Alt. symbols: RNF53 | BRCC1 | PPP1R53 | FANCS

Approved name: BRCA1 DNA repair associated
Alt. names: breast cancer 1, early onset, breast cancer 1 | BRCA1/BRCA2-containing complex, subunit 1, protein phosphatase 1, regulatory subunit 53, Fanconi anemia, complementation group S

Location: 17q21.31: 43044295 - 43170245 (-)
Gene type: protein_coding, 41 transcripts.

Scores: LoFtool: 0.002070 | pLI: 0.00000000 | LOEUF: 0.915

HGNC: 1100

NCBI: 672, RefSeq: NG_005905.2

Ensembl: ENSG00000012048.26

LRG_292 | Status: public

OMIM: 113705

Expression | ProteinAtlas

BRCA1 encodes an E3 ubiquitin (Ub) ligase that specifically mediates the formation of 'Lys-6'-linked polyUb chains and plays a central role in DNA repair by facilitating cellular responses to DNA damage. Its E3 Ub ligase activity is required for its tumor suppressor function. The BRCA1-BARD1 heterodimer coordinates a diverse range of cellular pathways such as DNA damage repair, ubiquitination and transcriptional regulation to maintain genomic stability. Amongst other roles, BRCA1 is important for recombinational repair via interactions with PALB2 and FANCD2, regulating centrosomal microtubule nucleation, G2-M cell cycle checkpoint and progression, cell cycle arrest after exposure to ionizing irradiation in both S and G2 phase, and transcriptional regulation of P21 in response to DNA damage (PMID 20160719).

Monoallelic BRCA1 mutations are associated with an autosomal dominant hereditary cancer predisposition syndrome predominantly featuring increased risk for breast (in both females and males) and ovarian cancer (including fallopian tube and primary peritoneal cancers) [MIM:604370], and to a lesser extent other cancers such as prostate and pancreatic cancers (~2-fold increased risk for the latter) [MIM:614320]. Women with a BRCA1 mutation have an estimated 50-87% lifetime risk of breast cancer, wit h the lower risk estimates derived from population-based data and the higher estimates derived from patients ascertained through high-risk clinics. BRCA1-associated breast cancers tend to occur pre-menopausally, though some women and families have later onset. The lifetime risk of ovarian cancer is estimated to be as high as 44%, with average age at diagnosis around 50 years. For female BRCA1 mutation carriers who have had breast cancer, the risk for a second primary breast cancer is estimated at 30% in ten years, with a lifetime estimate of 40-60%, depending on the age at diagnosis of the first breast cancer (i.e. women diagnosed with breast cancer at a younger age will have a higher chance of a second primary breast cancer than those first diagnosed at later ages). For males, the lifetime risk of breast cancer and the lifetime risk of prostate cancer are also slightly increased. Biallelic missense, nonsense, and frameshift BRCA1 mutations are associated with Fanconi anemia, complementation group S [MIM:617883], an autosomal recessive disorder characterized by developmental delay apparent from infancy, short stature, microcephaly, and coarse dysmorphic features. Some patients may have radial ray anomalies, bone marrow failure and cytopenias, and increased risk of cancer. As for other FA subtypes, patient cells show defective DNA repair and increased stress-induced chromosomal breakage. Additionally, these patients may have a family history of cancer in members who are heterozygous mutation carriers. [Load More]