CCNK (Cyclin K)
A regulatory subunit of CDK12/CDK13 complexes involved in transcription and RNA processing
Gene Information Card
| Symbol | CCNK |
|---|---|
| Full Name | Cyclin K |
| Gene Type | Protein coding |
| Chromosomal Location | 14q32.2 |
| NCBI Gene ID | 8812 ncbi.nlm.nih.gov/gene/8812 |
| Ensembl ID | ENSG00000100811 |
| UniProt ID | O75907 |
| OMIM ID | 603544 |
| HGNC ID | 1596 |
| Aliases | CPC, CPR4, MGC9115 |
Description
CCNK encodes Cyclin K, a cyclin family protein that binds and activates cyclin-dependent kinases CDK12 and CDK13. The complex phosphorylates RNA polymerase II, regulating transcription elongation, RNA splicing, and DNA damage response. Cyclin K is essential for embryonic development and cell cycle progression.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Breast cancer | CCNK amplification/overexpression drives CDK12 hyperactivation, enhancing transcription of DNA repair genes | PMID: 30523277 |
| Ovarian cancer | CCNK copy number gains correlate with poor prognosis and chemoresistance | PMID: 29348427 |
| Colorectal cancer | CCNK upregulation promotes proliferation via CDK12-mediated transcription | PMID: 31073040 |
| Neurodevelopmental disorders | De novo missense variants in CCNK impair CDK12 binding, leading to transcriptional dysregulation | PMID: 31474318 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Testis | 18.5 | High |
| Bone marrow | 12.3 | Medium |
| Lymph node | 10.1 | Medium |
| Brain | 6.8 | Low |
| Liver | 4.2 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK293 | 15.2 | High expression |
| HeLa | 13.7 | High expression |
| MCF7 | 11.9 | Medium expression |
| HepG2 | 8.5 | Medium expression |
| K562 | 6.1 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.832C>T (p.Arg278Cys) | Missense | Rare | Reduced CDK12 binding; associated with neurodevelopmental delay |
| c.1045_1046insA (p.Thr349Asnfs*5) | Frameshift | Very rare | Loss of function; predicted protein truncation |
| c.1234G>A (p.Glu412Lys) | Missense | Rare | Impaired kinase activation; reported in cancer |
Mutation functional classification
Loss of Function (LOF)
Frameshift and nonsense variants that truncate Cyclin K, abolishing CDK12/13 binding and kinase activity.
Gain of Function (GOF)
Amplification or overexpression of CCNK leading to hyperactive CDK12 signaling in cancers.
Dominant Negative (DN)
Missense variants (e.g., p.Arg278Cys) that retain partial binding but disrupt complex function.
View complete mutation data：
Gene Ontology (GO)
Pathways
• CDK12-mediated transcription elongation (Reactome: R-HSA-6804756)
• RNA polymerase II transcription (KEGG: hsa03040)
• DNA damage response (PID: DNA_DAMAGE_PATHWAY)
Protein Summary
Cyclin K is a 580-amino-acid protein with a cyclin N-terminal domain and a C-terminal region that mediates CDK12/CDK13 interaction. It shuttles between nucleus and cytoplasm, but predominantly localizes to nuclear speckles. Post-translational modifications include phosphorylation and ubiquitination, regulating its stability and activity.
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