BRCA1

BRCA1 is a critical tumor suppressor protein that functions as a central hub for maintaining genomic stability. Its primary molecular function is as a RING-type E3 ubiquitin ligase (in complex with BARD1) that catalyzes K6-linked polyubiquitin chains. BRCA1 orchestrates the cellular response to DNA double-strand breaks through multiple mechanisms: promoting homologous recombination repair via DNA end resection and RAD51 loading, regulating cell cycle checkpoints (particularly S-phase and G2/M), and maintaining centrosome stability. The protein contains three key domains: an N-terminal RING domain mediating E3 ligase activity, a large central region with nuclear localization signals and protein interaction sites, and C-terminal BRCT domains that bind phosphoproteins. BRCA1 forms at least four major complexes (BRCA1-A through BRCA1-D) that execute distinct functions in the DNA damage response. Germline pathogenic variants in BRCA1 cause hereditary breast and ovarian cancer syndrome, with carriers having approximately 66% risk of breast cancer and 41% risk of ovarian cancer by age 70.

Disorders

Relationship is the entry's genetic[].relationship_type. untyped means the entry has a genetic record for the gene but does not type it; its free-text association is shown instead.

An entry matches when ClinGen's MONDO disease is the entry's own disease term, a subtype term, or an exact-match mapping. An amber status marks an entry ClinGen supports the gene for (Definitive, Strong or Moderate) whose own record does not type it. A Limited, Disputed or Refuted tier on such an entry is not a gap.

• dna_repair_synthetic_lethality via Fallopian Tube Cancer, Ovarian High-Grade Serous Carcinoma named in the module itself