{"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":[],"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"}],"hgnc":"HGNC:24224","ensembl":"ENSG00000167258","uniprot":"Q9NYV4","entrez":"51755","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)"],"targetClass":"kinase","prevalence":[]},"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/"}]}}