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10 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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CCNK
cyclin K
Chromosome 14 · 14q32.2
NCBI Gene: 8812Ensembl: ENSG00000090061.18HGNC: HGNC:1596UniProt: O75909
97PubMed Papers
21Diseases
0Drugs
1Pathogenic Variants
FUNCTIONAL ROLE
Highly ConstrainedTranscription Factor
CLINICAL
OMIM Disease Gene
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
positive regulation of transcription elongation by RNA polymerase IIhost-mediated suppression of viral genome replicationprotein bindingRNA polymerase II CTD heptapeptide repeat kinase activityHIV infectionintellectual developmental disorder with hypertelorism and distinctive faciesneurodegenerative diseasecancer
✦AI Summary

CCNK encodes cyclin K, a regulatory subunit of cyclin-dependent kinases (CDKs) that plays a critical role in transcriptional regulation and DNA damage response. CCNK primarily functions by forming complexes with CDK12 and CDK13, which phosphorylate the C-terminal domain of RNA polymerase II to regulate transcription elongation 12. The protein is essential for neural development, as CCNK deficiency causes intellectual disability syndrome characterized by deficient neural progenitor cell (NPC) proliferation and enhanced apoptotic cell death through dysregulated WNT5A signaling 3. CCNK demonstrates clinical relevance as a therapeutic target in cancer, where its degradation compromises CDK12 function, reduces DNA damage response gene expression, and induces cell death 24. In prostate cancer, CCNK downregulation promotes androgen receptor variant expression and creates vulnerability to PARP inhibitor treatment 5. Multiple molecular glue degraders have been developed that selectively target CCNK for ubiquitination and proteasomal degradation by promoting interactions between CDK12-CCNK complexes and CUL4-DDB1 E3 ubiquitin ligases 126. These compounds show broad-spectrum antitumor activity and represent a promising therapeutic approach for cancer treatment.

Sources cited
1
CCNK forms complexes with CDK12 and molecular glue degraders promote CCNK degradation via CUL4-DDB1 interaction
PMID: 32494016
2
CCNK degradation compromises CDK12 function and reduces DNA damage response gene expression
PMID: 32804079
3
CCNK deficiency causes intellectual disability syndrome with deficient neural progenitor cell proliferation through WNT5A signaling
PMID: 37597256
4
CCNK/CDK12 degradation shows antitumor activity in colorectal cancer models
PMID: 34289372
5
CCNK downregulation promotes androgen receptor variant expression and PARP inhibitor vulnerability in prostate cancer
PMID: 36129942
6
Molecular glue degraders targeting CCNK show broad-spectrum antitumor activity with favorable pharmacokinetics
PMID: 41165741
Disease Associationsⓘ21
HIV infectionOpen Targets
0.56Moderate
intellectual developmental disorder with hypertelorism and distinctive faciesOpen Targets
0.53Moderate
neurodegenerative diseaseOpen Targets
0.43Moderate
cancerOpen Targets
0.08Suggestive
lung cancerOpen Targets
0.08Suggestive
neoplasmOpen Targets
0.06Suggestive
atrial fibrillationOpen Targets
0.05Suggestive
endometrial cancerOpen Targets
0.05Suggestive
breast cancerOpen Targets
0.05Suggestive
atrial heart septal defectOpen Targets
0.04Suggestive
heart diseaseOpen Targets
0.04Suggestive
HydrocephalusOpen Targets
0.03Suggestive
posterior cortical atrophyOpen Targets
0.03Suggestive
prostate cancerOpen Targets
0.03Suggestive
exostosisOpen Targets
0.03Suggestive
leukemiaOpen Targets
0.02Suggestive
lung adenocarcinomaOpen Targets
0.02Suggestive
breast neoplasmOpen Targets
0.02Suggestive
colonic neoplasmOpen Targets
0.02Suggestive
Neurodevelopmental disorderOpen Targets
0.01Suggestive
Intellectual developmental disorder with hypertelorism and distinctive faciesUniProt
Pathogenic Variants1
NM_001099402.2(CCNK):c.331A>G (p.Lys111Glu)Pathogenic
Intellectual developmental disorder with hypertelorism and distinctive facies
☆☆☆☆2018→ Residue 111
View on ClinVar ↗
Related Genes
NELFEProtein interaction100%BRD4Protein interaction95%GTF2F1Protein interaction93%SUPT5HProtein interaction92%CCNCProtein interaction92%CDK7Protein interaction92%
Tissue Expression6 tissues
Brain
100%
Bone Marrow
80%
Lung
29%
Ovary
27%
Heart
27%
Liver
12%
Gene Interaction Network
Click a node to explore
CCNKNELFEBRD4GTF2F1SUPT5HCCNCCDK7
PROTEIN STRUCTURE
Preparing viewer…
PDB2I53 · 1.50 Å · X-ray
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
0.34Highly Constrained
pLIⓘ
1.00Intolerant
Observed/Expected LoF0.19 [0.11–0.34]
RankingsWhere CCNK stands among ~20K protein-coding genes
  • #4,923of 20,598
    Most Researched97 · top quartile
  • #4,897of 5,498
    Most Pathogenic Variants1
  • #1,465of 17,882
    Most Constrained (LOEUF)0.34 · top 10%
Genes detectedCCNK
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
The CDK inhibitor CR8 acts as a molecular glue degrader that depletes cyclin K.
PMID: 32494016
Nature · 2020
1.00
2
Discovery of a molecular glue promoting CDK12-DDB1 interaction to trigger cyclin K degradation.
PMID: 32804079
Elife · 2020
0.90
3
CCNK Gene Deficiency Influences Neural Progenitor Cells Via Wnt5a Signaling in CCNK-Related Syndrome.
PMID: 37597256
Ann Neurol · 2023
0.80
4
Rational discovery of molecular glue degraders via scalable chemical profiling.
PMID: 32747809
Nat Chem Biol · 2020
0.70
5
Discovery of Highly Potent and Orally Available CCNK Molecular Glue Degraders as Broad-Spectrum Antitumor Agents.
PMID: 41165741
J Med Chem · 2025
0.60