{"gene":{"symbol":"BRCA1","name":"BRCA1 DNA Repair Associated","protein":"Breast cancer type 1 susceptibility protein","ncbi_gene_id":"672","locus":"17q21.31","summary":"BRCA1 is a tumor suppressor gene encoding a protein essential for homologous-recombination repair of DNA double-strand breaks. Loss-of-function variants confer substantially elevated lifetime risk of breast and ovarian cancer, the basis of hereditary breast and ovarian cancer syndrome, with risks large enough to drive surveillance and risk-reducing surgical decisions. ClinVar records thousands of distinct BRCA1 variants; consumer SNP arrays test only a handful.","function":"BRCA1 encodes a large multi-domain nuclear protein that functions as a scaffold and regulator in homologous-recombination repair, the high-fidelity pathway for repairing DNA double-strand breaks: it recruits and stabilizes PALB2, which in turn recruits BRCA2 and the recombinase RAD51 to sites of damage, and it also participates in checkpoint signalling, transcriptional regulation and chromatin remodelling. When one allele carries a loss-of-function variant, cells still have a functional copy; risk arises from Knudson's two-hit model, where somatic loss of the remaining allele leaves the cell unable to repair double-strand breaks accurately, so mutations accumulate rapidly and malignant transformation becomes likely, particularly in breast and ovarian epithelium. The same defect underlies synthetic-lethal therapy with PARP inhibitors (olaparib, talazoparib, niraparib, rucaparib), which block the alternative single-strand-break repair pathway so that HRR-deficient cells cannot survive.","category":"disease_risk","key_variants":[{"rsid":"rs80357914","name":"185delAG (c.68_69delAG)","alleles":"An insertion-deletion site, not a single letter: this rsID covers both a two-base deletion (c.68_69del, known as 185delAG) and a duplication at the same place, and consumer files report insertions and deletions in their own notation. It can't be counted from an rsID lookup.","effect":"Frameshift that truncates the protein early. ClinVar: Pathogenic.","frequency_note":"Ashkenazi Jewish founder variant; ~1% carrier frequency in that population, far rarer elsewhere."},{"rsid":"rs80357906","name":"5382insC (c.5266dupC)","alleles":"A one-base duplication (c.5266dup, known as 5382insC), not a single letter; consumer files report insertions in their own notation. It can't be counted from an rsID lookup.","effect":"Frameshift. ClinVar: Pathogenic.","frequency_note":"Ashkenazi Jewish and Central/Eastern European founder variant."},{"rsid":"rs28897672","name":"C61G (c.181T>G)","alleles":"Plus strand, GRCh37 (as in 23andMe raw data): A reference, C variant. BRCA1 is on the minus strand, so C here is the G of c.181T>G (Cys61Gly).","effect":"Missense disrupting the RING domain; abolishes BRCA1–BARD1 ubiquitin ligase (E3) activity in vitro. ClinVar: Pathogenic.","frequency_note":"Polish founder variant."},{"rsid":null,"name":"Thousands of other variants across the gene","alleles":null,"effect":"ClinVar lists thousands of distinct BRCA1 variants classified across the full ACMG five-tier spectrum (Pathogenic, Likely Pathogenic, Variant of Uncertain Significance, Likely Benign, Benign). Most pathogenic variants are private to one or a few families. Most consumer arrays cover <0.1% of these.","frequency_note":null}],"phenotypes":["Pathogenic / likely pathogenic variant carrier: hereditary breast and ovarian cancer syndrome","Variant of uncertain significance (VUS)","Likely benign / benign"],"clinical_relevance":"BRCA1 is on the ACMG Secondary Findings list, the small set of genes where an incidentally discovered pathogenic variant should be reported because actionable preventive measures exist. Lifetime cancer risk for pathogenic-variant carriers (Kuchenbaecker et al., JAMA 2017): breast cancer ~72% (95% CI 65–79) by age 80 and ovarian cancer ~44% (95% CI 36–53) by age 80, with an elevated risk of contralateral breast cancer; the NCI also lists lifetime risks of up to 5% for pancreatic cancer (about 1.7% in the general population) and about 7–26% by age 80 for prostate cancer (about 10.6% in the general population). Risk-reducing options with established evidence: enhanced surveillance (annual MRI plus mammography from age 25–30), risk-reducing salpingo-oophorectomy and risk-reducing bilateral mastectomy. Therapeutic implications for diagnosed carriers: PARP inhibitor therapy, platinum-based chemotherapy considerations and informed surgical decisions. First-degree relatives have a 50% chance of carrying the same variant, so cascade testing and family communication are part of standard genetic counselling. If worried about BRCA1 because of family history, the right test is gene-panel or full-gene sequencing in a clinical lab with genetic counselling, not a consumer chip.","consumer_array_caveat":"A consumer SNP chip cannot detect the vast majority of BRCA1 pathogenic variants, only the specific founder variants its probes target; a 'negative' consumer result is not a clinically negative BRCA1 result. Consumer-grade arrays have well-documented false-positive rates in rare variants, so a positive result requires confirmation in a clinical laboratory before any clinical decision. Some services, including 23andMe, report the three Ashkenazi Jewish founder variants (185delAG, 5382insC and BRCA2 6174delT); that panel is genuinely informative for people of Ashkenazi ancestry, but for other populations the same three SNPs have very low prior probability and provide almost no information. A family history that concerns you is still a reason to seek genetic counselling, because the family variant may simply not be on the chip.","drugs":[{"drug":"olaparib","guideline":null,"level":null,"summary":"PARP inhibitor; synthetic-lethal therapy for HRR-deficient cells. The FDA label indicates it for ovarian cancer maintenance (BRCA-mutated, or HRD-positive with bevacizumab), germline BRCA-mutated HER2-negative early and metastatic breast cancer, germline BRCA-mutated metastatic pancreatic cancer and HRR gene-mutated metastatic castration-resistant prostate cancer, with patients selected by an FDA-approved companion diagnostic."},{"drug":"talazoparib","guideline":null,"level":null,"summary":"PARP inhibitor; synthetic-lethal therapy for HRR-deficient cells. The FDA label indicates it as a single agent for germline BRCA-mutated HER2-negative locally advanced or metastatic breast cancer (selected by an FDA-approved companion diagnostic) and, with enzalutamide, for HRR gene-mutated metastatic castration-resistant prostate cancer. It is not indicated for ovarian cancer."},{"drug":"niraparib","guideline":null,"level":null,"summary":"PARP inhibitor; synthetic-lethal therapy for HRR-deficient cells. The ZEJULA label indicates it only as maintenance for ovarian, fallopian tube or primary peritoneal cancer after response to platinum chemotherapy: first line when HRD-positive (BRCA mutation and/or genomic instability), and in germline BRCA-mutated recurrent disease, selected by an FDA-authorized companion diagnostic. It is not indicated for breast cancer."},{"drug":"rucaparib","guideline":null,"level":null,"summary":"PARP inhibitor; synthetic-lethal therapy for HRR-deficient cells. The FDA label indicates it as maintenance for BRCA-mutated (germline and/or somatic) recurrent ovarian, fallopian tube or primary peritoneal cancer after response to platinum chemotherapy, and for BRCA-mutated metastatic castration-resistant prostate cancer after androgen receptor-directed therapy. It is not indicated for breast cancer."}],"sources":[{"label":"ClinVar — BRCA1 entries","url":"https://www.ncbi.nlm.nih.gov/clinvar/?term=BRCA1%5Bgene%5D"},{"label":"OMIM 113705 — BRCA1","url":"https://www.omim.org/entry/113705"},{"label":"NCBI Gene 672","url":"https://www.ncbi.nlm.nih.gov/gene/672"},{"label":"Kuchenbaecker et al., JAMA 2017 (breast, ovarian and contralateral breast cancer risk in BRCA1/2 carriers)","url":"https://pubmed.ncbi.nlm.nih.gov/28632866/"},{"label":"Miller et al., Genet Med 2023 (ACMG SF v3.2 list including BRCA1)","url":"https://pubmed.ncbi.nlm.nih.gov/37347242/"},{"label":"Parsons et al., Am J Hum Genet 2024 (ClinGen ENIGMA BRCA1/BRCA2 variant curation expert panel specifications)","url":"https://pubmed.ncbi.nlm.nih.gov/39142283/"},{"label":"Tandy-Connor et al., Genet Med 2018 (false positives in direct-to-consumer raw genotype data)","url":"https://pubmed.ncbi.nlm.nih.gov/29565420/"},{"label":"National Cancer Institute, BRCA Gene Changes: Cancer Risk and Genetic Testing fact sheet 2024","url":"https://www.cancer.gov/about-cancer/causes-prevention/genetics/brca-fact-sheet"},{"label":"FDA De Novo DEN170046, 2018 (23andMe BRCA1/BRCA2 Selected Variants report: 185delAG, 5382insC, 6174delT)","url":"https://www.accessdata.fda.gov/cdrh_docs/reviews/DEN170046.pdf"},{"label":"Hashizume et al., J Biol Chem 2001 (BRCA1–BARD1 ubiquitin ligase inactivated by C61G)","url":"https://pubmed.ncbi.nlm.nih.gov/11278247/"},{"label":"FDA label, LYNPARZA (olaparib) 2025 (indications; companion diagnostic)","url":"https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=741ff3e3-dc1a-45a6-84e5-2481b27131aa"},{"label":"FDA label, TALZENNA (talazoparib) 2026 (indications; companion diagnostic)","url":"https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=13839d4f-6acf-4ffb-a128-79df59319273"},{"label":"FDA label, ZEJULA (niraparib) 2026 (indications; companion diagnostic)","url":"https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=b7f675e2-159c-490c-b6f4-3f16d9492b7d"},{"label":"FDA label, RUBRACA (rucaparib) 2025 (indications; companion diagnostic)","url":"https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=0295d202-1cfe-7659-e063-6294a90a476e"}],"related_blog":"/blog/genetic-risk-scores-explained/","disclaimer":"Educational information only, not medical advice or diagnosis. Consult a clinician before acting on genetic information."},"meta":{"disclaimer":"Educational information only, not medical advice or diagnosis. Consult a clinician before acting on genetic information.","api_version":"2026-09-20","docs":"https://deepdna.ai/docs/","status":"live","data_as_of":"2026-10-25T21:32:19.251Z","freshness":"https://deepdna.ai/api/v1/freshness"}}