CDK12/CRK7

CDK12, once named CRK7, is a transcriptional cyclin-dependent kinase that pairs with cyclin K and phosphorylates Ser2 of the RNA polymerase II C-terminal domain to drive elongation of long, complex genes. It is particularly required for expression of DNA damage response genes, and CDK12-mutant prostate cancers show genomic instability with an inflamed tumor microenvironment. Biallelic germline CDK12 variants cause a neurodevelopmental syndrome with intellectual disability and dysmorphic features. Its C-terminal RS-rich domain connects it to splicing regulation. CDK12, together with the paralog CDK13, defines a branch of transcriptional CDKs distinct from cell-cycle CDK1-6 and from CDK8/9.