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25 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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CCAR2
cell cycle and apoptosis regulator 2
Chromosome 8 · 8p21.3
NCBI Gene: 57805Ensembl: ENSG00000158941.18HGNC: HGNC:23360UniProt: Q8N163
292PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
FUNCTIONAL ROLE
Highly ConstrainedTranscription FactorTumor Suppressor
RESEARCH IMPACT
Trending
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
spindlenuclear bodyDBIRD complexenzyme inhibitor activityAbnormality of refractionhemorrhoidcholelithiasisneurodegenerative disease
✦AI Summary

CCAR2 (cell cycle and apoptosis regulator 2) is a multifunctional nuclear protein that integrates transcriptional regulation with apoptosis and cell cycle control. As a core component of the DBIRD complex, CCAR2 regulates alternative splicing and transcript elongation at A+T-rich genomic regions 1. CCAR2 functions as a negative regulator of multiple deacetylases and histone modifiers: it inhibits SIRT1 deacetylase activity, leading to p53 acetylation and p53-mediated apoptosis 23, and negatively regulates HDAC3 deacetylase activity 4. Beyond apoptosis regulation, CCAR2 controls metabolic processes through NR1D1 and SIRT1-dependent mechanisms 56. CCAR2 exhibits dual roles in cancer: it functions as a tumor suppressor by stabilizing p53 and regulating DNA damage responses 78, yet paradoxically promotes proliferation in p53-deficient cancers by stabilizing oncogenic transcription factors 9. High CCAR2 expression correlates with poor survival in squamous cell carcinoma and neuroblastoma 10. Recent evidence suggests CCAR2 plays roles in DNA damage repair, autophagy regulation, and metabolic control through SIRT1 interactions 1112. This functional duality—simultaneously promoting apoptosis and cell survival depending on cellular context—positions CCAR2 as a master regulator of metabolism, aging, and cancer progression 13.

Sources cited
1
As a core component of the DBIRD complex, CCAR2 regulates alternative splicing and transcript elongation at A+T-rich genomic regions .
PMID: 22446626
2
CCAR2 functions as a negative regulator of multiple deacetylases and histone modifiers: it inhibits SIRT1 deacetylase activity, leading to p53 acetylation and p53-mediated apoptosis , , and negatively regulates HDAC3 deacetylase activity .
PMID: 21030595
3
CCAR2 exhibits dual roles in cancer: it functions as a tumor suppressor by stabilizing p53 and regulating DNA damage responses , , yet paradoxically promotes proliferation in p53-deficient cancers by stabilizing oncogenic transcription factors .
PMID: 27725203
4
High CCAR2 expression correlates with poor survival in squamous cell carcinoma and neuroblastoma .
PMID: 30609639
5
This functional duality—simultaneously promoting apoptosis and cell survival depending on cellular context—positions CCAR2 as a master regulator of metabolism, aging, and cancer progression .
PMID: 33403784
Disease Associationsⓘ20
Abnormality of refractionOpen Targets
0.30Weak
hemorrhoidOpen Targets
0.30Weak
cholelithiasisOpen Targets
0.29Weak
neurodegenerative diseaseOpen Targets
0.29Weak
insomniaOpen Targets
0.28Weak
type 2 diabetes mellitusOpen Targets
0.26Weak
diabetes mellitusOpen Targets
0.24Weak
Age-related cataractOpen Targets
0.20Weak
Abnormality of the skeletal systemOpen Targets
0.17Weak
Parkinson diseaseOpen Targets
0.15Weak
chronic obstructive pulmonary diseaseOpen Targets
0.13Weak
neoplasmOpen Targets
0.11Weak
cancerOpen Targets
0.10Weak
post-traumatic stress disorderOpen Targets
0.08Suggestive
colorectal carcinomaOpen Targets
0.08Suggestive
osteosarcomaOpen Targets
0.08Suggestive
ovarian carcinomaOpen Targets
0.08Suggestive
systemic lupus erythematosusOpen Targets
0.07Suggestive
serous adenocarcinomaOpen Targets
0.07Suggestive
digestive system cancerOpen Targets
0.06Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
SIRT1Protein interaction100%TP53Protein interaction100%ATRProtein interaction100%RPS19BP1Protein interaction97%RANBP3Protein interaction93%MYCProtein interaction86%
Tissue Expression6 tissues
Bone Marrow
100%
Brain
84%
Ovary
71%
Lung
64%
Heart
50%
Liver
49%
Gene Interaction Network
Click a node to explore
CCAR2SIRT1TP53ATRRPS19BP1RANBP3MYC
PROTEIN STRUCTURE
Preparing viewer…
PDB8EZ6 · 2.00 Å · X-ray
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
0.29Highly Constrained
pLIⓘ
1.00Intolerant
Observed/Expected LoF0.20 [0.14–0.29]
RankingsWhere CCAR2 stands among ~20K protein-coding genes
  • #1,221of 20,598
    Most Researched292 · top 10%
  • #1,043of 17,882
    Most Constrained (LOEUF)0.29 · top 10%
Genes detectedCCAR2
Sources retrieved25 papers
Response time—
📄 Sources
25▼
1
Acetylation in the regulation of autophagy.
PMID: 35435793
Autophagy · 2023
1.00
2
The gut microbiota reprograms intestinal lipid metabolism through long noncoding RNA
PMID: 37616368
Science · 2023
0.90
3
CCAR1 and CCAR2 as gene chameleons with antagonistic duality: Preclinical, human translational, and mechanistic basis.
PMID: 33403784
Cancer Sci · 2020
0.80
4
Gut microbiota protect against colorectal tumorigenesis through lncRNA Snhg9.
PMID: 39755115
Dev Cell · 2025
0.72
5
Mechanistic insights into the dual role of CCAR2/DBC1 in cancer.
PMID: 37524873
Exp Mol Med · 2023
0.70