. This mass storage can be one or more hard disks that are typically packaged together with the processor and memory. Such hard disk are typically of 10 GB or greater storage capacity and more preferably have at least 40 GB of storage capacity. For example, in a preferred embodiment, described above, wherein a computer system of the invention comprises several nodes, each node can have its own hard drive. The head node preferably has a hard drive with at least 10 GB of storage capacity whereas each sibling node preferably has a hard drive with at least 40 GB of storage capacity. A computer system of the invention can further comprise other mass storage units including, for example, one or more floppy drives, one more CD-ROM drives, one or more DVD drives or one or more DAT drives.

Other external components typically include a user interface device 805, which is most typically a monitor and a keyboard together with a graphical input device 806 such as a “mouse.” The computer system is also typically linked to a network link 807 which can be, e.g., part of a local area network (“LAN”) to other, local computer systems and/or part of a wide area network (“WAN”), such as the Internet, that is connected to other, remote computer systems. For example, in the preferred embodiment, discussed above, wherein the computer system comprises a plurality of nodes, each node is preferably connected to a network, preferably an NFS network, so that the nodes of the computer system communicate with each other and, optionally, with other computer systems by means of the network and can thereby share data and processing tasks with one another.

Loaded into memory during operation of such a computer system are several software components that are also shown schematically in FIG. 8. The software components comprise both software components that are standard in the art and components that are special to the present invention. These software components are typically stored on mass storage such as the hard drive 804, but can be stored on other computer readable media as well including, for example, one or more floppy disks, one or more CD-ROMs, one or more DVDs or one or more DATs. Software component 810 represents an operating system which is responsible for managing the computer system and its network interconnections. The operating system can be, for example, of the Microsoft Windows™ family such as Windows 95, Window 98, Windows NT, Windows 2000 or Windows XP. Alternatively, the operating software can be a Macintosh operating system, a UNIX operating system or a LINUX operating system. Software components 811 comprises common languages and functions that are preferably present in the system to assist programs implementing methods specific to the present invention. Languages that can be used to program the analytic methods of the invention include, for example, C and C++, FORTRAN, PERL, H™L, JAVA, and any of the UNIX or LINUX shell command languages such as C shell script language. The methods of the invention can also be programmed or modeled in mathematical software packages that allow symbolic entry of equations and high-level specification of processing, including specific algorithms to be used, thereby freeing a user of the need to procedurally program individual equations and algorithms. Such packages include, e.g., Matlab from Mathworks (Natick, Mass.), Mathematica from Wolfram Research (Champaign, Ill.) or S-Plus from MathSoft (Seattle, Wash.).

Software component 812 comprises any analytic methods of the present invention described supra, preferably programmed in a procedural language or symbolic package. For example, software component 812 preferably includes programs that cause the processor to implement steps of accepting a plurality of measured signals and storing the measured signals in the memory. For example, the computer system can accept measured signals that are manually entered by a user (e.g., by means of the user interface). More preferably, however, the programs cause the computer system to retrieve measured signals from a database. Such a database can be stored on a mass storage (e.g., a hard drive) or other computer readable medium and loaded into the memory of the computer, or the compendium can be accessed by the computer system by means of the network 807.

In addition to the exemplary program structures and computer systems described herein, other, alternative program structures and computer systems will be readily apparent to the skilled artisan. Such alternative systems, which do not depart from the above described computer system and programs structures either in spirit or in scope, are therefore intended to be comprehended within the accompanying claims.

6. EXAMPLES

The following examples are presented by way of illustration of the present invention, and are not intended to limit the present invention in any way.

6.1. Identification of Phase-Specific Genes in CML

A set of 91 individual cases of CML, including chronic phase (N=42), accelerated phase by blast count criteria (N=9) or by the occurrence of additional clonal cytogenetic changes (N=8), blast crisis (N=28), and 4 cases of blast crisis in remission after chemotherapy were used to identify genes involved in progression from chronic phase to advanced disease (i.e., accelerated and blast phases). A pool of 200 chronic phase bone marrows was used as the reference. An ANOVA analysis revealed ˜3,000 genes differentially expressed across the different phases of disease using a minimum statistical significance cutoff of p<10⁻¹¹(Tables 1a and 1b). Sequences of polynucleotide probes used to detect these genes are listed in Table 8. This set of genes identified in the progression from chronic to blast phase is referred to here as the “phase reporter” gene set. FIG. 1 shows a “heat map” of the expression of the 3,000 phase reporter genes across the various phases of CML. This illustrates the global change of gene expression as the disease progresses from the chronic phase through the advanced phase of the disease.

The expression patterns were then examined to determine if progression of CML best fits a three-step model as often described in the literature (chronic phase to accelerated phase to blast crisis), or a two-step model (chronic phase to advanced phase, i.e., accelerated or blast phase). The gene expression patterns of accelerated phase cases were compared to those of the blast crisis cases (FIG. 5). The correlation between the expression profiles of accelerated cases and those of the blast phase was quite strong (r=0.81). Comparing differentially regulated genes between accelerated phase with blast phase, there are very few phase specific genes, i.e. genes only regulated in one phase but not in another. These observations suggest that the difference of gene expression changes between accelerated and blast phase is a quantitative one rather than a qualitative one that requires new gene expression or repression.

The biological functions of the genes associated with CML phases were also examined by applying a biological annotation program based on the GO and KEGG annotations. The functional groups most highly correlated with progression to blast crisis included increased expression of nuclear genes, mitochondrial genes, RNA binding genes, protein biosynthesis genes, and genes involved in chaperone function, all reflecting the increased proliferation and metabolism of progressive disease.

Progression was also associated with decreases in the expression levels of genes involved in structural integrity and adhesion, as well as decreases in the expression levels of genes involved in inflammatory and immune response. In addition, several proto-oncogenes and tumor suppressor genes were differentially expressed with progression. For example, N- and Hras, FLT3, yes, AF1q, CBFB, WT1, ORALOV1, PTNN11, and Bcl-2 demonstrated increased expression in blast crisis as compared to chronic phase. Analysis of the phase reporter genes suggested a relative decrease in MAPPK signaling in advanced phase as compared to chronic phase. The progression was also seen as associated with increases in alternative signal pathways. Thus, the cytoplasmic GTP protein Rras2 was highly over-expressed in advanced phases, as was ras signaling components RAB56 and RALGD5. Alterations of cytokine signaling were demonstrated by an increase in expression of TNF factors SF4 and 7, and SOCS2 and 4.

6.2. Identification of Progression- and Response-Specidic Genes

Next, how the phase reporter gene set was influenced by the gene expression signature of leukemia blasts and how they compared to normal immature CD34+ cells were investigated. First, the gene expression signatures of eight samples of normal CD34+ cells were compared with CML blast samples containing >70% blasts (FIG. 2a). It was found that the gene expression pattern of CML blast cells was very similar to normal CD34+ cells, suggesting that “progression” from the chronic phase to the advanced phase is functionally similar to a block or “reversion” towards a more primitive hematopoetic cell. To uncover genes that are unique to progression, the normal CD34+ signatures were mathematically subtracted from each of the disease samples and the phase reporter signals were searched for (FIG. 2c and FIG. 6). A set of 386 genes (p<10⁻⁸) were identified (FIG. 2c and Tables 2a and 2b). These genes are called the “progression genes.” A set of 368 genes with ANOVA p<0.1% were identified as differentially expressed between CML blast crisis and normal immature CD34+ cells were also identified (FIG. 2b and Tables 5a and 5b). These genes are called the “target genes.” There were 103 genes overlapping between these two sets (hypergeometric P-value: 1.3×10⁻⁹⁹). This gene set is enriched in genes that are diagnostic markers of progression and novel targets of therapy. Table 3 shows the “top ten” genes that are associated with progression, independent of normal CD34+ expression, based on log 10 ratio of expression compared to the chronic phase pool. These genes suggest a deregulation of genes of transcriptional regulation (GLI2, WT1, FOS, FOSB), signal transduction (SOCS2, Rras2, IL8), and apoptosis (GAS2). Moreover, two HSP 70 subunits are differentially down-regulated, suggesting an alteration of this component of the chaperone system in blast crisis. Also significantly associated with progression was the surface protein PRAME, which has an unknown function, but has been associated with myeloid malignancy (van Baren et al. 1998, Br J Haematol 102:1376; Watari et al. 2000, FEBS Lett 466:367). Gene functions overrepresented in blast crisis were predominated by changes in ribosome gene expression and increased in the beta-catenin/WNT signaling pathway. More significant changes in gene function were down-regulated in progression, including nucleosome assembly and chromatin structure, sugar catabolism and metabolism, differentiation, and apoptosis.

6.3. Identification of Signaling Pathways Associated with Progression

Multiple changes in several signaling pathways are represented in the progression gene set. Again, these genes were seen in the progression of chronic phase to advanced disease, but are differentially expressed compared to normal CD34+ cells. There was a deregulation of the betacatenin/WNT pathway. Expression of the cell surface protein cadherin was decreased, as was proto-cadhedrin, potentially leading to an activation of the beta-catenin/WNT signaling pathway by allowing more free beta-catenin to move to the cytoplasm. Moreover, the myogenesis transcription control gene MDFI (I-mfa), which complexes with axin (therefore potentially increasing free beta-catenin), was increased by approximately 7-fold. In all, 16 genes associated with the beta-catenin pathway were significantly over-expressed (e.g., PRICKLE1, CSNK1E, PLCB1, FZD2, LRP6, SMAD3, etc.). In summary, these findings strongly suggest aberrant activation of the betacatenin/WNT pathway during CML progression. Moreover, progression appears to be associated with a remodeling of several cytoskeletal and adhesion molecules, which may play a role in regulating proliferation. Thus there is an increase in CD47, Crebl1, and ITGA5 expression, and a decrease in proto-cadhedrin, cadhedrin, actin, and betaactin.

In addition, the abl family member abl2 (ARG) was significantly associated with disease progression; by contrast, abl1, which is both expressed from the normal chromosome 9 and the t(9;22) translocation, was not differentially expressed with progression. Advanced phase disease was associated with deregulation of transcription factors, differentiation and apoptosis. Both components of the AP-1 transcription complex, Jun B and Fos, show decreased expression in progression. In addition, the Kupple-like zinc finger GLI2 is highly over-expressed in progression. The block in differentiation may be facilitated by the up-regulation of MDFI, WT1, and AF1q, and the down regulation of GADD45. Apoptosis in blast cells appears to be inhibited by the over-expression of Bcl2, DAP, and the decrease in MCL1 and Acinus. Progression was also associated with alterations in normal protein chaperone and degradation processes, with a widespread decrease in the expression of HSP70 and DNAJ families of genes. In addition, proteosome components BMA1 PSME2, and TRIP12 were all significantly increased in advanced phase CML cases.

6.4. Identification of Progression-Specific Promoters

In order to examine if specific pathways were altered in progression, the progression and phase reporter gene sets were analyzed for aberrant expression of genes possessing known promoter sequences. Aberrant regulation of several sets of promoter controlled genes was revealed (Table 6). The most statistically significantly set of genes showing aberrant control in progression where those that contained a MZF promoter or a delta EF1 promoter sequence (p<10⁻¹⁵and <10⁻¹¹, respectively; FIGS. 3a and 3b). Also significantly associated with progression were genes bearing SPI-B, Yin Yang, and Ahr-ARNT promoter sequences (all with p values <10⁻⁹). 6.5. IDENTIFICATION OF IMATINIB RESPONSIVENESS REPORTER GENES

Gene expression profiles of patients who failed imatinib therapy were analyzed. A set of 21 cases of CML treated with the tyrosine kinase inhibitor imatinib mesylate, including 9 patients who initially achieved a complete cytogenetic remission (CCR) on imatinib therapy, but then relapsed, most back into an apparent chronic phase by morphology; 3 cases who had achieved a complete hematologic but no cytogenetic response; 3 late chronic phase patients before treatment with imatinib; and 6 cases of blast crisis was used. All but one of these the chronic phase patients who relapsed after a CCR had a point mutation in abl1, presumably abrogating imatinib activity (Table 7).

TABLE 7Characteristics of cases treated with imatinibPhase of Disease atPhase of disease atCODECase typeinitiation of imatinibtime of sampleCytogeneticsMutation(s) 2Imatinib failurechronicrelapsed chronic100% Ph+;M244VNEW: t(1; 12) in allcells 4Imatinib failurechronicrelapsed chronic100% Ph+T315I 5Imatinib failurechronicrelapsed chronic80% Ph+F359V 6Imatinib failurechronicrelapsed chronic100% Ph+M351T,F317L 8Imatinib failurechronicrelapsed chronic100% Ph+M351T10Imatinib failurechronicrelapsed chronic100% Ph+E255K11Imatinib failurechronic post-allorelapsed chronicnot availableT315IBMT12Imatinib failurechronicrelapsed chronic100% Ph+L248V14Imatinib failurechronicrelapsed chronic100% Ph+M351T,H396R15Pre-imatinibchronicchronic pre-treatment50% Ph+nonetreatment17Pre-imatinibchronicchronic pre-treatment100% Ph+nonetreatment18Pre-imatinibchronicCHR; no cytogenetic100% Ph+nonetreatmentresponse19Pre-imatinibchronicchronic pre-treatment45% t(9; 13; 22); 50%nonetreatmentt (9; 13; 22), −Y; 5%nl21Pre-imatinibchronicCHR; no cytogenetic100% Ph+nonetreatmentresponse22 (same pt asPre-imatinibchronicCHR; no cytogenetic100% Ph+ (3 of 18none13)treatmentresponsewith additional Ph)23Pre-imatinibmyeloid blast crisispre-treatment MBC100% Ph+nonetreatment24Pre-imatinibmyeloid blast crisispre-treatment MBC100% Ph+, t(2; 16)nonetreatment25Pre-imatinibmyeloid blast crisispre-treatment MBC100% Ph+, +8, isononetreatment17q26Pre-imatinibmyeloid blast crisisnot treatednot availableunknowntreatment27Pre-imatinibmyeloid blast crisisrelapsed MBC100% Ph+unknowntreatment29Pre-imatinibmyeloid blast crisisrelapsed MBCnot availableunknowntreatment29Pre-imatinibmyeloid blast crisisrelapsed MBCnot availableunknowntreatment

FIG. 4
a shows the expression pattern of 15 cases of clinical chronic phase CML patients, 3 with longstanding chronic phase before imatinib treatment, the other 12 who had initially a suboptimal response (achieving only a hematological response) or relapsed after an initial CCR. The association with the progression signature can be demonstrated by segregating all CML cases by the correlation of gene expression signature between the boundaries of “most chronic” and “most advanced” gene expression for all 3,000 genes in the phase reporter gene set (FIG. 4b). The majority of the poor response patients had gene expression profiles more consistent with advanced disease rather than chronic phase. Both cases with T315I mutations, which have been shown to have especially poor prognosis, have expression signatures more similar to advanced disease than chronic phase. However, while these imatinib failures shared much of the blast crisis signature, there were gene expression features that were unique to these cases. FIG. 4c compares relapsed imatinib cases against blast crisis cases. Several areas (boxed) indicate genes that are expressed in reverse direction in these two states. Table 4 lists genes in the first box which are strongly associated with imatinib failure. Examples of genes unique to imatinib failure are those of serine threonine kinases (CTRL, MAP21K14, CLK3), MAP kinase (MKNK2), and the tyrosine kinase oncogene FYN. The highest genes over-expressed in imatinib resistant cases were TCF7 (a putatively T cell specific transcription factor), two guanine nucleotide binding proteins (GNAZ and GNG11), and the MAF oncogene.

6.6. Discussion

The biology and treatment of CML is dictated by the phase of disease, since the efficacy of all therapies (transplantation, interferon, imatinib) works best in chronic phase, and worse in accelerated phase and blast crisis. Understanding the biology of progression provides clinical diagnostic markers of progression, and offer insights into new strategies for treatment. The data presented in these examples suggest that the progression of chronic phase CML to advanced phase CML is a two-step process, with progression associated with a block of differentiation and apoptosis, a shift towards turning on expression of genes involved in the nucleosome, while down-regulating histone transcription. Moreover, progression is associated with alterations in cell adhesion, and activation of alternative signaling pathways. In addition, it appears that relapse after initial successful treatment with imatinib may be associated with gene expression patterns similar to advanced phase CML, suggesting that the process of progression persists in a subpopulation of CML cells even in the background of apparent successful therapy.

The demonstration that the gene expression pattern between accelerated and blast phases are very similar suggests that the crucial steps in progression are at the transition of chronic to accelerated phase, before obvious morphologic, cytogenetic or clinical evidence of progression. This has obvious clinical implications, since these patients might benefit from aggressive therapy. In addition, the observation that gene signatures of blast crisis can be seen in accelerated phase patients by cytogenetic criteria only, and blast crisis cases in remission (both of which have low blast counts similar to patients with chronic phase disease), demonstrates two important points. First, it points out the difficulty of correlating morphology with the biology of the disease.

Secondly, the penetration of a progression gene expression signature into a “chronic phase” appearing bone marrow suggests that progression is not merely an absolute block of differentiation, but that abnormal gene expression signals “leak” from the presumably immature blast crisis precursors into more normal appearing differentiated cell. This is critically important since it provides the basis for testing for progression genes in unsorted bone marrow samples from “chronic phase” patients.

In addition, the finding that CML blasts share a gene expression profile with normal CD34+ cells has important biological considerations (Passegue et al., 2003, Proc Natl Acad Sci U S A 100 Suppl 1:11842). First, it implies that there may be a limited number of novel pathways active in CML blasts. This finding is obviously important (and encouraging) in the era of targeted therapeutics. It also may explain the relative resistance of blast crisis CML to chemotherapy. Normal hematopoetic stem cells are remarkably resistant to chemotherapy, and thus in AML and ALL, with remission comes the return of normal hematopoesis. Remission is rare in blast crisis CML, perhaps because the blast cells are similarly resistant to chemotherapy as their normal counterpart.

Bcr-Abl has a wholesale range of biological activities. Critical in the transformation process is the activation of the Ras/MAPK pathways, which has broad effects on changes in cell adhesion (through Rho), proliferation (MAPK pathway), and apoptosis (through Akt) (Faderl et al., 1999, N Engl J Med 341:164; Ren, 2002, Oncogene 21:8629). The efficacy of imatinib works through the blockade of these effects.

Imatinib works poorly on advanced phase disease, and it may be because these tumors are less reliant on the pathways that imatinib blocks than chronic phase disease. Thus, it was found that the MAPK pathway was relatively under-expressed in advanced disease compared to chronic phase, but other signaling pathways, including those involving cytokines (IL3RA, SOCS2), alternative ras pathways (Rras2), and those involved in cell adhesion (B-catenin/WNT) were activated. The activation of these pathways may allow progression even in the face of therapeutic blockade of Bcr-Abl activated pathways. In addition, abl2 (Abl related gene, or ARG) is also upregulated in progresson. As opposed to abl1 (which is a nuclear protein until involved in the chimeric Bcr-Abl protein, at which time it migrates to the cytoplasm), ARG is a cytoplasmic protein (Kruh et al., 1990, Proc Natl Acad Sci U S A 87:5802). The signaling targets of ARG are unknown, and although broadly expressed in tissue, its only known functional role apparent from knockout mouse models appears to be in the nervous system (Koleske et al., 1998, Neuron 21:1259; Perego et al., 1991, Oncogene 6:1899). ARG has been associated with myeloid leukemia in the contest of TEL/ARG translocations (Cazzaniga et al., 1999, Blood 94:4370; lijima et al., 2000, Blood 95:2126). ARG shares over 90% homology of its tyrosine kinase domain with abl1, and ARG tyrosine kinase activity is inhibited by imatinib at similar drug concentrations (Kruh et al., 1990, Proc Natl Acad Sci U S A 87:5802; Okuda et al., 2001, Blood 97:2440). However, given that Bcr-ABL amplification is considered to play a role in imatinib resistance (le Coutre et al. 2000, Blood 95:1758; Weisberg et al., 2000, Blood 95:3498), ARG over-expression in blast crisis could theoretically contribute to the relative resistance to imatinib found with progressive disease.

Two recent observations on the molecular biology of progression in CML are relevant to this study. First, activation of the beta-catenin pathway was observed in primary cell samples from patients with CML (Jamieson et al., 2004, N Engl J Med 351:657). Secondly, it was recently observed that mice deficient in Jun B develop a disease much like CML (Passegue et al., 2004, Cell 119:431). The data in these examples complement these findings, as we found broad dysregulation of WNT/beta-catenin pathway as well as decreased Jun B expression. A link between these pathways may be the gene MDFI (Imfa), an inhibitor of myogenic basic H-L-H transcription factors 4. MDFI interacts with axin, which is involved in binding and modulating free beta-catenin. Thus an increase in MDFI would effectively allow for more free beta-catenin to migrate to the nucleus, where it causes gene activation (Nelson et al., 2004, Science 303:1483). An increase in MDFI could also decrease the axinmediated activation of Jun (Kusano et al., 2002, Mol Cell Biol 22:6393). Thus, MDFI may play a central role in progression by both influencing the beta-catenin and Jun B pathways. Moreover, the fact that both Jun B and Fos were down-regulated in progression suggests that there may be a wholesale deregulation in AP-1 targets, which could have broad functional affects on differentiation, apoptosis, and cell cycle control (Hess et al., 2004, J Cell Sci 117:5965).

The analysis suggests that genes controlled by MZF1 and delta EF1 may be particularly important in progression. MZF1 is a member of the Kruppel family of zinc finger proteins, and was originally cloned from a cDNA library from a blast crisis CML patient (Hromas et al., 1991, J Biol Chem 266:14183). MZF1 appears to play a critical role in hematopoetic stem cell differentiation, including modulation of CD34 and c-myb expression (Gaboli et al., 2001, Genes Dev 15:1625; Perrotti et al., 1995, Mol Cell Biol 15:6075). MZF1 −/− knock-out mice display an increase in hemapoetic progenitor proliferation which continues in long-term culture conditions (Gaboli et al., 2001, Genes Dev 15:1625). These data support the findings found in our human studies described about that MZF1 deregulation may disrupt normal differentiation, promoting the progression to advanced disease. Delta EF1 is related to the Smad zinc finger proteins that play an important role in TGFbeta gene regulation. Delta EF1 has been shown to compete with basic helix-loop-helix activators, and is implicated in modulation of MyoD regulated pathways (Funahashi et al., 1993, Development 119:433; Sekido et al., 1994, Mol Cell Biol 14:5692). It is not known if delta EF1 directly influences MDFI expression.

Of note is that both MZF1 and delta EF1 have been shown to influence cadherin expression (Guaita et al., 2002, J Biol Chem 277:39209; Le et al., 2005, Exp Cell Res 302:129; Miyoshi et al., 2004, Br J Cancer 90:1265). Thus, the further study of the control of MZF1 and delta EF1 may be particularly fruitful in understanding the molecular mechanisms of CML progression. Given that efficacy of treatment in CML (be it with interferon, imatinib, or transplantation) is so intimately associated with phase of disease, those patients who fail therapy in chronic phase may have genetic features of advanced phase invisible to routine pathological and cytogenetic exam. Imatinib failures are a reasonable setting to explore this possibility. While imatinib can cause cytogenetic remissions in the majority of chronic phase cases, treatment failure, especially secondary to point mutations, is an increasingly important problem. It has previously been demonstrated that the probability of developing a point mutation depends largely on the time from diagnosis to initiation of therapy (Branford et al., 2003, Blood 102:276). This finding implies that the genetic mechanisms that lead to point mutations are relentless, and therefore the treatment of “late” chronic phase patients (i.e., >1 year from diagnosis) may be undermined by genetic changes that have already occurred. Branford et al. demonstrated that patients who developed point mutations had a very poor outcome, with approximately half dying within a year of relapse (Branford et al., 2003, Blood 102:276). These observations are in keeping with the demonstration in these examples that many imatinib failures have gene expression changes similar to advanced disease, despite their benign pathological appearance. Thus, resistance to imatinib may be ameliorated by either targeting pathways of progression (beta-catenin, JunB/Fos, etc.), or by targeting pathways specifically found activated in imatinib resistance cases (alternative kinases, protein transporters).

Several of the genes found in the progression set might serve as early markers of progression in diagnostic assays, and may serve as therapeutic targets, as well. For example, PRAME (Preferentially Expressed Antigen of Melanoma) was originally identified as a tumor antigen recognized by cytotoxic T-cells against a melanoma surface antigen (Matsushita et al., 2001, Br J Haematol 112:916, 2001; van Baren et al., 1998, Br J Haematol 102:1376). Like similar antigens MAGE, BAGE, and GAGE, which are expressed in some solid tumors; unlike these other antigens, however, PRAME has been found to be overexpressed in over 25% of leukemia, and has been found to be induced by Bcr-Abl in CML cell lines (Watari et al., 2000, FEBS Lett 466:367). Indeed, PRAME over-expression has been described as one of the few features that characterize the transient myeloproliferative syndrome of Down's syndrome from the progressive acute megakaryoblastic leukemia found in that disorder (McElwaine et al., 2004, Br J Haematol 125:729). While the function of PRAME is still unknown, its expression on the cell surface might be amenable to flow cytometry assays, as well as a target for immunologic (vaccine or cell-based) therapy. CD47, an integrin-like protein, is another potential diagnostic target discovered in our analysis of progression (Motegi et al., 2003, Embo J 22:2634; Okazawa et al., 2005, J Immunol 174:2004). In addition, the demonstration of aberrant regulation of alternative signaling pathways (FLT3; Rras2; beta-catenin. SOCS2), proteosomes, and chaperone proteins suggest that the targeting of several novel pathways may be needed in the treatment of advanced CML.

Compared to other types of leukemia, there have been few papers exploring the use of microarrays on the biology of CML. In sum, 23 patients of various stages have been studied, 10 on unsorted samples, 13 from AC133+ isolated cells. It is difficult to make a direct comparison of these studies and ours, given the different types of samples obtained, the difference in the array platforms (these studies used platforms examining 3,000-5,000 genes, compared to ˜24,000 genes in this current study). In general, however, the functional changes of progression, e.g., changes in differentiation, apoptosis, and cell adhesion, remained as common themes across the study. In contrast to one study, no significant differences in signatures obtained from bone marrow and peripheral blood (FIG. 7) were found, which may be important in future prospective studies of this disease in patients.

These findings have the potential to influence therapy of CML. Patients who present with gene expression patterns suggestive of advanced phase disease might benefit to move straight to transplantation if a donor exists, or if not, other investigation therapies. Moreover, PCR assays of individual genes (or small sets of genes) may be used to monitor patients early in the course of imatinib therapy for signs of progression to advanced disease. Microarray studies of large cohorts of patients treated with imatinib will likely identify gene patterns indicative of response that can be used immediately at diagnosis to tailor therapy.

6.7. Materials and Methods

Patient samples. All samples were obtained under the auspices of institutional review board approve protocols. Samples came from the FHCRC, the Southwest Oncology Group (SWOG) Myeloid Repository, the University of Oregon Health Sciences Center, the University of California, Los Angeles, or the University of Chicago. RNA extraction was either performed immediately, or in the case of samples stored in a liquid nitrogen repository, after thawing. All RNA samples were quality tested by analysis of ribosomal RNA peaks using an ABI Bioalyzer. The definition of chronic, accelerated and blast crisis was based on the criteria of Sokal (Sokal et al., 1984, Blood 63:789).

Amplification, labeling, and hybridization. The procedures of RNA amplification, labeling, and the hybridization to arrays, as well as the specifics of the array platforms, has been previously published (Hughes et al., 2001, Nat Biotechnol 19:342).

Analytic Methods and Results. Each individual sample was hybridized to a pool of chronic phase samples. The log 10 (Ratio) of intensity of individual samples to the pool were used for the subsequent analysis. Before selecting features by ANOVA, 25,000 genes on the array were first screened for evidence of differential regulation by requiring P-value of regulation <1% in more than 3 experiments. Where P-value of regulation is based on the platform error model. Features differentiating progression stages were selected by ANOVA test.

Functional annotation of gene lists. Genes represented on the microarray were annotated by assignment to GO Biological Process or Molecular Function categories (at the web address www.ebi.ac.uk/GOA/), or to KEGG pathways (at the web address www.genome.jp/kegg/pathway.html). Gene lists (input sets) were queried for enrichment of members of specific functional classes or pathways relative to the background frequency. The significance (P-value) of enrichment was computed using the hypergeometric probability distribution. Reported in each case are the numbers of genes in the input set (input gene count), number of genes in a particular category or pathway in the input set (overlap gene count), number of genes in a particular category among all genes present on the array (set gene count). The total number of unique genes on the array is 24132.

Methods to common promote site analysis. The common promoter sites were based on the predictions derived from the database (oPOSSUM) by Wasserman et al. (www.cisreg.ca). The hypergeometric P-value for enrichment of a particular binding site was computed by comparing the number of genes with the binding site from a signature gene set to that from a background set (i.e., all genes represented on the microarray).

Controls. We compared the genes found associated with progression to the genes found significantly over- and under-expressed with prolonged “transit time” from sample acquisition to RNA processing (Radich et al., 2004, Genomics 83:980). There gene signatures of the two data sets were different, excluding this artifact as contributing significantly to the progression gene set.

Lastly, we compared gene expression signatures from the sites contributing samples to confirm that there were no site-signatures confounding the analysis. We found no evidence of site-specific signatures.

As some samples of blast crisis came from peripheral blood rather than bone marrow, we compared three samples in which simultaneous samples were available from bone marrow and peripheral blood. Gene expression was extremely well correlated (r=0.97 to 0.99; FIG. 7).

TABLE 8The phase reporter genesPROBESEQSEQSUBSGENEDESCRIPTIONSP_XREF_KEYWORD_LISTID NO.ID NO.AB002301KIAA0303KIAA0303 proteinHypothetical protein, ATP-binding,13969Kinase, Serine/threonine-proteinkinase, TransferaseAB002313PLXNB2plexin B2Hypothetical protein23970AB002314KIAA0316KIAA0316 geneHypothetical protein33971productAB002331DATF1death associatedApoptosis, Nuclear protein, Zinc-43972transcription factor 1finger, Alternative splicingAB002336EPB41L1erythrocyteHypothetical protein, Structural53973membrane proteinprotein, Cytoskeleton, Actin-bindingband 4.1-like 1AB002337KIAA0339KIAA0339 geneHypothetical protein63974productAB002354KIAA0356pleckstrin homologyHypothetical protein73975domain containing,family M (with RUNdomain) member 1AB002359PFASphosphoribosylformylglycinamidinePurine biosynthesis, Ligase, ATP-83976synthase (FGARbinding, Glutamineamidotransferase)amidotransferase, HypotheticalproteinAB002360MCF2LMCF.2 cell lineHypothetical protein, Guanine-93977derived transformingnucleotide releasing factor, Proto-sequence-likeoncogeneAB002366KIAA0368KIAA0368Hypothetical protein103978AB002368XPO6exportin 6Hypothetical protein113979AB002369MTMR3myotubularin relatedHydrolase, Zinc-finger, Alternative123980protein 3splicing, Hypothetical proteinAB002373KIAA0375RUN and SH3Hypothetical protein, SH3 domain133981domain containing 2AB002377KIAA0379ankyrin repeatHypothetical protein, Repeat, ANK143982domain 28repeatAB002379DAAM2dishevelledCoiled coil, Alternative splicing153983associated activatorof morphogenesis 2AB004857SLC11A2solute carrier familyTransport, Iron transport,16398411 (proton-coupledTransmembrane, Glycoprotein,divalent metal ionAlternative splicing, Polymorphismtransporters),member 2AB006622KIAA0284KIAA0284Hypothetical protein173985AB007855TIX1zinc fingers andDNA-binding, Homeobox, Nuclear183986homeoboxes 3protein, Zinc-finger, Metal-binding,RepeatAB007863PIP3-Ephosphoinositide-Hypothetical protein193987binding protein PIP3-EAB007864KIAA0404KIAA0404 proteinHypothetical protein, Metal-binding,203988Oxidoreductase, ZincAB007888MBNL1muscleblind-likeHypothetical protein, Zinc-finger,213989(Drosophila)Repeat, Nuclear protein, RNA-binding, Alternative splicingAB007902AUTS2autism susceptibilityChromosomal translocation,223990candidate 2Polymorphism, Alternative splicingAB007915KIAA0446KIAA0446 geneHypothetical protein233991productAB007931RBAF600retinoblastoma-Hypothetical protein243992associated factor600AB007941KIAA0472dusty protein kinaseATP-binding, Transferase,253993Hypothetical protein, Kinase,Serine/threonine-protein kinaseAB007958KIAA0489KIAA0792 geneHypothetical protein263994productAB007962KIAA0493KIAA0493 protein273995AB007965CYHR1MRNA, chromosome2839961 specific transcriptKIAA0496.AB007972PPP1R12Bprotein phosphataseANK repeat, Myosin, Repeat2939971, regulatory(inhibitor) subunit12BAB011093P114-RHO-rho/rac guanineHypothetical protein303998GEFnucleotide exchangefactor (GEF) 18AB011105LAMA5laminin, alpha 5Laminin EGF-like domain, Signal,313999Glycoprotein, Basement membrane,Extracellular matrix, Coiled coil, Celladhesion, RepeatAB011112KIAA0540KIAA0540 proteinHypothetical protein, Repeat, WD324000repeatAB011114KIAA0542KIAA0542 geneHypothetical protein334001productAB011133KIAA0561microtubuleHypothetical protein, ATP-binding,344002associatedKinase, Serine/threonine-proteinserine/threoninekinase, Transferasekinase 3AB011136KIAA0564KIAA0564 proteinHypothetical protein, ATP-binding354003AB011153PLCB1phospholipase C,Hydrolase, Lipid degradation,364004beta 1Transducer, Phosphorylation,(phosphoinositide-Calcium, Alternative splicingspecific)AB011154RAB1AKIAA0582 proteinHypothetical protein374005AB011157PTDSRphosphatidylserineHypothetical protein, Receptor384006receptorAB011167KIAA0595peroxisomeHypothetical protein394007proliferativeactivated receptor,gamma, coactivator-related 1AB011171KIAA0599KIAA0599Hypothetical protein, Plasmid404008AB011173KIAA0601amine oxidaseHypothetical protein414009(flavin containing)domain 2AB011542EGFL5EGF-like-domain,Laminin EGF-like domain424010multiple 5AB012692CAC-1beta-casein-likeHypothetical protein434011proteinAB014516MECT1Homo sapiensTranscription regulation, DNA-444012mRNA for KIAA0616binding, Activator, Nuclear protein,protein, partial cds.Phosphorylation, Cell cycle,Alternative splicing, 3D-structure,Polymorphism, Hypothetical proteinAB014520PLXND1plexin D1Hypothetical protein454013AB014538KIAA0638pleckstrin homology-Hypothetical protein464014like domain, familyB, member 1AB014543KIAA0643KIAA0643 proteinHypothetical protein474015AB014548KIAA0648KIAA0648 proteinHypothetical protein484016AB014557KIAA0657KIAA0657 proteinHypothetical protein,494017Immunoglobulin domainAB014558CRY2cryptochrome 2Lyase, Hypothetical protein504018(photolyase-like)AB014564KIAA0664KIAA0664 proteinHypothetical protein, Initiation factor,514019Protein biosynthesisAB014566DAAM1dishevelledCoiled coil, Alternative splicing524020associated activatorof morphogenesis 1AB014567TIP120BTBP-interactingHypothetical protein534021proteinAB014568UNC84Bunc-84 homolog BTransmembrane, Nuclear protein,544022(C. elegans)Coiled coilAB014574KIAA0674KIAA0674 proteinHypothetical protein554023AB014578KIAA0678RME8 proteinHypothetical protein564024AB014589CSTF2Tcleavage stimulationHypothetical protein574025factor, 3′ pre-RNA,subunit 2, 64 kDa,tau variantAB014597GTARankyrin repeatHypothetical protein, ANK repeat,584026domain 17RepeatAB014600SIN3BSIN3 homolog B,Transcription regulation, Repressor,594027transcriptionalRepeat, Nuclear proteinregulator (yeast)AB014604OSBPL3oxysterol bindingLipid transport, Transport,604028protein-like 3Alternative splicingAB015330DKFZP761I2123hypothetical proteinHypothetical protein614029DKFZp761I2123AB015343HRIHFB2122Tara-like proteinCytoskeleton, Actin-binding, Coiled624030coil, Nuclear proteinAB018268KIAA0725SAM, WWE andHypothetical protein634031DDHD domaincontaining 1AB018325CENTD2centaurin, delta 2GTPase activation, Repeat, Zinc-644032finger, Alternative splicingAB018339SYNE1spectrin repeatStructural protein, Cytoskeleton,654033containing, nuclearActin-binding, Coiled coil,envelope 1Transmembrane, Repeat, Alternativesplicing, PolymorphismAB018348PCNXpecanex homologTransmembrane, Glycoprotein,664034(Drosophila)Alternative splicingAB018353UNC84Aunc-84 homolog ATransmembrane, Nuclear protein,674035(C. elegans)Coiled coil, Alternative splicingAB020627KIAA0820dynamin familyHydrolase, Motor protein, GTP-684036memberbinding, Microtubule, Multigenefamily, EndocytosisAB020636TIP120ATBP-interactingHypothetical protein694037proteinAB020637KIAA0830KIAA0830 proteinHypothetical protein704038AB020644FACL6acyl-CoA synthetaseLigase, Fatty acid metabolism,714039long-chain familyMagnesium, Multigene family,member 6Alternative splicing, Chromosomaltranslocation, Hypothetical proteinAB020649KIAA0842pleckstrin homologyHypothetical protein724040domain containing,family M (with RUNdomain) member 2AB020673MYH11myosin, heavyMyosin, Muscle protein, Coiled coil,734041polypeptide 11,Thick filament, Actin-binding,smooth muscleCalmodulin-binding, ATP-binding,Methylation, Multigene family, Proto-oncogene, ChromosomaltranslocationAB020684KIAA0877KIAA0877 proteinHypothetical protein744042AB020691KIAA0884GTPase activatingHypothetical protein754043RANGAP domain-like 1AB020695KIAA0888KIAA0888 proteinHypothetical protein764044AB020698USP19ubiquitin specificProtease, Ubl conjugation pathway,774045protease 19Hydrolase, Thiol protease, Multigenefamily, Zinc-finger, Metal-bindingAB020703DD5progestin inducedUbl conjugation pathway, Ligase,784046proteinNuclear protein, 3D-structureAB020704PPFIA4protein tyrosineHypothetical protein794047phosphatase,receptor type, fpolypeptide(PTPRF), interactingprotein (liprin), alpha 4AB023152KIAA0935mannosidase alphaHydrolase, Glycosidase, Signal,804048class 2B member 2Glycoprotein, Hypothetical proteinAB023154KIAA0937macrophageHypothetical protein, Metal-binding,814049expressed gene 1Zinc, Zinc-fingerAB023156SLC9A8solute carrier familyHypothetical protein8240509 (sodium/hydrogenexchanger), isoform 8AB023164KIAA0947KIAA0947 proteinHypothetical protein834051AB023210WDFY3WD repeat andHypothetical protein, Repeat, WD844052FYVE domainrepeatcontaining 3AB023211PADI2peptidyl arginineHydrolase, Calcium-binding,854053deiminase, type IIMultigene familyAB023212PCNXpecanex homologTransmembrane, Glycoprotein,864054(Drosophila)Alternative splicingAB023216KIAA0999KIAA0999 proteinHypothetical protein, ATP-binding,874055Kinase, Serine/threonine-proteinkinase, TransferaseAB023230KIAA1013GRP1-bindingHypothetical protein, Cytoskeleton884056protein GRSP1AB023233CHDC1calponin homologyHypothetical protein, Leucine-rich894057(CH) domainrepeat, Repeatcontaining 1AB025254PCTAIRE2BPtudor repeatHypothetical protein904058associator withPCTAIRE 2AB026054ZNF179zinc finger proteinZinc-finger914059179AB026436DUSP10dual specificityHydrolase, Nuclear protein,924060phosphatase 10Hypothetical proteinAB028972KIAA1049KIAA1049 proteinHypothetical protein934061AB028978KIAA1055KIAA1055 proteinHypothetical protein944062AB028980USP24ubiquitin specificHypothetical protein, Ubl conjugation954063protease 24pathway, Hydrolase, Thiol protease,Multigene familyAB028986USP22ubiquitin specificHypothetical protein, Protease, Ubl964064protease 22conjugation pathway, Hydrolase,Thiol protease, Multigene familyAB028989MAPK8IP3mitogen-activatedPhosphorylation, Coiled coil974065protein kinase 8interacting protein 3AB028994AMOTangiomotinHypothetical protein984066AB029030KIAA1107KIAA1107 proteinHypothetical protein994067AB029032FLJ21404hypothetical proteinHypothetical protein1004068KIAA1109AB029041KIAA1118likely ortholog ofHypothetical protein1014069mouse 5-azacytidineinduced gene 1AB032952KIAA1126KIAA1126 proteinHypothetical protein1024070AB032965CASKIN2CASK interactingHypothetical protein, ANK repeat,1034071protein 2RepeatAB032973LCHNLCHN proteinHypothetical protein1044072AB032976P66transcriptionHypothetical protein1054073repressor p66 betacomponent of theMeCP1 complexAB032993GRIPAP1GRIP1 associatedHypothetical protein1064074protein 1AB033009KIAA1183KIAA1183 proteinHypothetical protein1074075AB033037KIAA1211KIAA1211 proteinHypothetical protein1084076AB033050RAI17retinoic acid inducedHypothetical protein109407717AB033053ZNF295zinc finger proteinTranscription regulation, DNA-1104078295binding, Zinc-finger, Metal-binding,Nuclear protein, RepeatAB033055KIAA1229KIAA1229 proteinHypothetical protein1114079AB033068FZR1Fzr1 proteinHypothetical protein, Ubl conjugation1124080pathway, Cell cycle, Cell division,Mitosis, Repeat, WD repeat,Phosphorylation, Alternative splicingAB033070KIAA1244KIAA1244Hypothetical protein1134081AB033073KIAA1247sulfatase 2Hydrolase, Signal, Glycoprotein,1144082Endoplasmic reticulum, Golgi stackAB033085KIAA1259hypothetical proteinHypothetical protein, ATP-binding,1154083KIAA1259Helicase, HydrolaseAB033087TLE4transducin-likeTranscription regulation, Repressor,1164084enhancer of split 4Nuclear protein, Repeat, WD repeat,(E(sp1) homolog,Phosphorylation, Wnt signalingDrosophila)pathwayAB033091KIAA1265solute carrier familyHypothetical protein117408539 (zinc transporter),member 10AB033092MTA3metastasisHypothetical protein, Zinc-finger,1184086associated family,Nuclear protein, Alternative splicingmember 3AB033100KIAA1274KIAA protein (similarHypothetical protein1194087to mouse paladin)AB033108KCNH3potassium voltage-Hypothetical protein, Transport, Ion1204088gated channel,transport, Ionic channel, Voltage-subfamily H (eag-gated channel, Potassium channel,related), member 3Potassium transport,Transmembrane, Glycoprotein,Multigene familyAB033112BRPF3bromodomain andHypothetical protein, Zinc-finger,1214089PHD fingerBromodomaincontaining, 3AB033118ZDHHC8zinc finger, DHHCTransmembrane, Zinc-finger,1224090domain containing 8Hypothetical proteinAB037716KIAA1295KIAA1295 proteinHypothetical protein, SH3 domain1234091AB037720SH2BSH2-B homologHypothetical protein1244092AB037721STARD9START domainHypothetical protein1254093containing 9AB037722KIAA1301NEDD4-related E3Hypothetical protein1264094ubiquitin ligaseNEDL2AB037729RALGDSral guanineGuanine-nucleotide releasing factor,1274095nucleotide3D-structure, Hypothetical proteindissociationstimulatorAB037749KIAA1328KIAA1328 proteinHypothetical protein1284096AB037757KIAA1336WD repeat domainHypothetical protein, Repeat, WD129409735repeatAB037760ZNF398zinc finger proteinTranscription regulation, Activator,1304098398DNA-binding, Zinc-finger, Metal-binding, Nuclear protein, Repeat,Alternative splicingAB037771KIAA1350ubiquitin specificHypothetical protein1314099protease 53AB037787NLGN2neuroligin 2Cell adhesion, Glycoprotein, Signal,1324100TransmembraneAB037795KIAA1374KIAA1374 proteinHypothetical protein, Repeat, WD1334101repeatAB037802COG1component ofTransport, Protein transport, Golgi1344102oligomeric golgistack, Membranecomplex 1AB037813DKFZp762K222hypothetical proteinHypothetical protein1354103DKFZp762K222AB037814KIAA1393KIAA1393Hypothetical protein1364104AB037836PRex1phosphatidylinositolGuanine-nucleotide releasing factor,13741053,4,5-trisphosphate-Repeat, Alternative splicingdependent RACexchanger 1AB037845ARHGAP10Rho GTPaseHypothetical protein1384106activating protein 21AB037851KIAA1430KIAA1430 proteinHypothetical protein1394107AB037855KIAA1434hypothetical proteinHypothetical protein1404108KIAA1434AB037859MKL1megakaryoblasticTranscription regulation, Nuclear1414109leukemiaprotein, Coiled coil, Repeat,(translocation) 1Chromosomal translocation, ProtooncogeneAB037860NFIAnuclear factor I/AActivator, DNA replication, DNA-1424110binding, Nuclear protein,Transcription, Transcriptionregulation, Multigene familyAB037861DKFZP586J0619DKFZP586J0619Hypothetical protein1434111ProteinAB040881KIF1Bkinesin familyHypothetical protein, Motor protein,1444112member 1BMicrotubule, ATP-binding, Coiledcoil, Mitochondrion, Alternativesplicing, Disease mutation, Charcot-Marie-Tooth diseaseAB040900KIAA1467KIAA1467 proteinHypothetical protein1454113AB040907KIAA1474zinc finger proteinHypothetical protein, Metal-binding,1464114537Zinc, Zinc-fingerAB040908VPS18vacuolar proteinTransport, Protein transport,1474115sorting protein 18Membrane, Zinc-finger, Coiled coil,Alternative splicingAB040917KIAA1484leucine rich repeatHypothetical protein,1484116and fibronectin typeImmunoglobulin domainIII domain containing 1AB040930LRRN1leucine rich repeatHypothetical protein,1494117neuronal 1Immunoglobulin domainAB040942KIAA1509KIAA1509Hypothetical protein, Plasmid1504118AB040955KIAA1522KIAA1522 proteinHypothetical protein1514119AB040960FLJ22670lymphocyte alpha-Hypothetical protein, Kinase1524120kinaseAB040961DTX2deltex homolog 2Nuclear protein, Repeat, Metal-1534121(Drosophila)binding, Zinc, Zinc-finger, Alternativesplicing, PolymorphismAB040968HCN3hyperpolarizationTransport, Ion transport, Ionic1544122activated cyclicchannel, Voltage-gated channel,nucleotide-gatedPotassium channel, Potassium,potassium channel 3Potassium transport, Sodiumtransport, cAMP, cAMP-binding,Transmembrane, Glycoprotein,Sodium channelAB040969KIAA1536KIAA1536 proteinHypothetical protein1554123AB040972FLJ11560Homo sapiensHypothetical protein1564124mRNA for KIAA1539protein, partial cds.AF000560hypothetical proteinMetal-binding, Zinc, Zinc-finger1574125LOC126208AF007217TRIP11thyroid hormoneAntigen, Golgi stack, Coiled coil,1584126receptor interactorChromosomal translocation,11Hypothetical proteinAF011757S100A12S100 calciumCalcium-binding, Zinc, Metal-binding1594127binding protein A12(calgranulin C)AF016267TNFRSF10Ctumor necrosis factorReceptor, Apoptosis, Glycoprotein,1604128receptor superfamily,Repeat, GPI-anchor, Signal,member 10c, decoyLipoproteinwithout anintracellular domainAF016495AQP9aquaporin 9Transport, Repeat, Transmembrane1614129AF017433ZNF213zinc finger proteinTranscription regulation, DNA-1624130213binding, Zinc-finger, Metal-binding,Nuclear protein, RepeatAF026816ITPAinosineHydrolase, Nucleotide metabolism,1634131triphosphataseDisease mutation(nucleosidetriphosphatepyrophosphatase)AF031166SRP46Splicing factor,1644132arginine/serine-rich,46 kDAF034803PPFIBP2PTPRF interactingReceptor, Hypothetical protein1654133protein, bindingprotein 2 (liprin beta2)AF035307plexin C11664134AF038193ADP-ribosylationGTP-binding, Multigene family,1674135factor-like 3PolymorphismAF038535SYT7synaptotagmin VIITransmembrane, Repeat, Synapse1684136AF038554DENRdensity-regulatedHypothetical protein1694137proteinAF043469NXPH4serineTransferase, Methyltransferase,1704138hydroxymethyltransferase 2Pyridoxal phosphate, One-carbon(mitochondrial)metabolism, Mitochondrion, Transitpeptide, Glycoprotein, Repeat,Signal, Hypothetical proteinAF045229RGS10regulator of G-Signal transduction inhibitor,1714139protein signalling 10Lipoprotein, Palmitate, Alternativesplicing, PolymorphismAF049140UBE2V2ubiquitin-conjugatingLigase, Ubl conjugation pathway,1724140enzyme E2 variant 2Vitamin DAF052093NJMU-R1protein kinase Njmu-1734141R1AF052117chloride channel 4Ionic channel, Ion transport, Chloride1744142channel, Chloride, Voltage-gatedchannel, Transmembrane, CBSdomain, RepeatAF052159protein tyrosine1754143phosphatase-like(proline instead ofcatalytic arginine),member bAF052167MRS2LMRS2-like,Signal, Hypothetical protein1764144magnesiumhomeostasis factor(S. cerevisiae)AF052169LOC115207potassium channelHypothetical protein1774145tetramerisationdomain containing12AF052181epimorphin1784146AF055006SEC6SEC6-like 1 (S. cerevisiae)Hypothetical protein, Exocytosis,1794147Transport, Protein transport, Coiledcoil, Alternative splicingAF055012TGIF2TGFB-induced factorDNA-binding, Homeobox,18041482 (TALE familyTranscription regulation, Nuclearhomeobox)protein, PhosphorylationAF055016C13orf1chromosome 13Hypothetical protein1814149open reading frame 1AF055019homeodomainTransferase, Serine/threonine-1824150interacting proteinprotein kinase, ATP-binding, Nuclearkinase 2protein, Alternative splicingAF055029hypothetical protein1834151LOC151162AF055270SFRS7Homo sapiens heat-Nuclear protein, RNA-binding,1844152shock suppressedmRNA splicing, Alternative splicing,protein 1 (HSSG1)Phosphorylation, Repeat, Zinc-mRNA, completefinger, Hypothetical proteincds.AF059531PRMT3protein arginine N-Hypothetical protein, Transferase,1854153methyltransferase 3Methyltransferase, Zinc-fingerAF062341CTNND1catenin (cadherin-Cytoskeleton, Structural protein,1864154associated protein),Phosphorylation, Repeat, Celldelta 1adhesion, Coiled coil, Nuclearprotein, Alternative splicingAF063020PSIP2PC4 and SFRS1Receptor1874155interacting protein 1AF067972DNMT3ADNA (cytosine-5-)-Methyltransferase, Transferase,1884156methyltransferase 3Zinc-finger, Metal-binding, Nuclearalphaprotein, Hypothetical proteinAF068296MRPS35mitochondrialHypothetical protein, Ribosomal1894157ribosomal proteinprotein, MitochondrionS35AF070587Clone 24741 mRNA1904158sequenceAF070643LOC55977intraflagellar1914159transport proteinIFT20AF072810BAZ1BbromodomainTranscription regulation,1924160adjacent to zincBromodomain, Zinc-finger, Coiledfinger domain, 1Bcoil, Nuclear protein, Alternativesplicing, Williams-Beuren syndromeAF073519SERF1Asmall EDRK-richAlternative splicing1934161factor 1A (telomeric)AF073931CACNA1Hcalcium channel,Ionic channel, Transmembrane, Ion1944162voltage-dependent,transport, Voltage-gated channel,alpha 1H subunitCalcium channel, Glycoprotein,Repeat, Multigene family, Calcium-binding, Phosphorylation, AlternativesplicingAF077965CLN3ceroid-lipofuscinosis,Transmembrane, Lysosome,1954163neuronal 3, juvenileGlycoprotein, Alternative splicing,(Batten, Spielmeyer-Neuronal ceroid lipofuscinosis,Vogt disease)Disease mutationAF078843LOC51202DEAD (Asp-Glu-Ala-ATP-binding, Helicase, Hydrolase,1964164Asp) box polypeptideHypothetical protein47AF085243ZNF236zinc finger proteinMetal-binding, Nuclear protein, Zinc,1974165236Zinc-finger, Hypothetical protein,Transcription regulation, DNA-binding, Repeat, Alternative splicingAF090935C20orf3Homo sapiens cloneTransmembrane, Signal-anchor,1984166HQ0569.Glycoprotein, PolymorphismAF097021GW112differentially1994167expressed inhematopoieticlineagesAF112213C20orf24chromosome 20Alternative splicing2004168open reading frame24AF112219ESDesteraseHydrolase, Serine esterase,2014169D/formylglutathionePolymorphismhydrolaseAF113694NF2neurofibromin 2Structural protein, Cytoskeleton,2024170(bilateral acousticAnti-oncogene, Disease mutation,neuroma)Alternative splicing, Deafness, 3D-structureAF114264nexilinnexilin (F actinHypothetical protein2034171binding protein)AF116238PUS1pseudoundylateLyase, tRNA processing, Nuclear2044172synthase 1proteinAF117236MATR3matrin 3Nuclear protein, RNA-binding,2054173Repeat, Zinc-fingerAF119665PPpyrophosphataseHydrolase, Metal-binding,2064174(inorganic)MagnesiumAF119856PRO1851Homo sapiensAcute phase, Serine protease2074175mRNA for PK-120,inhibitor, Repeat, Signal, Multigenecomplete cds.family, Glycoprotein, Alternativesplicing, PolymorphismAF121856SNX6sorting nexin 6Hypothetical protein, Transport,2084176Protein transportAF126749SCA8SCA8 mRNA, repeat2094177regionAF127765CAPN3calpain 3, (p94)Hydrolase, Thiol protease, Calcium-2104178binding, Multigene family, Repeat,Disease mutation, Polymorphism,Alternative splicingAF131760LRP10low densityHypothetical protein, Plasmid2114179lipoprotein receptor-related protein 10AF131764MPP5membrane protein,Hypothetical protein, SH3 domain,2124180palmitoylated 5Membrane(MAGUK p55subfamily member 5)AF131768FLJ13657chromosome 9 openHypothetical protein2134181reading frame 82AF131774FLJ14800hypothetical proteinHypothetical protein2144182FLJ14800AF131775MGC5560hypothetical proteinHypothetical protein2154183MGC5560AF131784RAB27B, memberGTP-binding, Lipoprotein,2164184RAS oncogenePrenylationfamilyAF131803MGC5508hypothetical proteinHypothetical protein2174185MGC5508AF131812likely ortholog ofHypothetical protein2184186mouse monocytemacrophage 19AF131838FLJ12806hypothetical proteinHypothetical protein2194187FLJ12806AF131842KIAA1857netrin G2Hypothetical protein, EGF-like2204188domain, Laminin EGF-like domain,Neurogenesis, Glycoprotein, GPI-anchor, Membrane, Signal, Repeat,LipoproteinAF131859PAsulfide quinoneOxidoreductase, Flavoprotein, FAD,2214189reductase-likeNADP, Mitochondrion, Transit(yeast)peptide, PolymorphismAF134404FADS3fatty acid desaturase 3Heme2224190AF146277CD2APCD2-associatedSH3 domain, SH3-binding,2234191proteinPhosphorylation, Coiled coil, RepeatAF152338PCDHGC4protocadherinCalcium, Calcium-binding, Cell2244192gamma subfamily C, 3adhesion, Glycoprotein,Transmembrane, Alternativesplicing, Repeat, Signal, MultigenefamilyAF152339PCDHGC5protocadherinCalcium, Calcium-binding, Cell2254193gamma subfamily C, 3adhesion, Glycoprotein,Transmembrane, Alternativesplicing, Repeat, Signal, MultigenefamilyAF155107FLJ11806nuclear proteinPlasmid, Hypothetical protein2264194UKp68AF156603WBSCR14Williams BeurenTranscription regulation, Repressor,2274195syndromeNuclear protein, DNA-binding,chromosome regionWilliams-Beuren syndrome,14Alternative splicingAF161339ARHGAP9Rho GTPaseHypothetical protein, SH3 domain2284196activating protein 9AF161417DKFZp564D177nipsnap homolog 3AHypothetical protein2294197(C. elegans)AF161442HSPC324Similar to HSPC3242304198(LOC389811),mRNAAF167706CRIM1cysteine-rich motorSignal2314199neuron 1AF187859HSPBP1hsp70-interactingHypothetical protein2324200proteinAF202063FGFR4fibroblast growthATP-binding, Immunoglobulin2334201factor receptor 4domain, Kinase, Receptor,Transferase, Tyrosine-proteinkinase, Glycoprotein,Phosphorylation, Transmembrane,Repeat, Signal, Polymorphism, 3D-structureAF2099317h3hypothetical proteinHypothetical protein2344202FLJ13511AF212842LILRA3leukocyte Ig-likeReceptor, Repeat, Signal, Immune2354203receptor 9response, Immunoglobulin domain,Glycoprotein, Antigen, Multigenefamily, PolymorphismAF217798NDEL1nudE nuclearHypothetical protein2364204distribution gene Ehomolog like 1 (A. nidulans)AF220417LGTNligatinMembrane, Alternative splicing2374205AF222694LGALS12lectin, galactoside-Galectin, Lectin, Repeat, Nuclear2384206binding, soluble, 12protein, Alternative splicing(galectin 12)AF227924SIGLEC9sialic acid binding Ig-Cell adhesion, Lectin, Antigen,2394207like lectin 9Transmembrane, Signal,Glycoprotein, Immunoglobulindomain, Repeat, PolymorphismAF228704GSRglutathioneFAD, Flavoprotein, Oxidoreductase,2404208reductaseRedox-active center, NADP,Acetylation, Alternative initiation,Mitochondrion, Transit peptide, 3D-structure, PolymorphismAF232216PIH1Homo sapiens2414209pregnancy-inducedhypertensionsyndrome-relatedprotein (PIH1)mRNA, partial cds.AF237413RAP1GDS1RAP1, GTP-GDPGTPase activation, Repeat,2424210dissociationAlternative splicingstimulator 1AF241831HABP4hyaluronan bindingHypothetical protein2434211protein 4AF242771Mesenchymal stem2444212cell protein DSC96mRNA, partial cdsAF244088ZNF16zinc finger protein 16Hypothetical protein, Metal-binding,2454213(KOX 9)Nuclear protein, Zinc, Zinc-finger,Transcription regulation, DNA-binding, RepeatAF246221ITM2Bintegral membraneHypothetical protein,2464214protein 2BTransmembrane, Signal-anchor,Disease mutation, Amyloid,DeafnessAF257175PECIperoxisomal D3,D2-Isomerase, Peroxisome,2474215enoyl-CoAHypothetical proteinisomeraseAF260261ABI-2abl interactor 2Kinase, SH3 domain2484216AF272357NPDC1neural proliferation,Signal, Transmembrane,2494217differentiation andHypothetical proteincontrol, 1AI076473_RCrap2 interactingHypothetical protein2504218protein xAI282511_RCPTRFhypothetical proteinHypothetical protein2514219FLJ10534AI286310_RCHSPA5qu91g07.x1ATP-binding, Endoplasmic reticulum,2524220NCI_CGAP_Gas4SignalHomo sapiens cDNAcloneIMAGE: 1979484 3′similar togb: M19645_cds1 78 KDGLUCOSEREGULATEDPROTEINPRECURSOR(HUMAN); mRNAsequence.AI339981_RChypothetical protein2534221LOC153346AI347139_RChypothetical protein2544222MGC39372AI355990_RCqy51g12.x12554223NCI_CGAP_Brn23Homo sapiens cDNAcloneIMAGE: 2015590 3′,mRNA sequence.AI434777_RCCDNA FLJ44280 fis,2564224cloneTRACH2001684AI493593_RCth39c02.x12574225NCI_CGAP_Pan1Homo sapiens cDNAcloneIMAGE: 2120642 3′,mRNA sequence.AI668686_RCFLJ38281hypothetical proteinHypothetical protein, Metal-binding,2584226FLJ38281Zinc, Zinc-fingerAI677876_RCCDNA clone2594227IMAGE: 4648334,partial cdsAI695056_RCSarcoma antigen2604228NY-SAR-79 mRNA,partial cdsAI928427_RCTranscribed2614229sequencesAJ000480C8FWphosphoproteinATP-binding, Receptor, Transferase2624230regulated bymitogenic pathwaysAJ010228RFPL1ret finger protein-like 1Zinc-finger, Metal-binding2634231AJ010842NTPBPXPA binding protein 1GTP-binding2644232AJ011414plexin-plexin B1Hypothetical protein, Receptor,2654233B1/SEPSignalAJ133115THG-1TSC-22-likeHypothetical protein, Transcription2664234regulation, Repressor, NuclearproteinAJ225028GABBR1gamma-aminobutyricHypothetical protein, G-protein2674235acid (GABA) Bcoupled receptor, Postsynapticreceptor, 1membrane, Repeat, Signal,Transmembrane, Coiled coil, Sushi,Glycoprotein, Alternative splicing,Polymorphism, ReceptorAJ243107APAF1Homo sapiensApoptosis, ATP-binding, Repeat,2684236mRNA for apoptoticWD repeat, Alternative splicing, 3D-protease activatingstructurefactor-1 (Apaf-1gene) (short form).AJ249377IGHMimmunoglobulinImmunoglobulin domain,2694237lambda joining 3Immunoglobulin C region,Glycoprotein, Repeat, Pyrrolidonecarboxylic acid, Polymorphism,Membrane, Hypothetical protein,Receptor, T-cell, SignalAJ270996TRPM5transient receptorIonic channel, Transmembrane2704238potential cationchannel, subfamilyM, member 5AJ271684CLECSF5C-type (calciumTransmembrane, Lectin2714239dependent,carbohydrate-recognition domain)lectin, superfamilymember 5AJ272057STRAIT11499MID1 interactingHypothetical protein2724240G12-like proteinAK000001FLJ00001chromosome 9 openHypothetical protein2734241reading frame 28AK000004FGD3FGD1 family,2744242member 3AK000007FLJ00007hypothetical proteinSH3 domain2754243FLJ00007AK000014HYPEHuntingtinHypothetical protein2764244interacting protein EAK000035FLJ22390hypothetical proteinHypothetical protein2774245FLJ22390AK000168KIAA1919Homo sapiens cDNAHypothetical protein2784246FLJ20161 fis, cloneCOL09252, highlysimilar to L33930Homo sapiens CD24signal transducermRNA.AK000175hypothetical protein2794247LOC93444AK000212FLJ10140tRNA (5-Hypothetical protein, Transferase,2804248methylaminomethyl-Methyltransferase, tRNA processing2-thiouridylate)-methyltransferase 1AK000216FLJ20209hypothetical protein2814249FLJ20209AK000242RALGDSral guanineGuanine-nucleotide releasing factor,2824250nucleotide3D-structure, Hypothetical proteindissociationstimulatorAK000260CDK5RAP3Homo sapiens cDNA2834251FLJ20253 fis, cloneCOLF6895.AK000354KIAA1892KIAA1892Hypothetical protein, Repeat, WD2844252repeatAK000425FLJ25555hypothetical proteinHypothetical protein2854253FLJ25555AK000435LOC90987zinc finger proteinHypothetical protein, Metal-binding,2864254251Nuclear protein, Zinc, Zinc-fingerAK000539DKFZP564K0822hypothetical proteinHypothetical protein2874255DKFZp564K0822AK000552WDR5WD repeat domain 5Hypothetical protein, WD repeat,2884256RepeatAK000617NFRKBhypothetical proteinHypothetical protein, Ligase, Ubl2894257LOC92912conjugation pathwayAK000660cyclin-dependent2904258kinase 6AK000684FLJ22104hypothetical proteinHypothetical protein2914259FLJ22104AK000689CLONE24945arrestin domainHypothetical protein2924260containing 2AK000703FLJ20696hypothetical proteinHypothetical protein2934261FLJ20696AK000729solute carrier familyHypothetical protein294426236 (proton/aminoacid symporter),member 1AK000757BCL2L1sortilin 1Apoptosis, Mitochondrion,2954263Alternative splicing,Transmembrane, 3D-structureAK000787CDNA FLJ20780 fis,2964264clone COL04256AK000803hypothetical protein2974265LOC90624AK000808MGC4796Ser/Thr-like kinaseHypothetical protein, ATP-binding,2984266Kinase, Serine/threonine-proteinkinase, TransferaseAK000822DKFZP564M182DKFZP564M182Hypothetical protein2994267proteinAK000824TCTAT-cell leukemia3004268translocation alteredgeneAK000838KIAA1295KIAA1295 proteinHypothetical protein3014269AK000933opsin 3Photoreceptor, Retinal protein,3024270(encephalopsin,Transmembrane, Lipoprotein,panopsin)Palmitate, G-protein coupledreceptor, GTPase activationAK000939hypothetical protein3034271LOC286272AK0009673PAPphosphatidylinositol-Hypothetical protein30442723-phosphateassociated proteinAK001022ISL2ISL2 transcriptionHomeobox, DNA-binding,3054273factor,Developmental protein, NuclearLIM/homeodomain,protein, Repeat, LIM domain, Metal-(islet-2)binding, Zinc, Multigene familyAK001036MAD, mothersTranscription regulation, Multigene3064274againstfamily, Phosphorylationdecapentaplegichomolog 5(Drosophila)AK001069UPF3ACDNA FLJ10207 fis,3074275cloneHEMBA1005475AK001163PAICSphosphoribosylaminoimidazoleMultifunctional enzyme, Purine3084276carboxylase,biosynthesis, Ligase, Lyase,phosphoribosylaminoimidazoleDecarboxylasesuccinocarboxamidesynthetaseAK001166FLJ11252HBxAgHypothetical protein3094277transactivatedprotein 1AK001228chromosome 6 open3104278reading frame 107AK001319C8FWphosphoproteinATP-binding, Receptor, Transferase3114279regulated bymitogenic pathwaysAK001362ESDNendothelial andHypothetical protein3124280smooth muscle cell-derived neuropilin-like proteinAK001394hypothetical protein3134281DKFZp762K222AK001452FLJ10839Homo sapiens cDNAHypothetical protein3144282FLJ10590 fis, cloneNT2RP2004392,weakly similar toMNN4 PROTEIN.AK001469GNPNAT1glucosamine-Hypothetical protein, Transferase3154283phosphate N-acetyltransferase 1AK001478ARHUras homolog geneGTP-binding, Lipoprotein,3164284family, member UPrenylationAK001492FLJ10637hypothetical proteinHypothetical protein3174285FLJ10637AK001499FLJ10637hypothetical proteinHypothetical protein3184286FLJ10637AK001503CDNA FLJ10641 fis,Metal-binding, Zinc, Zinc-finger3194287cloneNT2RP2005748AK001526DKFZp667B1218hypothetical proteinHypothetical protein3204288DKFZp667B1218AK001536Human full-lengthPlasmid3214289cDNA 5-PRIME endof cloneCS0DK007YB08 ofHeLa cells of Homosapiens (human)AK001539TEM6tensin-like SH2Hypothetical protein3224290domain containing 1AK001565AP3M1adaptor-relatedGolgi stack, Protein transport,3234291protein complex 3,Transport, Hypothetical proteinmu 1 subunitAK001579ARAP3ARF-GAP, RHO-Hypothetical protein3244292GAP, ankyrin repeatand plekstrinhomology domains-containing protein 3AK001612hypothetical protein3254293LOC90784AK001630ETS1v-etsProto-oncogene, Nuclear protein,3264294erythroblastosisTranscription regulation, DNA-virus E26 oncogenebinding, Phosphorylation, Alternativehomolog 1 (avian)splicing, 3D-structureAK001731MGC17943hypothetical proteinHypothetical protein3274295MGC17943AK001758THOC2THO complex 2Transport, mRNA transport, mRNA3284296processing, mRNA splicing, Nuclearprotein, RNA-binding, AlternativesplicingAK001822chromosome 9 openHypothetical protein3294297reading frame 37AK001913CL25084XTP3-transactivatedHypothetical protein3304298protein BAK001980ADPRTL2ADP-Transferase, Glycosyltransferase,3314299ribosyltransferaseNAD, DNA-binding, Nuclear protein,(NAD+; poly(ADP-Alternative splicingribose) polymerase)-like 2AK002039MRVI1murine retrovirus3324300integration site 1homologAK002081FLJ10287hypothetical proteinHypothetical protein3334301FLJ10287AK002141PIK4CAHomo sapiens cDNATransferase, Kinase3344302FLJ11279 fis, clonePLACE1009444,highly similar toPHOSPHATIDYLINOSITOL4-KINASEALPHA (EC2.7.1.67).AK002146hypothetical protein3354303LOC153684AK002174KLHL5kelch-like 5Cytoskeleton, Actin-binding, Repeat,3364304(Drosophila)Kelch repeat, Alternative splicingAL049232Homo sapiens3374305mRNA; cDNADKFZp564P1816(from cloneDKFZp564P1816).AL049266Homo sapiens3384306mRNA; cDNADKFZp564F093(from cloneDKFZp564F093).AL049279MRNA; cDNA3394307DKFZp564I083(from cloneDKFZp564I083)AL049299DJ465N24.2.1hypothetical proteinHypothetical protein3404308dJ465N24.2.1AL049309SFRS12splicing factor,Nuclear protein, mRNA processing,3414309arginine/serine-richmRNA splicing, Spliceosome,12Alternative splicingAL049365FTLhypothetical proteinAcetylation, Iron storage, Multigene3424310MGC50853familyAL049381pre-B-cell leukemiaTranscription regulation, DNA-3434311transcription factor 1binding, Nuclear protein, Activator,Repressor, Homeobox, Proto-oncogene, Chromosomaltranslocation, Alternative splicing,Steroidogenesis, Sexualdifferentiation, 3D-structureAL049397CGI-146 proteinHypothetical protein3444312AL049415ADAM19a disintegrin andHydrolase, Metalloprotease, Zinc,3454313metalloproteinaseSignal, Glycoprotein, Zymogen,domain 19 (meltrinTransmembrane, EGF-like domain,beta)SH3-binding, Alternative splicing,Hypothetical proteinAL049431FLJ20619hypothetical proteinHypothetical protein3464314FLJ20619AL049450hypothetical protein3474315LOC339287AL049471AT rich interactiveHypothetical protein3484316domain 5B (MRF1-like)AL049962hypothetical protein3494317LOC286148AL049963LOC64116solute carrier familyHypothetical protein350431839 (zinc transporter),member 8AL050002hypothetical proteinHypothetical protein3514319LOC169611AL050021solute carrier familyHypothetical protein,35243207 (cationic aminoTransmembrane, Glycoprotein,acid transporter, y+Transport, Amino-acid transport,system), member 1ReceptorAL050022DKFZP564D116DKFZP564D116Hypothetical protein3534321proteinAL050050TULIP1GTPase activatingHypothetical protein3544322RANGAP domain-like 2 pseudogeneAL050060DKFZP566H073DKFZP566H073Hypothetical protein, Metal-binding,3554323proteinZinc, Zinc-fingerAL050091GRINL1Aglutamate receptor,Hypothetical protein, Receptor3564324ionotropic, N-methylD-aspartate-like 1AAL050126LAP1Blamina-associatedHypothetical protein3574325polypeptide 1BAL050148sorting nexin 1Transport, Protein transport, Golgi3584326stack, Alternative splicingAL050163PIK3APhematopoietic cellHypothetical protein,3594327signal transducerTransmembraneAL050164CDYLchromodomainHypothetical protein, Nuclear protein3604328protein, Y-likeAL050170SLC26A6solute carrier familyHypothetical protein,361432926, member 6Transmembrane, Alternativesplicing, PolymorphismAL050173C21orf25chromosome 21Hypothetical protein3624330open reading frame25AL050217BRD2dehydrogenase/reductaseOxidoreductase3634331(SDR family)member 1AL050346C22orf3chromosome 22Hypothetical protein3644332open reading frame 3AL079294MRNA full lengthHypothetical protein3654333insert cDNA cloneEUROIMAGE362780AL079298MCCC2methylcrotonoyl-Mitochondrion, Transit peptide,3664334Coenzyme ALigase, Disease mutation,carboxylase 2 (beta)Alternative splicingAL080110progestin andHypothetical protein3674335adipoQ receptorfamily member IIIAL080114chromosome 10Hypothetical protein3684336open reading frame72AL080125ZNF20zinc finger protein 20Hypothetical protein, Metal-binding,3694337(KOX 13)Nuclear protein, Zinc, Zinc-finger,Transcription regulation, DNA-binding, RepeatAL080156DKFZP434J214TCDD-inducibleHypothetical protein3704338poly(ADP-ribose)polymeraseAL080169DKFZP434C171DKFZP434C171Hypothetical protein3714339proteinAL080182N-deacetylase/N-Hypothetical protein, Transferase,3724340sulfotransferaseTransmembrane, Glycoprotein, Golgi(heparanstack, Signal-anchorglucosaminyl) 2AL080192hypothetical proteinHypothetical protein3734341LOC253782AL096745TBCDtubulin-specificHypothetical protein3744342chaperone dAL109669IL16interleukin 16Cytokine, Chemotaxis, Repeat, 3D-3754343(lymphocytestructurechemoattractantfactor)AL109693FLJ12587hypothetical proteinHypothetical protein3764344FLJ12587AL109695solute carrier organicTransmembrane, Transport, Ion3774345anion transportertransport, Glycoproteinfamily, member 3A1AL109699MRNA full lengthHypothetical protein3784346insert cDNA cloneEUROIMAGE375854AL109705MRNA full length3794347insert cDNA cloneEUROIMAGE 73337AL109786WDR9chromosome 21Bromodomain, Repeat, WD repeat3804348open reading frame107AL109817FTCDformiminotransferaseHypothetical protein, Transferase,3814349cyclodeaminaseLyase, Histidine metabolism,Multifunctional enzyme, Pyridoxalphosphate, Folate-binding,Alternative splicing, Diseasemutation, PolymorphismAL110152CD109 antigen (GovHypothetical protein3824350platelet alloantigens)AL110188ZNF10zinc finger protein 10Hypothetical protein, Metal-binding,3834351(KOX 1)Nuclear protein, Zinc, Zinc-finger,Transcription regulation, DNA-binding, RepeatAL110200Homo sapiens3844352mRNA; cDNADKFZp586B0922(from cloneDKFZp586B0922).AL110202PORIMINpro-oncosis receptorHypothetical protein, Receptor,3854353inducing membraneTransmembraneinjury geneAL110210PTPN23protein tyrosineHydrolase, Hypothetical protein,3864354phosphatase, non-Receptorreceptor type 23AL110218SLBselective LIM bindingHypothetical protein3874355factor, rat homologAL110238RRN3RNA polymerase IInitiation factor, Hypothetical protein3884356transcription factorRRN3AL110262NCBP2nuclear cap bindingTransport, mRNA transport, Nuclear3894357protein subunit 2,protein, RNA-binding, 3D-structure20 kDaAL110277KIAA0916protein associatedHypothetical protein3904358with MycAL117415ADAM33Homo sapiensHypothetical protein, Hydrolase,3914359mRNA; cDNAMetalloprotease, Zinc, Signal,DKFZp434K0521Glycoprotein, Zymogen,(from cloneTransmembrane, EGE-like domain,DKFZp434K0521).Alternative splicing, Integrin,ProteaseAL117435DKFZP434I216DKFZP434I216Hypothetical protein3924360proteinAL117448RAB6IP1RAB6 interactingHypothetical protein3934361protein 1AL117452FTHFSDC1formyltetrahydrofolateHypothetical protein3944362synthetase domaincontaining 1AL117457CFL2cofilin 2 (muscle)Nuclear protein, Actin-binding,3954363Cytoskeleton, Phosphorylation,Alternative splicingAL117458IHPK2inositolHypothetical protein, Kinase3964364hexaphosphatekinase 2AL117462ZFP385zinc finger proteinMetal-binding, Zinc, Zinc-finger,3974365385Hypothetical proteinAL117478AGS3G-protein signallingHypothetical protein3984366modulator 1 (AGS3-like, C. elegans)AL117519hypothetical proteinHypothetical protein, Metal-binding,3994367LOC152485Zinc, Zinc-fingerAL117573DKFZP434F2021DKFZP434F2021Hypothetical protein4004368proteinAL117578DKFZP434C128chromosome 21Hypothetical protein4014369open reading frame30AL117609DKFZp564O0463DKFZP564O0463Hypothetical protein, Repeat, WD4024370proteinrepeatAL117639FLJ12890CCR4-NOTHypothetical protein4034371transcriptioncomplex, subunit 10AL117643activin A receptor,Receptor, Transferase,4044372type IBSerine/threonine-protein kinase,ATP-binding, Transmembrane,Glycoprotein, Signal, Alternativesplicing, Phosphorylation,PolymorphismAL117645EG1endothelial-derivedHypothetical protein4054373gene 1AL117654ARHLDL receptorHypothetical protein4064374adaptor proteinAL122053TRIM3tripartite motif-Zinc-finger, Coiled coil, Alternative4074375containing 3splicingAL122091LOC56965hypothetical proteinHypothetical protein4084376from EUROIMAGE1977056AL122097FLJ12519hypothetical proteinHypothetical protein, Repeat, WD4094377FLJ12519repeatAL122098NICALNEDD9 interactingHypothetical protein, LIM domain,4104378protein with calponinMetal-binding, Zinc, Cytoskeletonhomology and LIMdomainsAL122123MRNA; cDNA4114379DKFZp434M038(from cloneDKFZp434M038)AL133021STAB2stabilin 2EGF-like domain, Laminin EGF-like4124380domain, Hypothetical protein,ReceptorAL133071DKFZp434I1117hypothetical proteinHypothetical protein4134381DKFZp434I1117AL133092DKFZp434I0428dispatched homologHypothetical protein41443821 (Drosophila)AL133094PHF10PHD finger proteinHypothetical protein415438310AL133115cytosolic ovarianBiological rhythms, Electron4164384carcinoma antigen 1transport, Growth regulation,Oxidoreductase, NAD, Membrane,Copper, GlycoproteinAL133116FKBP10Homo sapiensIsomerase, Rotamase, Endoplasmic4174385mRNA; cDNAreticulum, Calcium-binding,DKFZp586I0821Glycoprotein, Phosphorylation,(from cloneRepeat, Signal, Hypothetical proteinDKFZp586I0821).AL133117THO complex 2Transport, mRNA transport, mRNA4184386processing, mRNA splicing, Nuclearprotein, RNA-binding, AlternativesplicingAL133426AKAP13A kinase (PRKA)Kinase, Receptor, cAMP,4194387anchor protein 13Hypothetical proteinAL133572DKFZp434I0535Homo sapiensHypothetical protein4204388mRNA; cDNADKFZp434I0535(from cloneDKFZp434I0535);partial cds.AL133577MRNA; cDNA4214389DKFZp434G0972(from cloneDKFZp434G0972)AL133580SCOCshort coiled-coilHypothetical protein4224390proteinAL133581FLJ25785solute carrier familyHypothetical protein423439139 (zinc transporter),member 13AL133592MGC15548zinc finger proteinHypothetical protein, Metal-binding,4244392496Zinc, Zinc-fingerAL133622KIAA0876jumonji domainHypothetical protein4254393containing 2BAL133632DKFZp434E1818Similar toHypothetical protein, Metal-binding,4264394hypothetical proteinZinc, Zinc-finger(LOC389822),mRNAAL133645hypothetical protein4274395LOC90133AL133662KIAA0913KIAA0913 proteinHypothetical protein4284396AL136549CYFIP2cytoplasmic FMR1Hypothetical protein4294397interacting protein 2AL137273DKFZP434I0714hypothetical proteinHypothetical protein4304398DKFZP434I0714AL137298DNAJB6MRNA; cDNAChaperone, Alternative splicing4314399DKFZp434N2116(from cloneDKFZp434N2116)AL137302TEX27testis expressedHypothetical protein4324400sequence 27AL137397FLJ21820hypothetical proteinHypothetical protein4334401FLJ21820AL137421RBM10RNA binding motifHypothetical protein, Metal-binding,4344402protein 10Zinc, Zinc-finger, RNA-binding,Nuclear protein, RepeatAL137423GU2DEAD (Asp-Glu-Ala-ATP-binding, Helicase, Hydrolase,4354403Asp) box polypeptideHypothetical protein50AL137431WBSCR17Williams-BeurenTransferase, Hypothetical protein4364404syndromechromosome region17AL137442C20orf177chromosome 20Hypothetical protein4374405open reading frame177AL137473C20orf67Homo sapiensAlternative splicing, Hypothetical4384406mRNA; cDNAproteinDKFZp434E1723(from cloneDKFZp434E1723);partial cds.AL137477CDH24cadherin-like 24Hypothetical protein, Calcium,4394407Calcium-binding, Cell adhesion,Glycoprotein, Transmembrane,Repeat, Signal, Multigene family,Alternative splicing, PlasmidAL137480FNBP4formin bindingHypothetical protein4404408protein 4AL137491hypothetical protein4414409LOC148696AL137509DKFZp761A052hypothetical proteinHypothetical protein4424410DKFZp761A052AL137514IHPK2inositolHypothetical protein, Kinase4434411hexaphosphatekinase 2AL137516FLJ22059zinc finger proteinHypothetical protein, Metal-binding,4444412574Zinc, Zinc-finger, Nuclear proteinAL137557KIAA1529KIAA1529Hypothetical protein4454413AL137567KIAA1238KIAA1238 proteinHypothetical protein4464414AL137579SNX26sorting nexin 26Hypothetical protein, Transport,4474415Protein transportAL137597C20orf110chromosome 204484416open reading frame110AL137615MKNK2MAP kinase-Hypothetical protein, ATP-binding,4494417interactingKinase, Serine/threonine-proteinserine/threoninekinase, Transferase, Translationkinase 2regulation, Phosphorylation,Alternative splicingAL137631FBXW5Homo sapiensHypothetical protein, Repeat, WD4504418mRNA; cDNArepeatDKFZp434B205(from cloneDKFZp434B205);partial cds.AL137639KIAA0721TSPY-like 4Hypothetical protein4514419AL137648DKFZP434J1813ER-resident proteinRedox-active center, Hypothetical4524420ERdj5proteinAL137655Homo sapiensHypothetical protein4534421mRNA; cDNADKFZp434B2016(from cloneDKFZp434B2016).AL137662DKFZp434P086hypothetical proteinHypothetical protein, ATP-binding,4544422LOC340371TransferaseAL137663FLJ21791pleckstrin homology-Hypothetical protein4554423like domain, familyB, member 2AL137665TUBGCP6tubulin, gammaMicrotubule, Repeat, Alternative4564424complex associatedsplicingprotein 6AL137667MAPK8Homo sapiensTransferase, Serine/threonine-4574425mRNA; cDNAprotein kinase, ATP-binding,DKFZp434B231Phosphorylation, Alternative splicing(from cloneDKFZp434B231).AL137707LOC55901TPTE and PTENSignal4584426homologous inositollipid phosphatasepseudogeneAL137727C14orf9chromosome 14Hypothetical protein,4594427open reading frame 9Transmembrane, Alternative splicingAL137733hypothetical proteinHypothetical protein4604428LOC284701AL137736Rho guanineHypothetical protein4614429nucleotide exchangefactor (GEF) 19AL137764LOC64744hypothetical proteinHypothetical protein4624430AL133206AL157432TERAchromosome 12Hypothetical protein4634431open reading frame14AL157449LOC84687protein phosphataseHypothetical protein46444321, regulatory subunit9B, spinophilinAL157454FLJ21313HCV NS3-Hypothetical protein4654433transactivatedprotein 2AL157455Clone4664434IMAGE: 5288750,mRNAAL157457PP1628PH domain-Hypothetical protein4674435containing proteinAL157465FLJ20186hypothetical proteinHypothetical protein4684436FLJ20186AL157480SH3BP1lectin, galactoside-GTPase activation, SH3-binding,4694437binding, soluble, 1Hypothetical protein, Galectin,(galectin 1)Lectin, Multigene family, AcetylationAL157484MRNA; cDNA4704438DKFZp762M127(from cloneDKFZp762M127)AL161960FLJ21324chromosome 21Hypothetical protein4714439open reading frame97AL161972ICAM2hypothetical protein3D-structure, Cell4724440FLJ11724adhesion, Glycoprotein, Immunoglobulindomain, Repeat, Signal, TransmembraneAL161977PCTK3PCTAIRE proteinHypothetical protein, ATP-binding,4734441kinase 3Kinase, Serine/threonine-proteinkinase, TransferaseAL161983hypothetical protein4744442MGC39820AL161994HEI10cyclin B1 interactingUbl conjugation pathway, Ligase,4754443protein 1Nuclear protein, Metal-binding, Zinc,Coiled coil, Zinc-finger,Phosphorylation, Ubl conjugationAL162013PLXNA1Homo sapiensHypothetical protein4764444mRNA; cDNADKFZp761P19121(from cloneDKFZp761P19121);partial cds.AL162039MOB1, Mps One4774445Binder kinaseactivator-like 1A(yeast)AL162062LOC91010formin-like 3Hypothetical protein4784446AL353934MUS81MUS81Endonuclease, Hypothetical protein4794447endonucleasehomolog (yeast)AL353952PI4KIIphosphatidylinositolHypothetical protein, Kinase48044484-kinase type IIAL353953FLJ13055lipid phosphateHypothetical protein4814449phosphatase-relatedprotein type 2AL355708NEO1neogenin homolog 1Cell adhesion, Repeat, Signal,4824450(chicken)Transmembrane, Immunoglobulindomain, Glycoprotein, AlternativesplicingAW190932_RCGPIxl66g09.x1Gluconeogenesis, Glycolysis,4834451NCI_CGAP_Pan1Isomerase, Growth factor, Cytokine,Homo sapiens cDNADisease mutation, 3D-structure,cloneHypothetical proteinIMAGE: 2679712 3′,mRNA sequence.AW273216_RCring finger proteinHypothetical protein, Metal-binding,4844452149Zinc, Zinc-fingerAW419203_RCKIAA0601amine oxidaseHypothetical protein4854453(flavin containing)domain 2AW673036_RCPPP1R3Bhypothetical proteinHypothetical protein4864454LOC286044BE671663_RCEVIN2epidermodysplasiaTransmembrane, Hypothetical4874455verruciformis 2proteinBE672528_RCcyclin-dependent4884456kinase 6Contig10037_RChypothetical proteinHypothetical protein4894457DKFZp667C165Contig1007_RCLOC51754hypothetical proteinHypothetical protein4904458LOC283070Contig10162_RCMGC14276hypothetical proteinHypothetical protein4914459MGC14276Contig1030_RCFLJ00026dedicator ofGuanine-nucleotide releasing factor4924460cytokinesis 8Contig10363_RCMRF2AT rich interactiveHypothetical protein4934461domain 5B (MRF1-like)Contig10373_RChypothetical proteinHypothetical protein4944462MGC21854Contig10418_RCTranscribed4954463sequencesContig10429_RCDKFZp434H2111hypothetical proteinHypothetical protein4964464DKFZp434H2111Contig10531_RCmicrotubule-Microtubule, Cytoskeleton, Repeat,4974465associated proteinAlternative splicing, Acetylation,tauPhosphorylation, Glycoprotein,Polymorphism, Disease mutation,Alzheimer's disease, 3D-structure,Hypothetical proteinContig1056_RCLOC57106K562 cell-derivedHypothetical protein4984466leucine-zipper-likeprotein 1Contig1061_RCKIAA0924 proteinHypothetical protein, Metal-binding,4994467Nuclear protein, Zinc, Zinc-fingerContig10629_RCPERQ1PERQ amino acidHypothetical protein5004468rich, with GYFdomain 1Contig1063_RCTRIM33Homo sapiens cDNAHypothetical protein5014469FLJ35131 fis, clonePLACE6008824.Contig10670_RCTranscribed5024470sequencesContig10690_RCspleen tyrosineTransferase, Tyrosine-protein5034471kinasekinase, ATP-binding,Phosphorylation, SH2 domain,Repeat, Alternative splicing, 3D-structureContig10750_RCTranscribed5044472sequencesContig10844_RCCDNA FLJ31150 fis,Hypothetical protein5054473cloneIMR322001534Contig11012_RCleukocyte-derivedAminopeptidase5064474arginineaminopeptidaseContig11075_RCNFASCneurofascinCell adhesion, Repeat, Signal,5074475Transmembrane, Immunoglobulindomain, Glycoprotein, Alternativesplicing, Polymorphism, HypotheticalproteinContig11266_RCTranscribed5084476sequence withmoderate similarityto proteinref: NP_054848.1(H. sapiens)PRO0478 protein[Homo sapiens]Contig112_RCNICE-4NICE-4 proteinHypothetical protein5094477Contig1146_RCLOC90550chromosome 10Hypothetical protein5104478open reading frame42Contig11_RChypothetical proteinHypothetical protein5114479LOC90462Contig12140_RCTranscribed5124480sequencesContig12201_RCsplicing factor,Nuclear protein, RNA-binding,5134481arginine/serine-rich 5mRNA splicing, Alternative splicing,Repeat, Phosphorylation,Polymorphism, PlasmidContig12540_RCTranscribed5144482sequencesContig12750_RChypothetical proteinHypothetical protein5154483LOC257106Contig12755_RCGCN1L1homeodomainTransferase, Serine/threonine-5164484interacting proteinprotein kinase, ATP-binding, Nuclearkinase 2protein, Alternative splicingContig12820_RCFLJ21709nucleotide-bindingHypothetical protein5174485oligomerizationdomains 27Contig12855MAPK8IP2MRNA; cDNAKinase, SH3 domain, Alternative5184486DKFZp434J0428splicing(from cloneDKFZp434J0428)Contig1295_RCMDS033protein F25965Transmembrane, Golgi stack,5194487Endoplasmic reticulumContig13165_RCB4GALT6UDP-Transferase, Glycosyltransferase,5204488Gal:betaGlcNAcGlycoprotein, Transmembrane,beta 1,4-Signal-anchor, Golgi stack,galactosyltransferase,Manganese, Magnesium, Calcium,polypeptide 6Multigene familyContig13387_RCFLJ21458hypothetical proteinHypothetical protein5214489FLJ21458Contig13480_RCTranscribed5224490sequencesContig13510_RCzinc finger proteinHypothetical protein, Metal-binding,5234491325Nuclear protein, Zinc, Zinc-finger,Transcription regulation, DNA-binding, RepeatContig13609_RCTranscribed5244492sequencesContig13643_RCTranscribed5254493sequencesContig1366_RCDC-TM4F2tetraspanin similar toHypothetical protein,5264494TM4SF9TransmembraneContig13766_RCTranscribed5274495sequencesContig1386_RCSEMA4Bsema domain,Transmembrane, Immunoglobulin5284496immunoglobulindomain, Multigene family,domain (Ig),Neurogenesis, Developmentaltransmembraneprotein, Glycoprotein, Signal,domain (TM) andPolymorphismshort cytoplasmicdomain,(semaphorin) 4BContig1389_RCITPR1mitogen-activatedATP-binding, Kinase, Transferase,5294497protein kinase 9Serine/threonine-protein kinase,Phosphorylation, Alternative splicingContig14039_RCFOXE3forkhead box E3Transcription regulation, DNA-5304498binding, Nuclear proteinContig1403_RCLBHlikely ortholog ofHypothetical protein5314499mouse limb-bud andheart geneContig14172vitelliform macularIron storage, Iron, Metal-binding, 3D-5324500dystrophy (Beststructure, Transport, Ion transport,disease, bestrophin)Ionic channel, Chloride channel,Calcium, Alternative splicing,Disease mutation, Polymorphism,Vision, Transmembrane,PhosphorylationContig14197_RCTranscribed5334501sequencesContig1422_RChypothetical proteinHypothetical protein5344502FLJ38426Contig14282_RCTranscribed5354503sequencesContig14433_RCTranscribed5364504sequencesContig1447_RCEFG1mitochondrialElongation factor, Protein5374505elongation factor G1biosynthesis, Mitochondrion, Transitpeptide, GTP-bindingContig14520_RCTranscribed5384506sequencesContig14555_RCTranscribed5394507sequencesContig14581_RCTranscribed5404508sequencesContig14625_RCFLJ22021hypothetical proteinRepeat, WD repeat5414509FLJ22021Contig1462_RCC11orf15chromosome 11Transmembrane5424510open reading frame15Contig14658_RCzx08b09.s15434511Soares_total_fetus_Nb2HF8_9wHomosapiens cDNA cloneIMAGE: 785849 3′,mRNA sequence.Contig14720_RCTranscribed5444512sequencesContig14797_RCTranscribed5454513sequencesContig14899_RCLOC146853LOC1468535464514Contig1505_RCMGC4308hypothetical protein5474515MGC4308Contig151_RCELKSCDNA FLJ31750 fis,Hypothetical protein5484516cloneNT2RI2007406Contig15267_RCTranscribed5494517sequencesContig15281_RCChediak-HigashiProtein transport, Transport, Repeat,5504518syndrome 1WD repeat, Disease mutation,Alternative splicingContig1540_RCACTBserineTransferase, Acyltransferase,5514519palmitoyltransferase,Transmembrane, Pyridoxallong chain basephosphate, Endoplasmic reticulumsubunit 2Contig15580_RCLOC4011245524520(LOC401124),mRNAContig15607_RCTranscribed5534521sequencesContig15635_RCTranscribed5544522sequencesContig15647_RCTranscribed5554523sequencesContig15674_RCTranscribed5564524sequencesContig15898_RCTranscribed5574525sequence with weaksimilarity to proteinref: NP_055301.1(H. sapiens)neuronal threadprotein [Homosapiens]Contig16192_RCTranscribed5584526sequence withmoderate similarityto proteinref: NP_110386.1(H. sapiens) nuclearreceptor bindingfactor-2 [Homosapiens]Contig1619_RCNAPBN-ethylmaleimide-Hypothetical protein5594527sensitive factorattachment protein,betaContig1620_RCPPP1R16Aprotein phosphataseANK repeat, Repeat, Coiled coil,56045281, regulatoryLipoprotein, Prenylation, Membrane(inhibitor) subunit16AContig16217_RCTranscribed5614529sequencesContig1632_RCMGC17921chromosome 14Alternative splicing5624530open reading frame31Contig16376_RCDKFZP564B1162hypothetical proteinHypothetical protein5634531DKFZp564B1162Contig16437_RCTranscribed5644532sequencesContig16440_RCTranscribed5654533sequencesContig16441_RCTranscribed5664534sequencesContig16447_RCC16orf44chromosome 16Hypothetical protein5674535open reading frame44Contig16530_RCTranscribed5684536sequencesContig16736_RCCloneHypothetical protein5694537IMAGE: 5561763,mRNAContig16772_RCTranscribed5704538sequencesContig16786_RCTranscribed5714539sequencesContig1682_RCRCPRab coupling proteinHypothetical protein5724540Contig16908_RCMGC42174hypothetical proteinHypothetical protein5734541MGC42174Contig16931_RCYR-29TGF beta-inducibleNuclear protein5744542nuclear protein 1Contig1699_RCFLJ12438hypothetical proteinHypothetical protein5754543FLJ12438Contig17017_RCTranscribed5764544sequencesContig17084_RCDEAD (Asp-Glu-Ala-ATP-binding, Helicase, Hydrolase,5774545Asp) box polypeptideHypothetical protein31Contig17109_RCSimilar to Protein5784546C20orf27(LOC390690),mRNAContig17356_RChypothetical proteinHypothetical protein5794547FLJ13611Contig17607_RCTranscribed5804548sequencesContig1789_RCLAGYhomeodomain-onlyHypothetical protein, DNA-binding,5814549proteinHomeobox, Nuclear proteinContig178_RCsyntrophin, beta 2Actin-binding, Cytoskeleton,5824550(dystrophin-Microtubule, Calcium-binding,associated proteinCalmodulin-binding, Membrane,A1, 59 kDa, basicPhosphorylation, Repeat,component 2)Polymorphism, Multigene family,Alternative splicingContig17982_RChypothetical proteinHypothetical protein5834551FLJ14624Contig1798_RCMOX2antigen identified byAntigen, Neurone, T-cell, Signal,5844552monoclonal antibodyTransmembrane, ImmunoglobulinMRC OX-2domain, Glycoprotein, AlternativesplicingContig18246_RCoz78a12.x15854553Soares_senescent_fibroblasts_NbHSFHomo sapiens cDNAcloneIMAGE: 1681438 3′,mRNA sequence.Contig18286_RCpellino 3 alphaAlternative splicing5864554Contig18476_RCHomo sapiens, clone5874555IMAGE: 4830091,mRNA.Contig18493_RCoj35b09.s15884556NCI_CGAP_Lu5Homo sapiens cDNAcloneIMAGE: 1500281 3′,mRNA sequence.Contig18504_RCOR52K3Polfactory receptor,Hypothetical protein5894557family 52, subfamilyK, member 3pseudogeneContig19023_RCyf45a10.s2 Soares5904558fetal liver spleen1NFLS Homosapiens cDNA cloneIMAGE: 129786 3′,mRNA sequence.Contig19064_RChypothetical protein5914559LOC340351Contig19127_RCFLJ31295hypothetical proteinMetal-binding, Zinc, Zinc-finger,5924560FLJ31295Hypothetical proteinContig19210_RCTranscribed5934561sequencesContig1924_RCC20orf11chromosome 20Coiled coil5944562open reading frame11Contig19333_RCTranscribed5954563sequencesContig1951GNPATMRNA; cDNATransferase, Acyltransferase,5964564DKFZp686J23256Peroxisome, Membrane, Rhizomelic(from clonechondrodysplasia punctata, DiseaseDKFZp686J23256)mutationContig19700_RCTranscribed5974565sequencesContig19715_RCTranscribed5984566sequencesContig1990_RCLOC92799hypothetical proteinRepeat, WD repeat, Hypothetical5994567BC007653proteinContig19918_RCTranscribed6004568sequencesContig1991_RCPGA5pepsinogen 5, groupHydrolase, Aspartyl protease,6014569I (pepsinogen A)Digestion, Zymogen, Signal,Phosphorylation, 3D-structure,PolymorphismContig19931_RCTranscribed6024570sequencesContig20370_RCTranscribed6034571sequencesContig20391_RCTranscribed6044572sequence withstrong similarity toprotein pir: EFHU1(H. sapiens) EFHU1translationelongation factoreEF-1 alpha-1 chain —humanContig20427_RCTranscribed6054573sequencesContig20600_RCCDNA FLJ34654 fis,6064574cloneKIDNE2018294Contig20617_RCCDNA FLJ34031 fis,6074575cloneFCBBF2003895Contig20830_RCHomo sapiens cDNA6084576FLJ13550 fis, clonePLACE1007111.Contig20843_RCTranscribed6094577sequencesContig20864_RCFLJ22529hypothetical proteinHypothetical protein6104578FLJ22529Contig20913_RCFLJ12785hypothetical proteinHypothetical protein6114579FLJ12785Contig20979_RChypothetical protein6124580MGC35555Contig21098_RCMsx-interacting-zincMultigene family, Zinc-finger,6134581fingerNuclear protein, DNA-binding, Metal-binding, Alternative splicingContig21116_RCTranscribed6144582sequencesContig21200_RCTranscribed6154583sequencesContig21268_RCSimilar to6164584hypothetical proteinFLJ35867(LOC342357),mRNAContig2143_RCKIAA1771dedicator ofHypothetical protein, Guanine-6174585cytokinesis 7nucleotide releasing factor,Alternative splicingContig21627_RCCDNA FLJ39637 fis,Hypothetical protein6184586cloneSMINT2003003Contig21787_RCTranscribed6194587sequencesContig2179_RCFLJ32452hypothetical proteinHypothetical protein6204588FLJ32452Contig21839_RCow70g11.s16214589Soares_fetal_liver_spleen_1NFLS_S1Homo sapiens cDNAcloneIMAGE: 1652228 3′,mRNA sequence.Contig21847_RCKSP37Ksp37 protein6224590Contig21891_RCFLJ13231hypothetical proteinHypothetical protein6234591FLJ13231Contig21904immunoglobulin6244592superfamily, member 2Contig21997_RCTranscribed6254593sequencesContig22003_RCTranscribed6264594sequencesContig22025_RCFLJ10111v-akt murineHypothetical protein, ATP-binding,6274595thymoma viralTransferase, Serine/threonine-oncogene homolog 1protein kinase, Phosphorylation,Nuclear protein, KinaseContig22418_RCPTP4A3protein tyrosine6284596phosphatase typeIVA, member 3Contig22526_RCTranscribed6294597sequencesContig22551_RCTranscribed6304598sequencesContig2263_RCKIAA1949KIAA1949Hypothetical protein6314599Contig22844_RCDKFZp434H2111hypothetical proteinHypothetical protein6324600DKFZp434H2111Contig22901_RCAGENCOURT_66409436334601NIH_MGC_99Homo sapiens cDNAcloneIMAGE: 5434077 5′,mRNA sequence.Contig23240_RChypothetical proteinHypothetical protein6344602FLJ12525Contig23263_RCNR5A1Homo sapiens cDNAReceptor, Transcription regulation,6354603FLJ33539 fis, cloneDNA-binding, Nuclear protein, Zinc-BRAMY2007610,finger, Disease mutation,highly similar toHypothetical proteinSTEROIDOGENICFACTOR 1.Contig23280lecithin-cholesterolCholesterol metabolism, Lipid6364604acyltransferasemetabolism, Transferase,Acyltransferase, Signal,Glycoprotein, Polymorphism,Disease mutationContig23299_RCP5BTG3 associatedHypothetical protein6374605nuclear proteinContig2339_RCFLJ21032stearoyl-CoAHypothetical protein6384606desaturase 4Contig23423_RCTranscribed6394607sequencesContig23525_RCKIAA0140similar to CG9643-Hypothetical protein6404608PAContig23547_RCClone6414609IMAGE: 5214442,mRNAContig23593_RCTranscribed6424610sequencesContig23604_RCcarnitine O-Transferase, Acyltransferase, Fatty6434611octanoyltransferaseacid metabolism, Transport,PeroxisomeContig23667_RCWD repeat andNuclear protein, DNA-binding,6444612HMG-box DNARepeat, WD repeatbinding protein 1Contig24090CDNA FLJ37425 fis,6454613cloneBRAWH2001530Contig24094_RCCDNA FLJ30598 fis,6464614cloneBRAWH2009263Contig24098_RCglutamate receptor,Receptor, Signal, Transmembrane,6474615ionotropic, N-methylPostsynaptic membrane, Calcium,D-aspartate 2DGlycoprotein, Ionic channel,MagnesiumContig2429_RCFLJ40142 proteinHypothetical protein6484616Contig24450_RCTranscribed6494617sequencesContig24453_RCTranscribed6504618sequencesContig24600_RCTranscribed6514619sequencesContig25041_RCyx89b03.s1 Soares6524620melanocyte 2NbHMHomo sapiens cDNAcloneIMAGE: 268877 3′,mRNA sequence.Contig25058_RCTranscribed6534621sequencesContig2505_RCGLTPglycolipid transferTransport, Lipid transport, Repeat,6544622proteinAcetylationContig25107_RCferredoxin 1Metal-binding, Iron-sulfur, Iron, 2Fe—2S,6554623Electron transport,Mitochondrion, Transit peptideContig25126_RCTranscribed6564624sequencesContig2531_RCFLJ12484hypothetical proteinHypothetical protein6574625FLJ12484Contig25332_RCGDF11cytokine inducedNuclear protein, DNA-binding,6584626protein 29 kDaTranscription, Transcriptionregulation, Translation regulationContig25362_RCDKFZP566A1524hypothetical proteinHypothetical protein6594627DKFZp566A1524Contig25429_RCTranscribed6604628sequencesContig25435_RCFLJ10803hypothetical proteinHypothetical protein6614629FLJ10803Contig2544FLJ11526hypothetical proteinHypothetical protein6624630FLJ11526Contig25546_RCCCT6Aitchy homolog E3Ubl conjugation pathway, Ligase,6634631ubiquitin proteinNuclear protein, Repeat,ligase (mouse)Phosphorylation, Alternative splicingContig25595_RCKIAA1618KIAA1618Hypothetical protein6644632Contig256PSMD11wt73b11.x1Proteasome6654633Soares_thymus_NHFThHomo sapienscDNA cloneIMAGE: 2513085 3′similar toTR: Q26195 Q26195PVA1 GENE.;mRNA sequence.Contig25610_RCCDNA FLJ31796 fis,6664634cloneNT2RI2008841Contig25744_RCTranscribed6674635sequencesContig2576_RCDKFZP564O1664hypothetical proteinHypothetical protein6684636DKFZp564O1664Contig25770_RCClone6694637IMAGE: 4817413,mRNAContig25783_RCClone6704638IMAGE: 5555626,mRNAContig2578_RCORF1-FL49putative nuclearNuclear protein6714639protein ORF1-FL49Contig25827_RCFLJ13848hypothetical proteinHypothetical protein6724640FLJ13848Contig2584_RCribonuclease PHydrolase, Nuclear protein, tRNA6734641(14 kD)processingContig25861_RCTranscribed6744642sequencesContig25960_RCDKFZP564B0769chromosome 6 openHypothetical protein6754643reading frame 111Contig26014_RCSYTL3synaptotagmin-like 36764644Contig26019_RCmethionylAminopeptidase, Hypothetical6774645aminopeptidase 2protein, Hydrolase, Cobalt, 3D-structureContig26059_RCTranscribed6784646sequencesContig2608SLC2A4RGSLC2A4 regulatorTranscription regulation, DNA-6794647binding, Nuclear protein, Zinc-finger,Metal-binding, Alternative splicingContig26170_RCTranscribed6804648sequencesContig26332_RCTranscribed6814649sequencesContig263_RCMGC12435chromosome 146824650open reading frame168Contig26405_RCTSLL2immunoglobulinImmunoglobulin domain6834651superfamily, member4CContig26416_RCTranscribed6844652sequencesContig26461_RCTranscribed6854653sequencesContig2647_RCBCAT1branched chainTransferase, Aminotransferase,6864654aminotransferase 1,Hypothetical protein, Branched-chaincytosolicamino acid biosynthesis, PyridoxalphosphateContig2648_RCMGC15407similar to RIKEN6874655cDNA 4931428D14geneContig2657_RCMGC16207hypothetical proteinHypothetical protein6884656MGC16207Contig26622_RCBICBIC transcript6894657Contig26706_RCCDNA FLJ43676 fis,6904658cloneSYNOV4009129Contig26998_RCWD repeat domain 1Repeat, WD repeat, Actin-binding,6914659Cytoskeleton, Alternative splicing,Polymorphism, Hypothetical proteinContig27060_RCTranscribed6924660sequence withmoderate similarityto protein pdb: 1LBG(E. coli) B Chain B,Lactose OperonRepressor Bound To21-Base PairSymmetric OperatorDna, Alpha CarbonsOnlyContig27084_RCCDNA FLJ45493 fis,6934661cloneBRTHA2008598Contig27124_RCCDNA FLJ42250 fis,6944662cloneTKIDN2007828Contig27145_RCTranscribed6954663sequencesContig27228_RCamyloid beta (A4)Hypothetical protein6964664precursor protein-binding, family B,member 1interacting proteinContig2728_RCzinc finger proteinHypothetical protein, Metal-binding,6974665596Zinc, Zinc-fingerContig27338_RCTranscribed6984666sequencesContig27386_RCC7orf13chromosome 7 open6994667reading frame 13Contig27542_RCTranscribed7004668sequencesContig27558_RCFLJ13163MRNA; cDNAHypothetical protein, Kinase7014669DKFZp779J2459(from cloneDKFZp779J2459)Contig27725_RCTranscribed7024670sequencesContig27765_RCpotassium inwardly-Hypothetical protein, Ionic channel,7034671rectifying channel,Ion transport, Voltage-gatedsubfamily J, memberchannel, Transmembrane,15Potassium transportContig27776_RChypothetical proteinHypothetical protein7044672FLJ21106Contig27797_RCDnaJ (Hsp40)Chaperone, Repeat, Zinc, Metal-7054673homolog, subfamilybinding, Prenylation, Lipoprotein,A, member 2Membrane, Multigene familyContig27820_RCTranscribed7064674sequencesContig27837_RCTranscribed7074675sequence with weaksimilarity to proteinref: NP_060265.1(H. sapiens)hypothetical proteinFLJ20378 [Homosapiens]Contig27896_RCHSPC009 protein7084676Contig27915_RCMGC40042hypothetical proteinHypothetical protein7094677MGC40042Contig27977_RCTranscribed7104678sequencesContig28024_RCKIAA0955caspase recruitmentApoptosis, Nuclear protein,7114679domain family,Alternative splicing, Hypotheticalmember 8proteinContig28050_RCHomo sapiens cDNA7124680FLJ35764 fis, cloneTESTI2004906,weakly similar toH. sapiens mRNA forSIRP-beta1.Contig2811_RCC8orf2Homo sapiensTransmembrane, Alternative splicing7134681mRNA; cDNADKFZp667H242(from cloneDKFZp667H242);complete cds.Contig28164_RCTranscribed7144682sequencesContig28181_RCns17h07.s17154683NCI_CGAP_GCB1Homo sapiens cDNAcloneIMAGE: 1183933 3′,mRNA sequence.Contig28229_RCTranscribed7164684sequencesContig2823_RCFLJ23499chromosome 11Hypothetical protein7174685open reading frame 1Contig28286_RCTranscribed7184686sequencesContig28298_RCNUP62UI-H-Bl0p-abm-b-Nuclear protein, Transport,719468704-0-UI.s1Glycoprotein, Coiled coil, Repeat,NCI_CGAP_Sub2PolymorphismHomo sapiens cDNAcloneIMAGE: 2712150 3′,mRNA sequence.Contig28522_RCClone 24653 mRNA7204688sequenceContig28567_RCTranscribed7214689sequencesContig2857_RCDKFZp761G2113hypothetical proteinHypothetical protein7224690DKFZp761G2113Contig28707_RCADAMTS13a disintegrin-like andProtease, Hypothetical protein,7234691metalloproteaseSignal(reprolysin type) withthrombospondin type1 motif, 13Contig28760_RCcyclin-dependent7244692kinase 6Contig28766_RCTranscribed7254693sequencesContig28787_RChypothetical proteinHypothetical protein7264694LOC120526Contig2883_RCRALYCloneRibonucleoprotein, RNA-binding,7274695IMAGE: 5285100,Nuclear protein, Antigen, AlternativemRNAsplicing, PolymorphismContig28947_RCCDC25Acell division cycleCell division, Mitosis, Hydrolase,728469625AAlternative splicing, Multigene family,3D-structure, Hypothetical proteinContig28949Clone7294697IMAGE: 5268292,mRNAContig28996_RCNHL repeat7304698containing 1Contig29171_RCCDNA FLJ11544 fis,7314699cloneHEMBA1002826Contig29207_RCchromosome 207324700open reading frame78Contig29284_RCTranscribed7334701sequencesContig292_RCFLJ22386leucine zipperHypothetical protein7344702domain proteinContig2930_RCDAB2CDNA FLJ35517 fis,Alternative splicing, Phosphorylation7354703cloneSPLEN2000698Contig29349_RCTranscribed7364704sequencesContig29362_RChypothetical proteinHypothetical protein7374705LOC338692Contig29373_RC24b2/STAC2 protein7384706Contig29569_RChypothetical proteinHypothetical protein7394707MGC29898Contig29732_RChypothetical protein7404708LOC338758Contig29749_RCLOC85028PNAS-1237414709Contig29780_RCTranscribed7424710sequencesContig29802_RCprogrammed cellCalcium-binding, Repeat, Apoptosis7434711death 6Contig29860_RCNFAM1NFAT activationHypothetical protein, Signal,7444712molecule 1Transmembrane, Immunoglobulindomain, PhosphorylationContig2986_RCEEG1C1q domainHypothetical protein7454713containing 1Contig29887_RCDKFZp434J0617hypothetical proteinHypothetical protein7464714DKFZp434J0617Contig29890_RCFLJ32449ankyrin repeatHypothetical protein, ANK repeat,7474715domain 23RepeatContig29901_RCproteasomeProteasome, Hydrolase, Protease,7484716(prosome,Acetylation, Alternative splicing,macropain) subunit,Phosphorylation, Threonine proteasealpha type, 3Contig29921_RCFLJ22570Dok-like proteinHypothetical protein7494717Contig29940_RCCMYA1cardiomyopathyHypothetical protein7504718associated 1Contig29954_RCCATSPER2Clone7514719IMAGE: 5294645,mRNAContig29955_RCzj86d08.s17524720Soares_fetal_liver_spleen_1NFLS_S1Homo sapiens cDNAcloneIMAGE: 461775 3′,mRNA sequence.Contig29995_RCTranscribed7534721sequencesContig30052_RCC18B11C18B11 homologHypothetical protein7544722(44.9 kD)Contig30109_RCPRKWNK4protein kinase, lysineHypothetical protein, ATP-binding,7554723deficient 4Transferase, Kinase,Serine/threonine-protein kinaseContig30154_RCTranscribed7564724sequence withmoderate similarityto protein sp: P39194(H. sapiens)ALU7_HUMAN Alusubfamily SQsequencecontaminationwarning entryContig3015_RCpleckstrin homology7574725domain containing,family A(phosphoinositidebinding specific)member 2Contig30209_RCFLJ12649hypothetical proteinHypothetical protein7584726FLJ12649Contig30378_RCFLJ10178hypothetical proteinHypothetical protein7594727FLJ10178Contig30474_RCVITvitrinHypothetical protein7604728Contig30484_RCTranscribed7614729sequencesContig30496_RCZNF219LOC400176Transcription regulation, DNA-7624730(LOC387957),binding, Zinc-finger, Metal-binding,mRNANuclear protein, RepeatContig30736_RCTranscribed7634731sequencesContig30811_RCPRKRAMRNA; cDNAKinase7644732DKFZp686G1498(from cloneDKFZp686G1498)Contig30840_RCLOC63929hypothetical proteinHypothetical protein7654733LOC63929Contig30934_RCMGC33993hypothetical proteinHypothetical protein, Metal-binding,7664734MGC33993Zinc, Zinc-fingerContig3094_RCPINK1PTEN inducedHypothetical protein, ATP-binding,7674735putative kinase 1Kinase, Serine/threonine-proteinkinase, TransferaseContig30977_RChypothetical protein7684736LOC154790Contig30989_RCMGC10744hypothetical proteinHypothetical protein7694737MGC10744Contig31057_RCTranscribed7704738sequencesContig31186_RCHNRPDLheterogeneousNucleocapsid, Ribonucleoprotein7714739nuclearribonucleoprotein D-likeContig31361_RCdedicator ofHypothetical protein, Guanine-7724740cytokinesis 7nucleotide releasing factor,Alternative splicingContig31366_RCLNPEPhypothetical proteinHypothetical protein7734741FLJ39485Contig31421_RCthyroid hormoneProteasome, Ubl conjugation7744742receptor interactorpathway, Ligase12Contig31449_RCTranscribed7754743sequence with weaksimilarity to proteinsp: P39195(H. sapiens)ALU8_HUMAN Alusubfamily SXsequencecontaminationwarning entryContig3147_RCMUM2trafficking proteinTransport, Endoplasmic reticulum,7764744particle complex 1Golgi stack, Disease mutationContig31482_RCTranscribed7774745sequencesContig31495thyroid hormoneAntigen, Golgi stack, Coiled coil,7784746receptor interactorChromosomal translocation,11Hypothetical proteinContig31513_RCTranscribed7794747sequencesContig31525_RCTranscribed7804748sequence with weaksimilarity to proteinref: NP_079364.1(H. sapiens)hypothetical proteinFLJ13241 [Homosapiens]Contig31587_RCHuman full-lengthPlasmid7814749cDNA 5-PRIME endof cloneCS0DK007YB08 ofHeLa cells of Homosapiens (human)Contig31597_RCPDE4DIPchromosome 1Hypothetical protein7824750amplified sequence 3Contig31661_RChypothetical proteinHypothetical protein, Repeat, WD7834751FLJ10385repeatContig31664_RCMGC26979hypothetical proteinHypothetical protein7844752MGC26979Contig31699_RCCDNA FLJ27273 fis,7854753clone TMS00761Contig31740_RCPFN1hypothetical proteinMetal-binding, Zinc, Zinc-finger,7864754LOC285345Transcription regulation, DNA-binding, Nuclear protein, RepeatContig31864_RCFERM domainHypothetical protein7874755containing 3Contig31906_RCsimilar toHypothetical protein7884756hypothetical proteinFLJ13659Contig31911_RChypothetical proteinHypothetical protein7894757LOC349136Contig32027_RCCDNA FLJ46867 fis,7904758cloneUTERU3012293,weakly similar toHomo sapiens zincfinger protein 14(KOX 6) (ZNF14)Contig32059_RCMGC17919zinc finger and BTBZinc, Hypothetical protein, Metal-7914759domain containing 8binding, Zinc-fingerContig32081_RCFull length insert7924760cDNA cloneYP77A07Contig32103_RCClone7934761IMAGE: 4689481,mRNAContig32123_RCSimilar to ataxin 27944762binding protein 1isoform gamma;hexaribonucleotidebinding protein 1(LOC339162),mRNAContig32185_RCintimal thickness-7954763related receptorContig3228_RCVMP1hypothetical proteinHypothetical protein7964764LOC283680Contig32322_RCquaking homolog,Hypothetical protein7974765KH domain RNAbinding (mouse)Contig32323_RChypothetical proteinHypothetical protein7984766FLJ13105Contig32335_RCTranscribed7994767sequencesContig32377_RCubiquitin specificProtease8004768protease 51Contig32431_RCTranscribed8014769sequencesContig3250_RCLOC92399mitochondrialHypothetical protein8024770ribosome recyclingfactorContig32540_RCTranscribed8034771sequencesContig32550_RCZFP93zinc finger proteinTranscription regulation, DNA-8044772235binding, Zinc-finger, Metal-binding,Nuclear protein, RepeatContig32637_RCRAB27A, memberGTP-binding, Lipoprotein,8054773RAS oncogenePrenylation, Alternative splicing,familyDisease mutationContig32757FLJ21069hypothetical proteinHypothetical protein, ANK repeat,8064774FLJ21069RepeatContig32825_RCpolymerase (RNA) III8074775(DNA directed)(32 kD)Contig32920FUBP1nexilin (F actinHypothetical protein8084776binding protein)Contig33062_RCchromosome 17Hypothetical protein8094777open reading frame31Contig3311_RCMGC13186hypothetical proteinHypothetical protein, ATP-binding8104778MGC13186Contig33127_RCSequence 161 from8114779Patent WO0220754.Contig3313FLJ23153likely ortholog ofHypothetical protein8124780mouse tumornecrosis-alpha-induced adipose-related proteinContig33188_RCTranscribed8134781sequencesContig33207_RCTranscribed8144782sequencesContig33224_RCTranscribed8154783sequencesContig33273_RCchromodomainDNA-binding, Helicase, Hypothetical8164784helicase DNAprotein, ATP-binding, Hydrolasebinding protein 1-likeContig3331_RCMKI67IPMKI67 (FHA8174785domain) interactingnucleolarphosphoproteinContig33334_RCTranscribed8184786sequencesContig33369_RCTranscribed8194787sequence with weaksimilarity to proteinref: NP_062553.1(H. sapiens)hypothetical proteinFLJ11267 [Homosapiens]Contig33394_RCFLJ37318ubiquitin specificHypothetical protein8204788protease 54Contig3344MGC2835DEAD (Asp-Glu-Ala-ATP-binding, Helicase, Hydrolase,8214789Asp) box polypeptideHypothetical protein54Contig33442_RCMOB1, Mps OneHypothetical protein8224790Binder kinaseactivator-like 2A(yeast)Contig33464_RCSimilar to bA304I5.18234791(novel lipase)(LOC340654),mRNAContig33540_RCSEMA3Fob92d09.s1Signal, Immunoglobulin domain,8244792NCI_CGAP_GCB1Multigene family, Glycoprotein,Homo sapiens cDNAPolymorphismcloneIMAGE: 1338833 3′,mRNA sequence.Contig33574_RCTranscribed8254793sequencesContig3359_RCneuralized-likeHypothetical protein8264794(Drosophila)Contig33703_RCFLJ21438hypothetical proteinHypothetical protein8274795FLJ21438Contig33741_RCFLJ12428DEP domainHypothetical protein8284796containing 6Contig33760_RCchromosome 9 open8294797reading frame 71Contig33790_RCjun dimerizationDNA-binding, Nuclear protein8304798protein 2Contig33810_RCFLJ31528hypothetical proteinHypothetical protein8314799FLJ31528Contig33831_RCTranscribed8324800sequencesContig33852_RCOPRL1opiate receptor-like 1G-protein coupled receptor,8334801Transmembrane, Glycoprotein,Phosphorylation, Lipoprotein,Palmitate, Alternative splicingContig33888_RCow44c09.x18344802Soares_parathyroid_tumor_NbHPAHomo sapiens cDNAcloneIMAGE: 1649680 3′,mRNA sequence.Contig3390_RCFLJ12619chromosome 6 openHypothetical protein8354803reading frame 62Contig33951_RCnuclear poreNuclear protein, Transport8364804complex proteinContig33967_RCTranscribed8374805sequencesContig33987hypothetical proteinHypothetical protein8384806KIAA1109Contig33996_RCTranscribed8394807sequencesContig34019_RCMGC15827hypothetical proteinHypothetical protein8404808MGC15827Contig34051_RCTranscribed8414809sequencesContig34090_RCTranscribed8424810sequencesContig340_RCPPP1R15Bprotein phosphataseHypothetical protein84348111, regulatory(inhibitor) subunit15BContig34118_RCTranscribed8444812sequencesContig34231_RCyd77f12.s1 Soares8454813fetal liver spleen1NFLS Homosapiens cDNA cloneIMAGE: 114287 3′,mRNA sequence.Contig34286_RCTranscribed8464814sequencesContig34291_RCnuclear receptorTranscription regulation, Receptor,8474815subfamily 3, groupTrans-acting factor, Nuclear protein,C, member 1DNA-binding, Steroid-binding, Zinc-(glucocorticoidfinger, Phosphorylation, Ublreceptor)conjugation, Alternative initiation,Alternative splicing, Polymorphism,Disease mutationContig34302_RChypothetical protein8484816LOC150166Contig34303_RCSFXN5sideroflexin 5Transport, Iron transport, Iron,8494817Mitochondrion, TransmembraneContig34350_RCCDNA FLJ45384 fis,8504818cloneBRHIP3021987Contig34470_RCsimilar to kinesinHypothetical protein8514819family member 21A;N-5 kinesinContig34554_RCCDNA FLJ33367 fis,8524820cloneBRACE2005661Contig34593_RCTranscribed8534821sequencesContig34607_RCym49g02.s1 Soares8544822infant brain 1NIBHomo sapiens cDNAclone IMAGE: 515863′, mRNA sequence.Contig34634_RCGCN1L1homeodomainTransferase, Serine/threonine-8554823interacting proteinprotein kinase, ATP-binding, Nuclearkinase 2protein, Alternative splicingContig34672_RCTranscribed8564824sequencesContig3474_RCCDNA: FLJ225418574825fis, clone HSI00130Contig34768_RCchromosome 21Hypothetical protein8584826open reading frame59Contig34779_RCSH3-domain kinaseSH3 domain, Repeat, Membrane,8594827binding protein 1Nuclear protein, Coiled coil,Polymorphism, Alternative splicingContig34880_RCTranscribed8604828sequencesContig3495_RCMGC45416hypothetical proteinHypothetical protein8614829MGC45416Contig34983_RCTranscribed8624830sequencesContig34998_RCTMLHECDNA FLJ25895 fis,Hypothetical protein8634831clone CBR03553Contig34999_RCperiplakinKeratinization, Repeat, Coiled coil,8644832Cytoskeleton, Structural proteinContig35002_RCFLJ12994hypothetical proteinHypothetical protein8654833FLJ12994Contig35018_RCzr44a03.s18664834Soares_NhHMPu_S1 Homo sapienscDNA cloneIMAGE: 666220 3′,mRNA sequence.Contig35043Transcribed8674835sequencesContig35052_RCpituitary tumor-Transmembrane, Nuclear protein8684836transforming 1interacting proteinContig35076_RCSequence 226 from8694837Patent WO0220754.Contig35094_RCFLJ21478NOD9 proteinHypothetical protein8704838Contig35163_RCSimilar to8714839hypothetical proteinMG11009.4(LOC285344),mRNAContig35182_RCqb88b05.x18724840Soares_fetal_heart_NbHH19WHomosapiens cDNA cloneIMAGE: 1707153 3′,mRNA sequence.Contig35187_RCARL4ADP-ribosylationGTP-binding, Multigene family,8734841factor-like 4Nuclear proteinContig35251_RCCDNA: FLJ227198744842fis, clone HSI14307Contig35425_RChypothetical proteinHypothetical protein8754843LOC285831Contig35435_RCFLJ23447hypothetical proteinHypothetical protein8764844FLJ23447Contig35576_RCTranscribed8774845sequencesContig35608_RCdf54a02.y1 Morton8784846Fetal Cochlea Homosapiens cDNA cloneIMAGE: 2487051 5′,mRNA sequence.Contig35635_RCTAGAPT-cell activationHypothetical protein8794847GTPase activatingproteinContig35661_RCDSCR1L2Down syndromeAlternative splicing8804848critical region gene1-like 2Contig35685_RCFLJ13117spermatogenesisHypothetical protein8814849associated, serine-rich 2Contig35700_RCCDNA clone8824850IMAGE: 6702802,partial cdsContig35713_RCFIS8834851Contig35799_RCcentaurin, beta 2GTPase activation, Repeat, ANK8844852repeat, Zinc-fingerContig35874_RCTranscribed8854853sequencesContig35896_RCsignal transducerHypothetical protein, Repeat, WD8864854and activator ofrepeattranscription 3interacting protein 1Contig35940KIAA1733RPEL repeatHypothetical protein8874855containing 1Contig35958_RCMGC13071hypothetical proteinHypothetical protein, Metal-binding,8884856MGC13071Nuclear protein, Zinc, Zinc-fingerContig35976_RCfamily with sequenceSignal8894857similarity 3, member CContig3597_RCLENG5leukocyte receptorReceptor, Hypothetical protein8904858cluster (LRC)member 5Contig36020_RCMGC15634hypothetical proteinHypothetical protein8914859MGC15634Contig36075_RCTranscribed8924860sequencesContig36104_RCCCT6AIaa10b09.x1 8 5Chaperone, ATP-binding, Multigene8934861week embryofamilyanterior tongue 8 5EAT Homo sapienscDNA 3′, mRNAsequence.Contig36106_RCNCLhypothetical proteinHypothetical protein8944862LOC157697Contig36125_RCTranscribed8954863sequencesContig36129_RCMGC4707hypothetical proteinHypothetical protein8964864LOC283989Contig3612_RCKIAA1802chromosome 13Hypothetical protein, Metal-binding,8974865open reading frame 8Zinc, Zinc-fingerContig36152_RCsterile alpha motifHypothetical protein, ANK repeat,8984866domain containing 6RepeatContig36169_RCDKFZp547E052hypothetical proteinHypothetical protein8994867DKFZp547E052Contig36178_RCsialyltransferase 9Transferase, Glycosyltransferase,9004868(CMP-Glycoprotein, Transmembrane,NeuAc:lactosylceramideSignal-anchor, Golgi stackalpha-2,3-sialyltransferase;GM3 synthase)Contig36190_RCTranscribed9014869sequencesContig36193_RCinositol 1,4,5-Receptor, Transmembrane,9024870triphosphatePhosphorylation, Ionic channel, Ionreceptor, type 1transport, Calcium channelContig36195_RCFull length insert9034871cDNA cloneZD73D05Contig3626_RCFLJ13855hypothetical proteinHypothetical protein, Ligase, Ubl9044872FLJ13855conjugation pathwayContig36323_RCSFXN5sideroflexin 5Transport, Iron transport, Iron,9054873Mitochondrion, TransmembraneContig36359_RCTranscribed9064874sequencesContig36369_RCwe24d02.x19074875NCI_CGAP_Lu24Homo sapiens cDNAcloneIMAGE: 2342019 3′,mRNA sequence.Contig36409_RCTranscribed9084876sequencesContig36512_RCTranscribed9094877sequencesContig36525ARXaristaless relatedHomeobox, DNA-binding,9104878homeoboxDevelopmental protein, Nuclearprotein, Transcription regulation,Disease mutation, Triplet repeatexpansion, EpilepsyContig36617_RCchromosome 6 open9114879reading frame 182Contig36622_RCTranscribed9124880sequencesContig36628HANP19134881Contig36634_RCFLJ39514sec1 family domainHypothetical protein9144882containing 2Contig36720_RCTranscribed9154883sequencesContig36761_RCFLJ23403hypothetical proteinHypothetical protein9164884FLJ23403Contig36803_RCFLJ13952sorting nexin 22Hypothetical protein, Transport,9174885Protein transportContig36805_RCMGC15435zinc finger, BEDZinc-finger9184886domain containing 3Contig36810CDNA FLJ37425 fis,9194887cloneBRAWH2001530Contig36876_RCHomo sapiens cDNA9204888FLJ32044 fis, cloneNTONG2000985.Contig36879_RCClone9214889IMAGE: 4753714,mRNAContig36888_RCsuppression ofHypothetical protein9224890tumorigenicity 7 likeContig36939_RCTranscribed9234891sequencesContig3695_RCMGC17330HGFL geneHypothetical protein, Glycoprotein,9244892KringleContig36973_RCAGMATHomo sapiensPutrescine biosynthesis, Spermidine9254893cDNA: FLJ23384 fis,biosynthesis, Hydrolase,clone HEP16468.Manganese, Mitochondrion, TransitpeptideContig36976_RCDIBD1disrupted in bipolarHypothetical protein9264894affective disorder 1Contig36997_RCbiorefzinc finger proteinTranscription regulation, DNA-9274895481binding, Zinc-finger, Metal-binding,Nuclear protein, RepeatContig37016_RCING5inhibitor of growthHypothetical protein9284896family, member 5Contig37025_RCCDNA FLJ41484 fis,9294897cloneBRTHA2003030Contig37029_RCFLJ23153likely ortholog ofHypothetical protein9304898mouse tumornecrosis-alpha-induced adipose-related proteinContig37037_RCchromosome 139314899open reading frame25Contig37082_RCMGC2408hypothetical proteinHypothetical protein9324900MGC2408Contig37140_RCmembrane protein,Hypothetical protein, SH3 domain9334901palmitoylated 7(MAGUK p55subfamily member 7)Contig37142_RCHomo sapiens cDNA9344902FLJ12163 fis, cloneMAMMA1000594.Contig37219MDN1MDN1, midasinChaperone, ATP-binding, Repeat,9354903homolog (yeast)Nuclear proteinContig37262CloneHypothetical protein9364904IMAGE: 5263527,mRNAContig37300_RCKIAA1904KIAA1904 proteinHypothetical protein9374905Contig37306_RCMUC16mucin 16Hypothetical protein9384906Contig3734_RCRPS8CloneRibosomal protein9394907IMAGE: 4249217,mRNAContig37361_RCTranscribed9404908sequencesContig37364_RCTranscribed9414909sequencesContig37368_RCnemo like kinaseATP-binding, Kinase,9424910Serine/threonine-protein kinase,TransferaseContig37569_RCCDNA FLJ26339 fis,9434911clone HRT02975Contig37660_RCADAM6a disintegrin and9444912metalloproteinasedomain 6Contig37736_RCRAD1TranscribedHypothetical protein, Ribosome9454913sequence withbiogenesis, Nuclear protein, Cellmoderate similaritycycle, Exonucleaseto proteinref: NP_060312.1(H. sapiens)hypothetical proteinFLJ20489 [Homosapiens]Contig37763_RCTranscribed9464914sequence withmoderate similarityto proteinref: NP_002945.1(H. sapiens)ubiquitin andribosomal proteinS27a precursor;ubiquitin carboxylextension protein 80;40S ribosomalprotein S27a;ubiquitin; ubiquitin-CEP80 [Homosapiens]Contig37764_RCqa65f01.x19474915Soares_fetal_heart_NbHH19WHomosapiens cDNA cloneIMAGE: 1691641 3′,mRNA sequence.Contig37895_RCyh88d01.s1 Soares9484916placenta Nb2HPHomo sapiens cDNAcloneIMAGE: 136801 3′,mRNA sequence.Contig37950_RCqz91d12.x19494917Soares_pregnant_uterus_NbHPUHomosapiens cDNA cloneIMAGE: 2041943 3′,mRNA sequence.Contig37958KAI1hypothetical proteinGlycoprotein, Transmembrane,9504918LOC284023AntigenContig37991_RCLOC133308hypothetical proteinHypothetical protein9514919BC009732Contig38043_RChypothetical protein9524920LOC199675Contig38093_RCTranscribed9534921sequencesContig380_RCKIAA1724selenoprotein I, 1Hypothetical protein, Transferase,9544922Transmembrane, Selenium,SelenocysteineContig38117_RCTranscribed9554923sequencesContig38155_RCTranscribed9564924sequencesContig38169_RCFLJ13984hypothetical proteinHypothetical protein9574925FLJ13984Contig3820_RCLOC56898dehydrogenase/reductaseOxidoreductase, Hypothetical protein9584926(SDR family)member 6Contig38285_RCFLJ10462male sterility domainHypothetical protein9594927containing 1Contig38288_RCDKFZp762A2013quiescin Q6-like 1Hypothetical protein, Signal9604928Contig382_RCNLI-IFCTD (carboxy-Hypothetical protein, Nuclear protein9614929terminal domain,RNA polymerase II,polypeptide A) smallphosphatase 1Contig38320_RCTranscribed9624930sequencesContig38321_RCTranscribed9634931sequencesContig3834_RCMRNA; cDNA9644932DKFZp686K14148(from cloneDKFZp686K14148)Contig38398_RCTranscribed9654933sequencesContig38493_RCCDNA FLJ42010 fis,9664934cloneSPLEN2032036Contig38581_RCanaphase promotingUbl conjugation pathway, Cell cycle,9674935complex subunit 1Cell division, Mitosis, RepeatContig38603_RCTranscribed9684936sequencesContig38604_RCCDNA FLJ25042 fis,Hypothetical protein9694937clone CBL03351Contig38654_RCsolute carrier family970493828 (sodium-couplednucleosidetransporter),member 3Contig38669_RCHS2ST1heparan sulfate 2-O-Hypothetical protein, Transferase9714939sulfotransferase 1Contig38714_RCTranscribed9724940sequencesContig38721_RCMGC35163sterile alpha motifHypothetical protein9734941domain containing 3Contig38724_RCClone9744942IMAGE: 5275753,mRNAContig38726_RCSWI/SNF related,Hypothetical protein9754943matrix associated,actin dependentregulator ofchromatin, subfamilye, member 1Contig38731_RCfrizzled homolog 2Multigene family, G-protein coupled9764944(Drosophila)receptor, Transmembrane,Developmental protein, Wntsignaling pathway, Glycoprotein,SignalContig38778TRIM7tripartite motif-Zinc-finger, Zinc, Coiled coil, Metal-9774945containing 7binding, Polymorphism, AlternativesplicingContig38803_RCRho GTPaseGTPase activation, SH3-binding, 3D-9784946activating protein 1structureContig38877zv94e09.s19794947Soares_NhHMPu_S1Homo sapienscDNA cloneIMAGE: 767464 3′,mRNA sequence.Contig38944_RCTranscribed9804948sequencesContig39008_RCMYCL1v-mycNuclear protein, DNA-binding, Proto-9814949myelocytomatosisoncogeneviral oncogenehomolog 1, lungcarcinoma derived(avian)Contig39043_RCzl77f02.s19824950Stratagene colon(#937204) Homosapiens cDNA cloneIMAGE: 510651 3′,mRNA sequence.Contig39048_RCTAFA2 proteinHypothetical protein9834951Contig39116_RCa1/3GTPalpha-1,3-Glycosyltransferase, Transferase9844952galactosyltransferasepseudogeneContig3920_RCSP1Sp1 transcriptionHypothetical protein, Transcription9854953factorregulation, Activator, Zinc-finger,Metal-binding, DNA-binding, Nuclearprotein, Repeat, Glycoprotein, 3D-structureContig39236FLJ00026Homo sapiens,Hypothetical protein, Guanine-9864954Similar to RIKENnucleotide releasing factorcDNA 5830472H07gene, cloneMGC: 39702IMAGE: 5271738,mRNA, completecds.Contig39249THBS3thrombospondin 3Glycoprotein, Cell adhesion,9874955Calcium-binding, Repeat, EGF-likedomain, SignalContig39287_RCTranscribed9884956sequence withmoderate similarityto protein pir: E54024(H. sapiens) E54024protein kinaseContig39297_RCLOC148898hypothetical proteinHypothetical protein9894957BC007899Contig39364_RCUPF3BUPF3 regulator of9904958nonsense transcriptshomolog B (yeast)Contig39403_RChypothetical proteinHypothetical protein9914959FLJ34790Contig3940_RCC9orf19chromosome 9 openHypothetical protein9924960reading frame 19Contig39448_RCN-acetylneuraminate9934961pyruvate lyase(dihydrodipicolinatesynthase)Contig39496_RCFLJ22501Hermansky-PudlakHypothetical protein9944962syndrome 6Contig39545_RCMTIF3general transcriptionTranscription regulation, Zinc-finger,9954963factor IIIAMetal-binding, DNA-binding, RNA-binding, Repeat, Nuclear protein,PolymorphismContig39603_RCCNOT3CCR4-NOTHypothetical protein9964964transcriptioncomplex, subunit 3Contig39626_RCSTK35serine/threonineHypothetical protein, Transferase,9974965kinase 35Serine/threonine-protein kinase,ATP-binding, PhosphorylationContig39702_RCsimilar to PutativeHypothetical protein9984966protein C21orf56Contig39739_RCCDK9Full length insertTransferase, Serine/threonine-9994967cDNA cloneprotein kinase, ATP-binding, NuclearZA91F08protein, PolymorphismContig39797_RCTRIPINtripinHypothetical protein10004968Contig39810_RChypothetical proteinHypothetical protein10014969MGC43690Contig39878_RCBOPSET and MYNDTranscription regulation, Repressor,10024970domain containing 1DNA-binding, Nuclear protein, Zinc-finger, Metal-bindingContig39933_RCLOC90693Sequence 2 fromHypothetical protein10034971Patent WO0220754.Contig39989_RCMGC14289similar to RIKEN10044972cDNA 1200014N16geneContig40015_RCTranscribed10054973sequence withmoderate similarityto protein pdb: 1LBG(E. coli) B Chain B,Lactose OperonRepressor Bound To21-Base PairSymmetric OperatorDna, Alpha CarbonsOnlyContig40026_RCCDNA FLJ12935 fis,10064974cloneNT2RP2004982Contig40053_RCHNRPDheterogeneousNuclear protein, RNA-binding, DNA-10074975nuclearbinding, Ribonucleoprotein, Repeat,ribonucleoprotein DTranscription regulation, Telomere,(AU-rich elementAlternative splicing, 3D-structureRNA binding protein1, 37 kDa)Contig40055_RCTranscribed10084976sequencesContig40069_RCTranscribed10094977sequencesContig40093_RCfatty acid bindingTransport, Lipid-binding, Acetylation,10104978protein 3, musclePhosphorylation, 3D-structureand heart(mammary-derivedgrowth inhibitor)Contig40094_RCDKFZp434I099hypothetical proteinHypothetical protein10114979DKFZp434I099Contig40128_RChypoxia-inducibleTranscription regulation, Activator,10124980factor 1, alphaNuclear protein, DNA-binding,subunit (basic helix-Alternative splicing, Repeat,loop-helixAcetylation, Hydroxylation,transcription factor)Phosphorylation, S-nitrosylation,Polymorphism, 3D-structureContig40184SLC2A1solute carrier familyTransmembrane, Sugar transport,101349812 (facilitated glucoseTransport, Glycoprotein, Multigenetransporter),family, Disease mutation, 3D-member 1structureContig40212_RCCD5CD5 antigen (p56-Signal, Transmembrane,1014498262)Glycoprotein, T-cell, RepeatContig40237_RCFLJ12525hypothetical proteinHypothetical protein10154983FLJ12525Contig40252_RCCDNA cloneHypothetical protein10164984IMAGE: 3462401,partial cdsContig40340_RChypothetical proteinHypothetical protein10174985FLJ11000Contig40389_RCSimilar to RIKEN10184986cDNA 3830422K02(LOC387755),mRNAContig404Mesenchymal stem10194987cell protein DSC96mRNA, partial cdsContig40405_RCMGC10818chromosome 6 openHypothetical protein10204988reading frame 148Contig40410tc14e12.x1Hypothetical protein10214989Soares_NhHMPu_S1Homo sapienscDNA cloneIMAGE: 2063854 3′,mRNA sequence.Contig40450_RCTHAP domainHypothetical protein10224990containing 9Contig40552_RCFLJ25348hypothetical proteinHypothetical protein10234991FLJ25348Contig40651_RCTranscribed10244992sequencesContig40676_RCSequence 60 from10254993Patent WO0220754.Contig40830_RCTSGA14testis specific, 14Hypothetical protein10264994Contig40832_RCTranscribed10274995sequencesContig40897_RCDKFZP434J037likely ortholog of ratHypothetical protein, ATP-binding,10284996SNF1/AMP-activatedKinase, Serine/threonine-proteinprotein kinasekinase, TransferaseContig40960_RCFLJ36991zinc finger proteinHypothetical protein, Metal-binding,10294997565Nuclear protein, Zinc, Zinc-fingerContig40965_RCMGC4504hypothetical proteinHypothetical protein10304998MGC4504Contig40967_RCLOC38938810314999(LOC389388),mRNAContig41005_RCTranscribed10325000sequence withstrong similarity toprotein pdb: 1BGM(E. coli) O Chain O,Beta-GalactosidaseContig41035golgi phosphoprotein 410335001Contig41041_RCCDNA FLJ32274 fis,10345002clonePROST2000036Contig41080_RCTranscribed10355003sequencesContig41086_RCforkhead box P1Hypothetical protein, Transcription10365004regulation, DNA-binding, Zinc-finger,Metal-binding, Nuclear protein,Alternative splicingContig41094_RCEDG8endothelialHypothetical protein, Receptor10375005differentiation,sphingolipid G-protein-coupledreceptor, 8Contig41121_RCFCRH3Fc receptor-likeImmunoglobulin domain, Receptor10385006protein 3Contig41209_RCFLJ21432adiponectin receptor 2Fatty acid metabolism, Lipid10395007metabolism, Receptor,TransmembraneContig41226_RCMRNA; cDNAHypothetical protein10405008DKFZp434O232(from cloneDKFZp434O232)Contig412_RCFLJ22233Homo sapiens cDNAHypothetical protein10415009FLJ36755 fis, cloneUTERU2018180,weakly similar toNa+/Ca2+, K+-exchanging proteinhomolog C13D9.8.Contig41301LOC152217hypothetical proteinHypothetical protein10425010BC007882Contig41421_RCFLJ36156piwi-like 2Hypothetical protein10435011(Drosophila)Contig41448_RCdynamin 1-like10445012Contig41537MGC20496methylmalonicTransferase, Mitochondrion, Transit10455013aciduria (cobalaminpeptide, Polymorphism, Diseasedeficiency) type BmutationContig41560_RCCPT1AcarnitineTransferase, Acyltransferase,10465014palmitoyltransferaseMitochondrion, Outer membrane,1A (liver)Fatty acid metabolism, Transport,Transmembrane, Multigene familyContig41612_RChypothetical proteinHypothetical protein10475015LOC132241Contig41618_RCCloneHypothetical protein10485016IMAGE: 5315196,mRNAContig41638_RCSLC26A8solute carrier family1049501726, member 8Contig41656_RCSimilar to Eph10505018receptor A7, cloneIMAGE: 5273054,mRNAContig41701_RCTranscribed10515019sequencesContig41748_RCELMO3engulfment and cellApoptosis, Phagocytosis,10525020motility 3 (ced-12Cytoskeleton, Membrane, SH3-homolog, C. elegans)bindingContig41774_RCTranscribed10535021sequencesContig41781_RCARHGEF7Rho guanineGuanine-nucleotide releasing factor,10545022nucleotide exchangeSH3 domain, Alternative splicing,factor (GEF) 73D-structure, Hypothetical proteinContig41828_RCClone10555023IMAGE: 5310874,mRNAContig41864_RCZFP106zinc finger proteinHypothetical protein, Metal-binding,10565024106 homologRepeat, WD repeat, Zinc, Zinc-finger(mouse)Contig41869_RCSFRS3splicing factor,Nuclear protein, RNA-binding,10575025arginine/serine-rich 3mRNA splicing, Alternative splicing,Phosphorylation, RepeatContig41903_RCFLJ21657hypothetical proteinHypothetical protein10585026FLJ21657Contig41923_RCOATL1ornithineTransferase, Aminotransferase10595027aminotransferase-like 1Contig41936_RCMSL3L1male-specific lethalChromatin regulator, Nuclear106050283-like 1 (Drosophila)protein, Transcription regulation,Alternative splicingContig41983_RCym35b12.s1 Soares10615029infant brain 1NIBHomo sapiens cDNAclone IMAGE: 501443′, mRNA sequence.Contig42005_RCsplicing factor,Nuclear protein, RNA-binding,10625030arginine/serine-richmRNA splicing, Repeat11Contig42006_RCRasGEF domainHypothetical protein10635031family, member 1BContig42012_RCzinc finger, DHHCTransmembrane, Zinc-finger10645032domain containing21Contig42014_RCRNTREUSP6 N-terminal likeHypothetical protein10655033Contig42076_RCFLJ39091zinc binding alcoholHypothetical protein10665034dehydrogenase,domain containing 1Contig42105_RCMRNA; cDNA10675035DKFZp686P24244(from cloneDKFZp686P24244)Contig42146_RCchromosome 19Hypothetical protein10685036open reading frame12Contig42154_RCFLJ11795hypothetical proteinHypothetical protein10695037FLJ11795Contig42174FLJ33215hypothetical proteinHypothetical protein10705038FLJ33215Contig42177_RCzinc finger, DHHCHypothetical protein,10715039domain containingTransmembrane, Zinc-finger19Contig42185_RCTLR8toll-like receptor 8Hypothetical protein, Receptor,10725040Immune response, Inflammatoryresponse, Signal, Transmembrane,Repeat, Leucine-rich repeat,GlycoproteinContig421_RCKIAA1821rab11-familyHypothetical protein10735041interacting protein 4Contig42256_RCTranscribed10745042sequencesContig42263_RCPSMB5ATP synthase, H+Hydrogen ion transport, CF(0),10755043transporting,Mitochondrion, Transit peptide,mitochondrial F0Hypothetical proteincomplex, subunit s(factor B)Contig42270_RCsimilar to metallo-Hypothetical protein10765044beta-lactamasesuperfamily proteinContig42330_RCTranscribed10775045sequencesContig42342_RCCDNA FLJ39417 fis,Hypothetical protein10785046clonePLACE6016942Contig42418_RCTranscribed10795047sequence with weaksimilarity to proteinref: NP_060265.1(H. sapiens)hypothetical proteinFLJ20378 [Homosapiens]Contig42437_RCC1orf28casein kinase 1,Transferase, Serine/threonine-10805048epsilonprotein kinase, ATP-binding,Phosphorylation, Multigene familyContig42459_RCFLJ22021hypothetical proteinRepeat, WD repeat10815049FLJ22021Contig42566_RCFLJ14761hypothetical proteinHypothetical protein10825050FLJ14761Contig42591_RCshadow of prion10835051proteinContig42593_RCTranscribed10845052sequencesContig42597_RCwd88a09.x110855053NCI_CGAP_Lu24Homo sapiens cDNAcloneIMAGE: 2338648 3′,mRNA sequence.Contig42615_RCAMIDapoptosis-inducingHypothetical protein10865054factor (AIF)-homologousmitochondrion-associated inducerof deathContig42617_RCSNRPGHuman S6 H-8Ubiquitin conjugation, Hydrolase,10875055mRNA expressed inThiol protease, Multigene family,chromosome 6-Alternative splicingsuppressedmelanoma cells.Contig42666_RCchromosome 10Hypothetical protein10885056open reading frame47Contig42759_RCBCL11BB-cellB-cell, Metal-binding, Zinc, Zinc-10895057CLL/lymphoma 11Bfinger(zinc finger protein)Contig42787_RChypothetical proteinHypothetical protein10905058MGC5509Contig42824_RCFLJ10785ubiquitin specificUbl conjugation pathway, Hydrolase,10915059protease 40Thiol protease, Alternative splicing,Polymorphism, multigene familyContig42854CDNA FLJ33578 fis,10925060cloneBRAMY2011639Contig42903_RCTranscribed10935061sequence withstrong similarity toproteinref: NP_002745.1(H. sapiens)mitogen-activatedprotein kinase 13;mitogen-activatedprotein kinase p38delta; stress-activated proteinkianse 4 [Homosapiens]Contig42959_RCsolute carrier familyHypothetical protein109450625 (sodium/glucosecotransporter),member 10Contig42962_RCTranscribed10955063sequence with weaksimilarity to proteinpir: S41161(H. sapiens) S41161keratin 9,cytoskeletal - humanContig43022_RCsimilar to RIKEN10965064cDNA 2610524G09Contig43026_RChypothetical proteinHypothetical protein10975065DKFZp762C1112Contig43096_RCClone10985066IMAGE: 5743799,mRNAContig43169_RCDEAD (Asp-Glu-Ala-ATP-binding, Helicase, Hydrolase,10995067Asp) box polypeptideHypothetical protein51Contig43184_RCyg20d12.s1 Soares11005068infant brain 1NIBHomo sapiens cDNAclone IMAGE: 329183′, mRNA sequence.Contig43189_RCTranscribed11015069sequencesContig43241_RCADCY7adenylate cyclase 7Lyase, cAMP biosynthesis,11025070Transmembrane, Glycoprotein,Repeat, Metal-binding, MagnesiumContig43253_RCKIAA1858zinc finger proteinTranscription regulation, DNA-11035071469binding, Zinc-finger, Metal-binding,Nuclear protein, RepeatContig43262_RCTranscribed11045072sequencesContig43277_RCSimilar to KIAA172611055073protein(LOC340554),mRNAContig43289_RChypothetical protein11065074LOC170371Contig43385_RCDKFZp762O076hypothetical proteinHypothetical protein11075075DKFZp762O076Contig43436_RCFLJ32028hypothetical proteinHypothetical protein11085076FLJ32028Contig43486_RCDRB1developmentallyHypothetical protein11095077regulated RNA-binding protein 1Contig43506_RCGLI pathogenesis-11105078related 1 (glioma)Contig43513_RCTIGD7Homo sapiens cDNA11115079FLJ13533 fis, clonePLACE1006371.Contig43534ankyrin repeatHypothetical protein, ANK repeat,11125080domain 10RepeatContig43540_RCGRIM19FLJ44968 proteinOxidoreductase, Ubiquinone, NAD,11135081Apoptosis, Mitochondrion,Transmembrane, Acetylation,Hypothetical proteinContig43542_RCKIAA1718 proteinHypothetical protein11145082Contig43549_RCSNX5Homo sapiens, cloneHypothetical protein, Transport,11155083MGC: 3411Protein transportIMAGE: 3629947,mRNA, completecds.Contig43586_RChypothetical protein11165084LOC134218Contig43645_RChypothetical proteinHypothetical protein11175085LOC129607Contig43655_RCNAG14leucine rich repeatImmunoglobulin domain,11185086containing 4Hypothetical protein, SignalContig43658_RClikely ortholog of11195087mouse cancerrelated gene - liver 2Contig4365_RCTGOLN2trans-golgi networkHypothetical protein, Signal,11205088protein 2Transmembrane, Glycoprotein,Repeat, Golgi stack, AlternativesplicingContig43673_RCFLJ20481calpain small subunit 2Hypothetical protein11215089Contig43679_RCMEF-2myelin expressionHypothetical protein11225090factor 2Contig43694_RCTSPAN-2tetraspan 2Glycoprotein, Transmembrane11235091Contig43703_RCCDH13CDNA FLJ25967 fis,Cell adhesion, Glycoprotein,11245092clone CBR01929Calcium-binding, Repeat, GPI-anchor, SignalContig43724_RCFLJ13213hypothetical proteinHypothetical protein11255093FLJ13213Contig43746_RCCDNA FLJ41107 fis,11265094cloneBLADE2007923Contig43749_RCMGC14258Rho GTPaseHypothetical protein11275095activating protein 19Contig43750_RCcleavage and11285096polyadenylationspecific factor 6,68 kDaContig43817_RCRINZFzinc finger and BTBHypothetical protein, Metal-binding,11295097domain containingZinc, Zinc-finger10Contig438_RChypothetical proteinEGF-like domain, Hypothetical11305098MGC61716proteinContig4399_RCMYH9myosin, heavyMyosin, ATP-binding, Calmodulin-11315099polypeptide 9, non-binding, Actin-binding, Coiled coil,muscleMultigene family, Disease mutation,Deafness, Hypothetical proteinContig440MGC3165Homo sapiens, H2AAcetylation, Chromosomal11325100histone family,protein, DNA-binding, Multigenemember L, clonefamily, Nuclear protein, NucleosomeMGC: 3165coreIMAGE: 3355200,mRNA, completecds.Contig44059_RChypothetical proteinHypothetical protein11335101DKFZp564B1162Contig44078TA-WDRPT-cell activation WDHypothetical protein, Repeat, WD11345102repeat proteinrepeatContig44105OSBPL11oxysterol bindingHypothetical protein, Lipid transport,11355103protein-like 11TransportContig44124_RCCDNA FLJ30906 fis,Hypothetical protein11365104cloneFEBRA2006055Contig44133_RCFLJ11362hypothetical proteinHypothetical protein, ANK repeat,11375105FLJ11362RepeatContig44192_RCCas-Br-M (murine)Hypothetical protein, Ligase, Ubl11385106ecotropic retroviralconjugation pathway, Proto-transformingoncogene, Zinc-finger, SH2 domain,sequencePhosphorylation, Calcium-binding,3D-structureContig44226_RCTIGD2tigger transposable11395107element derived 2Contig44265_RCATPase,Hydrolase, Transmembrane,11405108aminophospholipidPhosphorylation, Magnesium, ATP-transporter (APLT),binding, Alternative splicing,Class I, type 8A,Multigene familymember 1Contig44278_RCDKFZp434K114WD repeat domainRepeat, WD repeat, Hypothetical1141510921protein, PlasmidContig44343CDNA FLJ26676 fis,11425110clone MPG03726Contig44358_RCDKFZp434N035HypotheticalHypothetical protein11435111LOC284874(LOC284874),mRNAContig44409similar to LL5 betaHypothetical protein11445112Contig44414_RCSLC30A1solute carrier familyZinc transport, Transport,1145511330 (zinc transporter),Transmembrane, Multigene familymember 1Contig44492_RCTranscribed11465114sequencesContig44518_RCFAM11Afamily with sequenceAntigen, Multigene family, Tumor11475115similarity 11,antigen, Hypothetical proteinmember AContig44521_RCLSM8 homolog, U6Nuclear protein, Ribonucleoprotein,11485116small nuclear RNAmRNA splicing, mRNA processing,associated (S. cerevisiae)RNA-binding, AcetylationContig44548_RChypothetical protein11495117LOC283508Contig44593_RCretinoblastomaHypothetical protein, Metal-binding,11505118binding protein 6Zinc, Zinc-fingerContig44595_RChypothetical proteinHypothetical protein11515119MGC45840Contig44596_RCPPIL3peptidylprolylIsomerase, Rotamase, Hypothetical11525120isomeraseprotein(cyclophilin)-like 3Contig44708_RCBCAT1Homo sapiensHypothetical protein, Transferase,11535121cDNA: FLJ21270 fis,Aminotransferase, Branched-chainclone COL01749.amino acid biosynthesis, PyridoxalphosphateContig44713transducin-likeTranscription regulation, Repressor,11545122enhancer of split 4Nuclear protein, Repeat, WD repeat,(E(sp1) homolog,Phosphorylation, Wnt signalingDrosophila)pathwayContig44720_RCFKSG32hypothetical proteinHypothetical protein11555123FKSG32Contig44723_RCHuman cAMP-11565124binding guaninenucleotide exchangefactor IV (cAMP-GEFIV) mRNA,clone W15, partialsequenceContig44757_RCVIMTranscribedHypothetical protein, Coiled coil,11575125sequence withIntermediate filament,strong similarity toPhosphorylation, 3D-structureprotein pir: A25074(H. sapiens) A25074vimentin - humanContig44817_RCC20orf147chromosome 20Hydrolase11585126open reading frame147Contig44874_RCLOC57805p30 DBC proteinHypothetical protein11595127Contig44877_RCKIAA1877beta-galactosideHypothetical protein, Transferase,11605128alpha-2,6-Glycosyltransferasesialyltransferase IIContig44964_RChypothetical gene11615129supported byBC017510;BC046919Contig45004_RChypothetical protein11625130LOC283129Contig45080_RCCUL5cullin 5Ubl conjugation pathway, Ubl11635131conjugation, ReceptorContig45085_RCATP6V0A2Homo sapiens cDNAHydrogen ion transport,11645132FLJ32238 fis, cloneTransmembrane, Glycoprotein,PLACE6004993.Hypothetical proteinContig45135CDNA: FLJ2238211655133fis, clone HRC07514Contig45201_RCC1QTNF2C1q and tumorCollagen, Signal11665134necrosis factorrelated protein 2Contig45290_RCSimilar to RIKEN11675135cDNA 3010021M21(LOC388185),mRNAContig45304_RCDEPC-1prostate cancer11685136antigen-1Contig45305_RCMGC3130hypothetical proteinHypothetical protein11695137MGC3130Contig45328_RCSimilar to Ab2-18311705138(LOC158830),mRNAContig45338_RCCSNK2A1casein kinase 2,Transferase, Serine/threonine-11715139alpha 1 polypeptideprotein kinase, ATP-binding, Wntsignaling pathway, 3D-structureContig45377_RCC10orf2progressive externalHypothetical protein, Helicase11725140ophthalmoplegia 1Contig45381_RChypothetical protein11735141LOC283663Contig45396_RCFLJ13197hypothetical proteinHypothetical protein11745142FLJ13197Contig45397_RCFLJ34299zinc finger protein 92Hypothetical protein, Metal-binding,11755143(HTF12)Nuclear protein, Zinc, Zinc-finger,Transcription regulation, DNA-binding, RepeatContig45437similar to RNAHypothetical protein11765144polymerase Btranscription factor 3Contig45440_RCSimilar to RIKEN11775145cDNA 9330196J05(LOC340075),mRNAContig45455_RCsoluble liver11785146antigen/liverpancreas antigenContig45457_RCCYP4F12cytochrome P450,Oxidoreductase, Monooxygenase,11795147family 4, subfamilyElectron transport, Membrane,F, polypeptide 12Heme, Microsome, Endoplasmicreticulum, PolymorphismContig45540_RCG protein-coupledReceptor11805148receptor 114Contig45544_RCprotein kinase,Hypothetical protein, Kinase11815149interferon-inducibledouble strandedRNA dependentactivatorContig45569_RCCDC14BCDC14 cell divisionHydrolase11825150cycle 14 homolog B(S. cerevisiae)Contig45624_RCHAKAICas-Br-M (murine)Hypothetical protein, Metal-binding,11835151ecotropic retroviralZinc, Zinc-fingertransformingsequence-like 1Contig45634_RCSimilar to FLJ46354Hypothetical protein11845152protein(LOC389694),mRNAContig45642_RCmitogen-activatedATP-binding, Kinase, Transferase,11855153protein kinaseSerine/threonine-protein kinase,kinase kinase 2Hypothetical proteinContig45790_RCKIAA0187ESTs, Moderately11865154similar to KIAA0187gene product [Homosapiens] [H. sapiens]Contig45800_RCMTX1metaxin 1Mitochondrion, Outer membrane,11875155Transmembrane, Transport, ProteintransportContig45816_RCMGC4832chromosome 13Hypothetical protein11885156open reading frame 3Contig45821_RCADCY4adenylate cyclase 4Hypothetical protein, Lyase, cAMP11895157biosynthesis, Transmembrane,Glycoprotein, Repeat, Metal-binding,MagnesiumContig45847_RCDKFZP761I2123hypothetical proteinHypothetical protein11905158DKFZp761I2123Contig45879_RCKIAA1145KIAA1145 proteinHypothetical protein,11915159TransmembraneContig45891_RCCDNA FLJ37509 fis,11925160cloneBRCAN1000065Contig45944_RCZNF335zinc finger proteinTranscription regulation, Zinc-finger,11935161335Metal-binding, Nuclear protein, DNA-binding, RepeatContig45945_RCTranscribed11945162sequencesContig4595hypotheticalHypothetical protein11955163LOC387763Contig45975_RCTranscribed11965164sequencesContig45984USP7ubiquitin specificUbl conjugation pathway, Hydrolase,11975165protease 7 (herpesThiol protease, Multigene family,virus-associated)Nuclear protein, 3D-structureContig46052_RCectonucleosideHydrolase, Transmembrane,11985166triphosphateAntigen, Glycoprotein, Calcium,diphosphohydrolase 1Magnesium, Alternative splicing,Lipoprotein, PalmitateContig46178_RCHomo sapiens, clone11995167IMAGE: 5276307,mRNA.Contig461_RCKIAA1836KIAA1836 proteinHypothetical protein12005168Contig46202MADMAX dimerizationNuclear protein, DNA-binding,12015169protein 1Transcription regulation, Repressor,3D-structureContig46218_RCSimilar to12025170diaphanous homolog3 (Drosophila), cloneIMAGE: 5277415,mRNAContig46244_RCClone12035171IMAGE: 111705mRNA sequenceContig46262_RCSimilar to120451722010300C02Rikprotein(LOC343990),mRNAContig46265_RCLOH11CR1J gene,12055173loss ofheterozygosity, 11,chromosomal region1 gene J productContig46294_RCTranscribed12065174sequence with weaksimilarity to proteinref: NP_060312.1(H. sapiens)hypothetical proteinFLJ20489 [Homosapiens]Contig46306_RCCDNA FLJ36097 fis,12075175cloneTESTI2020956Contig46343_RCSPP1suppressor ofSH2 domain, Growth regulation,12085176cytokine signaling 7Signal transduction inhibitorContig46375_RCCDNA FLJ26349 fis,12095177clone HRT04618Contig46376_RCzinc finger and BTBHypothetical protein, Metal-binding,12105178domain containingZinc, Zinc-finger10Contig46399_RCTranscribed12115179sequencesContig46416_RCMGC33212hypothetical protein12125180MGC33212Contig46421_RCTranscribed12135181sequence withmoderate similarityto proteinref: NP_005496.1(H. sapiens) CD36antigenContig46437_RCsynaptotagminTransport, Protein transport12145182binding, cytoplasmicRNA interactingproteinContig46443_RCsolute carrier familyHypothetical protein1215518326, member 11Contig46464_RCTranscribed12165184sequencesContig46482_RCMRNA; cDNA12175185DKFZp434C1435(from cloneDKFZp434C1435)Contig46506_RCMRNA; cDNA12185186DKFZp686C18110(from cloneDKFZp686C18110)Contig46536_RCLGI3leucine-rich repeatRepeat, Leucine-rich repeat, Signal,12195187LGI family, member 3Hypothetical proteinContig46563_RCTranscribed12205188sequencesContig46567Transcribed12215189sequencesContig46586UBE2D3ubiquitin-conjugatingHypothetical protein, Ligase, Ubl12225190enzyme E2D 3conjugation pathway, Multigene(UBC4/5 homolog,familyyeast)Contig46590RAD50CDNA FLJ46914 fis,Hypothetical protein12235191cloneSPLEN2027852Contig46591_RChypothetical protein12245192LOC90639Contig46601_RCCDNA FLJ42198 fis,12255193cloneTHYMU2034338Contig46602_RCzinc finger, CCHCHypothetical protein12265194domain containing 6Contig46634Transcribed12275195sequencesContig46700_RCLSP1small proline richPhosphorylation, T-cell12285196protein 4Contig46709_RCFLJ23045chromosome 20Transport, Protein transport,12295197open reading frameHypothetical protein23Contig46732_RCzinc finger proteinHypothetical protein, Zinc-finger,12305198207Metal-binding, DNA-binding, Nuclearprotein, Alternative splicingContig46747_RCparvin, gammaCell adhesion, Cytoskeleton, Actin-12315199binding, Repeat, Alternative splicingContig46860_RCFLJ20758 proteinHypothetical protein12325200Contig46881_RCTranscribed12335201sequencesContig46954_RCPNMA3paraneoplasticHypothetical protein12345202antigen MA3Contig46999_RCCDNA FLJ26950 fis,12355203clone RCT08544Contig47014_RCMGC24180hypothetical proteinHypothetical protein12365204MGC24180Contig47015_RChypothetical proteinHypothetical protein12375205FLJ21439Contig47025_RCHypothetical gene12385206supported byAK094796(LOC400764),mRNAContig47042FLJ20069Abelson helperHypothetical protein, Repeat, SH312395207integration sitedomain, WD repeatContig47081_RCLOC39275112405208(LOC392751),mRNAContig47096_RCPFKFB46-phosphofructo-2-Multifunctional enzyme, Transferase,12415209kinase/fructose-2,6-Kinase, Hydrolase, ATP-binding,biphosphatase 4Phosphorylation, Multigene family,3D-structureContig47184_RCLOC40081312425210(LOC400813),mRNAContig47203_RCsortilin-relatedEndocytosis, Receptor,12435211receptor, L(DLRTransmembrane, EGF-like domain,class) A repeats-Repeat, Glycoprotein, LDL, Lipidcontainingtransport, Cholesterol metabolism,SignalContig47221_RCVCPvalosin-containingATP-binding, Transport,12445212proteinPhosphorylation, Repeat, Golgistack, Endoplasmic reticulum,Hypothetical proteinContig47368_RCLOC92691hypothetical proteinHypothetical protein12455213BC008604Contig47441_RCubiquitin-conjugatingLigase, Ubl conjugation pathway,12465214enzyme E2 variant 2Vitamin DContig47464_RCZNF335zinc finger proteinTranscription regulation, Zinc-finger,12475215335Metal-binding, Nuclear protein, DNA-binding, RepeatContig47495_RCIDI2GTP binding protein 4GTP-binding, Nuclear protein12485216Contig47498_RCTMPRSS5transmembraneHydrolase, Serine protease,12495217protease, serine 5Transmembrane, Signal-anchor,(spinesin)GlycoproteinContig47539_RCSGT1, suppressor ofUbl conjugation pathway, Repeat,12505218G2 allele of SKP1TPR repeat(S. cerevisiae)Contig47582_RCFLJ22757family with sequenceHypothetical protein12515219similarity 31,member CContig47732_RCEPS8R3EPS8-like 3SH3 domain, Hypothetical protein,12525220ReceptorContig47770_RCLY6G6Clymphocyte antigenSignal125352216 complex, locusG6CContig47793_RCFLJ23311FLJ23311 proteinHypothetical protein12545222Contig47801_RCCDNA FLJ45814 fis,12555223cloneNT2RP7018126Contig47810_RCIMMP2LIMP2 innerCoated pits12565224mitochondrialmembrane protease-like (S. cerevisiae)Contig47814_RCHHGPphosphoribosylTransferase12575225transferase domaincontaining 1Contig47835_RCsimilar to RIKENHypothetical protein12585226cDNA 2600017H02Contig47863_RCFLJ11939latrophilin 1Hypothetical protein, Receptor,12595227TransmembraneContig47889_RCCOPS7BCOP9 constitutiveHypothetical protein12605228photomorphogenichomolog subunit 7B(Arabidopsis)Contig47900_RCFLJ12604hypothetical proteinHypothetical protein12615229FLJ12604Contig47912_RCNR1D2nuclear receptorHypothetical protein, Receptor,12625230subfamily 1, groupTranscription regulation, DNA-D, member 2binding, Nuclear protein, Zinc-finger,RepressorContig47922_RCBRAPBRCA1 associatedMetal-binding, Zinc, Zinc-finger12635231proteinContig47926_RCFLJ13057germ cell-lessHypothetical protein12645232homolog 1(Drosophila)Contig47942_RCLOC91893hypothetical proteinHypothetical protein12655233BC006136Contig47975_RCCDNA clone12665234IMAGE: 5757380,partial cdsContig47982_RChypothetical protein12675235LOC112868Contig48059FLJ12788hypothetical proteinHypothetical protein12685236FLJ12788Contig48144_RCFLJ11152chromosome 6 openHypothetical protein12695237reading frame 70Contig48156_RCproproteinCholesterol metabolism, Lipid12705238convertasemetabolism, Hydrolase, Protease,subtilisin/kexin type 9Serine protease, Calcium, Signal,Autocatalytic cleavage, Zymogen,Glycoprotein, Alternative splicing,Polymorphism, Disease mutationContig48168_RCLOC113246CDNA FLJ46484 fis,Hypothetical protein12715239cloneTHYMU3026350Contig48215_RCFLJ35801hypothetical proteinHypothetical protein12725240FLJ35801Contig48249_RCFLJ10849hypothetical proteinHypothetical protein12735241FLJ10849Contig48270_RCLOC144097hypothetical proteinHypothetical protein12745242BC007540Contig48277_RCFLJ36175hypothetical proteinRepeat, WD repeat, Hypothetical12755243FLJ36175proteinContig48290_RCMN7CDNA FLJ43285 fis,Hypothetical protein12765244cloneMESAN2000067Contig48355_RCmethionine12775245aminopeptidase 1DContig48371malateOxidoreductase, Tricarboxylic acid12785246dehydrogenase 1,cycle, NADNAD (soluble)Contig48406_RCchromosome 12Hypothetical protein12795247open reading frame 6Contig48466_RCFLJ12649hypothetical proteinHypothetical protein12805248FLJ12649Contig48472_RCMAD3MAX dimerizationHypothetical protein12815249protein 3Contig48480_RCring finger protein 24Zinc-finger12825250Contig48489_RCsimilar toHypothetical protein12835251K06A9.1b.pContig48506_RCKIAA1799KIAA1799 proteinHypothetical protein12845252Contig48529_RCCKLFSF2chemokine-likeChemotaxis, Cytokine,12855253factor super family 2TransmembraneContig48588_RCKIAA1706KIAA1706 proteinHypothetical protein12865254Contig48697_RCPFKFB26-phosphofructo-2-Multifunctional enzyme, Transferase,12875255kinase/fructose-2,6-Kinase, Hydrolase, ATP-binding,biphosphatase 2Phosphorylation, Alternative splicing,Multigene familyContig48722_RCClone12885256IMAGE: 5729395,mRNAContig48764_RCCDNA cloneHypothetical protein12895257MGC: 71984IMAGE: 4280819,complete cdsContig48806_RCSimilar to RIKEN12905258cDNA E130012A19(LOC390789),mRNAContig48830_RCRPL13ribosomal proteinRibosomal protein12915259L13Contig48834_RCYR-29KIAA0888 proteinNuclear protein12925260Contig48914_RChypothetical proteinHypothetical protein12935261MGC24133Contig48944_RCTranscribed12945262sequencesContig48951_RCchromosome 9 openHypothetical protein12955263reading frame 85Contig48983_RCCDNA FLJ14294 fis,12965264clonePLACE1008181Contig48988_RCLOC51099abhydrolase domainHypothetical protein12975265containing 5Contig49000_RCCDNA FLJ30257 fis,12985266cloneBRACE2002467Contig49012_RChypothetical proteinHypothetical protein12995267DKFZp434J0617Contig49063_RCA1BGalpha-1-BHypothetical protein,13005268glycoproteinImmunoglobulin domain,Glycoprotein, Plasma, Repeat,SignalContig49169_RCSUV39H2suppressor ofHypothetical protein, Transferase,13015269variegation 3-9Methyltransferase, Chromatinhomolog 2regulator, Nuclear protein,(Drosophila)Alternative splicingContig49185_RCMGC2744hypothetical proteinHypothetical protein13025270MGC2744Contig49233_RCNRBF-2nuclear receptorReceptor, Hypothetical protein13035271binding factor 2Contig49254_RCRAD53Homo sapiens, cloneHypothetical protein, ATP-binding,13045272MGC: 2637Kinase, Serine/threonine-proteinIMAGE: 3505128,kinase, Transferase, Cell cycle,mRNA, completePhosphorylation, Nuclear protein,cds.Disease mutation, Li-Fraumenisyndrome, 3D-structureContig49255_RCleucine-rich PPR-Hypothetical protein, Repeat13055273motif containingContig49279_RChypothetical proteinHypothetical protein13065274FLJ25461Contig49306_RCDKFZP586K0717ligand of numb-Zinc-finger, Repeat, Alternative13075275protein XsplicingContig49344FLJ22474growth hormoneHypothetical protein13085276regulated TBCprotein 1Contig49353_RCMGC41917zinc finger proteinHypothetical protein, Metal-binding,13095277550Nuclear protein, Zinc, Zinc-fingerContig49409ty82g05.x113105278NCI_CGAP_Kid11Homo sapiens cDNAcloneIMAGE: 2285624 3′,mRNA sequence.Contig49468_RCMRNA; cDNA13115279DKFZp667N1113(from cloneDKFZp667N1113)Contig49509_RCKIAA1673cytoplasmicHypothetical protein13125280polyadenylationelement bindingprotein 4Contig49522_RChypothetical proteinHypothetical protein13135281FLJ13105Contig49578_RCFLJ20274xj92d05.x1Hypothetical protein13145282Soares_NFL_T_GBC_S1Homo sapienscDNA cloneIMAGE: 2664681 3′,mRNA sequence.Contig49591_RCactivatingHypothetical protein13155283transcription factor 7interacting protein 2Contig49631_RCATP11CATPase, Class VI,Hydrolase, Transmembrane,13165284type 11CPhosphorylation, Magnesium, Metal-binding, ATP-binding, Multigenefamily, Alternative splicingContig49667_RCdeaminase domain13175285containing 1Contig49673_RCAD034RIO kinase 1 (yeast)Kinase, Hypothetical protein13185286Contig49725_RCLOC51611CDNA cloneTransferase, Methyltransferase,13195287IMAGE: 4821863,Alternative splicing, Hypotheticalpartial cdsproteinContig49738_RCATICaj25f09.s1Purine biosynthesis, Transferase,13205288Soares_testis_NHTHydrolase, Multifunctional enzymeHomo sapiens cDNAclone 1391369 3′,mRNA sequence.Contig49744_RCFLJ14166hypothetical proteinHypothetical protein13215289FLJ14166Contig49756_RCTranscribed13225290sequencesContig49849_RCC6orf1hypothetical proteinHypothetical protein13235291MGC57858Contig49855MGC33338hypothetical proteinHypothetical protein13245292MGC33338Contig49875Full length insert13255293cDNA YN61C04Contig49948_RCMGC27385potassium channelHypothetical protein13265294tetramerisationdomain containing 6Contig49966_RCCDNA FLJ31683 fis,13275295cloneNT2RI2005353Contig49983_RCMGC3121hypothetical proteinHypothetical protein13285296MGC3121Contig49991_RCTranscribed13295297sequence with weaksimilarity to proteinref: NP_062553.1(H. sapiens)hypothetical proteinFLJ11267 [Homosapiens]Contig50039_RCKIAA0140similar to CG9643-Hypothetical protein13305298PAContig50106_RCKIAA1708kinesin familyHypothetical protein13315299member 21AContig50117_RCTranscribed13325300sequencesContig50134_RCBITEp10-binding proteinHypothetical protein13335301Contig50137_RCMGC12992hypothetical proteinGTP-binding, Microtubules, Multigene13345302MGC12992familyContig50177_RCMBLRring finger proteinHypothetical protein, Metal-binding,13355303134Zinc, Zinc-fingerContig50190_RCLOC51005MRNA; cDNAGlycoprotein, Ion transport, Ionic13365304DKFZp313E2215channel, Transmembrane(from cloneDKFZp313E2215)Contig50194_RCC9orf16chromosome 9 openHypothetical protein, Coiled coil13375305reading frame 16Contig50211_RCMGC35392hypothetical proteinHypothetical protein13385306MGC35392Contig50220_RCFLJ13231hypothetical proteinHypothetical protein13395307FLJ13231Contig50232_RCDDX31DEAD (Asp-Glu-Ala-ATP-binding, Helicase, Hydrolase,13405308Asp) box polypeptideHypothetical protein31Contig50249_RCMGC23908similar to RNAHypothetical protein13415309polymerase Btranscription factor 3Contig50272_RCTranscribed13425310sequencesContig50273_RChypothetical proteinHypothetical protein13435311LOC255783Contig50275_RCgm117gm11713445312Contig50293_RCEGFR-RSrhomboid family 1Hypothetical protein, Receptor13455313(Drosophila)Contig50295_RCFLJ12541stimulated byHypothetical protein13465314retinoic acid gene 6Contig50298_RCFLJ32370hypothetical proteinHypothetical protein13475315FLJ32370Contig50324_RCLOC51044CDNA FLJ25011 fis,13485316clone CBL01244Contig50337_RCMGC4645hypothetical proteinHypothetical protein, Repeat, WD13495317MGC4645repeatContig50381_RCCD109CD109 antigen (GovHypothetical protein13505318platelet alloantigens)Contig50391_RCTranscribed13515319sequence withmoderate similarityto proteinref: NP_060312.1(H. sapiens)hypothetical proteinFLJ20489 [Homosapiens]Contig50436_RCCDNA FLJ37094 fis,13525320cloneBRACE2018337Contig50465_RCTranscribed13535321sequencesContig50483KIAA1718KIAA1718 proteinHypothetical protein13545322Contig50490_RCLOC90678leucine rich repeatHypothetical protein13555323and sterile alphamotif containing 1Contig50501_RCcoronin, actinActin-binding, Repeat, WD repeat,13565324binding protein, 2ACoiled coilContig50595_RChypothetical proteinHypothetical protein13575325LOC147111Contig50605_RCwj49g02.x113585326NCI_CGAP_Lu19Homo sapiens cDNAcloneIMAGE: 2406194 3′,mRNA sequence.Contig50669_RCKIF9kinesin familyHypothetical protein, Motor protein,13595327member 9Microtubule, ATP-binding, Coiledcoil, Alternative splicingContig50675BA108L7.2similar to ratHypothetical protein, Transport, Iron13605328tricarboxylatetransport, Mitochondrion,carrier-like proteinTransmembraneContig50687_RCMINA53hypothetical proteinHypothetical protein13615329DKFZp667G2110Contig506_RCKIAA1821rab11-familyHypothetical protein13625330interacting protein 4Contig50728_RCTranscribed13635331sequence with weaksimilarity to proteinref: NP_071385.1(H. sapiens)hypothetical proteinFLJ20958 [Homosapiens]Contig50747_RCMGC23427BTB (POZ) domain13645332containing 14AContig50759DKFZp761P1121hypothetical proteinHypothetical protein, RNA-binding,13655333DKFZp761P1121Repeat, Alternative splicingContig50787_RCFLJ31528hypothetical proteinHypothetical protein13665334FLJ31528Contig50814_RCMGC27027immune associatedHypothetical protein13675335nucleotideContig50831_RCLOC38986513685336(LOC389865),mRNAContig50838_RCLOC120224hypothetical proteinHypothetical protein13695337BC016153Contig50846_RCzinc finger CCCHHypothetical protein13705338type domaincontaining 5Contig50848_RCKIAA1705DDHD domainLipid degradation, Hydrolase,13715339containing 1Alternative splicingContig50891_RCHomo sapiens,ATP-binding, Kinase,13725340p21/Cdc42/Rac1-Serine/threonine-protein kinase,activated kinase 1Transferase, Apoptosis,(STE20 homolog,Phosphorylation, 3D-structureyeast), cloneMGC: 51883IMAGE: 5763796,mRNA, completecds.Contig50905_RCCDNA FLJ42250 fis,13735341cloneTKIDN2007828Contig50920_RCKIAA1847Homo sapiensHypothetical protein, Zinc-finger,13745342mRNA for KIAA1847Alternative splicingprotein, partial cds.Contig51020_RCMGC21874transcriptionalHypothetical protein13755343adaptor 2 (ADA2homolog, yeast)-betaContig51026_RCDKFZp762A2013quiescin Q6-like 1Hypothetical protein, Signal13765344Contig51068_RCCDNA clone13775345IMAGE: 5286843,partial cdsContig51070_RCFLJ25005FLJ25005 proteinHypothetical protein13785346Contig51087_RCNPEPL1aminopeptidase-like 1Hydrolase, Aminopeptidase, Zinc,13795347Manganese, Alternative splicingContig51103_RCJFC1NADPH oxidase-Hypothetical protein, Repeat,13805348related, C2 domain-Alternative splicingcontaining proteinContig51105_RCTranscribed13815349sequence with weaksimilarity to proteinref: NP_062553.1(H. sapiens)hypothetical proteinFLJ11267 [Homosapiens]Contig51128_RCMGC35182hypothetical proteinHypothetical protein13825350MGC35182Contig51151_RCASPAKAP-associated13835351sperm proteinContig51163_RChypothetical proteinHypothetical protein13845352MGC45871Contig51170_RCbruno-like 4, RNAHypothetical protein13855353binding protein(Drosophila)Contig51254_RCCLGlikely ortholog ofHypothetical protein13865354mouse common-sitelymphoma/leukemiaGEFContig51288_RCNR2C2nuclear receptorReceptor, Transcription regulation,13875355subfamily 2, groupDNA-binding, Nuclear protein, Zinc-C, member 2fingerContig51291_RCKIAA1977KIAA1977 proteinHypothetical protein, ANK repeat,13885356RepeatContig51297_RCFLJ33817hypothetical proteinHypothetical protein, Repeat, WD13895357FLJ33817repeatContig51311_RCKDELC1KDEL (Lys-Asp-Glu-Hypothetical protein13905358Leu) containing 1Contig51373_RCKIAA1688KIAA1688 proteinRepeat13915359Contig51414_RCFLJ23441hypothetical proteinHypothetical protein13925360FLJ23441Contig51417_RCSHANK3SH3 and multipleSH3-binding, Coiled coil,13935361ankyrin repeatChromosomal translocationdomains 3Contig51449_RCRAB15, memberHypothetical protein, Plasmid13945362RAS onocogenefamilyContig51519_RCspastic paraplegia 6Hypothetical protein13955363(autosomaldominant)Contig51526_RCRAB39BRAB39B, memberGTP-binding, Lipoprotein,13965364RAS oncogenePrenylation, Transport, ProteinfamilytransportContig51553_RCMGC3200hypothetical proteinHypothetical protein13975365MGC3200Contig51567_RChypothetical proteinHypothetical protein13985366MGC33371Contig51621_RCubiquitin specificHypothetical protein, Ubl conjugation13995367protease 13pathway, Hydrolase, Thiol protease,(isopeptidase T-3)Multigene family, RepeatContig51625_RCCloneHypothetical protein14005368IMAGE: 3868989,mRNA, partial cdsContig51660_RCIFRG2828 kD interferonTransmembrane14015369responsive proteinContig51687_RCKRTDAPKIPV46714025370Contig51723_RCSplicing factor,14035371arginine/serine-rich,46 kDContig51726_RCFLJ20739TranscribedHypothetical protein14045372sequence with weaksimilarity to proteinpir: S41161(H. sapiens) S41161keratin 9,cytoskeletal - humanContig51737_RCCDNA FLJ38931 fis,14055373cloneNT2NE2013189Contig51740_RCFLJ33282amyotrophic lateralHypothetical protein14065374sclerosis 2 (juvenile)chromosome region,candidate 4Contig51742_RCRISClikely homolog of ratHydrolase, Carboxypeptidase,14075375and mouse retinoid-Signal, Glycoprotein, Alternativeinducible serinesplicingcarboxypeptidaseContig51757lin-7 homolog A (C. elegans)14085376Contig51795_RCTGFBICDNA FLJ37830 fis,Extracellular matrix, Signal, Repeat,14095377cloneCell adhesion, Disease mutation,BRSSN2009395Amyloid, VisionContig51800Transcribed14105378sequence withstrong similarity toprotein pdb: 1BGM(E. coli) O Chain O,Beta-GalactosidaseContig51809_RCC21orf63chromosome 21Signal, Transmembrane, Repeat,14115379open reading frameGlycoprotein, Lectin, Alternative63splicingContig51821_RCTAF4BTAF4b RNATranscription regulation, Nuclear14125380polymerase II, TATAproteinbox binding protein(TBP)-associatedfactor, 105 kDaContig51882_RCMGC11335hypothetical proteinHypothetical protein14135381MGC11335Contig51888_RCpannexin 1Gap junction, Transmembrane,14145382PolymorphismContig51896_RCHT021HT02114155383Contig51917_RCWBSCR14Full length insertTranscription regulation, Repressor,14165384cDNA cloneNuclear protein, DNA-binding,YI46G04Williams-Beuren syndrome,Alternative splicingContig51929PAI-1 mRNA-bindingHypothetical protein14175385proteinContig51964_RCFLJ40629hypothetical proteinHypothetical protein14185386FLJ40629Contig51967_RCsolute carrier familyTransport, Symport,1419538716 (monocarboxylicTransmembrane, Multigene familyacid transporters),member 6Contig51974_RCTranscribedHypothetical protein, Phospholipid14205388sequencesbiosynthesis, Transferase,Acyltransferase, TransmembraneContig52062_RCFLJ31978hypothetical proteinHypothetical protein14215389FLJ31978Contig52099_RCCDNA FLJ41881 fis,14225390cloneOCBBF2021833Contig52186_RCzinc finger protein 67Metal-binding, Zinc, Zinc-finger14235391homolog (mouse)Contig52199_RCCDNA FLJ12540 fis,14245392cloneNT2RM4000425Contig52220_RCCDNA FLJ25573 fis,14255393clone JTH06531Contig52232_RCDERMO1twist homolog 2Differentiation, Developmental14265394(Drosophila)protein, Nuclear protein, DNA-binding, Repressor, TranscriptionregulationContig52242_RCCDNA FLJ12345 fis,Hypothetical protein14275395cloneMAMMA1002294Contig52312_RCTFEBtranscription factorTranscription regulation, DNA-14285396EBbinding, Nuclear protein, AlternativesplicingContig52317_RChypothetical proteinHypothetical protein, Ubiquinone14295397LOC91942Contig52320Full length insert14305398cDNA cloneYX81F03Contig52336_RCMGC2488homolog of yeastHypothetical protein14315399Mis12Contig52358_RCTranscribed14325400sequencesContig52405_RCEDG3endothelialG-protein coupled receptor,14335401differentiation,Transmembrane, Glycoproteinsphingolipid G-protein-coupledreceptor, 3Contig52414_RCCAMTA1calmodulin bindingHypothetical protein, ANK repeat,14345402transcriptionRepeatactivator 1Contig52443hypothetical protein14355403INM01Contig52482_RCPNPASEpolyribonucleotideHypothetical protein, Exonuclease,14365404nucleotidyltransferase 1Nucleotidyltransferase, TransferaseContig52486_RCPPARALCDNA FLJ31089 fis,14375405cloneIMR321000092Contig52520_RCMRNA full length14385406insert cDNA cloneEUROIMAGE2068962Contig52544_RCMGC17515hypothetical proteinHypothetical protein14395407MGC17515Contig52553_RCLOC197336similar to RIKENHypothetical protein, Repeat, WD14405408cDNA 3230401M21repeat[Mus musculus]Contig52561_RCCas-Br-M (murine)Hypothetical protein, Ligase, Ubl14415409ecotropic retroviralconjugation pathway, Proto-transformingoncogene, Zinc-finger, SH2 domain,sequencePhosphorylation, Calcium-binding,3D-structureContig52565_RCMAX dimerizationNuclear protein, DNA-binding,14425410protein 1Transcription regulation, Repressor,3D-structureContig52570_RCCDNA FLJ41853 fis,14435411cloneNT2RI3004161Contig52579_RCbreast cancer14445412membrane protein101Contig52609_RChypothetical proteinHypothetical protein14455413FLJ33814Contig52623_RCFLJ12888chromosome 9 openHypothetical protein14465414reading frame 76Contig52648_RCMGC2404acyl-Coenzyme AANK repeat, Repeat14475415binding domaincontaining 6Contig52659_RChypothetical proteinHypothetical protein14485416LOC255104Contig52715_RCTranscribed14495417sequencesContig52720_RCMGC2714hypothetical proteinHypothetical protein14505418MGC2714Contig52729_RCMGC3020hypothetical proteinHypothetical protein14515419MGC3020Contig5274_RCC21orf91chromosome 21Polymorphism14525420open reading frame91Contig52777_RCTranscribed14535421sequence withstrong similarity toproteinref: NP_286085.1 (E. coli)beta-D-galactosidase[Escherichia coliO157:H7 EDL933]Contig52786_RCZNF198zinc finger proteinHypothetical protein, Transcription14545422198regulation, Nuclear protein,Chromosomal translocation, Repeat,Zinc-fingerContig52792_RCMGC3062phosducin-like 314555423Contig52814_RCTranscribed14565424sequencesContig52891_RCmembraneHypothetical protein14575425associatedguanylate kinaseinteracting protein-like 1Contig52914_RCMGC4663cytochrome P450,Hypothetical protein14585426family 2, subfamilyR, polypeptide 1Contig52924_RCFLJ14827hypothetical proteinHypothetical protein14595427FLJ14827Contig52932_RCDKFZP566D1346hypothetical proteinHypothetical protein, ANK repeat,14605428DKFZp566D1346RepeatContig52945_RCKIAA1946KIAA1946 proteinHypothetical protein14615429Contig52971_RCSCAMP5secretory carrierHypothetical protein14625430membrane protein 5Contig52993_RCMAP3K3mitogen-activatedHypothetical protein, ATP-binding,14635431protein kinaseTransferase, Serine/threonine-kinase kinase 3protein kinaseContig52994_RCTranscribed14645432sequence with weaksimilarity to proteinref: NP_055301.1(H. sapiens)neuronal threadprotein [Homosapiens]Contig53047_RCTTYH1tweety homolog 114655433(Drosophila)Contig53066_RCARL5ADP-ribosylationGTP-binding, Multigene family14665434factor-like 5Contig53072_RCKIAA1474zinc finger proteinHypothetical protein, Metal-binding,14675435537Zinc, Zinc-fingerContig53080_RCCDNA FLJ31655 fis,14685436cloneNT2RI2004284Contig53149_RCRIN3Ras and RabGTPase activation, SH2 domain,14695437interactor 3Alternative splicing, PlasmidContig53177_RCCDNA FLJ90571 fis,14705438cloneOVARC1001725,highly similar toHomo sapienspatched relatedprotein TRC8(TRC8) gene.Contig53211_RCFLJ11588hypothetical proteinHypothetical protein14715439FLJ11588Contig53223PPP1R15Bprotein phosphataseHypothetical protein147254401, regulatory(inhibitor) subunit15BContig53226_RChypothetical proteinHypothetical protein14735441DKFZp762C1112Contig53243_RChypothetical proteinHypothetical protein14745442LOC257106Contig53253_RCWWP2Nedd-4-likeUbl conjugation pathway, Ligase,14755443ubiquitin-proteinRepeatligaseContig53260_RChypothetical proteinHypothetical protein14765444LOC196264Contig53307_RCLOC51184Homo sapiensHypothetical protein14775445mRNA full lengthinsert cDNA cloneEUROIMAGE1635059.Contig53323KIAA1608KIAA1608Hypothetical protein14785446Contig53342_RCTranscribed14795447sequencesContig53349_RCFLJ12287hypothetical proteinHypothetical protein, Signal,14805448FLJ12287 similar toTransmembrane, Immunoglobulinsemaphorinsdomain, Multigene family,Neurogenesis, Developmentalprotein, GlycoproteinContig53355_RCMGC10870hypothetical protein14815449MGC10870Contig53410_RCFLJ14596chromosome 9 openHypothetical protein14825450reading frame 54Contig53439_RCFLJ22457hypothetical proteinHypothetical protein14835451FLJ22457Contig53460_RCCDNA FLJ30010 fis,14845452clone3NB692000154Contig5348_RCTranscribed14855453sequence with weaksimilarity to proteinsp: Q13892(H. sapiens)BT33_HUMANTranscription factorBTF3 homolog 3Contig53517_RCPJA1praja 1Ubl conjugation pathway, Ligase,14865454Zinc-finger, Alternative splicingContig53555_RCmyotubularin relatedHydrolase, Zinc-finger, Alternative14875455protein 3splicing, Hypothetical proteinContig53566_RCLANCL2LanC lantibioticHypothetical protein14885456synthetasecomponent C-like 2(bacterial)Contig53585_RCCG005phosphonoformateHypothetical protein14895457immuno-associatedprotein 5Contig53615_RCMGC4692hypothetical protein14905458LOC283871Contig53635_RCFLJ39514sec1 family domainHypothetical protein14915459containing 2Contig53641_RCMAGE-E1melanoma antigen,Hypothetical protein14925460family D, 4Contig53696_RCMDS006x 006 protein14935461Contig53709_RCadaptor-relatedGolgi stack, Protein transport,14945462protein complex 1,Transport, Coated pits, Endocytosis,gamma 1 subunitPolymorphism, 3D-structure,Hypothetical proteinContig53719_RCFLJ30596hypothetical proteinHypothetical protein14955463FLJ30596Contig53746_RCDRLMnucleosomeHypothetical protein14965464assembly protein 1-like 5Contig53819_RCMGC11296breast cancer14975465metastasis-suppressor 1-likeContig53823_RCFLJ31295hypothetical proteinMetal-binding, Zinc, Zinc-finger,14985466FLJ31295Hypothetical proteinContig53829MGC3123hypothetical proteinHypothetical protein14995467MGC3123Contig53852_RCKIAA1577zinc finger, SWIMHypothetical protein15005468domain containing 6Contig53884_RCLOC59346PDZ and LIMHypothetical protein, LIM domain,15015469domain 2 (mystique)Metal-binding, ZincContig53909_RCMGC23947hypothetical proteinHypothetical protein15025470MGC23947Contig5392_RCTranscribed15035471sequencesContig53944_RCMI-ER1putative NFkBHypothetical protein15045472activating protein373Contig53985_RCFLJ30596hypothetical proteinHypothetical protein15055473FLJ30596Contig54010_RCMDS024chromosome 6 open15065474reading frame 75Contig54012_RCSAS10MRNA; cDNAHypothetical protein15075475DKFZp686C2051(from cloneDKFZp686C2051)Contig54048_RCGC1solute carrier familyMitochondrion, Inner membrane,1508547625 (mitochondrialRepeat, Transmembrane, Transport,carrier: glutamate),Symportmember 22Contig54066_RCDEDD2death effectorDNA-binding, Hypothetical protein15095477domain containing 2Contig54110_RCsplicing factor,mRNA processing, mRNA splicing,15105478arginine/serine-rich 1Nuclear protein, RNA-binding,(splicing factor 2,Repeat, Alternative splicing,alternate splicingAcetylation, Phosphorylationfactor)Contig54113_RCFLJ11785Rad50-interactingHypothetical protein15115479protein 1Contig54137_RCzinc finger protein 84Transcription regulation, DNA-15125480(HPF2)binding, Zinc-finger, Metal-binding,Nuclear protein, RepeatContig54184_RCMGC955hypothetical proteinHypothetical protein15135481MGC955Contig54317_RCMGC29956hypothetical proteinHypothetical protein15145482MGC29956Contig54321_RCDDX33DEAH (Asp-Glu-Ala-Hypothetical protein, ATP-binding,15155483His) box polypeptideHelicase, Hydrolase33Contig54342_RCMGC13096hypothetical proteinCytokine, Disease15165484MGC13096mutation, Gluconeogenesis, Glycolysis,Growth factor, Isomerase, NeuroneContig54371_RCGKAP42protein kinaseHypothetical protein, Kinase15175485anchoring proteinGKAP42Contig54463_RCCDNA FLJ12874 fis,15185486cloneNT2RP2003769Contig54503_RCkelch-like 11Hypothetical protein15195487(Drosophila)Contig54531_RCHomo sapiens cDNA15205488FLJ38849 fis, cloneMESAN2008936.Contig54559_RCankyrin repeat andANK repeat, Repeat15215489BTB (POZ) domaincontaining 1Contig54563_RCKNSL5kinesin familyMotor protein, Cell division,15225490member 23Microtubule, ATP-binding, Coiledcoil, Mitosis, Cell cycle, NuclearproteinContig54581_RCtumor suppressor15235491TSBF1Contig54609_RCPANK3pantothenate kinase 3Transferase, Kinase, ATP-binding,15245492Coenzyme A biosynthesisContig54614_RCFLJ14007hypothetical proteinHypothetical protein15255493FLJ14007Contig54659_RCHCCA2HCCA2 proteinHypothetical protein15265494Contig54667_RCERAP140nuclear receptorReceptor, Hypothetical protein15275495coactivator 7Contig54680_RCnucleotide-bindingHypothetical protein15285496oligomerizationdomains 27Contig54686_RCzinc finger proteinHypothetical protein15295497598Contig54716_RCKIAA0863KIAA0863 proteinHypothetical protein, Metal-binding,15305498Zinc, Zinc-fingerContig54718_RCFLJ37562hypothetical proteinHypothetical protein15315499FLJ37562Contig54729_RCchromosome 10Hypothetical protein15325500open reading frame30Contig54751_RCVIKvav-1 interactingMetal-binding, Zinc, Zinc-finger,15335501Kruppel-like proteinHypothetical proteinContig54757_RChypothetical proteinHypothetical protein15345502LOC129293Contig54802_RCGPR108G protein-coupledHypothetical protein15355503receptor 108Contig54829_RCTJP3tight junction proteinHypothetical protein153655043 (zona occludens 3)Contig54893_RCAPOBEC3Gapolipoprotein BHypothetical protein15375505mRNA editingenzyme, catalyticpolypeptide-like 3GContig54915_RCDR1Hypothetical geneTranscription, Phosphorylation,15385506supported byNuclear protein, 3D-structureAL832786(LOC400762),mRNAContig54932_RCBIVMbasic,Hypothetical protein15395507immunoglobulin-likevariable motifcontainingContig54961_RClemur tyrosineHypothetical protein, ATP-binding,15405508kinase 2Kinase, Transferase, Tyrosine-protein kinaseContig5498_RCC17orf26solute carrier familyHypothetical protein1541550939 (metal iontransporter),member 11Contig54999_RCFLJ12994hypothetical proteinHypothetical protein15425510FLJ12994Contig55004DKFZP564O0463mitochondrial folateMitochondrion, Inner membrane,15435511transporter/carrierRepeat, Transmembrane, TransportContig55022_RCALPasparaginase like 1Hypothetical protein15445512Contig55038_RCMCOLN1mucolipin 1Ionic channel, Transmembrane,15455513Hypothetical proteinContig55044_RCDECR22,4-dienoyl CoAOxidoreductase, Hypothetical protein15465514reductase 2,peroxisomalContig55069_RCHypothetical gene15475515supported byBC040598(LOC400960),mRNAContig55079_RCFLJ21613corneal woundHypothetical protein15485516healing-relatedproteinContig55114_RCchromosome 6 openHypothetical protein15495517reading frame 89Contig55121_RCP5326hypothetical proteinHypothetical protein15505518p5326Contig5513_RCTranscribed15515519sequencesContig55181_RCLOC115509hypothetical proteinHypothetical protein, Metal-binding,15525520BC014000Zinc, Zinc-fingerContig55193_RCHS6ST1heparan sulfate 6-O-Transferase15535521sulfotransferase 1Contig55254_RCLOC220074Hypothetical 55.1 kDa15545522protein F09G8.5in chromosome IIIContig55265_RCets variant gene 6Transcription regulation, Repressor,15555523(TEL oncogene)Nuclear protein, DNA-binding,Phosphorylation, Proto-oncogene,Chromosomal translocation, 3D-structureContig55334_RCDKFZp547C195hypothetical proteinHypothetical protein15565524DKFZp547C195Contig55337_RCMGC2454chromosome 2 openHypothetical protein,15575525reading frame 8Methyltransferase, TransferaseContig55351_RChypothetical proteinHypothetical protein15585526MGC45871Contig55365_RCCDNA clone15595527IMAGE: 6702802,partial cdsContig55375_RCC1QTNF6C1q and tumorCollagen, Signal15605528necrosis factorrelated protein 6Contig55377_RCDKFZp761H0421RUN domainHypothetical protein15615529containing 1Contig55397_RCCSPG6sterile alpha motifHypothetical protein, ANK repeat,15625530domain containing 6RepeatContig55468_RCsolute carrier familyHypothetical protein156355319 (sodium/hydrogenexchanger), isoform 9Contig55487_RCsolute carrier familyHypothetical protein1564553239 (zinc transporter),member 10Contig55522LOC40023615655533(LOC400236),mRNAContig55539_RCGAAI470Hypothetical protein15665534Contig55574_RCKIAA1940KIAA1940 proteinHypothetical protein15675535Contig55575_RCSDS3likely ortholog ofHypothetical protein15685536mouse Sds3Contig55618_RCMGC4825hypothetical proteinHypothetical protein15695537MGC4825Contig55671_RCnuclear factor ofTranscription regulation, Activator,15705538activated T-cells,Nuclear protein, DNA-binding,cytoplasmic,Alternative splicing, Phosphorylation,calcineurin-Repeat, 3D-structuredependent 2Contig55674_RCDUSP16LOC387840Hydrolase, Nuclear protein,15715539(LOC387840),Hypothetical proteinmRNAContig55709_RCchromosome 1415725540open reading frame35Contig55712_RChypothetical proteinHypothetical protein15735541LOC286257Contig55744_RCDIRC2disrupted in renalHypothetical protein15745542carcinoma 2Contig55759_RChypothetical proteinRepeat, ANK repeat, Alternative15755543LOC145758splicingContig55766_RCTOMM70Ahypothetical proteinMitochondrion, Outer membrane,15765544LOC348801Transmembrane, Repeat, TPRrepeatContig55767_RCFLJ22662hypothetical proteinHypothetical protein15775545FLJ22662Contig55814_RCprotein containing15785546single MORN motifin testisContig55886_RCzinc finger protein15795547181 (HHZ181)Contig55940_RCMGC13010hypothetical proteinHypothetical protein15805548MGC13010Contig55944_RCFLJ20958MRNA; cDNAHypothetical protein15815549DKFZp686A1197(from cloneDKFZp686A1197)Contig55950_RCFLJ22329hypothetical proteinHypothetical protein15825550FLJ22329Contig55966_RCDKFZP762N2316zinc finger proteinHypothetical protein, Metal-binding,15835551462Zinc, Zinc-fingerContig55979_RCMGC14136chromosome 21Hypothetical protein15845552open reading frame119Contig55_RCprotein kinase, AMP-Fatty acid biosynthesis,15855553activated, beta 2Phosphorylationnon-catalytic subunitContig56036_RCCD47CD47 antigen (Rh-Integrin, Cell adhesion, Antigen,15865554related antigen,Signal, Transmembrane,integrin-associatedGlycoprotein, Alternative splicingsignal transducer)Contig56052_RChypothetical protein15875555LOC203547Contig56056_RCTRUB1TruB pseudouridine15885556(psi) synthasehomolog 1 (E. coli)Contig56061_RCDEF6differentially15895557expressed in FDCP6 homolog (mouse)Contig56082_RCRNU2Homo sapiensHypothetical protein15905558mRNA; cDNADKFZp666D074(from cloneDKFZp666D074).Contig56147_RChypothetical proteinHypothetical protein15915559LOC338799Contig56167_RCBAALCbrain and acuteHypothetical protein15925560leukemia,cytoplasmicContig56179_RCMGC15523hypothetical proteinHypothetical protein15935561MGC15523Contig56229likely ortholog ofHypothetical protein15945562mouse zinc fingerprotein EZIContig56234_RCIMAGE3451454SVAP1 proteinHypothetical protein15955563Contig56242_RCFLJ23221hypothetical proteinHypothetical protein15965564FLJ23221Contig56253_RCFLJ21087brix domainNuclear protein15975565containing 1Contig56263_RCFLJ21080SET and MYNDZinc-finger, Hypothetical protein15985566domain containing 3Contig56298_RCFLJ13154hypothetical proteinHypothetical protein15995567FLJ13154Contig56303_RCLOC51112v-abl AbelsonTransferase, Tyrosine-protein16005568murine leukemiakinase, Proto-oncogene, ATP-viral oncogenebinding, Phosphorylation, SH2homolog 2 (arg,domain, SH3 domain, AlternativeAbelson-relatedsplicinggene)Contig56334_RCRAI16retinoic acid inducedHypothetical protein1601556916Contig56350_RCMGC4607cerebral cavernousHypothetical protein16025570malformation 2Contig56390_RCMGC26847sushi domain16035571containing 3Contig56395_RCFLJ14624hypothetical proteinHypothetical protein16045572FLJ14624Contig5639_RCphosphorylase,Transferase, Glycosyltransferase,16055573glycogen; liver (HersCarbohydrate metabolism, Glycogendisease, glycogenmetabolism, Allosteric enzyme,storage disease typePyridoxal phosphate,VI)Phosphorylation, Glycogen storagedisease, Disease mutation,Polymorphism, 3D-structureContig56503_RCMGC9753CAB2 proteinHypothetical protein16065574Contig56527_RCFLJ20758 proteinHypothetical protein16075575Contig56541_RCLSFR2dolichyl16085576pyrophosphatephosphatase 1Contig56544_RCH3F3Ahypothetical proteinNuclear protein, Chromosomal16095577FLJ20403protein, DNA-binding, Nucleosomecore, Multigene familyContig56572_RCDKFZP564B1162hypothetical proteinHypothetical protein16105578DKFZp564B1162Contig56583_RCPF20PF20Repeat, WD repeat, Hypothetical16115579proteinContig56587_RCHDAC10histone deacetylaseHydrolase, Nuclear protein,1612558010Chromatin regulator, Transcriptionregulation, Repressor,Polymorphism, Alternative splicingContig565_RCCDNA FLJ31683 fis,16135581cloneNT2RI2005353Contig56623_RCCas-Br-M (murine)Hypothetical protein, Ligase, Ubl16145582ecotropic retroviralconjugation pathway, Proto-transformingoncogene, Zinc-finger, SH2 domain,sequencePhosphorylation, Calcium-binding,3D-structureContig56662_RCMGC10963THAP domainZinc-finger, DNA-binding16155583containing 7Contig56671_RCFLJ12761mSin3A-associatedHypothetical protein16165584protein 130Contig56716_RCKIAA1754KIAA1754Hypothetical protein16175585Contig56735_RCCDNA FLJ90790 fis,Hypothetical protein16185586cloneTHYRO1001529,weakly similar toSERINEPALMITOYLTRANSFERASE2 (EC2.3.1.50).Contig56781_RCMGC11349hypothetical proteinHypothetical protein, Metal-binding,16195587MGC11349Zinc, Zinc-fingerContig56823_RCTranscribed16205588sequence withmoderate similarityto proteinref: NP_060265.1(H. sapiens)hypothetical proteinFLJ20378 [Homosapiens]Contig56944_RCASH1ash1 (absent, small,Hypothetical protein16215589or homeotic)-like(Drosophila)Contig57011_RCCDA11CDA11 proteinHypothetical protein16225590Contig57017_RCTFB2Mtranscription factorHypothetical protein16235591B2, mitochondrialContig57036_RChypothetical proteinFatty acid biosynthesis, Biotin,16245592LOC283445Ligase, Multifunctional enzyme,ATP-binding, Phosphorylation,Alternative splicingContig57057_RCMAP3K3hypothetical proteinHypothetical protein, LIM domain,16255593MGC10986Metal-binding, ZincContig57076_RCFBXO32F-box only proteinUbl conjugation pathway1626559432Contig57081_RCMSI2musashi homolog 2Hypothetical protein16275595(Drosophila)Contig57090_RCFull length insert16285596cDNA cloneYZ93G08Contig5716_RCCDNA FLJ38396 fis,16295597cloneFEBRA2007957Contig57173_RCKIAA1737KIAA1737Hypothetical protein16305598Contig571_RCST6GALNAC6CMP-NeuAC: (beta)-Glycosyltransferase, Transferase,16315599N-Hypothetical proteinacetylgalactosaminide(alpha)2,6-sialyltransferasemember VIContig57226_RCtubulin, beta, 2GTP-binding, Hypothetical protein,16325600Microtubule, Multigene familyContig57239_RCEPI64KIAA0114 geneHypothetical protein16335601productContig57270_RCABCC4ATP-bindingATP-binding, Glycoprotein,16345602cassette, sub-familyTransmembrane, Transport, RepeatC (CFTR/MRP),member 4Contig57290_RChypothetical protein16355603LOC286334Contig57417LOC80298transcriptionHypothetical protein16365604termination factor-like proteinContig57436_RCPPP2R5Eprotein phosphatasePhosphorylation, Multigene family163756052, regulatory subunitB (B56), epsilonisoformContig57458_RCIL6Rinterleukin 6 receptorReceptor, Transmembrane,16385606Glycoprotein, Immunoglobulindomain, Repeat, Alternative splicing,Signal, 3D-structureContig57493_RCMGC4399mitochondrial carrier16395607proteinContig57562_RCM11S1membraneGPI-anchor16405608component,chromosome 11,surface marker 1Contig57579ABTB1ankyrin repeat andANK repeat, Repeat16415609BTB (POZ) domaincontaining 1Contig57625_RCFLJ14225polycystic kidneyHypothetical protein16425610disease 1-likeContig57822_RCCDNA clone16435611IMAGE: 5286019,partial cdsContig57825_RCMGC18216hypothetical proteinHypothetical protein16445612MGC18216Contig57840_RCMBPCDNA cloneHypothetical protein, Myelin,16455613MGC: 70813Structural protein, Acetylation,IMAGE: 6060520,Methylation, Phosphorylation,complete cdsCitrullination, Autoimmuneencephalomyelitis, 3D-structure,Alternative splicingContig57957_RCCOL5A2similar to RIKENHypothetical protein16465614cDNA 5730578N08geneContig58042_RCCDNA FLJ39602 fis,16475615cloneSKNSH2005061Contig58113_RCFLJ14005hypothetical proteinHypothetical protein16485616LOC286044Contig58123_RCNFYBnuclear transcriptionTranscription regulation, DNA-16495617factor Y, betabinding, Activator, Nuclear protein,3D-structureContig58145_RCYEAsolute carrier familyHypothetical protein1650561835, member B4Contig58156_RCC20orf167deoxynucleotidyltransferase,Nuclear protein, Polymorphism16515619terminal,interacting protein 1Contig58193_RCTCF7L2transcription factorTranscription regulation, Activator,165256207-like 2 (T-cellRepressor, Trans-acting factor,specific, HMG-box)Nuclear protein, DNA-binding, Wntsignaling pathway, Alternativesplicing, 3D-structure, HypotheticalproteinContig58213_RCPPARBPPPAR bindingDNA-binding, Transcription16535621proteinregulation, Activator, Repeat,Nuclear protein, Alternative splicingContig58249_RCmoblakMOB1, Mps OneHypothetical protein16545622Binder kinaseactivator-like 2A(yeast)Contig58260_RCDGAT2diacylglycerol O-Hypothetical protein,16555623acyltransferaseAcyltransferase, Transferasehomolog 2 (mouse)Contig58275_RCgeneral transcription16565624factor IIIC,polypeptide 4,90 kDaContig58288_RCLOC89941ras homolog geneHypothetical protein, GTP-binding16575625family, member T2Contig58339_RCFLJ21616MRNA; cDNAHypothetical protein16585626DKFZp686E1648(from cloneDKFZp686E1648)Contig58353_RCFLJ13089hypothetical proteinHypothetical protein16595627FLJ13089Contig58491_RCTRIP11ah24a06.s1Hypothetical protein, Antigen, Golgi16605628Soares_parathyroid_tumor_NbHPAstack, Coiled coil, ChromosomalHomo sapiens cDNAtranslocationclone 1239730 3′,mRNA sequence.Contig58530_RCKIAA1560glycerol 3-phosphateHypothetical protein, Phospholipid16615629acyltransferase,biosynthesis, Transferase,mitochondrialAcyltransferase, Transmembrane,Mitochondrion, Transit peptideContig58595_RCAP1M1adaptor-relatedGolgi stack, Protein transport,16625630protein complex 1,Transport, Coated pits, Endocytosis,mu 1 subunitPhosphorylationContig58613VPS4Bvacuolar proteinATP-binding16635631sorting 4B (yeast)Contig58966_RCHLA-FmajorMHC16645632histocompatibilitycomplex, class I, FContig59120_RCFLJ37080adhesion moleculeHypothetical protein16655633AMICAContig59127_RCPCF11pre-mRNA cleavagemRNA processing, Nuclear protein16665634complex II proteinPcf11Contig59134_RChypothetical protein16675635LOC283481Contig59136_RCqp75d05.x116685636Soares_fetal_lung_NbHL19W Homosapiens cDNA cloneIMAGE: 1928841 3′similar to gb: D1453160S RIBOSOMALPROTEIN L9(HUMAN); mRNAsequence.Contig59187_RCNUDT3nudix (nucleosideHydrolase16695637diphosphate linkedmoiety X)-type motif 3Contig5954_RCsimilar to RIKENHypothetical protein, Iron, Iron-sulfur16705638cDNA B230118G17geneContig60075FLJ32468ESTs16715639Contig60315_RCMGC39807organic soluteHypothetical protein16725640transporter alphaContig6041_RCTranscribed16735641sequencesContig60509_RCGL004 proteinHypothetical protein16745642Contig60612_RCxylosyltransferase ITransferase, Glycosyltransferase16755643Contig6064_RCColorectal cancer-16765644related mRNAsequenceContig60981_RCp10-binding proteinHypothetical protein16775645Contig61061_RCRASGRP4RAS guanylHypothetical protein16785646releasing protein 4Contig6113_RCCDNA FLJ30090 fis,16795647cloneBNGH41000015Contig61227_RChypothetical proteinHypothetical protein, Repeat, WD16805648FLJ10055repeatContig61254_RCMGC5352hypothetical proteinHypothetical protein16815649MGC5352Contig61264_RCKIAA1833hypothetical proteinHypothetical protein16825650KIAA1833Contig61267_RCC20orf126chromosome 20Hypothetical protein16835651open reading frame126Contig61815LOC51063hypothetical proteinHypothetical protein16845652LOC51063Contig61848_RCTranscribed16855653sequence with weaksimilarity to proteinref: NP_060312.1(H. sapiens)hypothetical proteinFLJ20489 [Homosapiens]Contig61915_RCMGC2803hypothetical proteinHypothetical protein16865654MGC2803Contig61975MGC11242hypothetical proteinHypothetical protein16875655MGC11242Contig62149_RCchromosome 22Hypothetical protein16885656open reading frame23Contig6254_RCTranscribed16895657sequencesContig62568_RCMRPL24mitochondrialRibosomal protein, Hypothetical16905658ribosomal proteinproteinL24Contig62588_RChypothetical proteinDNA-binding, Metal-binding, Nuclear16915659LOC284323protein, Zinc-fingerContig62628_RCEIF3S9eukaryoticHypothetical protein, Initiation factor,16925660translation initiationProtein biosynthesis, RNA-bindingfactor 3, subunit 9eta, 116 kDaContig62675_RCsimilar to RIKENHypothetical protein169356611810056O20Contig62923_RCFLJ12697ubiquitin specificUbl conjugation pathway, Hydrolase,16945662protease 42Thiol protease, Multigene familyContig63026hypothetical protein16955663LOC285958Contig63079FLJ32332likely ortholog ofHypothetical protein16965664mouse proteinphosphatase 2C etaContig6323_RCFLJ12581Nanog homeoboxDNA-binding, Homeobox, Nuclear16975665protein, Hypothetical proteinContig63304LOC113444hypothetical proteinHypothetical protein16985666BC011880Contig63667_RCMCPRhypothetical proteinUbl conjugation pathway, Cell cycle,16995667LOC285069Cell division, Mitosis, RepeatContig6382_RCTranscribed17005668sequencesContig63913_RCMGC13016coiled-coil-helix-17015669coiled-coil-helixdomain containing 6Contig64214_RCMGC19604similar to RIKENHypothetical protein17025670cDNA B230118G17geneContig64297_RCKIAA1416KIAA1416 proteinHypothetical protein, Transcription17035671regulation, Hydrolase, Helicase,Chromatin regulator, Nuclearprotein, ATP-binding, DNA-binding,RepeatContig64390C20orf92COMM domainHypothetical protein17045672containing 7Contig64477Clone17055673IMAGE: 5742072,mRNAContig64502KIAA0303KIAA0303 proteinHypothetical protein, ATP-binding,17065674Kinase, Serine/threonine-proteinkinase, TransferaseContig64691UBBubiquitin BHypothetical protein17075675Contig64794FLJ21156Homo sapiensHypothetical protein17085676cDNA: FLJ21156 fis,clone CAS09878.Contig64940_RCORAOV1oral cancerHypothetical protein17095677overexpressed 1Contig65300_RCCDNA FLJ41454 fis,17105678cloneBRSTN2011597Contig65404CKLFSF3chemokine-likeChemotaxis, Cytokine,17115679factor super family 3Transmembrane, Alternative splicingContig65439C20orf178chromosome 20Hypothetical protein17125680open reading frame178Contig65459_RCformin bindingHypothetical protein, SH3 domain17135681protein 1Contig65478_RCphosphoglucomutaseHypothetical protein171456822-like 1Contig65900HMGN3high mobility groupNuclear protein, DNA-binding,17155683nucleosomal bindingHypothetical proteindomain 3Contig65934_RChypothetical geneHypothetical protein17165684supported byBC031661Contig66003_RCMY038retinoblastomaHypothetical protein, Metal-binding,17175685binding protein 6Zinc, Zinc-fingerContig66028_RCreversion-inducing-Signal, Glycoprotein, GPI-anchor,17185686cysteine-rich proteinSerine protease inhibitor,with kazal motifsMembrane, Anti-oncogene, Repeat,LipoproteinContig66129_RCCDNA FLJ13276 fis,17195687cloneOVARC1001040Contig66573_RCFLJ12567CloneHypothetical protein17205688IMAGE: 5538723,mRNAContig66615_RCUSP9YHuman S6 H-8Ubiquitin conjugation, Hydrolase,17215689mRNA expressed inThiol protease, Multigene family,chromosome 6-Alternative splicingsuppressedmelanoma cells.Contig66632_RChypothetical protein17225690LOC339324Contig66759_RCMGC16028MGC16028 similar17235691to RIKEN cDNA1700019E19 geneContig667_RCADAM17hypothetical proteinHydrolase, Metalloprotease, Zinc,17245692LOC285148Signal, Glycoprotein, Zymogen,Transmembrane, SH3-binding,Phosphorylation, Alternative splicing,3D-structureContig66868_RCze63e05.s1 Soares17255693retina N2b4HRHomo sapiens cDNAcloneIMAGE: 363680 3′,mRNA sequence.Contig66904_RCMGC4368hypothetical proteinHypothetical protein17265694MGC4368Contig684_RCRPS3Aring finger protein 12Transcription regulation, Zinc-finger,17275695Hypothetical protein, Metal-bindingContig693_RCNFIAnuclear factor I/AActivator, DNA replication, DNA-17285696binding, Nuclear protein,Transcription, Transcriptionregulation, Multigene familyContig706_RCCDNA FLJ32401 fis,17295697cloneSKMUS2000339Contig726_RCFLJ13725hypothetical proteinHypothetical protein17305698FLJ13725Contig732_RCFTH1transducer ofHypothetical protein17315699regulated cAMPresponse element-binding protein(CREB) 2Contig7401_RCFLJ22756PDZ domainHypothetical protein17325700containing 2Contig75_RCRPS6KA2ribosomal protein S6ATP-binding, Kinase,17335701kinase, 90 kDa,Serine/threonine-protein kinase,polypeptide 2Transferase, Repeat, Multigenefamily, Phosphorylation, NuclearproteinContig773FLJ20989hypothetical proteinHypothetical protein17345702FLJ20989Contig8210_RCDJ467N11.1dJ467N11.1 proteinATP-binding, Helicase, Hydrolase,17355703Hypothetical proteinContig830_RCC1orf13N-acetylneuraminate17365704pyruvate lyase(dihydrodipicolinatesynthase)Contig8371_RCTranscribed17375705sequencesContig842_RChuman T-cellTranscription regulation, DNA-17385706leukemia virusbinding, Nuclear proteinenhancer factorContig844_RCDKFZP566M1046hypothetical proteinHypothetical protein17395707DKFZp566M1046Contig8547_RCTranscribed17405708sequencesContig883_RCKIAA1813KIAA1813 proteinHypothetical protein17415709Contig8885_RCHCScytochrome c,Mitochondrion, Electron transport,17425710somaticRespiratory chain, Heme,Acetylation, Polymorphism,ApoptosisContig8909_RCMGC45404TAK1-bindingHypothetical protein17435711protein 3Contig8956_RCFLJ13158chromosome 6 openHypothetical protein17445712reading frame 134Contig8963_RCwi72b03.x117455713NCI_CGAP_Kid12Homo sapiens cDNAcloneIMAGE: 2398829 3′,mRNA sequence.Contig8980_RCDKFZP564B1162hypothetical proteinHypothetical protein17465714DKFZp564B1162Contig9042_RCTranscribed17475715sequencesContig9059_RCFLJ12118hypothetical proteinHypothetical protein17485716FLJ12118Contig9136_RCCDNA FLJ43053 fis,17495717cloneBRTHA3006856Contig9380_RCTranscribed17505718sequencesContig9514_RCTranscribed17515719sequencesContig9518_RCZNF287zinc finger proteinMetal-binding, Zinc, Zinc-finger,17525720287Transcription regulation, Nuclearprotein, DNA-binding, RepeatContig964_RCMGC10433hypothetical proteinHypothetical protein17535721MGC10433Contig9714_RCMRNA forHypothetical protein17545722hypothetical protein(ORF1), clone 00275Contig973_RCMRPL45mitochondrialRibosomal protein, Mitochondrion,17555723ribosomal proteinTransit peptideL45Contig9810_RCKCNE1potassium voltage-Transport, Ion transport, Ionic17565724gated channel, lsk-channel, Voltage-gated channel,related family,Potassium channel, Potassium,member 1Potassium transport,Transmembrane, Phosphorylation,Glycoprotein, Polymorphism,Disease mutation, Long QTsyndrome, DeafnessContig9965_RCDHODHdihydroorotatePyrimidine biosynthesis,17575725dehydrogenaseOxidoreductase, Flavoprotein, FAD,Transit peptide, Mitochondrion, 3D-structureD10040FACL2acyl-CoA synthetaseLigase, Fatty acid metabolism,17585726long-chain familyMagnesium, Multigene family,member 1Hypothetical proteinD13642SF3B3splicing factor 3b,Spliceosome, mRNA processing,17595727subunit 3, 130 kDamRNA splicing, Nuclear protein,Hypothetical proteinD16816REG1Bregenerating islet-Glycoprotein, Signal, Lectin,17605728derived 1 betaPyrrolidone carboxylic acid(pancreatic stoneprotein, pancreaticthread protein)D21064INPP5EpeptidaseHypothetical protein, Hydrolase,17615729(mitochondrialMetalloprotease, Mitochondrion,processing) alphaTransit peptideD25218RRS1RRS1 ribosomeRibosome biogenesis, Nuclear17625730biogenesis regulatorproteinhomolog (S. cerevisiae)D25328PFKPphosphofructokinase,Kinase, Transferase, Glycolysis,17635731plateletRepeat, Allosteric enzyme,Phosphorylation, Magnesium,Multigene familyD26070ITPR1inositol 1,4,5-Receptor, Transmembrane,17645732triphosphatePhosphorylation, Endoplasmicreceptor, type 1reticulum, Ionic channel, Iontransport, Calcium channel,Alternative splicing, RepeatD26362BRD3bromodomainBromodomain, Repeat, Nuclear17655733containing 3proteinD26488KIAA0007KIAA0007 proteinHypothetical protein, Repeat, WD17665734repeatD29954KIAA0056KIAA0056 proteinHypothetical protein17675735D29958KIAA0116KIAA0116 proteinExosome, Hydrolase, Nuclease,17685736Exonuclease, rRNA processing,Nuclear protein, RNA-binding,Polymorphism, Hypothetical proteinD31886RAB3GAPRAB3 GTPase-Hypothetical protein17695737ACTIVATINGPROTEIND31887KIAA0062solute carrier familyHypothetical protein1770573839 (zinc transporter),member 14D38435PMS2L1postmeioticHypothetical protein, DNA repair,17715739segregationAnti-oncogene, Nuclear protein,increased 2-like 6Polymorphism, Disease mutation,Hereditary nonpolyposis colorectalcancer, 3D-structureD38522SYT11Homo sapiensTransmembrane, Repeat, Synapse,17725740KIAA0080 mRNA,Hypothetical proteinpartial cds.D38549CYFIP1cytoplasmic FMR1Hypothetical protein17735741interacting protein 1D42043KIAA0084raft-linking proteinHypothetical protein17745742D42084METAP1methionylHydrolase, Aminopeptidase, Cobalt17755743aminopeptidase 1D43948KIAA0097KIAA0097 geneHypothetical protein, Repeat17765744productD43949KIAA0082KIAA0082Hypothetical protein17775745D50402SLC11A1solute carrier familyTransport, Iron transport,1778574611 (proton-coupledTransmembrane, Glycoprotein,divalent metal ionMacrophage, Polymorphismtransporters),member 1D50911GSA7KIAA0121 geneHypothetical protein17795747productD509186-Sepseptin 6Cell division, GTP-binding, Coiled17805748coil, Alternative splicingD63487KIAA0153KIAA0153 proteinHypothetical protein17815749D79998KCTD2potassium channelHypothetical protein17825750tetramerisationdomain containing 2D80007PDCD11programmed cellNuclear protein, rRNA processing,17835751death 11Repeat, PolymorphismD80010LPIN1lipin 1Nuclear protein, Polymorphism17845752D83781NUP160nucleoporin 160 kDaNuclear protein, Transport,17855753Alternative splicing, HypotheticalproteinD84294TTC3tetratricopeptideRepeat, TPR repeat, Zinc-finger,17865754repeat domain 3Alternative splicing, Polymorphism,Metal-bindingD86964DOCK2dedicator ofGuanine-nucleotide releasing factor,17875755cytokinesis 2Membrane, Cytoskeleton, SH3domain, Alternative splicing,PolymorphismD86973GCN1L1GCN1 generalHypothetical protein17885756control of amino-acidsynthesis 1-like 1(yeast)D86976HA-1minor17895757histocompatibilityantigen HA-1D87442NCSTNnicastrinTransmembrane, Glycoprotein,17905758Signal, Alternative splicingD87449SLC35D1solute carrier familyTransport, Sugar transport,1791575935 (UDP-glucuronicTransmembrane, Endoplasmicacid/UDP-N-reticulumacetylgalactosaminedual transporter),member D1D87453MRPS27mitochondrialHypothetical protein, Ribosomal17925760ribosomal proteinprotein, MitochondrionS27D87466KIAA0276KIAA0276 proteinHypothetical protein17935761G26403C9orf19chromosome 9 openHypothetical protein17945762reading frame 19J03077PSAPprosaposin (variantSignal, Glycoprotein, Lysosome,17955763Gaucher diseaseSphingolipid metabolism, Repeat,and variantGaucher disease, GM2-metachromaticgangliosidosis, Disease mutation,leukodystrophy)Metachromatic leukodystrophy,Alternative splicing, 3D-structureJ03796EPB41erythrocyteStructural protein, Alternative17965764membrane proteinsplicing, Cytoskeleton, Actin-binding,band 4.1Phosphorylation, Pyropoikilocytosis,(elliptocytosis 1, RH-Glycoprotein, Elliptocytosis,linked)Hereditary hemolytic anemia,Polymorphism, 3D-structureJ04162FCGR3AFc fragment of IgG,Receptor, IgG-binding protein,17975765low affinity IIIa,Transmembrane, Glycoprotein,receptor for (CD16)Signal, Immunoglobulin domain,Repeat, Multigene family,Polymorphism, GPI-anchor, 3D-structure, LipoproteinJ04178HEXAhexosaminidase AHydrolase, Glycosidase, Lysosome,17985766(alpha polypeptide)GM2-gangliosidosis, Signal,Zymogen, Glycoprotein, Diseasemutation, Polymorphism, 3D-structureK02276MYCv-mycProto-oncogene, Nuclear protein,17995767myelocytomatosisDNA-binding, Phosphorylation,viral oncogeneTranscription regulation, Activator,homolog (avian)Glycoprotein, Polymorphism, 3D-structure.K02403C4AcomplementComplement pathway, Plasma,18005768component 4AGlycoprotein, Sulfation, Signal,Inflammatory response,Polymorphism, Disease mutation,Blood group antigen, Thioester bondL00635FNTBfarnesyltransferase,Plasmid, Transferase,18015769CAAX box, betaPrenyltransferase, Repeat, ZincL08246MCL1myeloid cellApoptosis, Transmembrane,18025770leukemia sequenceDifferentiation, Alternative splicing1 (BCL2-related)L20688ARHGDIBRho GDPGTPase activation, 3D-structure18035771dissociation inhibitor(GDI) betaL21961IGL@Human IgImmunoglobulin domain,18045772rearranged lambda-Hypothetical protein,chain mRNA,Immunoglobulin C region, 3D-subgroup VL3, V-Jstructureregion, partial cds.L22005CDC34cell division cycle 34Ubl conjugation pathway, Ligase,18055773Multigene family, Hypotheticalprotein, Cell divisionL27943CDAcytidine deaminaseHydrolase, Zinc18065774L35035RPIAribose 5-phosphateIsomerase18075775isomerase A (ribose5-phosphateepimerase)L39061TAF1BTATA box bindingHypothetical protein18085776protein (TBP)-associated factor,RNA polymerase I,B, 63 kDaL40027GSK3Aglycogen synthaseTransferase, Serine/threonine-18095777kinase 3 alphaprotein kinase, ATP-binding,Multigene family, PhosphorylationM12679HLA-CmajorGlycoprotein, Signal,18105778histocompatibilityTransmembrane, Hypotheticalcomplex, class I, Cprotein, MHC, MHC I,Polymorphism, 3D-structure,Alternative splicingM12758HLA-CHuman MHC class IGlycoprotein, Transmembrane18115779HLA-A cell surfaceantigen mRNA,(HLA-A2, -B7, -C),clone JY103.M17733TMSB4Xthymosin, beta 4, X-Actin-binding, Cytoskeleton,18125780linkedAcetylationM26383IL8interleukin 8Cytokine, Chemotaxis, Inflammatory18135781response, Signal, Alternativesplicing, 3D-structureM31212MYL6myosin, lightMyosin, Muscle protein, Acetylation,18145782polypeptide 6, alkali,Alternative splicing, Multigene familysmooth muscle andnon-muscleM31523TCF3transcription factor 3Transcription regulation, DNA-18155783(E2Abinding, Nuclear protein, Proto-immunoglobulinoncogene, Chromosomalenhancer bindingtranslocation, Alternative splicing,factors E12/E47)Phosphorylation, 3D-structureM33552LSP1lymphocyte-specificT-cell, Phosphorylation,18165784protein 1PolymorphismM34671CD59CD59 antigen p18-20Antigen, Glycoprotein, GPI-anchor,18175785(antigen identifiedSignal, 3D-structure, Lipoproteinby monoclonalantibodies 16.3A5,EJ16, EJ30, EL32and G344)M37712CDC2L2Homo sapiensApoptosis, Transferase,18185786p58/GTA proteinSerine/threonine-protein kinase,kinase mRNA,ATP-binding, Cell cycle,complete cds.Phosphorylation, Alternative splicing,Alternative initiationM60721HLX1H2.0-like homeo boxDNA-binding, Homeobox, Nuclear181957871 (Drosophila)protein, Transcription regulationM63438IGKCImmunoglobulinHypothetical protein18205788kappa light chainmRNA, partial cdsM65292HFL1H factorRepeat, Glycoprotein, Sushi, Signal,18215789(complement)-like 1PolymorphismM74782IL3RAinterleukin 3Receptor, Transmembrane,18225790receptor, alpha (lowGlycoprotein, Signalaffinity)M83822LRBALPS-responsiveRepeat, WD repeat18235791vesicle trafficking,beach and anchorcontainingM90657TM4SF1Human tumorGlycoprotein, Antigen,18245792antigen (L6) mRNA,Transmembranecomplete cds.M91211AGERadvancedImmunoglobulin domain,18255793glycosylation endGlycoprotein, Transmembrane,product-specificRepeat, Signal, Alternative splicing,receptorPolymorphism, ReceptorM92439LRPPRCleucine-rich PPR-Hypothetical protein, Repeat18265794motif containingM92642COL16A1collagen, type XVI,Extracellular matrix, Connective18275795alpha 1tissue, Collagen, Hydroxylation,Repeat, SignalM94362LMNB2Human lamin B2Intermediate filament, Coiled coil,18285796(LAMB2) mRNA,Nuclear protein, Lipoprotein,partial cds.Prenylation, Phosphorylation,Hypothetical proteinNM_000016ACADMacyl-Coenzyme AOxidoreductase, Flavoprotein, FAD,18295797dehydrogenase, C-4Fatty acid metabolism,to C-12 straightMitochondrion, Transit peptide,chainDisease mutation, 3D-structureNM_000018ACADVLacyl-Coenzyme AOxidoreductase, Flavoprotein, FAD,18305798dehydrogenase, veryFatty acid metabolism,long chainMitochondrion, Transit peptide,Alternative splicing, Diseasemutation, Polymorphism,CardiomyopathyNM_000021PSEN1presenilin 1Transmembrane, Phosphorylation,18315799(Alzheimer diseaseEndoplasmic reticulum, Golgi stack,3)Alzheimer's disease, Diseasemutation, Polymorphism, AlternativesplicingNM_000022ADAadenosineHydrolase, Nucleotide metabolism,18325800deaminaseSCID, Hereditary hemolytic anemia,Disease mutation, PolymorphismNM_000026ADSLadenylosuccinatePurine biosynthesis, Lyase,18335801lyaseAlternative splicing, Diseasemutation, EpilepsyNM_000030AGXTalanine-glyoxylateAminotransferase, Transferase,18345802aminotransferasePyridoxal phosphate, Peroxisome,(oxalosis I;Mitochondrion, Disease mutation,hyperoxaluria I;Polymorphismglycolicaciduria;serine-pyruvateaminotransferase)NM_000034ALDOAaldolase A, fructose-Lyase, Schiff base, Glycolysis,18355803bisphosphateMultigene family, 3D-structure,Disease mutationNM_000045ARG1arginase, liverUrea cycle, Arginine metabolism,18365804Hydrolase, Manganese, Diseasemutation, PolymorphismNM_000056BCKDHBbranched chain ketoOxidoreductase, Mitochondrion,18375805acid dehydrogenaseTransit peptide, Disease mutation,E1, beta polypeptideMaple syrup urine disease, 3D-(maple syrup urinestructuredisease)NM_000070CAPN3calpain 3, (p94)Hydrolase, Thiol protease, Calcium-18385806binding, Multigene family, Repeat,Disease mutation, Polymorphism,Alternative splicingNM_000073CD3GCD3G antigen,Immunoglobulin domain, T-cell,18395807gamma polypeptideReceptor, Transmembrane,(TiT3 complex)Glycoprotein, SignalNM_000074TNFSF5tumor necrosis factorCytokine, Transmembrane,18405808(ligand) superfamily,Glycoprotein, Signal-anchor,member 5 (hyper-Antigen, Disease mutation,IgM syndrome)Polymorphism, 3D-structureNM_000081CHS1Chediak-HigashiProtein transport, Transport, Repeat,18415809syndrome 1WD repeat, Disease mutation,Alternative splicingNM_000082CKN1Cockayne syndromeNuclear protein, Repeat, WD repeat,184258101 (classical)Transcription regulation,Polymorphism, Cockayne'ssyndrome, Deafness, DwarfismNM_000095COMPcartilage oligomericHypothetical protein, Glycoprotein,18435811matrix proteinCell adhesion, Calcium-binding,(pseudoachondroplasia,Repeat, EGE-like domain, Signal,epiphysealDisease mutation, Polymorphismdysplasia 1, multiple)NM_000099CST3cystatin C (amyloidThiol protease inhibitor, Amyloid,18445812angiopathy andSignal, Disease mutation,cerebralPolymorphism, 3D-structurehemorrhage)NM_000100CSTBcystatin B (stefin B)Thiol protease inhibitor, Nuclear18455813protein, Acetylation, Diseasemutation, Epilepsy, 3D-structureNM_000101CYBAcytochrome b-245,Oxidoreductase, NADP, Electron18465814alpha polypeptidetransport, Membrane, Heme,Polymorphism, Disease mutation,Chronic granulomatous disease,Hypothetical proteinNM_000116TAZtafazzinAlternative splicing,18475815(cardiomyopathy,Transmembrane, Disease mutationdilated 3A (X-linked);endocardialfibroelastosis 2;Barth syndrome)NM_000120EPHX1epoxide hydrolase 1,Hydrolase, Endoplasmic reticulum,18485816microsomalDetoxification, Transmembrane,(xenobiotic)Aromatic hydrocarbons catabolism,Microsome, PolymorphismNM_000121EPORerythropoietinReceptor, Transmembrane,18495817receptorGlycoprotein, Signal,Phosphorylation, 3D-structureNM_000126ETFAelectron-transfer-Electron transport, Flavoprotein,18505818flavoprotein, alphaFAD, Mitochondrion, Transit peptide,polypeptide (glutaricDisease mutation, Glutaricaciduria,aciduria II)Polymorphism, 3D-structureNM_000130F5coagulation factor VBlood coagulation, Glycoprotein,18515819(proaccelerin, labileSulfation, Calcium, Signal, Zymogen,factor)Repeat, Polymorphism, Diseasemutation, Thrombophilia, 3D-structureNM_000143FHfumarate hydrataseLyase, Tricarboxylic acid cycle,18525820Mitochondrion, Transit peptide,Acetylation, Alternative initiation,Anti-oncogene, Disease mutationNM_000146FTLferritin, lightHypothetical protein, Iron storage,18535821polypeptideMetal-binding, AcetylationNM_000151G6PCglucose-6-Glycogen biosynthesis, Hydrolase,18545822phosphatase,Transmembrane, Glycoprotein,catalytic (glycogenEndoplasmic reticulum, Glycogenstorage disease typestorage disease, Disease mutation,I, von GierkePolymorphismdisease)NM_000156GAMTguanidinoacetate N-Transferase, Methyltransferase18555823methyltransferaseNM_000157GBAglucosidase, beta;Glycosidase, Hydrolase, Signal,18565824acid (includesHypothetical protein, Sphingolipidglucosylceramidase)metabolism, Glycoprotein,Lysosome, Membrane, Gaucherdisease, Disease mutation,Polymorphism, Alternative initiation,PharmaceuticalNM_000175GPIglucose phosphateGluconeogenesis, Glycolysis,18575825isomeraseIsomerase, Growth factor, Cytokine,Disease mutation, 3D-structure,Hypothetical proteinNM_000177GSNgelsolinCytoskeleton, Actin-binding, Repeat,18585826(amyloidosis, FinnishCalcium, Alternative initiation,type)Signal, Amyloid, Disease mutation,3D-structure, Phosphorylation, ActincappingNM_000181GUSBglucuronidase, betaHydrolase, Glycosidase, Lysosome,18595827Glycoprotein, Signal,Mucopolysaccharidosis, Diseasemutation, 3D-structure, Alternativesplicing, PolymorphismNM_000183HADHBhydroxyacyl-Fatty acid metabolism, Transferase,18605828Coenzyme AAcyltransferase, Mitochondrion,dehydrogenase/3-Transit peptide, Disease mutation,ketoacyl-CoenzymeHypothetical proteinA thiolase/enoyl-Coenzyme Ahydratase(trifunctionalprotein), betasubunitNM_000186HF1H factor 1Complement alternate pathway,18615829(complement)Plasma, Glycoprotein, Repeat,Sushi, Signal, 3D-structure,Polymorphism, Alternative splicingNM_000206IL2RGinterleukin 2Receptor, Transmembrane,18625830receptor, gammaGlycoprotein, Signal, Disease(severe combinedmutation, SCID, 3D-structureimmunodeficiency)NM_000211ITGB2integrin, beta 2Integrin, Cell adhesion, Receptor,18635831(antigen CD18 (p95),Transmembrane, Glycoprotein,lymphocyte function-Repeat, Signal, Disease mutation,associated antigenPyrrolidone carboxylic acid, 3D-1; macrophagestructureantigen 1 (mac-1)beta subunit)NM_000229LCATlecithin-cholesterolCholesterol metabolism, Lipid18645832acyltransferasemetabolism, Transferase,Acyltransferase, Signal,Glycoprotein, Polymorphism,Disease mutationNM_000235LIPAlipase A, lysosomalHydrolase, Lipid degradation,18655833acid, cholesterolGlycoprotein, Signal, Lysosome,esterase (WolmanDisease mutation, Polymorphismdisease)NM_000239LYZlysozyme (renalHydrolase, Glycosidase,18665834amyloidosis)Bacteriolytic enzyme, Signal,Amyloid, 3D-structure, Diseasemutation, PolymorphismNM_000243MEFVMediterranean feverInflammatory response, Actin-18675835binding, Metal-binding, Cytoskeleton,Microtubule, Nuclear protein, Zinc-finger, Zinc, Polymorphism, Diseasemutation, Alternative splicingNM_000249MLH1mutL homolog 1,DNA repair, Nuclear protein,18685836colon cancer,Disease mutation, Anti-oncogene,nonpolyposis type 2Polymorphism, Hereditary(E. coli)nonpolyposis colorectal cancerNM_000250MPOmyeloperoxidaseOxidoreductase, Peroxidase, Iron,18695837Heme, Calcium-binding,Glycoprotein, Signal, Oxidation,Lysosome, Alternative splicing,Polymorphism, Disease mutation,3D-structureNM_000254MTR5-Transferase, Methyltransferase,18705838methyltetrahydrofolate-Methionine biosynthesis, VitaminhomocysteineB12, Cobalt, Disease mutation,methyltransferasePolymorphismNM_000265NCF1neutrophil cytosolicSH3 domain, Repeat,18715839factor 1 (47 kDa,Polymorphism, Disease mutation,chronicChronic granulomatous disease, 3D-granulomatousstructuredisease, autosomal1)NM_000269NME1non-metastatic cellsTransferase, Kinase, ATP-binding,187258401, protein (NM23A)Nuclear protein, Anti-oncogene,expressed inDisease mutation, 3D-structureNM_000270NPnucleosideHypothetical protein, Transferase,18735841phosphorylaseGlycosyltransferase, Polymorphism,Disease mutation, 3D-structureNM_000285PEPDpeptidase DCollagen degradation, Hydrolase,18745842Dipeptidase, Metalloprotease,Manganese, Acetylation,Polymorphism, Disease mutationNM_000288PEX7peroxisomalRepeat, WD repeat, Peroxisome,18755843biogenesis factor 7Transport, Protein transport,Rhizomelic chondrodysplasiapunctata, Disease mutation,PolymorphismNM_000289PFKMphosphofructokinase,Glycolysis, Kinase, Transferase,18765844muscleRepeat, Allosteric enzyme,Phosphorylation, Magnesium,Multigene family, Alternative splicing,Disease mutation, Glycogen storagediseaseNM_000291PGK1phosphoglycerateTransferase, Kinase, Multigene18775845kinase 1family, Glycolysis, Acetylation,Disease mutation, Polymorphism,Hereditary hemolytic anemiaNM_000295SERPINA1serine (or cysteine)Serpin, Serine protease inhibitor,18785846proteinase inhibitor,Glycoprotein, Plasma,clade A (alpha-1Polymorphism, Acute phase, Signal,antiproteinase,3D-structure, Disease mutation,antitrypsin), member 1Protease inhibitorNM_000297PKD2polycystic kidneyIonic channel, Glycoprotein, Coiled18795847disease 2coil, Transmembrane, Calcium-(autosomalbinding, Disease mutation,dominant)PolymorphismNM_000302PLODprocollagen-lysine,Oxidoreductase, Dioxygenase,188058482-oxoglutarate 5-Signal, Iron, Vitamin C, Glycoprotein,dioxygenase (lysineEndoplasmic reticulum, Membrane,hydroxylase, Ehlers-Polymorphism, Disease mutation,Danlos syndromeEhlers-Danlos syndrometype VI)NM_000305PON2paraoxonase 2Hydrolase, Glycoprotein, Signal,18815849Membrane, Multigene family,Polymorphism, Alternative splicingNM_000307POU3F4POU domain, classTranscription regulation, Nuclear188258503, transcription factor 4protein, DNA-binding, Homeobox,Disease mutation, DeafnessNM_000320QDPRquinoidTetrahydrobiopterin biosynthesis,18835851dihydropteridineOxidoreductase, NADP, 3D-reductasestructure, Polymorphism,Phenylketonuria, Disease mutationNM_000321RB1retinoblastoma 1Transcription regulation, DNA-18845852(includingbinding, Nuclear protein,osteosarcoma)Phosphorylation, Anti-oncogene,Disease mutation, 3D-structureNM_000327ROM1retinal outerVision, Cell adhesion,18855853segment membranePhotoreceptor, Transmembrane,protein 1Polymorphism, Disease mutation,Retinitis pigmentosaNM_000376VDRvitamin D (1,25-Receptor, Transcription regulation,18865854dihydroxyvitamin D3)DNA-binding, Nuclear protein, Zinc-receptorfinger, Phosphorylation, Diseasemutation, 3D-structureNM_000377WASWiskott-AldrichRepeat, Disease mutation,18875855syndrome (eczema-Phosphorylation, 3D-structurethrombocytopenia)NM_000380XPAxerodermaDNA repair, DNA-binding, Zinc-18885856pigmentosum,finger, Nuclear protein, Xerodermacomplementationpigmentosum, Disease mutation,group APolymorphism, 3D-structureNM_000386BLMHbleomycin hydrolaseHydrolase, Thiol protease,18895857Polymorphism, 3D-structure,Hypothetical proteinNM_000392ABCC2ATP-bindingATP-binding, Glycoprotein,18905858cassette, sub-familyTransmembrane, Transport, Repeat,C (CFTR/MRP),Disease mutation, Polymorphismmember 2NM_000394CRYAAcrystallin, alpha AEye lens protein, Acetylation,18915859Glycoprotein, Disease mutation,VisionNM_000397CYBBcytochrome b-245,Oxidoreductase, NADP, Electron18925860beta polypeptidetransport, Transmembrane, FAD,(chronicHeme, Glycoprotein, Voltage-gatedgranulomatouschannel, Ionic channel, Diseasedisease)mutation, Chronic granulomatousdiseaseNM_000399EGR2early growthTranscription regulation, Activator,18935861response 2 (Krox-20DNA-binding, Nuclear protein,homolog,Repeat, Zinc-finger, Metal-binding,Drosophila)Alternative splicing, Diseasemutation, Charcot-Marie-Toothdisease, Dejerine-Sottas syndromeNM_000401EXT2exostoses (multiple) 2Transferase, Glycosyltransferase,18945862Endoplasmic reticulum, Golgi stack,Transmembrane, Signal-anchor,Glycoprotein, Anti-oncogene,Disease mutation, Hereditarymultiple exostoses, AlternativesplicingNM_000402G6PDglucose-6-phosphateOxidoreductase, NADP, Glucose18955863dehydrogenasemetabolism, Disease mutation,Polymorphism, Hereditary hemolyticanemia, Alternative splicing,AcetylationNM_000404GLB1galactosidase, beta 1Hydrolase, Glycosidase, Lysosome,18965864Signal, Alternative splicing,Glycoprotein, Polymorphism,Disease mutationNM_000405GM2AGM2 gangliosideSignal, Glycoprotein, Lysosome,18975865activator proteinSphingolipid metabolism, GM2-gangliosidosis, Disease mutation,Polymorphism, 3D-structureNM_000407GP1BBglycoprotein lbHypothetical protein, Cell division,18985866(platelet), betaGTP-binding, Coiled coil, Platelet,polypeptideTransmembrane, Glycoprotein,Hemostasis, Blood coagulation,Signal, Phosphorylation, Celladhesion, Leucine-rich repeatNM_000418IL4Rinterleukin 4 receptorReceptor, Transmembrane,18995867Glycoprotein, Signal, Diseasemutation, Polymorphism, 3D-structureNM_000425L1CAML1 cell adhesionNeurogenesis, Cell adhesion,19005868moleculeDevelopmental protein,(hydrocephalus,Glycoprotein, Transmembrane,stenosis of aqueductRepeat, Antigen, Immunoglobulinof Sylvius 1, MASAdomain, Signal, Disease mutation,(mental retardation,Alternative splicingaphasia, shufflinggait and adductedthumbs) syndrome,spastic paraplegia 1)NM_000433NCF2neutrophil cytosolicSH3 domain, Repeat, TPR repeat,19015869factor 2 (65 kDa,Chronic granulomatous disease,chronicDisease mutation, 3D-structuregranulomatousdisease, autosomal2)NM_000434NEU1sialidase 1Hydrolase, Glycosidase, Signal,19025870(lysosomal sialidase)Repeat, Glycoprotein, Diseasemutation, Polymorphism,PhosphorylationNM_000436OXCT3-oxoacid CoAMitochondrion, Transferase, Transit19035871transferasepeptide, Disease mutation,PolymorphismNM_000445PLEC1plectin 1,Coiled coil, Repeat, Structural19045872intermediate filamentprotein, Cytoskeleton, Actin-binding,binding proteinPhosphorylation, Alternative splicing,500 kDaEpidermolysis bullosa, DiseasemutationNM_000454SOD1superoxideAntioxidant, Oxidoreductase, Metal-19055873dismutase 1, solublebinding, Copper, Zinc, Acetylation,(amyotrophic lateral3D-structure, Amyotrophic lateralsclerosis 1 (adult))sclerosis, Disease mutationNM_000456SUOXsulfite oxidaseOxidoreductase, Mitochondrion,19065874Heme, Molybdenum, Transit peptide,Disease mutation, 3D-structureNM_000462UBE3Aubiquitin proteinLigase, Nuclear protein, Ubl19075875ligase E3A (humanconjugation pathway, Alternativepapilloma virus E6-splicing, Disease mutation,associated protein,Polymorphism, 3D-structure,AngelmanHypothetical proteinsyndrome)NM_000476AK1adenylate kinase 1Transferase, Kinase, ATP-binding,19085876Acetylation, Disease mutationNM_000480AMPD3adenosineHydrolase, Nucleotide metabolism,19095877monophosphateMultigene family, Polymorphism,deaminase (isoformAlternative splicingE)NM_000481AMTaminomethyltransferaseHypothetical protein, Transferase,19105878(glycineAminotransferase, Mitochondrion,cleavage systemTransit peptide, Disease mutationprotein T)NM_000487ARSAarylsulfatase AHydrolase, Signal, Glycoprotein,19115879Lysosome, Disease mutation,Metachromatic leukodystrophy,Sphingolipid metabolism,Polymorphism, 3D-structureNM_000497CYP11B1cytochrome P450,Steroidogenesis, Electron transport,19125880family 11, subfamilySteroid metabolism, Oxidoreductase,B, polypeptide 1Monooxygenase, Mitochondrion,Membrane, Heme, Transit peptide,Polymorphism, Disease mutationNM_000502EPXeosinophilOxidoreductase, Peroxidase, Iron,19135881peroxidaseHeme, Glycoprotein, Signal, DiseasemutationNM_000507FBP1fructose-1,6-Hydrolase, Carbohydrate19145882bisphosphatase 1metabolism, Gluconeogenesis, Zinc,Allosteric enzyme, Disease mutation,Polymorphism, 3D-structure,Hypothetical proteinNM_000512GALNSgalactosamine (N-Hypothetical protein19155883acetyl)-6-sulfatesulfatase (Morquiosyndrome,mucopolysaccharidosistype IVA)NM_000517HBA2hemoglobin, alpha 2Heme, Oxygen transport, Transport,19165884Erythrocyte, Disease mutation,Polymorphism, Acetylation, 3D-structureNM_000525KCNJ11potassium inwardly-Ionic channel, Ion transport, Voltage-19175885rectifying channel,gated channel, Transmembrane,subfamily J, memberPotassium transport, Polymorphism,11Disease mutation, Diabetes mellitusNM_000528MAN2B1mannosidase, alpha,Glycosidase, Hydrolase,19185886class 2B, member 1Glycoprotein, Lysosome, Zymogen,Signal, Disease mutation,PolymorphismNM_000532PCCBpropionyl CoenzymeHypothetical protein, Mitochondrion,19195887A carboxylase, betaTransit peptide, Ligase, DiseasepolypeptidemutationNM_000542SFTPBsurfactant,Surface film, Gaseous exchange,19205888pulmonary-Glycoprotein, Repeat,associated protein BPolymorphism, 3D-structureNM_000558HBA1hemoglobin, alpha 2Heme, Oxygen transport, Transport,19215889Erythrocyte, Disease mutation,Polymorphism, Acetylation, 3D-structureNM_000565IL6Rinterleukin 6 receptorReceptor, Transmembrane,19225890Glycoprotein, Immunoglobulindomain, Repeat, Alternative splicing,Signal, 3D-structureNM_000569FCGR3AFc fragment of IgG,IgG-binding protein, Receptor,19235891low affinity IIIa,Transmembrane, Glycoprotein,receptor for (CD16)Signal, Immunoglobulin domain,Repeat, Multigene family,Polymorphism, GPI-anchor, 3D-structure, LipoproteinNM_000573CR1complementComplement pathway, Glycoprotein,19245892component (3b/4b)Transmembrane, Repeat, Signal,receptor 1, includingReceptor, Sushi, Blood groupKnops blood groupantigen, Polymorphism, Pyrrolidonesystemcarboxylic acid, 3D-structureNM_000578SLC11A1solute carrier familyTransport, Iron transport,1925589311 (proton-coupledTransmembrane, Glycoprotein,divalent metal ionMacrophage, Polymorphismtransporters),member 1NM_000581GPX1glutathioneOxidoreductase, Peroxidase,19265894peroxidase 1Selenium, Selenocysteine,Erythrocyte, Polymorphism,Hypothetical proteinNM_000584IL8interleukin 8Cytokine, Chemotaxis, Inflammatory19275895response, Signal, Alternativesplicing, 3D-structureNM_000591CD14CD14 antigenImmune response, Inflammatory19285896response, Signal, GPI-anchor,Repeat, Leucine-rich repeat,Glycoprotein, Antigen, LipoproteinNM_000607ORM1orosomucoid 1Glycoprotein, Plasma, Acute phase,19295897Signal, Lipocalin, Polymorphism,Multigene family, Pyrrolidonecarboxylic acidNM_000608ORM2orosomucoid 1Glycoprotein, Plasma, Acute phase,19305898Signal, Lipocalin, Multigene family,Polymorphism, Pyrrolidonecarboxylic acidNM_000631NCF4neutrophil cytosolicSH3 domain, Alternative splicing,19315899factor 4, 40 kDa3D-structureNM_000632ITGAMintegrin, alpha MIntegrin, Cell adhesion, Receptor,19325900(complementGlycoprotein, Transmembrane,component receptorSignal, 3D-structure, Repeat,3, alpha; also knownMagnesium, Calciumas CD11b (p170),macrophage antigenalpha polypeptide)NM_000633BCL2B-cellProto-oncogene, Apoptosis,19335901CLL/lymphoma 2Alternative splicing,Transmembrane, Mitochondrion,Phosphorylation, Chromosomaltranslocation, Polymorphism,Disease mutation, 3D-structureNM_000634IL8RAinterleukin 8G-protein coupled receptor,19345902receptor, alphaTransmembrane, Glycoprotein,Chemotaxis, Polymorphism, 3D-structure, ReceptorNM_000651CR1complementComplement pathway, Glycoprotein,19355903component (3b/4b)Transmembrane, Repeat, Signal,receptor 1, includingReceptor, Sushi, Blood groupKnops blood groupantigen, Polymorphism, Pyrrolidonesystemcarboxylic acid, 3D-structureNM_000655SELLselectin LEGF-like domain, Cell adhesion,19365904(lymphocyteTransmembrane, Glycoprotein,adhesion moleculeLectin, Selectin, Signal, Sushi,1)Repeat, 3D-structureNM_000671ADH5alcoholOxidoreductase, Zinc, Metal-binding,19375905dehydrogenase 5NAD, Multigene family, Acetylation,(class III), chi3D-structurepolypeptideNM_000675ADORA2Aadenosine A2aG-protein coupled receptor,19385906receptorTransmembrane, Glycoprotein, 3D-structure, PolymorphismNM_000688ALAS1aminolevulinate,Heme biosynthesis, Transferase,19395907delta-, synthase 1Acyltransferase, Mitochondrion,Transit peptide, Pyridoxalphosphate, Multigene familyNM_000690ALDH2aldehydeOxidoreductase, NAD,19405908dehydrogenase 2Mitochondrion, Transit peptide,familyPolymorphism, 3D-structure(mitochondrial)NM_000694ALDH3B1aldehydeOxidoreductase, NAD19415909dehydrogenase 3family, member B1NM_000698ALOX5arachidonate 5-Oxidoreductase, Dioxygenase, Iron,19425910lipoxygenaseLeukotriene biosynthesis, CalciumNM_000701ATP1A1ATPase, Na+/K+Hydrolase, Sodium/potassium19435911transporting, alpha 1transport, Transmembrane,polypeptidePhosphorylation, Magnesium, Metal-binding, ATP-binding, Multigenefamily, Alternative splicingNM_000712BLVRAbiliverdin reductase AOxidoreductase, NAD, NADP, Zinc,19445912PolymorphismNM_000714BZRPbenzodiazapineMitochondrion, Receptor,19455913receptor (peripheral)Transmembrane, PolymorphismNM_000717CA4carbonic anhydraseGPI-anchor, Membrane, Lyase, Zinc,19465914IVSignal, 3D-structure, LipoproteinNM_000718CACNA1Bcalcium channel,Ionic channel, Transmembrane, Ion19475915voltage-dependent,transport, Voltage-gated channel,L type, alpha 1BCalcium channel, Glycoprotein,subunitRepeat, Multigene family, Calcium-binding, Phosphorylation, ATP-binding, Alternative splicingNM_000732CD3DCD3D antigen, deltaImmunoglobulin domain, T-cell,19485916polypeptide (TiT3Receptor, Transmembrane,complex)Glycoprotein, SignalNM_000734CD3ZCD3Z antigen, zetaT-cell, Receptor, Transmembrane,19495917polypeptide (TiT3Signal, Repeat, Alternative splicing,complex)Phosphorylation, 3D-structureNM_000748CHRNB2cholinergic receptor,Postsynaptic membrane, Ionic19505918nicotinic, betachannel, Glycoprotein, Signal,polypeptide 2Transmembrane, Multigene family,(neuronal)Disease mutation, EpilepsyNM_000749CHRNB3cholinergic receptor,Postsynaptic membrane, Ionic19515919nicotinic, betachannel, Glycoprotein, Signal,polypeptide 3Transmembrane, Multigene familyNM_000752LTB4Rleukotriene B4Apoptosis, 3D-structure, RNA-19525920receptor 2binding, Repeat, G-protein coupledreceptor, Transmembrane,GlycoproteinNM_000757CSF1colony stimulatingCytokine, Growth factor,19535921factor 1Glycoprotein, Proteoglycan,(macrophage)Transmembrane, Signal, Alternativesplicing, 3D-structureNM_000760CSF3Rcolony stimulatingCell adhesion, Receptor, Repeat,19545922factor 3 receptorSignal, Transmembrane,(granulocyte)Immunoglobulin domain,Glycoprotein, Alternative splicing,Polymorphism, 3D-structureNM_000778CYP4A11cytochrome P450,Heme, Monooxygenase,19555923family 4, subfamilyOxidoreductase, Electron transport,A, polypeptide 11Membrane, Microsome,Endoplasmic reticulum,PolymorphismNM_000801FKBP1AFK506 bindingIsomerase, Rotamase, 3D-structure19565924protein 1A, 12 kDaNM_000804FOLR3folate receptor 3Receptor, Glycoprotein, Signal,19575925(gamma)Folate-binding, Multigene family,Alternative splicingNM_000819GARTphosphoribosylglycinamideMultifunctional enzyme, Purine19585926formyltransferase,biosynthesis, Ligase, Transferase,phosphoribosylglycinamideAlternative splicing, Polymorphismsynthetase,phosphoribosylaminoimidazolesynthetaseNM_000846GSTA2glutathione S-Transferase, Multigene family,19595927transferase A2Polymorphism, 3D-structureNM_000856GUCY1A3guanylate cyclase 1,Lyase, cGMP biosynthesis,19605928soluble, alpha 3Multigene familyNM_000857GUCY1B3guanylate cyclase 1,Lyase, cGMP biosynthesis,19615929soluble, beta 3Alternative splicingNM_000871HTR65-hydroxytryptamineG-protein coupled receptor,19625930(serotonin) receptor 6Transmembrane, Glycoprotein,Multigene familyNM_000876IGF2Rinsulin-like growthTransmembrane, Transport,19635931factor 2 receptorGlycoprotein, Repeat, Receptor,Lysosome, Signal, Polymorphism,3D-structureNM_000877IL1R1interleukin 1Receptor, Repeat, Signal,19645932receptor, type ITransmembrane, Immunoglobulindomain, Glycoprotein,Phosphorylation, 3D-structureNM_000878IL2RBinterleukin 2Receptor, Transmembrane,19655933receptor, betaGlycoprotein, Signal, 3D-structureNM_000883IMPDH1IMP (inosineOxidoreductase, NAD, GMP19665934monophosphate)biosynthesis, Purine biosynthesis,dehydrogenase 1Multigene family, Repeat, CBSdomain, Alternative splicing, Vision,Retinitis pigmentosa, DiseasemutationNM_000895LTA4Hleukotriene A4Multifunctional enzyme, Hydrolase,19675935hydrolaseLeukotriene biosynthesis,Metalloprotease, Metal-binding, Zinc,3D-structureNM_000903NQO1NAD(P)HOxidoreductase, NAD, NADP,19685936dehydrogenase,Flavoprotein, FAD, Multigene family,quinone 1Polymorphism, 3D-structureNM_000904NQO2NAD(P)HOxidoreductase, Flavoprotein, FAD,19695937dehydrogenase,Multigene family, Zinc, 3D-structurequinone 2NM_000918P4HBprocollagen-proline,Redox-active center, Isomerase,197059382-oxoglutarate 4-Endoplasmic reticulum, Repeat,dioxygenase (prolineSignal, 3D-structure, Hypothetical4-hydroxylase), betaproteinpolypeptide (proteindisulfide isomerase;thyroid hormonebinding protein p55)NM_000952PTAFRplatelet-activatingG-protein coupled receptor,19715939factor receptorTransmembrane, Glycoprotein,Chemotaxis, Polymorphism,Hypothetical proteinNM_000954PTGDSprostaglandin D2Isomerase, Prostaglandin19725940synthase 21 kDabiosynthesis, Transport,(brain)Glycoprotein, Signal, Membrane,Lipocalin, PolymorphismNM_000963PTGS2prostaglandin-Oxidoreductase, Dioxygenase,19735941endoperoxidePeroxidase, Glycoprotein,synthase 2Prostaglandin biosynthesis, Heme,(prostaglandin G/HIron, Signal, Membrane,synthase andPolymorphismcyclooxygenase)NM_000966RARGretinoic acidReceptor, Transcription regulation,19745942receptor, gammaDNA-binding, Nuclear protein, Zinc-finger, Multigene family, Alternativesplicing, 3D-structureNM_000969RPL5ribosomal protein L5Ribosomal protein, rRNA-binding,19755943Hydrolase, Metalloprotease,Aminopeptidase, Zinc, NuclearproteinNM_000985RPL17ribosomal proteinHypothetical protein, Ribosomal19765944L17proteinNM_000992RPL29ribosomal proteinMethylation, Ribosomal protein,19775945L29Repeat, Heparin-bindingNM_000995RPL34ribosomal proteinRibosomal protein19785946L34NM_001006RPS3Aribosomal proteinRibosomal protein19795947S3ANM_001017RPS13ribosomal proteinRibosomal protein19805948S13NM_001048SSTsomatostatinCleavage on pair of basic residues,19815949Hormone, Signal, PharmaceuticalNM_001051SSTR3somatostatinG-protein coupled receptor,19825950receptor 3Transmembrane, Glycoprotein,Multigene family, PolymorphismNM_001052SSTR4somatostatinG-protein coupled receptor,19835951receptor 4Transmembrane, Glycoprotein,Multigene family, Lipoprotein,Palmitate, Phosphorylation,PolymorphismNM_001054SULT1A2sulfotransferaseTransferase, Steroid metabolism,19845952family, cytosolic, 1A,Polymorphismphenol-preferring,member 2NM_001055SULT1A1sulfotransferaseTransferase, Catecholamine19855953family, cytosolic, 1A,metabolism, Steroid metabolism,phenol-preferring,Polymorphismmember 1NM_001060TBXA2Rthromboxane A2G-protein coupled receptor,19865954receptorTransmembrane, Glycoprotein,Disease mutation, Alternativesplicing, Polymorphism, 3D-structure, Hypothetical protein,Metal-binding, Nuclear protein, Zinc,Zinc-fingerNM_001062TCN1transcobalamin ITransport, Cobalt transport,19875955(vitamin B12 bindingGlycoprotein, Signalprotein, R binderfamily)NM_001064TKTtransketolaseTransferase, Thiamine19885956(Wernicke-Korsakoffpyrophosphate, Calcium-bindingsyndrome)NM_001065TNFRSF1Atumor necrosis factorReceptor, Apoptosis,19895957receptor superfamily,Transmembrane, Glycoprotein,member 1ARepeat, Signal, Disease mutation,Polymorphism, 3D-structureNM_001066TNFRSF1Btumor necrosis factorReceptor, Apoptosis,19905958receptor superfamily,Transmembrane, Glycoprotein,member 1BRepeat, Signal, Phosphorylation,Pharmaceutical, Polymorphism, 3D-structureNM_001082CYP4F2cytochrome P450,Heme, Monooxygenase,19915959family 4, subfamilyOxidoreductase, Electron transport,F, polypeptide 2Membrane, Microsome,Endoplasmic reticulum,Polymorphism, NADPNM_001087AAMPangio-associated,Repeat, WD repeat19925960migratory cell proteinNM_001089ABCA3ATP-bindingATP-binding, Transport,19935961cassette, sub-familyTransmembraneA (ABC1), member 3NM_001090ABCF1ATP-bindingATP-binding19945962cassette, sub-familyF (GCN20), member 1NM_001091ABP1amiloride bindingSignal, Glycoprotein,19955963protein 1 (amineOxidoreductase, Copper, Heparin-oxidase (copper-binding, TPQ, Alternative splicing,containing))Polymorphism, Metal-bindingNM_001099ACPPacid phosphatase,Hydrolase, Glycoprotein, Signal, 3D-19965964prostatestructureNM_001101ACTBactin, betaHypothetical protein, Structural19975965protein, Multigene family,Methylation, Acetylation,Cytoskeleton, 3D-structureNM_001102ACTN1actinin, alpha 1Cytoskeleton, Actin-binding,19985966Calcium-binding, Repeat, Multigenefamily, PhosphorylationNM_001105ACVR1activin A receptor,Receptor, Transferase,19995967type ISerine/threonine-protein kinase,ATP-binding, Transmembrane,Glycoprotein, SignalNM_001107ACYP1acylphosphatase 1,Hydrolase, Acetylation, Multigene20005968erythrocytefamily(common) typeNM_001109ADAM8a disintegrin andHydrolase, Metalloprotease, Zinc,20015969metalloproteinaseSignal, Glycoprotein,domain 8Transmembrane, Antigen, EGF-likedomainNM_001120TETRANtetracyclineTransmembrane20025970transporter-likeproteinNM_001129AEBP1AE binding protein 1Carboxypeptidase20035971NM_001140ALOX15arachidonate 15-Oxidoreductase, Dioxygenase, Iron,20045972lipoxygenaseLeukotriene biosynthesisNM_001150ANPEPalanyl (membrane)Angiogenesis, Hydrolase,20055973aminopeptidaseAminopeptidase, Metalloprotease,(aminopeptidase N,Zinc, Signal-anchor,aminopeptidase M,Transmembrane, Glycoprotein,microsomalSulfation, Polymorphismaminopeptidase,CD13, p150)NM_001152SLC25A5solute carrier familyMitochondrion, Inner membrane,2006597425 (mitochondrialRepeat, Transmembrane, Transport,carrier; adenineMultigene familynucleotidetranslocator),member 5NM_001153ANXA4annexin A4Annexin, Calcium/phospholipid-20075975binding, RepeatNM_001155ANXA6annexin A6Annexin, Calcium/phospholipid-20085976binding, Repeat, Acetylation,Phosphorylation, 3D-structureNM_001157ANXA11annexin A11Annexin, Calcium/phospholipid-20095977binding, Repeat, PolymorphismNM_001172ARG2arginase, type IIUrea cycle, Arginine metabolism,20105978Hydrolase, Manganese, Transitpeptide, Mitochondrion, Receptor,Transmembrane, Transport, Proteintransport, Coiled coil, AlternativesplicingNM_001175ARHGDIBRho GDPGTPase activation, 3D-structure20115979dissociation inhibitor(GDI) betaNM_001181ASGR2asialoglycoproteinLectin, Glycoprotein, Receptor,20125980receptor 2Endocytosis, Transmembrane,Calcium, Signal-anchor,Phosphorylation, Alternative splicingNM_001182ALDH7A1aldehydeOxidoreductase, NAD20135981dehydrogenase 7family, member A1NM_001183ATP6IP1ATPase, H+Hypothetical protein, ATP synthesis,20145982transporting,Hydrogen ion transport, Hydrolase,lysosomal accessoryATP-binding, Transmembrane,protein 1Glycoprotein, SignalNM_001184ATRataxia telangiectasiaKinase, Transferase20155983and Rad3 relatedNM_001196BIDBH3 interactingApoptosis, 3D-structure20165984domain deathagonistNM_001199BMP1bone morphogeneticGrowth factor, Cytokine, Repeat,20175985protein 1Osteogenesis, Chondrogenesis,Hydrolase, Metalloprotease, EGF-like domain, Zinc, Calcium, Signal,Glycoprotein, Zymogen, Alternativesplicing, CollagenNM_001206BTEB1basic transcriptionTranscription regulation, DNA-20185986element bindingbinding, Nuclear protein, Repeat,protein 1Zinc-finger, Metal-bindingNM_001207BTF3basic transcriptionTranscription regulation, Nuclear20195987factor 3protein, Alternative splicingNM_001208BTF3L1basic transcriptionTranscription regulation, Nuclear20205988factor 3, like 1proteinNM_001212C1QBPcomplementMitochondrion, Transit peptide, 3D-20215989component 1, qstructure, Hypothetical proteinsubcomponentbinding proteinNM_001222CAMK2Gcalcium/calmodulin-Alternative splicing20225990dependent proteinkinase (CaM kinase)II gammaNM_001237CCNA2cyclin A2Cyclin, Cell cycle, Cell division,20235991Mitosis, 3D-structureNM_001252TNFSF7tumor necrosis factorCytokine, Transmembrane,20245992(ligand) superfamily,Glycoprotein, Signal-anchor, Antigenmember 7NM_001256CDC27cell division cycle 27Repeat, TPR repeat, Nuclear20255993protein, PolymorphismNM_001259CDK6cyclin-dependentTransferase, Serine/threonine-20265994kinase 6protein kinase, ATP-binding, Cellcycle, Cell division, Phosphorylation,3D-structureNM_001266CES1carboxylesterase 1Glycoprotein, Hydrolase, Serine20275995(monocyte/macrophageesterase, Endoplasmic reticulum,serine esteraseSignal, Multigene family,1)Polymorphism, Hypothetical proteinNM_001276CHI3L1chitinase 3-like 1Glycoprotein, Signal, 3D-structure20285996(cartilageglycoprotein-39)NM_001282AP2B1adaptor-relatedHypothetical protein, Coated pits,20295997protein complex 2,3D-structurebeta 1 subunitNM_001284AP3S1adaptor-relatedGolgi stack, Protein transport,20305998protein complex 3,Transportsigma 1 subunitNM_001286CLCN6chloride channel 6Ionic channel, Ion transport, Chloride20315999channel, Chloride, Voltage-gatedchannel, Transmembrane, CBSdomain, Repeat, Alternative splicingNM_001288CLIC1chloride intracellularIonic channel, Ion transport, Chloride20326000channel 1channel, Chloride, Voltage-gatedchannel, Nuclear protein, 3D-structureNM_001292CLK3CDC-like kinase 3Transferase, Serine/threonine-20336001protein kinase, ATP-binding,Tyrosine-protein kinase,Phosphorylation, Nuclear protein,Alternative splicingNM_001293CLNS1Achloride channel,Nuclear protein, Polymorphism20346002nucleotide-sensitive,1ANM_001294CLPTM1cleft lip and palateTransmembrane20356003associatedtransmembraneprotein 1NM_001305CLDN4claudin 4Tight junction, Transmembrane,20366004Williams-Beuren syndromeNM_001313CRMP1collapsin responseRepeat, WD repeat20376005mediator protein 1NM_001315MAPK14mitogen-activatedATP-binding, Kinase, Transferase,20386006protein kinase 14Serine/threonine-protein kinase,Phosphorylation, Alternative splicing,3D-structureNM_001317CSH1chorionicChorion, Hormone, Placenta,20396007somatomammotropinMultigene family, Signalhormone 1(placental lactogen)NM_001325CSTF2cleavage stimulationRNA-binding, Repeat,20406008factor, 3′ pre-RNA,Phosphorylation, Nuclear proteinsubunit 2, 64 kDaNM_001331CTNND1catenin (cadherin-Cytoskeleton, Structural protein,20416009associated protein),Phosphorylation, Repeat, Celldelta 1adhesion, Coiled coil, Nuclearprotein, Alternative splicingNM_001338CXADRcoxsackie virus andImmunoglobulin domain, Receptor,20426010adenovirus receptorTransmembrane, Glycoprotein,Signal, Repeat, 3D-structureNM_001346DGKGdiacylglycerolTransferase, Kinase, Calcium-20436011kinase, gammabinding, Phorbol-ester binding,90 kDaRepeat, Multigene family, AlternativesplicingNM_001357DDX9DEAH (Asp-Glu-Ala-Helicase, RNA-binding, DNA-20446012His) box polypeptide 9binding, Repeat, Nuclear protein,ATP-bindingNM_001358DDX15DEAH (Asp-Glu-Ala-mRNA processing, mRNA splicing,20456013His) box polypeptideHelicase, ATP-binding, Nuclear15proteinNM_001363DKC1dyskeratosisTelomere, RNA-binding, Nuclear20466014congenita 1,protein, Disease mutationdyskerinNM_001381DOK1docking protein 1,Phosphorylation, Alternative splicing2047601562 kDa (downstreamof tyrosine kinase 1)NM_001383DPH2L1diptheria toxin20486016resistance proteinrequired fordiphthamidebiosynthesis-like 1(S. cerevisiae)NM_001388DRG2developmentallyGTP-binding20496017regulated GTPbinding protein 2NM_001406EFNB3ephrin-B3Developmental protein,20506018Neurogenesis, Transmembrane,Glycoprotein, Signal, PolymorphismNM_001415EIF2S3eukaryoticInitiation factor, Protein biosynthesis,20516019translation initiationGTP-binding, Polymorphismfactor 2, subunit 3gamma, 52 kDaNM_001419ELAVL1ELAV (embryonicRNA-binding, Repeat20526020lethal, abnormalvision, Drosophila)-like 1 (Hu antigen R)NM_001421ELF4E74-like factor 4 (ets20536021domain transcriptionfactor)NM_001423EMP1epithelial membraneTransmembrane, Glycoprotein20546022protein 1NM_001431EPB41L2erythrocyteHypothetical protein, Structural20556023membrane proteinprotein, Cytoskeleton, Actin-bindingband 4.1-like 2NM_001432EREGepiregulinAngiogenesis, Growth factor,20566024Mitogen, Glycoprotein, EGF-likedomain, Transmembrane, SignalNM_001440EXTL3exostoses (multiple)-Transferase, Glycosyltransferase,20576025like 3Endoplasmic reticulum,Transmembrane, Signal-anchor,GlycoproteinNM_001444FABP5fatty acid bindingTransport, Lipid-binding, 3D-20586026protein 5 (psoriasis-structureassociated)NM_001449FHL1four and a half LIMCoiled coil, Transcription regulation,20596027domains 1Nuclear protein, Disease mutation,Anhidrotic ectodermal dysplasia,Repeat, LIM domain, Metal-binding,Zinc, Developmental protein,Differentiation, Zinc-fingerNM_001455FOXO3Aforkhead box O3ATranscription regulation, DNA-20606028binding, Nuclear protein, Apoptosis,Chromosomal translocation, Proto-oncogene, PhosphorylationNM_001456FLNAfilamin A, alphaCytoskeleton, Actin-binding, Repeat,20616029(actin binding proteinPhosphorylation, Polymorphism,280)Disease mutation, Multigene family,Hypothetical proteinNM_001462FPRL1formyl peptideG-protein coupled receptor,20626030receptor-like 1Transmembrane, Glycoprotein,Chemotaxis, Repeat, WD repeatNM_001465FYBFYN binding proteinSH3 domain, Phosphorylation,20636031(FYB-120/130)Nuclear protein, Coiled coil,Alternative splicingNM_001467G6PT1solute carrier familyTransmembrane, Transport, Sugar2064603237 (glycerol-6-transport, Endoplasmic reticulum,phosphateAlternative splicing, Glycogentransporter),storage disease, Disease mutationmember 4NM_001469G22P1thyroid autoantigenHelicase, Nuclear protein, DNA-2065603370 kDa (Ku antigen)binding, Phosphorylation, Antigen,Systemic lupus erythematosus,Acetylation, 3D-structureNM_001478GALGTUDP-N-acetyl-alpha-Hypothetical protein, Transferase,20666034D-galactosamine:(N-Glycosyltransferase,acetylneuraminyl)-Transmembrane, Signal-anchor,galactosylglucosylceramideGolgi stack, Glycoprotein,N-Polymorphismacetylgalactosaminyltransferase(GalNAc-T)NM_001482GATMglycineTransferase, Mitochondrion, Transit20676035amidinotransferasepeptide, 3D-structure, Alternative(L-arginine:glycinesplicingamidinotransferase)NM_001483GBASglioblastoma20686036amplified sequenceNM_001487GCN5L1GCN5 general20696037control of amino-acidsynthesis 5-like 1(yeast)NM_001493GDI1GDP dissociationGTPase activation, Disease20706038inhibitor 1mutationNM_001500GMDSGDP-mannose 4,6-Lyase, NADP20716039dehydrataseNM_001503GPLD1glycosylphosphatidylHydrolase, Glycoprotein, Signal,20726040inositol specificHypothetical proteinphospholipase D1NM_001504CXCR3chemokine (C—X—CG-protein coupled receptor,20736041motif) receptor 3Transmembrane, Glycoprotein,Antigen, PolymorphismNM_001517GTF2H4general transcriptionTranscription regulation, DNA repair,20746042factor IIH,Nuclear proteinpolypeptide 4,52 kDaNM_001518GTF2Igeneral transcriptionTranscription regulation, DNA-20756043factor II, ibinding, Nuclear protein,Phosphorylation, Repeat, Williams-Beuren syndrome, AlternativesplicingNM_001519BRF1BRF1 homolog,Transcription regulation, Activator,20766044subunit of RNANuclear protein, Repeat, Zinc-finger,polymerase IIIMetal-binding, Zinc, Alternativetranscriptionsplicing, Hypothetical proteininitiation factor IIIB(S. cerevisiae)NM_001520GTF3C1general transcription20776045factor IIIC,polypeptide 1, alpha220 kDaNM_001528HGFACHGF activatorHydrolase, Glycoprotein, Plasma,20786046Serine protease, Kringle, Signal,EGF-like domain, Repeat, ZymogenNM_001531MR1majorMHC, Glycoprotein, Transmembrane20796047histocompatibilitycomplex, class I-relatedNM_001536HRMT1L2HMT1 hnRNPTransferase, Methyltransferase,20806048methyltransferase-Nuclear protein, Alternative splicinglike 2 (S. cerevisiae)NM_001538HSF4F-box and leucine-Transcription regulation, Nuclear20816049rich repeat protein 8protein, DNA-binding, Activator,Repressor, Heat shock, Multigenefamily, Alternative splicingNM_001539DNAJA1DnaJ (Hsp40)Chaperone, Repeat, Zinc, Metal-20826050homolog, subfamilybinding, Prenylation, Lipoprotein,A, member 1Multigene familyNM_001550IFRD1interferon-related20836051developmentalregulator 1NM_001551IGBP1immunoglobulinB-cell activation, Phosphorylation20846052(CD79A) bindingprotein 1NM_001554CYR61cysteine-rich,Plasmid, Chemotaxis, Cell adhesion,20856053angiogenic inducer,Growth factor binding, Heparin-61binding, SignalNM_001557IL8RBinterleukin 8G-protein coupled receptor,20866054receptor, betaTransmembrane, Glycoprotein,Chemotaxis, Polymorphism,ReceptorNM_001558IL10RAinterleukin 10Receptor, Transmembrane,20876055receptor, alphaGlycoprotein, Signal, Polymorphism,3D-structureNM_001567INPPL1inositolDNA repair20886056polyphosphatephosphatase-like 1NM_001572IRF7interferon regulatoryTranscription regulation, DNA-20896057factor 7binding, Nuclear protein, Activator,Alternative splicing, CollagenNM_001607ACAA1acetyl-Coenzyme AAcyltransferase, Transferase, Fatty20906058acyltransferase 1acid metabolism, Peroxisome,(peroxisomal 3-Transit peptide, Polymorphismoxoacyl-CoenzymeA thiolase)NM_001618ADPRTADP-Transferase, Glycosyltransferase,20916059ribosyltransferaseNAD, DNA-binding, Nuclear protein,(NAD+; poly (ADP-ADP-ribosylation, Zinc-finger, Zinc,ribose) polymerase)PolymorphismNM_001619ADRBK1adrenergic, beta,Kinase, Receptor, Transferase,20926060receptor kinase 1Serine/threonine-protein kinase,ATP-binding, Multigene family, 3D-structureNM_001621AHRaryl hydrocarbonCell cycle, Transcription regulation,20936061receptorActivator, Receptor, DNA-binding,Nuclear protein, Repeat,PolymorphismNM_001628AKR1B1aldo-keto reductaseOxidoreductase, NADP, Acetylation,20946062family 1, member B13D-structure, Polymorphism(aldose reductase)NM_001629ALOX5AParachidonate 5-Transmembrane, Leukotriene20956063lipoxygenase-biosynthesisactivating proteinNM_001632ALPPalkalineHydrolase, Zinc, Magnesium,20966064phosphatase,Phosphorylation, Transmembrane,placental (ReganPlacenta, Multigene family,isozyme)Glycoprotein, GPI-anchor, Signal,3D-structure, LipoproteinNM_001634AMD1adenosylmethionineSpermidine biosynthesis, Lyase,20976065decarboxylase 1Decarboxylase, Pyruvate, Zymogen,3D-structureNM_001637AOAHacyloxyacylHydrolase, Signal, Transmembrane,20986066hydrolaseGlycoprotein(neutrophil)NM_001643APOA2apolipoprotein A-IITransport, Lipid transport, HDL,20996067Signal, Pyrrolidone carboxylic acid,3D-structureNM_001654ARAF1v-raf murineTransferase, Serine/threonine-21006068sarcoma 3611 viralprotein kinase, Proto-oncogene,oncogene homolog 1Metal-binding, Zinc, ATP-binding,Phorbol-ester binding, KinaseNM_001657AREGamphiregulinGlycoprotein, Cytokine, Growth21016069(schwannoma-factor, EGF-like domain, Signal,derived growthTransmembranefactor)NM_001662ARF5ADP-ribosylationGTP-binding, Multigene family,21026070factor 5Myristate, Protein transport, Golgistack, LipoproteinNM_001665ARHGras homolog geneGTP-binding, Prenylation,21036071family, member GLipoprotein(rho G)NM_001667ARL2sorting nexin 15GTP-binding, Multigene family,21046072Hypothetical protein, Transport,Protein transport, Alternative splicingNM_001670ARVCFarmadillo repeatHypothetical protein, Cell adhesion,21056073gene deletes inCytoskeleton, Structural protein,velocardiofacialRepeat, Coiled coil, AlternativesyndromesplicingNM_001671ASGR1asialoglycoproteinLectin, Glycoprotein, Receptor,21066074receptor 1Endocytosis, Transmembrane,Calcium, Signal-anchor,Phosphorylation, 3D-structureNM_001677ATP1B1ATPase, Na+/K+Transferase, Kinase, ATP-binding,21076075transporting, beta 1Sodium/potassium transport,polypeptideTransmembrane, Glycoprotein,Multigene family, Signal-anchor,Alternative splicingNM_001678ATP1B2ATPase, Na+/K+Sodium/potassium transport,21086076transporting, beta 2Transmembrane, Glycoprotein,polypeptideMultigene family, Signal-anchorNM_001679ATP1B3ATPase, Na+/K+Sodium/potassium transport,21096077transporting, beta 3Transmembrane, Glycoprotein,polypeptideMultigene family, Signal-anchorNM_001681ATP2A2ATPase, Ca++Hydrolase, Calcium transport,21106078transporting, cardiacTransmembrane, Phosphorylation,muscle, slow twitch 2ATP-binding, Metal-binding,Magnesium, Calcium-binding,Multigene family, Alternative splicing,Disease mutation, EpilepsyNM_001693ATP6V1B2ATPase, H+Hydrolase, ATP synthesis, Hydrogen21116079transporting,ion transport, Multigene familylysosomal 56/58 kDa,V1 subunit B,isoform 2NM_001706BCL6B-cellNuclear protein, Transcription21126080CLL/lymphoma 6regulation, Activator, DNA-binding,(zinc finger proteinZinc-finger, Metal-binding, Repeat,51)Proto-oncogene, Chromosomaltranslocation, PolymorphismNM_001712CEACAM1carcinoembryonicAlternative splicing, Immunoglobulin21136081antigen-related celldomain, Signal, Transmembrane,adhesion molecule 1Glycoprotein, Repeat, Pyrrolidone(biliary glycoprotein)carboxylic acid, Hypothetical proteinNM_001714BICD1Bicaudal D homologGolgi stack, Coiled coil, Alternative211460821 (Drosophila)splicingNM_001716BLR1Burkitt lymphomaB-cell activation, G-protein coupled21156083receptor 1, GTPreceptor, Transmembrane,binding proteinGlycoprotein, Alternative splicing,(chemokine (C—X—CPolymorphismmotif) receptor 5)NM_001721BMXBMX non-receptorTransferase, Tyrosine-protein21166084tyrosine kinasekinase, Phosphorylation, ATP-binding, SH3 domain, SH2 domainNM_001725BPIbactericidal/permeability-Antibiotic, Signal, Transmembrane,21176085increasingGlycoprotein, 3D-structureproteinNM_001728BSGbasigin (OK bloodImmunoglobulin domain,21186086group)Transmembrane, Glycoprotein,Signal, Antigen, Blood groupantigen, PolymorphismNM_001730KLF5Kruppel-like factor 5Transcription regulation, DNA-21196087(intestinal)binding, Nuclear protein, Repeat,Zinc-finger, Metal-binding, ActivatorNM_001731BTG1B-cell translocationProto-oncogene, Chromosomal21206088gene 1, anti-translocationproliferativeNM_001736C5R1complementG-protein coupled receptor,21216089component 5Transmembrane, Glycoprotein,receptor 1 (C5aSulfation, Chemotaxisligand)NM_001745CAMLGcalcium modulatingTransmembrane21226090ligandNM_001747CAPGcapping proteinNuclear protein, Actin-binding,21236091(actin filament),Repeat, 3D-structure, Actin cappinggelsolin-likeNM_001749CAPNS1calpain, smallCalcium-binding, Repeat, 3D-21246092subunit 1structureNM_001750CASTcalpastatinRepeat, Thiol protease inhibitor,21256093Alternative splicing, Phosphorylation,Signal transduction inhibitorNM_001767CD2CD2 antigen (p50),Immunoglobulin domain, T-cell,21266094sheep red blood cellGlycoprotein, Antigen,receptorTransmembrane, Cell adhesion,Repeat, Signal, Polymorphism, 3D-structureNM_001769CD9CD9 antigen (p24)Glycoprotein, Antigen,21276095Transmembrane, Lipoprotein,PhosphorylationNM_001771CD22CD22 antigenCell adhesion, Lectin, Antigen,21286096Transmembrane, Signal,Glycoprotein, Immunoglobulindomain, Repeat, Phosphorylation,Alternative splicing, PolymorphismNM_001773CD34CD34 antigenCell adhesion, Antigen, Signal,21296097Transmembrane, Glycoprotein,Phosphorylation, Alternative splicingNM_001774CD37CD37 antigenGlycoprotein, Antigen,21306098Transmembrane, HypotheticalproteinNM_001776ENTPD1ectonucleosideHydrolase, Transmembrane,21316099triphosphateAntigen, Glycoprotein, Calcium,diphosphohydrolase 1Magnesium, Alternative splicing,Lipoprotein, PalmitateNM_001777CD47CD47 antigen (Rh-Cell adhesion, Antigen, Signal,21326100related antigen,Transmembrane, Glycoprotein,integrin-associatedAlternative splicingsignal transducer)NM_001780CD63CD63 antigenGlycoprotein, Antigen,21336101(melanoma 1Transmembrane, Lysosomeantigen)NM_001781CD69CD69 antigen (p60,Antigen, Signal-anchor,21346102early T-cellTransmembrane, Lectin,activation antigen)Glycoprotein, Phosphorylation, 3D-structureNM_001800CDKN2Dcyclin-dependentCell cycle, Anti-oncogene, Repeat,21356103kinase inhibitor 2DANK repeat, 3D-structure(p19, inhibits CDK4)NM_001803CDW52CDW52 antigenAntigen, Signal, Glycoprotein, GPI-21366104(CAMPATH-1anchor, Membrane, Polymorphism,antigen)LipoproteinNM_001805CEBPECCAAT/enhancerTranscription regulation, Activator,21376105binding proteinDNA-binding, Nuclear protein,(C/EBP), epsilonPhosphorylationNM_001806CEBPGCCAAT/enhancerTranscription regulation, Activator,21386106binding proteinDNA-binding, Nuclear protein(C/EBP), gammaNM_001808CELLcarboxyl ester lipase21396107pseudogeneNM_001815CEACAM3carcinoembryonicImmunoglobulin domain, Antigen,21406108antigen-related cellSignal, Glycoprotein,adhesion molecule 3Transmembrane, Alternativesplicing, PolymorphismNM_001816CEACAM8carcinoembryonicImmunoglobulin domain, Antigen,21416109antigen-related cellSignal, Glycoprotein, GPI-anchor,adhesion molecule 8Repeat, Polymorphism, LipoproteinNM_001817CEACAM4carcinoembryonicAntigen21426110antigen-related celladhesion molecule 4NM_001828CLCCharot-LeydenHydrolase, Serine esterase, Lipid21436111crystal proteindegradation, Galectin, Acetylation,3D-structure, PolymorphismNM_001835CLTCL1clathrin, heavyCoated pits, Alternative splicing21446112polypeptide-like 1NM_001838CCR7chemokine (C—CG-protein coupled receptor,21456113motif) receptor 7Transmembrane, Glycoprotein,SignalNM_001839CNN3calponin 3, acidicCalmodulin-binding, Actin-binding,21466114Multigene family, RepeatNM_001853COL9A3collagen, type IX,Hypothetical protein, Collagen,21476115alpha 3Extracellular matrix, Connectivetissue, Repeat, Hydroxylation,Glycoprotein, Signal, PolymorphismNM_001882CRHBPcorticotropinGlycoprotein, Signal21486116releasing hormonebinding proteinNM_001889CRYZcrystallin, zetaOxidoreductase, NADP, Zinc21496117(quinone reductase)NM_001894CSNK1Ecasein kinase 1,Transferase, Serine/threonine-21506118epsilonprotein kinase, ATP-binding,Phosphorylation, Multigene familyNM_001907CTRLchymotrypsin-likeHydrolase, Protease, Serine21516119protease, Transferase,Serine/threonine-protein kinase,ATP-binding, Phosphorylation, Golgistack, Nuclear protein, Glycoprotein,Zymogen, SignalNM_001909CTSDcathepsin DHydrolase, Aspartyl protease,21526120(lysosomal aspartylGlycoprotein, Lysosome, Signal,protease)Zymogen, Polymorphism,Alzheimer's disease, 3D-structureNM_001911CTSGcathepsin GHydrolase, Serine protease,21536121Zymogen, Glycoprotein, Signal,Polymorphism, 3D-structureNM_001921DCTDdCMP deaminaseHydrolase, Allosteric enzyme,21546122Nucleotide biosynthesis, ZincNM_001925DEFA4defensin, alpha 4,Defensin, Antibiotic, Fungicide,21556123corticostatinSignalNM_001939DRP2dystrophin relatedStructural protein, Cytoskeleton,21566124protein 2Repeat, Zinc-fingerNM_001940DRPLAdentatorubral-Triplet repeat expansion,21576125pallidoluysianPolymorphism, Epilepsyatrophy (atrophin-1)NM_001946DUSP6dual specificityHydrolase, Polymorphism,21586126phosphatase 6Alternative splicing, 3D-structureNM_001951E2F5E2F transcriptionTranscription regulation, Activator,21596127factor 5, p130-DNA-binding, Nuclear protein,bindingPolymorphismNM_001953ECGF1endothelial cellTransferase, Glycosyltransferase,21606128growth factor 1Growth factor, Chemotaxis,(platelet-derived)Angiogenesis, Repeat,Polymorphism, Disease mutationNM_001964EGR1early growthTranscription regulation, Activator,21616129response 1DNA-binding, Nuclear protein,Repeat, Zinc-finger, Metal-bindingNM_001965EGR4early growthNuclear protein, Transcription21626130response 4regulation, DNA-binding, Zinc-finger,Metal-binding, RepeatNM_001970EIF5AeukaryoticProtein biosynthesis, Initiation factor,21636131translation initiationHypusine, 3D-structurefactor 5ANM_001972ELA2elastase 2,Hydrolase, Serine protease,21646132neutrophilGlycoprotein, Signal, 3D-structure,Disease mutationNM_001992F2Rcoagulation factor IIG-protein coupled receptor,21656133(thrombin) receptorTransmembrane, Glycoprotein,Signal, Blood coagulation,Phosphorylation, Polymorphism, 3D-structure, ReceptorNM_001995FACL1fatty-acid-CoenzymeLigase, Fatty acid metabolism,21666134A ligase, long-chain 2Magnesium, Multigene family,Hypothetical proteinNM_001996FBLN1fibulin 1Signal, Alternative splicing,21676135Glycoprotein, Extracellular matrix,Repeat, EGF-like domain, Calcium-binding, Chromosomal translocation,Polymorphism, Hypothetical proteinNM_001999FBN2fibrillin 2 (congenitalHypothetical protein, EGF-like21686136contracturaldomain, Extracellular matrix,arachnodactyly)Calcium-binding, Glycoprotein,Repeat, Signal, Multigene family,Disease mutation, PolymorphismNM_002000FCARFc fragment of IgA,Receptor, Glycoprotein,21696137receptor forTransmembrane, IgA-bindingprotein, Immunoglobulin domain,Repeat, Signal, Alternative splicingNM_002003FCN1ficolinLectin, Collagen, Repeat,21706138(collagen/fibrinogenGlycoprotein, Signal, Multigenedomain containing) 1familyNM_002005FESfeline sarcomaTransferase, Tyrosine-protein21716139oncogenekinase, Proto-oncogene, ATP-binding, Phosphorylation, SH2domainNM_002010FGF9fibroblast growthGrowth factor, Differentiation,21726140factor 9 (glia-Mitogen, Heparin-binding,activating factor)Glycoprotein, 3D-structureNM_002013FKBP3FK506 bindingIsomerase, Rotamase, Nuclear21736141protein 3, 25 kDaprotein, 3D-structureNM_002014FKBP4FK506 bindingIsomerase, Rotamase, Repeat, TPR21746142protein 4, 59 kDarepeat, Nuclear protein,Phosphorylation, 3D-structureNM_002017FLI1Friend leukemiaTranscription regulation, Activator,21756143virus integration 1DNA-binding, Nuclear protein,Alternative splicing, Proto-oncogene,Chromosomal translocation, 3D-structureNM_002018FLIIflightless I homologDevelopmental protein, Repeat,21766144(Drosophila)Leucine-rich repeatNM_002029FPR1formyl peptideG-protein coupled receptor,21776145receptor 1Transmembrane, Glycoprotein,Chemotaxis, PolymorphismNM_002032FTH1ferritin, heavyTransport, Ion transport, Ionic21786146polypeptide 1channel, Chloride channel, Chloride,Calcium, Alternative splicing,Disease mutation, Polymorphism,Vision, Transmembrane,Phosphorylation, Iron storage, Metal-binding, 3D-structureNM_002033FUT4fucosyltransferase 4Transferase, Glycosyltransferase,21796147(alpha (1, 3)Transmembrane, Glycoprotein,fucosyltransferase,Signal-anchor, Golgi stackmyeloid-specific)NM_002035FVT1follicular lymphomaProto-oncogene, Chromosomal21806148variant translocation 1translocation, Oxidoreductase,SignalNM_002037FYNFYN oncogeneHypothetical protein, ATP-binding,21816149related to SRC,SH3 domain, Transferase, Kinase,FGR, YESTyrosine-protein kinase, Proto-oncogene, Phosphorylation,Myristate, SH2 domain, Palmitate,Lipoprotein, 3D-structure,PolymorphismNM_002046GAPDglyceraldehyde-3-Glycolysis, NAD, Oxidoreductase,21826150phosphateMultigene familydehydrogenaseNM_002051GATA3GATA bindingHypothetical protein, Transcription21836151protein 3regulation, Activator, DNA-binding,Zinc-finger, Nuclear protein, T-cell,Alternative splicingNM_002061GCLMglutamate-cysteineLigase, Glutathione biosynthesis21846152ligase, modifiersubunitNM_002064GLRXglutaredoxinRedox-active center, Electron21856153(thioltransferase)transport, Acetylation,Polymorphism, 3D-structureNM_002068GNA15guanine nucleotideGTP-binding, Transducer, Multigene21866154binding protein (Gfamily, ADP-ribosylationprotein), alpha 15(Gq class)NM_002069GNAI1guanine nucleotideHypothetical protein, GTP-binding,21876155binding protein (GTransducer, ADP-ribosylation,protein), alphaMultigene family, Myristate,inhibiting activityPalmitate, Lipoprotein, 3D-structurepolypeptide 1NM_002070GNAI2guanine nucleotideGTP-binding, Transducer, ADP-21886156binding protein (Gribosylation, Multigene family,protein), alphaMyristate, Palmitate, Lipoproteininhibiting activitypolypeptide 2NM_002073GNAZguanine nucleotideGTP-binding, Transducer, ADP-21896157binding protein (Gribosylation, Multigene family,protein), alpha zLipoprotein, Palmitate, Myristate,polypeptideMembraneNM_002081GPC1glypican 1Proteoglycan, Heparan sulfate,21906158Glycoprotein, Signal, GPI-anchor,LipoproteinNM_002082GPRK6G protein-coupledTransferase, Serine/threonine-21916159receptor kinase 6protein kinase, ATP-binding,Phosphorylation, Lipoprotein,Palmitate, Alternative splicing,Kinase, Receptor, HypotheticalproteinNM_002086GRB2growth factorSH2 domain, SH3 domain, Repeat,21926160receptor-boundAlternative splicing, 3D-structureprotein 2NM_002087GRNgranulinCytokine, Repeat, Glycoprotein,21936161Signal, Alternative splicing,Polymorphism, 3D-structure,Hypothetical proteinNM_002092GRSF1G-rich RNAHypothetical protein, RNA-binding,21946162sequence bindingRepeatfactor 1NM_002093GSK3Bglycogen synthaseTransferase, Serine/threonine-21956163kinase 3 betaprotein kinase, ATP-binding, Wntsignaling pathway, Phosphorylation,Multigene family, Alternative splicing,3D-structureNM_002096GTF2F1general transcriptionTranscription regulation, DNA-21966164factor IIF,binding, Nuclear protein,polypeptide 1,Phosphorylation, 3D-structure74 kDaNM_002097GTF3Ageneral transcriptionTranscription regulation, Zinc-finger,21976165factor IIIAMetal-binding, DNA-binding, RNA-binding, Repeat, Nuclear protein,Polymorphism, Initiation factorNM_002103GYS1glycogen synthase 1Glycogen biosynthesis, Transferase,21986166(muscle)Glycosyltransferase, Allostericenzyme, Phosphorylation, Diseasemutation, Diabetes mellitus,Polymorphism, Hypothetical proteinNM_002104GZMKgranzyme K (serineHydrolase, Serine protease,21996167protease, granzymeZymogen, Signal, 3D-structure3; tryptase II)NM_002105H2AFXH2A histone family,Chromosomal protein, Nucleosome22006168member Xcore, Nuclear protein, DNA-binding,Multigene family, AcetylationNM_002107H3F3AH3 histone, familyNuclear protein, Chromosomal220161693Aprotein, DNA-binding, Nucleosomecore, Multigene familyNM_002108HALhistidine ammonia-Lyase, Histidine metabolism,22026170lyasePolymorphismNM_002109HARShistidyl-tRNAAminoacyl-tRNA synthetase, Protein22036171synthetasebiosynthesis, Ligase, ATP-binding,Hypothetical protein, Repeat, WDrepeatNM_002110HCKhemopoietic cellTransferase, Tyrosine-protein22046172kinasekinase, Phosphorylation, ATP-binding, Lipoprotein, Myristate,Palmitate, SH2 domain, SH3domain, Alternative initiation, 3D-structureNM_002115HK3hexokinase 3 (whiteKinase, Transferase, Glycolysis,22056173cell)Allosteric enzyme, Repeat, ATP-binding, MembraneNM_002131HMGA1high mobility groupNuclear protein, Chromosomal22066174AT-hook 1protein, DNA-binding, Repeat,Transcription regulation, Alternativesplicing, Phosphorylation,Acetylation, Chromosomaltranslocation, 3D-structureNM_002133HMOX1heme oxygenaseCyclin, Heme, Oxidoreductase,22076175(decycling) 1Microsome, Multigene family, 3D-structureNM_002134HMOX2heme oxygenaseHeme, Oxidoreductase, Microsome,22086176(decycling) 2Multigene family, RepeatNM_002136HNRPA1heterogeneousHypothetical protein, Nucleocapsid,22096177nuclearRibonucleoprotein, Nuclear protein,ribonucleoprotein A1RNA-binding, Repeat, Methylation,Alternative splicing, 3D-structure,PolymorphismNM_002139RBMXRNA binding motifHypothetical protein, Nuclear22106178protein, X-linkedprotein, RNA-binding,Ribonucleoprotein, GlycoproteinNM_002155HSPA6heat shock 70 kDaATP-binding, Heat shock, Multigene22116179protein 6 (HSP70B′)familyNM_002156HSPD1heat shock 60 kDaChaperone, ATP-binding,22126180protein 1Mitochondrion, Transit peptide(chaperonin)NM_002157HSPE1heat shock 10 kDaChaperone, Mitochondrion, Heat22136181protein 1shock, Acetylation(chaperonin 10)NM_002162ICAM3intercellularImmunoglobulin domain, Cell22146182adhesion molecule 3adhesion, Glycoprotein,Transmembrane, Repeat, Signal,PhosphorylationNM_002180IGHMBP2immunoglobulin muHydrolase, Helicase, ATP-binding,22156183binding protein 2DNA-binding, Nuclear protein,Transcription regulation, Activator,3D-structureNM_002191INHAinhibin, alphaGrowth factor, Hormone,22166184Glycoprotein, Signal, PolymorphismNM_002194INPP1inositolHydrolase, Lithium22176185polyphosphate-1-phosphataseNM_002205ITGA5integrin, alpha 5Integrin, Cell adhesion, Receptor,22186186(fibronectin receptor,Glycoprotein, Transmembrane,alpha polypeptide)Signal, Calcium, RepeatNM_002209ITGALintegrin, alpha LIntegrin, Cell adhesion, Receptor,22196187(antigen CD11AGlycoprotein, Transmembrane,(p180), lymphocyteSignal, 3D-structure, Magnesium,function-associatedCalcium, Repeat, Alternativeantigen 1; alphasplicing, Hypothetical proteinpolypeptide)NM_002218ITIH4inter-alpha (globulin)Acute phase, Serine protease22206188inhibitor H4 (plasmainhibitor, Repeat, Signal, MultigeneKallikrein-sensitivefamily, Glycoprotein, Alternativeglycoprotein)splicing, PolymorphismNM_002220ITPKAinositol 1,4,5-Kinase, Transferase, Calmodulin-22216189trisphosphate 3-bindingkinase ANM_002222ITPR1inositol 1,4,5-Receptor, Transmembrane,22226190triphosphatePhosphorylation, Endoplasmicreceptor, type 1reticulum, Ionic channel, Iontransport, Calcium channel,Alternative splicing, RepeatNM_002226JAG2jagged 2Calcium-binding, EGF-like domain,22236191Glycoprotein, Developmentalprotein, Repeat, Signal,Transmembrane, Alternative splicingNM_002228JUNv-jun sarcoma virusProto-oncogene, Transcription2224619217 oncogeneregulation, DNA-binding, 3D-homolog (avian)structure, Nuclear protein,Phosphorylation, PolymorphismNM_002236KCNF1potassium voltage-Transport, Ion transport, Ionic22256193gated channel,channel, Voltage-gated channel,subfamily F, member 1Potassium channel, Potassium,Potassium transport,Transmembrane, Multigene familyNM_002243KCNJ15potassium inwardly-Hypothetical protein, Ionic channel,22266194rectifying channel,Ion transport, Voltage-gatedsubfamily J, memberchannel, Transmembrane,15Potassium transportNM_002250KCNN4potassiumIonic channel, Transmembrane, Ion22276195intermediate/smalltransport, Calmodulin-bindingconductancecalcium-activatedchannel, subfamilyN, member 4NM_002258KLRB1killer cell lectin-like22286196receptor subfamilyB, member 1NM_002267KPNA3karyopherin alpha 3Hypothetical protein, Transport,22296197(importin alpha 4)Protein transport, Repeat, Nuclearprotein, PolymorphismNM_002271KPNB3karyopherinHypothetical protein, Transport,22306198(importin) beta 3Protein transport, Repeat, Nuclearprotein, PolymorphismNM_002273KRT8keratin 8Intermediate filament, Coiled coil,22316199Keratin, PhosphorylationNM_002275KRT15keratin 15Intermediate filament, Coiled coil,22326200KeratinNM_002277KRTHA1keratin, hair, acidic, 1Intermediate filament, Coiled coil,22336201KeratinNM_002278KRTHA2keratin, hair, acidic, 2Intermediate filament, Coiled coil,22346202KeratinNM_002282KRTHB3keratin, hair, basic, 3Coiled coil, Intermediate filament22356203NM_002296LBRlamin B receptorReceptor, Transmembrane,22366204Phosphorylation, Nuclear protein,DNA-bindingNM_002298LCP1lymphocyte cytosolicCalcium-binding, Phosphorylation,22376205protein 1 (L-plastin)Actin-binding, Repeat,PolymorphismNM_002299LCTlactaseHydrolase, Glycosidase, Zymogen,22386206Signal, Transmembrane, RepeatNM_002300LDHBlactateOxidoreductase, NAD, Glycolysis,22396207dehydrogenase BMultigene family, Disease mutation,3D-structureNM_002306LGALS3lectin, galactoside-Galectin, Lectin, IgE-binding protein,22406208binding, soluble, 3Repeat, Phosphorylation,(galectin 3)Acetylation, Nuclear protein,Polymorphism, 3D-structureNM_002311LIG3ligase III, DNA, ATP-DNA repair, DNA replication, DNA22416209dependentrecombination, Cell division, Ligase,ATP-binding, Zinc-finger, Nuclearprotein, Alternative splicing, 3D-structure, Hypothetical proteinNM_002313ABLIM1actin binding LIMLIM domain, Metal-binding, Zinc,22426210protein 1Hypothetical proteinNM_002316LMX1BLIM homeoboxDNA-binding, Homeobox, LIM22436211transcription factor 1,domain, Metal-binding, Nuclearbetaprotein, Zinc, Developmental protein,Repeat, Activator, Transcriptionregulation, Alternative splicing,Disease mutationNM_002332LRP1low densityReceptor, Transmembrane, Repeat,22446212lipoprotein-relatedEndocytosis, Glycoprotein, Signal,protein 1 (alpha-2-Calcium-binding, EGF-like domain,macroglobulinCoated pits, 3D-structure,receptor)PolymorphismNM_002335LRP5low densityReceptor, Lipoprotein22456213lipoprotein receptor-related protein 5NM_002337LRPAP1low densitySignal, Heparin-binding,22466214lipoprotein receptor-Glycoprotein, Antigen, 3D-structure,related proteinPolymorphismassociated protein 1NM_002339LSP1lymphocyte-specificT-cell, Phosphorylation,22476215protein 1PolymorphismNM_002341LTBlymphotoxin betaCytokine, Transmembrane,22486216(TNF superfamily,Glycoprotein, Signal-anchor,member 3)Alternative splicing, PolymorphismNM_002343LTFlactotransferrinGlycoprotein, Iron transport, Metal-22496217binding, Transport, Repeat, Signal,Polymorphism, 3D-structureNM_002357MADMAX dimerizationNuclear protein, DNA-binding,22506218protein 1Transcription regulation, Repressor,3D-structureNM_002375MAP4microtubule-Hypothetical protein, Microtubule,22516219associated protein 4Repeat, Phosphorylation, AlternativesplicingNM_002382MAXMAX proteinHypothetical protein, Transcription22526220regulation, Activator, Repressor,Nuclear protein, DNA-binding,Phosphorylation, Alternative splicing,3D-structureNM_002394SLC3A2solute carrier familyGlycoprotein, Transmembrane,225362213 (activators ofSignal-anchordibasic and neutralamino acidtransport), member 2NM_002402MESTmesoderm specificAromatic hydrocarbons catabolism,22546222transcript homologDetoxification, Hydrolase,(mouse)Hypothetical proteinNM_002406MGAT1mannosyl (alpha-Transferase, Glycosyltransferase,225562231,3-)-glycoproteinTransmembrane, Signal-anchor,beta-1,2-N-Golgi stack, Hypothetical proteinacetylglucosaminyltransferaseNM_002419MAP3K11mitogen-activatedATP-binding, Kinase, SH3 domain,22566224protein kinaseSerine/threonine-protein kinase,kinase kinase 11TransferaseNM_002424MMP8matrixHydrolase, Metalloprotease,22576225metalloproteinase 8Glycoprotein, Calcium-binding,(neutrophilMetal-binding, Zinc, Zymogen,collagenase)Collagen degradation, Extracellularmatrix, Signal, 3D-structureNM_002431MNAT1menage a trois 1Transcription regulation, Cell cycle,22586226(CAK assemblyNuclear protein, Zinc-finger, 3D-factor)structureNM_002432MNDAmyeloid cell nuclearInterferon induction, Nuclear protein,22596227differentiationDNA-binding, Transcriptionantigenregulation, Activator, Repressor,PolymorphismNM_002435MPImannose phosphateIsomerase, Zinc, Disease mutation22606228isomeraseNM_002442MSI1musashi homolog 1RNA-binding22616229(Drosophila)NM_002453MTIF2mitochondrialInitiation factor, Protein biosynthesis,22626230translational initiationGTP-binding, Transit peptide,factor 2Mitochondrion, PolymorphismNM_002455MTX1metaxin 1Mitochondrion, Outer membrane,22636231Transmembrane, Transport, ProteintransportNM_002475MLC1SAmyosin light chain 1Myosin, Muscle protein, Multigene22646232slow afamilyNM_002483CEACAM6carcinoembryonicImmunoglobulin domain, Signal,22656233antigen-related cellAntigen, Glycoprotein, GPI-anchor,adhesion molecule 6Repeat, Lipoprotein(non-specific crossreacting antigen)NM_002486NCBP1nuclear cap bindingTransport, mRNA transport, Nuclear22666234protein subunit 1,protein, RNA-binding, 3D-structure80 kDaNM_002492NDUFB5NADHOxidoreductase, NAD, Ubiquinone,22676235dehydrogenaseMitochondrion, Transit peptide(ubiquinone) 1 betasubcomplex, 5,16 kDaNM_002495NDUFS4NADHOxidoreductase, NAD, Ubiquinone,22686236dehydrogenaseMitochondrion, Transit peptide,(ubiquinone) Fe—SPolymorphismprotein 4, 18 kDa(NADH-coenzyme Qreductase)NM_002499NEO1neogenin homolog 1Cell adhesion, Repeat, Signal,22696237(chicken)Transmembrane, Immunoglobulindomain, Glycoprotein, AlternativesplicingNM_002512NME2non-metastatic cellsTransferase, Kinase, ATP-binding,227062382, protein (NM23B)Nuclear protein, Anti-oncogeneexpressed inDNA-binding, Transcriptionregulation, Activator, 3D-structureNM_002517NPAS1neuronal PASRepeat, DNA-binding, Nuclear22716239domain protein 1protein, Transcription regulationNM_002520NPM1nucleophosminHypothetical protein, Transcription22726240(nucleolarregulation, Nuclear protein, DNA-phosphoprotein B23,binding, Zinc-finger, Proto-numatrin)oncogene, Chromosomaltranslocation, Alternative splicing,Repeat, Coiled coil, 3D-structure,Metal-binding, Receptor, Multigenefamily, Phosphorylation, RNA-NM_002524NRASneuroblastoma RASHypothetical protein, RNA-binding,22736241viral (v-ras)Repeat, Alternative splicing, Proto-oncogene homologoncogene, GTP-binding, Prenylation,Lipoprotein, Disease mutationNM_002528NTHL1nth endonuclease III-Hydrolase, Nuclease, Endonuclease,22746242like 1 (E. coli)Multifunctional enzyme, DNA repair,Glycosidase, Lyase, Iron-sulfur, 4Fe—4S,Nuclear protein, PolymorphismNM_002532NUP88nucleoporin 88 kDaNuclear protein, Transport, Coiled22756243coilNM_002541OGDHoxoglutarate (alpha-Glycolysis, Oxidoreductase,22766244ketoglutarate)Flavoprotein, Thiaminedehydrogenasepyrophosphate, Mitochondrion,(lipoamide)Transit peptide, Hypothetical proteinNM_002543OLR1oxidised low densityLectin, Lipoprotein, Receptor22776245lipoprotein (lectin-like) receptor 1NM_002553ORC5Lorigin recognitionDNA replication, Nuclear protein,22786246complex, subunit 5-ATP-binding, Polymorphismlike (yeast)NM_002555SLC22A1Lsolute carrier familyHypothetical protein2279624722 (organic cationtransporter),member 1-likeNM_002557OVGP1oviductalGlycoprotein, Fertilization, Signal,22806248glycoprotein 1,Polymorphism120 kDa (mucin 9,oviductin)NM_002564P2RY2purinergic receptorG-protein coupled receptor,22816249P2Y, G-proteinTransmembrane, Glycoproteincoupled, 2NM_002573PAFAH1B3platelet-activatingHydrolase, Lipid degradation22826250factoracetylhydrolase,isoform lb, gammasubunit 29 kDaNM_002574PRDX1peroxiredoxin 1Antioxidant, Peroxidase,22836251Oxidoreductase, Redox-activecenterNM_002576PAK1p21/Cdc42/Rac1-Apoptosis, Transferase,22846252activated kinase 1Serine/threonine-protein kinase,(STE20 homolog,ATP-binding, Phosphorylation, 3D-yeast)structure, KinaseNM_002585PBX1pre-B-cell leukemiaTranscription regulation, DNA-22856253transcription factor 1binding, Nuclear protein, Activator,Repressor, Homeobox, Proto-oncogene, Chromosomaltranslocation, Alternative splicing,Steroidogenesis, Sexualdifferentiation, 3D-structure,PhosphorylationNM_002587PCDH1protocadherin 1Cell adhesion, Transmembrane,22866254(cadherin-like 1)Calcium-binding, Repeat, Signal,Alternative splicingNM_002598PDCD2programmed cellZinc-finger, DNA-binding, Nuclear22876255death 2protein, ApoptosisNM_002601PDE6DphosphodiesteraseHydrolase, cGMP, Vision, 3D-228862566D, cGMP-specific,structurerod, deltaNM_002608PDGFBplatelet-derivedMitogen, Growth factor, Proto-22896257growth factor betaoncogene, Platelet, Signal,polypeptide (simianPharmaceutical, 3D-structure,sarcoma viral (v-sis)Polymorphism, Chromosomaloncogene homolog)translocationNM_002611PDK2pyruvateKinase, Transferase, Transit peptide,22906258dehydrogenaseMitochondrion, Multigene familykinase, isoenzyme 2NM_002613PDPK13-phosphoinositideTransferase, Serine/threonine-22916259dependent proteinprotein kinase, ATP-binding,kinase-1Phosphorylation, Membrane,Alternative splicing, KinaseNM_002616PER1period homolog 1Transcription regulation, Nuclear22926260(Drosophila)protein, Repeat, Biological rhythms,Alternative splicingNM_002621PFCproperdin P factor,Signal, Complement alternate22936261complementpathway, Glycoprotein, Repeat,Disease mutationNM_002629PGAM1phosphoglycerateIsomerase, Hydrolase, Glycolysis,22946262mutase 1 (brain)Acetylation, 3D-structureNM_002631PGDphosphogluconateOxidoreductase, Pentose shunt,22956263dehydrogenaseNADPNM_002633PGM1phosphoglucomutase 1Isomerase, Phosphorylation,22966264Magnesium, Polymorphism,Alternative splicing, HypotheticalproteinNM_002635SLC25A3solute carrier familyMitochondrion, Inner membrane,2297626525 (mitochondrialRepeat, Transit peptide,carrier; phosphateTransmembrane, Transport,carrier), member 3Symport, Alternative splicing,Hypothetical proteinNM_002640SERPINB8serine (or cysteine)Protease inhibitor, Serine protease22986266proteinase inhibitor,inhibitor, Serpinclade B (ovalbumin),member 8NM_002649PIK3CGphosphoinositide-3-Kinase, Transferase, Multigene22996267kinase, catalytic,family, 3D-structuregamma polypeptideNM_002650PIK4CAphosphatidylinositolTransferase, Kinase, Alternative230062684-kinase, catalytic,splicingalpha polypeptideNM_002651PIK4CBphosphatidylinositolTransferase, Kinase, Golgi stack,230162694-kinase, catalytic,Phosphorylation, Alternative splicingbeta polypeptideNM_002653PITX1paired-likeHomeobox, DNA-binding,23026270homeodomainDevelopmental protein, Nucleartranscription factor 1protein, Transcription regulation,ActivatorNM_002654PKM2pyruvate kinase,Transferase, Kinase, Glycolysis,23036271muscleMultigene family, Magnesium,Alternative splicing, HypotheticalproteinNM_002655PLAG1pleiomorphicMetal-binding, Zinc, Zinc-finger23046272adenoma gene 1NM_002659PLAURplasminogenReceptor, Signal, Glycoprotein, GPI-23056273activator, urokinaseanchor, Repeat, Alternative splicing,receptorPolymorphism, Lipoprotein, KinaseNM_002661PLCG2phospholipase C,Hydrolase, Lipid degradation,23066274gamma 2Transducer, SH2 domain, SH3(phosphatidylinositoldomain, Repeat, Calcium-binding,specific)PhosphorylationNM_002668PLP2proteolipid protein 2Transmembrane, Glycoprotein,23076275(colonic epithelium-Polymorphismenriched)NM_002676PMM1phosphomannomutase 1Isomerase23086276NM_002685PMSCL2polymyositis/sclerodermaHydrolase, Nuclease, Exonuclease,23096277autoantigen 2,rRNA processing, Nuclear protein,100 kDaRNA-binding, Antigen, Alternativesplicing, Hypothetical proteinNM_002686PNMTphenylethanolamineTransferase, Methyltransferase,23106278N-methyltransferaseCatecholamine biosynthesis, 3D-structureNM_002688PNUTL1peanut-like 1Hypothetical protein, Cell division,23116279(Drosophila)GTP-binding, Coiled coil, Platelet,Transmembrane, Glycoprotein,Hemostasis, Blood coagulation,Signal, Phosphorylation, Celladhesion, Leucine-rich repeatNM_002691POLD1polymerase (DNADNA replication, DNA-binding, DNA-23126280directed), delta 1,directed DNA polymerase,catalytic subunitTransferase, Hydrolase,125 kDaExonuclease, Zinc-finger, Nuclearprotein, PolymorphismNM_002692POLE2polymerase (DNATransferase, DNA-directed DNA23136281directed), epsilon 2polymerase, DNA replication, DNA-(p59 subunit)binding, Nuclear proteinNM_002710PPP1CCprotein phosphataseHydrolase, Metal-binding, Iron,231462821, catalytic subunit,Manganese, Glycogen metabolism,gamma isoformMultigene family, Cell division,Alternative splicing, 3D-structureNM_002720PPP4Cprotein phosphataseHydrolase, Metal-binding, Iron,231562834 (formerly X),Manganesecatalytic subunitNM_002727PRG1proteoglycan 1,Glycoprotein, Proteoglycan, Repeat,23166284secretory granuleSignalNM_002728PRG2proteoglycan 2, boneEosinophil, Signal, Immune23176285marrow (natural killerresponse, Antibiotic, Lectin,cell activator,Proteoglycan, Glycoprotein, Heparin-eosinophil granulebinding, 3D-structuremajor basic protein)NM_002731PRKACBprotein kinase,ATP-binding, Kinase,23186286cAMP-dependent,Serine/threonine-protein kinase,catalytic, betaTransferase, Nuclear protein, cAMP,Myristate, Phosphorylation,Multigene family, LipoproteinNM_002733PRKAG1protein kinase, AMP-Fatty acid biosynthesis, Repeat,23196287activated, gamma 1CBS domain, Hypothetical proteinnon-catalytic subunitNM_002738PRKCB1protein kinase C,Transferase, Serine/threonine-23206288beta 1protein kinase, Membrane, ATP-binding, Calcium-binding, Metal-binding, Zinc, Repeat, Phorbol-esterbinding, Phosphorylation, AlternativesplicingNM_002741PRKCL1protein kinase C-like 1Transferase, ATP-binding,23216289Serine/threonine-protein kinase,Phosphorylation, Polymorphism, 3D-structureNM_002745MAPK1mitogen-activatedTransferase, Serine/threonine-23226290protein kinase 1protein kinase, ATP-binding, Cellcycle, Phosphorylation, 3D-structureNM_002748MAPK6mitogen-activatedKinase, Transferase,23236291protein kinase 6Serine/threonine-protein kinase,ATP-binding, Cell cycleNM_002749MAPK7mitogen-activatedATP-binding, Kinase,23246292protein kinase 7Serine/threonine-protein kinase,Transferase, Cell cycle,Phosphorylation, Cell adhesion,Extracellular matrix, Glycoprotein,Calcium, SignalNM_002756MAP2K3mitogen-activatedTransferase, Serine/threonine-23256293protein kinaseprotein kinase, Tyrosine-proteinkinase 3kinase, ATP-binding,Phosphorylation, Alternative splicing,Disease mutationNM_002757MAP2K5mitogen-activatedATP-binding, Kinase,23266294protein kinaseSerine/threonine-protein kinase,kinase 5TransferaseNM_002758MAP2K6mitogen-activatedTransferase, Serine/threonine-23276295protein kinaseprotein kinase, Tyrosine-proteinkinase 6kinase, ATP-binding,Phosphorylation, Alternative splicingNM_002764PRPS1phosphoribosylNucleotide biosynthesis,23286296pyrophosphateTransferase, Kinase, Magnesium,synthetase 1Multigene family, Gout, DiseasemutationNM_002765PRPS2phosphoribosylNucleotide biosynthesis,23296297pyrophosphateTransferase, Kinase, Magnesium,synthetase 2Multigene familyNM_002767PRPSAP2phosphoribosylNucleotide biosynthesis23306298pyrophosphatesynthetase-associated protein 2NM_002770PRSS2protease, serine, 2Hydrolase, Protease, Serine23316299(trypsin 2)protease, Digestion, Pancreas,Zymogen, Calcium-binding, Signal,Multigene familyNM_002777PRTN3proteinase 3 (serineCollagen degradation, Hydrolase,23326300proteinase,Serine protease, Signal, Zymogen,neutrophil, WegenerGlycoprotein, Polymorphism, 3D-granulomatosisstructureautoantigen)NM_002782PSG6pregnancy specificImmunoglobulin domain,23336301beta-1-glycoprotein 6Glycoprotein, Signal, Multigenefamily, Repeat, Polymorphism,Alternative splicing, Hypotheticalprotein, Flavoprotein, Lyase,Thiamine pyrophosphateNM_002786PSMA1proteasomeProteasome, Hydrolase, Protease,23346302(prosome,Acetylation, Alternative splicing,macropain) subunit,Threonine proteasealpha type, 1NM_002788PSMA3proteasomeProteasome, Hydrolase, Protease,23356303(prosome,Acetylation, Alternative splicing,macropain) subunit,Phosphorylation, Threonine proteasealpha type, 3NM_002790PSMA5proteasomeProteasome, Hydrolase, Protease,23366304(prosome,Threonine proteasemacropain) subunit,alpha type, 5NM_002793PSMB1proteasomeProteasome, Hydrolase, Protease,23376305(prosome,Threonine proteasemacropain) subunit,beta type, 1NM_002794PSMB2proteasomeProteasome, Hydrolase, Protease,23386306(prosome,Threonine proteasemacropain) subunit,beta type, 2NM_002796PSMB4proteasomeProteasome, Hydrolase, Protease,23396307(prosome,Zymogen, Polymorphism, Threoninemacropain) subunit,proteasebeta type, 4NM_002805PSMC5proteasomeATP-binding, Proteasome23406308(prosome,macropain) 26Ssubunit, ATPase, 5NM_002807PSMD1proteasomeProteasome, Repeat23416309(prosome,macropain) 26Ssubunit, non-ATPase, 1NM_002809PSMD3proteasomeHypothetical protein, Proteasome23426310(prosome,macropain) 26Ssubunit, non-ATPase, 3NM_002815PSMD11proteasomeProteasome23436311(prosome,macropain) 26Ssubunit, non-ATPase, 11NM_002818PSME2proteasomeProteasome, Interferon induction23446312(prosome,macropain) activatorsubunit 2 (PA28beta)NM_002821PTK7PTK7 proteinATP-binding, Immunoglobulin23456313tyrosine kinase 7domain, Receptor, Transferase,Transmembrane, Signal,Glycoprotein, Cell adhesion, Repeat,Hypothetical protein, Kinase,Tyrosine-protein kinaseNM_002824PTMSparathymosinHypothetical protein, Immune23466314response, AcetylationNM_002826QSCN6quiescin Q6Redox-active center23476315NM_002831PTPN6protein tyrosineHydrolase, SH2 domain, Repeat,23486316phosphatase, non-Phosphorylation, Alternative splicing,receptor type 63D-structureNM_002842PTPRHprotein tyrosineSignal23496317phosphatase,receptor type, HNM_002843PTPRJprotein tyrosineSignal, Glycoprotein,23506318phosphatase,Transmembrane, Repeat,receptor type, JHydrolase, Disease mutation,ReceptorNM_002850PTPRSprotein tyrosineHydrolase, Receptor, Glycoprotein,23516319phosphatase,Signal, Transmembrane, Cellreceptor type, Sadhesion, Immunoglobulin domain,Alternative splicing, RepeatNM_002852PTX3pentaxin-relatedPentaxin, Glycoprotein, Signal23526320gene, rapidlyinduced by IL-1 betaNM_002859PXNhypothetical proteinCytoskeleton, Phosphorylation, LIM23536321FLJ23042domain, Repeat, Metal-binding, Zinc,Alternative splicing, 3D-structure,Hypothetical proteinNM_002862PYGBphosphorylase,Carbohydrate metabolism,23546322glycogen; brainGlycosyltransferase, Pyridoxalphosphate, Transferase, Glycogenmetabolism, Allosteric enzyme,PhosphorylationNM_002863PYGLphosphorylase,Transferase, Glycosyltransferase,23556323glycogen; liver (HersCarbohydrate metabolism, Glycogendisease, glycogenmetabolism, Allosteric enzyme,storage disease typePyridoxal phosphate,VI)Phosphorylation, Glycogen storagedisease, Disease mutation,Polymorphism, 3D-structureNM_002865RAB2RAB2, member RASGTP-binding, Transport, Protein23566324oncogene familytransport, Endoplasmic reticulum,Golgi stack, Lipoprotein, PrenylationNM_002872RAC2ras-related C3GTP-binding, Prenylation,23576325botulinum toxinLipoprotein, 3D-structuresubstrate 2 (rhofamily, small GTPbinding proteinRac2)NM_002878RAD51L3RAD51-like 3 (S. cerevisiae)DNA damage, DNA repair, DNA23586326recombination, DNA-binding, ATP-binding, Nuclear protein, Alternativesplicing, Hypothetical proteinNM_002880RAF1v-raf-1 murineHypothetical protein, Metal-binding,23596327leukemia viralZinc, Zinc-finger, Transferase,oncogene homolog 1Serine/threonine-protein kinase,Proto-oncogene, ATP-binding,Phorbol-ester binding,Phosphorylation, 3D-structure,RepeatNM_002881RALBv-ral simianGTP-binding, Prenylation,23606328leukemia viralLipoproteinoncogene homologB (ras related; GTPbinding protein)NM_002883RANGAP1Ran GTPaseHypothetical protein, GTPase23616329activating protein 1activation, Repeat, Leucine-richrepeat, Ubl conjugationNM_002887RARSarginyl-tRNAAminoacyl-tRNA synthetase, Protein23626330synthetasebiosynthesis, Ligase, ATP-binding,Alternative initiationNM_002893RBBP7retinoblastomaNuclear protein, Repeat, WD repeat23636331binding protein 7NM_002896RBM4RNA binding motifZinc-finger23646332protein 4NM_002897RBMS1RNA binding motif,DNA-binding, DNA replication, RNA-23656333single strandedbinding, Nuclear protein,interacting protein 1PhosphorylationNM_002901RCN1reticulocalbin 1, EF-Calcium-binding, Endoplasmic23666334hand calciumreticulum, Signal, Glycoprotein,binding domainRepeat, PolymorphismNM_002902RCN2reticulocalbin 2, EF-Calcium-binding, Endoplasmic23676335hand calciumreticulum, Signal, Repeatbinding domainNM_002903RCV1recoverinCalcium-binding, Repeat, Myristate,23686336Vision, LipoproteinNM_002905RDH5retinolOxidoreductase, NAD, Membrane,23696337dehydrogenase 5Vision, Disease mutation,(11-cis and 9-cis)PolymorphismNM_002910RENBPrenin binding proteinIsomerase23706338NM_002918RFX1regulatory factor X, 1DNA-binding, Transcription23716339(influences HLAregulation, Activator, Nuclearclass II expression)protein, 3D-structureNM_002922RGS1regulator of G-Signal transduction inhibitor, B-cell23726340protein signalling 1activation, PhosphorylationNM_002923RGS2regulator of G-Signal transduction inhibitor, Cell23736341protein signalling 2,cycle, Phosphorylation24 kDaNM_002934RNASE2ribonuclease, RNaseHydrolase, Nuclease, Endonuclease,23746342A family, 2 (liver,Chemotaxis, Eosinophil,eosinophil-derivedGlycoprotein, Signal, Polymorphism,neurotoxin)3D-structureNM_002935RNASE3ribonuclease, RNaseHydrolase, Nuclease, Endonuclease,23756343A family, 3Eosinophil, Glycoprotein, Antibiotic,(eosinophil cationicSignal, Polymorphism, 3D-structureprotein)NM_002936RNASEH1ribonuclease H1Hydrolase, Nuclease, Endonuclease,23766344MagnesiumNM_002939RNHribonuclease/angiogeninRepeat, Leucine-rich repeat, 3D-23776345inhibitorstructure, Polymorphism,Hypothetical proteinNM_002940ABCE1ATP-bindingCapsid assembly, Chaperone,23786346cassette, sub-familyMitochondrion, ATP-binding, RepeatE (OABP), member 1NM_002953RPS6KA1ribosomal protein S6Transferase, Serine/threonine-23796347kinase, 90 kDa,protein kinase, ATP-binding, Repeat,polypeptide 1Multigene familyNM_002957RXRAretinoid X receptor,Receptor, Transcription regulation,23806348alphaDNA-binding, Nuclear protein, Zinc-finger, Multigene family, 3D-structure, PolymorphismNM_002961S100A4S100 calciumCalcium-binding, 3D-structure23816349binding protein A4(calcium protein,calvasculin,metastasin, murineplacental homolog)NM_002964S100A8S100 calciumMacrophage, Calcium-binding, 3D-23826350binding protein A8structure(calgranulin A)NM_002965S100A9S100 calciumCalcium-binding, Macrophage,23836351binding protein A9Phosphorylation, Polymorphism, 3D-(calgranulin B)structureNM_002967SAFBscaffold attachmentTranscription regulation, Repressor,23846352factor BNuclear protein, DNA-binding, RNA-binding, PhosphorylationNM_002969MAPK12mitogen-activatedTransferase, Serine/threonine-23856353protein kinase 12protein kinase, ATP-binding, Cellcycle, Phosphorylation,Polymorphism, 3D-structureNM_002978SCNN1Dsodium channel,Ion transport, Sodium transport,23866354nonvoltage-gated 1,Ionic channel, Transmembrane,deltaGlycoprotein, Alternative splicing,Sodium channelNM_002984CCL4chemokine (C—CCytokine, Chemotaxis, Inflammatory23876355motif) ligand 4response, Signal, 3D-structureNM_002985CCL5chemokine (C—CCytokine, Chemotaxis, T-cell, Signal,23886356motif) ligand 5Inflammatory response, 3D-structureNM_003003SEC14L1SEC14-like 1 (S. cerevisiae)23896357NM_003006SELPLGselectin P ligandHypothetical protein, Cell adhesion,23906358Glycoprotein, Transmembrane,Signal, Repeat, Polymorphism,Sulfation, 3D-structure, Lectin,SelectinNM_003011SETSET translocationProto-oncogene, Chromosomal23916359(myeloid leukemia-translocation, Nuclear protein,associated)PhosphorylationNM_003021SGTsmall glutamine-richChaperone, Repeat, TPR repeat,23926360tetratricopeptideHypothetical proteinrepeat (TPR)-containing, alphaNM_003040SLC4A2solute carrier familyTransmembrane, Glycoprotein,239363614, anion exchanger,Transport, Antiport, Ion transport,member 2Anion exchange, Lipoprotein,(erythrocytePalmitate, Alternative splicingmembrane proteinband 3-like 1)NM_003044SLC6A12solute carrier familyNeurotransmitter transport,239463626 (neurotransmitterTransport, Transmembrane,transporter,Glycoprotein, Symportbetaine/GABA),member 12NM_003055SLC18A3cholineTransport, Neurotransmitter23956363acetyltransferasetransport, Transmembrane,GlycoproteinNM_003056SLC19A1solute carrier familyFolate-binding, Transport,2396636419 (folateTransmembrane, Glycoproteintransporter),member 1NM_003057SLC22A1solute carrier familyTransmembrane2397636522 (organic cationtransporter),member 1NM_003059SLC22A4solute carrier familyTransmembrane2398636622 (organic cationtransporter),member 4NM_003064SLPIsecretory leukocyteSerine protease inhibitor, Repeat,23996367protease inhibitorSignal(antileukoproteinase)NM_003066SLPIsecretory leukocyteSerine protease inhibitor, Repeat,24006368protease inhibitorSignal(antileukoproteinase)NM_003071SMARCA3SWI/SNF related,ATP-binding, DNA-binding, Helicase,24016369matrix associated,Hydrolase, Metal-binding, Zinc, Zinc-actin dependentfingerregulator ofchromatin, subfamilya, member 3NM_003073SMARCB1SWI/SNF related,Hypothetical protein, Transcription24026370matrix associated,regulation, Activator, Nuclearactin dependentprotein, Alternative splicing, Anti-regulator ofoncogenechromatin, subfamilyb, member 1NM_003074SMARCC1SWI/SNF related,DNA-binding, Nuclear protein24036371matrix associated,actin dependentregulator ofchromatin, subfamilyc, member 1NM_003077SMARCD2SWI/SNF related,24046372matrix associated,actin dependentregulator ofchromatin, subfamilyd, member 2NM_003079SMARCE1SWI/SNE related,24056373matrix associated,actin dependentregulator ofchromatin, subfamilye, member 1NM_003084SNAPC3small nuclear RNAHypothetical protein, Transcription24066374activating complex,regulation, DNA-bindingpolypeptide 3,50 kDaNM_003085SNCBsynuclein, betaPhosphorylation, Repeat24076375NM_003086SNAPC4small nuclear RNADNA-binding, Nuclear protein,24086376activating complex,Hypothetical proteinpolypeptide 4,190 kDaNM_003088FSCN1fascin homolog 1,Actin-binding, Acetylation,24096377actin-bundlingPhosphorylation, 3D-structure,proteinHypothetical protein(Strongylocentrotuspurpuratus)NM_003090SNRPA1small nuclearNuclear protein, RNA-binding,24106378ribonucleoproteinRibonucleoprotein, Leucine-richpolypeptide A′repeat, Repeat, 3D-structureNM_003092SNRPB2small nuclearmRNA processing, mRNA splicing,24116379ribonucleoproteinNuclear protein, RNA-binding,polypeptide B″Ribonucleoprotein, Repeat,Systemic lupus erythematosus, 3D-structureNM_003093SNRPCsmall nuclearNuclear protein, RNA-binding,24126380ribonucleoproteinRibonucleoprotein, Zinc-fingerpolypeptide CNM_003094SNRPEsmall nuclearNuclear protein, Ribonucleoprotein,24136381ribonucleoproteinSystemic lupus erythematosus,polypeptide EmRNA splicing, mRNA processing,RNA-bindingNM_003100SNX2sorting nexin 2Transport, Protein transport24146382NM_003104SORDsorbitolOxidoreductase, Zinc, Metal-binding,24156383dehydrogenaseNAD, Acetylation, PolymorphismNM_003105SORL1sortilin-relatedEndocytosis, Receptor,24166384receptor, L(DLRTransmembrane, EGF-like domain,class) A repeats-Repeat, Glycoprotein, LDL, Lipidcontainingtransport, Cholesterol metabolism,SignalNM_003107SOX4SRY (sexDNA-binding, Nuclear protein,24176385determining regionTranscription regulation, ActivatorY)-box 4NM_003120SPI1spleen focus formingProto-oncogene, DNA-binding,24186386virus (SFFV) proviralTranscription regulation, Activator,integration oncogeneNuclear proteinspi1NM_003135SRP19signal recognitionSignal recognition particle, RNA-24196387particle 19 kDabinding, Ribonucleoprotein, 3D-structureNM_003141SSA1Sjogren syndromeSystemic lupus erythematosus, Zinc-24206388antigen A1 (52 kDa,finger, Antigen, RNA-binding,ribonucleoproteinRibonucleoprotein, DNA-binding,autoantigen SS-PolymorphismA/Ro)NM_003143SSBP1single-stranded DNADNA-binding, DNA replication,24216389binding protein 1Mitochondrion, Transit peptide, 3D-structureNM_003146SSRP1structure specificDNA-binding, Nuclear protein24226390recognition protein 1NM_003150STAT3signal transducerHypothetical protein, Transcription24236391and activator ofregulation, Activator, DNA-binding,transcription 3Nuclear protein, Phosphorylation,(acute-phaseSH2 domainresponse factor)NM_003153STAT6signal transducerTranscription regulation, Repressor,24246392and activator ofAlternative splicing, Activator, DNA-transcription 6,binding, Nuclear protein,interleukin-4 inducedPhosphorylation, SH2 domain,PolymorphismNM_003163STX1B1Human mRNA forNeurotransmitter transport, Coiled24256393SYNTAXIN1B,coil, Transmembranecomplete cds.NM_003168SUPT4H1suppressor of Ty 4Nuclear protein, Transcription, Zinc-24266394homolog 1 (S. cerevisiae)fingerNM_003169SUPT5Hsuppressor of Ty 524276395homolog (S. cerevisiae)NM_003171SUPV3L1suppressor of var1,ATP-binding, Helicase, Hydrolase242863963-like 1 (S. cerevisiae)NM_003174SVILsupervillin24296397NM_003177SYKspleen tyrosineTransferase, Tyrosine-protein24306398kinasekinase, ATP-binding,Phosphorylation, SH2 domain,Repeat, Alternative splicing, 3D-structureNM_003190TAPBPTAP binding proteinImmunoglobulin domain, Signal,24316399(tapasin)Transmembrane, Endoplasmicreticulum, Microsome, Alternativesplicing, PolymorphismNM_003191TARShypothetical proteinAminoacyl-tRNA synthetase, Protein24326400MGC9344biosynthesis, Ligase, ATP-bindingNM_003193TBCEtubulin-specific24336401chaperone eNM_003197TCEB1LS-phase kinase-Ubl conjugation pathway, Alternative24346402associated proteinsplicing, 3D-structure1A (p19A)NM_003199TCF4transcription factor 4Transcription regulation, DNA-24356403binding, Activator, Nuclear protein,Alternative splicingNM_003201TFAMtranscription factorTranscription regulation, DNA-24366404A, mitochondrialbinding, Activator, Mitochondrion,Transit peptide, Repeat,PolymorphismNM_003202TCF7transcription factor 7Transcription regulation, Activator,24376405(T-cell specific,Repressor, Trans-acting factor,HMG-box)Nuclear protein, DNA-binding, Wntsignaling pathway, Alternativesplicing, Alternative promoter usageNM_003203C2orf3chromosome 2 open24386406reading frame 3NM_003205TCF12transcription factorTranscription regulation, DNA-2439640712 (HTF4, helix-binding, Nuclear protein,loop-helixDevelopmental proteintranscription factors4)NM_003217TEGTtestis enhancedApoptosis, Transmembrane24406408gene transcript (BAXinhibitor 1)NM_003226TFF3trefoil factor 3Signal, 3D-structure24416409(intestinal)NM_003227TFR2transferrin receptor 2Transmembrane, Glycoprotein,24426410Receptor, Signal-anchor, Alternativesplicing, Disease mutationNM_003236TGFAtransforming growthEGF-like domain, Growth factor,24436411factor, alphaMitogen, Glycoprotein,Transmembrane, Signal, 3D-structure, Lipoprotein, PalmitateNM_003245TGM3transglutaminase 3Transferase, Acyltransferase,24446412(E polypeptide,Calcium-binding, Zymogen,protein-glutamine-Keratinization, 3D-structuregamma-glutamyltransferase)NM_003248THBS4thrombospondin 4Glycoprotein, Cell adhesion,24456413Calcium-binding, Repeat, EGF likedomain, SignalNM_003252TIAL1TIA1 cytotoxicRNA-binding, Apoptosis, Repeat24466414granule-associatedRNA binding protein-like 1NM_003255TIMP2tissue inhibitor ofHypothetical protein,24476415metalloproteinase 2Metalloprotease inhibitor, Signal, 3D-structureNM_003263TLR1toll-like receptor 1Receptor, Immune response,24486416Inflammatory response, Signal,Transmembrane, Repeat, Leucine-rich repeat, Glycoprotein, 3D-structureNM_003274TMEM1transmembraneTransport, Endoplasmic reticulum,24496417protein 1Golgi stack, PolymorphismNM_003281TNNI1troponin I, skeletal,Muscle protein, Actin-binding, Ubl24506418slowconjugation pathway, Hydrolase,Thiol protease, Multigene familyNM_003288TPD52L2tumor protein D52-Coiled coil, Alternative splicing24516419like 2NM_003289TPM2tropomyosin 2 (beta)Muscle protein, Cytoskeleton, Actin-24526420binding, Coiled coil, Alternativesplicing, Multigene family,Acetylation, Disease mutationNM_003290TPM4tropomyosin 4Muscle protein, Cytoskeleton, Actin-24536421binding, Coiled coil, Alternativesplicing, Multigene familyNM_003299TRA1tumor rejectionChaperone, Endoplasmic reticulum,24546422antigen (gp96) 1Glycoprotein, Calcium-binding,SignalNM_003307TRPM2Homo sapiensIonic channel, Transmembrane, Ion24556423transient receptortransport, Calcium channel,potential cationAlternative splicingchannel, subfamilyM, member 2(TRPM2), mRNA.NM_003310TSSC1tumor suppressingRepeat, WD repeat24566424subtransferablecandidate 1NM_003316TTC3tetratricopeptideMetal-binding, Zinc, Zinc-finger,24576425repeat domain 3Repeat, TPR repeat, Alternativesplicing, PolymorphismNM_003326TNFSF4tumor necrosis factorCytokine, Transmembrane,24586426(ligand) superfamily,Glycoprotein, Signal-anchormember 4 (tax-transcriptionallyactivatedglycoprotein 1,34 kDa)NM_003329TXNthioredoxinRedox-active center, Electron24596427transport, 3D-structureNM_003330TXNRD1thioredoxinRedox-active center,24606428reductase 1Oxidoreductase, NADP,Flavoprotein, FADNM_003331TYK2tyrosine kinase 2Transferase, Tyrosine-protein24616429kinase, ATP-binding,Phosphorylation, SH2 domain,RepeatNM_003332TYROBPTYRO proteinTransmembrane, Signal,24626430tyrosine kinasePhosphorylation, Polymorphism,binding proteinReceptorNM_003338UBE2D1ubiquitin-conjugatingUbl conjugation pathway, Ligase,24636431enzyme E2D 1Multigene family(UBC4/5 homolog,yeast)NM_003341UBE2E1ubiquitin-conjugatingUbl conjugation pathway, Ligase,24646432enzyme E2E 1Multigene family(UBC4/5 homolog,yeast)NM_003343UBE2G2ubiquitin-conjugatingUbl conjugation pathway, Ligase,24656433enzyme E2G 2Multigene family, Hypothetical(UBC7 homolog,proteinyeast)NM_003348UBE2Nubiquitin-conjugatingUbl conjugation pathway, Ligase,24666434enzyme E2NMultigene family, 3D-structure(UBC13 homolog,yeast)NM_003358UCP2uncoupling protein 2Mitochondrion, Inner membrane,24676435(mitochondrial,Repeat, Transmembrane, Transport,proton carrier)PolymorphismNM_003355UGCGUDP-glucoseTransferase, Glycosyltransferase,24686436ceramideTransmembrane, Signal-anchor,glucosyltransferaseEndoplasmic reticulumNM_003362UNGuracil-DNADNA repair, Hydrolase, Glycosidase,24696437glycosylaseNuclear protein, Mitochondrion,Transit peptide, Disease mutation,Alternative splicing, 3D-structureNM_003364UPuridineTransferase, Glycosyltransferase,24706438phosphorylase 1Alternative splicingNM_003366UQCRC2ubiquinol-Mitochondrion, Inner membrane,24716439cytochrome cElectron transport, Respiratoryreductase corechain, Oxidoreductase, Transitprotein IIpeptideNM_003370VASPvasodilator-Phosphorylation, Actin-binding, 3D-24726440stimulatedstructurephosphoproteinNM_003374VDAC1voltage-dependentOuter membrane, Porin,24736441anion channel 1Mitochondrion, AcetylationNM_003375VDAC2voltage-dependentOuter membrane, Porin,24746442anion channel 2Mitochondrion, Alternative splicing,PolymorphismNM_003377VEGFBvascular endothelialMitogen, Growth factor,24756443growth factor BGlycoprotein, Signal, Heparin-binding, Alternative splicing,Multigene familyNM_003387WASPIPWiskott-AldrichActin-binding, Repeat,24766444syndrome proteinPolymorphisminteracting proteinNM_003389CORO2Acoronin, actinActin-binding, Repeat, WD repeat,24776445binding protein, 2ACoiled coilNM_003403YY1YY1 transcriptionTranscription regulation, Repressor,24786446factorActivator, Nuclear protein, Zinc-finger, Metal-binding, DNA-binding,Repeat, 3D-structureNM_003407ZFP36zinc finger proteinNuclear protein, Repeat, Metal-2479644736, C3H type,binding, Zinc-finger, DNA-bindinghomolog (mouse)NM_003426ZNF74zinc finger protein 74Transcription regulation, DNA-24806448(Cos52)binding, RNA-binding, Zinc-finger,Metal-binding, Nuclear protein,Repeat, Alternative splicing,PolymorphismNM_003451ZNF177zinc finger proteinTranscription regulation, DNA-24816449177binding, Zinc-finger, Metal-binding,Nuclear protein, Repeat,Hypothetical proteinNM_003457ZNF207zinc finger proteinZinc-finger, Metal-binding, DNA-24826450207binding, Nuclear protein, Alternativesplicing, Hypothetical proteinNM_003461ZYXzyxinLIM domain, Metal-binding, Zinc,24836451Repeat, Cell adhesion, ReceptorNM_003465CHIT1chitinase 1Carbohydrate metabolism, Chitin24846452(chitotriosidase)degradation, Polysaccharidedegradation, Hydrolase,Glycosidase, Chitin-binding, Signal,Alternative splicing, 3D-structureNM_003466PAX8paired box gene 8DNA-binding, Developmental24856453protein, Nuclear protein, Paired box,Transcription, Transcriptionregulation, Differentiation, Alternativesplicing, Disease mutation,PolymorphismNM_003467CXCR4chemokine (C—X—CG-protein coupled receptor,24866454motif) receptor 4Receptor, Transmembrane,Glycoprotein, Sulfation, Antigen,Alternative splicingNM_003475C11orf13chromosome 11Coiled coil, Alternative splicing24876455open reading frame13NM_003477PDX1pyruvateTransit peptide, Mitochondrion,24886456dehydrogenaseLipoyl, Hypothetical protein,complex, component XAcyltransferase, TransferaseNM_003489NRIP1nuclear receptorTranscription regulation, Nuclear24896457interacting protein 1proteinNM_003493HIST3H3histone 3, H3Nuclear protein, Chromosomal24906458protein, DNA-binding, Nucleosomecore, Multigene family, Acetylation,MethylationNM_003494DYSFdysferlin, limb girdleTransmembrane, Repeat, Disease24916459muscular dystrophymutation, Hypothetical protein2B (autosomalrecessive)NM_003498SNNstanninTransmembrane, HSSypothetical24926460proteinNM_003507FZD7frizzled homolog 7Multigene family, G-protein coupled24936461(Drosophila)receptor, Transmembrane,Developmental protein, Wntsignaling pathway, Glycoprotein,SignalNM_003508FZD9frizzled homolog 9Multigene family, G-protein coupled24946462(Drosophila)receptor, Transmembrane,Developmental protein, Wntsignaling pathway, Glycoprotein,SignalNM_003530HIST1H3Dhistone 1, H3dNuclear protein, Chromosomal24956463protein, DNA-binding, Nucleosomecore, Multigene family, Acetylation,MethylationNM_003532HIST1H3Ehistone 1, H3cNuclear protein, Chromosomal24966464protein, DNA-binding, Nucleosomecore, Multigene family, Acetylation,MethylationNM_003534HIST1H3Ghistone 1, H3gNuclear protein, Chromosomal24976465protein, DNA-binding, Nucleosomecore, Multigene family, Acetylation,MethylationNM_003535HIST1H3Jhistone 1, H3jNuclear protein, Chromosomal24986466protein, DNA-binding, Nucleosomecore, Multigene family, Acetylation,MethylationNM_003549HYAL3hyaluronoglucosaminidase 3EGE-like domain24996467NM_003560PLA2G6phospholipase A2,Hypothetical protein, ANK repeat,25006468group VI (cytosolic,Repeat, Hydrolase, Lipidcalcium-degradation, Membrane, Alternativeindependent)splicingNM_003562SLC25A11solute carrier familyMitochondrion, Inner membrane,2501646925 (mitochondrialRepeat, Transmembrane, Transportcarrier; oxoglutaratecarrier), member 11NM_003565ULK1unc-51-like kinase 1Hypothetical protein, ATP-binding,25026470(C. elegans)Transferase, Serine/threonine-protein kinaseNM_003570CMAHMRNA for CMP-N-25036471acetylneuraminicacid hydroxylase,complete cds.NM_003577UTF1undifferentiated25046472embryonic celltranscription factor 1NM_003579RAD54LRAD54-like (S. cerevisiae)ATP-binding, DNA repair, Helicase,25056473HydrolaseNM_003587DDX16DEAH (Asp-Glu-Ala-ATP-binding, Helicase, Hydrolase,25066474His) box polypeptidemRNA processing, mRNA splicing,16Nuclear proteinNM_00359SUPT3Hsuppressor of Ty 3Transcription regulation, Activator,25076475homolog (S. cerevisiae)Nuclear protein, Alternative splicingNM_003601SMARCA5SWI/SNF related,ATP-binding, DNA-binding, Helicase,25086476matrix associated,Hydrolase, Nuclear proteinactin dependentregulator ofchromatin, subfamilya, member 5NM_003618MAP4K3mitogen-activatedATP-binding, Kinase, Transferase25096477protein kinasekinase kinase kinase 3NM_003624RANBP3RAN binding protein 3Hypothetical protein25106478NM_003634NIPSNAP1nipsnap homolog 1Polymorphism25116479(C. elegans)NM_003635NDST2N-deacetylase/N-Hypothetical protein, Transferase,25126480sulfotransferaseTransmembrane, Glycoprotein, Golgi(heparanstack, Signal-anchorglucosaminyl) 2NM_003636KCNAB2potassium voltage-Ionic channel, Ion transport,25136481gated channel,Potassium transport, Voltage-gatedshaker-relatedchannel, Alternative splicingsubfamily, betamember 2NM_003639IKBKGinhibitor of kappaCoiled coil, Transcription regulation,25146482light polypeptideNuclear protein, Disease mutation,gene enhancer in B-Anhidrotic ectodermal dysplasia,cells, kinase gammaRepeat, LIM domain, Metal-binding,Zinc, Developmental protein,Differentiation, Zinc-fingerNM_003644GAS7growth arrest-Neurogenesis, Developmental25156483specific 7protein, Coiled coil, Proto-oncogene,Chromosomal translocation,Alternative splicingNM_003648DGKDdiacylglycerolTransferase, Kinase, Phorbol-ester25166484kinase, delta 130 kDabinding, Repeat, Multigene familyNM_003650CST7cystatin FThiol protease inhibitor,25176485(leukocystatin)Glycoprotein, SignalNM_003655CBX4chromobox homologChromatin regulator, Nuclear251864864 (Pc class homolog,protein, Transcription regulation,Drosophila)Repressor, Alternative splicingNM_003668MAPKAPK5mitogen-activatedHypothetical protein, ATP-binding,25196487protein kinase-Kinase, Serine/threonine-proteinactivated proteinkinase, Transferasekinase 5NM_003674CDK10cyclin-dependentTransferase, Serine/threonine-25206488kinase (CDC2-like)protein kinase, ATP-binding, Kinase,10CyclinNM_003680YARStyrosyl-tRNAAminoacyl-tRNA synthetase, Protein25216489synthetasebiosynthesis, Ligase, ATP-binding,RNA-binding, tRNA-binding, 3D-structureNM_003681PDXKpyridoxalTransferase, Kinase, Alternative25226490(pyridoxine, vitaminsplicingB6) kinaseNM_003682MADDMAP-kinaseHypothetical protein, Kinase25236491activating deathdomainNM_003685KHSRPKH-type splicingTransport, mRNA transport, mRNA25246492regulatory proteinprocessing, mRNA splicing,(FUSE bindingTranscription regulation, Trans-protein 2)acting factor, Nuclear protein, DNA-binding, RNA-binding, RepeatNM_003686EXO1exonuclease 1Exonuclease, Hypothetical protein25256493NM_003690PRKRAprotein kinase,Hypothetical protein, Kinase25266494interferon-inducibledouble strandedRNA dependentactivatorNM_003707RUVBL1RuvB-like 1 (E. coli)Transcription, DNA recombination,25276495ATP-binding, Hydrolase, Helicase,Nuclear proteinNM_003709KLF7Kruppel-like factor 7Transcription regulation, Activator,25286496(ubiquitous)Zinc-finger, Metal-binding, DNA-binding, Nuclear protein, RepeatNM_003713PPAP2Bphosphatidic acidCollagen, Hydrolase, Hypothetical25296497phosphatase typeprotein2BNM_003725RODH3-hydroxysteroidOxidoreductase25306498epimeraseNM_003726SCAP1src family associatedSH3 domain25316499phosphoprotein 1NM_003730RNASE6PLribonuclease T2Hydrolase, Nuclease, Endonuclease,25326500Glycoprotein, Signal, Alternativesplicing, Polymorphism, HypotheticalproteinNM_003734AOC3amine oxidase,Oxidoreductase, Copper, TPQ,25336501copper containing 3Glycoprotein, Transmembrane,(vascular adhesionSignal-anchor, Cell adhesion,protein 1)Polymorphism, Metal-bindingNM_003748ALDH4A1aldehydeOxidoreductase, NAD, Proline25346502dehydrogenase 4metabolism, Mitochondrion, Transitfamily, member A1peptide, Polymorphism, DiseasemutationNM_003750EIF3S10eukaryoticInitiation factor, Protein biosynthesis,25356503translation initiationRepeat, Phosphorylationfactor 3, subunit 10theta, 150/170 kDaNM_003754EIF3S5eukaryoticInitiation factor, Protein biosynthesis,25366504translation initiationPolymorphism, Hypothetical proteinfactor 3, subunit 5epsilon, 47 kDaNM_003755EIF3S4eukaryoticInitiation factor, Protein biosynthesis,25376505translation initiationRNA-bindingfactor 3, subunit 4delta, 44 kDaNM_003756EIF3S3eukaryoticInitiation factor, Protein biosynthesis25386506translation initiationfactor 3, subunit 3gamma, 40 kDaNM_003758EIF3S1eukaryoticHypothetical protein, Initiation factor,25396507translation initiationProtein biosynthesisfactor 3, subunit 1alpha, 35 kDaNM_003764STX11syntaxin 11Coiled coil, Membrane,25406508PolymorphismNM_003765STX10syntaxin 10Coiled coil, Transmembrane,25416509Transport, Protein transport, Golgistack, Alternative splicingNM_003769SFRS9splicing factor,Nuclear protein, RNA-binding,25426510arginine/serine-rich 9mRNA splicing, Repeat,PhosphorylationNM_003776MRPL40mitochondrialRibosomal protein, Mitochondrion,25436511ribosomal proteinTransit peptide, PolymorphismL40NM_003782B3GALT4UDP-Transferase, Glycosyltransferase,25446512Gal: betaGlcNAcGlycoprotein, Transmembrane,beta 1,3-Signal-anchor, Golgi stackgalactosyltransferase,polypeptide 4NM_003786ABCC3ATP-bindingATP-binding, Glycoprotein,25456513cassette, sub-familyTransmembrane, Transport, Repeat,C (CFTR/MRP),Alternative splicingmember 3NM_003791MBTPS1membrane-boundHydrolase, Protease, Serine25466514transcription factorprotease, Lipid metabolism,protease, site 1Cholesterol metabolism, Signal,Transmembrane, Endoplasmicreticulum, Golgi stack, Zymogen,Autocatalytic cleavage, Glycoprotein,CalciumNM_003796C19orf2chromosome 19Nuclear protein25476515open reading frame 2NM_003801GPAA1GPAA1P anchorHypothetical protein25486516attachment protein 1homolog (yeast)NM_003805CRADDCASP2 and RIPK1Apoptosis, 3D-structure25496517domain containingadaptor with deathdomainNM_003807TNFSF14tumor necrosis factorCytokine, Transmembrane,25506518(ligand) superfamily,Glycoprotein, Signal-anchor,member 14Alternative splicingNM_003808TNFSF13tumor necrosis factorCytokine, Immune response,25516519(ligand) superfamily,Glycoprotein, Alternative splicingmember 13NM_003815ADAM15a disintegrin andHydrolase, Metalloprotease, Zinc,25526520metalloproteinaseSignal, Glycoprotein, Zymogen,domain 15Transmembrane, EGF-like domain,(metargidin)SH3-binding, PhosphorylationNM_003820TNFRSF14tumor necrosis factorReceptor, Transmembrane,25536521receptor superfamily,Glycoprotein, Repeat, Signal,member 14Polymorphism, 3D-structure(herpesvirus entrymediator)NM_003829MPDZmultiple PDZ domainHypothetical protein25546522proteinNM_003830SIGLEC5sialic acid binding Ig-Cell adhesion, Lectin,25556523like lectin 5Transmembrane, Signal,Glycoprotein, Immunoglobulindomain, Repeat, Antigen,PolymorphismNM_003841TNFRSF10Ctumor necrosis factorReceptor, Apoptosis, Glycoprotein,25566524receptor superfamily,Repeat, GPI-anchor, Signal,member 10c, decoyLipoproteinwithout anintracellular domainNM_003846PEX11Bperoxisomal25576525biogenesis factor11BNM_003852TIF1transcriptionalElongation factor, Protein25586526intermediary factor 1biosynthesis, GTP-binding,Methylation, Multigene family,Transcription regulation, Repressor,DNA-binding, Bromodomain, Zinc-finger, Alternative splicing, Nuclearprotein, Coiled coil, RepeatNM_003853IL18RAPinterleukin 18Receptor25596527receptor accessoryproteinNM_003866INPP4BinositolHypothetical protein25606528polyphosphate-4-phosphatase, type II,105 kDaNM_003877SOCS2suppressor ofSH2 domain, Growth regulation,25616529cytokine signaling 2Signal transduction inhibitorNM_003887DDEF2development andHypothetical protein, ANK repeat,25626530differentiationRepeat, SH3 domainenhancing factor 2NM_003893LDB1LIM domain binding 1DNA-binding, Homeobox, Nuclear25636531proteinNM_003895SYNJ1synaptojanin 1Hydrolase, Alternative splicing,25646532Repeat, Endocytosis, RNA-binding,Multigene family, HypotheticalproteinNM_003896SIAT9sialyltransferase 9Transferase, Glycosyltransferase,25656533(CMP-Glycoprotein, Transmembrane,NeuAc: lactosylceramideSignal-anchor, Golgi stackalpha-2,3-sialyltransferase;GM3 synthase)NM_003897IER3immediate earlyGlycoprotein, Transmembrane,25666534response 3Signal-anchorNM_003899ARHGEF7Rho guanineHypothetical protein, SH3 domain,25676535nucleotide exchangeGuanine-nucleotide releasing factor,factor (GEF) 7Alternative splicing, 3D-structureNM_003900SQSTM1sequestosome 1Hypothetical protein25686536NM_003903CDC16CDC16 cell divisionUbl conjugation pathway, Cell cycle,25696537cycle 16 homolog (S. cerevisiae)Cell division, Mitosis, Repeat, TPRrepeat, Alternative splicingNM_003904ZNF259zinc finger proteinNuclear protein, Zinc-finger25706538259NM_003905APPBP1amyloid betaHypothetical protein25716539precursor proteinbinding protein 1,59 kDaNM_003909CPNE3copine IIIRepeat, Phosphorylation,25726540Transferase, Serine/threonine-protein kinaseNM_003915CPNE1copine IRepeat25736541NM_003923FOXH1forkhead box H1Transcription regulation, Activator,25746542DNA-binding, Nuclear protein,PolymorphismNM_003931WASF1WAS protein family,Actin-binding25756543member 1NM_003938AP3D1adaptor-relatedGolgi stack, Protein transport,25766544protein complex 3,Transport, Alternative splicing,delta 1 subunitPolymorphismNM_003940USP13ubiquitin specificUbl conjugation pathway, Hydrolase,25776545protease 13Thiol protease, Multigene family,(isopeptidase T-3)Repeat, Hypothetical proteinNM_003943GENX-genethonin 1257865463414NM_003945ATP6V0EATPase, H+Hydrolase, Hydrogen ion transport,25796547transporting,Transmembranelysosomal 9 kDa, V0subunit eNM_003951SLC25A14solute carrier familyMitochondrion, Repeat,2580654825 (mitochondrialTransmembrane, Transport,carrier, brain),Alternative splicingmember 14NM_003953MPZL1myelin protein zero-Hypothetical protein25816549like 1NM_003954MAP3K14mitogen-activatedHypothetical protein, Transferase,25826550protein kinaseSerine/threonine-protein kinase,kinase kinase 14ATP-binding, PhosphorylationNM_003967PNRputativeG-protein coupled receptor,25836551neurotransmitterReceptor, TransmembranereceptorNM_003975SH2D2ASH2 domain proteinAngiogenesis, Phosphorylation, SH2258465522Adomain, SH3-binding, AlternativesplicingNM_003977AIParyl hydrocarbonRepeat, TPR repeat25856553receptor interactingproteinNM_003978PSTPIP1proline-serine-SH3 domain25866554threoninephosphataseinteracting protein 1NM_003983SLC7A6solute carrier familyHypothetical protein258765557 (cationic aminoacid transporter, y+system), member 6NM_004031IRF7interferon regulatoryTranscription regulation, DNA-25886556factor 7binding, Nuclear protein, Activator,Alternative splicing, CollagenNM_004033ANXA6annexin A6Annexin, Calcium/phospholipid-25896557binding, Repeat, Acetylation,Phosphorylation, 3D-structureNM_004037AMPD2adenosineHydrolase, Nucleotide metabolism,25906558monophosphateMultigene family, Alternative splicingdeaminase 2(isoform L)NM_004039ANXA2annexin A2Annexin, Calcium, Calcium-binding,25916559Calcium/phospholipid-binding,Repeat, Phosphorylation,Acetylation, PolymorphismNM_004044ATIC5-aminoimidazole-4-Purine biosynthesis, Transferase,25926560carboxamideHydrolase, Multifunctional enzymeribonucleotideformyltransferase/IMPcyclohydrolaseNM_004046ATP5A1ATP synthase, H+ATP synthesis, ATP-binding, CF(1),25936561transporting,Hydrogen ion transport, Hydrolase,mitochondrial F1Ion transport, Transport,complex, alphaMitochondrion, Transit peptide,subunit, isoform 1,Pyrrolidone carboxylic acid,cardiac muscleHypothetical proteinNM_004047ATP6V0BATPase, H+Hydrolase, Hydrogen ion transport,25946562transporting,ATP synthesis, Transmembranelysosomal 21 kDa,V0 subunit c″NM_004049BCL2A1BCL2-related proteinApoptosis25956563A1NM_004053BYSLbystin-likeCell adhesion25966564NM_004054C3AR1complementG-protein coupled receptor,25976565component 3aTransmembrane, Glycoprotein,receptor 1ChemotaxisNM_004060CCNG1cyclin G1Cyclin, Cell cycle, Cell division,25986566Mitosis, Nuclear proteinNM_004070CLCNKAchloride channel KaIonic channel, Ion transport, Chloride25996567channel, Chloride, Voltage-gatedchannel, Transmembrane, CBSdomain, RepeatNM_004073CNKcytokine-inducibleTransferase, Serine/threonine-26006568kinaseprotein kinase, ATP-binding, Repeat,Phosphorylation, Hypotheticalprotein, KinaseNM_004079CTSScathepsin SHydrolase, Thiol protease,26016569Lysosome, Zymogen, Signal, 3D-structureNM_004084DEFA1defensin, alpha 1,Defensin, Antibiotic, Antiviral,26026570myeloid-relatedFungicide, Signal, 3D-structuresequenceNM_004090DUSP3dual specificityHydrolase, 3D-structure,26036571phosphatase 3Hypothetical protein(vaccinia virusphosphatase VH1-related)NM_004092ECHS1enoyl Coenzyme AFatty acid metabolism, Lyase,26046572hydratase, shortMitochondrion, Transit peptidechain, 1,mitochondrialNM_004094EIF2S1eukaryoticInitiation factor, Protein biosynthesis,26056573translation initiationTranslation regulation, RNA-binding,factor 2, subunit 1Phosphorylation, 3D-structurealpha, 35 kDaNM_004099STOMstomatinErythrocyte, Transmembrane,26066574Phosphorylation, Lipoprotein,Palmitate, Hypothetical protein,Transducer, Prenylation, MultigenefamilyNM_004105EFEMP1EGF-containingRepeat, EGF-like domain, Calcium-26076575fibulin-likebinding, Glycoprotein, Signal,extracellular matrixDisease mutation, Polymorphism,protein 1Alternative splicingNM_004106FCER1GFc fragment of IgE,IgE-binding protein, Receptor,26086576high affinity I,Transmembrane, Signalreceptor for; gammapolypeptideNM_004107FCGRTFc fragment of IgG,IgG-binding protein, Receptor,26096577receptor, transporter,Transmembrane, Glycoprotein,alphaSignal, Immunoglobulin domain, 3D-structureNM_004108FCN2ficolinLectin, Collagen, Repeat,26106578(collagen/fibrinogenGlycoprotein, Signal, Multigenedomain containingfamilylectin) 2 (hucolin)NM_004109FDX1ferredoxin 1Metal-binding, Iron-sulfur, Iron, 2Fe—2S,26116579Electron transport,Mitochondrion, Transit peptideNM_004115FGF14fibroblast growthGrowth factor26126580factor 14NM_004119FLT3fms-related tyrosineSignal, Transferase, Tyrosine-26136581kinase 3protein kinase, Receptor,Transmembrane, Glycoprotein,Phosphorylation, ATP-binding,Immunoglobulin domainNM_004122GHSRgrowth hormoneG-protein coupled receptor,26146582secretagogueTransmembrane, Glycoprotein,receptorAlternative splicingNM_004126GNG11guanine nucleotideTransducer, Prenylation, Lipoprotein,26156583binding protein (GMultigene familyprotein), gamma 11NM_004128GTF2F2general transcriptionTranscription regulation, DNA-26166584factor IIF,binding, Helicase, ATP-binding,polypeptide 2,Nuclear protein, 3D-structure30 kDaNM_004130GYGglycogeninTransferase, Glycogen biosynthesis,26176585Acetylation, Phosphorylation,Glycoprotein, Alternative splicing,Hypothetical proteinNM_004131GZMBgranzyme BHydrolase, Serine protease,26186586(granzyme 2,Zymogen, Signal, T-cell, Cytolysis,cytotoxic T-Apoptosis, Glycoprotein, 3D-lymphocyte-structure, Proteaseassociated serineesterase 1)NM_004134HSPA9Bheat shock 70 kDaATP-binding, Heat shock,26196587protein 9B (mortalin-Chaperone, Mitochondrion, Transit2)peptideNM_004147DRG1developmentallyGTP-binding, Hypothetical protein26206588regulated GTPbinding protein 1NM_004148NINJ1ninjurin 1Cell adhesion, Transmembrane,26216589Hypothetical proteinNM_004152OAZ1ornithine26226590decarboxylaseantizyme 1NM_004168SDHAsuccinateTricarboxylic acid cycle,26236591dehydrogenaseFlavoprotein, FAD, Oxidoreductase,complex, subunit A,Electron transport, Mitochondrion,flavoprotein (Fp)Transit peptide, Disease mutation,Leigh syndromeNM_004177STX3Asyntaxin 3ANeurotransmitter transport, Coiled26246592coil, Transmembrane, AlternativesplicingNM_004178TARBP2TAR (HIV) RNAHypothetical protein, RNA-binding,26256593binding protein 2Repeat, Nuclear proteinNM_004180TANKTRAF familyZinc-finger, Metal-binding,26266594member-associatedAlternative splicing, 3D-structureNFKB activatorNM_004183VMD2vitelliform macularTransport, Ion transport, Ionic26276595dystrophy (Bestchannel, Chloride channel, Chloride,disease, bestrophin)Calcium, Alternative splicing,Disease mutation, Polymorphism,Vision, Transmembrane,Phosphorylation, Iron storage, Metal-binding, 3D-structureNM_004207SLC16A3solute carrier familyTransport, Symport,2628659616 (monocarboxylicTransmembrane, Multigene familyacid transporters),member 3NM_004221NK4natural killer cellSignal26296597transcript 4NM_004225MFHAS1malignant fibrousGTP-binding26306598histiocytomaamplified sequence 1NM_004235KLF4Kruppel-like factor 4Transcription regulation, Activator,26316599(gut)Zinc-finger, Metal-binding, DNA-binding, Nuclear protein, RepeatNM_004239TRIP11thyroid hormoneHypothetical protein, Antigen, Golgi26326600receptor interactorstack, Coiled coil, Chromosomal11translocationNM_004244CD163CD163 antigenSignal, Antigen26336601NM_004245TGM5transglutaminase 5Transferase, Acyltransferase,26346602Calcium-binding, Polymorphism,Alternative splicingNM_004252SLC9A3R1solute carrier family263566039 (sodium/hydrogenexchanger), isoform3 regulatory factor 1NM_004255COX5Acytochrome cOxidoreductase, Heme,26366604oxidase subunit VaMitochondrion, Inner membrane,Transit peptideNM_004258IGSF2immunoglobulin26376605superfamily, member 2NM_004263SEMA4Fsema domain,Signal, Transmembrane,26386606immunoglobulinImmunoglobulin domain, Multigenedomain (Ig),family, Neurogenesis,transmembraneDevelopmental protein,domain (TM) andGlycoprotein, Alternative splicingshort cytoplasmicdomain,(semaphorin) 4FNM_004265FADS2fatty acid desaturase 2Hypothetical protein, Heme26396607NM_004272HOMER1homer homolog 1Coiled coil, Alternative splicing26406608(Drosophila)NM_004279PMPCBpeptidaseChaperone, Nuclear protein,26416609(mitochondrialPhosphorylation, Hydrolase,processing) betaMetalloprotease, Zinc,Mitochondrion, Transit peptide,Hypothetical proteinNM_004295TRAF4TNF receptor-Apoptosis, Developmental protein,26426610associated factor 4Nuclear protein, Zinc-finger, Coiledcoil, Repeat, Alternative splicingNM_004300ACP1acid phosphatase 1,Hydrolase, Acetylation, Alternative26436611solublesplicing, Polymorphism, 3D-structureNM_004305BIN1bridging integrator 1Alternative splicing, SH3 domain,26446612Coiled coil, Endocytosis, Anti-oncogene, Differentiation,Phosphorylation, HypotheticalproteinNM_004309ARHGDIARho GDPGTPase activation, 3D-structure26456613dissociation inhibitor(GDI) alphaNM_004313ARRB2arrestin, beta 2Sensory transduction, Nuclear26466614protein, Alternative splicingNM_004331BNIP3LBCL2/adenovirusApoptosis, Transmembrane,26476615E1B 19 kDaMitochondrioninteracting protein 3-likeNM_004334BST1bone marrowHydrolase, NAD, Glycoprotein, GPI-26486616stromal cell antigen 1anchor, Signal, 3D-structure,Lipoprotein, Hypothetical proteinNM_004336BUB1BUB1 buddingTransferase, Serine/threonine-26496617uninhibited byprotein kinase, ATP-binding, Cellbenzimidazoles 1cycle, Nuclear protein, Mitosis,homolog (yeast)Phosphorylation, PolymorphismNM_004337C8orf1chromosome 8 openMeiosis26506618reading frame 1NM_004345CAMPcathelicidinAntibiotic, Signal, Pyrrolidone26516619antimicrobial peptidecarboxylic acidNM_004350RUNX3runt-relatedTranscription regulation, DNA-26526620transcription factor 3binding, Nuclear protein, ATP-binding, Alternative splicingNM_004358CDC25Bcell division cycleCell division, Mitosis, Hydrolase,2653662125BAlternative splicing, Multigene family,3D-structureNM_004360CDH1cadherin 1, type 1,Elongation factor, Protein26546622E-cadherinbiosynthesis, GTP-binding,(epithelial)Methylation, Multigene family,Ribosomal protein, Repeat,Hypothetical protein, Cell adhesion,Glycoprotein, Transmembrane,Calcium-binding, Signal,Phosphorylation, Disease mutation,Polymorphism, 3D-structureNM_004368CNN2calponin 2Calmodulin-binding, Actin-binding,26556623Multigene family, RepeatNM_004374COX6Ccytochrome cOxidoreductase, Inner membrane,26566624oxidase subunit VIcMitochondrionNM_004375COX11COX11 homolog,Copper, Mitochondrion,26576625cytochrome cTransmembrane, Transit peptide,oxidase assemblyTransport, Protein transport, SH3-protein (yeast)binding, Membrane, Golgi stack,Phosphorylation, HypotheticalproteinNM_004380CREBBPCREB bindingTransferase, Transcription26586626protein (Rubinstein-regulation, Nuclear protein,Taybi syndrome)Activator, Bromodomain,Chromosomal translocation, Zinc-finger, Repeat, Disease mutation,3D-structureNM_004381CREBL1cAMP responsiveGlycoprotein, Cell adhesion, Repeat,26596627element bindingEGF-like domain, Coiled coil,protein-like 1Extracellular matrix, Alternativesplicing, Signal, Ehlers-Danlossyndrome, Transcription regulation,DNA-binding, Activator, Unfoldedprotein response, Nuclear protein,Endoplasmic reticuNM_004385CSPG2chondroitin sulfateGlycoprotein, Proteoglycan, Lectin,26606628proteoglycan 2Extracellular matrix, Sushi, Signal,(versican)Repeat, EGF-like domain, Calcium,Immunoglobulin domain, Hyaluronicacid, Alternative splicingNM_004390CTSHcathepsin HHydrolase, Protease, Thiol protease,26616629Lysosome, Glycoprotein, Zymogen,Signal, 3D-structureNM_004398DDX10DEAD (Asp-Glu-Ala-Helicase, ATP-binding, RNA-binding26626630Asp) box polypeptide10NM_004409DMPKdystrophiaTransferase, Serine/threonine-26636631myotonica-proteinprotein kinase, ATP-binding, Coiledkinasecoil, Alternative splicingNM_004417DUSP1dual specificityHydrolase, Cell cycle26646632phosphatase 1NM_004418DUSP2dual specificityHydrolase, Nuclear protein, 3D-26656633phosphatase 2structureNM_004424E4F1E4F transcriptionMetal-binding, Zinc, Zinc-finger26666634factor 1NM_004427PHC2polyhomeotic-like 2Hypothetical protein26676635(Drosophila)NM_004446EPRSglutamyl-prolyl-tRNAAminoacyl-tRNA synthetase, Protein26686636synthetasebiosynthesis, Ligase, ATP-binding,Multifunctional enzyme, Repeat, 3D-structureNM_004450ERHenhancer of26696637rudimentaryhomolog(Drosophila)NM_004453ETFDHelectron-transferring-Oxidoreductase, Electron transport,26706638flavoproteinFlavoprotein, FAD, Iron-sulfur, 4Fe—4S,dehydrogenaseMitochondrion, Transit peptide,Ubiquinone, Transmembrane,GlutaricaciduriaNM_004475FLOT2flotillin 2Cell adhesion, Membrane26716639NM_004477FRG1FSHD region gene 1Multigene family26726640NM_004479FUT7fucosyltransferase 7Transferase, Glycosyltransferase,26736641(alpha (1, 3)Transmembrane, Glycoprotein,fucosyltransferase)Signal-anchor, Golgi stackNM_004480FUT8fucosyltransferase 8Transferase, Glycosyltransferase,26746642(alpha (1, 6)Transmembrane, Signal-anchor,fucosyltransferase)Golgi stack, SH3 domain, SH3-binding, Alternative splicingNM_004482GALNT3UDP-N-acetyl-alpha-Transferase26756643D-galactosamine:polypeptideN-acetylgalactosaminyltransferase 3(GalNAc-T3)NM_004483GCSHglycine cleavageMitochondrion, Transit peptide,26766644system protein HLipoyl(aminomethylcarrier)NM_004485GNG4guanine nucleotideTransducer, Prenylation, Lipoprotein,26776645binding protein (GMultigene familyprotein), gamma 4NM_004489GPS2G protein pathwayHypothetical protein26786646suppressor 2NM_004492GTF2A2general transcriptionTranscription regulation, Nuclear26796647factor IIA, 2, 12 kDaproteinNM_004497FOXA3forkhead box A3DNA-binding, Nuclear protein,26806648Transcription regulation, Activator,PolymorphismNM_004504HRBHIV-1 Rev bindingNuclear protein, Transport, Repeat,26816649proteinDNA-binding, Zinc-fingerNM_004506HSF2heat shockHeat shock, Transcription regulation,26826650transcription factor 2Nuclear protein, DNA-binding,Activator, Phosphorylation,Multigene familyNM_004513IL16interleukin 16Cytokine, Chemotaxis, Repeat, 3D-26836651(lymphocytestructurechemoattractantfactor)NM_004515ILF2interleukin enhancer26846652binding factor 2,45 kDaNM_004516ILF3interleukin enhancerHypothetical protein, Transcription26856653binding factor 3,regulation, DNA-binding, RNA-90 kDabinding, Nuclear protein, Repeat,Phosphorylation, Methylation,Alternative splicingNM_004524LLGL2lethal giant larvaeRepeat, WD repeat26866654homolog 2(Drosophila)NM_004529MLLT3myeloid/lymphoid orTranscription regulation, Activator,26876655mixed-lineageNuclear protein, Chromosomalleukemia (trithoraxtranslocation, Proto-oncogenehomolog,Drosophila);translocated to, 3NM_004537NAP1L1nucleosomeNuclear protein26886656assembly protein 1-like 1NM_004554NFATC4nuclear factor ofHypothetical protein, Transcription26896657activated T-cells,regulation, Activator, Nuclearcytoplasmic,protein, DNA-binding, Repeat,calcineurin-Phosphorylationdependent 4NM_004563PCK2phosphoenolpyruvateGluconeogenesis, Lyase,26906658carboxykinase 2Decarboxylase, GTP-binding,(mitochondrial)Mitochondrion, Transit peptide,ManganeseNM_004566PFKFB36-phosphofructo-2-Kinase, Hydrolase, Multifunctional26916659kinase/fructose-2,6-enzyme, Transferase, ATP-binding,biphosphatase 3Phosphorylation, Multigene family,Alternative splicingNM_004569PIGHphosphatidylinositolHypothetical protein, Transferase,26926660glycan, class HGlycosyltransferaseNM_004573PLCB2phospholipase C,Hydrolase, Lipid degradation,26936661beta 2Transducer, CalciumNM_004578RAB4ARAB4A, memberGTP-binding, Lipoprotein,26946662RAS oncogenePrenylation, Protein transport,familyPhosphorylationNM_004580RAB27ARAB27A, memberGTP-binding, Lipoprotein,26956663RAS oncogenePrenylation, Alternative splicing,familyDisease mutationNM_004583RAB5CRAB5C, memberGTP-binding, Lipoprotein,26966664RAS oncogenePrenylation, Protein transportfamilyNM_004603STX1Asyntaxin 1A (brain)Neurotransmitter transport, Coiled26976665coil, Transmembrane, Antigen,Alternative splicing, Williams-BeurensyndromeNM_004618TOP3AtopoisomeraseIsomerase, Topoisomerase, DNA-26986666(DNA) III alphabinding, Repeat, Zinc-finger,Alternative splicing, PolymorphismNM_004629FANCGFanconi anemia,DNA repair, Nuclear protein26996667complementationgroup GNM_004632DAP3death associatedApoptosis, Ribosomal protein,27006668protein 3MitochondrionNM_004633IL1R2interleukin 1Immunoglobulin domain, Receptor,27016669receptor, type IIGlycoprotein, Transmembrane,Signal, RepeatNM_004635MAPKAPK3mitogen-activatedATP-binding, Kinase,27026670protein kinase-Serine/threonine-protein kinase,activated proteinTransferasekinase 3NM_004637RAB7RAB7, member RASGTP-binding, Lipoprotein,27036671oncogene familyPrenylation, Protein transport,Hypothetical proteinNM_004642CDK2AP1CDK2-associatedAnti-oncogene27046672protein 1NM_004648PTPNS1protein tyrosineRepeat, Signal, Transmembrane,27056673phosphatase, non-Immunoglobulin domain, SH3-receptor typebinding, Glycoprotein,substrate 1Phosphorylation, Alternative splicing,PolymorphismNM_004651USP11ubiquitin specificUbl conjugation pathway, Hydrolase,27066674protease 11Thiol protease, Nuclear protein,Multigene familyNM_004664LIN7Alin-7 homolog A (C. elegans)27076675NM_004665VNN2vanin 2Hydrolase, Signal, Glycoprotein,27086676GPI-anchor, LipoproteinNM_004666VNN1vanin 1Hydrolase, Signal, Glycoprotein,27096677GPI-anchor, LipoproteinNM_004668MGAMmaltase-Multifunctional enzyme,27106678glucoamylaseTransmembrane, Glycoprotein,(alpha-glucosidase)Hydrolase, Glycosidase, Repeat,Signal-anchor, SulfationNM_004682PSIP2PC4 and SFRS127116679interacting protein 1NM_004689MTA1metastasisZinc-finger, Nuclear protein,27126680associated 1Alternative splicingNM_004694SLC16A6solute carrier familyTransport, Symport,2713668116 (monocarboxylicTransmembrane, Multigene familyacid transporters),member 6NM_004706ARHGEF1Rho guanineGuanine-nucleotide releasing factor,27146682nucleotide exchangeGTPase activation, Coiled coil,factor (GEF) 1Alternative splicing, Phosphorylation,3D-structureNM_004708PDCD5programmed cellApoptosis27156683death 5NM_004712HGShepatocyte growthKinase27166684factor-regulatedtyrosine kinasesubstrateNM_004720EDG4endothelialG-protein coupled receptor,27176685differentiation,Transmembrane, Glycoprotein,lysophosphatidicMultigene family, Lipoprotein,acid G-protein-Palmitatecoupled receptor, 4NM_004726REPS2RALBP1 associatedCalcium-binding, Coiled coil,27186686Eps domainPhosphorylation, Alternative splicing,containing 2Repeat, 3D-structureNM_004727SLC24A1solute carrier familyVision, Transport, Antiport, Symport,2719668724Calcium transport, Transmembrane,(sodium/potassium/calciumGlycoprotein, Phosphorylation,exchanger),Signal, Repeat, Alternative splicingmember 1NM_004729ALTEAc-like transposable27206688elementNM_004741NOLC1nucleolar and coiled-Nuclear protein, Phosphorylation,27216689body phosphoprotein 1Repeat, GTP-binding, ATP-binding,Alternative splicingNM_004748CPR8cell cycleHypothetical protein27226690progression 8proteinNM_004749CPR2cell cycleHypothetical protein27236691progression 2proteinNM_004756NUMBLnumb homolog27246692(Drosophila)-likeNM_004757SCYE1small inducibleProtein biosynthesis, RNA-binding,27256693cytokine subfamilytRNA-binding, Cytokine, 3D-E, member 1structure(endothelialmonocyte-activating)NM_004762PSCD1pleckstrin homology,Guanine-nucleotide releasing factor,27266694Sec7 and coiled-coilCoiled coil, Alternative splicing, 3D-domains 1 (cytohesin 1)structureNM_004774PPARBPPPAR bindingDNA-binding, Transcription27276695proteinregulation, Activator, Repeat,Nuclear protein, Alternative splicingNM_004779CNOT8CCR4-NOTCoiled coil, Nuclear protein,27286696transcriptionAlternative splicing, Hypotheticalcomplex, subunit 8protein, Molybdenum cofactorbiosynthesis, Disease mutation,Transcription regulation, RepressorNM_004781VAMP3vesicle-associatedSynapse, Synaptosome,27296697membrane protein 3Transmembrane, Coiled coil,(cellubrevin)Multigene familyNM_004786TXNLthioredoxin-like,Redox-active center, Electron2730669832 kDatransport, 3D-structureNM_004800TM9SF2transmembrane 9Signal, Transmembrane27316699superfamily member 2NM_004802OTOFotoferlinTransmembrane, Repeat, Alternative27326700splicing, DeafnessNM_004808NMT2N-Transferase, Acyltransferase27336701myristoyltransferase 2NM_004814HPRP8BPU5 snRNP-specificRepeat, WD repeat, Hypothetical2734670240 kDa proteinprotein(hPrp8-binding)NM_004817TJP2tight junction proteinTight junction, SH3 domain, Repeat,273567032 (zona occludens 2)Membrane, Alternative splicing,Alternative promoter usage, Nuclearprotein, PhosphorylationNM_004834MAP4K4mitogen-activatedATP-binding, Serine/threonine-27366704protein kinaseprotein kinase, Transferase,kinase kinase kinase 4Alternative splicingNM_004848C1orf38chromosome 1 openHypothetical protein27376705reading frame 38NM_004854CHST10carbohydrateTransferase27386706sulfotransferase 10NM_004856KIF23anaphase-promotingMotor protein, Cell division,27396707complex subunit 7Microtubule, ATP-binding, Coiledcoil, Mitosis, Cell cycle, NuclearproteinNM_004862LITAFlipopolysaccharide-Hypothetical protein, Transcription27406708induced TNF factorregulation, Nuclear proteinNM_004868GPSN2glycoprotein,Transmembrane, Glycoprotein,27416709synaptic 2Alternative splicingNM_004875POLR1Cpolymerase (RNA) IHypothetical protein, Transferase,27426710polypeptide C,DNA-directed RNA polymerase,30 kDaTranscription, Nuclear protein,Alternative splicingNM_004877GMFGglia maturationGrowth factor, Ribosomal protein27436711factor, gammaNM_004878PTGESprostaglandin EHypothetical protein,27446712synthaseTransmembraneNM_004879EI24etoposide induced274567132.4 mRNANM_004889ATP5J2ATP synthase, H+ATP synthesis, Hydrogen ion27466714transporting,transport, CF(0), Mitochondrion,mitochondrial F0Acetylation, Alternative splicingcomplex, subunit f,isoform 2NM_004900APOBEC3Bapolipoprotein BHydrolase27476715mRNA editingenzyme, catalyticpolypeptide-like 3BNM_004900RNPC2RNA-binding regionTranscription regulation, Activator,27486716(RNP1, RRM)Nuclear protein, RNA-binding,containing 2mRNA-processing, mRNA splicing,Repeat, Altemative splicing,PolymorphismNM_004905PRDX6peroxiredoxin 6Hydrolase, Oxidoreductase,27496717Peroxidase, Lipid degradation,Antioxidant, Redox-active center,Multifunctional enzyme, Lysosome,3D-structureNM_004907ETR101immediate earlyATP-binding, Coiled coil,27506718proteinMicrotubules, Motor proteinNM_004910PITPNM1phosphatidylinositolHypothetical protein27516719transfer protein,membrane-associated 1NM_004915ABCG1ATP-bindingATP-binding, Transport, Hypothetical27526720cassette, sub-familyprotein, Lipid transport,G (WHITE), member 1Transmembrane, Alternativesplicing, PolymorphismNM_004916WWOXHumanOxidoreductase27536721oxidoreductase(HHCMA56) mRNA,complete cds.NM_004920AATKapoptosis-Kinase, Hypothetical protein, ATP-27546722associated tyrosinebinding, TransferasekinaseNM_004924ACTN4actinin, alpha 4Actin-binding, Calcium-binding,27556723Repeat, Multigene family, Diseasemutation, Nuclear protein,Hypothetical proteinNM_004928C21orf2chromosome 21Alternative splicing, Polymorphism27566724open reading frame 2NM_004930CAPZBcapping proteinCytoskeleton, Actin-binding,27576725(actin filament)Alternative splicing, Actin cappingmuscle Z-line, betaNM_004939DDX1DEAD (Asp-Glu-Ala-Hydrolase, ATP-binding, Helicase,27586726Asp) box polypeptide 1RNA-bindingNM_004945DNM2dynamin 2Hydrolase, Motor protein, GTP-27596727binding, Microtubule, Multigenefamily, Endocytosis, Alternativesplicing, Hypothetical proteinNM_004954MARK2MAP/microtubuleATP-binding, Kinase,27606728affinity-regulatingSerine/threonine-protein kinase,kinase 2TransferaseNM_004974KCNA2potassium voltage-Transport, Ion transport, Ionic27616729gated channel,channel, Voltage-gated channel,shaker-relatedPotassium channel, Potassiumsubfamily, member 2transport, Potassium,Transmembrane, Glycoprotein,Phosphorylation, Multigene familyNM_004979KCND1potassium voltage-Transport, Ion transport, Ionic27626730gated channel, Shal-channel, Voltage-gated channel,related subfamily,Potassium channel, Potassiummember 1transport, Potassium,Transmembrane, Multigene familyNM_004994MMP9matrixHydrolase, Metalloprotease,27636731metalloproteinase 9Glycoprotein, Zinc, Zymogen,(gelatinase B, 92 kDaCalcium, Collagen degradation,gelatinase, 92 kDaExtracellular matrix, Repeat, Signal,type IV collagenase)Polymorphism, 3D-structureNM_005000NDUFA5NADHHypothetical protein,27646732dehydrogenaseOxidoreductase, NAD, Ubiquinone,(ubiquinone) 1 alphaMitochondrion, Acetylationsubcomplex, 5,13 kDaNM_005003NDUFAB1NADHFatty acid biosynthesis,27656733dehydrogenasePhosphopantetheine, Mitochondrion,(ubiquinone) 1,Transit peptide, Oxidoreductasealpha/betasubcomplex, 1, 8 kDaNM_005009NME4non-metastatic cellsTransferase, Kinase, ATP-binding,276667344, protein expressedMitochondrion, Transit peptide, 3D-instructureNM_005011NRF1nuclear respiratoryTranscription regulation, DNA-27676735factor 1binding, Activator, Nuclear protein,Phosphorylation, Alternative splicingNM_005022PFN1profilin 1Actin-binding, Cytoskeleton,27686736Multigene family, Acetylation, 3D-structureNM_005024SERPINB10serine (or cysteine)Serpin, Serine protease inhibitor27696737proteinase inhibitor,clade B (ovalbumin),member 10NM_005025SERPINI1serine (or cysteine)Serpin, Serine protease inhibitor,27706738proteinase inhibitor,Glycoprotein, Signal, Diseaseclade Imutation(neuroserpin).member 1NM_005026PIK3CDphosphoinositide-3-Kinase, Transferase, Multigene27716739kinase, catalytic,familydelta polypeptideNM_005029PITX3paired-likeHomeobox, DNA-binding,27726740homeodomainDevelopmental protein, Nucleartranscription factor 3protein, Disease mutationNM_005030PLKpolo-like kinaseTransferase, Serine/threonine-27736741(Drosophila)protein kinase, ATP-binding, Repeat,Nuclear protein, PhosphorylationNM_005040PRCPprolylcarboxypeptidaseHydrolase, Carboxypeptidase,27746742(angiotensinaseGlycoprotein, Zymogen, Signal,C)LysosomeNM_005044PRKXprotein kinase, X-ATP-binding, Kinase,27756743linkedSerine/threonine-protein kinase,Transferase, Tyrosine-proteinkinase, cAMPNM_005055RAPSNreceptor-associatedSynapse, Postsynaptic membrane,27766744protein of theCytoskeleton, Phosphorylation,synapse, 43 kDMyristate, Zinc-finger, Repeat, TPRrepeat, Alternative splicing,Lipoprotein, Metal-binding, ReceptorNM_005056RBBP2retinoblastomaTrans-acting factor, Nuclear protein,27776745binding protein 2Repeat, Zinc-fingerNM_005061RPL3Lribosomal proteinRibosomal protein27786746L3-likeNM_005066SFPQsplicing factorNuclear protein, RNA-binding, DNA-27796747proline/glutaminebinding, mRNA splicing, Repeat,rich (polypyrimidineAlternative splicingtract binding proteinassociated)NM_005084PLA2G7phospholipase A2,Hydrolase, Lipid degradation,27806748group VII (platelet-Glycoprotein, Signal, Polymorphism,activating factorDisease mutationacetylhydrolase,plasma)NM_005085NUP214nucleoporin 214 kDaHypothetical protein, Repeat, WD27816749repeat, Nuclear protein, Transport,Proto-oncogene, Chromosomaltranslocation, GlycoproteinNM_005091PGLYRPpeptidoglycanAntibiotic, Immune response, Signal27826750recognition proteinNM_005096ZNF261zinc finger proteinHypothetical protein, Chromosomal27836751261translocation, Transmembrane,Alternative splicingNM_005099ADAMTS4a disintegrin-like andHydrolase, Metalloprotease, Zinc,27846752metalloproteaseSignal, Glycoprotein, Zymogen,(reprolysin type) withExtracellular matrix, Hypotheticalthrombospondin typeprotein1 motif, 4NM_005106DLEC1deleted in lung andHypothetical protein27856753esophageal cancer 1NM_005111CRYZL1crystallin, zetaOxidoreductase, NADP, Alternative27866754(quinone reductase)-splicinglike 1NM_005112WDR1WD repeat domain 1Repeat, WD repeat, Hypothetical27876755protein, Actin-binding, Cytoskeleton,Alternative splicing, PolymorphismNM_005134PPP4R1protein phosphataseHypothetical protein278867564, regulatory subunit 1NM_005137DGCR2DiGeorge syndromeCell adhesion, Receptor, Signal,27896757critical region gene 2Transmembrane, Lectin,GlycoproteinNM_005139ANXA3annexin A3Annexin, Calcium/phospholipid-27906758binding, Repeat, Phospholipase A2inhibitor, 3D-structure,PolymorphismNM_005143HPhaptoglobinGlycoprotein, Serine protease27916759homolog, Sushi, Hemoglobin-binding, Signal, Repeat,PolymorphismNM_005148UNC119unc-119 homolog (C. elegans)Vision, Alternative splicing27926760NM_005151USP14ubiquitin specificUbl conjugation pathway, Hydrolase,27936761protease 14 (tRNA-Thiol protease, Multigene familyguaninetransglycosylase)NM_005165ALDOCaldolase C, fructose-Lyase, Schiff base, Glycolysis,27946762bisphosphateMultigene familyNM_005167ARHChypothetical proteinDNA condensation, Mitosis, Cell27956763MGC19531cycle, ATP-binding, Coiled coil,Nuclear protein, Alternative splicing,Hypothetical protein, Proto-oncogene, GTP-binding, Prenylation,LipoproteinNM_005173ATP2A3ATPase, Ca++Hydrolase, Calcium transport,27966764transporting,Transmembrane, Phosphorylation,ubiquitousATP-binding, Metal-binding,Magnesium, Calcium-binding,Multigene family, Alternative splicingNM_005174ATP5C1ATP synthase, H+ATP synthesis, CF(1), Hydrogen ion27976765transporting,transport, Hydrolase, Mitochondrion,mitochondrial F1Transit peptide, Alternative splicing,complex, gammaHypothetical proteinpolypeptide 1NM_005180BMI1B lymphoma Mo-Chromatin regulator, Nuclear27986766MLV insertion regionprotein, Transcription regulation,(mouse)Repressor, Zinc-finger, Proto-oncogeneNM_005185CALML3calmodulin-like 3Calcium-binding, Repeat,27996767Methylation, 3D-structureNM_005190CCNCcyclin CCyclin, Cell cycle, Cell division,28006768Nuclear protein, TranscriptionregulationNM_005195CEBPDKIAA0146 proteinTranscription regulation, Activator,28016769DNA-binding, Nuclear proteinNM_005197CHES1checkpointTranscription regulation, Activator,28026770suppressor 1DNA-binding, Nuclear protein,Alternative splicingNM_005199CHRNGcholinergic receptor,Receptor, Postsynaptic membrane,28036771nicotinic, gammaIonic channel, Glycoprotein, Signal,polypeptideTransmembraneNM_005213CSTAcystatin A (stefin A)Thiol protease inhibitor, 3D-structure28046772NM_005217DEFA3defensin, alpha 3,Defensin, Antibiotic, Antiviral,28056773neutrophil-specificFungicide, Signal, 3D-structureNM_005224DRIL1dead ringer-like 1Transcription regulation, Activator,28066774(Drosophila)DNA-binding, Nuclear proteinNM_005231EMS1ems1 sequencePhosphorylation, Repeat, SH328076775(mammary tumordomain, Cytoskeletonand squamous cellcarcinoma-associated (p80/85src substrate)NM_005239ETS2v-etsProto-oncogene, DNA-binding,28086776erythroblastosisNuclear proteinvirus E26 oncogenehomolog 2 (avian)NM_005248FGRGardner-RasheedTransferase, Tyrosine-protein28096777feline sarcoma viralkinase, Proto-oncogene, ATP-(v-fgr) oncogenebinding, Phosphorylation, SH2homologdomain, SH3 domainNM_005252FOSv-fos FBJ murineProto-oncogene, Nuclear protein,28106778osteosarcoma viralPhosphorylation, DNA-binding, 3D-oncogene homologstructureNM_005253FOSL2FOS-like antigen 2Nuclear protein, DNA-binding28116779NM_005255GAKcyclin G associatedTransferase, Serine/threonine-28126780kinaseprotein kinase, ATP-binding, Nuclearprotein, Endoplasmic reticulum, CellcycleNM_005256GAS2growth arrest-Growth arrest, Phosphorylation,28136781specific 2Apoptosis, Cell cycle, CytoskeletonNM_005263GFI1growth factorTranscription regulation, Zinc-finger,28146782independent 1DNA-binding, Nuclear protein, Metal-binding, Repeat, Disease mutationNM_005270GLI2GLI-Kruppel familyTranscription regulation, Zinc-finger,28156783member GLI2Metal-binding, DNA-binding, Nuclearprotein, Repeat, Alternative splicingNM_005271GLUD1glutamateOxidoreductase, NADP,28166784dehydrogenase 1Mitochondrion, Transit peptide,Polymorphism, Disease mutation,Multigene family, 3D-structureNM_005273GNB2guanine nucleotideTransducer, Repeat, WD repeat,28176785binding protein (GMultigene familyprotein), betapolypeptide 2NM_005274GNG5guanine nucleotideTransducer, Prenylation, Lipoprotein,28186786binding protein (GMultigene familyprotein), gamma 5NM_005286GPR8G protein-coupledTranscription regulation, Zinc-finger,28196787receptor 8DNA-binding, Nuclear protein,Repeat, G-protein coupled receptor,Transmembrane, Glycoprotein,Lipoprotein, Palmitate,Phosphorylation, PolymorphismNM_005291GPR17G protein-coupledG-protein coupled receptor,28206788receptor 17Transmembrane, Glycoprotein,Alternative splicing, ReceptorNM_005327HADHSCL-3-hydroxyacyl-Fatty acid metabolism,28216789Coenzyme AOxidoreductase, NAD,dehydrogenase,Mitochondrion, Transit peptide, 3D-short chainstructureNM_005335HCLS1hematopoietic cell-Repeat, SH3 domain,28226790specific LynPhosphorylationsubstrate 1NM_005340HINT1histidine triadHydrolase, Acetylation, 3D-structure28236791nucleotide bindingprotein 1NM_005345HSPA1Aheat shock 70 kDaATP-binding, Chaperone, Heat28246792protein 1Ashock, Multigene family, 3D-structureNM_005346HSPA1Bheat shock 70 kDaATP-binding, Chaperone, Heat28256793protein 1Bshock, Multigene family, 3D-structureNM_005357LIPElipase, hormone-Hydrolase, Lipid degradation,28266794sensitivePhosphorylationNM_005358LMO7LIM domain only 7LIM domain, Metal-binding, Zinc,28276795Hypothetical protein, Zinc-fingerNM_005360MAFv-mafProto-oncogene, Transcription28286796musculoaponeuroticregulation, DNA-binding, Nuclearfibrosarcomaprotein, Alternative splicing,oncogene homologChromosomal translocation(avian)NM_005379MYO1Amyosin IAMyosin, Actin-binding, ATP-binding,28296797Calmodulin-binding, Repeat,Multigene family, Polymorphism,Disease mutation, DeafnessNM_005381NCLnucleolinHypothetical protein28306798NM_005402RALAv-ral simianGTP-binding, Prenylation,28316799leukemia viralLipoproteinoncogene homologA (ras related)NM_005428VAV1vav 1 oncogeneHypothetical protein, SH3 domain,28326800Proto-oncogene, Phorbol-esterbinding, Zinc, SH2 domain, Guanine-nucleotide releasing factor, Repeat,PhosphorylationNM_005433YES1v-yes-1 YamaguchiProto-oncogene, Tyrosine-protein28336801sarcoma viralkinase, Phosphorylation,oncogene homolog 1Transferase, ATP-binding, Myristate,SH3 domain, SH2 domain,LipoproteinNM_005436D10S170DNA segment onProto-oncogene, Chromosomal28346802chromosome 10translocation, SH3-binding, Repeat(unique) 170NM_005439MLF2myeloid leukemiaNuclear protein28356803factor 2NM_005441CHAF1Bchromatin assemblyDNA replication, DNA repair, Cell28366804factor 1, subunit Bcycle, Nuclear protein,(p60)Phosphorylation, Repeat, WD repeatNM_005451ENIGMAenigma (LIM domainLIM domain, Metal-binding, Zinc28376805protein)NM_005463HNRPDLheterogeneousNucleocapsid, Ribonucleoprotein28386806nuclearribonucleoprotein D-likeNM_005466MED6mediator of RNATranscription regulation, Activator,28396807polymerase IIReceptor, Nuclear proteintranscription, subunit6 homolog (yeast)NM_005472KCNE3potassium voltage-Transport, Ion transport, Ionic28406808gated channel, lsk-channel, Voltage-gated channel,related family,Potassium channel, Potassium,member 3Potassium transport,Transmembrane, Glycoprotein,Disease mutationNM_005479FRAT1frequentlyWnt signaling pathway, Proto-28416809rearranged inoncogene, 3D-structureadvanced T-celllymphomasNM_005480TROAPtrophinin associatedCell adhesion, Repeat, Cytoskeleton28426810protein (tastin)NM_005488TOM1target of myb1Hypothetical protein, Transport,28436811(chicken)Protein transport, Membrane, 3D-structureNM_005490SH2D3ASH2 domainHypothetical protein28446812containing 3ANM_005498AP1M2adaptor-relatedGolgi stack, Protein transport,28456813protein complex 1,Transport, Coated pits, Endocytosis,mu 2 subunitPhosphorylation, Alternative splicingNM_005499UBA2SUMO-1 activatingCyclin, Hypothetical protein28466814enzyme subunit 2NM_005501ITGA3integrin, alpha 3Integrin, Cell adhesion, Receptor,28476815(antigen CD49C,Glycoprotein, Transmembrane,alpha 3 subunit ofSignal, Phosphorylation, Repeat,VLA-3 receptor)Alternative splicing, CalciumNM_005504BCAT1branched chainTransferase, Aminotransferase,28486816aminotransferase 1,Branched-chain amino acidcytosolicbiosynthesis, Pyridoxal phosphate,Hypothetical proteinNM_005505SCARB1scavenger receptorTranscription regulation, Nuclear28496817class B, member 1protein, Receptor, Transmembrane,Glycoprotein, Polymorphism,Alternative splicingNM_005507CFL1cofilin 1 (non-Nuclear protein, Actin-binding,28506818muscle)Cytoskeleton, PhosphorylationNM_005510DOM3Zdom-3 homolog ZTransferase, Serine/threonine-28516819(C. elegans)protein kinase, ATP-binding,Manganese, Nuclear protein,Alternative splicingNM_005512GARPglycoprotein AGlycoprotein, Leucine-rich repeat,28526820repetitionsRepeat, Transmembrane, SignalpredominantNM_005514HLA-BmajorGlycoprotein, MHC I, Signal,28536821histocompatibilityTransmembrane, Polymorphism, 3D-complex, class I, Bstructure, Alternative splicing,Hypothetical protein, SulfationNM_005516HLA-EmajorGlycoprotein, Transmembrane,28546822histocompatibilityHypothetical protein, MHC I, Signal,complex, class I, EPolymorphism, 3D-structureNM_005517HMGN2high-mobility groupHypothetical protein, Microtubule,28556823nucleosomal bindingGTP-binding, Multigene family,domain 2Nuclear protein, DNA-binding,PolymorphismNM_005527HSPA1Lheat shock 70 kDaATP-binding, Multigene family,28566824protein 1-likePolymorphismNM_005534IFNGR2interferon gammaReceptor, Transmembrane,28576825receptor 2 (interferonGlycoprotein, Signal, Repeatgamma transducer1)NM_005541INPP5Dinositol28586826polyphosphate-5-phosphatase,145 kDaNM_005548KARSlysyl-tRNAAminoacyl-tRNA synthetase, Protein28596827synthetasebiosynthesis, Ligase, ATP-binding,PolymorphismNM_005564LCN2lipocalin 2Glycoprotein, Lipocalin, Signal, 3D-28606828(oncogene 24p3)structure, Pyrrolidone carboxylic acidNM_005565LCP2lymphocyte cytosolicSH2 domain, Phosphorylation28616829protein 2 (SH2domain containingleukocyte protein of76 kDa)NM_005574LMO2LIM domain only 2Proto-oncogene, Repeat, LIM28626830(rhombotin-like 1)domain, Metal-binding, Zinc, Nuclearprotein, Alternative splicing,Chromosomal translocationNM_005578LPPLIM domainLIM domain, Metal-binding, Zinc28636831containing preferredtranslocation partnerin lipomaNM_005586MDFIMyoD family inhibitorDifferentiation28646832NM_005590MRE11AMRE11 meioticDNA repair, Hydrolase, Nuclease,28656833recombination 11Endonuclease, Exonuclease,homolog A (S. cerevisiae)Nuclear protein, Manganese,Meiosis, Alternative splicing,Disease mutation, Polymorphism,Hypothetical proteinNM_005598NHLH1nescient helix loopDNA-binding, Transcription28666834helix 1regulation, DifferentiationNM_005601NKG7natural killer cellTransmembrane28676835group 7 sequenceNM_005605PPP3CCprotein phosphataseHypothetical protein, Hydrolase,286868363 (formerly 2B),Iron, Manganese, Calmodulin-catalytic subunit,binding, Metal-binding, Zinc,gamma isoformMultigene family(calcineurin Agamma)NM_005607PTK2PTK2 proteinHypothetical protein, ATP-binding,28696837tyrosine kinase 2Transferase, Kinase, Tyrosine-protein kinase, Phosphorylation,Alternative splicing, 3D-structureNM_005608PTPRCAPprotein tyrosineTransmembrane, Phosphorylation28706838phosphatase,receptor type, C-associated proteinNM_005611RBL2retinoblastoma-like 2ATP-binding, Kinase,28716839(p130)Serine/threonine-protein kinase,Transferase, Transcriptionregulation, DNA-binding, Nuclearprotein, Cell cycle, Phosphorylation,Anti-oncogeneNM_005620S100A11S100 calciumCalcium-binding28726840binding protein A11(calgizzarin)NM_005621S100A12S100 calciumCalcium-binding, Zinc, Metal-28736841binding protein A12binding, Antibiotic, Fungicide, 3D-(calgranulin C)structureNM_005623CCL8chemokine (C—CCytokine, Chemotaxis, Signal,28746842motif) ligand 8Heparin-binding, Inflammatoryresponse, Polymorphism,Pyrrolidone carboxylic acid, 3D-structureNM_005625SDCBPsyndecan bindingCytoskeleton, Membrane,28756843protein (syntenin)Endoplasmic reticulum, Nuclearprotein, Phosphorylation, Repeat,PolymorphismNM_005646TARBP1TAR (HIV) RNA28766844binding protein 1NM_005647TBL1Xtransducin (beta)-likeRepeat, WD repeat287768451X-linkedNM_005654NR2F1nuclear receptorReceptor, Transcription regulation,28786846subfamily 2, group F,DNA-binding, Nuclear protein, Zinc-member 1finger, ActivatorNM_005658TRAF1TNF receptor-Apoptosis, Coiled coil28796847associated factor 1NM_005687FRSBphenylalanyl-tRNAAminoacyl-tRNA synthetase, Protein28806848synthetase beta-biosynthesis, Ligase, ATP-bindingsubunitNM_005690DNM1Ldynamin 1-likeHypothetical protein28816849NM_005697SCAMP2secretory carrierTransmembrane, Transport, Protein28826850membrane protein 2transport, Multigene familyNM_005704PTPRUprotein tyrosineGlycoprotein, Hydrolase, Receptor,28836851phosphatase,Repeat, Signal, Transmembrane,receptor type, UImmunoglobulin domainNM_005710PQBP1polyglutamineNuclear protein28846852binding protein 1NM_005713COL4A3BPcollagen, type IV,Transferase, Kinase,28856853alpha 3Serine/threonine-protein kinase,(GoodpastureCoiled coil, Alternative splicingantigen) bindingproteinNM_005716RGS19IP1regulator of G-28866854protein signalling 19interacting protein 1NM_005717ARPC5actin related proteinCytoskeleton288768552/3 complex, subunit5, 16 kDaNM_005720ARPC1Bactin related proteinHypothetical protein, Repeat, WD288868562/3 complex, subunitrepeat, Polymorphism1B, 41 kDaNM_005724TSPAN-3transmembrane 4Glycoprotein, Transmembrane28896857superfamily member 8NM_005725TSPAN-2tetraspan 2Glycoprotein, Transmembrane28906858NM_005730OS4CTD (carboxy-Hypothetical protein, Nuclear protein28916859terminal domain,RNA polymerase II,polypeptide A) smallphosphatase 2NM_005731ARPC2actin related proteinCytoskeleton289268602/3 complex, subunit2, 34 kDaNM_005732RAD50RAD50 homolog (S. cerevisiae)28936861NM_005733KIF20Akinesin familyMotor protein, Microtubule, ATP-28946862member 20Abinding, Coiled coil, Golgi stack,Protein transport, TransportNM_005736ACTR1AARP1 actin-relatedStructural protein, Cytoskeleton,28956863protein 1 homolog A,Multigene familycentractin alpha(yeast)NM_005737ARL7ADP-ribosylationGTP-binding, Multigene family,28966864factor-like 7Nuclear proteinNM_005741ZNF263zinc finger proteinTranscription regulation, Zinc-finger,28976865263Metal-binding, Nuclear protein, DNA-binding, Repeat, RepressorNM_005759ABI-2abl-interactor 2Kinase, SH3 domain28986866NM_005761PLXNC1plexin C128996867NM_005762TRIM28tripartite motif-Transcription regulation, Repressor,29006868containing 28Nuclear protein, Zinc-finger, Repeat,3D-structureNM_005770SERF2small EDRK-richHypothetical protein29016869factor 2NM_005771RDHLdehydrogenase/reductaseOxidoreductase29026870(SDR family)member 9NM_005772PLAARNA terminalRepeat, WD repeat, Hypothetical29036871phosphate cyclase-protein, Nuclear proteinlike 1NM_005773ZNF256zinc finger proteinTranscription regulation, DNA-29046872256binding, Zinc-finger, Metal-binding,Nuclear protein, RepeatNM_005787NOT56Lasparagine-linkedHypothetical protein, Transferase,29056873glycosylation 3Glycosyltransferase,homolog (yeast,Transmembrane, Endoplasmicalpha-1,3-reticulum, Disease mutationmannosyltransferase)NM_005797EVA1epithelial V-likeCell adhesion, Immunoglobulin29066874antigen 1domain, Transmembrane,Glycoprotein, SignalNM_005803FLOT1flotillin 1Membrane29076875NM_005805PSMD14proteasomeProteasome29086876(prosome,macropain) 26Ssubunit, non-ATPase, 14NM_005811GDF11growth differentiationGrowth factor, Cytokine,29096877factor 11Glycoprotein, SignalNM_005826HNRPRheterogeneousNucleocapsid, Ribonucleoprotein,29106878nuclearNuclear protein, RNA-binding,ribonucleoprotein RRepeatNM_005833RAB9P40Rab9 effector p4029116879NM_005834TIMM17Btranslocase of innerTransport, Protein transport,29126880mitochondrialTranslocation, Mitochondrion, Innermembrane 17membrane, Transmembranehomolog B (yeast)NM_005836UK114translational inhibitorNuclear protein29136881protein p14.5NM_005845ABCC4ATP-bindingATP-binding, Glycoprotein,29146882cassette, sub-familyTransmembrane, Transport, RepeatC (CFTR/MRP),member 4NM_005849IGSF6immunoglobulinSignal, Hypothetical protein29156883superfamily, member 6NM_005855RAMP1receptor (calcitonin)Signal, Transmembrane, Transport,29166884activity modifyingReceptorprotein 1NM_005860FSTL3follistatin-like 3Glycoprotein, Repeat, Signal,29176885(secretedChromosomal translocation, Proto-glycoprotein)oncogeneNM_005862STAG1stromal antigen 1Mitosis, Cell cycle, Chromosome29186886partition, Nuclear protein,PhosphorylationNM_005863NET1neuroepithelial cell29196887transforming gene 1NM_005865PRSS16protease, serine, 16Hydrolase, Serine protease, Signal29206888(thymus)NM_005866SR-BP1opioid receptor,Hypothetical protein, Receptor29216889sigma 1NM_005873RGS19regulator of G-Signal transduction inhibitor,29226890protein signalling 19Membrane, Lipoprotein, Palmitate,Phosphorylation, Autophagy, 3D-structureNM_005874LILRB2leukocyteReceptor, Repeat, Signal,29236891immunoglobulin-likeTransmembrane, Immune response,receptor, subfamilyImmunoglobulin domain,B (with TM and ITIMPhosphorylation, Glycoprotein,domains), member 2Antigen, Multigene family,Alternative splicing, PolymorphismNM_005884PAK4p21(CDKN1A)-Hypothetical protein, ATP-binding,29246892activated kinase 4Transferase, Serine/threonine-protein kinase, Phosphorylation,Alternative splicingNM_005886KATNB1katanin p80 (WDRepeat, WD repeat29256893repeat containing)subunit B 1NM_005888SLC25A3solute carrier familyMitochondrion, Inner membrane,2926689425 (mitochondrialRepeat, Transit peptide,carrier; phosphateTransmembrane, Transport,carrier), member 3Symport, Alternative splicing,Hypothetical proteinNM_005891ACAT2acetyl-Coenzyme AChaperone, ATP-binding, Multigene29276895acetyltransferase 2family, Transferase(acetoacetylCoenzyme Athiolase)NM_005892FMNLformin-like 1Hypothetical protein29286896NM_005898M11S1membraneGPI-anchor29296897component,chromosome 11,surface marker 1NM_005900MADH1MAD, mothersTranscription regulation,29306898againstPhosphorylation, Multigene family,decapentaplegic3D-structurehomolog 1(Drosophila)NM_005902MADH3MAD, mothersTranscription regulation,29316899againstPhosphorylation, Multigene family,decapentaplegic3D-structurehomolog 3(Drosophila)NM_005917MDH1malateOxidoreductase, Tricarboxylic acid29326900dehydrogenase 1,cycle, NADNAD (soluble)NM_005931MICBMHC class IGlycoprotein, Transmembrane, MHC29336901polypeptide-relatedsequence BNM_005932MIPEPmitochondrialHydrolase, Metalloprotease, Zinc,29346902intermediateTransit peptide, Mitochondrion,peptidaseMagnesium, Manganese, Calcium,Cobalt, IronNM_005935MLLT2myeloid/lymphoid orAlternative splicing, Chromosomal29356903mixed-lineagetranslocation, Proto-oncogene, DNA-leukemia (trithoraxbinding, Bromodomain, Nuclearhomolog,protein, Zinc-finger, Metal-binding,Drosophila);Transcription regulation, Repeat,translocated to, 2Hypothetical protein,Serine/threonine-protein kinase,Transferase, ATP-binding, TranNM_005950MT1Gmetallothionein 1GMetal-binding, Metal-thiolate cluster,29366904Zinc, Copper, Cadmium, AcetylationNM_005952MT1Xmetallothionein 1XHypothetical protein, Metal-binding,29376905Metal-thiolate cluster, Zinc, Copper,Cadmium, AcetylationNM_005953MT2Ametallothionein 2AMetal-binding, Metal-thiolate cluster,29386906Zinc, Acetylation, 3D-structureNM_005954MT3metallothionein 3Metal-binding, Metal-thiolate cluster,29396907(growth inhibitoryZinc, Copper, Acetylationfactor (neurotrophic))NM_005955MTF1metal-regulatoryHypothetical protein, Metal-binding,29406908transcription factor 1Zinc, Zinc-fingerNM_005965MYLKmyosin, lightImmunoglobulin domain, Kinase,29416909polypeptide kinaseATP-binding, Repeat,Serine/threonine-protein kinase,Transferase, Calmodulin-binding,Phosphorylation, Alternativeinitiation, Alternative splicingNM_005969NAP1L4nucleosomeNuclear protein29426910assembly protein 1-like 4NM_005975PTK6PTK6 proteinTransferase, Tyrosine-protein29436911tyrosine kinase 6kinase, ATP-binding, SH2 domain,SH3 domain, PhosphorylationNM_005979S100A13S100 calciumCalcium-binding29446912binding protein A13NM_005980S100PS100 calciumCalcium-binding, Placenta, 3D-29456913binding protein PstructureNM_005988SPRR2Asmall proline-richKeratinocyte, Repeat, Multigene29466914protein 2AfamilyNM_005990STK10serine/threonineKinase, Transferase,29476915kinase 10Serine/threonine-protein kinase,ATP-binding, Phosphorylation,Coiled coilNM_005998CCT3chaperoninChaperone, ATP-binding, Multigene29486916containing TCP1,family, Hypothetical proteinsubunit 3 (gamma)NM_006002UCHL3ubiquitin carboxyl-Ubl conjugation pathway, Hydrolase,29496917terminal esterase L3Thiol protease, Multigene family, 3D-(ubiquitinstructurethiolesterase)NM_006018HM74putative chemokineG-protein coupled receptor,29506918receptorTransmembraneNM_006019TCIRG1T-cell, immuneHydrogen ion transport,29516919regulator 1, ATPase,Transmembrane, Glycoprotein,H+ transporting,Alternative splicing, Hypotheticallysosomal V0 proteinproteina isoform 3NM_006022TSC22transforming growthHypothetical protein, Transcription29526920factor beta-regulation, Repressor, Nuclearstimulated proteinproteinTSC-22NM_006027EXO1exonuclease 1Exonuclease, Hypothetical protein29536921NM_006029PNMA1paraneoplasticAntigen, Tumor antigen, Nuclear29546922antigen MA1proteinNM_006031PCNT2pericentrin 2Coiled coil, Hypothetical protein29556923(kendrin)NM_006034TP53I11tumor protein p53Hypothetical protein29566924inducible protein 11NM_006053TCIRG1T-cell, immuneHydrogen ion transport,29576925regulator 1, ATPase,Transmembrane, Glycoprotein,H+ transporting,Alternative splicing, Hypotheticallysosomal V0 proteinproteina isoform 3NM_006054RTN3reticulon 3Hypothetical protein,29586926Transmembrane, EndoplasmicreticulumNM_006055LANCL1LanC lantibioticTransmembrane29596927synthetasecomponent C-like 1(bacterial)NM_006060ZNFN1A1zinc finger protein,Transcription regulation, Activator,29606928subfamily 1A, 1Zinc-finger, Metal-binding, DNA-(lkaros)binding, Nuclear protein, Repeat,Alternative splicingNM_006061SGP28cysteine-richGlycoprotein, Signal, Multigene29616929secretory protein 3family, PolymorphismNM_006069MRVI1murine retrovirus29626930integration site 1homologNM_006070TFGTRK-fused geneHypothetical protein, Ligase, GMP29636931biosynthesis, Purine biosynthesis,ATP-binding, GlutamineamidotransferaseNM_006079CITED2Cbp/p300-interactingTranscription regulation, Nuclear29646932transactivator, withprotein, Alternative splicingGlu/Asp-richcarboxy-terminaldomain, 2NM_006088TUBB2tubulin, beta, 2Microtubule, GTP-binding, Multigene29656933family, Hypothetical proteinNM_006093PRG3proteoglycan 329666934NM_006097MYL9myosin, lightMyosin, Calcium-binding, Muscle29676935polypeptide 9,protein, Phosphorylation,regulatoryAcetylation, Multigene familyNM_006103WFDC2WAP four-disulfideSerine protease inhibitor, Repeat,29686936core domain 2Signal, Glycoprotein, AlternativesplicingNM_006107LUC7Aacid-induciblePhosphorylation, Hypothetical29696937phosphoproteinproteinNM_006109SKB1SKB1 homolog (S. pombe)Transferase, Methyltransferase,29706938Alternative splicingNM_006111ACAA2acetyl-Coenzyme AAcyltransferase, Transferase, Fatty29716939acyltransferase 2acid metabolism, Mitochondrion,(mitochondrial 3-Transit peptideoxoacyl-CoenzymeA thiolase)NM_006113VAV3vav 3 oncogeneSH3 domain, Phorbol-ester binding,29726940Zinc, SH2 domain, Repeat, Guanine-nucleotide releasing factor,Alternative splicingNM_006115PRAMEpreferentiallyAntigen29736941expressed antigen inmelanomaNM_006117PECIperoxisomal D3,D2-Isomerase, Hypothetical protein,29746942enoyl-CoAPeroxisomeisomeraseNM_006135CAPZA1capping proteinActin-binding, Multigene family, 3D-29756943(actin filament)structure, Actin cappingmuscle Z-line, alpha 1NM_006138MS4A3membrane-spanningReceptor, Transmembrane,297669444-domains,Alternative splicing, Multigene familysubfamily A,member 3(hematopoietic cell-specific)NM_006139CD28CD28 antigen (Tp44)Immunoglobulin domain, T-cell,29776945Glycoprotein, Signal,Transmembrane, Alternative splicingNM_006140CSF2RAcolony stimulatingReceptor, Transmembrane,29786946factor 2 receptor,Glycoprotein, Signal, Alternativealpha, low-affinitysplicing(granulocyte-macrophage)NM_006142SFNstratifinMultigene family29796947NM_006144GZMAgranzyme AHydrolase, Serine protease,29806948(granzyme 1,Zymogen, Signal, T-cell, Cytolysis,cytotoxic T-Apoptosis, 3D-structurelymphocyte-associated serineesterase 3)NM_006145DNAJB1DnaJ (Hsp40)Heat shock, Chaperone, 3D-29816949homolog, subfamilystructureB, member 1NM_006147IRF6interferon regulatoryTranscription regulation, DNA-29826950factor 6binding, Nuclear protein,Polymorphism, Disease mutationNM_006148LASP1LIM and SH3 protein 1LIM domain, Metal-binding, Zinc,29836951SH3 domainNM_006159NELL2NEL-like 2 (chicken)EGF-like domain, Glycoprotein,29846952Repeat, SignalNM_006161NEUROG1neurogenin 1DNA-binding, Nuclear protein,29856953Transcription regulation, Activator,Neurogenesis, Developmentalprotein, DifferentiationNM_006176NRGNneurogranin (proteinCalmodulin-binding,29866954kinase C substrate,Phosphorylation, NeuroneRC3)NM_006185NUMA1nuclear mitoticImmunoglobulin domain,29876955apparatus protein 1Glycoprotein, Signal, Alternativesplicing, Hypothetical proteinNM_006196PCBP1poly(rC) bindingNuclear protein, RNA-binding,29886956protein 1Ribonucleoprotein, DNA-binding,Phosphorylation, RepeatNM_006202PDE4AphosphodiesteraseHydrolase, cAMP, Alternative298969574A, cAMP-specificsplicing, Multigene family(phosphodiesteraseE2 dunce homolog,Drosophila)NM_006205PDE6HphosphodiesteraseHydrolase, cGMP, Vision299069586H, cGMP-specific,cone, gammaNM_006214PHYHphytanoyl-CoAOxidoreductase, Peroxisome,29916959hydroxylaseVitamin C, Iron, Transit peptide,(Refsum disease)Disease mutation, Deafness,Retinitis pigmentosa, Hydrolase,cGMP, Vision, Prenylation,Lipoprotein, Membrane, Hypotheticalprotein, CollagenNM_006224PITPNphosphotidylinositolLipid-binding, Transport29926960transfer proteinNM_006225PLCD1phospholipase C,Hydrolase, Lipid degradation,29936961delta 1Transducer, Calcium-binding,RepeatNM_006238PPARDperoxisomeReceptor, Transcription regulation,29946962proliferativeActivator, DNA-binding, Nuclearactivated receptor,protein, Zinc-finger, Multigene family,delta3D-structure, Metal-bindingNM_006242PPP1R3Dprotein phosphataseHydrolase, Glycogen metabolism299569631, regulatory subunit3DNM_006243PPP2R5Aprotein phosphatasePhosphorylation, Multigene family299669642, regulatory subunitB (B56), alphaisoformNM_006244PPP2R5Bprotein phosphatasePhosphorylation, Alternative splicing,299769652, regulatory subunitMultigene familyB (B56), betaisoformNM_006254PRKCDprotein kinase C,ATP-binding, Transferase,29986966deltaScrine/threonine-protein kinase,Phorbol-ester binding, Zinc, Repeat,Polymorphism, Phosphorylation,MembraneNM_006272S100BS100 calciumCalcium-binding, Zinc, Metal-29996967binding protein, betabinding, 3D-structure(neural)NM_006284TAF10TAF10 RNATranscription regulation, Nuclear30006968polymerase II, TATAprotein, Polymorphismbox binding protein(TBP)-associatedfactor, 30 kDaNM_006287TFPItissue factorSerine protease inhibitor,30016969pathway inhibitorGlycoprotein, Repeat, Blood(lipoprotein-coagulation, Signal, Alternativeassociatedsplicing, 3D-structure, Polymorphismcoagulation inhibitor)NM_006289TLN1talin 1Hypothetical protein, Structural30026970protein, CytoskeletonNM_006290TNFAIP3tumor necrosisApoptosis, DNA-binding, Zinc-finger,30036971factor, alpha-inducedRepeat, Hypothetical proteinprotein 3NM_006291TNFAIP2tumor necrosisAngiogenesis30046972factor, alpha-inducedprotein 2NM_006304DSS1split hand/footPolymorphism, 3D-structure30056973malformation(ectrodactyly) type 1NM_006310NPEPPSaminopeptidaseHydrolase, Metalloprotease,30066974puromycin sensitiveAminopeptidase, Zinc, NuclearproteinNM_006314CNK1connector enhancerHypothetical protein, Kinase30076975of KSR-like(Drosophila kinasesuppressor of ras)NM_006317BASP1brain abundant,Membrane, Myristate, Neurone,30086976membrane attachedLipoproteinsignal protein 1NM_006319CDIPTCDP-diacylglycerol-Transferase, Phospholipid30096977inositol 3-biosynthesis, Transmembrane,phosphatidyltransferaseMagnesium, Manganese(phosphatidylinositolsynthase)NM_006321ARIH2ariadne homolog 2Ubl conjugation pathway, Nuclear30106978(Drosophila)protein, Coiled coil, Zinc-finger,RepeatNM_006323SEC24BSEC24 related geneTransport, Protein transport, Golgi30116979family, member B (S. cerevisiae)stack, Endoplasmic reticulum,Multigene familyNM_006324CFDP1craniofacial30126980development protein 1NM_006327TIMM23translocase of innerTransport, Protein transport,30136981mitochondrialTranslocation, Mitochondrion, Innermembrane 23membrane, Outer membrane,homolog (yeast)TransmembraneNM_006342TACC3transforming, acidicCoiled coil30146982coiled-coil containingprotein 3NM_006344HML2C-type (calciumLectin30156983dependent,carbohydrate-recognition domain)lectin, superfamilymember 13(macrophage-derived)NM_006345C4orf1solute carrier familyHypothetical protein3016698430 (zinc transporter),member 9NM_006346PIBF1progesterone-30176985induced blockingfactor 1NM_006351TIMM44translocase of innerMitochondrion, Inner membrane,30186986mitochondrialTransport, Protein transport,membrane 44Translocation, Transit peptide, ATP-homolog (yeast)binding, ReceptorNM_006353HMGN4high mobility groupNuclear protein, DNA-binding30196987nucleosomal bindingdomain 4NM_006355TRIM38tripartite motif-Zinc-finger, Polymorphism30206988containing 38NM_006360GA17dendritic cell proteinHypothetical protein30216989NM_006362NXF1nuclear RNA exportTransport, mRNA transport, Nuclear30226990factor 1protein, RNA-binding, Repeat,Leucine-rich repeat, Multigenefamily, 3D-structureNM_006367CAPCAP, adenylateMembrane, Multigene family30236991cyclase-associatedprotein 1 (yeast)NM_006374STK25serine/threonineHypothetical protein, ATP-binding,30246992kinase 25 (STE20Transferase, Serine/threonine-homolog, yeast)protein kinase, PhosphorylationNM_006377UNC13unc-13 homolog BPhorbol-ester binding30256993(C. elegans)NM_006383KIP2DNA-dependentCalcium-binding, Repeat30266994protein kinasecatalytic subunit-interacting protein 2NM_006386DDX17DEAD (Asp-Glu-Ala-ATP-binding, RNA-binding, Helicase,30276995Asp) box polypeptideNuclear protein17NM_006387CHERPcalcium homeostasis30286996endoplasmicreticulum proteinNM_006389HYOU1hypoxia up-regulated 1ATP-binding, Chaperone,30296997Endoplasmic reticulum, Signal,GlycoproteinNM_006395GSA7APG7 autophagy 7-Hypothetical protein30306998like (S. cerevisiae)NM_006399BATFbasic leucine zipperTranscription regulation, DNA-30316999transcription factor,binding, Repressor, Phosphorylation,ATF-likeNuclear proteinNM_006403NEDD9neural precursor cellPhosphorylation, SH3 domain, Cell30327000expressed,adhesion, Growth regulation,developmentallyCytoskeleton, Mitosis, Nucleardown-regulated 9proteinNM_006404PROCRprotein C receptor,Blood coagulation, Receptor, Signal,30337001endothelial (EPCR)Transmembrane, Glycoprotein,Antigen, Polymorphism, 3D-structureNM_006405TM9SF1transmembrane 9Hypothetical protein, Plasmid,30347002superfamily member 1Signal, Transmembrane,GlycoproteinNM_006406PRDX4peroxiredoxin 4Antioxidant, Peroxidase,30357003Oxidoreductase, Redox-activecenterNM_006421BIG1brefeldin A-inhibitedGuanine-nucleotide releasing factor30367004guanine nucleotide-exchange protein 1NM_006429CCT7chaperoninChaperone, ATP-binding, Multigene30377005containing TCP1,familysubunit 7 (eta)NM_006430CCT4chaperoninChaperone, ATP-binding, Multigene30387006containing TCP1,family, Hypothetical proteinsubunit 4 (delta)NM_006431CCT2chaperoninATP-binding, Chaperone, Multigene30397007containing TCP1,familysubunit 2 (beta)NM_006433GNLYgranulysinAntibiotic, Fungicide, Signal, T-cell,30407008Alternative splicing, 3D-structureNM_006435IFITM2interferon inducedInterferon induction,30417009transmembraneTransmembrane, Polymorphismprotein 2 (1-8D)NM_006441MTHFS5,10-Ligase, Folate-binding, Acetylation,30427010methenyltetrahydrofolateMagnesium, Hypothetical proteinsynthetase (5-formyltetrahydrofolatecyclo-ligase)NM_006451PAIP1poly(A) bindingHypothetical protein30437011protein interactingNM_004920AATKapoptosis-Kinase, Hypothetical protein, ATP-27546722associated tyrosinebinding, TransferasekinaseNM_004924ACTN4actinin, alpha 4Actin-binding, Calcium-binding,27556723Repeat, Multigene family, Diseasemutation, Nuclear protein,Hypothetical proteinNM_004928C21orf2chromosome 21Alternative splicing, Polymorphism27566724open reading frame 2NM_004930CAPZBcapping proteinCytoskeleton, Actin-binding,27576725(actin filament)Alternative splicing, Actin cappingmuscle Z-line, betaNM_004939DDX1DEAD (Asp-Glu-Ala-Hydrolase, ATP-binding, Helicase,27586726Asp) box polypeptide 1RNA-bindingNM_004945DNM2dynamin 2Hydrolase, Motor protein, GTP-27596727binding, Microtubule, Multigenefamily, Endocytosis, Alternativesplicing, Hypothetical proteinNM_004954MARK2MAP/microtubuleATP-binding, Kinase,27606728affinity-regulatingSerine/threonine-protein kinase,kinase 2TransferaseNM_004974KCNA2potassium voltage-Transport, Ion transport, Ionic27616729gated channel,channel, Voltage-gated channel,shaker-relatedPotassium channel, Potassiumsubfamily, member 2transport, Potassium,Transmembrane, Glycoprotein,Phosphorylation, Multigene familyNM_004979KCND1potassium voltage-Transport, Ion transport, Ionic27626730gated channel, Shal-channel, Voltage-gated channel,related subfamily,Potassium channel, Potassiummember 1transport, Potassium,Transmembrane, Multigene familyNM_004994MMP9matrixHydrolase, Metalloprotease,27636731metalloproteinase 9Glycoprotein, Zinc, Zymogen,(gelatinase B, 92 kDaCalcium, Collagen degradation,gelatinase, 92 kDaExtracellular matrix, Repeat, Signal,type IV collagenase)Polymorphism, 3D-structureNM_005000NDUFA5NADHHypothetical protein,27646732dehydrogenaseOxidoreductase, NAD, Ubiquinone,(ubiquinone) 1 alphaMitochondrion, Acetylationsubcomplex, 5,13 kDaNM_005003NDUFAB1NADHFatty acid biosynthesis,27656733dehydrogenasePhosphopantetheine, Mitochondrion,(ubiquinone) 1,Transit peptide, Oxidoreductasealpha/betasubcomplex, 1, 8 kDaNM_005009NME4non-metastatic cellsTransferase, Kinase, ATP-binding,276667344, protein expressedMitochondrion, Transit peptide, 3D-instructureNM_005011NRF1nuclear respiratoryTranscription regulation, DNA-27676735factor 1binding, Activator, Nuclear protein,Phosphorylation, Alternative splicingNM_005022PFN1profilin 1Actin-binding, Cytoskeleton,27686736Multigene family, Acetylation, 3D-structureNM_005024SERPINB10serine (or cysteine)Serpin, Serine protease inhibitor27696737proteinase inhibitor,clade B (ovalbumin),member 10NM_005025SERPINI1serine (or cysteine)Serpin, Serine protease inhibitor,27706738proteinase inhibitor,Glycoprotein, Signal, Diseaseclade Imutation(neuroserpin).member 1NM_005026PIK3CDphosphoinositide-3-Kinase, Transferase, Multigene27716739kinase, catalytic,familydelta polypeptideNM_005029PITX3paired-likeHomeobox, DNA-binding,27726740homeodomainDevelopmental protein, Nucleartranscription factor 3protein, Disease mutationNM_005030PLKpolo-like kinaseTransferase, Serine/threonine-27736741(Drosophila)protein kinase, ATP-binding, Repeat,Nuclear protein, PhosphorylationNM_005040PRCPprolylcarboxypeptidaseHydrolase, Carboxypeptidase,27746742(angiotensinaseGlycoprotein, Zymogen, Signal,C)LysosomeNM_005044PRKXprotein kinase, X-ATP-binding, Kinase,27756743linkedSerine/threonine-protein kinase,Transferase, Tyrosine-proteinkinase, cAMPNM_005055RAPSNreceptor-associatedSynapse, Postsynaptic membrane,27766744protein of theCytoskeleton, Phosphorylation,synapse, 43 kDMyristate, Zinc-finger, Repeat, TPRrepeat, Alternative splicing,Lipoprotein, Metal-binding, ReceptorNM_005056RBBP2retinoblastomaTrans-acting factor, Nuclear protein,27776745binding protein 2Repeat, Zinc-fingerNM_005061RPL3Lribosomal proteinRibosomal protein27786746L3-likeNM_005066SFPQsplicing factorNuclear protein, RNA-binding, DNA-27796747proline/glutaminebinding, mRNA splicing, Repeat,rich (polypyrimidineAlternative splicingtract binding proteinassociated)NM_005084PLA2G7phospholipase A2,Hydrolase, Lipid degradation,27806748group VII (platelet-Glycoprotein, Signal, Polymorphism,activating factorDisease mutationacetylhydrolase,plasma)NM_005085NUP214nucleoporin 214 kDaHypothetical protein, Repeat, WD27816749repeat, Nuclear protein, Transport,Proto-oncogene, Chromosomaltranslocation, GlycoproteinNM_005091PGLYRPpeptidoglycanAntibiotic, Immune response, Signal27826750recognition proteinNM_005096ZNF261zinc finger proteinHypothetical protein, Chromosomal27836751261translocation, Transmembrane,Alternative splicingNM_005099ADAMTS4a disintegrin-like andHydrolase, Metalloprotease, Zinc,27846752metalloproteaseSignal, Glycoprotein, Zymogen,(reprolysin type) withExtracellular matrix, Hypotheticalthrombospondin typeprotein1 motif, 4NM_005106DLEC1deleted in lung andHypothetical protein27856753esophageal cancer 1NM_005111CRYZL1crystallin, zetaOxidoreductase, NADP, Alternative27866754(quinone reductase)-splicinglike 1NM_005112WDR1WD repeat domain 1Repeat, WD repeat, Hypothetical27876755protein, Actin-binding, Cytoskeleton,Alternative splicing, PolymorphismNM_005134PPP4R1protein phosphataseHypothetical protein278867564, regulatory subunit 1NM_005137DGCR2DiGeorge syndromeCell adhesion, Receptor, Signal,27896757critical region gene 2Transmembrane, Lectin,GlycoproteinNM_005139ANXA3annexin A3Annexin, Calcium/phospholipid-27906758binding, Repeat, Phospholipase A2inhibitor, 3D-structure,PolymorphismNM_005143HPhaptoglobinGlycoprotein, Serine protease27916759homolog, Sushi, Hemoglobin-binding, Signal, Repeat,PolymorphismNM_005148UNC119unc-119 homolog (C. elegans)Vision, Alternative splicing27926760NM_005151USP14ubiquitin specificUbl conjugation pathway, Hydrolase,27936761protease 14 (tRNA-Thiol protease, Multigene familyguaninetransglycosylase)NM_005165ALDOCaldolase C, fructose-Lyase, Schiff base, Glycolysis,27946762bisphosphateMultigene familyNM_005167ARHChypothetical proteinDNA condensation, Mitosis, Cell27956763MGC19531cycle, ATP-binding, Coiled coil,Nuclear protein, Alternative splicing,Hypothetical protein, Proto-oncogene, GTP-binding, Prenylation,LipoproteinNM_005173ATP2A3ATPase, Ca++Hydrolase, Calcium transport,27966764transporting,Transmembrane, Phosphorylation,ubiquitousATP-binding, Metal-binding,Magnesium, Calcium-binding,Multigene family, Alternative splicingNM_005174ATP5C1ATP synthase, H+ATP synthesis, CF(1), Hydrogen ion27976765transporting,transport, Hydrolase, Mitochondrion,mitochondrial F1Transit peptide, Alternative splicing,complex, gammaHypothetical proteinpolypeptide 1NM_005180BMI1B lymphoma Mo-Chromatin regulator, Nuclear27986766MLV insertion regionprotein, Transcription regulation,(mouse)Repressor, Zinc-finger, Proto-oncogeneNM_005185CALML3calmodulin-like 3Calcium-binding, Repeat,27996767Methylation, 3D-structureNM_005190CCNCcyclin CCyclin, Cell cycle, Cell division,28006768Nuclear protein, TranscriptionregulationNM_005195CEBPDKIAA0146 proteinTranscription regulation, Activator,28016769DNA-binding, Nuclear proteinNM_005197CHES1checkpointTranscription regulation, Activator,28026770suppressor 1DNA-binding, Nuclear protein,Alternative splicingNM_005199CHRNGcholinergic receptor,Receptor, Postsynaptic membrane,28036771nicotinic, gammaIonic channel, Glycoprotein, Signal,polypeptideTransmembraneNM_005213CSTAcystatin A (stefin A)Thiol protease inhibitor, 3D-structure28046772NM_005217DEFA3defensin, alpha 3,Defensin, Antibiotic, Antiviral,28056773neutrophil-specificFungicide, Signal, 3D-structureNM_005224DRIL1dead ringer-like 1Transcription regulation, Activator,28066774(Drosophila)DNA-binding, Nuclear proteinNM_005231EMS1ems1 sequencePhosphorylation, Repeat, SH328076775(mammary tumordomain, Cytoskeletonand squamous cellcarcinoma-associated (p80/85src substrate)NM_005239ETS2v-etsProto-oncogene, DNA-binding,28086776erythroblastosisNuclear proteinvirus E26 oncogenehomolog 2 (avian)NM_005248FGRGardner-RasheedTransferase, Tyrosine-protein28096777feline sarcoma viralkinase, Proto-oncogene, ATP-(v-fgr) oncogenebinding, Phosphorylation, SH2homologdomain, SH3 domainNM_005252FOSv-fos FBJ murineProto-oncogene, Nuclear protein,28106778osteosarcoma viralPhosphorylation, DNA-binding, 3D-oncogene homologstructureNM_005253FOSL2FOS-like antigen 2Nuclear protein, DNA-binding28116779NM_005255GAKcyclin G associatedTransferase, Serine/threonine-28126780kinaseprotein kinase, ATP-binding, Nuclearprotein, Endoplasmic reticulum, CellcycleNM_005256GAS2growth arrest-Growth arrest, Phosphorylation,28136781specific 2Apoptosis, Cell cycle, CytoskeletonNM_005263GFI1growth factorTranscription regulation, Zinc-finger,28146782independent 1DNA-binding, Nuclear protein, Metal-binding, Repeat, Disease mutationNM_005270GLI2GLI-Kruppel familyTranscription regulation, Zinc-finger,28156783member GLI2Metal-binding, DNA-binding, Nuclearprotein, Repeat, Alternative splicingNM_005271GLUD1glutamateOxidoreductase, NADP,28166784dehydrogenase 1Mitochondrion, Transit peptide,Polymorphism, Disease mutation,Multigene family, 3D-structureNM_005273GNB2guanine nucleotideTransducer, Repeat, WD repeat,28176785binding protein (GMultigene familyprotein), betapolypeptide 2NM_005274GNG5guanine nucleotideTransducer, Prenylation, Lipoprotein,28186786binding protein (GMultigene familyprotein), gamma 5NM_005286GPR8G protein-coupledTranscription regulation, Zinc-finger,28196787receptor 8DNA-binding, Nuclear protein,Repeat, G-protein coupled receptor,Transmembrane, Glycoprotein,Lipoprotein, Palmitate,Phosphorylation, PolymorphismNM_005291GPR17G protein-coupledG-protein coupled receptor,28206788receptor 17Transmembrane, Glycoprotein,Alternative splicing, ReceptorNM_005327HADHSCL-3-hydroxyacyl-Fatty acid metabolism,28216789Coenzyme AOxidoreductase, NAD,dehydrogenase,Mitochondrion, Transit peptide, 3D-short chainstructureNM_005335HCLS1hematopoietic cell-Repeat, SH3 domain,28226790specific LynPhosphorylationsubstrate 1NM_005340HINT1histidine triadHydrolase, Acetylation, 3D-structure28236791nucleotide bindingprotein 1NM_005345HSPA1Aheat shock 70 kDaATP-binding, Chaperone, Heat28246792protein 1Ashock, Multigene family, 3D-structureNM_005346HSPA1Bheat shock 70 kDaATP-binding, Chaperone, Heat28256793protein 1Bshock, Multigene family, 3D-structureNM_005357LIPElipase, hormone-Hydrolase, Lipid degradation,28266794sensitivePhosphorylationNM_005358LMO7LIM domain only 7LIM domain, Metal-binding, Zinc,28276795Hypothetical protein, Zinc-fingerNM_005360MAFv-mafProto-oncogene, Transcription28286796musculoaponeuroticregulation, DNA-binding, Nuclearfibrosarcomaprotein, Alternative splicing,oncogene homologChromosomal translocation(avian)NM_005379MYO1Amyosin IAMyosin, Actin-binding, ATP-binding,28296797Calmodulin-binding, Repeat,Multigene family, Polymorphism,Disease mutation, DeafnessNM_005381NCLnucleolinHypothetical protein28306798NM_005402RALAv-ral simianGTP-binding, Prenylation,28316799leukemia viralLipoproteinoncogene homologA (ras related)NM_005428VAV1vav 1 oncogeneHypothetical protein, SH3 domain,28326800Proto-oncogene, Phorbol-esterbinding, Zinc, SH2 domain, Guanine-nucleotide releasing factor, Repeat,PhosphorylationNM_005433YES1v-yes-1 YamaguchiProto-oncogene, Tyrosine-protein28336801sarcoma viralkinase, Phosphorylation,oncogene homolog 1Transferase, ATP-binding, Myristate,SH3 domain, SH2 domain,LipoproteinNM_005436D10S170DNA segment onProto-oncogene, Chromosomal28346802chromosome 10translocation, SH3-binding, Repeat(unique) 170NM_005439MLF2myeloid leukemiaNuclear protein28356803factor 2NM_005441CHAF1Bchromatin assemblyDNA replication, DNA repair, Cell28366804factor 1, subunit Bcycle, Nuclear protein,(p60)Phosphorylation, Repeat, WD repeatNM_005451ENIGMAenigma (LIM domainLIM domain, Metal-binding, Zinc28376805protein)NM_005463HNRPDLheterogeneousNucleocapsid, Ribonucleoprotein28386806nuclearribonucleoprotein D-likeNM_005466MED6mediator of RNATranscription regulation, Activator,28396807polymerase IIReceptor, Nuclear proteintranscription, subunit6 homolog (yeast)NM_005472KCNE3potassium voltage-Transport, Ion transport, Ionic28406808gated channel, lsk-channel, Voltage-gated channel,related family,Potassium channel, Potassium,member 3Potassium transport,Transmembrane, Glycoprotein,Disease mutationNM_005479FRAT1frequentlyWnt signaling pathway, Proto-28416809rearranged inoncogene, 3D-structureadvanced T-celllymphomasNM_005480TROAPtrophinin associatedCell adhesion, Repeat, Cytoskeleton28426810protein (tastin)NM_005488TOM1target of myb1Hypothetical protein, Transport,28436811(chicken)Protein transport, Membrane, 3D-structureNM_005490SH2D3ASH2 domainHypothetical protein28446812containing 3ANM_005498AP1M2adaptor-relatedGolgi stack, Protein transport,28456813protein complex 1,Transport, Coated pits, Endocytosis,mu 2 subunitPhosphorylation, Alternative splicingNM_005499UBA2SUMO-1 activatingCyclin, Hypothetical protein28466814enzyme subunit 2NM_005501ITGA3integrin, alpha 3Integrin, Cell adhesion, Receptor,28476815(antigen CD49C,Glycoprotein, Transmembrane,alpha 3 subunit ofSignal, Phosphorylation, Repeat,VLA-3 receptor)Alternative splicing, CalciumNM_005504BCAT1branched chainTransferase, Aminotransferase,28486816aminotransferase 1,Branched-chain amino acidcytosolicbiosynthesis, Pyridoxal phosphate,Hypothetical proteinNM_005505SCARB1scavenger receptorTranscription regulation, Nuclear28496817class B, member 1protein, Receptor, Transmembrane,Glycoprotein, Polymorphism,Alternative splicingNM_005507CFL1cofilin 1 (non-Nuclear protein, Actin-binding,28506818muscle)Cytoskeleton, PhosphorylationNM_005510DOM3Zdom-3 homolog ZTransferase, Serine/threonine-28516819(C. elegans)protein kinase, ATP-binding,Manganese, Nuclear protein,Alternative splicingNM_005512GARPglycoprotein AGlycoprotein, Leucine-rich repeat,28526820repetitionsRepeat, Transmembrane, SignalpredominantNM_005514HLA-BmajorGlycoprotein, MHC I, Signal,28536821histocompatibilityTransmembrane, Polymorphism, 3D-complex, class I, Bstructure, Alternative splicing,Hypothetical protein, SulfationNM_005516HLA-EmajorGlycoprotein, Transmembrane,28546822histocompatibilityHypothetical protein, MHC I, Signal,complex, class I, EPolymorphism, 3D-structureNM_005517HMGN2high-mobility groupHypothetical protein, Microtubule,28556823nucleosomal bindingGTP-binding, Multigene family,domain 2Nuclear protein, DNA-binding,PolymorphismNM_005527HSPA1Lheat shock 70 kDaATP-binding, Multigene family,28566824protein 1-likePolymorphismNM_005534IFNGR2interferon gammaReceptor, Transmembrane,28576825receptor 2 (interferonGlycoprotein, Signal, Repeatgamma transducer1)NM_005541INPP5Dinositol28586826polyphosphate-5-phosphatase,145 kDaNM_005548KARSlysyl-tRNAAminoacyl-tRNA synthetase, Protein28596827synthetasebiosynthesis, Ligase, ATP-binding,PolymorphismNM_005564LCN2lipocalin 2Glycoprotein, Lipocalin, Signal, 3D-28606828(oncogene 24p3)structure, Pyrrolidone carboxylic acidNM_005565LCP2lymphocyte cytosolicSH2 domain, Phosphorylation28616829protein 2 (SH2domain containingleukocyte protein of76 kDa)NM_005574LMO2LIM domain only 2Proto-oncogene, Repeat, LIM28626830(rhombotin-like 1)domain, Metal-binding, Zinc, Nuclearprotein, Alternative splicing,Chromosomal translocationNM_005578LPPLIM domainLIM domain, Metal-binding, Zinc28636831containing preferredtranslocation partnerin lipomaNM_005586MDFIMyoD family inhibitorDifferentiation28646832NM_005590MRE11AMRE11 meioticDNA repair, Hydrolase, Nuclease,28656833recombination 11Endonuclease, Exonuclease,homolog A (S. cerevisiae)Nuclear protein, Manganese,Meiosis, Alternative splicing,Disease mutation, Polymorphism,Hypothetical proteinNM_005598NHLH1nescient helix loopDNA-binding, Transcription28666834helix 1regulation, DifferentiationNM_005601NKG7natural killer cellTransmembrane28676835group 7 sequenceNM_005605PPP3CCprotein phosphataseHypothetical protein, Hydrolase,286868363 (formerly 2B),Iron, Manganese, Calmodulin-catalytic subunit,binding, Metal-binding, Zinc,gamma isoformMultigene family(calcineurin Agamma)NM_005607PTK2PTK2 proteinHypothetical protein, ATP-binding,28696837tyrosine kinase 2Transferase, Kinase, Tyrosine-protein kinase, Phosphorylation,Alternative splicing, 3D-structureNM_005608PTPRCAPprotein tyrosineTransmembrane, Phosphorylation28706838phosphatase,receptor type, C-associated proteinNM_005611RBL2retinoblastoma-like 2ATP-binding, Kinase,28716839(p130)Serine/threonine-protein kinase,Transferase, Transcriptionregulation, DNA-binding, Nuclearprotein, Cell cycle, Phosphorylation,Anti-oncogeneNM_005620S100A11S100 calciumCalcium-binding28726840binding protein A11(calgizzarin)NM_005621S100A12S100 calciumCalcium-binding, Zinc, Metal-28736841binding protein A12binding, Antibiotic, Fungicide, 3D-(calgranulin C)structureNM_005623CCL8chemokine (C—CCytokine, Chemotaxis, Signal,28746842motif) ligand 8Heparin-binding, Inflammatoryresponse, Polymorphism,Pyrrolidone carboxylic acid, 3D-structureNM_005625SDCBPsyndecan bindingCytoskeleton, Membrane,28756843protein (syntenin)Endoplasmic reticulum, Nuclearprotein, Phosphorylation, Repeat,PolymorphismNM_005646TARBP1TAR (HIV) RNA28766844binding protein 1NM_005647TBL1Xtransducin (beta)-likeRepeat, WD repeat287768451X-linkedNM_005654NR2F1nuclear receptorReceptor, Transcription regulation,28786846subfamily 2, group F,DNA-binding, Nuclear protein, Zinc-member 1finger, ActivatorNM_005658TRAF1TNF receptor-Apoptosis, Coiled coil28796847associated factor 1NM_005687FRSBphenylalanyl-tRNAAminoacyl-tRNA synthetase, Protein28806848synthetase beta-biosynthesis, Ligase, ATP-bindingsubunitNM_005690DNM1Ldynamin 1-likeHypothetical protein28816849NM_005697SCAMP2secretory carrierTransmembrane, Transport, Protein28826850membrane protein 2transport, Multigene familyNM_005704PTPRUprotein tyrosineGlycoprotein, Hydrolase, Receptor,28836851phosphatase,Repeat, Signal, Transmembrane,receptor type, UImmunoglobulin domainNM_005710PQBP1polyglutamineNuclear protein28846852binding protein 1NM_005713COL4A3BPcollagen, type IV,Transferase, Kinase,28856853alpha 3Serine/threonine-protein kinase,(GoodpastureCoiled coil, Alternative splicingantigen) bindingproteinNM_005716RGS19IP1regulator of G-28866854protein signalling 19interacting protein 1NM_005717ARPC5actin related proteinCytoskeleton288768552/3 complex, subunit5, 16 kDaNM_005720ARPC1Bactin related proteinHypothetical protein, Repeat, WD288868562/3 complex, subunitrepeat, Polymorphism1B, 41 kDaNM_005724TSPAN-3transmembrane 4Glycoprotein, Transmembrane28896857superfamily member 8NM_005725TSPAN-2tetraspan 2Glycoprotein, Transmembrane28906858NM_005730OS4CTD (carboxy-Hypothetical protein, Nuclear protein28916859terminal domain,RNA polymerase II,polypeptide A) smallphosphatase 2NM_005731ARPC2actin related proteinCytoskeleton289268602/3 complex, subunit2, 34 kDaNM_005732RAD50RAD50 homolog (S. cerevisiae)28936861NM_005733KIF20Akinesin familyMotor protein, Microtubule, ATP-28946862member 20Abinding, Coiled coil, Golgi stack,Protein transport, TransportNM_005736ACTR1AARP1 actin-relatedStructural protein, Cytoskeleton,28956863protein 1 homolog A,Multigene familycentractin alpha(yeast)NM_005737ARL7ADP-ribosylationGTP-binding, Multigene family,28966864factor-like 7Nuclear proteinNM_005741ZNF263zinc finger proteinTranscription regulation, Zinc-finger,28976865263Metal-binding, Nuclear protein, DNA-binding, Repeat, RepressorNM_005759ABI-2abl-interactor 2Kinase, SH3 domain28986866NM_005761PLXNC1plexin C128996867NM_005762TRIM28tripartite motif-Transcription regulation, Repressor,29006868containing 28Nuclear protein, Zinc-finger, Repeat,3D-structureNM_005770SERF2small EDRK-richHypothetical protein29016869factor 2NM_005771RDHLdehydrogenase/reductaseOxidoreductase29026870(SDR family)member 9NM_005772PLAARNA terminalRepeat, WD repeat, Hypothetical29036871phosphate cyclase-protein, Nuclear proteinlike 1NM_005773ZNF256zinc finger proteinTranscription regulation, DNA-29046872256binding, Zinc-finger, Metal-binding,Nuclear protein, RepeatNM_005787NOT56Lasparagine-linkedHypothetical protein, Transferase,29056873glycosylation 3Glycosyltransferase,homolog (yeast,Transmembrane, Endoplasmicalpha-1,3-reticulum, Disease mutationmannosyltransferase)NM_005797EVA1epithelial V-likeCell adhesion, Immunoglobulin29066874antigen 1domain, Transmembrane,Glycoprotein, SignalNM_005803FLOT1flotillin 1Membrane29076875NM_005805PSMD14proteasomeProteasome29086876(prosome,macropain) 26Ssubunit, non-ATPase, 14NM_005811GDF11growth differentiationGrowth factor, Cytokine,29096877factor 11Glycoprotein, SignalNM_005826HNRPRheterogeneousNucleocapsid, Ribonucleoprotein,29106878nuclearNuclear protein, RNA-binding,ribonucleoprotein RRepeatNM_005833RAB9P40Rab9 effector p4029116879NM_005834TIMM17Btranslocase of innerTransport, Protein transport,29126880mitochondrialTranslocation, Mitochondrion, Innermembrane 17membrane, Transmembranehomolog B (yeast)NM_005836UK114translational inhibitorNuclear protein29136881protein p14.5NM_005845ABCC4ATP-bindingATP-binding, Glycoprotein,29146882cassette, sub-familyTransmembrane, Transport, RepeatC (CFTR/MRP),member 4NM_005849IGSF6immunoglobulinSignal, Hypothetical protein29156883superfamily, member 6NM_005855RAMP1receptor (calcitonin)Signal, Transmembrane, Transport,29166884activity modifyingReceptorprotein 1NM_005860FSTL3follistatin-like 3Glycoprotein, Repeat, Signal,29176885(secretedChromosomal translocation, Proto-glycoprotein)oncogeneNM_005862STAG1stromal antigen 1Mitosis, Cell cycle, Chromosome29186886partition, Nuclear protein,PhosphorylationNM_005863NET1neuroepithelial cell29196887transforming gene 1NM_005865PRSS16protease, serine, 16Hydrolase, Serine protease, Signal29206888(thymus)NM_005866SR-BP1opioid receptor,Hypothetical protein, Receptor29216889sigma 1NM_005873RGS19regulator of G-Signal transduction inhibitor,29226890protein signalling 19Membrane, Lipoprotein, Palmitate,Phosphorylation, Autophagy, 3D-structureNM_005874LILRB2leukocyteReceptor, Repeat, Signal,29236891immunoglobulin-likeTransmembrane, Immune response,receptor, subfamilyImmunoglobulin domain,B (with TM and ITIMPhosphorylation, Glycoprotein,domains), member 2Antigen, Multigene family,Alternative splicing, PolymorphismNM_005884PAK4p21(CDKN1A)-Hypothetical protein, ATP-binding,29246892activated kinase 4Transferase, Serine/threonine-protein kinase, Phosphorylation,Alternative splicingNM_005886KATNB1katanin p80 (WDRepeat, WD repeat29256893repeat containing)subunit B 1NM_005888SLC25A3solute carrier familyMitochondrion, Inner membrane,2926689425 (mitochondrialRepeat, Transit peptide,carrier; phosphateTransmembrane, Transport,carrier), member 3Symport, Alternative splicing,Hypothetical proteinNM_005891ACAT2acetyl-Coenzyme AChaperone, ATP-binding, Multigene29276895acetyltransferase 2family, Transferase(acetoacetylCoenzyme Athiolase)NM_005892FMNLformin-like 1Hypothetical protein29286896NM_005898M11S1membraneGPI-anchor29296897component,chromosome 11,surface marker 1NM_005900MADH1MAD, mothersTranscription regulation,29306898againstPhosphorylation, Multigene family,decapentaplegic3D-structurehomolog 1(Drosophila)NM_005902MADH3MAD, mothersTranscription regulation,29316899againstPhosphorylation, Multigene family,decapentaplegic3D-structurehomolog 3(Drosophila)NM_005917MDH1malateOxidoreductase, Tricarboxylic acid29326900dehydrogenase 1,cycle, NADNAD (soluble)NM_005931MICBMHC class IGlycoprotein, Transmembrane, MHC29336901polypeptide-relatedsequence BNM_005932MIPEPmitochondrialHydrolase, Metalloprotease, Zinc,29346902intermediateTransit peptide, Mitochondrion,peptidaseMagnesium, Manganese, Calcium,Cobalt, IronNM_005935MLLT2myeloid/lymphoid orAlternative splicing, Chromosomal29356903mixed-lineagetranslocation, Proto-oncogene, DNA-leukemia (trithoraxbinding, Bromodomain, Nuclearhomolog,protein, Zinc-finger, Metal-binding,Drosophila);Transcription regulation, Repeat,translocated to, 2Hypothetical protein,Serine/threonine-protein kinase,Transferase, ATP-binding, TranNM_005950MT1Gmetallothionein 1GMetal-binding, Metal-thiolate cluster,29366904Zinc, Copper, Cadmium, AcetylationNM_005952MT1Xmetallothionein 1XHypothetical protein, Metal-binding,29376905Metal-thiolate cluster, Zinc, Copper,Cadmium, AcetylationNM_005953MT2Ametallothionein 2AMetal-binding, Metal-thiolate cluster,29386906Zinc, Acetylation, 3D-structureNM_005954MT3metallothionein 3Metal-binding, Metal-thiolate cluster,29396907(growth inhibitoryZinc, Copper, Acetylationfactor (neurotrophic))NM_005955MTF1metal-regulatoryHypothetical protein, Metal-binding,29406908transcription factor 1Zinc, Zinc-fingerNM_005965MYLKmyosin, lightImmunoglobulin domain, Kinase,29416909polypeptide kinaseATP-binding, Repeat,Serine/threonine-protein kinase,Transferase, Calmodulin-binding,Phosphorylation, Alternativeinitiation, Alternative splicingNM_005969NAP1L4nucleosomeNuclear protein29426910assembly protein 1-like 4NM_005975PTK6PTK6 proteinTransferase, Tyrosine-protein29436911tyrosine kinase 6kinase, ATP-binding, SH2 domain,SH3 domain, PhosphorylationNM_005979S100A13S100 calciumCalcium-binding29446912binding protein A13NM_005980S100PS100 calciumCalcium-binding, Placenta, 3D-29456913binding protein PstructureNM_005988SPRR2Asmall proline-richKeratinocyte, Repeat, Multigene29466914protein 2AfamilyNM_005990STK10serine/threonineKinase, Transferase,29476915kinase 10Serine/threonine-protein kinase,ATP-binding, Phosphorylation,Coiled coilNM_005998CCT3chaperoninChaperone, ATP-binding, Multigene29486916containing TCP1,family, Hypothetical proteinsubunit 3 (gamma)NM_006002UCHL3ubiquitin carboxyl-Ubl conjugation pathway, Hydrolase,29496917terminal esterase L3Thiol protease, Multigene family, 3D-(ubiquitinstructurethiolesterase)NM_006018HM74putative chemokineG-protein coupled receptor,29506918receptorTransmembraneNM_006019TCIRG1T-cell, immuneHydrogen ion transport,29516919regulator 1, ATPase,Transmembrane, Glycoprotein,H+ transporting,Alternative splicing, Hypotheticallysosomal V0 proteinproteina isoform 3NM_006022TSC22transforming growthHypothetical protein, Transcription29526920factor beta-regulation, Repressor, Nuclearstimulated proteinproteinTSC-22NM_006027EXO1exonuclease 1Exonuclease, Hypothetical protein29536921NM_006029PNMA1paraneoplasticAntigen, Tumor antigen, Nuclear29546922antigen MA1proteinNM_006031PCNT2pericentrin 2Coiled coil, Hypothetical protein29556923(kendrin)NM_006034TP53I11tumor protein p53Hypothetical protein29566924inducible protein 11NM_006053TCIRG1T-cell, immuneHydrogen ion transport,29576925regulator 1, ATPase,Transmembrane, Glycoprotein,H+ transporting,Alternative splicing, Hypotheticallysosomal V0 proteinproteina isoform 3NM_006054RTN3reticulon 3Hypothetical protein,29586926Transmembrane, EndoplasmicreticulumNM_006055LANCL1LanC lantibioticTransmembrane29596927synthetasecomponent C-like 1(bacterial)NM_006060ZNFN1A1zinc finger protein,Transcription regulation, Activator,29606928subfamily 1A, 1Zinc-finger, Metal-binding, DNA-(lkaros)binding, Nuclear protein, Repeat,Alternative splicingNM_006061SGP28cysteine-richGlycoprotein, Signal, Multigene29616929secretory protein 3family, PolymorphismNM_006069MRVI1murine retrovirus29626930integration site 1homologNM_006070TFGTRK-fused geneHypothetical protein, Ligase, GMP29636931biosynthesis, Purine biosynthesis,ATP-binding, GlutamineamidotransferaseNM_006079CITED2Cbp/p300-interactingTranscription regulation, Nuclear29646932transactivator, withprotein, Alternative splicingGlu/Asp-richcarboxy-terminaldomain, 2NM_006088TUBB2tubulin, beta, 2Microtubule, GTP-binding, Multigene29656933family, Hypothetical proteinNM_006093PRG3proteoglycan 329666934NM_006097MYL9myosin, lightMyosin, Calcium-binding, Muscle29676935polypeptide 9,protein, Phosphorylation,regulatoryAcetylation, Multigene familyNM_006103WFDC2WAP four-disulfideSerine protease inhibitor, Repeat,29686936core domain 2Signal, Glycoprotein, AlternativesplicingNM_006107LUC7Aacid-induciblePhosphorylation, Hypothetical29696937phosphoproteinproteinNM_006109SKB1SKB1 homolog (S. pombe)Transferase, Methyltransferase,29706938Alternative splicingNM_006111ACAA2acetyl-Coenzyme AAcyltransferase, Transferase, Fatty29716939acyltransferase 2acid metabolism, Mitochondrion,(mitochondrial 3-Transit peptideoxoacyl-CoenzymeA thiolase)NM_006113VAV3vav 3 oncogeneSH3 domain, Phorbol-ester binding,29726940Zinc, SH2 domain, Repeat, Guanine-nucleotide releasing factor,Alternative splicingNM_006115PRAMEpreferentiallyAntigen29736941expressed antigen inmelanomaNM_006117PECIperoxisomal D3,D2-Isomerase, Hypothetical protein,29746942enoyl-CoAPeroxisomeisomeraseNM_006135CAPZA1capping proteinActin-binding, Multigene family, 3D-29756943(actin filament)structure, Actin cappingmuscle Z-line, alpha 1NM_006138MS4A3membrane-spanningReceptor, Transmembrane,297669444-domains,Alternative splicing, Multigene familysubfamily A,member 3(hematopoietic cell-specific)NM_006139CD28CD28 antigen (Tp44)Immunoglobulin domain, T-cell,29776945Glycoprotein, Signal,Transmembrane, Alternative splicingNM_006140CSF2RAcolony stimulatingReceptor, Transmembrane,29786946factor 2 receptor,Glycoprotein, Signal, Alternativealpha, low-affinitysplicing(granulocyte-macrophage)NM_006142SFNstratifinMultigene family29796947NM_006144GZMAgranzyme AHydrolase, Serine protease,29806948(granzyme 1,Zymogen, Signal, T-cell, Cytolysis,cytotoxic T-Apoptosis, 3D-structurelymphocyte-associated serineesterase 3)NM_006145DNAJB1DnaJ (Hsp40)Heat shock, Chaperone, 3D-29816949homolog, subfamilystructureB, member 1NM_006147IRF6interferon regulatoryTranscription regulation, DNA-29826950factor 6binding, Nuclear protein,Polymorphism, Disease mutationNM_006148LASP1LIM and SH3 protein 1LIM domain, Metal-binding, Zinc,29836951SH3 domainNM_006159NELL2NEL-like 2 (chicken)EGF-like domain, Glycoprotein,29846952Repeat, SignalNM_006161NEUROG1neurogenin 1DNA-binding, Nuclear protein,29856953Transcription regulation, Activator,Neurogenesis, Developmentalprotein, DifferentiationNM_006176NRGNneurogranin (proteinCalmodulin-binding,29866954kinase C substrate,Phosphorylation, NeuroneRC3)NM_006185NUMA1nuclear mitoticImmunoglobulin domain,29876955apparatus protein 1Glycoprotein, Signal, Alternativesplicing, Hypothetical proteinNM_006196PCBP1poly(rC) bindingNuclear protein, RNA-binding,29886956protein 1Ribonucleoprotein, DNA-binding,Phosphorylation, RepeatNM_006202PDE4AphosphodiesteraseHydrolase, cAMP, Alternative298969574A, cAMP-specificsplicing, Multigene family(phosphodiesteraseE2 dunce homolog,Drosophila)NM_006205PDE6HphosphodiesteraseHydrolase, cGMP, Vision299069586H, cGMP-specific,cone, gammaNM_006214PHYHphytanoyl-CoAOxidoreductase, Peroxisome,29916959hydroxylaseVitamin C, Iron, Transit peptide,(Refsum disease)Disease mutation, Deafness,Retinitis pigmentosa, Hydrolase,cGMP, Vision, Prenylation,Lipoprotein, Membrane, Hypotheticalprotein, CollagenNM_006224PITPNphosphotidylinositolLipid-binding, Transport29926960transfer proteinNM_006225PLCD1phospholipase C,Hydrolase, Lipid degradation,29936961delta 1Transducer, Calcium-binding,RepeatNM_006238PPARDperoxisomeReceptor, Transcription regulation,29946962proliferativeActivator, DNA-binding, Nuclearactivated receptor,protein, Zinc-finger, Multigene family,delta3D-structure, Metal-bindingNM_006242PPP1R3Dprotein phosphataseHydrolase, Glycogen metabolism299569631, regulatory subunit3DNM_006243PPP2R5Aprotein phosphatasePhosphorylation, Multigene family299669642, regulatory subunitB (B56), alphaisoformNM_006244PPP2R5Bprotein phosphatasePhosphorylation, Alternative splicing,299769652, regulatory subunitMultigene familyB (B56), betaisoformNM_006254PRKCDprotein kinase C,ATP-binding, Transferase,29986966deltaScrine/threonine-protein kinase,Phorbol-ester binding, Zinc, Repeat,Polymorphism, Phosphorylation,MembraneNM_006272S100BS100 calciumCalcium-binding, Zinc, Metal-29996967binding protein, betabinding, 3D-structure(neural)NM_006284TAF10TAF10 RNATranscription regulation, Nuclear30006968polymerase II, TATAprotein, Polymorphismbox binding protein(TBP)-associatedfactor, 30 kDaNM_006287TFPItissue factorSerine protease inhibitor,30016969pathway inhibitorGlycoprotein, Repeat, Blood(lipoprotein-coagulation, Signal, Alternativeassociatedsplicing, 3D-structure, Polymorphismcoagulation inhibitor)NM_006289TLN1talin 1Hypothetical protein, Structural30026970protein, CytoskeletonNM_006290TNFAIP3tumor necrosisApoptosis, DNA-binding, Zinc-finger,30036971factor, alpha-inducedRepeat, Hypothetical proteinprotein 3NM_006291TNFAIP2tumor necrosisAngiogenesis30046972factor, alpha-inducedprotein 2NM_006304DSS1split hand/footPolymorphism, 3D-structure30056973malformation(ectrodactyly) type 1NM_006310NPEPPSaminopeptidaseHydrolase, Metalloprotease,30066974puromycin sensitiveAminopeptidase, Zinc, NuclearproteinNM_006314CNK1connector enhancerHypothetical protein, Kinase30076975of KSR-like(Drosophila kinasesuppressor of ras)NM_006317BASP1brain abundant,Membrane, Myristate, Neurone,30086976membrane attachedLipoproteinsignal protein 1NM_006319CDIPTCDP-diacylglycerol-Transferase, Phospholipid30096977inositol 3-biosynthesis, Transmembrane,phosphatidyltransferaseMagnesium, Manganese(phosphatidylinositolsynthase)NM_006321ARIH2ariadne homolog 2Ubl conjugation pathway, Nuclear30106978(Drosophila)protein, Coiled coil, Zinc-finger,RepeatNM_006323SEC24BSEC24 related geneTransport, Protein transport, Golgi30116979family, member B (S. cerevisiae)stack, Endoplasmic reticulum,Multigene familyNM_006324CFDP1craniofacial30126980development protein 1NM_006327TIMM23translocase of innerTransport, Protein transport,30136981mitochondrialTranslocation, Mitochondrion, Innermembrane 23membrane, Outer membrane,homolog (yeast)TransmembraneNM_006342TACC3transforming, acidicCoiled coil30146982coiled-coil containingprotein 3NM_006344HML2C-type (calciumLectin30156983dependent,carbohydrate-recognition domain)lectin, superfamilymember 13(macrophage-derived)NM_006345C4orf1solute carrier familyHypothetical protein3016698430 (zinc transporter),member 9NM_006346PIBF1progesterone-30176985induced blockingfactor 1NM_006351TIMM44translocase of innerMitochondrion, Inner membrane,30186986mitochondrialTransport, Protein transport,membrane 44Translocation, Transit peptide, ATP-homolog (yeast)binding, ReceptorNM_006353HMGN4high mobility groupNuclear protein, DNA-binding30196987nucleosomal bindingdomain 4NM_006355TRIM38tripartite motif-Zinc-finger, Polymorphism30206988containing 38NM_006360GA17dendritic cell proteinHypothetical protein30216989NM_006362NXF1nuclear RNA exportTransport, mRNA transport, Nuclear30226990factor 1protein, RNA-binding, Repeat,Leucine-rich repeat, Multigenefamily, 3D-structureNM_006367CAPCAP, adenylateMembrane, Multigene family30236991cyclase-associatedprotein 1 (yeast)NM_006374STK25serine/threonineHypothetical protein, ATP-binding,30246992kinase 25 (STE20Transferase, Serine/threonine-homolog, yeast)protein kinase, PhosphorylationNM_006377UNC13unc-13 homolog BPhorbol-ester binding30256993(C. elegans)NM_006383KIP2DNA-dependentCalcium-binding, Repeat30266994protein kinasecatalytic subunit-interacting protein 2NM_006386DDX17DEAD (Asp-Glu-Ala-ATP-binding, RNA-binding, Helicase,30276995Asp) box polypeptideNuclear protein17NM_006387CHERPcalcium homeostasis30286996endoplasmicreticulum proteinNM_006389HYOU1hypoxia up-regulated 1ATP-binding, Chaperone,30296997Endoplasmic reticulum, Signal,GlycoproteinNM_006395GSA7APG7 autophagy 7-Hypothetical protein30306998like (S. cerevisiae)NM_006399BATFbasic leucine zipperTranscription regulation, DNA-30316999transcription factor,binding, Repressor, Phosphorylation,ATF-likeNuclear proteinNM_006403NEDD9neural precursor cellPhosphorylation, SH3 domain, Cell30327000expressed,adhesion, Growth regulation,developmentallyCytoskeleton, Mitosis, Nucleardown-regulated 9proteinNM_006404PROCRprotein C receptor,Blood coagulation, Receptor, Signal,30337001endothelial (EPCR)Transmembrane, Glycoprotein,Antigen, Polymorphism, 3D-structureNM_006405TM9SF1transmembrane 9Hypothetical protein, Plasmid,30347002superfamily member 1Signal, Transmembrane,GlycoproteinNM_006406PRDX4peroxiredoxin 4Antioxidant, Peroxidase,30357003Oxidoreductase, Redox-activecenterNM_006421BIG1brefeldin A-inhibitedGuanine-nucleotide releasing factor30367004guanine nucleotide-exchange protein 1NM_006429CCT7chaperoninChaperone, ATP-binding, Multigene30377005containing TCP1,familysubunit 7 (eta)NM_006430CCT4chaperoninChaperone, ATP-binding, Multigene30387006containing TCP1,family, Hypothetical proteinsubunit 4 (delta)NM_006431CCT2chaperoninATP-binding, Chaperone, Multigene30397007containing TCP1,familysubunit 2 (beta)NM_006433GNLYgranulysinAntibiotic, Fungicide, Signal, T-cell,30407008Alternative splicing, 3D-structureNM_006435IFITM2interferon inducedInterferon induction,30417009transmembraneTransmembrane, Polymorphismprotein 2 (1-8D)NM_006441MTHFS5,10-Ligase, Folate-binding, Acetylation,30427010methenyltetrahydrofolateMagnesium, Hypothetical proteinsynthetase (5-formyltetrahydrofolatecyclo-ligase)NM_006451PAIP1poly(A) bindingHypothetical protein30437011protein interactingprotein 1NM_006452PAICSphosphoribosylaminoimidazoleMultifunctional enzyme, Purine30447012carboxylase,biosynthesis, Ligase, Lyase,phosphoribosylaminoimidazoleDecarboxylasesuccinocarboxamidesynthetaseNM_006455SC65synaptonemalNuclear protein, Antigen30457013complex proteinSC65NM_006456STHMsialyltransferaseTransferase, Glycosyltransferase,30467014Glycoprotein, Transmembrane,Signal-anchor, Golgi stackNM_006461SPAG5sperm associatedHypothetical protein30477015antigen 5NM_006465DRIL2dead ringer30487016(Drosophila)-like 2(bright and deadringer)NM_006469IVNS1ABPinfluenza virus NS1AHypothetical protein30497017binding proteinNM_006471MLC-Bmyosin regulatoryMyosin, Calcium-binding, Muscle30507018light chain MRCL3protein, Phosphorylation,Acetylation, Multigene familyNM_006472TXNIPthioredoxin30517019interacting proteinNM_006477RRP22RAS-related onGTP-binding, Prenylation,30527020chromosome 22LipoproteinNM_006480RGS14regulator of G-Repeat, Thiol protease inhibitor,30537021protein signalling 14Alternative splicing, Phosphorylation,Signal transduction inhibitorNM_006495EVI2Becotropic viralProto-oncogene, Transmembrane,30547022integration site 2BGlycoprotein, SignalNM_006542SPHARS-phase response30557023(cyclin-related)NM_006545NPR2Lhomologous to yeastHypothetical protein30567024nitrogen permease(candidate tumorsuppressor)NM_006560CUGBP1CUG triplet repeat,Hypothetical protein, mRNA30577025RNA binding protein 1processing, RNA-binding, Repeat,Nuclear protein, Alternative splicingNM_006567FARS1phenylalanine-tRNAAminoacyl-tRNA synthetase30587026synthetase 1(mitochondrial)NM_006568CGR19cell growth regulatorMetal-binding, Zinc, Zinc-finger30597027with ring fingerdomain 1NM_006575MAP4K5mitogen-activatedATP-binding, Kinase, Transferase,30607028protein kinaseTyrosine-protein kinase,kinase kinase kinase 5Serine/threonine-protein kinaseNM_006578GNB5guanine nucleotideRepeat, WD repeat, Transducer,30617029binding protein (GAlternative splicing, Multigene family,protein), beta 5Hypothetical proteinNM_006589C1orf2chromosome 1 openHypothetical protein30627030reading frame 2NM_006598SLC12A7solute carrier familyTransport, Ion transport, Symport,3063703112Potassium, Potassium transport,(potassium/chlorideTransmembrane, Alternative splicingtransporters),member 7NM_006636MTHFD2methyleneMultifunctional enzyme, One-carbon30647032tetrahydrofolatemetabolism, Oxidoreductase, NAD,dehydrogenaseHydrolase, Mitochondrion, Transit(NAD+ dependent),peptide, MagnesiummethenyltetrahydrofolatecyclohydrolaseNM_006638RNASEP1ribonuclease P1Hydrolase, Nuclear protein, tRNA30657033processingNM_006643SDCCAG3serologically definedHypothetical protein30667034colon cancer antigen 3NM_006644HSPH1heat shockATP-binding, Heat shock, Multigene30677035105 kDa/110 kDafamily, Alternative splicingprotein 1NM_006646WASF3WAS protein family,Actin-binding, Coiled coil30687036member 3NM_006650CPLX2complexin 2Neurotransmitter transport30697037NM_006660CLPXClpX caseinolyticHypothetical protein, ATP-binding,30707038protease X homologChaperone, Mitochondrion, Transit(E. coli)peptide, Zinc-fingerNM_006667PGRMC1progesteroneReceptor, Steroid-binding,30717039receptor membraneTransmembrane, Microsomecomponent 1NM_006669LILRB1leukocyteReceptor, Repeat, Signal,30727040immunoglobulin-likeTransmembrane, Immune response,receptor, subfamilyImmunoglobulin domain,B (with TM and ITIMPhosphorylation, Glycoprotein,domains), member 1Antigen, Multigene family,Alternative splicing, Polymorphism,3D-structureNM_006676USP20ubiquitin specificUbl conjugation pathway, Hydrolase,30737041protease 20Thiol protease, Multigene familyNM_006680ME3malic enzyme 3,Oxidoreductase, NADP,30747042NADP(+)-Mitochondrion, Transit peptidedependent,mitochondrialNM_006681NMUneuromedin UNeuropeptide, Cleavage on pair of30757043basic residues, Amidation, SignalNM_006682FGL2fibrinogen-like 2T-cell, Glycoprotein, Signal,30767044PolymorphismNM_006700FLN29FLN29 gene product30777045NM_006704SUGT1SGT1, suppressor ofUbl conjugation pathway, Repeat,30787046G2 allele of SKP1TPR repeat(S. cerevisiae)NM_006705GADD45Ggrowth arrest andDifferentiation, Apoptosis30797047DNA-damage-inducible, gammaNM_006706TCERG1transcription30807048elongation regulator1 (CA150)NM_006708GLO1glyoxalase ILyase, Zinc, Polymorphism, 3D-30817049structureNM_006710COP9COP9 signalosome30827050subunit 8NM_006719ABLIM1actin binding LIMLIM domain, Metal-binding, Zinc,30837051protein 1Hypothetical proteinNM_006721ADKadenosine kinaseTransferase, Kinase, Purine salvage,30847052Magnesium, Alternative splicing, 3D-structureNM_006732FOSBFBJ murineNuclear protein, DNA-binding30857053osteosarcoma viraloncogene homolog BNM_006747SIPA1signal-inducedGTPase activation, Coiled coil,30867054proliferation-Nuclear protein, Membraneassociated gene 1NM_006748SLASrc-like-adaptorSH2 domain, SH3 domain,30877055Myristate, Phosphorylation,LipoproteinNM_006750SNTB2syntrophin, beta 2Actin-binding, Cytoskeleton,30887056(dystrophin-Microtubule, Calcium-binding,associated proteinCalmodulin-binding, Membrane,A1, 59 kDa, basicPhosphorylation, Repeat,component 2)Polymorphism, Multigene family,Alternative splicingNM_006755TALDO1transaldolase 1Hypothetical protein, Pentose shunt,30897057Transferase, Disease mutation, 3D-structureNM_006756TCEA1transcriptionTranscription regulation, Zinc-finger,30907058elongation factor ADNA-binding, Nuclear protein,(SII), 1Alternative splicing, 3D-structureNM_006760UPK2uroplakin 2Endoplasmic reticulum, Signal,30917059Transmembrane, GlycoproteinNM_006761YWHAEtyrosine 3-Neurone, Acetylation, Multigene30927060monooxygenase/tryptophanfamily5-monooxygenaseactivation protein,epsilon polypeptideNM_006762LAPTM5Lysosomal-Transmembrane, Lysosome30937061associatedmultispanningmembrane protein-5NM_006763BTG2BTG family, member 2Signal30947062NM_006770MARCOmacrophageCollagen, Transmembrane,30957063receptor withReceptor, Glycoprotein, Signal-collagenousanchorstructureNM_006783GJB6gap junction protein,Gap junction, Transmembrane,30967064beta 6 (connexin 30)Deafness, Disease mutationNM_006784WDR3WD repeat domain 3WD repeat, Repeat, Nuclear protein30977065NM_006787MAGED2melanoma antigen,Antigen, Multigene family,30987066family D, 2Polymorphism, Alternative splicingNM_006795EHD1EH-domainCalcium-binding, ATP-binding,30997067containing 1Coiled coilNM_006801KDELR1KDEL (Lys-Asp-Glu-Endoplasmic reticulum,31007068Leu) endoplasmicTransmembrane, Protein transport,reticulum proteinReceptor, Hypothetical protein,retention receptor 1TransportNM_006805HNRPA0heterogeneousNuclear protein, RNA-binding,31017069nuclearRibonucleoprotein, Repeat,ribonucleoprotein A0MethylationNM_006806BTG3BTG family, member 3Alternative splicing31027070NM_006810PDIRfor protein disulfideIsomerase, Redox-active center,31037071isomerase-relatedEndoplasmic reticulum, Repeat,SignalNM_006812OS-9amplified inHypothetical protein, Signal,31047072osteosarcomaAlternative splicing, PolymorphismNM_006818AF1QALL1-fused geneProto-oncogene, Chromosomal31057073from chromosometranslocation1qNM_006823PKIAprotein kinaseProtein kinase inhibitor, 3D-structure31067074(cAMP-dependent,catalytic) inhibitoralphaNM_006824EBNA1BP2EBNA1 bindingRibosome biogenesis, Nuclear31077075protein 2protein, Coiled coilNM_006825CKAP4cytoskeleton-Hypothetical protein31087076associated protein 4NM_006826YWHAQtyrosine 3-Transcription regulation, Repressor,31097077monooxygenase/tryptophanActivator, Nuclear protein, Zinc-5-finger, Metal-binding, DNA-binding,monooxygenaseRepeat, 3D-structure, Tight junction,activation protein,Immunoglobulin domain,theta polypeptideGlycoprotein, Transmembrane,Signal, Neurone, Phosphorylation,Multigene familyNM_006827TMP21transmembraneTransport, Protein transport,31107078trafficking proteinTransmembrane, Signal,Glycoprotein, Golgi stack,PolymorphismNM_006838METAP2methionylHydrolase, Aminopeptidase, Cobalt,31117079aminopeptidase 23D-structure, Hypothetical proteinNM_006840LILRB5leukocyteReceptor, Repeat, Signal,31127080immunoglobulin-likeTransmembrane, Immune response,receptor, subfamilyImmunoglobulin domain,B (with TM and ITIMPhosphorylation, Glycoprotein,domains), member 2Antigen, Multigene family,Alternative splicingNM_006863LILRA1leukocyteImmune response, Receptor,31137081immunoglobulin-likeRepeat, Signal, Transmembrane,receptor, subfamilyImmunoglobulin domain,B (with TM and ITIMGlycoprotein, Antigen, Alternativedomains), member 1splicing, Multigene familyNM_006864LILRB3leukocyteReceptor, Repeat, Signal,31147082immunoglobulin-likeTransmembrane, Immune response,receptor, subfamilyImmunoglobulin domain,B (with TM and ITIMPhosphorylation, Glycoprotein,domains), member 3Antigen, Multigene family,Alternative splicing, PolymorphismNM_006865LILRA3leukocyteReceptor, Repeat, Signal, Immune31157083immunoglobulin-likeresponse, Immunoglobulin domain,receptor, subfamilyGlycoprotein, Antigen, MultigeneA (without TMfamily, Polymorphismdomain), member 3NM_006866LILRA2leukocyteImmune response, Receptor,31167084immunoglobulin-likeRepeat, Signal, Transmembrane,receptor, subfamilyImmunoglobulin domain,B (with TM and ITIMGlycoprotein, Antigen, Alternativedomains), member 1splicing, Polymorphism, MultigenefamilyNM_006868RAB31RAB31, memberGTP-binding, Lipoprotein,31177085RAS oncogenePrenylationfamilyNM_006869CENTA1centaurin, alpha 131187086NM_006876B3GNT6UDP-Transferase, Glycosyltransferase,31197087GlcNAc:betaGalTransmembrane, Signal-anchor,beta-1,3-N-Glycoprotein, Golgi stackacetylglucosaminyltransferase 6NM_006890CEACAM7carcinoembryonicImmunoglobulin domain, Antigen,31207088antigen-related cellMembrane, Signal, Glycoprotein,adhesion molecule 7Lipoprotein, GPI-anchor, Repeat,Alternative splicingNM_006892DNMT3BDNA (cytosine-5-)-Transferase, Methyltransferase,31217089methyltransferase 3Zinc-finger, Zinc, Metal-binding,betaNuclear protein, Ubl conjugation,Alternative splicing, DiseasemutationNM_006913RNF5ring finger protein 5Hypothetical protein31227090NM_006923SDF2stromal cell-derivedSignal, Repeat31237091factor 2NM_006930SKP1AS-phase kinase-Ubl conjugation pathway, Alternative31247092associated proteinsplicing, 3D-structure1A (p19A)NM_006931SLC2A3solute carrier familySugar transport, Transmembrane,312570932 (facilitated glucoseTransport, Glycoprotein, Multigenetransporter),familymember 3NM_006932SMTNsmoothelinStructural protein, Alternative31267094splicingNM_006936SMT3H1SMT3 suppressor ofUbl conjugation pathway31277095mif two 3 homolog 1(yeast)NM_006938SNRPD1small nuclearNuclear protein, Ribonucleoprotein,31287096ribonucleoprotein D1mRNA splicing, mRNA processing,polypeptide 16 kDaSystemic lupus erythematosus,Repeat, Methylation, 3D-structureNM_006941SOX10SRY (sexTranscription regulation, DNA-31297097determining regionbinding, Nuclear protein, DiseaseY)-box 10mutation, Hirschsprung disease,DeafnessNM_006945SPRR2Bsmall proline-richKeratinocyte, Repeat, Multigene31307098protein 2BfamilyNM_006947SRP72signal recognitionATP-binding, Kinase, Transferase,31317099particle 72 kDaSignal recognition particle,RibonucleoproteinNM_006987RPH3ALrabphilin 3A-likeHypothetical protein31327100(without C2domains)NM_006993NPM3nucleophosmin/nucleoplasmin, 3Nuclear protein, Chaperone,31337101PhosphorylationNM_007000UPK1Auroplakin 1AHypothetical protein,31347102Transmembrane, GlycoproteinNM_007007CPSF6cleavage and31357103polyadenylationspecific factor 6,68 kDaNM_007008RTN4reticulon 4Endoplasmic reticulum, Alternative31367104splicing, Transmembrane,Hypothetical proteinNM_007014WWP2Nedd-4-likeUbl conjugation pathway, Ligase,31377105ubiquitin-proteinRepeatligaseNM_007022101F6putative tumor31387106suppressor 101F6NM_007024PL6placental protein 6Transmembrane31397107NM_007032HRIHFB2122Tara-like proteinHypothetical protein, Cytoskeleton,31407108Actin-binding, Coiled coil, NuclearproteinNM_007033RER1RER1 homolog (S. cerevisiae)Transmembrane, Golgi stack31417109NM_007034DNAJB4DnaJ (Hsp40)Chaperone, Heat shock31427110homolog, subfamilyB, member 4NM_007043HRB2HIV-1 rev binding31437111protein 2NM_007054KIF3Akinesin familyMotor protein, Microtubule, ATP-31447112member 3Abinding, Coiled coil, NeuroneNM_007056SWAP2splicing factor,mRNA processing, mRNA splicing,31457113arginine/serine-richNuclear protein, Alternative splicing,16 (suppressor-of-Polymorphismwhite-apricothomolog,Drosophila)NM_007059KPTNkaptin (actin binding31467114protein)NM_007062PWP1nuclearRepeat, WD repeat, Nuclear protein,31477115phosphoproteinPhosphorylationsimilar to S. cerevisiaePWP1NM_007063TBC1D8TBC1 domain family,GTPase activation31487116member 8 (withGRAM domain)NM_007065CDC37CDC37 cell divisionChaperone31497117cycle 37 homolog (S. cerevisiae)NM_007070FAP48glomulin, FKBPCoiled coil, Phosphorylation,31507118associated proteinAlternative splicing, Diseasemutation, PolymorphismNM_007074CORO1Acoronin, actinActin-binding, Repeat, WD repeat,31517119binding protein, 1ACoiled coil, PolymorphismNM_007077AP4S1adaptor-relatedCoated pits, Endocytosis31527120protein complex 4,sigma 1 subunitNM_007098CLTCL1clathrin, heavyCoated pits, Alternative splicing31537121polypeptide-like 1NM_007099ACP1acid phosphatase 1,Hydrolase, Acetylation, Alternative31547122solublesplicing, Polymorphism, 3D-structureNM_007108TCEB2transcriptionTranscription regulation, Ubl31557123elongation factor Bconjugation pathway, Nuclear(SIII), polypeptide 2protein, 3D-structure(18 kDa, elongin B)NM_007115TNFAIP6tumor necrosisCell adhesion, Signal, Glycoprotein,31567124factor, alpha-inducedPolymorphism, 3D-structureprotein 6NM_007145ZNF146zinc finger proteinZinc-finger, DNA-binding, Metal-31577125146binding, Nuclear protein, RepeatNM_007152ZNF195zinc finger proteinZinc-finger, Metal-binding, DNA-31587126195binding, Nuclear protein, AlternativesplicingNM_007161LST1leukocyte specificSignal, Immune response, Cell31597127transcript 1shape, Transmembrane, Alternativesplicing, ReceptorNM_007169PEMTphosphatidylethanolPhospholipid biosynthesis,31607128amine N-Transferase, Methyltransferase,methyltransferaseTransmembrane, Mitochondrion,Endoplasmic reticulum,PolymorphismNM_007172NUP50nucleoporin 50 kDaHypothetical protein, Nuclear31617129protein, Transport, Protein transport,Repeat, PorinNM_007178UNRIPunr-interactingHypothetical protein, Repeat, WD31627130proteinrepeatNM_007186CEP2centrosomal protein 2Cell cycle, Coiled coil,31637131Phosphorylation, Alternative splicing,PolymorphismNM_007205TREX2three prime repairHypothetical protein, Proteasome,31647132exonuclease 2ExonucleaseNM_007208MRPL3mitochondrialRibosomal protein, Mitochondrion31657133ribosomal protein L3NM_007212RNF2ring finger protein 2Metal-binding, Zinc, Zinc-finger31667134NM_007213JM4JM4 protein31677135NM_007219RNF24ring finger protein 24Zinc-finger31687136NM_007222ZHX1zinc-fingers andHomeobox, Metal-binding, Nuclear31697137homeoboxes 1protein, Zinc, Zinc-fingerNM_007238PXMP4peroxisomalPeroxisome, Transmembrane,31707138membrane protein 4,Glycoprotein, Polymorphism24 kDaNM_007240DUSP12dual specificityHydrolase, Zinc, Metal-binding31717139phosphatase 12NM_007248TREX1three prime repairHypothetical protein, Exonuclease31727140exonuclease 1NM_007255B4GALT7xylosylprotein betaGlycosyltransferase, Transferase,317371411,4-Glycoprotein, Transmembrane,galactosyltransferase,Signal-anchor, Golgi stack,polypeptide 7Multigene family, Disease mutation,(galactosyltransferaseEhlers-Danlos syndromeI)NM_007274BACHbrain acyl-CoAHydrolase, Serine esterase, Repeat,31747142hydrolaseAlternative splicingNM_007278GABARAPGABA(A) receptor-Receptor31757143associated proteinNM_007284PTK9Lprotein tyrosineHypothetical protein, Kinase31767144kinase 9-like (A6-related protein)NM_007311BZRPbenzodiazapineMitochondrion, Receptor,31777145receptor (peripheral)Transmembrane, PolymorphismNM_007317KIF22kinesin familyDNA-binding, Motor protein,31787146member 22Microtubule, ATP-binding, Coiledcoil, Nuclear proteinNM_007318PSEN1presenilin 1Transmembrane, Phosphorylation,31797147(Alzheimer diseaseEndoplasmic reticulum, Golgi stack,3)Alzheimer's disease, Diseasemutation, Polymorphism, AlternativesplicingNM_007320RANBP3RAN binding protein 3Hypothetical protein31807148NM_007334KLRD1killer cell lectin-likeAntigen, Receptor, Glycoprotein,31817149receptor subfamilyTransmembrane, Signal-anchor,D, member 1Lectin, Alternative splicing, 3D-structureNM_007346OGFRopioid growth factorReceptor, Growth regulation,31827150receptorRepeat, Alternative splicingNM_007360D12S2489Ekiller cell lectin-likeReceptor, Transmembrane,31837151receptor subfamilyMultigene family, Signal-anchor,K, member 1Lectin, Glycoprotein, Polymorphism,3D-structureNM_007375TARDBPTAR DNA bindingDNA-binding, RNA-binding, Nuclear31847152proteinprotein, Transcription regulation,Repressor, mRNA processing,mRNA splicing, RepeatNM_009588LTBlymphotoxin betaCytokine, Transmembrane,31857153(TNF superfamily,Glycoprotein, Signal-anchor,member 3)Alternative splicing, PolymorphismNM_012062DNM1Ldynamin 1-likeHypothetical protein31867154NM_012064MIPmajor intrinsicGap junction, Transport,31877155protein of lens fiberTransmembrane, Phosphorylation,Eye lens proteinNM_012079DGAT1diacylglycerol O-Transferase, Acyltransferase,31887156acyltransferaseTransmembrane, Endoplasmichomolog 1 (mouse)reticulum, Hypothetical proteinNM_012084GLUD2glutamateHypothetical protein31897157dehydrogenase 2NM_012086GTF3C3general transcriptionHypothetical protein31907158factor IIIC,polypeptide 3,102 kDaNM_012089ABCB10ATP-bindingATP-binding, Transmembrane,31917159cassette, sub-familyTransport, Mitochondrion, InnerB (MDR/TAP),membrane, Transit peptide,member 10PolymorphismNM_012094PRDX5peroxiredoxin 5Antioxidant, Peroxisome,31927160Mitochondrion, Transit peptide,Alternative initiation, Polymorphism,3D-structureNM_012100DNPEPaspartylHydrolase, Aminopeptidase,31937161aminopeptidaseMetalloprotease, Zinc, HypotheticalproteinNM_012108BRDG1BCR downstream31947162signaling 1NM_012114CASP14caspase 14,Hydrolase, Thiol protease,31957163apoptosis-relatedApoptosis, Zymogencysteine proteaseNM_012124CHORDC1cysteine and31967164histidine-rich domain(CHORD)-containing, zincbinding protein 1NM_012130CLDN14claudin 14Tight junction, Transmembrane,31977165Polymorphism, Disease mutation,DeafnessNM_012142CCNDBP1cyclin D-typeCyclin, Hypothetical protein31987166binding-protein 1NM_012143TFIP11tuftelin interactingBiomineralization, Nuclear protein,31997167protein 11Alternative splicingNM_012151F8Acoagulation factorHypothetical protein32007168VIII-associated(intronic transcript)NM_012168FBXO2F-box only protein 2Ubl conjugation pathway32017169NM_012185FOXE2forkhead box E2DNA-binding, Nuclear protein,32027170Transcription regulationNM_012198GCAgrancalcin, EF-handCalcium-binding, Repeat, 3D-32037171calcium bindingstructureproteinNM_012203GRHPRglyoxylateHypothetical protein,32047172reductase/hydroxypyruvateOxidoreductase, PyruvatereductaseNM_012214MGAT4Amannosyl (alpha-Glycosyltransferase, Transferase320571731,3-)-glycoproteinbeta-1,4-N-acetylglucosaminyltransferase,isoenzyme ANM_012218ILF3interleukin enhancerHypothetical protein, Transcription32067174binding factor 3,regulation, DNA-binding, RNA-90 kDabinding, Nuclear protein, Repeat,Phosphorylation, Methylation,Alternative splicingNM_012228PILBpilin-like transcriptionHypothetical protein32077175factorNM_012229NT5C25′-nucleotidase,Hydrolase, Allosteric enzyme32087176cytosolic IINM_012236SCMH1sex comb on midleg32097177homolog 1(Drosophila)NM_012244SLC7A8solute carrier familyHypothetical protein, Transport,321071787 (cationic aminoAmino-acid transport,acid transporter, y+Transmembranesystem), member 8NM_012250RRAS2related RAS viral (r-GTP-binding, Prenylation,32117179ras) oncogeneLipoprotein, Proto-oncogene,homolog 2Disease mutationNM_012255XRN25′-3′mRNA processing, Hydrolase,32127180exoribonuclease 2Nuclease, Exonuclease, Nuclearprotein, RNA-binding, Zinc-fingerNM_012258HEY1hairy/enhancer-of-Hypothetical protein, Transcription32137181split related withregulation, DNA-binding, NuclearYRPW motif 1proteinNM_012262HS2ST1heparan sulfate 2-O-Hypothetical protein, Transferase32147182sulfotransferase 1NM_012282KCNE1Lpotassium voltage-Transmembrane, Glycoprotein,32157183gated channel, lsk-Alport syndrome, Deafness,related family,Elliptocytosismember 1-likeNM_012286MORF4L2mortality factor 4 like 2Growth regulation, Nuclear protein32167184NM_012290TLK1tousled-like kinase 1ATP-binding, Kinase,32177185Serine/threonine-protein kinase,Transferase, Chromatin regulator,Cell cycle, DNA damage, Nuclearprotein, Coiled coil, Phosphorylation,Alternative splicingNM_012295CABIN1calcineurin bindingHypothetical protein,32187186protein 1Phosphorylation, Repeat, TPRrepeatNM_012329MMDmonocyte toTransmembrane32197187macrophagedifferentiation-associatedNM_012331MSRAmethionine sulfoxideOxidoreductase32207188reductase ANM_012341CRFGGTP binding protein 4GTP-binding, Nuclear protein32217189NM_012342NMAputativeTransmembrane, Signal,32227190transmembraneGlycoproteinproteinNM_012343NNTnicotinamideOxidoreductase, NAD, NADP,32237191nucleotideTransmembrane, Mitochondrion,transhydrogenaseTransit peptide, 3D-structure,Hypothetical proteinNM_012347FBXO9F-box only protein 9Hypothetical protein, Ubl conjugation32247192pathway, TPR repeatNM_012383OSTF1osteoclastHypothetical protein, ANK repeat,32257193stimulating factor 1Repeat, SH3 domainNM_012384GMEB2glucocorticoidTrans-acting factor, Nuclear protein,32267194modulatory elementDNA-binding, Coiled coilbinding protein 2NM_012387PADI4peptidyl arginineHydrolase, Calcium-binding,32277195deiminase, type IVMultigene familyNM_012390PROL5proline rich 5Saliva32287196(salivary)NM_012392PEFPEF protein with aCalcium-binding32297197long N-terminalhydrophobic domain(peflin)NM_012400PLA2G2Dphospholipase A2,Hydrolase, Lipid degradation, Signal,32307198group IIDCalcium, PolymorphismNM_012403ANP32Cacidic (leucine-rich)32317199nuclearphosphoprotein 32family, member CNM_012413QPCTglutaminyl-peptideTransferase, Acyltransferase, Signal,32327200cyclotransferasePolymorphism(glutaminyl cyclase)NM_012434SLC17A5solute carrier familyTransmembrane, Hypothetical3233720117 (anion/sugarprotein, Sugar transporttransporter),member 5NM_012445SPON2spondin 2,Hypothetical protein, Matrix protein32347202extracellular matrixproteinNM_012446SSBP2single-stranded DNADNA-binding, Nuclear protein32357203binding protein 2NM_012455TICSEC7 homolog32367204NM_012460TIMM9translocase of innerTransport, Protein transport,32377205mitochondrialTranslocation, Mitochondrion, Innermembrane 9membrane, Hypothetical proteinhomolog (yeast)NM_012463ATP6V0A2ATPase, H+Hydrogen ion transport,32387206transporting,Transmembrane, Glycoprotein,lysosomal V0Hypothetical proteinsubunit a isoform 2NM_012483GNLYgranulysinAntibiotic, Fungicide, Signal, T-cell,32397207Alternative splicing, 3D-structureNM_012484HMMRhyaluronan-Hyaluronic acid, Alternative splicing,32407208mediated motilityRepeat, Glycoprotein, Antigenreceptor (RHAMM)NM_012485HMMRhyaluronan-Hyaluronic acid, Alternative splicing,32417209mediated motilityRepeat, Glycoprotein, Antigenreceptor (RHAMM)NM_013229APAF1apoptotic proteaseApoptosis, ATP-binding, Repeat,32427210activating factorWD repeat, Alternative splicing, 3D-structureNM_013235RNASE3Lnuclear RNase IIIRibosome biogenesis, Hydrolase,32437211DroshaNuclease, Endonuclease, Repeat,RNA-binding, Nuclear protein,Alternative splicingNM_013236E46Llike mouse brainHypothetical protein32447212protein E46NM_013242GTL3likely ortholog of32457213mouse gene traplocus 3NM_013248NXT1NTF2-like exportTransport, Protein transport, Nuclear32467214factor 1protein, 3D-structureNM_013252CLECSF5C-type (calciumTransmembrane, Lectin32477215dependent,carbohydrate-recognition domain)lectin, superfamilymember 5NM_013258ASCapoptosis-Apoptosis, Anti-oncogene,32487216associated speck-Alternative splicinglike proteincontaining a CARDNM_013259NP25neuronal protein32497217NM_013272SLC21A11solute carrier organicTransmembrane, Transport, Ion32507218anion transportertransport, Glycoproteinfamily, member 3A1NM_013285HUMAUANTIGnucleolar GTPaseGTP-binding, Nuclear protein32517219NM_013286KIAA0800chromosome 3p21.1Hypothetical protein32527220gene sequenceNM_013289KIR3DL1killer cellReceptor, Immunoglobulin domain,32537221immunoglobulin-likeGlycoprotein, Signal,receptor, threeTransmembrane, Repeat, Multigenedomains, longfamily, Polymorphism, 3D-structure,cytoplasmic tail, 1Alternative splicingNM_013296MCLCLGN proteinHypothetical protein, Repeat, TPR32547222repeat, PhosphorylationNM_013300HSU79274protein predicted byHypothetical protein32557223clone 23733NM_013301HSU79303protein predicted byHypothetical protein32567224clone 23882NM_013312HOOK2hook homolog 2Hypothetical protein32577225(Drosophila)NM_013319TERE1transitional epithelia32587226response proteinNM_013323SNX11sorting nexin 11Transport, Protein transport32597227NM_013328P5CR2pyrroline 5-Hypothetical protein32607228carboxylatereductase isoformNM_013330NME7non-metastatic cellsTransferase, Kinase, ATP-binding,326172297, protein expressedSodium/potassium transport,in (nucleoside-Transmembrane, Glycoprotein,diphosphate kinase)Multigene family, Signal-anchor,Alternative splicingNM_013341PTD004hypothetical proteinGTP-binding, Alternative splicing32627230PTD004NM_013351TBX21T-box 21Transcription regulation, DNA-32637231binding, Nuclear protein, ActivatorNM_013354CNOT7CCR4-NOTTranscription regulation, Repressor,32647232transcriptionNuclear protein, Hypothetical proteincomplex, subunit 7NM_013363PCOLCE2procollagen C-Collagen32657233endopeptidaseenhancer 2NM_013363PNMA3paraneoplasticHypothetical protein32667234antigen MA3NM_013368RBT1RPA-binding trans-Hypothetical protein32677235activatorNM_013382POMT2protein-O-Transferase, Glycosyltransferase,32687236mannosyltransferase 2Endoplasmic reticulum,Transmembrane, Glycoprotein,Repeat, Alternative splicingNM_013383TCFL4transcription factor-Transcription regulation, Repressor,32697237like 4Nuclear protein, DNA-binding,Alternative splicing, ReceptorNM_013392NRBPnuclear receptorHypothetical protein, ATP-binding,32707238binding proteinTransferase, Nuclear protein,ReceptorNM_013395AD013Homo sapiensHypothetical protein,32717239proteinx0008Transmembrane(AD013) mRNA,complete cds.NM_013403STRN4striatin, calmodulinCalmodulin-binding, Repeat, WD32727240binding protein 4repeat, Coiled coilNM_013412RABL2ARAB, member ofHypothetical protein, GTP-binding,32737241RAS oncogeneAlternative splicingfamily-like 2ANM_013416NCF4neutrophil cytosolicSH3 domain, Alternative splicing,32747242factor 4, 40 kDa3D-structureNM_013421GGT1gamma-Glutathione biosynthesis,32757243glutamyltransferase 1Transferase, Acyltransferase,Signal-anchor, Transmembrane,Zymogen, Glycoprotein, Sialic acid,Alternative splicing, Alternativepromoter usageNM_013430GGT1gamma-Glutathione biosynthesis,32767244glutamyltransferase 1Transferase, Acyltransferase,Signal-anchor, Transmembrane,Zymogen, Glycoprotein, Sialic acid,Alternative splicing, Alternativepromoter usageNM_013439PILR(ALPHA)pairedReceptor32777245immunoglobin-liketype 2 receptoralphaNM_013440PILR(BETA)pairedMeiosis, Cell cycle, Chromosome32787246immunoglobin-likepartition, Nuclear protein, Alternativetype 2 receptor betasplicing, Hypothetical protein,ReceptorNM_013444UBQLN2ubiquilin 2Hypothetical protein32797247NM_013448BAZ1AbromodomainTranscription regulation,32807248adjacent to zincBromodomain, Zinc-finger, Coiledfinger domain, 1Acoil, Nuclear protein, AlternativesplicingNM_013940OR10H1olfactory receptor,32817249family 10, subfamilyH, member 1NM_013943CLIC4chloride intracellularHypothetical protein, Ionic channel,32827250channel 4Ion transport, Chloride channel,Voltage-gated channelNM_013951PAX8paired box gene 8DNA-binding, Developmental32837251protein, Nuclear protein, Paired box,Transcription, Transcriptionregulation, Differentiation, Alternativesplicing, Disease mutation,PolymorphismNM_013956NRG1neuregulin 1EGF-like domain, Growth factor,32847252Transmembrane, Multigene family,Alternative splicing, Immunoglobulindomain, Glycoprotein,Polymorphism, 3D-structure,Chromosomal translocationNM_013974DDAH2dimethylarginineHydrolase32857253dimethylaminohydrolase 2NM_013975LIG3ligase III, DNA, ATP-DNA repair, DNA replication, DNA32867254dependentrecombination, Cell division, Ligase,ATP-binding, Zinc-finger, Nuclearprotein, Alternative splicing, 3D-structure, Hypothetical proteinNM_013979BNIP1BCL2/adenovirusApoptosis, Alternative splicing,32877255E1B 19 kDaTransmembraneinteracting protein 1NM_013992PAX8paired box gene 8DNA-binding, Developmental32887256protein, Nuclear protein, Paired box,Transcription, Transcriptionregulation, Differentiation, Alternativesplicing, Disease mutation,PolymorphismNM_013995LAMP2lysosomal-Transmembrane, Glycoprotein,32897257associatedLysosome, Signal, Alternativemembrane protein 2splicing, PolymorphismNM_014000VCLvinculinCell adhesion, Actin-binding,32907258Cytoskeleton, Structural protein,Phosphorylation, Repeat, Alternativesplicing, LipoproteinNM_014011SOCS5suppressor ofSH2 domain, Growth regulation,32917259cytokine signaling 5Signal transduction inhibitorNM_014018MRPS28mitochondrialRibosomal protein, Mitochondrion32927260ribosomal proteinS28NM_014029RAC2ras-related C3GTP-binding, Prenylation,32937261botulinum toxinLipoprotein, 3D-structuresubstrate 2 (rhofamily, small GTPbinding proteinRac2)NM_014030GIT1G protein-coupledHypothetical protein, GTPase32947262receptor kinase-activation, Repeat, ANK repeat,interactor 1Zinc-fingerNM_014038BZW2basic leucine zipperHypothetical protein32957263and W2 domains 2NM_014042DKFZP564M082DKFZP564M082Hypothetical protein32967264proteinNM_014050MRPL42mitochondrialRibosomal protein, Mitochondrion32977265ribosomal proteinL42NM_014051PTD011transmembraneTransmembrane32987266protein 14ANM_014052GW128GW128 protein32997267NM_014055CDV-1carnitine deficiency-Hypothetical protein33007268associated geneexpressed inventricle 1NM_014056HIG1likely ortholog ofHypothetical protein33017269mouse hypoxiainduced gene 1NM_014060MCT-1malignant T cell33027270amplified sequence 1NM_014061MAGEH1APR-1 proteinAntigen33037271NM_014062ART-4likely ortholog ofHypothetical protein33047272mouse nin onebinding proteinNM_014063HIP-55src homology 3Hypothetical protein, SH3 domain33057273domain-containingprotein HIP-55NM_014078MRPL13mitochondrialRibosomal protein, Mitochondrion33067274ribosomal proteinL13NM_014080DUOX2dual oxidase 2Peroxidase33077275NM_014147CAPRIHSPC047 proteinGTPase activation, Repeat33087276NM_014165C6orf66chromosome 6 open33097277reading frame 66NM_014170HSPC135HSPC135 proteinHypothetical protein33107278NM_014175MRPL15mitochondrialHypothetical protein33117279ribosomal proteinL15NM_014177HSPC154HSPC154 protein33127280NM_014180MRPL22mitochondrialHypothetical protein, Ribosomal33137281ribosomal proteinproteinL22NM_014182ORMDL2ORM1-like 2 (S. cerevisiae)Hypothetical protein, Nuclear33147282protein, DNA-binding, Transcription,Transcription regulation, Translationregulation, ReceptorNM_014184HSPC163HSPC163 proteinHypothetical protein,33157283TransmembraneNM_014204BOKHomo sapiens Bcl-233167284related ovarian killer(BOK) mRNA,complete cds.NM_014207CD5CD5 antigen (p56-62)Signal, Transmembrane,33177285Glycoprotein, T-cell, RepeatNM_014214IMPA2inositol(myo)-1(or 4)-Hydrolase33187286monophosphatase 2NM_014216ITPK1inositol 1,3,4-Kinase, Hypothetical protein33197287triphosphate 5/6kinaseNM_014221MTCP1mature T-cellProto-oncogene, Mitochondrion,33207288proliferation 1Alternative splicing, Chromosomaltranslocation, 3D-structureNM_014223NFYCnuclear transcriptionTranscription regulation, DNA-33217289factor Y, gammabinding, Activator, Nuclear protein,Alternative splicing, 3D-structureNM_014225PPP2R1Aprotein phosphataseHypothetical protein, Multigene332272902 (formerly 2A),family, Acetylation, Repeat,regulatory subunit APolymorphism, 3D-structure(PR 65), alphaisoformNM_014231VAMP1vesicle-associatedMitochondrion, Synapse,33237291membrane protein 1Synaptosome, Transmembrane,(synaptobrevin 1)Coiled coil, Alternative splicing,Multigene familyNM_014232VAMP2vesicle-associatedHypothetical protein, Synapse,33247292membrane protein 2Synaptosome, Transmembrane,(synaptobrevin 2)Coiled coil, Acetylation, Multigenefamily, 3D-structureNM_014239EIF2B2eukaryoticInitiation factor, Protein biosynthesis,33257293translation initiationDisease mutationfactor 2B, subunit 2beta, 39 kDaNM_014241PTPLAprotein tyrosineATP-binding, Chaperone33267294phosphatase-like(proline instead ofcatalytic arginine),member aNM_014242ZNF237zinc finger protein33277295237NM_014245RNF7ring finger protein 7Ubl conjugation pathway, Zinc, Zinc-33287296finger, Metal-binding,Phosphorylation, Alternative splicingNM_014252SLC25A15solute carrier familyMitochondrion, Inner membrane,3329729725 (mitochondrialRepeat, Transmembrane, Transport,carrier; ornithineDisease mutation, Polymorphismtransporter) member15NM_014253ODZ1odz, odd Oz/ten-mEGF-like domain33307298homolog1 (Drosophila)NM_014254TMEM5transmembraneTransmembrane33317299protein 5NM_014268MAPRE2microtubule-T-cell33327300associated protein,RP/EB family,member 2NM_014280DNAJC8DnaJ (Hsp40)Chaperone33337301homolog, subfamilyC, member 8NM_014292CBX6chromobox homolog 6Chromatin regulator, Nuclear33347302protein, Transcription regulation,RepressorNM_014297YF13H12ethylmalonic33357303encephalopathy 1NM_014306HSPC117hypothetical proteinHypothetical protein33367304HSPC117NM_014313SMP1small membraneTransmembrane, Polymorphism33377305protein 1NM_014326DAPK2death-associatedTransferase, Serine/threonine-33387306protein kinase 2protein kinase, Calmodulin-binding,Phosphorylation, ATP-binding,ApoptosisNM_014330PPP1R15Aprotein phosphataseHypothetical protein333973071, regulatory(inhibitor) subunit15ANM_014335CRI1CREBBP/EP300Hypothetical protein33407308inhibitory protein 1NM_014339IL17Rinterleukin 17Receptor, Transmembrane, Signal,33417309receptorGlycoproteinNM_014341MTCH1mitochondrial carrier33427310homolog 1 (C. elegans)NM_014343CLDN15claudin 15Tight junction, Transmembrane33437311NM_014350GG2-1TNF-induced protein33447312NM_014357XP5small proline rich-like33457313(epidermaldifferentiationcomplex) 1BNM_014359OPTCopticinGlycoprotein, Extracellular matrix,33467314Signal, Repeat, Leucine-rich repeat,SulfationNM_014362HIBCH3-hydroxyisobutyryl-Hydrolase33477315Coenzyme AhydrolaseNM_014366E2IG3nucleosteminHypothetical protein33487316NM_014373GPCR1G protein-coupledReceptor33497317receptor 160NM_014381MLH3mutL homolog 3 (E. coli)DNA repair, Nuclear protein,33507318Polymorphism, Alternative splicing,Hereditary nonpolyposis colorectalcancer, Disease mutation,Hypothetical proteinNM_014399NET-6transmembrane 4Glycoprotein, Transmembrane33517319superfamily member13NM_014403SIAT7Dsialyltransferase 7DTransferase, Glycosyltransferase,33527320((alpha-N-Glycoprotein, Transmembrane,acetylneuraminyl-Signal-anchor, Golgi stack2,3-beta-galactosyl-1,3)-N-acetylgalactosaminidealpha-2,6-sialyltransferase)NM_014413HRIheme-regulatedTransferase, Kinase,33537321initiation factor 2-Serine/threonine-protein kinase,alpha kinaseProtein synthesis inhibitor, ATP-binding, Repeat, Phosphorylation,Alternative splicing, Polymorphism,Protein biosynthesisNM_014425INVSinversinANK repeat, Repeat33547322NM_014426SNX5sorting nexin 5Transport, Protein transport,33557323Hypothetical proteinNM_014430CIDEBcell death-inducingApoptosis, 3D-structure, RNA-33567324DFFA-like effector bbinding, Repeat, G-protein coupledreceptor, Transmembrane,GlycoproteinNM_014434NR1NADPH-dependent33577325FMN and FADcontainingoxidoreductaseNM_014437SLC39A1solute carrier familyTransport, Zinc transport,3358732639 (zinc transporter),Transmembranemember 1NM_014446MIBPintegrin beta 133597327binding protein 3NM_014450SITSHP2-interactingSignal33607328transmembraneadaptor proteinNM_014453BC-2putative breast33617329adenocarcinomamarker (32 kD)NM_014465SULT1B1sulfotransferaseHypothetical protein, Transferase33627330family, cytosolic, 1B,member 1NM_014473HSA9761putativerRNA processing, Transferase,33637331dimethyladenosineMethyltransferasetransferaseNM_014481APEX2APEX nucleaseEndonuclease33647332(apurinic/apyrimidinicendonuclease) 2NM_014499P2RY10purinergic receptorReceptor, Transmembrane33657333P2Y, G-proteincoupled, 10NM_014503DRIMdown-regulated in33667334metastasisNM_014517UBP1upstream bindingHypothetical protein33677335protein 1 (LBP-1a)NM_014520MYBBP1AMYB binding proteinHypothetical protein33687336(P160) 1aNM_014575SCHIP1schwannominHypothetical protein33697337interacting protein 1NM_014593CGBPCpG binding proteinHypothetical protein, Transcription33707338regulation, Activator, DNA-binding,Zinc-finger, Metal-binding, Coiledcoil, Nuclear proteinNM_014624S100A6S100 calciumMitogen, Cell cycle, Calcium-binding,33717339binding protein A6Polymorphism, 3D-structure(calcyclin)NM_014630KIAA0211KIAA0211 geneHypothetical protein, Transcription33727340productregulation, DNA-binding, Zinc-finger,Metal-binding, Nuclear protein,RepeatNM_014638KIAA0450KIAA0450 geneHypothetical protein33737341productNM_014639KIAA0372KIAA0372Hypothetical protein33747342NM_014659KIAA0377KIAA0377 geneHypothetical protein33757343productNM_014671KIAA0010ubiquitin-proteinHypothetical protein, Ligase33767344isopeptide ligase(E3)NM_014675KIAA0445ciliary rootlet coiled-Hypothetical protein33777345coil, rootletinNM_014678KIAA0685KIAA0685Hypothetical protein33787346NM_014684KIAA0373KIAA0373 geneHypothetical protein, Coiled coil33797347productNM_014685HERPUD1homocysteine-Hypothetical protein, Unfolded33807348inducible,protein response, Endoplasmicendoplasmicreticulum, Transmembrane,reticulum stress-Alternative splicinginducible, ubiquitin-like domain member 1NM_014688RNTREUSP6 N-terminal likeHypothetical protein33817349NM_014698KIAA0792KIAA0792 geneHypothetical protein33827350productNM_014699KIAA0296KIAA0296 geneHypothetical protein, Transcription33837351productregulation, DNA-binding, Zinc-finger,Metal-binding, Nuclear protein,RepeatNM_014707HDAC9histone deacetylase 9Hydrolase, Nuclear protein,33847352Chromatin regulator, Transcriptionregulation, Repressor, Alternativesplicing, Hypothetical proteinNM_014710KIAA0443G protein-coupledHypothetical protein33857353receptor-associatedsorting proteinNM_014716CENTB1centaurin, beta 1GTPase activation, Repeat, ANK33867354repeat, Zinc-fingerNM_014718CLSTN3calsyntenin 3Cell adhesion, Glycoprotein,33877355Transmembrane, Calcium-binding,Repeat, SignalNM_014724ZNF305zinc finger proteinTranscription regulation, DNA-33887356305binding, Zinc-finger, Metal-binding,Nuclear protein, RepeatNM_014727WBP7myeloid/lymphoid orDNA-binding, Bromodomain,33897357mixed-lineageNuclear protein, Zinc-finger, Metal-leukemia 4binding, Transcription regulation,Alternative splicing, RepeatNM_014729TOXthymus high mobilityHypothetical protein33907358group box proteinTOXNM_014732KIAA0513KIAA0513 geneHypothetical protein33917359productNM_014735KIAA0215PHD finger proteinZinc-finger3392736016NM_014737RASSF2Ras associationHypothetical protein33937361(RaIGDS/AF-6)domain family 2NM_014739BTFBcl-2-associatedHypothetical protein33947362transcription factorNM_014740KIAA0111DEAD (Asp-Glu-Ala-ATP-binding, RNA-binding, DNA-33957363Asp) box polypeptidebinding, Helicase, Nuclear protein,48rRNA processingNM_014750DLG7discs, large homologHypothetical protein339673647 (Drosophila)NM_014751MTSS1metastasisCytoskeleton, Actin-binding, Coiled33977365suppressor 1coil, Anti-oncogene, AlternativesplicingNM_014753KIAA0187BMS1-like, ribosomeRibosome biogenesis, Nuclear33987366assembly proteinprotein, ATP-binding(yeast)NM_014763MRPL19mitochondrialRibosomal protein, Mitochondrion,33997367ribosomal proteinTransit peptideL19NM_014764DAZAP2DAZ associatedHypothetical protein34007368protein 2NM_014765TOMM20-translocase of outerTransport, Protein transport, Outer34017369PENDINGmitochondrialmembrane, Mitochondrion,membrane 20Transmembranehomolog (yeast)NM_014767SPOCK2sparc/osteonectin,Extracellular matrix, Proteoglycan,34027370cwcv and kazal-likeHeparan sulfate, Glycoprotein,domainsCalcium-binding, Signalproteoglycan(testican) 2NM_014776GIT2G protein-coupledGTPase activation, Repeat, ANK34037371receptor kinase-repeat, Zinc-finger, Alternativeinteractor 2splicing, Hypothetical proteinNM_014792KIAA0125KIAA0125Hypothetical protein34047372NM_014807KIAA0285KIAA0285 geneHypothetical protein34057373productNM_014808FARP2FERM, RhoGEF andHypothetical protein34067374pleckstrin domainprotein 2NM_014815TRAP100thyroid hormoneTranscription regulation, Zinc-finger,34077375receptor-associatedRepeat, ATP-binding, Nuclearprotein (100 kDa)proteinNM_014820TOMM70Atranslocase of outerMitochondrion, Outer membrane,34087376mitochondrialTransmembrane, Repeat, TPRmembrane 70repeathomolog A (yeast)NM_014830KIAA0352KIAA0352 geneHypothetical protein, Transcription34097377productregulation, DNA-binding, Zinc-finger,Metal-binding, Nuclear protein,RepeatNM_014835OSBPL2oxysterol bindingLipid transport, Transport,34107378protein-like 2Alternative splicingNM_014838ZBED4zinc finger, BEDRepeat, Zinc-finger34117379domain containing 4NM_014844KIAA0329KIAA0329Hypothetical protein34127380NM_014846KIAA0196KIAA0196 geneHypothetical protein34137381productNM_014861KIAA0703KIAA0703 geneHydrolase, Calcium transport,34147382productTransmembrane, Phosphorylation,ATP-binding, Metal-binding,Magnesium, Calcium-binding,Multigene familyNM_014863GALNAC4S-B cell RAGHypothetical protein, Transferase341573836STassociated proteinNM_014865CNAP1chromosomeDNA condensation, Mitosis, Cell34167384condensation-relatedcycle, Nuclear protein,SMC-associatedPhosphorylationprotein 1NM_014869KIAA0763KIAA0763 geneHypothetical protein34177385productNM_014872KIAA0354zinc finger and BTBHypothetical protein, Metal-binding,34187386domain containing 5Zinc, Zinc-fingerNM_014873KIAA0205KIAA0205 geneHypothetical protein, Phospholipid34197387productbiosynthesis, Transferase,Acyltransferase, TransmembraneNM_014874MFN2mitofusin 2Hypothetical protein34207388NM_014878KIAA0020minorHypothetical protein, RNA-binding,34217389histocompatibilityRepeat, Nuclear proteinantigen HA-8NM_014882KIAA0053KIAA0053 geneHypothetical protein34227390productNM_014886YR-29TGF beta-inducibleNuclear protein34237391nuclear protein 1NM_014888FAM3Cfamily with sequenceSignal34247392similarity 3, member CNM_014889PITRM1pitrilysinMetalloprotease, Protease,34257393metalloproteinase 1Hypothetical proteinNM_014897KIAA0924KIAA0924 proteinHypothetical protein, Metal-binding,34267394Nuclear protein, Zinc, Zinc-fingerNM_014899RHOBTB3Rho-related BTBRepeat34277395domain containing 3NM_014902KIAA0964disks large-Membrane, Alternative splicing34287396associated protein 4NM_014907KIAA0967KIAA0967 proteinHypothetical protein34297397NM_014913KIAA0863KIAA0863 proteinHypothetical protein, Metal-binding,34307398Zinc, Zinc-fingerNM_014915KIAA1074KIAA1074 proteinANK repeat, Repeat, Hypothetical34317399proteinNM_014929KIAA0971KIAA0971 proteinHypothetical protein34327400NM_014931KIAA1115KIAA1115 proteinHypothetical protein34337401NM_014937SAC2inositolHypothetical protein34347402polyphosphate-5-phosphatase FNM_014940KIAA0872HSV-1 stimulation-Hypothetical protein34357403related gene 1NM_014944CLSTN1calsyntenin 1Cell adhesion, Glycoprotein,34367404Transmembrane, Calcium-binding,Repeat, SignalNM_014947KIAA1041KIAA1041 proteinHypothetical protein, Transcription34377405regulation, DNA-binding, NuclearproteinNM_014949KIAA0907KIAA0907 proteinHypothetical protein34387406NM_014953DIS3mitotic controlExosome, Hydrolase, Nuclease,34397407protein dis3 homologExonuclease, rRNA processing,Nuclear protein, RNA-binding,Hypothetical proteinNM_014965KIAA1042OGT(O-Glc-NAcGlycoprotein, Coiled coil,34407408transferase)-Hypothetical proteininteracting protein106 KDaNM_014966DDX30DEAH (Asp-Glu-Ala-ATP-binding, Helicase, Hydrolase,34417409His) box polypeptideHypothetical protein30NM_014967KIAA1018KIAA1018 proteinHypothetical protein34427410NM_014977ACINUSapoptotic chromatinApoptosis, Nuclear protein,34437411condensationAlternative splicinginducer in thenucleusNM_015057KIAA0916protein associatedHypothetical protein34447412with MycNM_015156RCORREST corepressorDNA-binding, Nuclear protein,34457413Hypothetical proteinNM_015239AGTPBP1ATP/GTP bindingHypothetical protein34467414protein 1NM_015310EFA6RADP-ribosylationHypothetical protein, Guanine-34477415factor guaninenucleotide releasing factornucleotide factor 6NM_015361R3HDMR3H domain (bindsHypothetical protein34487416single-strandednucleic acids)containingNM_015368PANX1pannexin 1Gap junction, Transmembrane,34497417PolymorphismNM_015379BRI3brain protein I3Transmembrane34507418NM_015383DJ328E19.C1.1hypothetical proteinHypothetical protein34517419DJ328E19.C1.1NM_015392NPDC1neural proliferation,Hypothetical protein, Signal,34527420differentiation andTransmembranecontrol, 1NM_015400DKFZP586N0721DKFZP586N0721Hypothetical protein34537421proteinNM_015420DKFZP564O0463DKFZP564O0463Repeat, WD repeat, Mitochondrion,34547422proteinInner membrane, Transmembrane,Transport, Hypothetical proteinNM_015462DKFZP586L0724DKFZP586L0724Hypothetical protein34557423proteinNM_015492DKFZP434H132DKFZP434H132Hypothetical protein34567424proteinNM_015515KRT23keratin 23 (histoneHypothetical protein, Intermediate34577425deacetylasefilament, Coiled coil, Keratininducible)NM_015524C6orf4chromosome 6 openAlternative splicing34587426reading frame 4NM_015527DKFZP434P1750DKFZP434P1750Hypothetical protein34597427proteinNM_015530GORASP2golgi reassemblyHypothetical protein34607428stacking protein 2,55 kDaNM_015556KIAA0440signal-inducedHypothetical protein34617429proliferation-associated 1 like 1NM_015599PGM3phosphoglucomutase 3Hypothetical protein, Isomerase,34627430Phosphorylation, PolymorphismNM_015610DKFZP434J154DKFZP434J154Repeat, WD repeat, Hypothetical34637431proteinproteinNM_015629PRPF31TCF3 (E2A) fusionHypothetical protein34647432partner (in childhoodLeukemia)NM_015640PAI-RBP1PAI-1 mRNA-bindingHypothetical protein34657433proteinNM_015644ARPC4actin related proteinCytoskeleton, Hypothetical protein,346674342/3 complex, subunitLigase4, 20 kDaNM_015654DKFZP564C103DKFZP564C103Hypothetical protein34677435proteinNM_015684ATP5SATP synthase, H+Hydrogen ion transport, CF(0),34687436transporting,Mitochondrion, Transit peptide,mitochondrial F0Hypothetical proteincomplex, subunit s(factor B)NM_015696CL683glutathioneHypothetical protein,34697437peroxidase 6Oxidoreductase, Peroxidase, SignalNM_015699DJ159A19.3hypothetical proteinHypothetical protein34707438DJ159A19.3NM_015711GLTSCR1glioma tumor34717439suppressorcandidate regiongene 1NM_015722CALCYONcalcyon proteinTransmembrane, Glycoprotein34727440NM_015836WARS2tryptophanyl tRNAAminoacyl-tRNA synthetase, Protein34737441synthetase 2biosynthesis, Ligase, ATP-binding,(mitochondrial)Mitochondrion, Transit peptideNM_015838FCN2ficolinLectin, Collagen, Repeat,34747442(collagen/fibrinogenGlycoprotein, Signal, Multigenedomain containingfamilylectin) 2 (hucolin)NM_015839FCN2ficolinLectin, Collagen, Repeat,34757443(collagen/fibrinogenGlycoprotein, Signal, Multigenedomain containingfamilylectin) 2 (hucolin)NM_015853LOC51035ORFHypothetical protein34767444NM_015855WIT-1Wilms tumorPolymorphism34777445associated proteinNM_015868KIR2DL3killer cellReceptor, Immunoglobulin domain,34787446immunoglobulin-likeGlycoprotein, Signal,receptor, twoTransmembrane, Repeat, Multigenedomains, longfamily, Polymorphism, 3D-structure,cytoplasmic tail, 3Alternative splicingNM_015872ZFP67zinc finger protein 67Metal-binding, Zinc, Zinc-finger34797447homolog (mouse)NM_015905TIF1transcriptionalElongation factor, Protein34807448intermediary factor 1biosynthesis, GTP-binding,Methylation, Multigene family,Transcription regulation, Repressor,DNA-binding, Bromodomain, Zinc-finger, Alternative splicing, Nuclearprotein, Coiled coil, RepeatNM_015907LAP3leucineHydrolase, Aminopeptidase,34817449aminopeptidase 3Acetylation, Zinc, Magnesium,ManganeseNM_015908ARS2arsenate resistanceHypothetical protein, Alternative34827450protein ARS2splicingNM_015932C13orf12chromosome 13Hypothetical protein34837451open reading frame12NM_015942LOC51001CGI-12 proteinHypothetical protein34847452NM_015945OVCOV1solute carrier familyHypothetical protein3485745335, member C2NM_015956MRPL4mitochondrialRibosomal protein34867454ribosomal protein L4NM_015958LOC51611CGI-30 proteinTransferase, Methyltransferase,34877455Alternative splicing, HypotheticalproteinNM_015959LOC51075thioredoxin-relatedHypothetical protein34887456transmembraneprotein 2NM_015963LOC51078THAP domainZinc-finger, DNA-binding34897457containing 4NM_015967PTPN22protein tyrosineHydrolase, Alternative splicing,34907458phosphatase, non-Hypothetical proteinreceptor type 22(lymphoid)NM_015971MRPS7mitochondrialRibosomal protein34917459ribosomal protein S7NM_015984UCHL5ubiquitin carboxyl-Hypothetical protein, Ubl conjugation34927460terminal hydrolasepathway, Hydrolase, Thiol protease,L5Proteasome, Alternative splicing,PolymorphismNM_015999LOC51094adiponectin receptor 1Fatty acid metabolism, Lipid34937461metabolism, Receptor,TransmembraneNM_016006CGI-58abhydrolase domainHypothetical protein34947462containing 5NM_016017UCHL5ubiquitin carboxyl-Hypothetical protein, Hydrolase, Ubl34957463terminal hydrolaseconjugation pathway, Thiol protease,L5Proteasome, Alternative splicing,PolymorphismNM_016022LOC51107likely ortholog of C. elegansTransmembrane, Golgi stack,34967464anteriorEndoplasmic reticulum, Alternativepharynx defective 1AsplicingNM_016026RDH11retinolOxidoreductase, NADP, Signal-34977465dehydrogenase 11anchor, Transmembrane,(all-trans and 9-cis)Endoplasmic reticulum, AlternativesplicingNM_016039LOC51637chromosome 14Hypothetical protein34987466open reading frame166NM_016045C20orf45chromosome 2034997467open reading frame45NM_016052LOC51018CGI-115 protein35007468NM_016055MRPL48mitochondrialRibosomal protein, Mitochondrion35017469ribosomal proteinL48NM_016056LOC51643CGI-119 proteinTransmembrane, Polymorphism35027470NM_016058LOC51002CGI-121 protein35037471NM_016064PILBmethionine sulfoxideHypothetical protein35047472reductase BNM_016072LOC51026CGI-141 proteinHypothetical protein,35057473TransmembraneNM_016075C13orf9chromosome 13Hypothetical protein35067474open reading frame 9NM_016082CDK5RAP1CDK5 regulatoryAlternative splicing35077475subunit associatedprotein 1NM_016093RPL26L1ribosomal proteinRibosomal protein35087476L26-like 1NM_016096LOC51123HSPC038 proteinMetal-binding, Zinc, Zinc-finger35097477NM_016101HSPC031comparative geneHypothetical protein35107478identificationtranscript 37NM_016120RNF12ring finger protein 12Hypothetical protein, Metal-binding,35117479Zinc, Zinc-finger, TranscriptionregulationNM_016122LOC51134NY-REN-58 antigen35127480NM_016126LOC51668HSPCO34 protein35137481NM_016127MGC8721hypothetical proteinHypothetical protein35147482MGC8721NM_016129COPS4COP9 constitutiveHypothetical protein35157483photomorphogenichomolog subunit 4(Arabidopsis)NM_016143NSFL1CNSFL1 (p97)Hypothetical protein35167484cofactor (p47)NM_016167RANBP9retinoic acidHypothetical protein35177485repressible proteinNM_016175SQSTM1truncated calciumHypothetical protein35187486binding proteinNM_016183C1orf33chromosome 1 openHypothetical protein, Ribosomal35197487reading frame 33proteinNM_016184CLECSF6C-type (calciumReceptor, Lectin35207488dependent,carbohydrate-recognition domain)lectin, superfamilymember 6NM_016187BIN2bridging integrator 2Hypothetical protein35217489NM_016194GNB5guanine nucleotideRepeat, WD repeat, Transducer,35227490binding protein (GAlternative splicing, Multigene family,protein), beta 5Hypothetical proteinNM_016199LSM7LSM7 homolog, U6Nuclear protein, Ribonucleoprotein,35237491small nuclear RNAmRNA splicing, mRNA processing,associated (S. cerevisiae)RNA-bindingNM_016202LOC51157LDL induced ECMetal-binding, Zinc, Zinc-finger35247492proteinNM_016207CPSF3cleavage andmRNA processing, Nuclear protein,35257493polyadenylationRNA-bindingspecific factor 3,73 kDaNM_016208VPS28vacuolar proteinTransport, Protein transport35267494sorting 28 (yeast)NM_016214COL18A1collagen, type XVIII,Collagen, Extracellular matrix,35277495alpha 1Connective tissue, Repeat,Hydroxylation, Cell adhesion,Glycoprotein, Signal, Alternativesplicing, Polymorphism, 3D-structureNM_016221DCTN4dynactin 4 (p62)Hypothetical protein35287496NM_016229LOC51700cytochrome b5Hypothetical protein35297497reductase b5R.2NM_016237ANAPC5anaphase promotingUbl conjugation pathway, Cell cycle,35307498complex subunit 5Cell division, Mitosis, Repeat, TPRrepeat, Alternative splicingNM_016258HGRG8high-glucose-35317499regulated protein 8NM_016271RNF138ring finger proteinHypothetical protein, Metal-binding,35327500138Zinc, Zinc-fingerNM_016274CKIP-1CK2 interactingHypothetical protein35337501protein 1; HQ0024cproteinNM_016283TAF9TAF9 RNAATP-binding, Transcription35347502polymerase II, TATAregulation, Nuclear protein,box binding proteinPolymorphism, Hypothetical protein,(TBP)-associatedCell cyclefactor, 32 kDaNM_016293BIN2bridging integrator 2Hypothetical protein35357503NM_016299HSP70-4likely ortholog ofATP-binding35367504mouse heat shockprotein, 70 kDa 4NM_016304C15orf15chromosome 15Ribosomal protein35377505open reading frame15NM_016306DNAJB11DnaJ (Hsp40)Chaperone, Endoplasmic reticulum,35387506homolog, subfamilySignal, PolymorphismB, member 11NM_016309LCMT1leucine carboxylHypothetical protein,35397507methyltransferase 1Methyltransferase, TransferaseNM_016312WBP11WW domain bindingHypothetical protein35407508protein 11NM_016316REV1LREV1-like (yeast)Transferase, Integrin, Hypothetical35417509proteinNM_016326CKLFchemokine-likeChemotaxis, Cytokine,35427510factorTransmembrane, Alternative splicingNM_016327UPB1ureidopropionase,Hydrolase, Allosteric enzyme, Zinc35437511betaNM_016331LOC51193zinc finger proteinMetal-binding, Zinc, Zinc-finger35447512ANC_2H01NM_016332SEPX1selenoprotein X, 1Oxidoreductase, Metal-binding, Zinc,35457513Selenium, SelenocysteineNM_016333SRRM2serine/arginineHypothetical protein35467514repetitive matrix 2NM_016334SH120putative G-proteinReceptor35477515coupled receptorNM_016354SLC21A12solute carrier organicTransmembrane, Transport, Ion35487516anion transportertransport, Glycoprotein, Alternativefamily, member 4A1splicingNM_016355LOC51202DEAD (Asp-Glu-Ala-ATP-binding, Helicase, Hydrolase,35497517Asp) box polypeptideHypothetical protein47NM_016362GHRLghrelin precursorHormone, Cleavage on pair of basic35507518residues, Signal, Lipoprotein,Alternative splicingNM_016364DUSP13dual specificityHydrolase35517519phosphatase 13NM_016373WWOXWW domainOxidoreductase35527520containingoxidoreductaseNM_016377AKAP7A kinase (PRKA)Membrane, Myristate, Palmitate,35537521anchor protein 7Lipoprotein, Alternative splicingNM_016381TREX1three prime repairExonuclease, Hypothetical protein35547522exonuclease 1NM_016385CYLDcylindromatosisHypothetical protein35557523(turban tumorsyndrome)NM_016387HSPC060hypothetical protein35567524HSPC060NM_016391HSPC111hypothetical proteinHypothetical protein, Nuclear protein35577525HSPC111NM_016397TH1LTH1-likeTranscription regulation, Repressor,35587526(Drosophila)Nuclear protein, Alternative splicing,Alternative initiationNM_016399HSPC132hypothetical proteinHypothetical protein35597527HSPC132NM_016403HSPC148hypothetical proteinHypothetical protein35607528HSPC148NM_016407C20orf43chromosome 20Alternative splicing35617529open reading frame43NM_016418NF2neurofibromin 2Structural protein, Cytoskeleton,35627530(bilateral acousticAnti-oncogene, Disease mutation,neuroma)Alternative splicing, Deafness, 3D-structureNM_016424LUC7Acisplatin resistance-Phosphorylation, Hypothetical35637531associatedproteinoverexpressedproteinNM_016431MAPK8IP2mitogen-activatedSH3 domain, Alternative splicing35647532protein kinase 8interacting protein 2NM_016441CRIM1cysteine-rich motorSignal35657533neuron 1NM_016463HSPC195hypothetical proteinHypothetical protein35667534HSPC195NM_016465LOC51238blocked early inHypothetical protein35677535transport 1 homolog(S. cerevisiae) likeNM_016468C14orf112chromosome 14Hypothetical protein35687536open reading frame112NM_016477FOXP1forkhead box P1Hypothetical protein, Transcription35697537regulation, DNA-binding, Zinc-finger,Metal-binding, Nuclear protein,Alternative splicingNM_016479SCOTINscotinHypothetical protein35707538NM_016501FLJ10597hypothetical proteinHypothetical protein35717539FLJ10597NM_016503MRPL30mitochondrialHypothetical protein35727540ribosomal proteinL30NM_016507CRK7CDC2-relatedTransferase, Serine/threonine-35737541protein kinase 7protein kinase, ATP-binding, NuclearproteinNM_016524LOC51760B/K proteinHypothetical protein35747542NM_016533NINJ2ninjurin 2Cell adhesion, Transmembrane35757543NM_016538SIRT7sirtuin (silent matingHydrolase, NAD, Metal-binding,35767544type informationZinc, Alternative splicingregulation 2homolog) 7 (S. cerevisiae)NM_016565E2IG2E2IG2 protein35777545NM_016567BCCIPBRCA2 andHelicase, Hypothetical protein35787546CDKN1A interactingproteinNM_016572USP21ubiquitin specificHypothetical protein, Ubl conjugation35797547protease 21pathway, Hydrolase, Thiol protease,Multigene familyNM_016573LOC51291Gem-interacting35807548proteinNM_016574DRD2dopamine receptorG-protein coupled receptor,35817549D2Transmembrane, Glycoprotein,Multigene family, Alternative splicing,Disease mutation, Polymorphism,3D-structureNM_016582FLJ20539solute carrier familyHypothetical protein3582755015, member 3NM_016594FKBP11FK506 bindingIsomerase, Rotamase, Signal35837551protein 11, 19 kDaNM_016598ZDHHC3zinc finger, DHHCTransmembrane, Golgi stack, Zinc-35847552domain containing 3finger, Alternative splicingNM_016603C5orf5chromosome 5 openGTPase activation35857553reading frame 5NM_016608ALEX1ALEX1 proteinHypothetical protein35867554NM_016610TLR8toll-like receptor 8Hypothetical protein, Receptor,35877555Immune response, Inflammatoryresponse, Signal, Transmembrane,Repeat, Leucine-rich repeat,GlycoproteinNM_016612MSCPmitochondrial soluteHypothetical protein35887556carrier proteinNM_016616TXNDC3thioredoxin domainRedox-active center35897557containing 3(spermatozoa)NM_016619PLAC8placenta-specific 835907558NM_016623BM-009hypothetical proteinHypothetical protein35917559BM-009NM_016626LOC51320hypothetical proteinMetal-binding, Zinc, Zinc-finger35927560LOC51320NM_016630ACP33acid cluster proteinHypothetical protein3593756133NM_016639TNFRSF12Atumor necrosis factorReceptor, Angiogenesis, Apoptosis,35947562receptor superfamily,Transmembrane, Signal, Alternativemember 12AsplicingNM_016640MRPS30mitochondrialRibosomal protein, Mitochondrion35957563ribosomal proteinS30NM_016733LIMK2LIM domain kinase 2Transferase, Serine/threonine-35967564protein kinase, ATP-binding, Repeat,LIM domain, Metal-binding, Zinc,Kinase, Tyrosine-protein kinase,Hypothetical proteinNM_016826OGG18-oxoguanine DNAHydrolase, Nuclease, Endonuclease,35977565glycosylaseLyase, DNA repair, Glycosidase,Multifunctional enzyme, Nuclearprotein, Mitochondrion, Alternativesplicing, Polymorphism, 3D-structure, Transferase,Serine/threonine-protein kinase,Calmodulin-binding,Phosphorylation,NM_016827OGG18-oxoguanine DNAHydrolase, Nuclease, Endonuclease,35987566glycosylaseLyase, DNA repair, Glycosidase,Multifunctional enzyme, Nuclearprotein, Mitochondrion, Alternativesplicing, Polymorphism, 3D-structure, Transferase,Serine/threonine-protein kinase,Calmodulin-binding,Phosphorylation,NM_016836RBMS1RNA binding motif,DNA-binding, DNA replication, RNA-35997567single strandedbinding, Nuclear protein,interacting protein 1PhosphorylationNM_016839RBMS1RNA binding motif,DNA-binding, DNA replication, RNA-36007568single strandedbinding, Nuclear protein,interacting protein 1PhosphorylationNM_016936UBN1ubinuclein 136017569NM_016951CKLFchemokine-likeChemotaxis, Cytokine,36027570factorTransmembrane, Alternative splicingNM_017409HOXC10homeo box C10Homeobox, DNA-binding,36037571Developmental protein, Nuclearprotein, Transcription regulationNM_017414USP18ubiquitin specificUbl conjugation pathway, Hydrolase,36047572protease 18Thiol protease, Multigene familyNM_017415KLHL3kelch-like 3Cytoskeleton, Actin-binding, Kelch36057573(Drosophila)repeat, Repeat, Alternative splicingNM_017421COQ3coenzyme Q3Transferase36067574homolog,methyltransferase(yeast)NM_017424CECR1cat eye syndromeHydrolase, Signal, Hypothetical36077575chromosome region,proteincandidate 1NM_017426NUP54nucleoporin 54 kDaHypothetical protein, Transport,36087576Nuclear protein, Repeat,Glycoprotein, Alternative splicingNM_017451BAIAP2BAI1-associatedReceptor, SH3 domain, Hypothetical36097577protein 2protein, ATP-binding, TransferaseNM_017455SDFR1stromal cell derivedImmunoglobulin domain,36107578factor receptor 1Hypothetical protein, ReceptorNM_017456PSCD1pleckstrin homology,Guanine-nucleotide releasing factor,36117579Sec7 and coiled-coilCoiled coil, Alternative splicing, 3D-domains 1(cytohesinstructure1)NM_017491WDR1WD repeat domain 1Repeat, WD repeat, Hypothetical36127580protein, Actin-binding, Cytoskeleton,Alternative splicing, PolymorphismNM_017493HSHIN1HIV-1 induced36137581protein HIN-1NM_017535DKFZp566H0824hypothetical proteinHypothetical protein36147582DKFZp566H0824NM_017544NRFNF-kappa B-Transcription regulation, Repressor,36157583repressing factorDNA-binding, Nuclear proteinNM_017546C40hypothetical proteinHypothetical protein36167584C40NM_017555EGLN2egl nine homolog 2Oxidoreductase, Dioxygenase,36177585(C. elegans)Nuclear protein, Iron, Vitamin CNM_017567NAGKN-acetylglucosamineKinase, Transferase, ATP-binding,36187586kinasePhosphorylation, HypotheticalproteinNM_017571LOC55580hypothetical proteinHypothetical protein36197587LOC55580NM_017572MKNK2MAP kinase-Hypothetical protein, ATP-binding,36207588interactingKinase, Serine/threonine-proteinserine/threoninekinase, Transferase, Translationkinase 2regulation, Phosphorylation,Alternative splicingNM_017596KIAA0449KIAA0449 proteinHypothetical protein, Repeat, WD36217589repeatNM_017622FLJ20014hypothetical proteinHypothetical protein36227590FLJ20014NM_017631FLJ20035hypothetical proteinHypothetical protein36237591FLJ20035NM_017633C6orf37chromosome 6 openHypothetical protein36247592reading frame 37NM_017646IPTtRNAHypothetical protein, Transferase36257593isopentenyltransferase 1NM_017664ANKRD10ankyrin repeatHypothetical protein, ANK repeat,36267594domain 10RepeatNM_017681FLJ20130hypothetical proteinHypothetical protein, Porin36277595FLJ20130NM_017694FLJ20160FLJ20160 proteinHypothetical protein36287596NM_017700FLJ20184hypothetical proteinHypothetical protein36297597FLJ20184NM_017703FBXL12F-box and leucine-Ubl conjugation pathway, Repeat,36307598rich repeat proteinLeucine-rich repeat, Alternative12splicingNM_017714C20orf13chromosome 20Hydrolase36317599open reading frame13NM_017730FLJ20259FLJ20259 proteinHypothetical protein36327600NM_017735FLJ20272hypothetical proteinHypothetical protein36337601FLJ20272NM_017737FLJ20275transducer of Cdc42-Hypothetical protein, SH3 domain36347602dependent actinassembly 1NM_017740ZDHHC7zinc finger, DHHCTransmembrane, Zinc-finger,36357603domain containing 7Alternative splicingNM_017742FLJ20281zinc finger, CCHCHypothetical protein, Zinc-finger36367604domain containing 2NM_017746FLJ20287hypothetical protein-Hypothetical protein36377605FLJ20287NM_017756FLJ20306hypothetical proteinHypothetical protein36387606FLJ20306NM_017775FLJ20343hypothetical proteinHypothetical protein36397607FLJ20343NM_017785FLJ20364hypothetical proteinHypothetical protein36407608FLJ20364NM_017787FLJ20154chromosome 10Hypothetical protein36417609open reading frame26NM_017801CKLFSF6chemokine-likeChemotaxis, Cytokine,36427610factor super family 6TransmembraneNM_017803FLJ20399hypothetical proteinHypothetical protein36437611FLJ20399NM_017812FLJ20420hypothetical proteinHypothetical protein36447612FLJ20420NM_017814FLJ20422hypothetical proteinHypothetical protein36457613FLJ20422NM_017816LYARhypothetical proteinHypothetical protein36467614FLJ20425NM_017817RAB20RAB20, memberGTP-binding, Lipoprotein,36477615RAS oncogenePrenylation, Protein transport,familyPolymorphismNM_017819FLJ20432hypothetical proteinHypothetical protein36487616FLJ20432NM_017820FLJ20433hypothetical proteinHypothetical protein36497617FLJ20433NM_017821RHBDL2rhomboid, veinlet-Hydrolase, Protease, Serine36507618like 2 (Drosophila)protease, TransmembraneNM_017824FLJ20445hypothetical proteinHypothetical protein36517619FLJ20445NM_017836FLJ20473hypothetical proteinHypothetical protein36527620FLJ20473NM_017838NOLA2nucleolar protein36537621family A, member 2(H/ACA smallnucleolar RNPs)NM_017840MRPL16mitochondrialRibosomal protein, Hypothetical36547622ribosomal proteinproteinL16NM_017844ANKMY1ankyrin repeat andHypothetical protein, ANK repeat,36557623MYND domainRepeat, Zinc-finger, Alternativecontaining 1splicingNM_017847C1orf27chromosome 1 openHypothetical protein36567624reading frame 27NM_017849FLJ20507hypothetical proteinHypothetical protein36577625FLJ20507NM_017850FLJ20508hypothetical proteinHypothetical protein36587626FLJ20508NM_017859URKL1uridine kinase-like 1Transferase, Kinase, ATP-binding36597627NM_017866FLJ20533hypothetical proteinHypothetical protein36607628FLJ20533NM_017874C20orf27chromosome 20Hypothetical protein36617629open reading frame27NM_017885FLJ20568host cell factor C1Hypothetical protein36627630regulator 1 (XPO1dependant)NM_017895DDX27DEAD (Asp-Glu-Ala-Hydrolase, Helicase, ATP-binding,36637631Asp) box polypeptideNuclear protein, Alternative splicing27NM_017899TSChypothetical proteinCalcium-binding, Hypothetical36647632FLJ20607proteinNM_017900FLJ20608aurora-A kinaseHypothetical protein, Nuclear protein36657633interacting proteinNM_017906FLJ20624PAK1 interactingHypothetical protein, Repeat, WD36667634protein 1repeatNM_017907FLJ20625hypothetical proteinHypothetical protein36677635FLJ20625NM_017910FLJ20628hypothetical proteinHypothetical protein36687636FLJ20628NM_017942BTBD1BTB (POZ) domain36697637containing 1NM_017952FLJ20758FLJ20758 proteinHypothetical protein36707638NM_017953FLJ20729hypothetical proteinHypothetical protein36717639FLJ20729NM_017956FLJ20772hypothetical proteinHypothetical protein36727640FLJ20772NM_017983KIAA1001hypothetical proteinHypothetical protein, Repeat, WD36737641FLJ10055repeatNM_018007FBXO4Homo sapiens cDNAUbl conjugation pathway,36747642FLJ10141 fis, cloneHypothetical proteinHEMBA1003199.NM_018024FLJ10204hypothetical proteinHypothetical protein36757643FLJ10204NM_018044WBSCR20AWilliams BeurenNuclear protein, Transport,36767644syndromeTransmembrane, Repeat,chromosome regionHypothetical protein20ANM_018045FLJ10276hypothetical proteinHypothetical protein36777645FLJ10276NM_018050FLJ10298hypothetical proteinHypothetical protein36787646FLJ10298NM_018051FLJ10300hypothetical proteinHypothetical protein, Repeat, WD36797647FLJ10300repeatNM_018053FLJ10307hypothetical proteinHypothetical protein36807648FLJ10307NM_018056FLJ10315hypothetical proteinHypothetical protein36817649FLJ10315NM_018059FLJ10324hypothetical proteinHypothetical protein36827650FLJ10324NM_018067FLJ10350hypothetical proteinHypothetical protein36837651FLJ10350NM_018075FLJ10375hypothetical proteinHypothetical protein36847652FLJ10375NM_018087FLJ10407hypothetical proteinHypothetical protein36857653FLJ10407NM_018089FLJ10415hypothetical proteinHypothetical protein, ANK repeat,36867654FLJ10415RepeatNM_018093FLJ10439hypothetical proteinHypothetical protein, Repeat, WD36877655FLJ10439repeatNM_018099FLJ10462hypothetical proteinHypothetical protein36887656FLJ10462NM_018100FLJ10466EF-hand domain (C-Hypothetical protein36897657terminal) containing 1NM_018113LIMRlipocalin-interactingHypothetical protein, Receptor36907658membrane receptorNM_018119SINRNA polymerase IIITransferase, DNA-directed RNA3691765980 kDa subunitpolymerase, Transcription, NuclearRPC5protein, Alternative splicingNM_018125FLJ10521hypothetical proteinHypothetical protein36927660FLJ10521NM_018127ELAC2elaC homolog 2 (E. coli)Hypothetical protein36937661NM_018128SRRhypothetical proteinIsomerase, Pyridoxal phosphate,36947662FLJ10534Hypothetical proteinNM_018137PRMT6protein arginine N-Transferase, Methyltransferase,36957663methyltransferase 6Nuclear protein, MethylationNM_018140FLJ10565hypothetical proteinHypothetical protein36967664FLJ10565NM_018142FLJ10569hypothetical proteinHypothetical protein36977665FLJ10569NM_018147FAIMFas apoptoticApoptosis, Alternative splicing36987666inhibitory moleculeNM_018158SLC4A1APsolute carrier familyHypothetical protein, Transcription369976674 (anion exchanger),regulation, Nuclear protein, Antigen,member 1, adaptorAlternative splicingproteinNM_018161FLJ10631NAD synthetase 1Hypothetical protein37007668NM_018169FLJ10652hypothetical proteinHypothetical protein37017669FLJ10652NM_018170FLJ10656hypothetical proteinKinase, Hypothetical protein37027670FLJ10656NM_018174VCY2IP1VCY2 interactingHypothetical protein37037671protein 1NM_018182FLJ10700hypothetical proteinHypothetical protein37047672FLJ10700NM_018191RCBTB1regulator ofHypothetical protein37057673chromosomecondensation(RCC1) and BTB(POZ) domaincontaining protein 1NM_018194FLJ10724melanoma antigenHypothetical protein37067674recognized by Tcells 2NM_018195FLJ10726hypothetical proteinHypothetical protein37077675FLJ10726NM_018197ZFP64zinc finger protein 64Transcription regulation, Zinc-finger,37087676homolog (mouse)Metal-binding, Nuclear protein, DNA-binding, Repeat, Alternative splicingNM_018203FLJ10748hypothetical proteinHypothetical protein37097677FLJ10748NM_018208FLJ10761putativeTransferase, Kinase37107678ethanolamine kinaseNM_018209ARFGAP1ADP-ribosylationTransport, Protein transport,37117679factor GTPaseGTPase activation, Golgi stack,activating protein 1Zinc-finger, Alternative splicing,PolymorphismNM_018217C20orf31chromosome 20Hydrolase, Glycosidase,37127680open reading frameGlycoprotein, Signal, Polymorphism31NM_018226RNPEPL1arginylAminopeptidase, Hydrolase, Zinc,37137681aminopeptidaseMetalloprotease(aminopeptidase B)-like 1NM_018235FLJ10830cytosolic nonspecificHydrolase, Carboxypeptidase,37147682dipeptidase (ECMetalloprotease, Hypothetical3.4.13.18)proteinNM_018243FLJ10849hypothetical proteinHypothetical protein37157683FLJ10849NM_018246FLJ10853hypothetical proteinHypothetical protein37167684FLJ10853NM_018255STATIP1signal transducerHypothetical protein, Repeat, WD37177685and activator ofrepeattranscription 3interacting protein 1NM_018256WDR12WD repeat domainRepeat, WD repeat, Polymorphism3718768612NM_018257C20orf36chromosome 20Transcription regulation, Zinc-finger,37197687open reading frameDNA-binding, Nuclear protein,36Repeat, Alternative splicingNM_018259FLJ10890hypothetical proteinHypothetical protein37207688FLJ10890NM_018264FLJ10900hypothetical proteinHypothetical protein37217689FLJ10900NM_018265FLJ10901hypothetical proteinHypothetical protein37227690FLJ10901NM_018267H2AFJH2A histone family,Hypothetical protein37237691member JNM_018275FLJ10925hypothetical proteinHypothetical protein37247692FLJ10925NM_018306FLJ11036hypothetical proteinHypothetical protein37257693FLJ11036NM_018317FLJ11082hypothetical proteinHypothetical protein37267694FLJ11082NM_018319TDP1tyrosyl-DNAHypothetical protein, Hydrolase,37277695phosphodiesterase 1DNA repair, Repeat, Nuclear protein,3D-structure, Disease mutationNM_018321RAD1BRIXHypothetical protein, Ribosome37287696biogenesis, Nuclear protein, Cellcycle, ExonucleaseNM_018322C6orf64chromosome 6 openHypothetical protein, Dynein37297697reading frame 64NM_018324FLJ11106hypothetical proteinHypothetical protein37307698FLJ11106NM_018326HIMAP4immunity associatedGTP-binding, Coiled coil,37317699protein 4PolymorphismNM_018332DDX19hypothetical proteinATP-binding, Helicase, Hydrolase,37327700FLJ11126RNA-binding, Nuclear protein,Hypothetical proteinNM_018333FLJ20666hypothetical proteinHypothetical protein37337701FLJ20666NM_018358FLJ11198ATP-bindingHypothetical protein, ATP-binding37347702cassette, sub-familyF (GCN20), member 3NM_018359FLJ11200hypothetical proteinHypothetical protein37357703FLJ11200NM_018361FLJ11210acid acyltransferase-Phospholipid biosynthesis,37367704epsilonTransferase, Acyltransferase,TransmembraneNM_018371ChGnchondroitin beta1,4Transferase, Hypothetical protein37377705N-acetylgalactosaminyltransferaseNM_018373SYNJ2BPsynaptojanin 2Mitochondrion, Outer membrane,37387706binding proteinTransmembraneNM_018379FLJ11280hypothetical proteinHypothetical protein37397707FLJ11280NM_018386FLJ11305hypothetical proteinHypothetical protein37407708FLJ11305NM_018387STRBPspermatidHypothetical protein37417709perinuclear RNAbinding proteinNM_018391FLJ23277ubiquitin specificHypothetical protein, Protease37427710protease 31NM_018394FLJ11342hypothetical proteinHypothetical protein37437711FLJ11342NM_018399VNN3vanin 3Hydrolase, Signal, Glycoprotein,37447712GPI-anchor, LipoproteinNM_018403HSA275986transcription factorHypothetical protein37457713SMIFNM_018404CENTA2centaurin, alpha 2GTPase activation, Repeat, Zinc-37467714fingerNM_018407LAPTM4Blysosomal37477715associated proteintransmembrane 4betaNM_018421TBC1D2TBC1 domain family,Hypothetical protein, GTPase37487716member 2activation, AntigenNM_018422DKFZp761K1423hypothetical proteinHypothetical protein37497717DKFZp761K1423NM_018423DKFZp761p1010protein kinaseATP-binding, Kinase, Receptor,37507718STYK1Transferase, Tyrosine-proteinkinase, Hypothetical proteinNM_018441PECRperoxisomal trans 2-Oxidoreductase37517719enoyl CoA reductaseNM_018443ZNF302zinc finger proteinHypothetical protein, Metal-binding,37527720302Zinc, Zinc-finger, Transcriptionregulation, DNA-binding, Nuclearprotein, Repeat, Alternative splicingNM_018449UBAP2ubiquitin associatedHypothetical protein37537721protein 2NM_018452C6orf35chromosome 6 openHypothetical protein37547722reading frame 35NM_018457DKFZP564J157DKFZp564J157Hypothetical protein37557723proteinNM_018465MDS030chromosome 9 openHypothetical protein37567724reading frame 46NM_018472HT011uncharacterizedHypothetical protein37577725hypothalamusprotein HT011NM_018480HT007uncharacterizedHypothetical protein37587726hypothalamusprotein HT007NM_018485GPR77G protein-coupledG-protein coupled receptor,37597727receptor 77Transmembrane, GlycoproteinNM_018486HDAC8histone deacetylase 8Hydrolase, Nuclear protein,37607728Chromatin regulator, Transcriptionregulation, Repressor, AlternativesplicingNM_018491LOC55871COBW-like proteinHypothetical protein37617729NM_018515PRO2176EST, Highly similar37627730to hypotheticalprotein PRO2176[Homo sapiens][H. sapiens]NM_018520PRO2268hypothetical protein37637731PRO2268NM_018533RAB7Homo sapiens cDNAGTP-binding, Lipoprotein,37647732FLJ20819 fis, clonePrenylation, Protein transport,ADSE00511.Hypothetical proteinNM_018556SIRPB2signal-regulatoryRepeat, Signal, Transmembrane,37657733protein beta 2Immunoglobulin domain,Glycoprotein, Alternative splicingNM_018569PRO0971hypothetical proteinHypothetical protein37667734PRO0971NM_018572PRO1051E2F transcription37677735factor 3NM_018590PRO0082chondroitin sulfateHypothetical protein, Transferase37687736GalNAcT-2NM_018594PRO0823FYN binding proteinSH3 domain, Phosphorylation,37697737(FYB-120/130)Nuclear protein, Coiled coil,Alternative splicingNM_018615PRO2032Homo sapiens37707738hypothetical proteinPRO2032(PRO2032), mRNA.NM_018638EKI1ethanolamine kinaseTransferase, Kinase37717739NM_018643TREM1triggering receptorReceptor37727740expressed onmyeloid cells 1NM_018648NOLA3nucleolar protein37737741family A, member 3(H/ACA smallnucleolar RNPs)NM_018676THSD1thrombospondin,Signal37747742type I, domain 1NM_018687LOC55908hepatocellular37757743carcinoma-associated geneTD26NM_018688BIN3bridging integrator 3Septation, Cytoskeleton, Coiled coil,37767744Hypothetical proteinNM_018690APOB48Rapolipoprotein B48Hypothetical protein, Lipoprotein,37777745receptorReceptorNM_018699PRDM5PR domainTranscription regulation, DNA-37787746containing 5binding, Zinc-finger, Metal-binding,Nuclear protein, RepeatNM_018728MYO5Cmyosin VCMyosin, Repeat, ATP-binding,37797747Calmodulin-binding, Actin-binding,Coiled coil, PolymorphismNM_018834MATR3matrin 3Nuclear protein, RNA-binding,37807748Repeat, Zinc-fingerNM_018839NSFL1CNSFL1 (p97)Hypothetical protein37817749cofactor (p47)NM_018840C20orf24chromosome 20Alternative splicing, Membrane, SH237827750open reading framedomain, SH3 domain, Myristate,24Phosphorylation, Alternativeinitiation, LipoproteinNM_018939PCDHB6protocadherin beta 6Calcium-binding, Cell adhesion,37837751Glycoprotein, Signal, Repeat,Transmembrane, Multigene familyNM_018959DAZAP1DAZ associatedHypothetical protein37847752protein 1NM_018961UBASH3Aubiquitin associatedNuclear protein, SH3 domain,37857753and SH3 domainAlternative splicingcontaining, ANM_018983NOLA1nucleolar protein37867754family A, member 1(H/ACA smallnucleolar RNPs)NM_018996FLJ20015KIAA1582 proteinHypothetical protein37877755NM_019002ETAA16ETAA16 protein37887756NM_019009TOLLIPtoll interactingHypothetical protein, Immune37897757proteinresponse, Inflammatory responseNM_019012PEPP2phosphoinositol 3-Hypothetical protein37907758phosphate-bindingprotein-2NM_019018FLJ11127hypothetical proteinHypothetical protein37917759FLJ11127NM_019042FLJ20485hypothetical proteinHypothetical protein, tRNA37927760FLJ20485processing, LyaseNM_019057FLJ10404hypothetical proteinHypothetical protein37937761FLJ10404NM_019063EML4echinodermMicrotubule, Repeat, WD repeat,37947762microtubuleHypothetical proteinassociated-proteinlike 4NM_019067FLJ10613hypothetical proteinHypothetical protein37957763FLJ10613NM_019084FLJ10895hypothetical proteinHypothetical protein37967764FLJ10895NM_019096GTPBP2GTP binding protein 2GTP-binding, Protein biosynthesis,37977765Hypothetical proteinNM_019112ABCA7ATP-bindingATP-binding, Hypothetical protein37987766cassette, sub-familyA (ABC1), member 7NM_019554S100A4S100 calciumCalcium-binding, 3D-structure37997767binding protein A4(calcium protein,calvasculin,metastasin, murineplacental homolog)NM_019604CRTAMclass-I MHC-38007768restricted T cellassociated moleculeNM_019848P3solute carrier familyTransmembrane, Transport,3801776910 (sodium/bile acidSymportcotransporterfamily), member 3NM_019892PPI5PIVinositol38027770polyphosphate-5-phosphatase, 72 kDaNM_019896POLE4polymerase (DNA-DNA-directed DNA polymerase,38037771directed), epsilon 4DNA-binding, Nuclear protein(p12 subunit)NM_020038ABCC3ATP-bindingATP-binding, Glycoprotein,38047772cassette, sub-familyTransmembrane, Transport, Repeat,C (CFTR/MRP),Alternative splicingmember 3NM_020123SMBPSM-11044 bindingHypothetical protein, Signal,38057773proteinTransmembraneNM_020133LPAAT-1-acylglycerol-3-Phospholipid biosynthesis,38067774deltaphosphate O-Transferase, Acyltransferase,acyltransferase 4Transmembrane(lysophosphatidicacid acyltransferase,delta)NM_020134DPYSL5dihydropyrimidinase-Hypothetical protein38077775like 5NM_020135WHIPWerner helicaseATP-binding, Helicase, Hypothetical38087776interacting protein 1proteinNM_020139LOC56898dehydrogenase/reductaseOxidoreductase, Hypothetical protein38097777(SDR family)member 6NM_020143LOC56902putatative 28 kDaHypothetical protein38107778proteinNM_020149MEIS2Meis1, myeloidHypothetical protein, Homeobox,38117779ecotropic viralDNA-binding, Nuclear protein,integration site 1Alternative splicinghomolog 2 (mouse)NM_020152C21orf7chromosome 21Alternative splicing, Hypothetical38127780open reading frame 7proteinNM_020158RRP46exosome componentExosome, Hydrolase, Nuclease,38137781Rrp46Exonuclease, rRNA processing,Nuclear protein, RNA-binding,AntigenNM_020166MCCC1methylcrotonoyl-Mitochondrion, Ligase, Biotin, ATP-38147782Coenzyme Abinding, Transit peptide, Diseasecarboxylase 1mutation, Polymorphism(alpha)NM_020179FN5FN5 protein38157783NM_020184CNNM4cyclin M4Hypothetical protein38167784NM_020188DC13DC13 protein38177785NM_020193C11ORF30chromosome 11Hypothetical protein38187786open reading frame30NM_020198GK001GK001 proteinHypothetical protein38197787NM_020200HHGPphosphoribosylTransferase38207788transferase domaincontaining 1NM_020201NT5M5′,3′-nucleotidase,Nucleotide metabolism, Hydrolase,38217789mitochondrialMitochondrion, Nucleotide-binding,Magnesium, Transit peptide, 3D-structureNM_020216RNPEParginylAminopeptidase, Hydrolase, Zinc,38227790aminopeptidaseMetalloprotease(aminopeptidase B)NM_020229PRDM11PR domainHypothetical protein38237791containing 11NM_020231MDS010x 010 proteinHypothetical protein38247792NM_020234MDS009x 009 proteinHypothetical protein38257793NM_020236MRPL1mitochondrialHypothetical protein, Ribosomal38267794ribosomal protein L1proteinNM_020239SPEC1small protein effectorHypothetical protein382777951 of Cdc42NM_020243TOMM22translocase of outerReceptor, Translocation, Transport,38287796mitochondrialProtein transport, Outer membrane,membrane 22Mitochondrion, Transmembranehomolog (yeast)NM_020313LOC57019hypothetical proteinHypothetical protein38297797LOC57019NM_020314MGC16824esophageal cancerHypothetical protein38307798associated proteinNM_020322ACCN3amiloride-sensitiveIonic channel38317799cation channel 3NM_020344SLC24A2solute carrier familyVision, Transport, Antiport, Symport,3832780024Calcium transport, Potassium(sodium/potassium/calciumtransport, Sodium transport,exchanger),Transmembrane, Glycoprotein,member 2Signal, Repeat, Alternative splicingNM_020347LZTFL1leucine zipper38337801transcription factor-like 1NM_020350AGTRAPangiotensin IIReceptor38347802receptor-associatedproteinNM_020357PCNPPEST-containingNuclear protein38357803nuclear proteinNM_020360PLSCR3phospholipidHypothetical protein,38367804scramblase 3Transmembrane, Lipoprotein,Calcium-binding, SH3-binding,Repeat, Phosphorylation, Palmitate,PolymorphismNM_020365EIF2B3eukaryoticInitiation factor, Protein biosynthesis,38377805translation initiationAlternative splicing, Diseasefactor 2B, subunit 3mutation, Hypothetical proteingamma, 58 kDaNM_020366RPGRIP1retinitis pigmentosa38387806GTPase regulatorinteracting protein 1NM_020370GPR84G protein-coupledReceptor38397807receptor 84NM_020371AVENapoptosis, caspaseApoptosis38407808activation inhibitorNM_020385XPMC2HXPMC2 preventsHypothetical protein38417809mitotic catastrophe 2homolog (Xenopuslaevis)NM_020390EIF5A2eukaryoticInitiation factor, Hypothetical protein38427810translation initiationfactor 5A2NM_020394LOC57116zinc finger proteinMetal-binding, Zinc, Zinc-finger38437811SBZF3NM_020399PISTgolgi associatedHypothetical protein38447812PDZ and coiled-coilmotif containingNM_020401NUP107nuclear poreNuclear protein, Transport38457813complex proteinNM_020406PRV1polycythemia rubraSignal, Receptor38467814vera 1NM_020408CGI-203chromosome 6 openHypothetical protein38477815reading frame 149NM_020410CGI-152cation-transportingHydrolase, Transmembrane,38487816ATPasePhosphorylation, Magnesium, ATP-binding, Alternative splicing,Hypothetical proteinNM_020414DDX24DEAD (Asp-Glu-Ala-Hydrolase, Helicase, ATP-binding,38497817Asp) box polypeptideRNA-binding24NM_020415RETNresistinHormone, Signal, Diabetes mellitus,38507818ObesityNM_020466DJ122O8.2hypothetical proteinHypothetical protein38517819dJ122O8.2NM_020469ABOABO blood groupTransferase, Glycosyltransferase,38527820(transferase A, alphaBlood group antigen, Golgi stack,1-3-N-Metal-binding, Manganese, Signal-acetylgalactosaminylanchor, Transmembrane,transferase;Glycoprotein, Polymorphism, 3D-transferase B, alphastructure1-3-galactosyltransferase)NM_020480ANK1ankyrin 1,ANK repeat, Repeat, Cytoskeleton,38537821erythrocyticAlternative splicing, Phosphorylation,Lipoprotein, Disease mutation,Elliptocytosis, PolymorphismNM_020484AF011757Homo sapiens38547822RAGE bindingprotein (AF011757),mRNA.NM_020530OSMoncostatin MGrowth regulation, Cytokine,38557823Glycoprotein, Signal, 3D-structureNM_020533MCOLN1mucolipin 1Hypothetical protein, Ionic channel,38567824TransmembraneNM_020548DBIdiazepam bindingTransport, Lipid-binding, Acetylation,38577825inhibitor (GABAAlternative splicingreceptor modulator,acyl-Coenzyme Abinding protein)NM_020632ATP6V0A4ATPase, H+Hydrogen ion transport,38587826transporting,Transmembrane, Glycoprotein,lysosomal V0Disease mutation, Hypotheticalsubunit a isoform 4proteinNM_020639ANKRD3ankyrin repeatANK repeat, Repeat, Hypothetical38597827domain 3protein, ATP-binding, Kinase,Serine/threonine-protein kinase,Transferase, Alternative splicingNM_020648TWSG1twisted gastrulationHypothetical protein, Signal38607828homolog 1(Drosophila)NM_020652ZNF286zinc finger proteinTranscription regulation, Zinc-finger,38617829286Metal-binding, Nuclear protein, DNA-binding, RepeatNM_020659TTYH1tweety homolog 138627830(Drosophila)NM_020664DECR22,4-dienoyl CoAHypothetical protein, Oxidoreductase38637831reductase 2,peroxisomalNM_020686NPD0094-aminobutyrate38647832aminotransferaseNM_020905RDH14retinolOxidoreductase, NADP38657833dehydrogenase 14(all-trans and 9-cis)NM_020980AQP9aquaporin 9Transport, Repeat, Transmembrane38667834NM_020983ADCY6adenylate cyclase 6Lyase, cAMP biosynthesis,38677835Transmembrane, Glycoprotein,Repeat, Metal-binding, Magnesium,Alternative splicingNM_020995HPRhaptoglobin-relatedHydrolase, Protease, Serine38687836proteinproteaseNM_020999NEUROG3neurogenin 338697837NM_021018HIST1H3Fhistone 1, H3fNuclear protein, Chromosomal38707838protein, DNA-binding, Nucleosomecore, Multigene family, Acetylation,MethylationNM_021019MYL6myosin, lightMyosin, Muscle protein, Acetylation,38717839polypeptide 6, alkali,Alternative splicing, Multigene familysmooth muscle andnon-muscleNM_021025TLX3T-cell leukemia,Homeobox, DNA-binding, Nuclear38727840homeobox 3protein, Developmental proteinNM_021031CYCLHomo sapiensHypothetical protein38737841cytochrome c-likeantigen (CYCL),mRNANM_021039S100A14S100 calciumTranscription regulation, DNA-38747842binding protein A14binding, Nuclear protein,(calgizzarin)Hypothetical protein, Calcium-bindingNM_021074NDUFV2NADHOxidoreductase, NAD, Ubiquinone,38757843dehydrogenaseMitochondrion, Transit peptide,(ubiquinone)Metal-binding, Iron-sulfur, Iron, 2Fe—2S,flavoprotein 2,Polymorphism24 kDaNM_021075NDUFV3NADHHypothetical protein38767844dehydrogenase(ubiquinone)flavoprotein 3,10 kDaNM_021078GCN5L2GCN5 generalTranscription regulation,38777845control of amino-acidTransferase, Nuclear protein,synthesis 5-like 2Bromodomain, Alternative splicing,(yeast)3D-structureNM_021079NMT1N-Acyltransferase, Transferase,38787846myristoyltransferase 1Alternative splicingNM_021090MTMR3myotubularin relatedHydrolase, Zinc-finger, Alternative38797847protein 3splicingNM_021103TMSB10thymosin, beta 10Actin-binding, Cytoskeleton,38807848AcetylationNM_021106RGS3regulator of G-Hypothetical protein, Signal38817849protein signalling 3transduction inhibitor, Alternativesplicing, PhosphorylationNM_021131PPP2R4protein phosphataseAlternative splicing388278502A, regulatorysubunit B′ (PR 53)NM_021173POLD4polymerase (DNA-DNA-directed DNA polymerase,38837851directed), delta 4DNA replication, Nuclear proteinNM_021178HEI10chromosome 14Ubl conjugation pathway, Ligase,38847852open reading frameNuclear protein, Metal-binding, Zinc,18Coiled coil, Zinc-finger,Phosphorylation, Ubl conjugationNM_021197WFDC1WAP four-disulfideSerine protease inhibitor, Signal38857853core domain 1NM_021198NLI-IFCTD (carboxy-Hypothetical protein, Nuclear protein38867854terminal domain,RNA polymerase II,polypeptide A) smallphosphatase 1NM_021199SQRDLsulfide quinoneOxidoreductase, Flavoprotein, FAD,38877855reductase-likeNADP, Mitochondrion, Transit(yeast)peptide, PolymorphismNM_021212ZFHCF-bindingDNA-binding, Nuclear protein38887856transcription factorZhangfeiNM_021238TERATERA proteinHypothetical protein38897857NM_021242STRAIT11499MID1 interactingHypothetical protein38907858G12-like proteinNM_021251CAPN10calpain 10Hydrolase, Thiol protease, Repeat,38917859Alternative splicing, Polymorphism,Diabetes mellitusNM_021259TMEM8transmembraneCell adhesion, Signal,38927860protein 8 (fiveTransmembrane, EGF-like domain,membrane-spanningGlycoproteindomains)S73288smallsmall proline-rich38937861proline-richprotein 1AproteinSPRKS74639IGHMClone I50Immunoglobulin domain,38947862immunoglobulinImmunoglobulin C region,heavy chain variableGlycoprotein, Repeat, Pyrrolidoneregion mRNA, partialcarboxylic acid, Polymorphism,cdsMembrane, Hypothetical protein,Receptor, T-cell, SignalS77356ATP5OATP synthase, H+Hydrolase, ATP synthesis, CF(1),38957863transporting,Hydrogen ion transport,mitochondrial F1Mitochondrion, Transit peptide,complex, O subunitPolymorphism(oligomycinsensitivity conferringprotein)S80864cytochromecytochrome c-likeHypothetical protein38967864c-likeantigenpolypeptideS90469PORP450 (cytochrome)Oxidoreductase, Flavoprotein, FMN,38977865oxidoreductaseFAD, NADP, Endoplasmic reticulum,Membrane, Acetylation,Polymorphism, 3D-structureU00946KIAA0344protein kinase, lysineHypothetical protein, ATP-binding,38987866deficient 1Kinase, Serine/threonine-proteinkinase, TransferaseU01147ABRactive BCR-relatedGuanine-nucleotide releasing factor,38997867geneAlternative splicingU02032RPL23Aribosomal proteinRibosomal protein, rRNA-binding39007868L23aU09196POLD4polymerase (DNA-DNA-directed DNA polymerase,39017869directed), delta 4DNA replication, Nuclear proteinU14383MUC8Human mucin39027870(MUC8) mRNA,partial cds.U20180IREB2iron-responsiveIron-sulfur, 4Fe—4S, RNA-binding,39037871element bindingHypothetical proteinprotein 2U25750hypothetical proteinHypothetical protein39047872MGC20235U36759PTCRApre T-cell antigen39057873receptor alphaU37689POLR2Hpolymerase (RNA) IITransferase, DNA-directed RNA39067874(DNA directed)polymerase, Transcription, Nuclearpolypeptide HproteinU41387DDX21DEAD (Asp-Glu-Ala-Helicase, RNA-binding, ATP-binding,39077875Asp) box polypeptideNuclear protein, Antigen, Repeat21U43431TOP3AtopoisomeraseIsomerase, Topoisomerase, DNA-39087876(DNA) III alphabinding, Repeat, Zinc-finger,Alternative splicing, PolymorphismU43604Human unidentified39097877mRNA, partialsequence.U56725HSPA2Human heat shockATP-binding, Chaperone, Heat39107878protein mRNA,shock, Multigene familycomplete cds.U58033MTMR2myotubularin relatedHydrolase, Charcot-Marie-Tooth39117879protein 2diseaseU64205MARK3MAP/microtubuleTransferase, Serine/threonine-39127880affinity-regulatingprotein kinase, ATP-binding,kinase 3Alternative splicing, PlasmidU66702PTPRN2protein tyrosineHypothetical protein, Hydrolase,39137881phosphatase,Receptor, Glycoprotein, Signal,receptor type, NTransmembrane, Diabetes mellitus,polypeptide 2Alternative splicingU68382MAN2B1mannosidase, alpha,Glycosidase, Hydrolase,39147882class 2B, member 1Glycoprotein, Lysosome, Zymogen,Signal, Disease mutation,PolymorphismU68494solute carrier family3915788330 (zinc transporter),member 1U69127FUBP3far upstreamTranscription regulation, Transacting39167884element (FUSE)factor, Nuclear protein, DNA-binding protein 3binding, Repeat, Alternative splicingU69645ZNF32zinc finger protein 32Hypothetical protein, Metal-binding,39177885(KOX 30)Zinc, Zinc-finger, Transcriptionregulation, DNA-binding, Nuclearprotein, RepeatU72882IFI35interferon-inducedInterferon induction, Alternative39187886protein 35splicingU79246DIS3FLJ22624 proteinHypothetical protein39197887U79260MGC5149fatsoHypothetical protein39207888U79277tyrosine 3-Neurone, Phosphorylation,39217889monooxygenase/tryptophanAcetylation, Multigene family, 3D-5-structuremonooxygenaseactivation protein,zeta polypeptideU79280PIPPINRNA-binding proteinHypothetical protein, mRNA39227890pippinprocessing, RNA-binding, NuclearproteinU79282hypothetical proteinHypothetical protein39237891LOC137886U79290Human clone 2390839247892mRNA sequenceU79298MGC39325hypothetical proteinHypothetical protein39257893MGC39325U79458WBP2Human WW domainHypothetical protein39267894binding protein-2mRNA, completecds.U80628TK2thymidine kinase 2,Kinase, Transferase, DNA synthesis,39277895mitochondrialATP-binding, Mitochondrion, Transitpeptide, Alternative splicingU82277LILRA2leukocyteImmune response, Receptor,39287896immunoglobulin-likeRepeat, Signal, Transmembrane,receptor, subfamilyImmunoglobulin domain,B (with TM and ITIMGlycoprotein, Antigen, Alternativedomains), member 1splicing, Polymorphism, Multigenefamily, Phosphorylation, 3D-structureU83115AIM1absent in melanoma 1Repeat, Lectin39297897U90878PDLIM1PDZ and LIMCytoskeleton, LIM domain, Metal-39307898domain 1 (elfin)binding, ZincU90909MISSchromosome 14Hypothetical protein39317899open reading frame32U90911WIREWIRE protein39327900U90916sortilin-relatedEndocytosis, Receptor,39337901receptor, L(DLRTransmembrane, EGF-like domain,class) A repeats-Repeat, Glycoprotein, LDL, Lipidcontainingtransport, Cholesterol metabolism,SignalW61000_RCNORE1Ras associationHypothetical protein39347902(RalGDS/AF-6)domain family 5X00437IGHMHuman mRNA for T-Immunoglobulin domain,39357903cell specific protein.Immunoglobulin C region,Glycoprotein, Repeat, Pyrrolidonecarboxylic acid, Polymorphism,Membrane, Hypothetical protein,Receptor, T-cell, SignalX04201TPM3tropomyosin 3Hypothetical protein, Muscle protein,39367904Cytoskeleton, Actin-binding, Coiledcoil, Alternative splicing, Multigenefamily, Disease mutationX04526GNB1Human liver mRNATransducer, Repeat, WD repeat,39377905for beta-subunitMultigene family, 3D-structuresignal transducingproteins Gs/Gi (beta-G).X07618CYP2D6cytochrome P450,Heme, Monooxygenase,39387906family 2, subfamilyOxidoreductase, Electron transport,D, polypeptide 6Membrane, Microsome,Endoplasmic reticulum,PolymorphismX13956MGC10471hypothetical protein39397907MGC10471X15183HSPCAheat shock 90 kDaHeat shock, Chaperone, ATP-39407908protein 1, alphabinding, Phosphorylation, 3Dstructure, Hypothetical protein,PlasmidX51630WT1Wilms tumor 1Zinc-finger, Metal-binding, DNA-39417909binding, Repeat, Nuclear protein,Transcription regulation, Alternativesplicing, Anti-oncogene, Diseasemutation, Chromosomaltranslocation, 3D-structureX52015IL1RNinterleukin 1 receptorGlycoprotein, Signal, Alternative39427910antagonistsplicing, 3D-structureX52882TCP1t-complex 1Chaperone, ATP-binding, Multigene39437911familyX56789TTS-2.2transport-secretionHypothetical protein39447912protein 2.2X57352IFITM3interferon inducedInterferon induction,39457913transmembraneTransmembraneprotein 3 (1-8 U)X58536HLA-CmajorGlycoprotein, Signal,39467914histocompatibilityTransmembrane, Hypotheticalcomplex, class I, Cprotein, MHC, MHC I,Polymorphism, 3D-structure,Alternative splicingX58794AZU1azurocidin 1Serine protease homolog,39477915(cationicGlycoprotein, Chemotaxis, Antibiotic,antimicrobial proteinHeparin-binding, Signal, 3D-37)structureX59417PSMA6proteasomeProteasome, Hydrolase, Protease,39487916(prosome,Threonine proteasemacropain) subunit,alpha type, 6X61079IGHMT cell receptorImmunoglobulin domain,39497917alpha-chain (TCRImmunoglobulin C region,Valpha20Jalpha9.14)Glycoprotein, Repeat, PyrrolidonemRNA, partial cds.carboxylic acid, Polymorphism,Membrane, Hypothetical protein,Receptor, T-cell, SignalX62535DGKAdiacylglycerolHypothetical protein, Kinase,39507918kinase, alpha 80 kDaTransferase, Calcium-binding,Phorbol-ester binding, Repeat,Multigene familyX63417IRLBc-myc promoter-DNA-binding, Hypothetical protein39517919binding proteinX69115ZNF37Azinc finger proteinHypothetical protein, Metal-binding,3952792037a (KOX 21)Nuclear protein, Zinc, Zinc-finger,Transcription regulation, DNA-binding, RepeatX71490ATP6V0D1H. sapiens mRNA forHydrolase, ATP synthesis, Hydrogen39537921vacuolar protonion transportATPase, subunit D.X78817ARHGAP4Rho GTPaseGTPase activation, SH3 domain,39547922activating protein 4Coiled coilX87949HSPA5heat shock 70 kDaATP-binding, Endoplasmic reticulum,39557923protein 5 (glucose-Signalregulated protein,78 kDa)X89214hprH. sapiens mRNA forHydrolase, Protease, Serine39567924haptoglobin relatedproteaseprotein.X94232MAPRE2microtubule-T-cell39577925associated protein,RP/EB family,member 2X98258MPHOSPH9M-phasePhosphorylation, Golgi stack,39587926phosphoprotein 9Membrane, Coiled coilX98261ZWINTASZW10 interactorPhosphorylation, Nuclear protein,39597927Coiled coilX98411MYO1Fmyosin IFMyosin, ATP-binding, Actin-binding,39607928Calmodulin-binding, SH3 domain,Multigene familyY00433GPX1glutathioneOxidoreductase, Peroxidase,39617929peroxidase 1Selenium, Selenocysteine,Erythrocyte, Polymorphism,Hypothetical proteinY00816CR1complementComplement pathway, Glycoprotein,39627930component (3b/4b)Transmembrane, Repeat, Signal,receptor 1, includingReceptor, Sushi, Blood groupKnops blood groupantigen, Polymorphism, Pyrrolidonesystemcarboxylic acid, 3D-structureY14442OR1F1olfactory receptor,G-protein coupled receptor,39637931family 1, subfamilyTransmembrane, Glycoprotein,F, member 1Multigene family, OlfactionY18490LST1leukocyte specificImmune response, Cell shape,39647932transcript 1Transmembrane, Alternative splicingZ15114PRKCGprotein kinase C,Transferase, Serine/threonine-39657933gammaprotein kinase, ATP-binding,Calcium-binding, Metal-binding,Zinc, Repeat, Phorbol-ester binding,Phosphorylation, PolymorphismZ34893IGHMClone P2-114 anti-Immunoglobulin domain,39667934oxidized LDLImmunoglobulin C region,immunoglobulinGlycoprotein, Repeat, Pyrrolidoneheavy chain Fabcarboxylic acid, Polymorphism,mRNA, partial cdsMembrane, Hypothetical protein,Receptor, T-cell, SignalZ48314MUC5ACmucin 5, subtypes ARepeat, Glycoprotein, Signal,39677935and C,Polymorphism, Hypothetical proteintracheobronchial/gastricZ49105SSX2synovial sarcoma, XChromosomal translocation, Proto-39687936breakpoint 2oncogene, Multigene family,Transcription regulation

7. References Cited

All references cited herein are incorporated herein by reference in their entirety and for all purposes to the same extent as if each individual publication or patent or patent application was specifically and individually indicated to be incorporated by reference in its entirety for all purposes.

Many modifications and variations of the present invention can be made without departing from its spirit and scope, as will be apparent to those skilled in the art. The specific embodiments described herein are offered by way of example only, and the invention is to be limited only by the terms of the appended claims along with the full scope of equivalents to which such claims are entitled.

Genes associate with progression and response in chronic myeloid leukemia and uses thereof

Information

Publication Number

Date Filed

Date Published

Inventors

CPC

US Classifications

International Classifications

Abstract

Description

Claims

Parent Case Info

Government Interests

Provisional Applications (1)