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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.
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'.
CIViC 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.
In plain words · 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.
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.
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.
No product in this corpus aims at CDK12 yet. Kinases are switched on by binding ATP inside the cell, so most drugs are small molecules shaped to plug that ATP pocket.
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.)
Sources: UniProt Q9NYV4; CIViC gene CDK12; IntOGen CDK12; Human Protein Atlas CDK12 tissue; Open Targets ENSG00000167258 associations
First described 1998. 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". Source.
Sources: HGNC HGNC:24224 (approved symbol, name, aliases, locus and cross-references (hgnc_complete_set.txt)); UniProt Q9NYV4 (protein name, function text, keywords and locations (REST API)); CIViC gene CDK12 (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)); Open Targets ENSG00000167258 (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)); IntOGen CDK12 (driver in 17 cohorts (Act 2, LoF 15); Compendium_Cancer_Genes.tsv release 20240920, CC0 1.0)
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).
RNA: low tissue specificity, detected in all normal tissues.
Medium: Adipose tissue, Caudate, Esophagus, Heart muscle, Hippocampus, Liver, Salivary gland, Seminal vesicle.
HPA CDK12 tissue · HPA CDK12 pathology · HPA protein class: Essential proteins
Human Protein Atlas version 25.1, antibody staining at reliability approved, enhanced or supported; used under CC BY-SA 3.0. Staining counts are patients per level in the atlas cohort, not population prevalence.
| Cancer | Prevalence | Measure | Note | Source |
|---|---|---|---|---|
| Prostate cancer | 1-6% | Biallelic inactivating mutation | 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. | cBioPortal (TCGA) |
Approximate, population-level figures; the measure column says what was counted. Ranges show the midpoint as a bar.
It splits the alterations into two groups with different practical meanings. The repair defects are present at diagnosis at close to their castration-resistant prevalence, so testing early is worthwhile; AR, TP53 and RB1 changes accumulate later, so a diagnostic sample does not answer questions about the disease in front of you at relapse.
It fills the gap between the primary-tumour atlases and the castration-resistant series by describing the disease at the moment most treatment decisions are actually made, and it identifies SPOP as a favourable marker rather than a neutral one.
Germline and tumour testing for homologous recombination repair genes is now standard in metastatic prostate cancer, and olaparib is approved for BRCA-mutated disease after a hormonal agent.
What a prostate cancer sequencing report looks like in practice, and the numerical basis for two clinical rules: do not expect checkpoint immunotherapy to work unless the tumour is mismatch repair deficient, and do not treat a CDK12 alteration as if it were a BRCA alteration.
It shows that the commonest driver event in advanced prostate cancer is invisible to the panels used to test for it, and that the shape of the structural damage in a genome tells you which repair pathway failed, which is information a mutation list does not carry.
Query for this target: (TITLE:"CDK12" OR ABSTRACT:"CDK12" OR TITLE:"cyclin dependent kinase 12" OR ABSTRACT:"cyclin dependent kinase 12" OR TITLE:"Cyclin-dependent kinase 12" OR ABSTRACT:"Cyclin-dependent kinase 12" OR TITLE:"CRK7" OR ABSTRACT:"CRK7" OR TITLE:"KIAA0904" OR ABSTRACT:"KIAA0904" OR TITLE:"CRKRS" OR ABSTRACT:"CRKRS") AND (cancer OR tumor OR tumour OR oncology OR carcinoma OR lymphoma OR leukemia OR leukaemia OR myeloma OR sarcoma OR melanoma OR glioma). Results are unfiltered search hits about CDK12, not a curated reading list.
Shares Homologous recombination repair gene mutation in prostate cancer, Skin cancer (all types), CIViC, Gastric & gastro-oesophageal junction cancer.
Shares Homologous recombination repair gene mutation in prostate cancer, Skin cancer (all types), CIViC, IntOGen.
Shares Homologous recombination repair gene mutation in prostate cancer, CIViC, Gastric & gastro-oesophageal junction cancer, Ovarian cancer.
Shares Homologous recombination repair gene mutation in prostate cancer, CIViC, Gastric & gastro-oesophageal junction cancer, Ovarian cancer.
Shares Homologous recombination repair gene mutation in prostate cancer, CIViC, IntOGen, Gastric & gastro-oesophageal junction cancer.
Shares Oncogenic genomic alterations, clinical phenotypes and outcomes in metastatic castration-sensitive prostate cancer, Skin cancer (all types), CIViC, IntOGen.
Shares Genomics of lethal prostate cancer at diagnosis and castration resistance, PROfound: olaparib for metastatic castration-resistant prostate cancer with homologous recombination repair gene alterations, Genome-wide loss of heterozygosity (gLOH), Test every man for DNA repair faults on the day his prostate cancer is found to have spread, not three treatments later.
Shares Prospective comprehensive genomic profiling of 3,476 primary and metastatic prostate tumours, Test every man for DNA repair faults on the day his prostate cancer is found to have spread, not three treatments later, Prostate cancer.