CCAR2
cell cycle and apoptosis regulator 2
Basic information
Region (hg38): 8:22604757-22620964
Previous symbols: [ "KIAA1967" ]
Links
Phenotypes
GenCC
Source:
No genCC data.
ClinVar
This is a list of variants' phenotypes submitted to
- not_specified (127 variants)
- CCAR2-related_disorder (22 variants)
- not_provided (11 variants)
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the CCAR2 gene is commonly pathogenic or not. These statistics are base on transcript: NM_001393997.1. Only rare variants are included in the table.
In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.
Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUSVUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 14 | 20 | ||||
| missense | 122 | 131 | ||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 1 | |||||
| Total | 0 | 0 | 122 | 22 | 8 |
Loading clinvar variants...
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| CCAR2 | protein_coding | protein_coding | ENST00000308511 | 20 | 16883 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 0.941 | 0.0590 | 125730 | 0 | 18 | 125748 | 0.0000716 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 0.733 | 498 | 546 | 0.912 | 0.0000341 | 5924 |
| Missense in 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 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.0000289 | 0.0000289 |
| Ashkenazi Jewish | 0.0000999 | 0.0000992 |
| East Asian | 0.00 | 0.00 |
| Finnish | 0.0000466 | 0.0000462 |
| European (Non-Finnish) | 0.0000974 | 0.0000967 |
| Middle Eastern | 0.00 | 0.00 |
| South Asian | 0.000133 | 0.000131 |
| Other | 0.00 | 0.00 |
dbNSFP
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}.;
- Pathway
- Regulation of HSF1-mediated heat shock response;Cellular responses to stress;Cellular responses to external stimuli;Cellular response to heat stress
(Consensus)
Recessive Scores
- pRec
- 0.234
Intolerance Scores
- loftool
- rvis_EVS
- -0.81
- rvis_percentile_EVS
- 12.07
Haploinsufficiency Scores
- pHI
- 0.709
- hipred
- Y
- hipred_score
- 0.568
- ghis
- 0.621
Essentials
- essential_gene_CRISPR
- E
- essential_gene_CRISPR2
- essential_gene_gene_trap
- N
- gene_indispensability_pred
- gene_indispensability_score
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Ccar2
- Phenotype
- adipose tissue phenotype (the observable morphological and physiological characteristics of mammalian fat tissue that are manifested through development and lifespan); growth/size/body region phenotype; immune system phenotype; homeostasis/metabolism phenotype; liver/biliary system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan);
Gene ontology
- Biological process
- regulation of transcription, DNA-templated;mRNA processing;cellular response to DNA damage stimulus;cell cycle;RNA splicing;response to UV;Wnt signaling pathway;negative regulation of cell growth;regulation of protein stability;negative regulation of proteasomal ubiquitin-dependent protein catabolic process;regulation of DNA-templated transcription, elongation;regulation of circadian rhythm;positive regulation of apoptotic process;negative regulation of catalytic activity;mitochondrial fragmentation involved in apoptotic process;negative regulation of transcription, DNA-templated;rhythmic process;positive regulation of canonical Wnt signaling pathway;regulation of protein deacetylation;regulation of cellular response to heat;negative regulation of intrinsic apoptotic signaling pathway in response to DNA damage;positive regulation of nucleic acid-templated transcription;positive regulation of DNA damage checkpoint
- Cellular component
- nuclear chromatin;nucleus;nucleoplasm;cytoplasm;mitochondrial matrix;DBIRD complex
- Molecular function
- RNA polymerase II complex binding;RNA binding;enzyme inhibitor activity;protein binding;enzyme binding;nuclear receptor transcription coactivator activity