CDK12

Tumour Suppressor
Cyclin-dependent kinase 12 UniProt accession Q9NYV4

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 estrogen inhibitors

Source: UniProt

Interacts with CCNL1 and CCNL2 (By similarity). Interacts with CCNK

(Microbial infection) Interacts with human herpes virus 1 (HHV-1) transcriptional regulator ICP22

Source: UniProt
Nucleus, Nucleus speckle
Source: UniProt

Widely expressed

Source: UniProt
  • Unknown disease
Source: UniProt

Click a pathway to open the interactive Reactome viewer.

Pathway list and interactive viewer: Reactome

Synthetic Lethal Network

Genes with an experimentally identified or computationally predicted synthetic-lethal relationship to CDK12, aggregated across our SSL data sources. Click any partner node to view that gene’s page.

Nodes and edges are coloured by the SSL data source. Partners appearing in more than one source are shown in grey.

BioGRID SLOrth SynLethDB MexDrugs Multi-source
Sources: BioGRID, SLOrth, SynLethDB, MexDrugs

Clinical Trials

Total Trials Found: 11

NCT ID Condition Brief Title Phase Status
NCT03570619 Metastatic Castration Resistant Prostate Cancer, Metastatic Cancer, Solid Tumor Immunotherapy in Patients With Metastatic Cancers and CDK12 Mutations PHASE2 COMPLETED
NCT06663007 Prostate Cancer, CDK12 Gene Mutation RC48 Monotherapy or Combination With Envafolimab for CDK12 Alterations mCRPC With Standard Treatment Failure PHASE1, PHASE2 RECRUITING
NCT04272034 Advanced Solid Tumors, MSI-H/dMMR Tumors, Cutaneous Squamous Cell Carcinoma, Urothelial Carcinoma, HCC, Cervical Cancer, Esophageal Squamous Cell Carcinoma, Merkel Cell Carcinoma, Small-cell Lung Cancer, Mesothelioma, PD-L1 Amplified Tumor (9p24.1), Nasopharyngeal Carcinoma, Cyclin-dependent Kinase 12 Mutated Tumors, Basal Cell Carcinoma (Unresectable or Metastatic), Sarcomatoid Renal Cell Carcinoma, Clear Cell Ovarian or Endometrial Carcinoma, Anal Carcinoma, Squamous Cell Penile Carcinoma, DNA Polymerase Epsilon Mutated Tumors (P286R and V411L) Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of INCB099318 in Participants With Advanced Solid Tumors PHASE1 TERMINATED
NCT04019964 Prostate Cancer, Recurrent Prostate Cancer Nivolumab in Biochemically Recurrent dMMR Prostate Cancer PHASE2 COMPLETED
NCT04030559 ATM Gene Mutation, BRCA1 Gene Mutation, BRCA2 Gene Mutation, BRIP1 Gene Mutation, CDK12 Gene Mutation, CHEK1 Gene Mutation, CHEK2 Gene Mutation, DNA Damage Response Gene Mutation, DNA Repair Gene Mutation, FANCA Gene Mutation, FANCD2 Gene Mutation, FANCL Gene Mutation, GEN1 Gene Mutation, NBN Gene Mutation, Prostate Carcinoma, RAD51 Gene Mutation, RAD51C Gene Mutation Niraparib Before Surgery in Treating Patients With High Risk Localized Prostate Cancer and DNA Damage Response Defects PHASE2 ACTIVE_NOT_RECRUITING
NCT07435584 Colorectal Cancer Everolimus in CDK12-Deficient Metastatic Colorectal Cancer (EVER-RECODE) PHASE1, PHASE2 NOT_YET_RECRUITING
NCT05005728 Metastatic Castration-Resistant Prostate Cancer XmAb®20717 (Vudalimab) Alone or in Combination With Chemotherapy or Targeted Therapy in Patients With Metastatic Castration-Resistant Prostate Cancer PHASE2 COMPLETED
NCT05011383 Metastatic Prostate Cancer High Dose Testosterone for ATM, CDK12 or CHEK2 Altered Prostate Cancers PHASE2 RECRUITING
NCT02952534 Metastatic Castration Resistant Prostate Cancer A Study of Rucaparib in Patients With Metastatic Castration-resistant Prostate Cancer and Homologous Recombination Gene Deficiency PHASE2 COMPLETED
NCT05787587 Advanced or Metastatic Solid Tumors, Breast Cancer, Ovarian Cancer, Prostate Cancer, Endometrial Cancer, Colorectal Cancer, Head and Neck Cancers, Extensive Stage Small Cell Lung Cancer (ES-SCLC), NSCLC A Study of PARG Inhibitor IDE161 in Participants With Advanced Solid Tumors PHASE1 RECRUITING