Cyclin-dependent kinase 12 (CDK12)

Cyclin-dependent kinase 12 (CDK12) is a serine/threonine protein kinase that plays a central role in regulating gene transcription, RNA splicing, translation, DNA damage response (DDR), cell cycle progression, and cell proliferation. It regulates the expression of genes involved in DNA repair pathways, especially those required for homologous recombination repair. Mutations or structural rearrangements involving CDK12 have been implicated in various cancers. It forms an active complex with cyclin K and phosphorylates the C-terminal domain (CTD) of RNA polymerase II.

CDK12 inhibitors (in development) act by selectively blocking the kinase activity of CDK12, disrupting its function in regulating transcription and DNA repair.