BRCA1 Gene Complete Identifier and Functional Mapping Reference
Provide a comprehensive cross-database identifier and functional mapping reference for human BRCA1 — a definitive lookup resource covering: ### Section 1: Gene identifiers For human gene BRCA1, list ALL gene-level database identifiers. Required: - HGNC ID and approved symbol - Ensembl gene ID (ENSG...) - NCBI Entrez Gene ID - OMIM gene/locus ID - Genomic location: chromosome, start position, end position, strand (GRCh38) ### Section 2: Transcript identifiers For human gene BRCA1, list ALL transcript-level identifiers. Required: - Ensembl transcripts: ALL ENST IDs with biotype. Total count. - RefSeq transcripts: ALL NM_ mRNA accessions. Mark which is MANE Select. - CCDS IDs. - For the CANONICAL/MANE SELECT transcript: ALL exon IDs (ENSE) with genomic coordinates and total exon count. ### Section 3: Protein identifiers For human gene BRCA1 protein product(s), list ALL protein-level identifiers. Required: - UniProt accessions: ALL entries (reviewed and unreviewed). Mark the canonical reviewed entry. - RefSeq protein: ALL NP_ accessions. - Protein domains and families: list ALL annotated domains/families with identifiers, including name, type (domain/family/superfamily), and ID. - Antibody availability: known antibody resources for the protein. ### Section 4: Structure For human gene BRCA1 protein, list ALL structural data. Required: - Experimental structures: ALL PDB IDs. For each: experimental method (X-ray/NMR/Cryo-EM) and resolution. Total count. - Predicted structures: AlphaFold model ID and confidence metrics (pLDDT). ### Section 5: Cross-species orthologs For human gene BRCA1, list orthologous genes in key model organisms. Organisms: - Mouse (Mus musculus): gene ID, symbol - Rat (Rattus norvegicus): gene ID, symbol - Zebrafish (Danio rerio): gene ID, symbol - Fruit fly (Drosophila melanogaster): gene ID, symbol - Worm (C. elegans): gene ID, symbol - Yeast (S. cerevisiae): gene ID, symbol ### Section 6: Clinical variants & AI predictions For human gene BRCA1, summarize clinical variants and AI predictions. Clinical variant annotations (ClinVar): - Total variant count (approximate is fine) - Breakdown by classification: Pathogenic, Likely Pathogenic, VUS, Likely Benign, Benign - TOP 30 pathogenic/likely pathogenic variants with: variant ID, HGVS notation, associated condition AI-based variant effect predictions: - Splice effect predictions: total count + TOP 30 with delta scores if known - Missense pathogenicity from AlphaMissense — total count + TOP 30 likely-pathogenic with am_pathogenicity scores. ### Section 7: Pathways & Gene Ontology For human gene BRCA1, list biological pathways and Gene Ontology annotations. Pathway membership: - ALL biological pathways this gene participates in, with pathway IDs and names - Total pathway count Gene Ontology: - Biological Process: count and TOP 20 terms with GO IDs - Molecular Function: count and TOP 20 terms with GO IDs - Cellular Component: count and TOP 20 terms with GO IDs ### Section 8: Protein interactions & networks For human gene BRCA1 protein, summarize protein interactions and networks. Protein-protein interactions (STRING, IntAct, BioGRID, etc.): - Total interaction count (approximate) - TOP 30 highest-confidence interacting proteins with scores/evidence Protein similarity: - Structural/embedding similarity (e.g. Foldseek, ESM): TOP 20 similar proteins with scores - Sequence homology: TOP 20 homologous proteins with identity/similarity ### Section 9: Transcription factor regulatory data For human gene BRCA1, summarize transcription factor regulatory data. If BRCA1 is a transcription factor: - Downstream targets: total count + TOP 30 with regulation type (activates/represses) and evidence - DNA binding motifs from JASPAR — all known motif IDs and motif family classification. Regardless: - Upstream regulators: TFs that regulate BRCA1 — names with evidence type (ChIP-seq / predicted / experimentally validated) If BRCA1 is not a transcription factor, say so briefly and skip the downstream/motif sections. ### Section 10: Drug & pharmacology data For human gene BRCA1 protein as a drug target, summarize pharmacology data. If BRCA1 is a known drug target: - Targeting molecules: total count in ChEMBL/DrugBank + TOP 30 by development phase (molecule ID, name, mechanism, highest phase) - Clinical trials: TOP 20 involving drugs targeting this gene — trial ID, phase, status, intervention - Pharmacogenomics: known drug-gene interactions affecting drug response + dosing guidelines if any If BRCA1 is not currently a drug target, say so briefly. ### Section 11: Expression profiles For human gene BRCA1, summarize expression profiles. Tissue expression (GTEx, HPA, Bgee, etc.): - TOP 30 tissues with expression scores/levels (direction, units if known) - Note tissue-specific or tissue-enriched patterns Cell type expression (Tabula Sapiens, HCA, etc.): - TOP 30 cell types with expression scores - Note cell-type-specific patterns Single-cell expression: notable datasets or cell populations of interest for this gene. ### Section 12: Disease associations For human gene BRCA1, summarize disease associations. Mendelian / monogenic disease: - Diseases caused by mutations in BRCA1: disease name, disease ID (OMIM/Orphanet/Mondo), inheritance pattern, evidence level - Include all directly linked conditions Phenotype associations: - Clinical phenotypes associated with the gene (HPO terms where known) - TOP 30 phenotype terms with HPO IDs Complex-disease / GWAS: - Traits and diseases significantly associated via GWAS: trait name, variant, effect size, study where known - TOP 30 GWAS associations
Executive summary
BRCA1 (chromosome 17q, HGNC:1100) is a major hereditary breast and ovarian cancer susceptibility gene encoding a 1863-amino-acid RING-type E3 ubiquitin ligase (UniProt P38398, 207,721 Da) that functions as a master coordinator of DNA double-strand break repair, cell cycle checkpoints, and transcriptional regulation. Pathogenic germline variants cause autosomal dominant hereditary breast-ovarian cancer syndrome (OMIM:604370) and, via biallelic mutations, Fanconi anemia complementation group S (OMIM:617883). The ClinVar database catalogues approximately 15,445 variants, of which ~500+ are pathogenic and ~4,000+ remain of uncertain significance, with AlphaMissense predicting over 900 likely pathogenic missense variants and SpliceAI flagging 3,719 variants with splice-altering potential. BRCA1 is not itself a small-molecule drug target but is clinically actionable through synthetic lethality: FDA- and EMA-approved PARP inhibitors such as olaparib (Lynparza) require prospective BRCA1/2 mutation testing before use across breast, ovarian, pancreatic, and prostate cancers. The protein engages a broad interaction network of ~6,120 STRING partners anchored by PALB2, TP53, ATM, BRCA2, and RAD51, and its expression is ubiquitous but highest in germ cells and proliferative tissues, consistent with its central role in maintaining genomic integrity.
BRCA1 — Reference
Cross-database identifier and functional mapping reference for BRCA1.
Gene identifiers
| Identifier | Value |
|---|---|
| HGNC ID | HGNC:1100 |
| Approved symbol | BRCA1 |
| Ensembl gene ID | ENSG00000012048 |
| NCBI Entrez Gene ID | 672 |
| OMIM locus ID | 113705 |
| Chromosome | 17 |
| Start (GRCh38) | 43,044,292 |
| End (GRCh38) | 43,170,245 |
| Strand | − (minus) |
Transcript identifiers
Ensembl transcripts: 47 total
| ENST ID | Biotype |
|---|---|
| ENST00000352993 | protein_coding |
| ENST00000354071 | retained_intron |
| ENST00000357654 | protein_coding |
| ENST00000461221 | nonsense_mediated_decay |
| ENST00000461574 | protein_coding |
| ENST00000461798 | nonsense_mediated_decay |
| ENST00000468300 | protein_coding |
| ENST00000470026 | protein_coding |
| ENST00000471181 | protein_coding |
| ENST00000472490 | retained_intron |
| ENST00000473961 | protein_coding |
| ENST00000476777 | protein_coding |
| ENST00000477152 | protein_coding |
| ENST00000478531 | protein_coding |
| ENST00000484087 | protein_coding |
| ENST00000489037 | protein_coding |
| ENST00000491747 | protein_coding |
| ENST00000492859 | nonsense_mediated_decay |
| ENST00000493795 | protein_coding |
| ENST00000493919 | protein_coding |
| ENST00000494123 | protein_coding |
| ENST00000497488 | protein_coding |
| ENST00000586385 | protein_coding |
| ENST00000591534 | protein_coding |
| ENST00000591849 | protein_coding |
| ENST00000618469 | protein_coding |
| ENST00000621897 | protein_coding_CDS_not_defined |
| ENST00000634433 | protein_coding |
| ENST00000642945 | nonsense_mediated_decay |
| ENST00000644379 | protein_coding |
| ENST00000644555 | protein_coding |
| ENST00000652672 | protein_coding |
| ENST00000700081 | retained_intron |
| ENST00000700082 | retained_intron |
| ENST00000700083 | retained_intron |
| ENST00000700182 | protein_coding |
| ENST00000700183 | nonsense_mediated_decay |
| ENST00000700184 | retained_intron |
| ENST00000700185 | protein_coding_CDS_not_defined |
| ENST00000700186 | protein_coding_CDS_not_defined |
| ENST00000713676 | protein_coding |
| ENST00000899954 | protein_coding |
| ENST00000921914 | protein_coding |
| ENST00000921915 | protein_coding |
| ENST00000921916 | protein_coding |
| ENST00000945268 | protein_coding |
| ENST00000945269 | protein_coding |
Summary: 30 protein_coding, 5 retained_intron, 5 nonsense_mediated_decay, 2 protein_coding_CDS_not_defined
RefSeq transcripts
MANE Select: NM_007294 (maps to ENST00000357654)
Additional RefSeq mRNA accessions (100+ identified): NM_001407571, NM_001407581, NM_001407582, NM_001407583, NM_001407585, NM_001407587, NM_001407590, NM_001407591, NM_001407593, NM_001407594, NM_001407596, NM_001407597, NM_001407598, NM_001407602, NM_001407603, NM_001407605, NM_001407610, NM_001407611, NM_001407612, NM_001407613, NM_001407614, NM_001407615, NM_001407616, NM_001407617, NM_001407618, NM_001407619, NM_001407620, NM_001407621, NM_001407622, NM_001407623, NM_001407624, NM_001407625, NM_001407626, NM_001407627, NM_001407628, NM_001407629, NM_001407630, NM_001407631, NM_001407632, NM_001407633, NM_001407634, NM_001407635, NM_001407636, NM_001407637, NM_001407638, NM_001407639, NM_001407640, NM_001407641, NM_001407642, NM_001407644, NM_001407645, NM_001407646, NM_001407647, NM_001407648, NM_001407649, NM_001407652, NM_001407653, NM_001407654, NM_001407655, NM_001407656, NM_001407657, NM_001407658, NM_001407659, NM_001407660, NM_001407661, NM_001407662, NM_001407663, NM_001407664, NM_001407665, NM_001407666, NM_001407667, NM_001407668, NM_001407669, NM_001407670, NM_001407671, NM_001407672, NM_001407673, NM_001407674, NM_001407675, NM_001407676, NM_001407677, NM_001407678, NM_001407679, NM_001407680, NM_001407681, NM_001407682, NM_001407683, NM_001407684, NM_001407685, NM_001407686, NM_001407687, NM_001407688, NM_001407689, NM_001407690, NM_001407691, NM_001407692, NM_001407694, NM_001407695, NM_001407696, NM_001407697
CCDS IDs: 5 total
- CCDS11453 (linked to MANE Select NM_007294)
- CCDS11454
- CCDS11455
- CCDS11456
- CCDS11459
MANE Select transcript exons: ENST00000357654 (NM_007294) — 23 exons
| Exon ID | Start | End | Strand | Chromosome |
|---|---|---|---|---|
| ENSE00001852567 | 43125271 | 43125364 | − | 17 |
| ENSE00001917948 | 43104122 | 43104261 | − | 17 |
| ENSE00003510592 | 43115726 | 43115779 | − | 17 |
| ENSE00003531836 | 43104868 | 43104956 | − | 17 |
| ENSE00003541068 | 43106456 | 43106533 | − | 17 |
| ENSE00003559512 | 43124017 | 43124115 | − | 17 |
| ENSE00004011550 | 43097244 | 43097289 | − | 17 |
| ENSE00004011551 | 43057052 | 43057135 | − | 17 |
| ENSE00004011552 | 43047643 | 43047703 | − | 17 |
| ENSE00004011553 | 43051063 | 43051117 | − | 17 |
| ENSE00004011554 | 43070928 | 43071238 | − | 17 |
| ENSE00004011556 | 43067608 | 43067695 | − | 17 |
| ENSE00004011558 | 43090944 | 43091032 | − | 17 |
| ENSE00004011559 | 43095846 | 43095922 | − | 17 |
| ENSE00004011560 | 43082404 | 43082575 | − | 17 |
| ENSE00004011561 | 43076488 | 43076614 | − | 17 |
| ENSE00004011562 | 43074331 | 43074521 | − | 17 |
| ENSE00004011563 | 43099775 | 43099880 | − | 17 |
| ENSE00004011564 | 43044295 | 43045802 | − | 17 |
| ENSE00004011565 | 43063874 | 43063951 | − | 17 |
| ENSE00004011566 | 43091435 | 43094860 | − | 17 |
| ENSE00004011567 | 43063333 | 43063373 | − | 17 |
| ENSE00004011568 | 43049121 | 43049194 | − | 17 |
Protein identifiers
UniProt accessions (22 entries)
Canonical reviewed:
- P38398 - Breast cancer type 1 susceptibility protein (1863 aa, mass 207721 Da)
Other entries (reviewed and unreviewed):
- A0A0U1RRA9
- A0A2R8Y6Y9
- A0A2R8Y7V5
- A0A494C182
- A0A8V8TPY7
- A0A9Y1QPT7
- A0A9Y1QQK3
- C6YB45
- C9IZW4
- E7ENB7
- E7EQW4
- E7EUM2
- E7EWN5
- E9PC22
- G1UI37
- H0Y850
- H0Y8B8
- H0Y8D8
- K7EJW3
- K7EPC7
- Q3B891
RefSeq protein accessions (NP_) — 55 isoforms
NP_001394500.1, NP_001394512.1, NP_001394522.1, NP_001394523.1, NP_001394525.1, NP_001394526.1, NP_001394527.1, NP_001394532.1, NP_001394534.1, NP_001394539.1, NP_001394540.1, NP_001394541.1, NP_001394542.1, NP_001394543.1, NP_001394544.1, NP_001394545.1, NP_001394546.1, NP_001394547.1, NP_001394548.1, NP_001394549.1, NP_001394550.1, NP_001394551.1, NP_001394552.1, NP_001394553.1, NP_001394554.1, NP_001394555.1, NP_001394556.1, NP_001394557.1, NP_001394558.1, NP_001394559.1, NP_001394560.1, NP_001394561.1, NP_001394562.1, NP_001394563.1, NP_001394564.1, NP_001394565.1, NP_001394566.1, NP_001394567.1, NP_001394568.1, NP_001394569.1, NP_001394570.1, NP_001394571.1, NP_001394573.1, NP_001394574.1, NP_001394575.1, NP_001394576.1, NP_001394577.1, NP_001394578.1, NP_001394581.1, NP_001394582.1, NP_001394583.1, NP_001394584.1, NP_001394586.1, NP_001394604.1, NP_001394605.1
Protein domains and families
| ID | Name | Type | Database |
|---|---|---|---|
| IPR001357 | BRCT domain | Domain | InterPro |
| IPR001841 | Zinc finger, RING-type | Domain | InterPro |
| IPR011364 | BRCA1 | Family | InterPro |
| IPR013083 | Znf_RING/FYVE/PHD | Homologous_superfamily | InterPro |
| IPR017907 | Znf_RING_CS | Conserved_site | InterPro |
| IPR018957 | Zinc finger, C3HC4 RING-type | Domain | InterPro |
| IPR025994 | BRCA1, serine-rich domain | Domain | InterPro |
| IPR031099 | BRCA1-associated | Family | InterPro |
| IPR036420 | BRCT domain superfamily | Homologous_superfamily | InterPro |
| PF00097 | Zinc finger C3HC4 type (RING finger) | Domain | Pfam |
| PF00533 | BRCT domain | Domain | Pfam |
| PF12820 | BRCA1 serine-rich domain | Domain | Pfam |
Antibody availability
Antibody data via direct biobtree mapping (»uniprot»antibody) returned no results. Available through Human Protein Atlas (HPA) database linked to UniProt P38398 (ENSG00000012048). Commercial antibody sources available from major vendors (e.g., Abcam, Santa Cruz, Sigma-Aldrich, Cell Signaling Technology) with extensive BRCA1-specific monoclonal and polyclonal antibodies documented in scientific literature (>100 publications).
Structure
Experimental structures: 33 PDB entries
X-ray crystallography (26 structures):
- 1JNX (2.5 Å)
- 1N5O (2.8 Å)
- 1T15 (1.85 Å)
- 1T29 (2.3 Å)
- 1T2U (2.8 Å)
- 1T2V (3.3 Å)
- 1Y98 (2.5 Å)
- 2ING (3.6 Å)
- 3COJ (3.21 Å)
- 3K0H (2.7 Å)
- 3K0K (2.7 Å)
- 3K15 (2.8 Å)
- 3K16 (3.0 Å)
- 3PXA (2.55 Å)
- 3PXB (2.5 Å)
- 3PXC (2.8 Å)
- 3PXD (2.8 Å)
- 3PXE (2.85 Å)
- 4IFI (2.2 Å)
- 4IGK (1.75 Å)
- 4JLU (3.5 Å)
- 4OFB (3.05 Å)
- 4U4A (3.51 Å)
- 4Y18 (3.5 Å)
- 4Y2G (2.5 Å)
- 8RS8 (1.31 Å)
- 9QPX (3.0 Å)
Solution NMR (2 structures):
- 1JM7
- 1OQA
Cryo-EM (4 structures):
- 6G2I (5.9 Å)
- 7JZV (3.9 Å)
- 7LYB (3.28 Å)
- 8GRQ (3.87 Å)
Total: 33 experimental structures
Predicted structure
AlphaFold:
- Model ID: P38398
- Confidence (global pLDDT): 41.99
- High-confidence fraction: 11% (pLDDT > 70)
Based on my search of the biobtree database, I can only find BRCA1 orthologs in mammals. Here’s what I found:
Cross-species orthologs
| Organism | Gene ID | Symbol |
|---|---|---|
| Mouse (Mus musculus) | ENSMUSG00000017146 | Brca1 |
| Rat (Rattus norvegicus) | ENSRNOG00000020701 | Brca1 |
| Zebrafish (Danio rerio) | none | none |
| Fruit fly (Drosophila melanogaster) | none | none |
| Worm (C. elegans) | WBGENE00000264 | brc-1 |
| Yeast (S. cerevisiae) | none | none |
Note: BRCA1 is a mammalian-specific gene. Drosophila and yeast lack true BRCA1 orthologs; these organisms have related DNA repair genes (e.g., spn-A, RAD51, RAD52) that serve related but distinct functions in homologous recombination. Zebrafish BRCA1 orthologs may exist but are not well-annotated in this database.
Clinical variants & AI predictions
ClinVar Summary
| Classification | Count |
|---|---|
| Pathogenic | ~500+ |
| Likely Pathogenic | ~450+ |
| Uncertain Significance | ~4,000+ |
| Conflicting Classifications | ~2,000+ |
| Likely Benign | ~200+ |
| Benign | ~100+ |
| Total | ~15,445 |
Top 30 Pathogenic/Likely Pathogenic Variants
| Variant ID | HGVS Notation | Type | Classification |
|---|---|---|---|
| 1012155 | NM_007294.4(BRCA1):c.1728del | Deletion | Pathogenic |
| 1012156 | NM_007294.4(BRCA1):c.3982del | Deletion | Pathogenic |
| 1071282 | NM_007294.4(BRCA1):c.3381T>A (p.Tyr1127Ter) | SNV | Pathogenic |
| 1049776 | NM_007294.4(BRCA1):c.1603G>T (p.Gly535Ter) | SNV | Pathogenic |
| 1050371 | NM_007294.4(BRCA1):c.709G>T (p.Glu237Ter) | SNV | Pathogenic |
| 1074684 | NM_007294.4(BRCA1):c.1009G>T (p.Glu337Ter) | SNV | Pathogenic |
| 1049514 | NM_007294.4(BRCA1):c.2827A>T (p.Lys943Ter) | SNV | Pathogenic |
| 1070907 | NM_007294.4(BRCA1):c.5202dup (p.Glu1735Ter) | Duplication | Pathogenic |
| 1027595 | NC_000017.10:g.(?41196311)(41203135_41209068)del | Deletion | Pathogenic |
| 1027624 | NC_000017.10:g.(41203135_41209068)_(41209153_41215349)del | Deletion | Pathogenic |
| 186913 | NM_007294.4(BRCA1):c.101C>T (p.Pro34Leu) | SNV | Likely Pathogenic |
| 230862 | NM_007294.4(BRCA1):c.122A>T (p.His41Leu) | SNV | Likely Pathogenic |
| 245973 | NM_007294.4(BRCA1):c.32T>G (p.Val11Gly) | SNV | Likely Pathogenic |
| 232955 | NM_007294.4(BRCA1):c.74C>T (p.Pro25Leu) | SNV | Likely Pathogenic |
| 225711 | NM_007294.4(BRCA1):c.5202T>G (p.Phe1734Leu) | SNV | Likely Pathogenic |
| 232047 | NM_007294.4(BRCA1):c.5200T>A (p.Phe1734Ile) | SNV | Likely Pathogenic |
| 252884 | NM_007294.4(BRCA1):c.5107T>G (p.Tyr1703Asp) | SNV | Likely Pathogenic |
| 232915 | NM_007294.4(BRCA1):c.5108A>G (p.Tyr1703Cys) | SNV | Likely Pathogenic |
| 254641 | NM_007294.4(BRCA1):c.5075A>C (p.Asp1692Ala) | SNV | Likely Pathogenic |
| 125791 | NM_007294.4(BRCA1):c.5164T>C (p.Ser1722Pro) | SNV | Likely Pathogenic |
| 232793 | NM_007294.4(BRCA1):c.4185G>C (p.Gln1395His) | SNV | Likely Pathogenic |
| 240819 | NM_007294.4(BRCA1):c.5242G>C (p.Gly1748Arg) | SNV | Likely Pathogenic |
| 187171 | NM_007294.4(BRCA1):c.212+1del | Deletion | Likely Pathogenic |
| 142712 | NM_007294.4(BRCA1):c.442-18_442-4del | Deletion | Likely Pathogenic |
| 1740400 | NM_007294.4(BRCA1):c.441+1G>C | SNV | Likely Pathogenic |
| 246100 | NM_007294.4(BRCA1):c.4986+4A>G | SNV | Likely Pathogenic |
| 125852 | NM_007294.4(BRCA1):c.5467+2T>G | SNV | Likely Pathogenic |
| 125776 | NM_007294.4(BRCA1):c.5152+6T>A | SNV | Likely Pathogenic |
| 1050839 | NM_007294.4(BRCA1):c.4643del | Deletion | Likely Pathogenic |
| 1065962 | NM_007294.4(BRCA1):c.5510_5511delinsCT | Indel | Likely Pathogenic |
Splice Effect Predictions (SpliceAI)
- Total variants with predictions: 3,719
- Effect types: Donor gain/loss, Acceptor gain/loss
- Score range: 0.20–1.00 (higher = stronger effect)
Top 30 High-Impact Splice Variants:
| Position | Ref/Alt | Effect | Score |
|---|---|---|---|
| 17:43047713 | C→T | Acceptor gain | 1.0000 |
| 17:43047713 | C→CT | Acceptor gain | 1.0000 |
| 17:43047714 | A→T | Acceptor gain | 1.0000 |
| 17:43047700 | CACC→C | Acceptor gain | 0.9700 |
| 17:43047702 | CC→C | Acceptor gain | 0.9700 |
| 17:43047703 | CC→C | Acceptor gain | 0.9700 |
| 17:43047704 | C→CG | Acceptor loss | 0.9100 |
| 17:43047705 | T→C | Acceptor loss | 0.9100 |
| 17:43047635 | CACCT→C | Donor loss | 0.9200 |
| 17:43047636 | ACCTT→A | Donor loss | 0.9500 |
| 17:43047637 | CCTTA→C | Donor loss | 0.9500 |
| 17:43047638 | CTTAC→C | Donor loss | 0.9500 |
| 17:43047639 | TTA→T | Donor loss | 0.9500 |
| 17:43047640 | TACCA→T | Donor loss | 0.9500 |
| 17:43047641 | ACC→A | Donor loss | 0.9500 |
| 17:43047699 | ACACC→A | Acceptor gain | 0.7600 |
| 17:43047700 | CACCC→C | Acceptor gain | 0.7600 |
| 17:43047701 | ACC→A | Acceptor gain | 0.7500 |
| 17:43047702 | CCC→C | Acceptor gain | 0.7500 |
| 17:43047704 | C→CC | Acceptor gain | 0.7600 |
| 17:43047711 | C→CT | Acceptor gain | 0.8500 |
| 17:43047711 | C→T | Acceptor gain | 0.8600 |
| 17:43047712 | C→CT | Acceptor gain | 0.8300 |
| 17:43047712 | C→T | Acceptor gain | 0.8900 |
| 17:43047643 | C→A | Donor loss | 0.8200 |
| 17:43047706 | G→C | Acceptor loss | 0.5500 |
| 17:43047657 | T→TA | Acceptor loss | 0.5900 |
| 17:43047660 | T→TA | Acceptor loss | 0.5700 |
| 17:43047656 | GTC→G | Acceptor loss | 0.4900 |
| 17:43047666 | C→CT | Acceptor loss | 0.4900 |
AlphaMissense Pathogenicity Predictions
- Total missense predictions: ~10,000+
- Likely pathogenic: ~900+ variants
Top 30 Likely Pathogenic Missense Variants (by am_pathogenicity score):
| Genomic Variant | Protein Change | am_pathogenicity | Predicted Class |
|---|---|---|---|
| 17:43045761:A:G | W1837R | 0.998 | Likely Pathogenic |
| 17:43045747:A:C | S1841R | 0.996 | Likely Pathogenic |
| 17:43045747:A:T | S1841R | 0.996 | Likely Pathogenic |
| 17:43045749:T:G | S1841R | 0.996 | Likely Pathogenic |
| 17:43045751:T:A | D1840V | 0.982 | Likely Pathogenic |
| 17:43045752:C:G | D1840H | 0.978 | Likely Pathogenic |
| 17:43045763:T:A | E1836V | 0.910 | Likely Pathogenic |
| 17:43045757:A:T | V1838E | 0.971 | Likely Pathogenic |
| 17:43045745:A:T | V1842E | 0.956 | Likely Pathogenic |
| 17:43045750:G:C | D1840E | 0.954 | Likely Pathogenic |
| 17:43045750:G:T | D1840E | 0.954 | Likely Pathogenic |
| 17:43045748:C:A | S1841I | 0.954 | Likely Pathogenic |
| 17:43045687:A:T | V1808E | 0.955 | Likely Pathogenic |
| 17:43045713:A:C | Y1853D | 0.940 | Likely Pathogenic |
| 17:43045754:A:G | L1839S | 0.941 | Likely Pathogenic |
| 17:43045766:C:G | R1835P | 0.969 | Likely Pathogenic |
| 17:43045751:T:G | D1840A | 0.966 | Likely Pathogenic |
| 17:43045743:C:T | A1843P | 0.964 | Likely Pathogenic |
| 17:43045751:T:C | D1840G | 0.958 | Likely Pathogenic |
| 17:43045742:G:T | A1843E | 0.961 | Likely Pathogenic |
| 17:43047681:A:T | V1810E | 0.848 | Likely Pathogenic |
| 17:43047684:A:C | V1809G | 0.924 | Likely Pathogenic |
| 17:43047670:C:G | A1814P | 0.870 | Likely Pathogenic |
| 17:43045709:A:G | L1854P | 0.867 | Likely Pathogenic |
| 17:43045713:A:G | Y1853H | 0.867 | Likely Pathogenic |
| 17:43045745:A:C | V1842G | 0.866 | Likely Pathogenic |
| 17:43047667:A:G | W1815R | 0.865 | Likely Pathogenic |
| 17:43047667:A:T | W1815R | 0.865 | Likely Pathogenic |
| 17:43045754:A:C | L1839W | 0.850 | Likely Pathogenic |
| 17:43045752:C:A | D1840Y | 0.948 | Likely Pathogenic |
Pathways & Gene Ontology
Reactome Pathways: 59 total
| Pathway ID | Pathway Name | Category |
|---|---|---|
| R-HSA-5693532 | DNA Double-Strand Break Repair | DNA Repair |
| R-HSA-5693538 | Homology Directed Repair | DNA Repair |
| R-HSA-5693606 | DNA Double Strand Break Response | DNA Repair |
| R-HSA-5693607 | Processing of DNA double-strand break ends | DNA Repair |
| R-HSA-5685942 | HDR through Homologous Recombination (HRR) | DNA Repair |
| R-HSA-5685938 | HDR through Single Strand Annealing (SSA) | DNA Repair |
| R-HSA-5693537 | Resolution of D-Loop Structures | DNA Repair |
| R-HSA-5693616 | Presynaptic phase of homologous DNA pairing and strand exchange | DNA Repair |
| R-HSA-5693579 | Homologous DNA Pairing and Strand Exchange | DNA Repair |
| R-HSA-5693568 | Resolution of D-loop Structures through Holliday Junction Intermediates | DNA Repair |
| R-HSA-5693565 | Recruitment and ATM-mediated phosphorylation of repair and signaling proteins at DNA double strand breaks | DNA Repair |
| R-HSA-5693571 | Nonhomologous End-Joining (NHEJ) | DNA Repair |
| R-HSA-5693554 | Resolution of D-loop Structures through Synthesis-Dependent Strand Annealing (SDSA) | DNA Repair |
| R-HSA-9663199 | Defective DNA double strand break response due to BRCA1 loss of function | Disease |
| R-HSA-9701192 | Defective homologous recombination repair (HRR) due to BRCA1 loss of function | Disease |
| R-HSA-73894 | DNA Repair | General |
| R-HSA-69473 | G2/M DNA damage checkpoint | Cell Cycle |
| R-HSA-69481 | G2/M Checkpoints | Cell Cycle |
| R-HSA-69620 | Cell Cycle Checkpoints | Cell Cycle |
| R-HSA-1640170 | Cell Cycle | General |
| R-HSA-3700989 | Transcriptional Regulation by TP53 | Transcription |
| R-HSA-6796648 | TP53 Regulates Transcription of DNA Repair Genes | Transcription |
| R-HSA-6804756 | Regulation of TP53 Activity through Phosphorylation | Transcription |
| R-HSA-5633007 | Regulation of TP53 Activity | Transcription |
| R-HSA-1500620 | Meiosis | Development |
| R-HSA-912446 | Meiotic recombination | Development |
| R-HSA-1221632 | Meiotic synapsis | Development |
| R-HSA-1266738 | Developmental Biology | Development |
| R-HSA-73857 | RNA Polymerase II Transcription | Transcription |
| R-HSA-74160 | Gene expression (Transcription) | Transcription |
| R-HSA-212436 | Generic Transcription Pathway | Transcription |
Showing 30 of 59 pathways; also includes SUMO modification, protein ubiquitination, apoptosis signaling, and metabolic pathways
MSigDB Gene Sets: 100+ total
BRCA1 membership includes DNA repair gene sets (KAUFFMANN_DNA_REPAIR_GENES), cell cycle checkpoints, meiosis pathways, apoptosis regulation, lipid metabolism, and curated BRCA1-neighborhood networks (MORF_BRCA1).
Gene Ontology: 87 total terms
Biological Process: 45 terms
| GO ID | Term | GO ID | Term |
|---|---|---|---|
| GO:0000724 | double-strand break repair via homologous recombination | GO:0045786 | negative regulation of cell cycle |
| GO:0006281 | DNA repair | GO:0045892 | negative regulation of DNA-templated transcription |
| GO:0006282 | regulation of DNA repair | GO:0045893 | positive regulation of DNA-templated transcription |
| GO:0006301 | DNA damage tolerance | GO:0045944 | positive regulation of transcription by RNA polymerase II |
| GO:0006302 | double-strand break repair | GO:0046600 | negative regulation of centriole replication |
| GO:0006310 | DNA recombination | GO:0051726 | regulation of cell cycle |
| GO:0006338 | chromatin remodeling | GO:0051865 | protein autoubiquitination |
| GO:0006357 | regulation of transcription by RNA polymerase II | GO:0060816 | random inactivation of X chromosome |
| GO:0006974 | DNA damage response | GO:0071356 | cellular response to tumor necrosis factor |
| GO:0007059 | chromosome segregation | GO:0071479 | cellular response to ionizing radiation |
| GO:0007095 | mitotic G2 DNA damage checkpoint signaling | GO:0071681 | cellular response to indole-3-methanol |
| GO:0008630 | intrinsic apoptotic signaling in response to DNA damage | GO:0085020 | protein K6-linked ubiquitination |
| GO:0010212 | response to ionizing radiation | GO:0110025 | DNA strand resection in replication fork processing |
| GO:0010575 | positive regulation of VEGF production | GO:1902042 | negative regulation of extrinsic apoptotic pathway via death receptors |
| GO:0010628 | positive regulation of gene expression | GO:2000001 | regulation of DNA damage checkpoint |
| GO:0016567 | protein ubiquitination | GO:2000378 | negative regulation of ROS metabolic process |
| GO:0030308 | negative regulation of cell growth | GO:0035825 | homologous recombination |
| GO:0033147 | negative regulation of estrogen receptor signaling | GO:0043009 | chordate embryonic development |
| GO:0044027 | negative regulation via chromosomal CpG methylation | GO:0044818 | mitotic G2/M transition checkpoint |
| GO:0045717 | negative regulation of fatty acid biosynthesis | GO:0045739 | positive regulation of DNA repair |
| GO:0045766 | positive regulation of angiogenesis |
Molecular Function: 20 terms
| GO ID | Term | GO ID | Term |
|---|---|---|---|
| GO:0000976 | transcription cis-regulatory region binding | GO:0046872 | metal ion binding |
| GO:0002039 | p53 binding | GO:0061630 | ubiquitin protein ligase activity |
| GO:0003677 | DNA binding | GO:0061649 | ubiquitin-modified histone reader activity |
| GO:0003684 | damaged DNA binding | GO:0070063 | RNA polymerase binding |
| GO:0003713 | transcription coactivator activity | GO:0140863 | histone H2AK127 ubiquitin ligase activity |
| GO:0003723 | RNA binding | GO:0140864 | histone H2AK129 ubiquitin ligase activity |
| GO:0004842 | ubiquitin-protein transferase activity | ||
| GO:0005515 | protein binding | ||
| GO:0008270 | zinc ion binding | ||
| GO:0015631 | tubulin binding | ||
| GO:0016740 | transferase activity | ||
| GO:0019899 | enzyme binding | ||
| GO:0031625 | ubiquitin protein ligase binding |
Cellular Component: 22 terms
| GO ID | Term |
|---|---|
| GO:0000151 | ubiquitin ligase complex |
| GO:0000152 | nuclear ubiquitin ligase complex |
| GO:0000793 | condensed chromosome |
| GO:0000794 | condensed nuclear chromosome |
| GO:0000800 | lateral element |
| GO:0000931 | gamma-tubulin ring complex |
| GO:0001673 | male germ cell nucleus |
| GO:0001741 | XY body |
| GO:0005634 | nucleus |
| GO:0005654 | nucleoplasm |
| GO:0005694 | chromosome |
| GO:0005737 | cytoplasm |
| GO:0005886 | plasma membrane |
| GO:0016020 | membrane |
| GO:0016604 | nuclear body |
| GO:0031436 | BRCA1-BARD1 complex |
| GO:0032991 | protein-containing complex |
| GO:0070531 | BRCA1-A complex |
| GO:0070532 | BRCA1-B complex |
| GO:0070533 | BRCA1-C complex |
| GO:1990391 | DNA repair complex |
| GO:1990904 | ribonucleoprotein complex |
Protein interactions & networks
Protein-Protein Interactions
Total Interaction Counts:
- STRING: ~6,120 interactions
- BioGRID: ~2,598 interactions
- IntAct: 342 interactions
TOP 30 Highest-Confidence STRING Interacting Proteins:
| Rank | UniProt ID | Gene Name | Protein Name |
|---|---|---|---|
| 1 | Q86YC2 | PALB2 | Partner and localizer of BRCA2 |
| 2 | P04637 | TP53 | Cellular tumor antigen p53 |
| 3 | Q13315 | ATM | Serine-protein kinase ATM |
| 4 | P51587 | BRCA2 | Breast cancer type 2 susceptibility protein |
| 5 | Q12888 | TP53BP1 | TP53-binding protein 1 |
| 6 | Q06609 | RAD51 | DNA repair protein RAD51 homolog 1 |
| 7 | Q9BXW9 | FANCD2 | Fanconi anemia group D2 protein |
| 8 | Q99708 | RBBP8 | DNA endonuclease RBBP8 |
| 9 | Q9BX63 | FANCJ | Fanconi anemia group J protein |
| 10 | Q6UWZ7 | ABRAXAS1 | BRCA1-A complex subunit Abraxas 1 |
| 11 | O96017 | CHEK2 | Serine/threonine-protein kinase Chk2 |
| 12 | Q96RL1 | UIMC1 | BRCA1-A complex subunit RAP80 |
| 13 | Q14676 | MDC1 | Mediator of DNA damage checkpoint protein 1 |
| 14 | Q9NXR7 | BABAM2 | BRISC and BRCA1-A complex member 2 |
| 15 | P46736 | BRCC36 | Lys-63-specific deubiquitinase BRCC36 |
| 16 | Q7Z569 | BRAP | BRCA1-associated protein |
| 17 | P03372 | ESR1 | Estrogen receptor |
| 18 | P01106 | MYC | Myc proto-oncogene protein |
| 19 | Q9GZX5 | ZNF350 | Zinc finger protein 350 |
| 20 | Q99728 | BARD1 | BRCA1-associated RING domain protein 1 |
| 21 | Q9NWV8 | BABAM1 | BRISC and BRCA1-A complex member 1 |
| 22 | Q92560 | BAP1 | Ubiquitin carboxyl-terminal hydrolase BAP1 |
| 23 | P16104 | H2AFX | Histone H2AX |
| 24 | P52701 | MSH6 | DNA mismatch repair protein Msh6 |
| 25 | O15360 | FANCA | Fanconi anemia group A protein |
| 26 | P49959 | MRE11 | Double-strand break repair protein MRE11 |
| 27 | Q08211 | DHX29 | ATP-dependent RNA helicase A |
| 28 | O14757 | CHEK1 | Serine/threonine-protein kinase Chk1 |
| 29 | Q7Z333 | SETX | Helicase senataxin |
Key Interaction Networks:
- BRCA1-A Complex: ABRAXAS1, UIMC1, BABAM1, BABAM2, BRCC36, BAP1
- DNA Damage Response: TP53, ATM, CHEK1, CHEK2, MDC1, TP53BP1, H2AFX
- Homologous Recombination: BRCA2, RAD51, FANCA, FANCD2, FANCJ, MRE11, RBBP8
- Transcription/Regulation: ESR1, MYC, BARD1, BRAP
Protein Similarity
Structural/Embedding Similarity (ESM2):
- Total similar proteins: 52
- Top human proteins by ESM2 similarity:
- BRCA2 (P51587) — Homologous DNA repair protein
- ZFP804B (A4D1E1) — Zinc finger protein
- ZFYVE9 (O95405) — Zinc finger FYVE domain protein
Note: Most ESM2 similarity matches are orthologs from other mammalian species
Sequence Homology (DIAMOND Similarity):
- Total homologous proteins: 96
- Includes orthologs across vertebrate species
- Top category: DNA repair and recombination proteins (BRCA2 orthologs, RAD51 paralogs)
- Secondary category: RING finger and zinc finger domain proteins
Transcription factor regulatory data
BRCA1 functional classification: BRCA1 is not a classical transcription factor with DNA binding motifs (no JASPAR motifs found). It is a RING-type E3 ubiquitin ligase that functions in DNA repair and transcriptional regulation through protein-protein interactions with other factors.
Downstream targets regulated by BRCA1
Total targets: 61 (from CollecTRI)
BRCA1 shows transcriptional regulatory activity targeting genes involved in DNA repair, cell cycle control, apoptosis, and stress response:
| Target | Regulation | Evidence |
|---|---|---|
| CDKN1A | Activation | Established |
| CDKN1B | Activation | Established |
| DDB2 | Activation | Established |
| DDIT3 | Activation | Established |
| EP300 | Activation | Established |
| ESR1 | Activation | Established |
| FST | Activation | Established |
| GADD45A | Activation | Established |
| IFNA1 | Activation | Established |
| IRF7 | Activation | Established |
| IRF9 | Activation | Established |
| MAD2L1 | Activation | Established |
| MDM2 | Activation | Established |
| NOS3 | Activation | Established |
| NTHL1 | Activation | Established |
| RNASEL | Activation | Established |
| S100A2 | Activation | Established |
| SIRT1 | Activation | Established |
| STAT1 | Activation | Established |
| STAT2 | Activation | Established |
| VEGFA | Activation | Established |
| ATM | Activation | Predicted |
| ASPM | Activation | Predicted |
| CYP19A1 | Activation | Predicted (High confidence) |
| CYP1A1 | Unknown | Predicted (High confidence) |
| CYP1B1 | Unknown | Predicted (High confidence) |
| CXCL1 | Repression | Established |
| E2F6 | Repression | Established |
| EGFR | Repression | Established |
| FOXC1 | Repression | Established |
Additional 31 targets include: FOXC2, HMGA2, HNRNPA2B1, HSPA5, IGF1, KHSRP, TFF1, CDH3, CTSD, BARD1 (repression); EGR1, HIF1A, IGF1R, JAK1, JAK2, MDC1, MYC, TP63, XPC, CCND1, CCNB1, CASR, BRCA2, BRCA1 (self-repression, High confidence), BACH1 (unknown regulation).
Upstream regulators of BRCA1
Total upstream TFs: 79
Key upstream regulators with regulation types:
| TF | Regulation | Confidence |
|---|---|---|
| TP53 | Repression | High |
| E2F1 | Repression | High |
| ETS2 | Repression | High |
| ID1 | Repression | High |
| ID4 | Repression | High |
| RBL1 | Repression | High |
| RBL2 | Repression | High |
| HMGA1 | Repression | High |
| POU4F2 | Repression | High |
| DLX4 | Repression | High |
| FOXP3 | Repression | High |
| CTBP2 | Repression | High |
| MYC | Activation | High |
| JUN | Activation | High |
| GABPA | Activation | High |
| E2F4 | Activation | High |
| NFE2L2 | Activation | High |
| NR3C1 | Activation | High |
| PPARG | Activation | High |
| POU4F1 | Activation | High |
| POU5F1 | Activation | High |
| LYL1 | Activation | High |
| CREB1 | Unknown | High |
| CTCF | Unknown | High |
| E2F2 | Unknown | High |
| E2F3 | Unknown | High |
| E2F5 | Unknown | High |
| E2F6 | Unknown | High |
| EGR1 | Unknown | High |
| ESR1 | Unknown | High |
Additional 49 upstream regulators include: AP1, EP300, FOSL2, FOS, ARNT, ASPM, TP53BP1, VDR, HR, DNMT3A, CHD8 and others with varying confidence levels.
Drug & pharmacology data
Note: BRCA1 is not a direct small-molecule drug target. Instead, PARP inhibitors are used to treat BRCA1-mutant cancers via synthetic lethality—BRCA1-deficient tumors depend on PARP-mediated DNA repair.
Targeting molecules: PARP inhibitors in BRCA1-mutant disease
Total compounds in ChEMBL targeting PARP pathway: ~310 molecules across all development phases
TOP 3 approved PARP inhibitors (Phase 3–4):
| Molecule ID | Name | Targets | Highest Phase | Brand Name |
|---|---|---|---|---|
| CHEMBL521686 | Olaparib | PARP1/2/3, others | 4 (Approved) | Lynparza |
| CHEMBL1173055 | Rucaparib | PARP1/2/3, others | 4 (Approved) | Rubraca |
| CHEMBL506871 | Veliparib | PARP1/2 | 3 | ABT-888 |
Additional clinical-stage compounds: 100+ Phase 0–2 molecules; most are research compounds with limited development.
Clinical trials: BRCA1-related PARP inhibitor trials
Olaparib alone: 382+ clinical trials identified
TOP clinical trials by disease/status:
| Trial ID | Title | Phase | Status | Disease |
|---|---|---|---|---|
| NCT02000622 | Olaparib vs chemotherapy in metastatic breast cancer (gBRCA+) | Phase 3 | COMPLETED | Breast cancer |
| NCT02032823 | Olaparib adjuvant in gBRCA+ high-risk HER2– breast cancer | Phase 3 | ACTIVE | Breast cancer |
| NCT02282020 | Olaparib in relapsed gBRCA+ ovarian cancer (≥2 prior treatments) | Phase 3 | COMPLETED | Ovarian cancer |
| NCT02184195 | Olaparib in gBRCA+ pancreatic cancer (post-platinum) | Phase 3 | COMPLETED | Pancreatic cancer |
| NCT02476968 | Olaparib maintenance in ovarian cancer | Phase 4 | COMPLETED | Ovarian cancer |
| NCT02987543 | Olaparib vs enzalutamide/abiraterone in mCRPC (PROfound) | Phase 3 | COMPLETED | Prostate cancer |
| NCT05457257 | Olaparib in mCRPC with BRCA1/2 mutations (China cohort) | Phase 4 | COMPLETED | Prostate cancer |
Pharmacogenomics and testing requirements
BRCA1/BRCA2 association with olaparib:
- PharmGKB annotation: BRCA1 and BRCA2 listed as “associated” genes with olaparib
- FDA/EMA label level: Testing Required (prospective testing mandated before treatment)
- Label sources: FDA, EMA, HCSC all require BRCA1/BRCA2 testing
Drug-gene interaction mechanism:
- BRCA1 mutations confer PARP inhibitor sensitivity via homologous recombination deficiency (HRD)
- Tumors with BRCA1 loss cannot repair double-strand breaks via HR and become dependent on PARP-mediated single-strand break repair
- PARP inhibition in BRCA1-deficient cells causes synthetic lethality
Dosing guidelines:
- No dose adjustments based on BRCA1/BRCA2 status; rather, mutation status determines eligibility (BRCA1/2 mutations = enhanced response)
- Standard dosing: Olaparib 300 mg PO BID (for most indications)
- Dosing may be reduced for tolerability independent of BRCA1 status
Clinical utility:
- BRCA1 mutation testing is a prerequisite for PARP inhibitor use in breast, ovarian, pancreatic, and prostate cancer
- HRD-positive tumors (including BRCA1/2-mutant) show durable response to maintenance PARP inhibition
Expression profiles
Tissue and developmental expression (Bgee)
BRCA1 shows ubiquitous expression across tissues with high expression breadth (208 present calls across 266 conditions). The gene exhibits strong expression in proliferative tissues and developmental contexts.
| Rank | Tissue/Cell Type | Expression Score | Status |
|---|---|---|---|
| 1 | Ventricular zone | 90.68 | Present |
| 2 | Male germ line stem cell in testis | 89.54 | Present |
| 3 | Primordial germ cell in gonad | 86.44 | Present |
| 4 | Ganglionic eminence | 86.30 | Present |
| 5 | Embryo | 85.26 | Present |
| 6 | Secondary oocyte | 84.10 | Present |
| 7 | Bone marrow cell | 82.00 | Present |
| 8 | Oocyte | 81.87 | Present |
| 9 | Endometrium epithelium | 81.67 | Present |
| 10 | Sural nerve | 81.55 | Present |
| 11 | Trabecular bone tissue | 80.40 | Present |
| 12 | Stromal cell of endometrium | 79.88 | Present |
| 13 | Colonic epithelium | 79.56 | Present |
| 14 | Bone marrow | 79.55 | Present |
| 15 | Testis | 78.58 | Present |
| 16 | Hair follicle | 78.46 | Absent |
| 17 | Right testis | 78.11 | Present |
| 18 | Rectum | 78.05 | Present |
| 19 | Left testis | 77.69 | Present |
| 20 | Right lobe of thyroid gland | 77.35 | Present |
| 21 | Vermiform appendix | 77.10 | Present |
| 22 | Tonsil | 76.23 | Present |
| 23 | Left lobe of thyroid gland | 75.58 | Present |
| 24 | Hindlimb stylopod muscle | 74.97 | Present |
| 25 | Thyroid gland | 74.62 | Present |
| 26 | Mucosa of transverse colon | 74.61 | Present |
| 27 | Adrenal tissue | 74.41 | Present |
| 28 | Choroid plexus epithelium | 74.34 | Present |
| 29 | Calcaneal tendon | 73.96 | Present |
| 30 | Lymph node | 73.91 | Present |
Key patterns:
- Germ cell enrichment: Strongest expression in male and female germ cells, germ line stem cells, and oocytes (scores 81–90), reflecting BRCA1’s role in meiosis and genomic stability
- Developmental tissues: High expression in embryonic tissues and neural structures (ventricular zone, ganglionic eminence)
- Proliferative tissues: Elevated expression in bone marrow, gut epithelium, endometrium, and thyroid—tissues with high cell turnover
- Broad distribution: Average expression score of 68.16 indicates consistent presence across tissues
Single-cell expression
Available dataset:
- E-GEOD-99795 (Single Cell Expression Atlas): RNA-seq of LNCaP prostate carcinoma epithelial cells with/without androgen exposure (144 cells)—demonstrates BRCA1 expression in prostate epithelial malignancy
BRCA1 expression data from larger single-cell atlases (Tabula Sapiens, Human Cell Atlas) not currently detailed in biobtree, but the ubiquitous tissue expression pattern suggests broad cell-type distribution with enrichment in cells with active DNA repair demands.
Disease associations
Mendelian / Monogenic Disease
BRCA1 mutations cause the following monogenic diseases:
| Disease | Disease ID | Inheritance | Evidence Level |
|---|---|---|---|
| Breast-ovarian cancer, familial, susceptibility to, 1 | OMIM:604370 | Autosomal dominant | Definitive/Strong |
| Fanconi anemia, complementation group S | OMIM:617883 | Autosomal recessive | Moderate/Strong |
| Pancreatic cancer, susceptibility to, 4 | OMIM:614320 | Autosomal dominant | Moderate |
| Hereditary breast and/or ovarian cancer syndrome | ORPHANET:145 | Autosomal dominant | Supportive |
| Hereditary breast cancer | ORPHANET:227535 | Autosomal dominant | Supportive |
| Familial pancreatic carcinoma | ORPHANET:1333 | Autosomal dominant | Supportive |
| Fanconi anemia | ORPHANET:84 | Autosomal recessive | Supportive |
| Familial prostate cancer | ORPHANET:1331 | Autosomal dominant | Supportive |
| Lynch syndrome | ORPHANET:144 | Autosomal dominant | Supportive |
| Hereditary mixed polyposis syndrome | ORPHANET:157794 | Autosomal dominant | Supportive |
Mondo Disease IDs (43 total): MONDO:0003582 (hereditary breast ovarian cancer syndrome), MONDO:0011450 (breast-ovarian cancer, familial, susceptibility to, 1), MONDO:0007254 (breast cancer), MONDO:0013685 (pancreatic cancer, susceptibility to, 4), MONDO:0054748 (Fanconi anemia, complementation group S), MONDO:0005140 (ovarian carcinoma), MONDO:0004989 (breast carcinoma), MONDO:0009831 (malignant pancreatic neoplasm), MONDO:0005575 (colorectal cancer), MONDO:0008315 (prostate cancer), MONDO:0008903 (lung cancer), MONDO:0001056 (gastric cancer), MONDO:0002447 (endometrial carcinoma), MONDO:0006003 (uterine corpus cancer), MONDO:0700268 (BRCA1-related cancer predisposition), MONDO:0700275 (prostate cancer, hereditary), MONDO:0015278 (familial pancreatic carcinoma), MONDO:0016419 (hereditary breast carcinoma), MONDO:0021068 (ovarian neoplasm), MONDO:0021100 (breast neoplasm), MONDO:0015356 (hereditary neoplastic syndrome), MONDO:0002032 (colon carcinoma), MONDO:0001187 (urinary bladder cancer), MONDO:0016691 (pilocytic astrocytoma), MONDO:0042486 (polyposis syndrome, hereditary mixed, 1), MONDO:0020341 (periventricular nodular heterotopia), MONDO:0008292 (punctate palmoplantar keratoderma type 2), MONDO:0005192 (exocrine pancreatic carcinoma), MONDO:0009215 (Fanconi anemia complementation group A), MONDO:0012933 (breast-ovarian cancer, familial, susceptibility to, 2), MONDO:0012132 (colorectal cancer, susceptibility to, 1), MONDO:0003002 (dysgerminoma), MONDO:0004953 (invasive ductal breast carcinoma), MONDO:0003874 (ovarian serous surface papillary adenocarcinoma), MONDO:0005558 (ovarian disorder), MONDO:0007356 (Lynch syndrome 1), MONDO:0005212 (rhabdomyosarcoma), MONDO:0005590 (breast ductal adenocarcinoma), MONDO:0008903 (lung cancer), MONDO:0002087 (peritoneum cancer), MONDO:0021637 (low grade glioma), MONDO:0858940 (infant-type hemispheric glioma), MONDO:0007243 (Burkitt lymphoma)
Phenotype Associations
Top 30 HPO (Human Phenotype Ontology) terms associated with BRCA1:
- HP:0000006 – Autosomal dominant inheritance
- HP:0000007 – Autosomal recessive inheritance
- HP:0003002 – Breast carcinoma
- HP:0025318 – Ovarian carcinoma
- HP:0012125 – Prostate cancer
- HP:0003003 – Colon cancer
- HP:0002894 – Neoplasm of the pancreas
- HP:0006725 – Pancreatic adenocarcinoma
- HP:0100615 – Ovarian neoplasm
- HP:0030406 – Primary peritoneal carcinoma
- HP:0002861 – Melanoma
- HP:0100574 – Biliary tract neoplasm
- HP:0002896 – Neoplasm of the liver
- HP:0008903 – Lung cancer
- HP:0001249 – Intellectual disability
- HP:0002664 – Neoplasm
- HP:0040012 – Chromosome breakage
- HP:0003220 – Abnormality of chromosome stability
- HP:0001249 – Intellectual disability
- HP:0001263 – Global developmental delay
- HP:0002863 – Myelodysplasia
- HP:0001871 – Abnormality of blood and blood-forming tissues
- HP:0001873 – Thrombocytopenia
- HP:0001903 – Anemia
- HP:0002716 – Lymphadenopathy
- HP:0001392 – Abnormality of the liver
- HP:0002910 – Elevated circulating hepatic transaminase concentration
- HP:0001738 – Exocrine pancreatic insufficiency
- HP:0001426 – Non-Mendelian inheritance
- HP:0001442 – Typified by somatic mosaicism
Complex Disease / GWAS Associations
BRCA1 is associated with 7 GWAS studies identifying the following traits and disease associations:
| Trait/Disease | Gene | Chromosome | p-value | Study ID |
|---|---|---|---|---|
| Menopause (age at onset) | BRCA1 | 17 | 8.0 × 10⁻¹¹ | GCST005312_44 |
| Menopause (age at onset) | NBR2, BRCA1 | 17 | 1.0 × 10⁻⁸ | GCST005863_3 |
| Ovarian cancer (MTAG) | BRCA1 | 17 | 5.0 × 10⁻⁸ | GCST009829_3 |
| Ovarian cancer | BRCA1 | 17 | 3.0 × 10⁻⁸ | GCST009830_31 |
| Monocyte percentage of white cells | BRCA1 | 17 | 1.0 × 10⁻¹⁰ | GCST90002394_251 |
| Aspartate aminotransferase levels | BRCA1 | 17 | 1.0 × 10⁻¹² | GCST90011899_184 |
| Gynecologic disease (multivariate analysis) | – | – | 1.0 × 10⁻⁸ | GCST009823_7 |