CCAR2
protein-codingcell cycle and apoptosis regulator 2
Gene summary
Enables RNA polymerase II complex binding activity and enzyme inhibitor activity. Involved in several processes, including regulation of gene expression; regulation of protein metabolic process; and regulation of signal transduction. Located in several cellular components, including mitochondrial matrix; nuclear body; and spindle. Part of DBIRD complex. [provided by Alliance of Genome Resources, Jun 2026]
Previous symbols:
- KIAA1967
MANE transcript
NM_001393997.1
Inheritance
—
ClinVar variants
U:138B:30
Top phenotype
CCAR2-related disorder
gnomAD constraint
pLI —, LoF o/e 0.19
Max pathogenic AF
—
Genomic locus
chr8:22,604,757-22,620,964
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~16.2 kbLoading mutation effect viewer...
GenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
No GenCC data available for this gene.
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to CCAR2 variants in ClinVar
not specifiedTotal: 142
CCAR2-related disorderTotal: 23
not providedTotal: 14
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_001393997.1. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 14 | 6 | 20 | |||
| missense | 135 | 8 | 2 | 145 | ||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 1 | 1 | ||||
| splice donor/acceptor (+/-2bp) | 2 | 2 | ||||
| Total | 0 | 0 | 138 | 22 | 8 | 168 |
Loading ClinVar variants...
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
Showing 4 of 56 transcripts
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_001380926.1 | 20 | MANE Select | |
| Ensembl | ENSP00000310670.4 | 20 | MANE Select | |
| RefSeq | NP_001349997.1 | 20 | Standard | |
| RefSeq | NP_001349998.1 | 20 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Regulation of HSF1-mediated heat shock response
- Cellular responses to stress
- Cellular responses to external stimuli
- Cellular response to heat stress
Biological Process
- regulation of transcription, DNA-templated
- mRNA processing
- cellular response to DNA damage stimulus
- cell cycle
- RNA splicing
Molecular Function
- RNA polymerase II complex binding
- RNA binding
- enzyme inhibitor activity
- protein binding
- enzyme binding
Cellular Component
- nuclear chromatin
- nucleus
- nucleoplasm
- cytoplasm
- mitochondrial matrix
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000308511
- Coding exons
- 20
- Length
- 16883
- Individuals with no LoFs
- 125730
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 18
- Defined
- 125748
- p
- 0.0000716
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.733 | 498 | 546 | 0.912 | 0.0000341 | 5924 |
| Missense (PolyPhen) | 156 | 220.46 | 0.7076 | 2374 | ||
| Synonymous | -3.66 | 288 | 219 | 1.31 | 0.0000127 | 1920 |
| Loss of Function | 5.27 | 9 | 48.6 | 0.185 | 0.00000253 | 531 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0.000029 | 0.000029 | rare |
| Ashkenazi Jewish | 0.00010 | 0.000099 | rare |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0.000047 | 0.000046 | rare |
| European (Non-Finnish) | 0.000097 | 0.000097 | rare |
| South Asian | 0.00013 | 0.00013 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Core component of the DBIRD complex, a multiprotein complex that acts at the interface between core mRNP particles and RNA polymerase II (RNAPII) and integrates transcript elongation with the regulation of alternative splicing: the DBIRD complex affects local transcript elongation rates and alternative splicing of a large set of exons embedded in (A + T)-rich DNA regions. Inhibits SIRT1 deacetylase activity leading to increasing levels of p53/TP53 acetylation and p53-mediated apoptosis. Inhibits SUV39H1 methyltransferase activity. As part of a histone H3- specific methyltransferase complex may mediate ligand-dependent transcriptional activation by nuclear hormone receptors. Plays a critical role in maintaining genomic stability and cellular integrity following UV-induced genotoxic stress. Regulates the circadian expression of the core clock components NR1D1 and ARNTL/BMAL1. Enhances the transcriptional repressor activity of NR1D1 through stabilization of NR1D1 protein levels by preventing its ubiquitination and subsequent degradation (PubMed:18235501, PubMed:18235502, PubMed:19131338, PubMed:19218236, PubMed:22446626, PubMed:23352644, PubMed:23398316). Represses the ligand-dependent transcriptional activation function of ESR2 (PubMed:20074560). Acts as a regulator of PCK1 expression and gluconeogenesis by a mechanism that involves, at least in part, both NR1D1 and SIRT1 (PubMed:24415752). Negatively regulates the deacetylase activity of HDAC3 and can alter its subcellular localization (PubMed:21030595). Positively regulates the beta- catenin pathway (canonical Wnt signaling pathway) and is required for MCC-mediated repression of the beta-catenin pathway (PubMed:24824780). Represses ligand-dependent transcriptional activation function of NR1H2 and NR1H3 and inhibits the interaction of SIRT1 with NR1H3 (PubMed:25661920). Plays an important role in tumor suppression through p53/TP53 regulation; stabilizes p53/TP53 by affecting its interaction with ubiquitin ligase MDM2 (PubMed:25732823). Represses the transcriptional activator activity of BRCA1 (PubMed:20160719). Inhibits SIRT1 in a CHEK2 and PSEM3-dependent manner and inhibits the activity of CHEK2 in vitro (PubMed:25361978). {ECO:0000269|PubMed:18235501, ECO:0000269|PubMed:18235502, ECO:0000269|PubMed:19131338, ECO:0000269|PubMed:19218236, ECO:0000269|PubMed:20074560, ECO:0000269|PubMed:20160719, ECO:0000269|PubMed:21030595, ECO:0000269|PubMed:22446626, ECO:0000269|PubMed:23352644, ECO:0000269|PubMed:23398316, ECO:0000269|PubMed:24415752, ECO:0000269|PubMed:24824780, ECO:0000269|PubMed:25361978, ECO:0000269|PubMed:25661920, ECO:0000269|PubMed:25732823}.;
Recessive Scores
- pRec
- 0.234
Intolerance Scores
- RVIS EVS
- -0.81
- RVIS percentile EVS
- 12.07
Essentials
- Essential (CRISPR)
- E
- Essential (gene trap)
- N
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |