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10 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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CCNC
cyclin C
Chromosome 6 · 6q16.2
NCBI Gene: 892Ensembl: ENSG00000112237.13HGNC: HGNC:1581UniProt: E5RFK5
96PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
FUNCTIONAL ROLE
Transcription Factor
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
protein bindingcyclin-dependent protein serine/threonine kinase regulator activityidentical protein bindingregulation of transcription by RNA polymerase IIneurodegenerative diseasecanceralcohol drinkingSjogren syndrome
✦AI Summary

CCNC (cyclin C) is a regulatory component of the Mediator kinase module, a multi-subunit complex that serves as a coactivator for RNA polymerase II-dependent gene transcription 1. CCNC binds to and activates CDK8/19 kinase, which phosphorylates the C-terminal domain of RNA polymerase II to modulate transcription initiation complex formation. The Mediator kinase module functions as a signal transducer, conveying regulatory information from gene-specific transcription factors to the basal transcription machinery 1. Mechanistically, CCNC regulates immune cell function and tumor biology through distinct pathways. In T and NK cells, CCNC deletion enhances effector activity and antitumor potency, associated with increased IL-2 receptor expression and cytokine secretion 23. Conversely, CCNC suppresses CD155 transcription by inhibiting FOSL2 activity; loss of CCNC promotes CD155 upregulation and immune evasion 4. Clinically, CCNC dysregulation associates with cancer progression. CCNC deletions occur in acute lymphoblastic leukemia 5, while elevated CCNC/CDK8 expression correlates with shorter relapse-free survival in breast cancer and reduced chemotherapy response 6. Gene amplification of CCNC occurs in ~10% of breast cancers 6. CCNC polymorphisms associate with pubertal timing variation and subsequent cardiovascular and metabolic disease risk 7. These findings suggest CCNC as both a tumor suppressor and therapeutic target in cancer immunotherapy.

Sources cited
1
CCNC is a component of the Mediator kinase module and functions in signal-dependent gene regulation through CDK8 kinase activity
PMID: 26182352
2
CCNC deletion enhances T cell effector activity and antitumor potency with increased IL-2 receptor expression
PMID: 36356142
3
CCNC ablation significantly improved NK cell antitumor activity and enhanced metabolic fitness and cytokine secretion
PMID: 40845844
4
CCNC suppresses CD155 transcription through FOSL2 inhibition; CCNC loss promotes CD155 upregulation and immune evasion
PMID: 41265176
5
CCNC gene is located on chromosome 6q21 and is deleted in a subset of acute lymphoblastic leukemias
PMID: 8833152
6
Elevated CCNC expression correlates with shorter relapse-free survival in breast cancer and reduced chemotherapy response; gene amplification occurs in ~10% of breast cancers
PMID: 26452386
7
CCNC polymorphisms associate with pubertal timing and subsequent cardiovascular disease and osteoporosis risk
PMID: 39824883
Disease Associationsⓘ20
neurodegenerative diseaseOpen Targets
0.55Moderate
cancerOpen Targets
0.38Weak
alcohol drinkingOpen Targets
0.27Weak
Sjogren syndromeOpen Targets
0.27Weak
rhabdomyosarcomaOpen Targets
0.20Weak
hepatocellular carcinomaOpen Targets
0.19Weak
colon adenocarcinomaOpen Targets
0.19Weak
breast carcinomaOpen Targets
0.19Weak
rectal adenocarcinomaOpen Targets
0.19Weak
gastric adenocarcinomaOpen Targets
0.19Weak
prostate adenocarcinomaOpen Targets
0.19Weak
lung adenocarcinomaOpen Targets
0.19Weak
chronic lymphocytic leukemiaOpen Targets
0.19Weak
bile duct adenocarcinomaOpen Targets
0.18Weak
bladder transitional cell carcinomaOpen Targets
0.18Weak
head and neck squamous cell carcinomaOpen Targets
0.18Weak
Hepatobiliary NeoplasmOpen Targets
0.18Weak
oral cavity carcinomaOpen Targets
0.18Weak
skin carcinomaOpen Targets
0.18Weak
urinary bladder carcinomaOpen Targets
0.18Weak
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
MAGEA1Shared pathway100%MED19Protein interaction100%MED4Protein interaction100%MED10Protein interaction100%MED12Protein interaction100%MED14Protein interaction100%
Tissue Expression6 tissues
Liver
100%
Bone Marrow
87%
Brain
49%
Heart
45%
Lung
40%
Ovary
38%
Gene Interaction Network
Click a node to explore
CCNCMAGEA1MED19MED4MED10MED12MED14
PROTEIN STRUCTURE
Preparing viewer…
PDB5XS2 · 2.04 Å · X-ray
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
0.74LoF Tolerant
pLIⓘ
0.75Intermediate
Observed/Expected LoF0.23 [0.10–0.74]
RankingsWhere CCNC stands among ~20K protein-coding genes
  • #4,973of 20,598
    Most Researched96 · top quartile
  • #5,770of 17,882
    Most Constrained (LOEUF)0.74
Genes detectedCCNC
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
Genome-wide CRISPR screens identify critical targets to enhance CAR-NK cell antitumor potency.
PMID: 40845844
Cancer Cell · 2025
1.00
2
Enhanced T cell effector activity by targeting the Mediator kinase module.
PMID: 36356142
Science · 2022
0.90
3
Cross-trait multivariate GWAS confirms health implications of pubertal timing.
PMID: 39824883
Nat Commun · 2025
0.80
4
Control of acute myeloid leukemia by a trifunctional NKp46-CD16a-NK cell engager targeting CD123.
PMID: 36635380
Nat Biotechnol · 2023
0.70
5
Molecular cloning and chromosomal localization of the human cyclin C (CCNC) and cyclin E (CCNE) genes: deletion of the CCNC gene in human tumors.
PMID: 8833152
Genomics · 1996
0.60