{"entity":{"id":"cdk12","kind":"target","name":"CDK12","aka":["cyclin dependent kinase 12","Cyclin-dependent kinase 12","CRK7","KIAA0904","CRKRS"],"tldr":"CDK12 (Cyclin-dependent kinase 12) is a protein kinase, an enzyme that switches other proteins on by adding phosphate groups. The public catalogues list it as a drug target, an oncogene driver, a tumour suppressor, a biomarker and a fusion partner, and clinical evidence ties its variants to diagnosis, prognosis or drug response. Tied to Prostate cancer, Ovarian cancer, Breast cancer and 5 more.","summary":"Cyclin-dependent kinase that phosphorylates the C-terminal domain (CTD) of the large subunit of RNA polymerase II (POLR2A), thereby acting as a key regulator of transcription elongation. Regulates the expression of genes involved in DNA repair and is required for the maintenance of genomic stability. Preferentially phosphorylates 'Ser-5' in CTD repeats that are already phosphorylated at 'Ser-7', but can also phosphorylate 'Ser-2'.\n\nCIViC holds 9 clinical evidence items and 0 assertions across 4 variants, naming Olaparib, Talazoparib, Enzalutamide and Rucaparib and others. Open Targets scores its association with cancer at 0.80 (direct and indirect evidence; datatypes clinical 0.17, affected pathway 0.76, literature 0.99, genetic association 0.32, somatic mutation 0.92). IntOGen calls it a driver in 17 cohorts (2 activating, 15 loss-of-function), covering Bladder Urothelial Carcinoma, Renal Clear Cell Carcinoma, Cervical Squamous Cell Carcinoma, Diffuse Large B-Cell Lymphoma, NOS, Melanoma, Ovarian Epithelial Tumour and others.","asOf":"2026-09-23","links":[{"label":"HGNC HGNC:24224","url":"https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:24224"},{"label":"UniProt Q9NYV4","url":"https://www.uniprot.org/uniprotkb/Q9NYV4/entry"},{"label":"NCBI Gene 51755","url":"https://www.ncbi.nlm.nih.gov/gene/51755"},{"label":"Ensembl ENSG00000167258","url":"https://www.ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000167258"}],"tags":["cancer-genes-wave"],"related":["civic","open-targets","intogen"],"cancers":["prostate","ovarian","breast-cancer","urothelial","rcc","cervical","gastric","skin-cancer"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-quigley-structural-variation-mcrpc-cell-2018","paper-mateo-genomics-lethal-prostate-diagnosis-castration-resistance-jci-2020","paper-stopsack-mcspc-genomic-alterations-outcomes-ccr-2020"],"journals":[],"dependsOn":[],"notes":["Written by scripts/fetch-cancer-genes.ts from CIViC, Open Targets, IntOGen, HGNC and UniProt; the function text is UniProt's, condensed and in UK spelling. Roles: Open Targets known-drug datatype score 0.17; IntOGen calls it an activating (Act) driver in 2 cohorts; IntOGen calls it a loss-of-function (LoF) driver in 15 cohorts; CIViC holds 9 clinical evidence items on its variants; UniProt disease notes describe a translocation or gene fusion involving the gene. Evidence tier \"clinical-evidence\" is the strongest of those signals.","Prevalence not recorded: none of the sources gives a positivity rate."],"provenance":{"editedBy":"scripts/fetch-cancer-genes.ts (CIViC, Open Targets, IntOGen, HGNC, UniProt)","editedOn":"2026-09-23"},"symbol":"CDK12","role":["drug-target","oncogene-driver","tumour-suppressor","biomarker","fusion-partner"],"evidenceTier":"clinical-evidence","sources":[{"label":"HGNC HGNC:24224","url":"https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:24224","note":"approved symbol, name, aliases, locus and cross-references (hgnc_complete_set.txt)"},{"label":"UniProt Q9NYV4","url":"https://www.uniprot.org/uniprotkb/Q9NYV4/entry","note":"protein name, function text, keywords and locations (REST API)"},{"label":"CIViC gene CDK12","url":"https://civicdb.org/features/12112","note":"9 evidence items, 0 assertions, 4 variants; diseases: Prostate Cancer, Castration-resistant Prostate Carcinoma, Breast Cancer, Ovarian Serous Carcinoma, Breast Carcinoma and 1 more (GraphQL API, CC0)"},{"label":"Open Targets ENSG00000167258","url":"https://platform.opentargets.org/target/ENSG00000167258/associations","note":"association with cancer (MONDO_0004992) 0.80; per-cancer scores at or above 0.5: colorectal cancer 0.52, prostate cancer 0.67, ovarian cancer 0.58, melanoma 0.59, skin cancer 0.56 (GraphQL API, CC0)"},{"label":"IntOGen CDK12","url":"https://www.intogen.org/search?gene=CDK12","note":"driver in 17 cohorts (Act 2, LoF 15); Compendium_Cancer_Genes.tsv release 20240920, CC0 1.0"}],"specificity":"tumour-specific","distribution":"many-types","specificityNote":"Tumour-specific alteration: the catalogues call it an oncogene driver (IntOGen cohort analysis finds it activated more often than chance) and a tumour suppressor (IntOGen finds it knocked out more often than chance) and a fusion partner (UniProt records a translocation), so the direction differs between cohorts but the alteration is somatic either way; what a medicine would aim at or exploit is the altered form or its loss, absent from normal cells; no corpus medicine is aimed at it yet. HPA CDK12: RNA low tissue specificity; high antibody staining in 34 normal tissues; highest cancer staining cervical cancer (12 of 12 high). Distribution: 8 cancer families in the corpus carry a prevalence row, label threshold or catalogue link for it (Prostate cancer, Ovarian cancer, Breast cancer (all types), Bladder & urothelial cancer, Renal cell carcinoma, Cervical cancer, Gastric & gastro-oesophageal junction cancer and more); Open Targets associates it with 1 specific cancer type at or above 0.5 (prostate adenocarcinoma). (Rule 6 of scripts/fetch-target-specificity.ts.)","specificitySources":[{"label":"UniProt Q9NYV4","url":"https://www.uniprot.org/uniprotkb/Q9NYV4/entry","note":"protein name, function text, keywords and locations (REST API)"},{"label":"CIViC gene CDK12","url":"https://civicdb.org/features/12112","note":"9 evidence items, 0 assertions, 4 variants; diseases: Prostate Cancer, Castration-resistant Prostate Carcinoma, Breast Cancer, Ovarian Serous Carcinoma, Breast Carcinoma and 1 more (GraphQL API, CC0)"},{"label":"IntOGen CDK12","url":"https://www.intogen.org/search?gene=CDK12","note":"driver in 17 cohorts (Act 2, LoF 15); Compendium_Cancer_Genes.tsv release 20240920, CC0 1.0"},{"label":"Human Protein Atlas CDK12 tissue","url":"https://www.proteinatlas.org/ENSG00000167258-CDK12/tissue","note":"RNA tissue and blood lineage specificity, normal tissue antibody staining (version 25.1, CC BY-SA 3.0)"},{"label":"Open Targets ENSG00000167258 associations","url":"https://platform.opentargets.org/target/ENSG00000167258/associations","note":"cancer associations at or above 0.5 (CC0)"}],"hgnc":"HGNC:24224","ensembl":"ENSG00000167258","uniprot":"Q9NYV4","entrez":"51755","firstDescribed":1998,"firstDescribedBasis":"sequence","firstDescribedNote":"Earliest sequence paper UniProt cites for the protein: Nagase et al, DNA Res, 1998, \"Prediction of the coding sequences of unidentified human genes. XII. The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro\".","firstDescribedSource":"https://pubmed.ncbi.nlm.nih.gov/10048485/","biology":"Cyclin-dependent kinase that phosphorylates the C-terminal domain (CTD) of the large subunit of RNA polymerase II (POLR2A), thereby acting as a key regulator of transcription elongation. Regulates the expression of genes involved in DNA repair and is required for the maintenance of genomic stability. Preferentially phosphorylates 'Ser-5' in CTD repeats that are already phosphorylated at 'Ser-7', but can also phosphorylate 'Ser-2'. Required for RNA splicing, possibly by phosphorylating SRSF1/SF2. Involved in regulation of MAP kinase activity, possibly leading to affect the response to oestrogen inhibitors. Location: Nucleus; Nucleus speckle (UniProt). Locus 17q12 (HGNC).","whereFound":["Prostate cancer: Open Targets association 0.67 with prostate cancer (MONDO_0008315); CIViC evidence names this disease","Ovarian cancer: Open Targets association 0.58 with ovarian cancer (MONDO_0008170); CIViC evidence names this disease","Breast cancer: CIViC evidence names this disease","Bladder & urothelial cancer: IntOGen driver in 1 cohort (BLCA)","Renal cell carcinoma: IntOGen driver in 1 cohort (CCRCC)","Cervical cancer: IntOGen driver in 1 cohort (CESC)","Prostate cancer: biallelic inactivating mutation 1-6% depending on disease state"],"targetClass":"kinase","prevalence":[{"cancerId":"prostate","pct":"1-6","measure":"Biallelic inactivating mutation","source":"https://www.cbioportal.org/study/summary?id=prad_tcga_pan_can_atlas_2018","note":"cBioPortal mutation: 9 of 494, 1.8%, in prad_tcga_pan_can_atlas_2018; 1 of 477, 0.2%, in prad_cpcg_2017; 33 of 1,013, 3.3%, in prad_p1000; 24 of 424, 5.7%, in prad_mcspc_mskcc_2020; 130 of 2,260, 5.8%, in prostate_msk_2024; 88 of 1,465, 6.0%, in prad_cdk12_mskcc_2020; 26 of 444, 5.9%, in prad_su2c_2019; 6 of 114, 5.3%, in nepc_wcm_2016."}]},"route":"/targets/cdk12/","neighbours":{"collection":[{"id":"civic","kind":"collection","name":"CIViC","route":"/collections/civic/"},{"id":"intogen","kind":"collection","name":"IntOGen","route":"/collections/intogen/"},{"id":"open-targets","kind":"collection","name":"Open Targets Platform","route":"/collections/open-targets/"}],"cancer":[{"id":"urothelial","kind":"cancer","name":"Bladder & urothelial cancer","route":"/cancers/urothelial/"},{"id":"breast-cancer","kind":"cancer","name":"Breast cancer (all types)","route":"/cancers/breast-cancer/"},{"id":"cervical","kind":"cancer","name":"Cervical cancer","route":"/cancers/cervical/"},{"id":"gastric","kind":"cancer","name":"Gastric & gastro-oesophageal junction cancer","route":"/cancers/gastric/"},{"id":"ovarian","kind":"cancer","name":"Ovarian cancer","route":"/cancers/ovarian/"},{"id":"prostate","kind":"cancer","name":"Prostate cancer","route":"/cancers/prostate/"},{"id":"rcc","kind":"cancer","name":"Renal cell carcinoma","route":"/cancers/rcc/"},{"id":"skin-cancer","kind":"cancer","name":"Skin cancer (all types)","route":"/cancers/skin-cancer/"}],"paper":[{"id":"paper-quigley-structural-variation-mcrpc-cell-2018","kind":"paper","name":"Genomic hallmarks and structural variation in metastatic prostate cancer","route":"/key-papers/paper-quigley-structural-variation-mcrpc-cell-2018/"},{"id":"paper-mateo-genomics-lethal-prostate-diagnosis-castration-resistance-jci-2020","kind":"paper","name":"Genomics of lethal prostate cancer at diagnosis and castration resistance","route":"/key-papers/paper-mateo-genomics-lethal-prostate-diagnosis-castration-resistance-jci-2020/"},{"id":"paper-stopsack-mcspc-genomic-alterations-outcomes-ccr-2020","kind":"paper","name":"Oncogenic genomic alterations, clinical phenotypes and outcomes in metastatic castration-sensitive prostate cancer","route":"/key-papers/paper-stopsack-mcspc-genomic-alterations-outcomes-ccr-2020/"},{"id":"paper-profound-nejm-2020","kind":"paper","name":"PROfound: olaparib for metastatic castration-resistant prostate cancer with homologous recombination repair gene alterations","route":"/key-papers/paper-profound-nejm-2020/"},{"id":"paper-chung-comprehensive-genomic-profiling-prostate-jco-po-2019","kind":"paper","name":"Prospective comprehensive genomic profiling of 3,476 primary and metastatic prostate tumours","route":"/key-papers/paper-chung-comprehensive-genomic-profiling-prostate-jco-po-2019/"}],"idea":[{"id":"idea-prostate-hrr-testing-at-metastatic-diagnosis","kind":"idea","name":"Test every man for DNA repair faults on the day his prostate cancer is found to have spread, not three treatments later","route":"/ideas/idea-prostate-hrr-testing-at-metastatic-diagnosis/"}],"term":[{"id":"genome-wide-loss-of-heterozygosity","kind":"term","name":"Genome-wide loss of heterozygosity (gLOH)","route":"/terms/genome-wide-loss-of-heterozygosity/"}],"biomarker":[{"id":"hrr-gene-mutation","kind":"biomarker","name":"Homologous recombination repair gene mutation in prostate cancer","route":"/biomarkers/hrr-gene-mutation/"}]}}