CDK12
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.
Overview
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.
- Target · the protein and the cell it sits on
- Drug · antibody, small molecule, cell or radioligand
- Effect · signal, damage or kill
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.
- 1 · What it is
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.
- 2 · What goes wrong in cancer
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.
- 3 · How drugs use it
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.
External identifiers
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)
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).
- 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)
Notes
top- 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.
Latest papers
topQuery 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.