CCAR2

cell cycle and apoptosis regulator 2

Basic information

Region (hg38): 8:22604756-22620964

Previous symbols: [ "KIAA1967" ]

Links

ENSG00000158941 ∙ NCBI:57805 ∙ OMIM:607359 ∙ HGNC:23360 ∙ Uniprot:Q8N163 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the CCAR2 gene.

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.

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.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				11	9	20
missense			46	6	2	54
nonsense						0
start loss						0
frameshift				1		1
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region				4	3	7
non coding			3	3		6
Total	0	0	49	21	11

Variants in CCAR2

This is a list of pathogenic ClinVar variants found in the CCAR2 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
8-22605806-G-A		CCAR2-related disorder	Likely benign (Apr 08, 2019)
8-22606110-C-T		CCAR2-related disorder	Benign (Oct 17, 2019)
8-22606144-A-C		not specified	Uncertain significance (Jun 29, 2023)
8-22606184-C-G		CCAR2-related disorder	Benign (Oct 17, 2019)
8-22606626-T-C		not specified	Uncertain significance (Jun 21, 2021)
8-22608000-T-G		CCAR2-related disorder	Likely benign (Mar 01, 2019)
8-22608004-C-G		not specified	Uncertain significance (Mar 21, 2022)
8-22608031-C-T		not specified	Uncertain significance (Dec 06, 2021)
8-22613025-A-C		not specified	Uncertain significance (May 04, 2022)
8-22613063-C-T		not specified	Uncertain significance (Mar 20, 2024)
8-22613072-G-T		not specified	Uncertain significance (Sep 26, 2023)
8-22613118-C-G		not specified	Uncertain significance (Apr 01, 2024)
8-22613126-A-G		not specified	Uncertain significance (Apr 22, 2024)
8-22614082-C-CT		CCAR2-related disorder	Likely benign (Apr 29, 2019)
8-22614188-C-G		not specified	Uncertain significance (Jan 29, 2024)
8-22614189-C-A		not specified	Uncertain significance (Nov 07, 2022)
8-22614208-C-A		not specified	Uncertain significance (Jan 19, 2022)
8-22614263-C-T		CCAR2-related disorder	Likely benign (Nov 26, 2019)
8-22614295-A-G		not specified	Uncertain significance (Jan 04, 2024)
8-22614311-G-A		CCAR2-related disorder	Benign (Oct 17, 2019)
8-22614470-G-A			Likely benign (May 23, 2018)
8-22614476-G-A		CCAR2-related disorder	Likely benign (May 20, 2019)
8-22614856-G-C		not specified	Uncertain significance (Feb 07, 2023)
8-22614858-A-G		CCAR2-related disorder	Likely benign (Oct 28, 2019)
8-22614912-C-T		CCAR2-related disorder	Likely benign (Feb 18, 2019)

GnomAD

Source: gnomAD

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: dbNSFP

• 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

• 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_gene_trap: N

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