BRCC3

BRCA1/BRCA2-containing complex subunit 3, the group of BRCA1 A complex|BRISC complex|JAMM/MPN+ metallopeptidase family

Basic information

Region (hg38): X:155071420-155123077

Previous symbols: [ "CXorf53" ]

Links

ENSG00000185515

∙ NCBI:79184 ∙ OMIM:300617 ∙ HGNC:24185 ∙ Uniprot:P46736 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

Moyamoya disease (Limited), mode of inheritance: AD

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the BRCC3 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the BRCC3 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						0
missense			3 clinvar			3
nonsense						0
start loss						0
frameshift						0
inframe indel				1 clinvar		1
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding					1 clinvar	1
Total	0	0	3	1	1

Variants in BRCC3

This is a list of pathogenic ClinVar variants found in the BRCC3 region.

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

Position	Phenotype	Significance	ClinVar
X-155071541-TGGTGCAGGC-T		Likely benign (Jan 01, 2023)	2661872
X-155071734-T-C	Hereditary cancer-predisposing syndrome	Likely benign (Dec 01, 2015)	223602
X-155073411-A-G		Uncertain significance (Nov 01, 2022)	2661873
X-155075674-T-C	Hereditary cancer-predisposing syndrome	Likely benign (Dec 01, 2015)	223597
X-155078908-A-G	Hereditary cancer-predisposing syndrome	Likely benign (-)	223603
X-155078944-A-G	Hereditary cancer-predisposing syndrome	Likely benign (Dec 01, 2015)	223600
X-155081868-C-A	Hereditary cancer-predisposing syndrome	Likely benign (Dec 01, 2015)	223598
X-155081874-G-A	Hereditary cancer-predisposing syndrome	Likely benign (Dec 01, 2015)	223599
X-155090380-C-T	Hereditary cancer-predisposing syndrome	Likely benign (Dec 01, 2015)	223596
X-155098992-A-G	Hereditary cancer-predisposing syndrome	Likely benign (Dec 01, 2015)	223601
X-155116069-C-G	not specified	Uncertain significance (Jan 03, 2024)	3134941
X-155116113-T-C	not specified	Uncertain significance (Apr 23, 2024)	2661874
X-155116702-A-G		Benign (Dec 31, 2019)	710187

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
BRCC3	protein_coding	protein_coding	ENST00000369462	11	51655

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00639	0.976	124646	2	4	124652	0.0000241

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.67	32	111	0.288	0.00000827	2067
Missense in Polyphen		2	39.088	0.051167		821
Synonymous	0.616	36	41.0	0.878	0.00000309	579
Loss of Function	2.08	6	14.6	0.412	0.00000116	236

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000369	0.0000369
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.0000639	0.0000442
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

Function: FUNCTION: Metalloprotease that specifically cleaves 'Lys-63'- linked polyubiquitin chains (PubMed:19214193, PubMed:20656690, PubMed:24075985, PubMed:26344097). Does not have activity toward 'Lys-48'-linked polyubiquitin chains. Component of the BRCA1-A complex, a complex that specifically recognizes 'Lys-63'-linked ubiquitinated histones H2A and H2AX at DNA lesions sites, leading to target the BRCA1-BARD1 heterodimer to sites of DNA damage at double-strand breaks (DSBs). In the BRCA1-A complex, it specifically removes 'Lys-63'-linked ubiquitin on histones H2A and H2AX, antagonizing the RNF8-dependent ubiquitination at double- strand breaks (DSBs) (PubMed:20656690). Catalytic subunit of the BRISC complex, a multiprotein complex that specifically cleaves 'Lys-63'-linked ubiquitin in various substrates (PubMed:20656690, PubMed:24075985, PubMed:26344097, PubMed:26195665). Mediates the specific 'Lys-63'-specific deubiquitination associated with the COP9 signalosome complex (CSN), via the interaction of the BRISC complex with the CSN complex (PubMed:19214193). The BRISC complex is required for normal mitotic spindle assembly and microtubule attachment to kinetochores via its role in deubiquitinating NUMA1 (PubMed:26195665). Plays a role in interferon signaling via its role in the deubiquitination of the interferon receptor IFNAR1; deubiquitination increases IFNAR1 activity by enhancing its stability and cell surface expression (PubMed:24075985, PubMed:26344097). Down-regulates the response to bacterial lipopolysaccharide (LPS) via its role in IFNAR1 deubiquitination (PubMed:24075985). {ECO:0000269|PubMed:14636569, ECO:0000269|PubMed:16707425, ECO:0000269|PubMed:17525341, ECO:0000269|PubMed:19202061, ECO:0000269|PubMed:19214193, ECO:0000269|PubMed:19261746, ECO:0000269|PubMed:19261748, ECO:0000269|PubMed:19261749, ECO:0000269|PubMed:20656690, ECO:0000269|PubMed:24075985, ECO:0000269|PubMed:26195665, ECO:0000269|PubMed:26344097}.;
Pathway: NOD-like receptor signaling pathway - Homo sapiens (human);Homologous recombination - Homo sapiens (human);HDR through Homologous Recombination (HR) or Single Strand Annealing (SSA);DNA Repair;Nonhomologous End-Joining (NHEJ);DNA Double-Strand Break Repair;Homology Directed Repair;Post-translational protein modification;Metabolism of proteins;G2/M DNA damage checkpoint;G2/M Checkpoints;Cell Cycle Checkpoints;Metalloprotease DUBs;Deubiquitination;Cell Cycle;Recruitment and ATM-mediated phosphorylation of repair and signaling proteins at DNA double strand breaks;DNA Double Strand Break Response;Processing of DNA double-strand break ends (Consensus)

Recessive Scores

pRec: 0.194

Intolerance Scores

loftool: 0.521
rvis_EVS: 0.21
rvis_percentile_EVS: 67.72

Haploinsufficiency Scores

pHI: 0.156
hipred: Y
hipred_score: 0.682
ghis: 0.559

Essentials

essential_gene_CRISPR: N
essential_gene_CRISPR2: N
essential_gene_gene_trap: N
gene_indispensability_pred: N
gene_indispensability_score: 0.237

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

Gene name: Brcc3
Phenotype

Zebrafish Information Network

Gene name: brcc3
Affected structure: vascular sprouts
Phenotype tag: abnormal
Phenotype quality: increased amount

Gene ontology

Biological process: DNA repair;double-strand break repair;double-strand break repair via nonhomologous end joining;cell cycle;response to X-ray;response to ionizing radiation;protein deubiquitination;positive regulation of DNA repair;regulation of catalytic activity;cell division;protein K63-linked deubiquitination;histone H2A K63-linked deubiquitination;signal transduction involved in G2 DNA damage checkpoint
Cellular component: ubiquitin ligase complex;nuclear ubiquitin ligase complex;spindle pole;nucleus;nucleoplasm;cytoplasm;cytosol;BRCA1-A complex;BRISC complex
Molecular function: thiol-dependent ubiquitin-specific protease activity;protein binding;metallopeptidase activity;enzyme regulator activity;polyubiquitin modification-dependent protein binding;thiol-dependent ubiquitinyl hydrolase activity;metal ion binding;Lys63-specific deubiquitinase activity