E3 ubiquitin-protein ligase that specifically mediates the formation of 'Lys-6'-linked polyubiquitin chains and plays a central role in DNA repair by facilitating cellular responses to DNA damage (PubMed:10500182, PubMed:12887909, PubMed:12890688, PubMed:14976165, PubMed:16818604, PubMed:17525340, PubMed:19261748). It is unclear whether it also mediates the formation of other types of polyubiquitin chains (PubMed:12890688). The BRCA1-BARD1 heterodimer coordinates a diverse range of cellular pathways such as DNA damage repair, ubiquitination and transcriptional regulation to maintain genomic stability (PubMed:12890688, PubMed:14976165, PubMed:20351172).
Regulates centrosomal microtubule nucleation (PubMed:18056443). Required for appropriate cell cycle arrests after ionizing irradiation in both the S-phase and the G2 phase of the cell cycle (PubMed:10724175, PubMed:11836499, PubMed:12183412, PubMed:19261748). Required for FANCD2 targeting to sites of DNA damage (PubMed:12887909).
Inhibits lipid synthesis by binding to inactive phosphorylated ACACA and preventing its dephosphorylation (PubMed:16326698). Contributes to homologous recombination repair (HRR) via its direct interaction with PALB2, fine-tunes recombinational repair partly through its modulatory role in the PALB2-dependent loading of BRCA2-RAD51 repair machinery at DNA breaks (PubMed:19369211). Component of the BRCA1-RBBP8 complex which regulates CHEK1 activation and controls cell cycle G2/M checkpoints on DNA damage via BRCA1-mediated ubiquitination of RBBP8 (PubMed:16818604).
Acts as a transcriptional activator (PubMed:20160719)
Heterodimer with BARD1 (PubMed:11573085, PubMed:12890688, PubMed:14976165). Part of the BRCA1-associated genome surveillance complex (BASC), which contains BRCA1, MSH2, MSH6, MLH1, ATM, BLM, PMS2 and the MRE11-RAD50-NBN protein (MRN) complex (PubMed:10783165). This association could be a dynamic process changing throughout the cell cycle and within subnuclear domains (PubMed:10783165).
Component of the BRCA1-A complex, at least composed of BRCA1, BARD1, UIMC1/RAP80, ABRAXAS1, BRCC3/BRCC36, BABAM2 and BABAM1/NBA1 (PubMed:19261746, PubMed:19261748, PubMed:19261749, PubMed:20351172). Interacts (via the BRCT domains) with ABRAXAS1 (phosphorylated form); this is important for recruitment to sites of DNA damage (PubMed:17525340, PubMed:17643121, PubMed:17643122, PubMed:23269703, PubMed:24316840, PubMed:26778126). Can form a heterotetramer with two molecules of ABRAXAS1 (phosphorylated form) (PubMed:26778126).
Component of the BRCA1-RBBP8 complex (PubMed:16101277). Interacts (via the BRCT domains) with RBBP8 ('Ser-327' phosphorylated form); the interaction ubiquitinates RBBP8, regulates CHEK1 activation, and involves RBBP8 in BRCA1-dependent G2/M checkpoint control on DNA damage (PubMed:16818604, PubMed:9811458). Associates with RNA polymerase II holoenzyme (PubMed:9662397).
Interacts with SMC1A, NELFB, DCLRE1C, CLSPN (PubMed:11739404, PubMed:11877377, PubMed:15096610, PubMed:15456891). Interacts with CHEK1, CHEK2, BAP1, BRCC3, UBXN1 and PCLAF (PubMed:10724175, PubMed:11836499, PubMed:14636569, PubMed:20351172, PubMed:21673012). Interacts (via BRCT domains) with BRIP1 (phosphorylated form) (PubMed:11301010, PubMed:15133502, PubMed:21473589).
Interacts with FANCD2 (ubiquitinated form) (PubMed:11239454). Interacts with H2AX (phosphorylated on 'Ser-140') (PubMed:12419185). Interacts (via the BRCT domains) with ACACA (phosphorylated form); the interaction prevents dephosphorylation of ACACA (PubMed:12360400, PubMed:16326698, PubMed:16698035, PubMed:18452305).
Part of a BRCA complex containing BRCA1, BRCA2 and PALB2 (PubMed:19369211). Interacts directly with PALB2; the interaction is essential for its function in HRR (PubMed:19369211, PubMed:28319063). Interacts directly with BRCA2; the interaction occurs only in the presence of PALB2 which serves as the bridging protein (PubMed:19369211).
Interacts (via the BRCT domains) with LMO4; the interaction represses the transcriptional activity of BRCA1 (PubMed:11751867). Interacts (via the BRCT domains) with CCAR2 (via N-terminus); the interaction represses the transcriptional activator activity of BRCA1 (PubMed:20160719). Interacts with EXD2 (PubMed:26807646).
Interacts (via C-terminus) with DHX9; this interaction is direct and links BRCA1 to the RNA polymerase II holoenzyme (PubMed:9662397). Interacts with DNA helicase ZGRF1; the interaction is increased following DNA damage induction (PubMed:34552057). Interacts with FBXO44; this interaction mediates BRCA1 ubiquitination and subsequent degradation (PubMed:23086937)
Isoform 1 and isoform 3 are widely expressed. Isoform 3 is reduced or absent in several breast and ovarian cancer cell lines
The BRCT domains recognize and bind phosphorylated pSXXF motif on proteins. The interaction with the phosphorylated pSXXF motif of ABRAXAS1, recruits BRCA1 at DNA damage sites
The RING-type zinc finger domain interacts with BAP1
A common malignancy originating from breast epithelial tissue. Breast neoplasms can be distinguished by their histologic pattern. Invasive ductal carcinoma is by far the most common type.
Breast cancer is etiologically and genetically heterogeneous. Important genetic factors have been indicated by familial occurrence and bilateral involvement. Mutations at more than one locus can be involved in different families or even in the same case.
A condition associated with familial predisposition to cancer of the breast and ovaries. Characteristic features in affected families are an early age of onset of breast cancer (often before age 50), increased chance of bilateral cancers (cancer that develop in both breasts, or both ovaries, independently), frequent occurrence of breast cancer among men, increased incidence of tumors of other specific organs, such as the prostate.
The term ovarian cancer defines malignancies originating from ovarian tissue. Although many histologic types of ovarian tumors have been described, epithelial ovarian carcinoma is the most common form. Ovarian cancers are often asymptomatic and the recognized signs and symptoms, even of late-stage disease, are vague.
Consequently, most patients are diagnosed with advanced disease.
A malignant neoplasm of the pancreas. Tumors can arise from both the exocrine and endocrine portions of the pancreas, but 95% of them develop from the exocrine portion, including the ductal epithelium, acinar cells, connective tissue, and lymphatic tissue.
A form of Fanconi anemia, a disorder affecting all bone marrow elements and resulting in anemia, leukopenia and thrombopenia. It is associated with cardiac, renal and limb malformations, dermal pigmentary changes, and a predisposition to the development of malignancies. At the cellular level it is associated with hypersensitivity to DNA-damaging agents, chromosomal instability (increased chromosome breakage) and defective DNA repair.
Click a pathway to open the interactive Reactome viewer.
Genes with an experimentally identified or computationally predicted synthetic-lethal relationship to BRCA1, aggregated across our SSL data sources. Click any partner node to view that gene’s page.
Nodes and edges are coloured by the SSL data source. Partners appearing in more than one source are shown in grey.
Total Trials Found: 377
| NCT ID | Condition | Brief Title | Phase | Status |
|---|---|---|---|---|
| NCT03205761 | Advanced Breast Cancer | Analysis of Olaparib Response in Patients With BRCA1 and/or 2 Promoter Methylation Diagnosed of Advanced Breast Cancer | PHASE2 | COMPLETED |
| NCT01608074 | BRCA1 Mutation, BRCA2 Mutation, Hereditary Breast and Ovarian Cancer | Radical Fimbriectomy for Young BRCA Mutation Carriers | NA | ACTIVE_NOT_RECRUITING |
| NCT03685331 | Metastatic Breast Cancer, Locally Advanced Breast Cancer, Advanced Breast Cancer, BRCA2 Mutation, BRCA1 Mutation | HOPE: Olaparib, Palbociclib and Fulvestrant in Patients With BRCA Mutation-associated, HR+, HER2-metastatic Breast Cancer | PHASE1 | COMPLETED |
| NCT02087592 | Hereditary Breast and Ovarian Cancer | Feasibility of Lifestyle Intervention in BRCA1/2 Mutation Carriers | NA | COMPLETED |
| NCT06177171 | BRCA1 Mutation, BRCA2 Mutation, BRCA Mutation, PALB2 Gene Mutation, Checkpoint Kinase 2 Gene Mutation, ATM Gene Mutation | Olaparib and ASTX727 in BRCA1/2- and Homologous Recombination Deficient (HRD)-Mutated Tumors | PHASE1 | RECRUITING |
| NCT02760849 | Deleterious BARD1 Gene Mutation, Deleterious BRCA1 Gene Mutation, Deleterious BRCA2 Gene Mutation, Deleterious BRIP1 Gene Mutation, Deleterious EPCAM Gene Mutation, Deleterious MLH1 Gene Mutation, Deleterious MSH2 Gene Mutation, Deleterious MSH6 Gene Mutation, Deleterious PALB2 Gene Mutation, Deleterious PMS2 Gene Mutation, Deleterious RAD51C Gene Mutation, Deleterious RAD51D Gene Mutation, Hereditary Breast and Ovarian Cancer Syndrome, Premenopausal | Surgery in Preventing Ovarian Cancer in Patients With Genetic Mutations | NA | ACTIVE_NOT_RECRUITING |
| NCT02341118 | Ovarian Cancer | Capturing BRCA1/2 Mutational Status in Women With High Grade Serous Ovarian Cancer and Impact on Clinical Outcome. | N/A | TERMINATED |
| NCT04718675 | Relapsed Solid Tumors, Refractory Solid Tumors, Non-Hodgkin Lymphoma, HGSOC, Platinum Resistant High Grade Serous Ovarian Cancer | A Study of KB-0742 in Participants With Relapsed or Refractory Solid Tumors Including Platinum Resistant High Grade Serous Ovarian Cancer (HGSOC) | PHASE1, PHASE2 | TERMINATED |
| NCT04089189 | Ovarian Cancer | Study of IMP4297 in Patients With BRCA1/2 Mutation Ovarian Cancer | PHASE2 | COMPLETED |
| NCT07197723 | BRCA1/2, Geneitic Testing | Study of How People Make Decisions About Prostate Cancer Risk | N/A | RECRUITING |