BRCA1

gene

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Also known as RNF53BRCC1PPP1R53FANCS

Summary

BRCA1 (BRCA1 DNA repair associated, HGNC:1100) is a protein-coding gene on chromosome 17q21.31, encoding Breast cancer type 1 susceptibility protein (P38398). 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. In precision oncology, BRCA1 Mutation confers sensitivity to Rucaparib in Ovarian Cancer (CIViC Level A); 42 further curated variant–drug associations are listed below. It is a selective cancer dependency (DepMap: 44.8% of cell lines) and haploinsufficient (ClinGen: sufficient evidence).

This gene encodes a 190 kD nuclear phosphoprotein that plays a role in maintaining genomic stability, and it also acts as a tumor suppressor. The BRCA1 gene contains 22 exons spanning about 110 kb of DNA. The encoded protein combines with other tumor suppressors, DNA damage sensors, and signal transducers to form a large multi-subunit protein complex known as the BRCA1-associated genome surveillance complex (BASC). This gene product associates with RNA polymerase II, and through the C-terminal domain, also interacts with histone deacetylase complexes. This protein thus plays a role in transcription, DNA repair of double-stranded breaks, and recombination. Mutations in this gene are responsible for approximately 40% of inherited breast cancers and more than 80% of inherited breast and ovarian cancers. Alternative splicing plays a role in modulating the subcellular localization and physiological function of this gene. Many alternatively spliced transcript variants, some of which are disease-associated mutations, have been described for this gene, but the full-length natures of only some of these variants has been described. A related pseudogene, which is also located on chromosome 17, has been identified.

Source: NCBI Gene 672 — RefSeq curated summary.

At a glance

Gene–disease (curated): BRCA1-related cancer predisposition (Definitive, ClinGen) — +5 more curated relationships
GWAS associations: 7
Clinical variants (ClinVar): 15,323 total — 3991 pathogenic, 326 likely-pathogenic
Phenotypes (HPO): 166
Druggable target: yes — 12 molecules with ChEMBL bioactivity
Precision-oncology evidence (CIViC): 43 curated variant–drug associations
Cancer driver (intOGen): loss-of-function (tumor-suppressor-like) across 4 cancer types
Cancer dependency (DepMap): dependent in 44.8% of screened cell lines
Dosage sensitivity (ClinGen): haploinsufficiency sufficient evidence, triplosensitivity no evidence
Transcription factor: yes — 61 downstream targets (CollecTRI)
MANE Select transcript: NM_007294

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:1100
Approved symbol	BRCA1
Name	BRCA1 DNA repair associated
Location	17q21.31
Locus type	gene with protein product
Status	Approved
Aliases	RNF53, BRCC1, PPP1R53, FANCS
Ensembl gene	ENSG00000012048
Ensembl biotype	protein_coding
OMIM	113705
Entrez	672

Gene structure

Transcript identifiers

Ensembl transcripts: 47 — 33 protein_coding, 6 retained_intron, 5 nonsense_mediated_decay, 3 protein_coding_CDS_not_defined

ENST00000352993, ENST00000354071, ENST00000357654, ENST00000461221, ENST00000461574, ENST00000461798, ENST00000468300, ENST00000470026, ENST00000471181, ENST00000472490, ENST00000473961, ENST00000476777, ENST00000477152, ENST00000478531, ENST00000484087, ENST00000489037, ENST00000491747, ENST00000492859, ENST00000493795, ENST00000493919, ENST00000494123, ENST00000497488, ENST00000586385, ENST00000591534, ENST00000591849, ENST00000618469, ENST00000621897, ENST00000634433, ENST00000642945, ENST00000644379, ENST00000644555, ENST00000652672, ENST00000700081, ENST00000700082, ENST00000700083, ENST00000700182, ENST00000700183, ENST00000700184, ENST00000700185, ENST00000700186, ENST00000713676, ENST00000899954, ENST00000921914, ENST00000921915, ENST00000921916, ENST00000945268, ENST00000945269

RefSeq mRNA: 368 — MANE Select: NM_007294 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, NM_001407698, NM_001407724, NM_001407725, NM_001407726, NM_001407727, NM_001407728, NM_001407729, NM_001407730, NM_001407731, NM_001407732, NM_001407733, NM_001407734, NM_001407735, NM_001407736, NM_001407737, NM_001407738, NM_001407739, NM_001407740, NM_001407741, NM_001407742, NM_001407743, NM_001407744, NM_001407745, NM_001407746, NM_001407747, NM_001407748, NM_001407749, NM_001407750, NM_001407751, NM_001407752, NM_001407838, NM_001407839, NM_001407841, NM_001407842, NM_001407843, NM_001407844, NM_001407845, NM_001407846, NM_001407847, NM_001407848, NM_001407849, NM_001407850, NM_001407851, NM_001407852, NM_001407853, NM_001407854, NM_001407858, NM_001407859, NM_001407860, NM_001407861, NM_001407862, NM_001407863, NM_001407874, NM_001407875, NM_001407879, NM_001407881, NM_001407882, NM_001407884, NM_001407885, NM_001407886, NM_001407887, NM_001407889, NM_001407894, NM_001407895, NM_001407896, NM_001407897, NM_001407898, NM_001407899, NM_001407900, NM_001407902, NM_001407904, NM_001407906, NM_001407907, NM_001407908, NM_001407909, NM_001407910, NM_001407915, NM_001407916, NM_001407917, NM_001407918, NM_001407919, NM_001407920, NM_001407921, NM_001407922, NM_001407923, NM_001407924, NM_001407925, NM_001407926, NM_001407927, NM_001407928, NM_001407929, NM_001407930, NM_001407931, NM_001407932, NM_001407933, NM_001407934, NM_001407935, NM_001407936, NM_001407937, NM_001407938, NM_001407939, NM_001407940, NM_001407941, NM_001407942, NM_001407943, NM_001407944, NM_001407945, NM_001407946, NM_001407947, NM_001407948, NM_001407949, NM_001407950, NM_001407951, NM_001407952, NM_001407953, NM_001407954, NM_001407955, NM_001407956, NM_001407957, NM_001407958, NM_001407959, NM_001407960, NM_001407962, NM_001407963, NM_001407964, NM_001407965, NM_001407966, NM_001407967, NM_001407968, NM_001407969, NM_001407970, NM_001407971, NM_001407972, NM_001407973, NM_001407974, NM_001407975, NM_001407976, NM_001407977, NM_001407978, NM_001407979, NM_001407980, NM_001407981, NM_001407982, NM_001407983, NM_001407984, NM_001407985, NM_001407986, NM_001407990, NM_001407991, NM_001407992, NM_001407993, NM_001408392, NM_001408396, NM_001408397, NM_001408398, NM_001408399, NM_001408400, NM_001408401, NM_001408402, NM_001408403, NM_001408404, NM_001408406, NM_001408407, NM_001408408, NM_001408409, NM_001408410, NM_001408411, NM_001408412, NM_001408413, NM_001408414, NM_001408415, NM_001408416, NM_001408418, NM_001408419, NM_001408420, NM_001408421, NM_001408422, NM_001408423, NM_001408424, NM_001408425, NM_001408426, NM_001408427, NM_001408428, NM_001408429, NM_001408430, NM_001408431, NM_001408432, NM_001408433, NM_001408434, NM_001408435, NM_001408436, NM_001408437, NM_001408438, NM_001408439, NM_001408440, NM_001408441, NM_001408442, NM_001408443, NM_001408444, NM_001408445, NM_001408446, NM_001408447, NM_001408448, NM_001408450, NM_001408451, NM_001408452, NM_001408453, NM_001408454, NM_001408455, NM_001408456, NM_001408457, NM_001408458, NM_001408459, NM_001408460, NM_001408461, NM_001408462, NM_001408463, NM_001408464, NM_001408465, NM_001408466, NM_001408467, NM_001408468, NM_001408469, NM_001408470, NM_001408472, NM_001408473, NM_001408474, NM_001408475, NM_001408476, NM_001408478, NM_001408479, NM_001408480, NM_001408481, NM_001408482, NM_001408483, NM_001408484, NM_001408485, NM_001408489, NM_001408490, NM_001408491, NM_001408492, NM_001408493, NM_001408494, NM_001408495, NM_001408496, NM_001408497, NM_001408498, NM_001408499, NM_001408500, NM_001408501, NM_001408502, NM_001408503, NM_001408504, NM_001408505, NM_001408506, NM_001408507, NM_001408508, NM_001408509, NM_001408510, NM_001408511, NM_001408512, NM_001408513, NM_001408514, NM_007294, NM_007297, NM_007298, NM_007299, NM_007300

CCDS: CCDS11453, CCDS11454, CCDS11455, CCDS11456, CCDS11459

Canonical transcript exons

ENST00000357654 — 23 exons

Exon	Start	End
ENSE00001852567	43125271	43125364
ENSE00001917948	43104122	43104261
ENSE00003510592	43115726	43115779
ENSE00003531836	43104868	43104956
ENSE00003541068	43106456	43106533
ENSE00003559512	43124017	43124115
ENSE00004011550	43097244	43097289
ENSE00004011551	43057052	43057135
ENSE00004011552	43047643	43047703
ENSE00004011553	43051063	43051117
ENSE00004011554	43070928	43071238
ENSE00004011556	43067608	43067695
ENSE00004011558	43090944	43091032
ENSE00004011559	43095846	43095922
ENSE00004011560	43082404	43082575
ENSE00004011561	43076488	43076614
ENSE00004011562	43074331	43074521
ENSE00004011563	43099775	43099880
ENSE00004011564	43044295	43045802
ENSE00004011565	43063874	43063951
ENSE00004011566	43091435	43094860
ENSE00004011567	43063333	43063373
ENSE00004011568	43049121	43049194

Expression profiles

Bgee: expression breadth ubiquitous, 208 present calls, max score 90.68.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 9.2565 / max 92.7145, expressed in 1744 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
166216	5.9038	1156
166220	2.2707	1310
166217	0.6502	296
166215	0.4127	249
166212	0.0191	7

Top tissues by expression

266 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
ventricular zone	UBERON:0003053	90.68	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	89.54	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	86.44	gold quality
ganglionic eminence	UBERON:0004023	86.30	gold quality
embryo	UBERON:0000922	85.26	gold quality
secondary oocyte	CL:0000655	84.10	gold quality
bone marrow cell	CL:0002092	82.00	gold quality
oocyte	CL:0000023	81.87	gold quality
endometrium epithelium	UBERON:0004811	81.67	gold quality
sural nerve	UBERON:0015488	81.55	gold quality
trabecular bone tissue	UBERON:0002483	80.40	gold quality
stromal cell of endometrium	CL:0002255	79.88	gold quality
colonic epithelium	UBERON:0000397	79.56	gold quality
bone marrow	UBERON:0002371	79.55	gold quality
testis	UBERON:0000473	78.58	gold quality
hair follicle	UBERON:0002073	78.46	gold quality
right testis	UBERON:0004534	78.11	gold quality
rectum	UBERON:0001052	78.05	gold quality
left testis	UBERON:0004533	77.69	gold quality
right lobe of thyroid gland	UBERON:0001119	77.35	gold quality
vermiform appendix	UBERON:0001154	77.10	gold quality
tonsil	UBERON:0002372	76.23	gold quality
left lobe of thyroid gland	UBERON:0001120	75.58	gold quality
hindlimb stylopod muscle	UBERON:0004252	74.97	gold quality
thyroid gland	UBERON:0002046	74.62	gold quality
mucosa of transverse colon	UBERON:0004991	74.61	gold quality
adrenal tissue	UBERON:0018303	74.41	gold quality
choroid plexus epithelium	UBERON:0003911	74.34	silver quality
calcaneal tendon	UBERON:0003701	73.96	gold quality
lymph node	UBERON:0000029	73.91	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-MTAB-6075	yes	440.30
E-GEOD-99795	yes	125.13
E-ANND-3	yes	6.90

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

61 targets.

Target	Regulation
AREG	Repression
ASPM	Activation
ATM	Activation
BACH1	Unknown
BARD1	Repression
BRCA1	Repression
BRCA2	Unknown
CASR	Unknown
CCNB1	Unknown
CCND1	Unknown
CDH3	Repression
CDKN1A	Activation
CDKN1B	Activation
CTSD	Repression
CXCL1	Repression
CYP19A1	Activation
CYP1A1	Unknown
CYP1B1	Unknown
DDB2	Activation
DDIT3	Activation
E2F6	Repression
EGFR	Repression
EGR1	Unknown
EP300	Activation
ESR1	Activation
FOS	Unknown
FOXC1	Repression
FOXC2	Repression
FST	Activation
GADD45A	Activation

Upstream regulators (CollecTRI, top): AHR, AP1, APEX1, ARNT, ASPM, BHLHE41, BRCA1, CHD8, CREB1, CREBBP, CTBP1, CTBP2, CTCF, CTCFL, CTNNBL1, DLX4, DNMT1, DNMT3A, DNMT3B, E2F1, E2F2, E2F3, E2F4, E2F5, E2F6, EGR1, EP300, ESR1, ETS2, EZH2, FOS, FOSL2, FOXA1, FOXC1, FOXP3, GABPA, HIF1A, HMGA1, HOXA9, HR

miRNA regulators (miRDB)

43 targeting BRCA1, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-493-5P	99.96	72.47	2382
HSA-MIR-1250-3P	99.96	70.04	4038
HSA-MIR-545-3P	99.95	70.74	2783
HSA-LET-7C-3P	99.95	73.42	2862
HSA-MIR-6499-3P	99.90	66.38	1212
HSA-MIR-5010-3P	99.83	70.60	2357
HSA-MIR-6875-3P	99.82	70.26	2983
HSA-MIR-944	99.82	70.85	3042
HSA-MIR-132-3P	99.73	70.56	1424
HSA-MIR-212-3P	99.73	70.65	1424
HSA-MIR-1303	99.65	69.77	1662
HSA-MIR-2113	99.58	71.22	1521
HSA-MIR-4441	99.49	66.56	3216
HSA-MIR-3915	99.45	68.49	1905
HSA-MIR-6839-3P	99.39	68.86	1301
HSA-MIR-4506	99.34	67.47	526
HSA-MIR-7158-5P	99.25	67.95	796
HSA-MIR-4291	99.20	68.88	2969
HSA-MIR-6071	99.16	67.77	1780
HSA-MIR-6749-3P	99.00	65.73	1443
HSA-MIR-224-3P	98.91	68.42	1815
HSA-MIR-522-3P	98.91	68.56	1817
HSA-MIR-760	98.81	66.65	1392
HSA-MIR-4656	98.79	66.22	1306
HSA-MIR-629-5P	98.78	68.72	1032
HSA-MIR-4742-3P	98.73	69.82	1803
HSA-MIR-6868-3P	98.63	69.64	2259
HSA-MIR-1246	98.54	66.21	959
HSA-MIR-6516-5P	98.42	70.19	1551

Functional genomics

ClinGen dosage: haploinsufficiency 3 (sufficient evidence), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map DepMap (CRISPR cell-line fitness): dependent in 44.8% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 40)

germline mutation analysis by RNA-based sequencing (PMID:11462239)
founder mutation in a highly homogeneous population from southern Italy (PMID:11462242)
BRCA1 protein can be evaluated by two-dimensional gene scanning and by single nucleotide polymorphism techniques. (PMID:11708324)
In BRCA1, two novel frame shift mutations were identified as 3761-3762delGA and 2616-2617ins10. (PMID:11748848)
These findings reveal a novel complex between BRCA1, LMO4, and CtIP and indicate a role for LMO4 as a repressor of BRCA1 activity in breast tissue. (PMID:11751867)
BRCA1 can up-regulate its targeted genes through protein-protein interactions and provide a novel mechanism by which BRCA1 participates in transcriptional regulation. (PMID:11777930)
Activation of the aromatic hydrocarbon receptor pathway is not sufficient for transcriptional repression of BRCA-1: requirements for metabolism of benzo[a]pyrene to 7r,8t-dihydroxy-9t,10-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene. (PMID:11782367)
p300 Modulates the BRCA1 inhibition of estrogen receptor activity. (PMID:11782371)
BRCA1 and BRCA2 mutations in Russian familial breast cancer (PMID:11793480)
Germline mutation in BRCA1 associated with hypersensitivity to radiation (PMID:11807777)
role in regulating G2M checkpoint by activating Chk1 kinase upon DNA damage (PMID:11836499)
A low frequency of recurrent BRCA1 mutations has been found in breast and ovarian cancers in Spain. (PMID:11857748)
A founder mutation of BRCA1 identified in the Chinese population is a recurrent BRCA1 germline mutation in ovarian cancer. (PMID:11857749)
plays similar role in both male and female breast carcinoma; loss of this protein associated with poor prognosis (PMID:11859870)
Structural determinants of BRCA1 translational regulation (PMID:11877386)
Distinct BRCA1 rearrangements involving the BRCA1 pseudogene suggest the existence of a recombination hot spot (PMID:11880951)
mutagenic sensitivity in blood of women carrying brca1 mutation (PMID:11890937)
complex with Nmi and c-Myc inhibits c-Myc-induced human telomerase reverse transcriptase gene promoter activity in breast cancer (PMID:11916966)
BARD1 induces BRCA1 intranuclear foci formation by increasing RING-dependent BRCA1 nuclear import and inhibiting BRCA1 nuclear export (PMID:11925436)
Autoubiquitination of the BRCA1*BARD1 RING ubiquitin ligase. (PMID:11927591)
Germline BRCA1 promoter deletions in UK and Australian familial breast cancer patients: Identification of a novel deletion consistent with BRCA1:psiBRCA1 recombination. (PMID:11933198)
first evidence of a BRCA1 mutation specific to Native North Americans. (PMID:11933205)
germline mutations in breast and/or ovarian carcinoma patients (PMID:11956590)
Expression of BRCA1 and BRCA2 in different tumor cell lines with various growth status (PMID:11983207)
a component of the IFN-gamma-regulated signaling pathway and may play a role in the regulation of IFN-gamma-mediated apoptosis. (PMID:12011077)
results suggest the presence of one or more genes on chromosome 5q33-34 that modify breast cancer risk in BRCA1 mutation carriers (PMID:12019214)
Cells from carriers of mutations in one allele of the BRCA1 or BRCA2 genes have no gross defects in their ability to rejoin radiation-induced DNA breaks. (PMID:12020440)
Following exposure to ionizing radiation (IR), the BRCA1-c-Abl complex is disrupted in an ATM-dependent manner, which correlates temporally with ATM-dependent phosphorylation of BRCA1 and ATM-dependent enhancement of the tyrosine kinase activity of c-Abl (PMID:12024016)
BRCA1 selectively coactivates the p53 transcription factor towards genes that direct DNA repair and cell cycle arrest but not towards those that direct apoptosis (PMID:12024039)
Three additional mutations are reported. (PMID:12030901)
transcriptionally regulates genes involved in breast tumorigenesis (PMID:12032322)
A change in the last base of BRCA1 exon 23, 5586G–>A, results in abnormal RNA splicing. (PMID:12034536)
pathological splice mutations outside the invariant AG/GT splice sites of exon 5 increase alternative transcript levels in the 5’ end of the gene (PMID:12037674)
JunB potentiates function of BRCA1 activation domain 1 (AD1) through a coiled-coil-mediated interaction (PMID:12080089)
BRCA1 transactivates the cyclin-dependent kinase inhibitor p27(Kip1). This may be a mechanism for BRCA1- induced growth inhibition. (PMID:12082635)
The BRCA1 suppressor hypothesis: an explanation for the tissue-specific tumor development in BRCA1 patients (PMID:12086871)
solution properties of the highly conserved C terminus of BRCA1, consisting of a tandem repeat of the BRCT domain (BRCT-tan), that plays a critical role in BRCA1-mediated tumor suppression (PMID:12096901)
BRCA1 exon 11 was studied by the protein truncation test, & BRCA1 exons 2, 3, 5, 13 & 20 by SSCP genomic DNA from early-onset breast cancer patients amplified by PCR. 3 frameshifts and a 12 bp duplication polymorphism were found. (PMID:12100744)
Findings demonstrate that a substantial proportion of Turkish ovarian cancer patients, both with and without a family history, carry BRCA1 mutations. (PMID:12112655)
Large rearrangements of exons 13 and 22 have been identified in the BRCA1 gene in German families with a strong history of breast and ovarian cancer. (PMID:12114493)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
mus_musculus	Brca1	ENSMUSG00000017146
rattus_norvegicus	Brca1	ENSRNOG00000020701
caenorhabditis_elegans		WBGENE00000264
caenorhabditis_elegans		WBGENE00018327

Protein

Protein identifiers

Breast cancer type 1 susceptibility protein — P38398 (reviewed: P38398)

Alternative names: RING finger protein 53, RING-type E3 ubiquitin transferase BRCA1

All UniProt accessions (22): P38398, A0A0U1RRA9, A0A2R8Y6Y9, A0A2R8Y7V5, A0A494C182, A0A8V8TPY7, A0A9Y1QPT7, A0A9Y1QQK3, C6YB45, C9IZW4, E7ENB7, E7EQW4, E7EUM2, E7EWN5, E9PC22, G1UI37, H0Y850, H0Y8B8, H0Y8D8, K7EJW3, K7EPC7, Q3B891

UniProt curated annotations — full annotation on UniProt →

Function. 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. It is unclear whether it also mediates the formation of other types of polyubiquitin chains. The BRCA1-BARD1 heterodimer coordinates a diverse range of cellular pathways such as DNA damage repair, ubiquitination and transcriptional regulation to maintain genomic stability. Regulates centrosomal microtubule nucleation. Required for appropriate cell cycle arrests after ionizing irradiation in both the S-phase and the G2 phase of the cell cycle. Required for FANCD2 targeting to sites of DNA damage. Inhibits lipid synthesis by binding to inactive phosphorylated ACACA and preventing its dephosphorylation. 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. 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. Acts as a transcriptional activator.

Subunit / interactions. Heterodimer with BARD1. 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. This association could be a dynamic process changing throughout the cell cycle and within subnuclear domains. Component of the BRCA1-A complex, at least composed of BRCA1, BARD1, UIMC1/RAP80, ABRAXAS1, BRCC3/BRCC36, BABAM2 and BABAM1/NBA1. Interacts (via the BRCT domains) with ABRAXAS1 (phosphorylated form); this is important for recruitment to sites of DNA damage. Can form a heterotetramer with two molecules of ABRAXAS1 (phosphorylated form). Component of the BRCA1-RBBP8 complex. 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. Associates with RNA polymerase II holoenzyme. Interacts with SMC1A, NELFB, DCLRE1C, CLSPN. Interacts with CHEK1, CHEK2, BAP1, BRCC3, UBXN1 and PCLAF. Interacts (via BRCT domains) with BRIP1 (phosphorylated form). Interacts with FANCD2 (ubiquitinated form). Interacts with H2AX (phosphorylated on ‘Ser-140’). Interacts (via the BRCT domains) with ACACA (phosphorylated form); the interaction prevents dephosphorylation of ACACA. Part of a BRCA complex containing BRCA1, BRCA2 and PALB2. Interacts directly with PALB2; the interaction is essential for its function in HRR. Interacts directly with BRCA2; the interaction occurs only in the presence of PALB2 which serves as the bridging protein. Interacts (via the BRCT domains) with LMO4; the interaction represses the transcriptional activity of BRCA1. Interacts (via the BRCT domains) with CCAR2 (via N-terminus); the interaction represses the transcriptional activator activity of BRCA1. Interacts with EXD2. Interacts (via C-terminus) with DHX9; this interaction is direct and links BRCA1 to the RNA polymerase II holoenzyme. Interacts with DNA helicase ZGRF1; the interaction is increased following DNA damage induction. Interacts with FBXO44; this interaction mediates BRCA1 ubiquitination and subsequent degradation.

Subcellular location. Nucleus. Chromosome. Cytoplasm Cytoplasm Cytoplasm.

Tissue specificity. Isoform 1 and isoform 3 are widely expressed. Isoform 3 is reduced or absent in several breast and ovarian cancer cell lines.

Post-translational modifications. Phosphorylated in response to IR, UV, and various stimuli that cause checkpoint activation, probably by ATM or ATR. Phosphorylation at Ser-988 by CHEK2 regulates mitotic spindle assembly. Phosphorylation by AURKA regulates centrosomal microtubule nucleation. Autoubiquitinated, undergoes ‘Lys-6’-linked polyubiquitination. ‘Lys-6’-linked polyubiquitination does not promote degradation. Ubiquitinated in a FBXO44-dependent manner; leading to proteasomal degradation.

Disease relevance. Breast cancer (BC) [MIM:114480] 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. Disease susceptibility is associated with variants affecting the gene represented in this entry. Mutations in BRCA1 are thought to be responsible for 45% of inherited breast cancer. Moreover, BRCA1 carriers have a 4-fold increased risk of colon cancer, whereas male carriers face a 3-fold increased risk of prostate cancer. Cells lacking BRCA1 show defects in DNA repair by homologous recombination. Breast-ovarian cancer, familial, 1 (BROVCA1) [MIM:604370] 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. Disease susceptibility is associated with variants affecting the gene represented in this entry. Mutations in BRCA1 are thought to be responsible for more than 80% of inherited breast-ovarian cancer. Ovarian cancer (OC) [MIM:167000] 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. Disease susceptibility is associated with variants affecting the gene represented in this entry. Pancreatic cancer 4 (PNCA4) [MIM:614320] 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. Disease susceptibility is associated with variants affecting the gene represented in this entry. Fanconi anemia, complementation group S (FANCS) [MIM:617883] 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. Disease susceptibility is associated with variants affecting the gene represented in this entry.

Activity regulation. The E3 ubiquitin-protein ligase activity is inhibited by phosphorylation by AURKA. Activity is increased by phosphatase treatment.

Domain organisation. 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.

Pathway. Protein modification; protein ubiquitination.

Polymorphism. There is evidence that the presence of the rare form of Gln-356-Arg and Leu-871-Pro polymorphisms may be associated with an increased risk for developing ovarian cancer.

Miscellaneous. May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay. Produced by alternative initiation at Met-18 of isoform 1. The N-terminus is confirmed by several cDNAs.

Isoforms (8)

UniProt ID	Names	Canonical?
P38398-1	1	yes
P38398-2	2
P38398-3	3, Delta11b
P38398-4	4, DeltaBRCA1(17aa)
P38398-5	5, Delta11, Delta772-3095
P38398-6	6
P38398-7	7
P38398-8	8

RefSeq proteins (368): NP_001394500, NP_001394510, NP_001394511, NP_001394512, NP_001394514, NP_001394516, NP_001394519, NP_001394520, NP_001394522, NP_001394523, NP_001394525, NP_001394526, NP_001394527, NP_001394531, NP_001394532, NP_001394534, NP_001394539, NP_001394540, NP_001394541, NP_001394542, NP_001394543, NP_001394544, NP_001394545, NP_001394546, NP_001394547, NP_001394548, NP_001394549, NP_001394550, NP_001394551, NP_001394552, NP_001394553, NP_001394554, NP_001394555, NP_001394556, NP_001394557, NP_001394558, NP_001394559, NP_001394560, NP_001394561, NP_001394562, NP_001394563, NP_001394564, NP_001394565, NP_001394566, NP_001394567, NP_001394568, NP_001394569, NP_001394570, NP_001394571, NP_001394573, NP_001394574, NP_001394575, NP_001394576, NP_001394577, NP_001394578, NP_001394581, NP_001394582, NP_001394583, NP_001394584, NP_001394585, NP_001394586, NP_001394587, NP_001394588, NP_001394589, NP_001394590, NP_001394591, NP_001394592, NP_001394593, NP_001394594, NP_001394595, NP_001394596, NP_001394597, NP_001394598, NP_001394599, NP_001394600, NP_001394601, NP_001394602, NP_001394603, NP_001394604, NP_001394605, NP_001394606, NP_001394607, NP_001394608, NP_001394609, NP_001394610, NP_001394611, NP_001394612, NP_001394613, NP_001394614, NP_001394615, NP_001394616, NP_001394617, NP_001394618, NP_001394619, NP_001394620, NP_001394621, NP_001394623, NP_001394624, NP_001394625, NP_001394626, NP_001394627, NP_001394653, NP_001394654, NP_001394655, NP_001394656, NP_001394657, NP_001394658, NP_001394659, NP_001394660, NP_001394661, NP_001394662, NP_001394663, NP_001394664, NP_001394665, NP_001394666, NP_001394667, NP_001394668, NP_001394669, NP_001394670, NP_001394671, NP_001394672, NP_001394673, NP_001394674, NP_001394675, NP_001394676, NP_001394677, NP_001394678, NP_001394679, NP_001394680, NP_001394681, NP_001394767, NP_001394768, NP_001394770, NP_001394771, NP_001394772, NP_001394773, NP_001394774, NP_001394775, NP_001394776, NP_001394777, NP_001394778, NP_001394779, NP_001394780, NP_001394781, NP_001394782, NP_001394783, NP_001394787, NP_001394788, NP_001394789, NP_001394790, NP_001394791, NP_001394792, NP_001394803, NP_001394804, NP_001394808, NP_001394810, NP_001394811, NP_001394813, NP_001394814, NP_001394815, NP_001394816, NP_001394818, NP_001394823, NP_001394824, NP_001394825, NP_001394826, NP_001394827, NP_001394828, NP_001394829, NP_001394831, NP_001394833, NP_001394835, NP_001394836, NP_001394837, NP_001394838, NP_001394839, NP_001394844, NP_001394845, NP_001394846, NP_001394847, NP_001394848, NP_001394849, NP_001394850, NP_001394851, NP_001394852, NP_001394853, NP_001394854, NP_001394855, NP_001394856, NP_001394857, NP_001394858, NP_001394859, NP_001394860, NP_001394861, NP_001394862, NP_001394863, NP_001394864, NP_001394865, NP_001394866, NP_001394867, NP_001394868, NP_001394869, NP_001394870, NP_001394871, NP_001394872, NP_001394873, NP_001394874, NP_001394875, NP_001394876, NP_001394877, NP_001394878, NP_001394879, NP_001394880, NP_001394881, NP_001394882, NP_001394883, NP_001394884, NP_001394885, NP_001394886, NP_001394887, NP_001394888, NP_001394889, NP_001394891, NP_001394892, NP_001394893, NP_001394894, NP_001394895, NP_001394896, NP_001394897, NP_001394898, NP_001394899, NP_001394900, NP_001394901, NP_001394902, NP_001394903, NP_001394904, NP_001394905, NP_001394906, NP_001394907, NP_001394908, NP_001394909, NP_001394910, NP_001394911, NP_001394912, NP_001394913, NP_001394914, NP_001394915, NP_001394919, NP_001394920, NP_001394921, NP_001394922, NP_001395321, NP_001395325, NP_001395326, NP_001395327, NP_001395328, NP_001395329, NP_001395330, NP_001395331, NP_001395332, NP_001395333, NP_001395335, NP_001395336, NP_001395337, NP_001395338, NP_001395339, NP_001395340, NP_001395341, NP_001395342, NP_001395343, NP_001395344, NP_001395345, NP_001395347, NP_001395348, NP_001395349, NP_001395350, NP_001395351, NP_001395352, NP_001395353, NP_001395354, NP_001395355, NP_001395356, NP_001395357, NP_001395358, NP_001395359, NP_001395360, NP_001395361, NP_001395362, NP_001395363, NP_001395364, NP_001395365, NP_001395366, NP_001395367, NP_001395368, NP_001395369, NP_001395370, NP_001395371, NP_001395372, NP_001395373, NP_001395374, NP_001395375, NP_001395376, NP_001395377, NP_001395379, NP_001395380, NP_001395381, NP_001395382, NP_001395383, NP_001395384, NP_001395385, NP_001395386, NP_001395387, NP_001395388, NP_001395389, NP_001395390, NP_001395391, NP_001395392, NP_001395393, NP_001395394, NP_001395395, NP_001395396, NP_001395397, NP_001395398, NP_001395399, NP_001395401, NP_001395402, NP_001395403, NP_001395404, NP_001395405, NP_001395407, NP_001395408, NP_001395409, NP_001395410, NP_001395411, NP_001395412, NP_001395413, NP_001395414, NP_001395418, NP_001395419, NP_001395420, NP_001395421, NP_001395422, NP_001395423, NP_001395424, NP_001395425, NP_001395426, NP_001395427, NP_001395428, NP_001395429, NP_001395430, NP_001395431, NP_001395432, NP_001395433, NP_001395434, NP_001395435, NP_001395436, NP_001395437, NP_001395438, NP_001395439, NP_001395440, NP_001395441, NP_001395442, NP_001395443, NP_009225, NP_009228, NP_009229, NP_009230, NP_009231 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001357	BRCT_dom	Domain
IPR001841	Znf_RING	Domain
IPR011364	BRCA1	Family
IPR013083	Znf_RING/FYVE/PHD	Homologous_superfamily
IPR017907	Znf_RING_CS	Conserved_site
IPR018957	Znf_C3HC4_RING-type	Domain
IPR025994	BRCA1_serine_dom	Domain
IPR031099	BRCA1-associated	Family
IPR036420	BRCT_dom_sf	Homologous_superfamily

Pfam: PF00097, PF00533, PF12820

Enzyme classification (BRENDA):

EC 2.3.2.27 — RING-type E3 ubiquitin transferase (BRENDA: 28 organisms, 138 substrates, 10 inhibitors, 1 Km, 1 kcat entries)

Substrate kinetics (BRENDA)

1 substrates with measured Km, best-characterized 1. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
[UBE2W]-S-UBIQUITINYL-L-CYSTEINE	0.3014	1

UniProt features (313 total): sequence variant 170, modified residue 30, mutagenesis site 27, strand 19, helix 15, cross-link 13, region of interest 9, sequence conflict 8, splice variant 8, compositionally biased region 5, turn 5, domain 2, chain 1, zinc finger region 1

Structure

Experimental structures (PDB)

33 structures, top 30 by resolution.

PDB	Method	Resolution (Å)
8RS8	X-RAY DIFFRACTION	1.31
4IGK	X-RAY DIFFRACTION	1.75
1T15	X-RAY DIFFRACTION	1.85
4IFI	X-RAY DIFFRACTION	2.2
1T29	X-RAY DIFFRACTION	2.3
1JNX	X-RAY DIFFRACTION	2.5
1Y98	X-RAY DIFFRACTION	2.5
3PXB	X-RAY DIFFRACTION	2.5
4Y2G	X-RAY DIFFRACTION	2.5
3PXA	X-RAY DIFFRACTION	2.55
3K0H	X-RAY DIFFRACTION	2.7
3K0K	X-RAY DIFFRACTION	2.7
1N5O	X-RAY DIFFRACTION	2.8
1T2U	X-RAY DIFFRACTION	2.8
3K15	X-RAY DIFFRACTION	2.8
3PXC	X-RAY DIFFRACTION	2.8
3PXD	X-RAY DIFFRACTION	2.8
3PXE	X-RAY DIFFRACTION	2.85
3K16	X-RAY DIFFRACTION	3
9QPX	X-RAY DIFFRACTION	3
4OFB	X-RAY DIFFRACTION	3.05
3COJ	X-RAY DIFFRACTION	3.21
7LYB	ELECTRON MICROSCOPY	3.28
1T2V	X-RAY DIFFRACTION	3.3
4JLU	X-RAY DIFFRACTION	3.5
4Y18	X-RAY DIFFRACTION	3.5
4U4A	X-RAY DIFFRACTION	3.51
2ING	X-RAY DIFFRACTION	3.6
8GRQ	ELECTRON MICROSCOPY	3.87
7JZV	ELECTRON MICROSCOPY	3.9

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P38398-F1	41.99	0.11

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (43): 1, 114, 395, 398, 423, 434, 551, 694, 708, 725, 753, 840, 988, 1009, 1143, 1189, 1191, 1211, 1217, 1218 …

Mutagenesis-validated functional residues (27):

Position	Phenotype
26	disrupts the interaction with e2 enzymes, thereby abolishing the e3 ubiquitin-protein ligase activity.
26	no ubiquitination of rbbp8. no restoration rbbp8-mediated focus formation or g2/m checkpoint control upon dna damage.
71	no effect on interaction with bap1.
1143	reduces in vitro phosphorylation by atr.
1239	no effect on in vitro phosphorylation by atr.
1280	reduces in vitro phosphorylation by atr.
1298	no effect on in vitro phosphorylation by atr.
1330	no effect on in vitro phosphorylation by atr.
1387	loss of ir-induced s-phase checkpoint. reduces in vitro phosphorylation by atr.
1394	reduces in vitro phosphorylation by atr.
1423	inhibition of the infrared-induced g2 arrest. reduces phosphorylation by atr.
1457	reduces in vitro phosphorylation by atr.
1466	no effect on in vitro phosphorylation by atr.
1524	no change in infrared s-phase delay; when associated with a-1387. no effect on in vitro phosphorylation by atr.
1655	abolishes interaction with brip1.
1656	no effect on affinity for a brip1 phosphopeptide.
1662	does not abolish abraxas1 binding, but abolishes formation of a heterotetramer with abraxas1.
1663	does not abolish abraxas1 binding, but abolishes formation of a heterotetramer with abraxas1.
1666	does not abolish abraxas1 binding, but impairs formation of a heterotetramer with abraxas1.
1670	impairs formation of a heterotetramer with abraxas1.
1671	impairs formation of a heterotetramer with abraxas1.
1700	strongly reduces affinity for a brip1 phosphopeptide.
1702	abolishes interaction with brip1.
1738	abolishes interaction with brip1.
1755	no effect on in vitro phosphorylation by atr.

Function

Pathways and Gene Ontology

Reactome pathways

59 pathways

ID	Pathway
R-HSA-1221632	Meiotic synapsis
R-HSA-3108214	SUMOylation of DNA damage response and repair proteins
R-HSA-5685938	HDR through Single Strand Annealing (SSA)
R-HSA-5685942	HDR through Homologous Recombination (HRR)
R-HSA-5689901	Metalloprotease DUBs
R-HSA-5693554	Resolution of D-loop Structures through Synthesis-Dependent Strand Annealing (SDSA)
R-HSA-5693565	Recruitment and ATM-mediated phosphorylation of repair and signaling proteins at DNA double strand breaks
R-HSA-5693568	Resolution of D-loop Structures through Holliday Junction Intermediates
R-HSA-5693571	Nonhomologous End-Joining (NHEJ)
R-HSA-5693579	Homologous DNA Pairing and Strand Exchange
R-HSA-5693607	Processing of DNA double-strand break ends
R-HSA-5693616	Presynaptic phase of homologous DNA pairing and strand exchange
R-HSA-6796648	TP53 Regulates Transcription of DNA Repair Genes
R-HSA-6804756	Regulation of TP53 Activity through Phosphorylation
R-HSA-69473	G2/M DNA damage checkpoint
R-HSA-8951664	Neddylation
R-HSA-8953750	Transcriptional Regulation by E2F6
R-HSA-912446	Meiotic recombination
R-HSA-9663199	Defective DNA double strand break response due to BRCA1 loss of function
R-HSA-9699150	Defective DNA double strand break response due to BARD1 loss of function
R-HSA-9701192	Defective homologous recombination repair (HRR) due to BRCA1 loss of function
R-HSA-9704331	Defective HDR through Homologous Recombination Repair (HRR) due to PALB2 loss of BRCA1 binding function
R-HSA-9704646	Defective HDR through Homologous Recombination Repair (HRR) due to PALB2 loss of BRCA2/RAD51/RAD51C binding function
R-HSA-9709570	Impaired BRCA2 binding to RAD51
R-HSA-9709603	Impaired BRCA2 binding to PALB2
R-HSA-9755511	KEAP1-NFE2L2 pathway
R-HSA-9825895	Regulation of MITF-M-dependent genes involved in DNA replication, damage repair and senescence
R-HSA-1266738	Developmental Biology
R-HSA-1474165	Reproduction
R-HSA-1500620	Meiosis

MSigDB gene sets: 991 (showing top): PID_FANCONI_PATHWAY, GOBP_DNA_TEMPLATED_DNA_REPLICATION_MAINTENANCE_OF_FIDELITY, REACTOME_MEIOTIC_RECOMBINATION, FXR_IR1_Q6, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, GOBP_REGULATION_OF_CELL_CYCLE_CHECKPOINT, GOBP_EMBRYO_DEVELOPMENT_ENDING_IN_BIRTH_OR_EGG_HATCHING, GOBP_RESPONSE_TO_IONIZING_RADIATION, GOBP_REGULATION_OF_MICROTUBULE_BASED_PROCESS, RODRIGUES_THYROID_CARCINOMA_POORLY_DIFFERENTIATED_UP, MORF_MSH3, REACTOME_MEIOTIC_SYNAPSIS, BIOCARTA_ATM_PATHWAY, GOBP_RESPONSE_TO_PEPTIDE, GOBP_CELLULAR_RESPONSE_TO_LIPID

GO Biological Process (45): double-strand break repair via homologous recombination (GO:0000724), DNA repair (GO:0006281), regulation of DNA repair (GO:0006282), DNA damage tolerance (GO:0006301), double-strand break repair (GO:0006302), chromatin remodeling (GO:0006338), regulation of transcription by RNA polymerase II (GO:0006357), fatty acid biosynthetic process (GO:0006633), DNA damage response (GO:0006974), chromosome segregation (GO:0007059), mitotic G2 DNA damage checkpoint signaling (GO:0007095), centrosome cycle (GO:0007098), intrinsic apoptotic signaling pathway in response to DNA damage (GO:0008630), response to ionizing radiation (GO:0010212), positive regulation of vascular endothelial growth factor production (GO:0010575), positive regulation of gene expression (GO:0010628), protein ubiquitination (GO:0016567), negative regulation of cell growth (GO:0030308), negative regulation of intracellular estrogen receptor signaling pathway (GO:0033147), homologous recombination (GO:0035825), chordate embryonic development (GO:0043009), negative regulation of gene expression via chromosomal CpG island methylation (GO:0044027), mitotic G2/M transition checkpoint (GO:0044818), negative regulation of fatty acid biosynthetic process (GO:0045717), positive regulation of DNA repair (GO:0045739), positive regulation of angiogenesis (GO:0045766), negative regulation of cell cycle (GO:0045786), negative regulation of DNA-templated transcription (GO:0045892), positive regulation of DNA-templated transcription (GO:0045893), positive regulation of transcription by RNA polymerase II (GO:0045944), negative regulation of centriole replication (GO:0046600), regulation of cell cycle (GO:0051726), protein autoubiquitination (GO:0051865), random inactivation of X chromosome (GO:0060816), cellular response to tumor necrosis factor (GO:0071356), cellular response to ionizing radiation (GO:0071479), cellular response to indole-3-methanol (GO:0071681), protein K6-linked ubiquitination (GO:0085020), DNA strand resection involved in replication fork processing (GO:0110025), negative regulation of extrinsic apoptotic signaling pathway via death domain receptors (GO:1902042)

GO Molecular Function (20): transcription cis-regulatory region binding (GO:0000976), p53 binding (GO:0002039), DNA binding (GO:0003677), damaged DNA binding (GO:0003684), transcription coactivator activity (GO:0003713), RNA binding (GO:0003723), ubiquitin-protein transferase activity (GO:0004842), zinc ion binding (GO:0008270), tubulin binding (GO:0015631), enzyme binding (GO:0019899), ubiquitin protein ligase binding (GO:0031625), identical protein binding (GO:0042802), ubiquitin-modified histone reader activity (GO:0061649), RNA polymerase binding (GO:0070063), histone H2AK127 ubiquitin ligase activity (GO:0140863), histone H2AK129 ubiquitin ligase activity (GO:0140864), protein binding (GO:0005515), transferase activity (GO:0016740), metal ion binding (GO:0046872), ubiquitin protein ligase activity (GO:0061630)

GO Cellular Component (22): ubiquitin ligase complex (GO:0000151), nuclear ubiquitin ligase complex (GO:0000152), lateral element (GO:0000800), gamma-tubulin ring complex (GO:0000931), male germ cell nucleus (GO:0001673), XY body (GO:0001741), nucleus (GO:0005634), nucleoplasm (GO:0005654), chromosome (GO:0005694), cytoplasm (GO:0005737), plasma membrane (GO:0005886), nuclear body (GO:0016604), BRCA1-BARD1 complex (GO:0031436), protein-containing complex (GO:0032991), BRCA1-A complex (GO:0070531), BRCA1-B complex (GO:0070532), BRCA1-C complex (GO:0070533), DNA repair complex (GO:1990391), ribonucleoprotein complex (GO:1990904), condensed chromosome (GO:0000793), condensed nuclear chromosome (GO:0000794), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-15 pathways:

Category	Pathways
HDR through Homologous Recombination (HRR) or Single Strand Annealing (SSA)	3
Meiosis	2
Resolution of D-Loop Structures	2
Diseases of DNA Double-Strand Break Repair	2
SUMO E3 ligases SUMOylate target proteins	1
Deubiquitination	1
DNA Double Strand Break Response	1
DNA Double-Strand Break Repair	1
HDR through Homologous Recombination (HRR)	1
Homologous DNA Pairing and Strand Exchange	1
Transcriptional Regulation by TP53	1
Regulation of TP53 Activity	1
G2/M Checkpoints	1
Post-translational protein modification	1
Generic Transcription Pathway	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
nuclear protein-containing complex	4
DNA damage response	3
protein binding	3
cellular anatomical structure	3
DNA metabolic process	2
DNA repair	2
cell cycle process	2
nucleic acid binding	2
histone H2A ubiquitin ligase activity	2
intracellular membraneless organelle	2
recombinational repair	1
double-strand break repair	1
regulation of DNA metabolic process	1
regulation of cellular response to stress	1
DNA replication	1
chromatin organization	1
regulation of DNA-templated transcription	1
transcription by RNA polymerase II	1
fatty acid metabolic process	1
lipid biosynthetic process	1
monocarboxylic acid biosynthetic process	1
cellular response to stress	1
mitotic G2 phase	1
mitotic DNA damage checkpoint signaling	1
mitotic G2/M transition checkpoint	1
microtubule organizing center organization	1
intrinsic apoptotic signaling pathway	1
response to radiation	1
positive regulation of cytokine production	1
vascular endothelial growth factor production	1
regulation of vascular endothelial growth factor production	1
gene expression	1
regulation of gene expression	1
positive regulation of macromolecule biosynthetic process	1
protein modification by small protein conjugation	1
regulation of cell growth	1
cell growth	1
negative regulation of growth	1
negative regulation of cellular process	1
estrogen receptor signaling pathway	1

Protein interactions and networks

STRING

6120 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
BRCA1	PALB2	Q86YC2	999
BRCA1	TP53	P04637	999
BRCA1	ATM	Q13315	999
BRCA1	BRCA2	P51587	999
BRCA1	TP53BP1	Q12888	999
BRCA1	RAD51	Q06609	999
BRCA1	FANCD2	Q9BXW9	998
BRCA1	RBBP8	Q99708	998
BRCA1	BRIP1	Q9BX63	997
BRCA1	ABRAXAS1	Q6UWZ7	997
BRCA1	CHEK2	O96017	997
BRCA1	UIMC1	Q96RL1	997
BRCA1	MDC1	Q14676	996
BRCA1	BABAM2	Q9NXR7	995
BRCA1	BRCC3	P46736	995
BRCA1	BRAP	Q7Z569	995
BRCA1	ESR1	P03372	995

IntAct

342 interactions, top by confidence:

A	B	Type	Score
BRCA1	BRIP1	psi-mi:“MI:0915”(physical association)	0.980
BRIP1	BRCA1	psi-mi:“MI:0914”(association)	0.980
BRIP1	BRCA1	psi-mi:“MI:0403”(colocalization)	0.980
BRCA1	BRIP1	psi-mi:“MI:0407”(direct interaction)	0.980
BRCA1	BARD1	psi-mi:“MI:0915”(physical association)	0.960
BRCA1	BARD1	psi-mi:“MI:0407”(direct interaction)	0.960
BARD1	BRCA1	psi-mi:“MI:0915”(physical association)	0.960
BRCA1	RBBP8	psi-mi:“MI:0915”(physical association)	0.930
RBBP8	BRCA1	psi-mi:“MI:0915”(physical association)	0.930
RBBP8	BRCA1	psi-mi:“MI:0407”(direct interaction)	0.930

BioGRID (2602): XRS2 (Synthetic Rescue), RAD55 (Synthetic Rescue), RAD51 (Synthetic Rescue), RAD50 (Synthetic Rescue), BUR2 (Synthetic Rescue), TMA22 (Synthetic Rescue), YGR053C (Synthetic Rescue), YAP3 (Synthetic Rescue), YAF9 (Synthetic Rescue), CDC21 (Synthetic Rescue), NPR1 (Synthetic Rescue), BEM4 (Synthetic Rescue), HDA3 (Synthetic Rescue), DAN1 (Synthetic Rescue), GYP5 (Synthetic Rescue)

ESM2 similar proteins: A0A140LI88, A4D1E1, D3Z987, D3ZUC6, E5FYH0, E5FYH1, E9Q3S4, F6ULY3, F7DF15, G3S077, G7H7V7, G7NY55, O35923, O54952, O88491, O95405, P38398, P48754, P51587, P97929, Q0VBV7, Q0VGT4, Q2M3C7, Q3V089, Q56UN5, Q5DTT3, Q5F2C3, Q5VWN6, Q61493, Q68DQ2, Q6J6I8, Q6J6I9, Q6J6J0, Q6NSW3, Q6ZP01, Q7TSY8, Q7Z570, Q80U44, Q864S8, Q864U1

Diamond homologs: A0A3B3IT33, A0JN74, A2XK56, A4QPC6, A6NCK2, A6NDI0, A6NGJ6, A6NI03, A6NLI5, A6NLU0, B1H278, B8B5U8, C9J1S8, D3YY23, D3Z8N2, F8VTS6, I1YAP6, O00478, O00481, O13033, O54952, O60106, O76064, P0CI25, P0CI26, P18892, P19474, P38398, P48754, P82456, P86448, P86449, Q14258, Q14527, Q1XHT8, Q28DS3, Q2HJ46, Q3C1V9, Q3TL54, Q4KLN8

SIGNOR signaling

83 interactions.

A	Effect	B	Mechanism
ATR	“up-regulates activity”	BRCA1	phosphorylation
CHEK2	up-regulates	BRCA1	phosphorylation
AURKA	up-regulates	BRCA1	phosphorylation
BRCA1	“up-regulates quantity by expression”	CDKN1B	“transcriptional regulation”
BRCA1	up-regulates	RBBP8	ubiquitination
CDK4	down-regulates	BRCA1	phosphorylation
AKT1	up-regulates	BRCA1	phosphorylation
ABRAXAS1	up-regulates	BRCA1	binding
UIMC1	up-regulates	BRCA1	binding
BARD1	up-regulates	BRCA1	binding
ATM	up-regulates	BRCA1	phosphorylation
CDK1	up-regulates	BRCA1	phosphorylation
CDK2	up-regulates	BRCA1	phosphorylation
BRCA1	“up-regulates quantity by expression”	ATM	“transcriptional regulation”
ATR	up-regulates	BRCA1	phosphorylation
CyclinD/CDK4	down-regulates	BRCA1	phosphorylation
AKT	up-regulates	BRCA1	phosphorylation
PALB2	“up-regulates activity”	BRCA1	binding
PPP1CA	“down-regulates activity”	BRCA1	dephosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 65 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
DNA Double Strand Break Response	8	68.0×	2e-11
Impaired BRCA2 binding to PALB2	6	48.9×	9e-08
Defective homologous recombination repair (HRR) due to BRCA1 loss of function	6	45.3×	1e-07
Defective HDR through Homologous Recombination Repair (HRR) due to PALB2 loss of BRCA1 binding function	6	45.3×	1e-07
Defective HDR through Homologous Recombination Repair (HRR) due to PALB2 loss of BRCA2/RAD51/RAD51C binding function	6	45.3×	1e-07
DNA Double-Strand Break Repair	10	44.3×	2e-12
Resolution of D-loop Structures through Synthesis-Dependent Strand Annealing (SDSA)	6	42.2×	2e-07
Homologous DNA Pairing and Strand Exchange	6	40.8×	2e-07

GO biological processes:

GO term	Partners	Fold	FDR
mitotic G2/M transition checkpoint	6	80.2×	2e-08
response to ionizing radiation	6	41.1×	6e-07
positive regulation of DNA repair	6	35.9×	1e-06
double-strand break repair	10	33.8×	2e-10
DNA damage checkpoint signaling	5	32.7×	2e-05
double-strand break repair via homologous recombination	8	20.8×	6e-07
meiotic cell cycle	5	20.4×	2e-04
DNA damage response	13	11.6×	2e-08

Disease & clinical

Cancer significance

From CIViC — curated cancer-variant interpretation:

BRCA1 mutations in the germline have become a hallmark for hereditary breast and ovarian cancers. Variants that have been demonstrated to reduce the function of the protein have been shown to increase the risk for these cancers, as well as prostate and pancreatic cancer. These findings have been the impetus for the increased popularity of genetic testing of healthy individuals to assess risk. Recent studies in ovarian cancer have also demonstrated that BRCA mutation status can predict treatment response. A number of trials assessing BRCA mutation status have shown an improved response to platinum agents, and more recently has led to the FDA-approval of PARP inhibitors for BRCA-positive ovarian cancers. These studies have resulted in the Society of Gynecologic Oncology to recommend germline BRCA testing in all patients with a diagnosis of ovarian cancer.

From intOGen — cancer-driver classification: loss-of-function (tumor-suppressor-like) across 4 cancer types — BLCA, BRCA, MEL, OVT.

Clinical variants and AI predictions

ClinVar

15323 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	3991
Likely pathogenic	326
Uncertain significance	2460
Likely benign	2706
Benign	729

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1012155	NM_007294.4(BRCA1):c.1728del (p.Glu577fs)	Pathogenic
1012156	NM_007294.4(BRCA1):c.3982del (p.Ser1328fs)	Pathogenic
1027595	NC_000017.10:g.(?41196311)(41203135_41209068)del	Pathogenic
1027624	NC_000017.10:g.(41203135_41209068)_(41209153_41215349)del	Pathogenic
1048829	NM_007294.4(BRCA1):c.5075-390_5193+2del	Pathogenic
1048853	NM_007294.4(BRCA1):c.302-167_441+3del	Pathogenic
1048961	NM_007294.4(BRCA1):c.4485-10_4491del	Pathogenic
1049014	NM_007294.4(BRCA1):c.5194-42_5277+2del	Pathogenic
1049017	NM_007294.4(BRCA1):c.5407-73_5467+4del	Pathogenic
1049053	NM_007294.4(BRCA1):c.5296del (p.Ile1766fs)	Pathogenic
1049103	NM_007294.4(BRCA1):c.5141_5144del (p.Val1714fs)	Pathogenic
1049236	NC_000017.11:g.43045676_43045803del	Pathogenic
1049239	NM_007294.4(BRCA1):c.1100del (p.Thr367fs)	Pathogenic
1049275	NM_007294.4(BRCA1):c.5280del (p.Phe1761fs)	Pathogenic
1049277	NM_007294.4(BRCA1):c.3914dup (p.Asp1305fs)	Pathogenic
1049380	NM_007294.4(BRCA1):c.81-1_134+2del	Pathogenic
1049514	NM_007294.4(BRCA1):c.2827A>T (p.Lys943Ter)	Pathogenic
1049561	NM_007294.4(BRCA1):c.5153-77_5193+4del	Pathogenic
1049567	NM_007294.4(BRCA1):c.2_80+4del	Pathogenic
1049576	NM_007294.4(BRCA1):c.5194-1_5277+2del	Pathogenic
1049707	NM_007294.4(BRCA1):c.705_4185+4del	Pathogenic
1049719	NM_007294.4(BRCA1):c.851del (p.Gln284fs)	Pathogenic
1049776	NM_007294.4(BRCA1):c.1603G>T (p.Gly535Ter)	Pathogenic
1049828	NM_007294.4(BRCA1):c.1848_1861del (p.Thr617fs)	Pathogenic
1049868	NM_007294.4(BRCA1):c.4358-1_4484+2del	Pathogenic
1049895	NM_007294.4(BRCA1):c.2365del (p.Ser789fs)	Pathogenic
1049912	NM_007294.4(BRCA1):c.5194-836_5277+3del	Pathogenic
1050026	NM_007294.4(BRCA1):c.5194-119_5277+3del	Pathogenic
1050145	NM_007294.4(BRCA1):c.66_67delinsTT (p.Leu22_Glu23delinsPheTer)	Pathogenic
1050253	NM_007294.4(BRCA1):c.4987-1331_5152+2del	Pathogenic

SpliceAI

3719 predictions. Top by Δscore:

Variant	Effect	Δscore
17:43045800:TTG:T	acceptor_gain	1.0000
17:43045801:TGCTG:T	acceptor_loss	1.0000
17:43047713:C:CT	acceptor_gain	1.0000
17:43047713:C:T	acceptor_gain	1.0000
17:43047714:A:T	acceptor_gain	1.0000
17:43049119:A:AC	donor_gain	1.0000
17:43049120:C:CC	donor_gain	1.0000
17:43049120:CTGTG:C	donor_gain	1.0000
17:43049195:C:CC	acceptor_gain	1.0000
17:43049195:CTAAA:C	acceptor_loss	1.0000
17:43057046:CTTTA:C	donor_loss	1.0000
17:43057047:TTTAC:T	donor_loss	1.0000
17:43057048:TTACC:T	donor_loss	1.0000
17:43057049:TACCT:T	donor_loss	1.0000
17:43057050:ACCT:A	donor_loss	1.0000
17:43057051:C:CG	donor_loss	1.0000
17:43057051:CCTTT:C	donor_gain	1.0000
17:43057131:TCATG:T	acceptor_gain	1.0000
17:43057132:CATG:C	acceptor_gain	1.0000
17:43057132:CATGC:C	acceptor_gain	1.0000
17:43057133:ATG:A	acceptor_gain	1.0000
17:43057134:TG:T	acceptor_gain	1.0000
17:43057136:C:CA	acceptor_loss	1.0000
17:43057136:C:CC	acceptor_gain	1.0000
17:43057137:T:A	acceptor_loss	1.0000
17:43070926:A:AC	donor_gain	1.0000
17:43070927:C:CC	donor_gain	1.0000
17:43070927:CAA:C	donor_gain	1.0000
17:43070954:C:CT	donor_gain	1.0000
17:43071234:TCCCT:T	acceptor_gain	1.0000

AlphaMissense

12463 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
17:43106487:A:G	C61R	0.999
17:43115731:A:C	F43L	0.999
17:43115731:A:T	F43L	0.999
17:43115733:A:G	F43L	0.999
17:43124027:A:G	C24R	0.999
17:43045761:A:G	W1837R	0.998
17:43045761:A:T	W1837R	0.998
17:43106486:C:G	C61S	0.998
17:43106487:A:T	C61S	0.998
17:43106529:A:G	C47R	0.998
17:43115730:A:G	C44R	0.998
17:43115745:A:G	C39R	0.998
17:43124018:A:G	C27R	0.998
17:43124025:A:C	C24W	0.998
17:43124026:C:G	C24S	0.998
17:43124027:A:T	C24S	0.998
17:43106478:A:G	C64R	0.997
17:43106527:G:C	C47W	0.997
17:43106528:C:G	C47S	0.997
17:43106528:C:T	C47Y	0.997
17:43106529:A:T	C47S	0.997
17:43115728:G:C	C44W	0.997
17:43115729:C:T	C44Y	0.997
17:43115744:C:G	C39S	0.997
17:43115745:A:T	C39S	0.997
17:43115756:A:T	V35D	0.997
17:43115779:A:C	C27W	0.997
17:43045747:A:C	S1841R	0.996
17:43045747:A:T	S1841R	0.996
17:43045749:T:G	S1841R	0.996

dbSNP variants (sampled 300 via entrez): RS1000020373 (17:43068028 A>G), RS1000051459 (17:43068485 A>G), RS1000070436 (17:43115432 G>A,C), RS1000082967 (17:43086221 C>A), RS1000126190 (17:43096997 T>G), RS1000166247 (17:43073350 C>A,T), RS1000243173 (17:43126312 C>T), RS1000263099 (17:43087877 G>C), RS1000323311 (17:43089159 A>T), RS1000330125 (17:43074880 C>A), RS1000348965 (17:43080033 CATG>C), RS1000401499 (17:43080555 A>C), RS1000484532 (17:43115783 G>A,C,T), RS1000494544 (17:43108499 T>C), RS1000510526 (17:43102543 G>A,C)

Disease associations

OMIM: gene MIM:113705 | disease phenotypes: MIM:604370, MIM:114480, MIM:614320, MIM:617883, MIM:109800, MIM:613659, MIM:260350, MIM:601228, MIM:114500, MIM:300049, MIM:167000, MIM:175860, MIM:227650, MIM:612555, MIM:608812, MIM:120435, MIM:176807, MIM:211980, MIM:113970

GenCC curated gene-disease

Disease	Classification	Inheritance
breast-ovarian cancer, familial, susceptibility to, 1	Definitive	Autosomal dominant
Fanconi anemia, complementation group S	Definitive	Autosomal recessive
BRCA1-related cancer predisposition	Definitive	Autosomal dominant
pancreatic cancer, susceptibility to, 4	Moderate	Autosomal dominant
hereditary breast ovarian cancer syndrome	Supportive	Autosomal dominant
Fanconi anemia	Supportive	Autosomal recessive

ClinGen Gene-Disease Validity (2)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
BRCA1-related cancer predisposition	Definitive	AD
Fanconi anemia, complementation group S	Definitive	AR

Mondo (44): hereditary breast ovarian cancer syndrome (MONDO:0003582), hereditary neoplastic syndrome (MONDO:0015356), breast-ovarian cancer, familial, susceptibility to, 1 (MONDO:0011450), hereditary breast carcinoma (MONDO:0016419), breast cancer (MONDO:0007254), pancreatic cancer, susceptibility to, 4 (MONDO:0013685), Fanconi anemia, complementation group S (MONDO:0054748), colon carcinoma (MONDO:0002032), urinary bladder cancer (MONDO:0001187), BRCA1-related cancer predisposition (MONDO:0700268), ovarian neoplasm (MONDO:0021068), breast carcinoma (MONDO:0004989), ovarian carcinoma (MONDO:0005140), malignant pancreatic neoplasm (MONDO:0009831), breast neoplasm (MONDO:0021100)

Orphanet (18): Hereditary breast and/or ovarian cancer syndrome (Orphanet:145), Inherited cancer-predisposing syndrome (Orphanet:140162), Hereditary breast cancer (Orphanet:227535), Familial pancreatic carcinoma (Orphanet:1333), Pilocytic astrocytoma (Orphanet:251612), Hereditary mixed polyposis syndrome (Orphanet:157794), Periventricular nodular heterotopia (Orphanet:98892), Rare ovarian cancer (Orphanet:213500), Punctate palmoplantar keratoderma type 2 (Orphanet:79502), Rare carcinoma of pancreas (Orphanet:217074), Fanconi anemia (Orphanet:84), Familial prostate cancer (Orphanet:1331), Lynch syndrome (Orphanet:144), Rhabdomyosarcoma (Orphanet:780), Infant-type hemispheric glioma (Orphanet:695136)

HPO phenotypes

166 total (30 of 166 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000007	Autosomal recessive inheritance
HP:0000010	Recurrent urinary tract infections
HP:0000027	Azoospermia
HP:0000028	Cryptorchidism
HP:0000035	Abnormal testis morphology
HP:0000047	Hypospadias
HP:0000072	Hydroureter
HP:0000079	Abnormality of the urinary system
HP:0000083	Renal insufficiency
HP:0000130	Abnormality of the uterus
HP:0000135	Hypogonadism
HP:0000175	Cleft palate
HP:0000189	Narrow palate
HP:0000215	Thick upper lip vermilion
HP:0000218	High palate
HP:0000238	Hydrocephalus
HP:0000252	Microcephaly
HP:0000268	Dolichocephaly
HP:0000280	Coarse facial features
HP:0000286	Epicanthus
HP:0000294	Low anterior hairline
HP:0000316	Hypertelorism
HP:0000324	Facial asymmetry
HP:0000340	Sloping forehead
HP:0000347	Micrognathia
HP:0000364	Hearing abnormality
HP:0000365	Hearing impairment
HP:0000377	Abnormal pinna morphology
HP:0000426	Prominent nasal bridge

GWAS associations

7 associations (top):

Study	Trait	p-value
GCST005312_40	Menopause (age at onset)	8.000000e-11
GCST005863_20	Menopause (age at onset)	1.000000e-08
GCST009823_7	Gynecologic disease (multivariate analysis)	1.000000e-08
GCST009829_3	Ovarian cancer (MTAG)	5.000000e-08
GCST009830_31	Ovarian cancer	3.000000e-08
GCST90002394_401	Monocyte percentage of white cells	1.000000e-10
GCST90011899_131	Aspartate aminotransferase levels	1.000000e-12

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0004704	age at menopause
EFO:0007989	monocyte percentage of leukocytes
EFO:0004736	aspartate aminotransferase measurement

MeSH disease descriptors (16)

Descriptor	Name	Tree numbers
D001943	Breast Neoplasms	C04.588.180; C17.800.090.500
D002051	Burkitt Lymphoma	C01.925.256.466.313.165; C01.925.928.313.165; C04.557.386.480.150.165; C15.604.515.569.480.150.165; C20.683.515.761.480.150.165
D018270	Carcinoma, Ductal, Breast	C04.557.470.200.025.232.500; C04.557.470.615.132.500; C04.588.180.390; C17.800.090.500.390
D004407	Dysgerminoma	C04.557.465.330.300
D005199	Fanconi Anemia	C15.378.050.085.080.280; C15.378.190.223.500.500.280; C16.320.077.280; C18.452.284.280
D061325	Hereditary Breast and Ovarian Cancer Syndrome	C04.588.180.483; C04.588.322.455.431; C04.700.517; C12.050.351.500.056.630.705.431; C12.050.351.937.418.685.431; C12.100.250.056.630.705.431; C12.900.418.685.431; C16.320.700.517; C17.800.090.500.483; C19.344.410.431; C19.391.630.705.431
D009386	Neoplastic Syndromes, Hereditary	C04.700; C16.320.700
D010049	Ovarian Diseases	C12.050.351.500.056.630; C12.100.250.056.630; C19.391.630
D010051	Ovarian Neoplasms	C04.588.322.455; C12.050.351.500.056.630.705; C12.050.351.937.418.685; C12.100.250.056.630.705; C12.900.418.685; C19.344.410; C19.391.630.705
D054091	Periventricular Nodular Heterotopia	C10.500.507.450.750; C16.131.666.507.450.750
D011471	Prostatic Neoplasms	C04.588.945.440.770; C12.100.500.260.750; C12.100.500.565.625; C12.200.294.260.750; C12.200.294.565.625; C12.200.758.409.750; C12.900.619.750
D012208	Rhabdomyosarcoma	C04.557.450.590.550.660; C04.557.450.795.550.660
C562840	Breast Cancer, Familial (supp.)
C537261	Lynch syndrome I (site-specific colonic cancer) (supp.)
C535837	Pancreatic carcinoma, familial (supp.)
C537243	Prostate cancer, familial (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5990 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

12 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 952,653 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL1534	RIBOFLAVIN	4	136,163
CHEMBL1563	DAUNORUBICIN HYDROCHLORIDE	4	28,670
CHEMBL1607	TOPOTECAN HYDROCHLORIDE	4	56,379
CHEMBL178	DAUNORUBICIN	4	203,756
CHEMBL359744	DOXORUBICIN HYDROCHLORIDE	4	141,917
CHEMBL704	MESALAMINE	4	52,574
CHEMBL932	DIPYRIDAMOLE	4	51,743
CHEMBL140	CURCUMIN	3	93,882
CHEMBL265502	SURAMIN	3	36,848
CHEMBL413376	SURAMIN HEXASODIUM	3	2,743
CHEMBL1473252	SODIUM TANSHINONE IIA SULFONATE	2	160
CHEMBL284328	HOMIDIUM BROMIDE	2	147,818

Clinical evidence (CIViC)

Drug × variant × indication: 43 predictive associations from 53 curated evidence items; also 3 predisposing, 3 prognostic.

Variant	Therapy	Indication	Effect	Level	CIViC
BRCA1 Mutation	Rucaparib	Ovarian Cancer	Sensitivity/Response	CIViC A	EID11136 +3
BRCA1 Mutation	Olaparib	Prostate Cancer	Sensitivity/Response	CIViC A	EID12943 +2
BRCA1 Mutation	Olaparib	Ovarian Cancer	Sensitivity/Response	CIViC A	EID7274 +2
BRCA1 Loss-of-function	Olaparib	Her2-receptor Negative Breast Cancer	Sensitivity/Response	CIViC A	EID11201 +1
BRCA1 Loss-of-function	Olaparib	Triple-receptor Negative Breast Cancer	Sensitivity/Response	CIViC A	EID11216
BRCA1 Loss-of-function	Olaparib	Pancreatic Adenocarcinoma	Sensitivity/Response	CIViC A	EID7384
BRCA1 Mutation	Olaparib	Castration-resistant Prostate Carcinoma	Sensitivity/Response	CIViC A	EID11203
BRCA1 Mutation	Talazoparib + Enzalutamide	Castration-resistant Prostate Carcinoma	Sensitivity/Response	CIViC A	EID11734
BRCA1 Mutation OR BRCA2 Mutation	Niraparib	Epithelial Ovarian Cancer	Sensitivity/Response	CIViC A	EID11243
BRCA1 Mutation OR BRCA2 Mutation	Rucaparib	Fallopian Tube, Ovarian Cancer, And Peritoneal Serous Carcinoma	Sensitivity/Response	CIViC A	EID11246
BRCA1 Mutation OR BRCA2 Mutation	Niraparib	Peritoneal Carcinoma	Sensitivity/Response	CIViC A	EID11304
BRCA1 Mutation OR BRCA2 Mutation	Niraparib	Fallopian Tube Carcinoma	Sensitivity/Response	CIViC A	EID11305
BRCA1 Mutation OR BRCA2 Mutation	Abiraterone + Niraparib	Castration-resistant Prostate Carcinoma	Sensitivity/Response	CIViC A	EID11738
BRCA1 Mutation OR BRCA2 Mutation	Rucaparib	Castration-resistant Prostate Carcinoma	Sensitivity/Response	CIViC A	EID12944
BRCA1 Mutation	Platinum Compound	Ovarian Carcinoma	Sensitivity/Response	CIViC B	EID1529 +1
BRCA1 Mutation	Rucaparib	Pancreatic Cancer	Sensitivity/Response	CIViC B	EID9291 +1
BRCA1 Loss-of-function	Olaparib	Ovarian Cancer	Sensitivity/Response	CIViC B	EID211
BRCA1 Loss-of-function	Talazoparib	Breast Cancer	Sensitivity/Response	CIViC B	EID4838
BRCA1 Loss-of-function	Talazoparib	Ovarian Cancer	Sensitivity/Response	CIViC B	EID4876
BRCA1 Loss-of-function OR BAP1 Loss-of-function	Rucaparib	Malignant Mesothelioma	Sensitivity/Response	CIViC B	EID11739
BRCA1 Mutation	Olaparib	Cancer	Sensitivity/Response	CIViC B	EID1370
BRCA1 Mutation	Cediranib + Olaparib	Ovarian Cancer	Sensitivity/Response	CIViC B	EID1677
BRCA1 Mutation	Cisplatin + Carboplatin	Triple-receptor Negative Breast Cancer	Sensitivity/Response	CIViC B	EID1684
BRCA1 Mutation	Olaparib	Her2-receptor Negative Breast Cancer	Sensitivity/Response	CIViC B	EID5830
BRCA1 Mutation	Olaparib	Pancreatic Cancer	Sensitivity/Response	CIViC B	EID5914
BRCA1 Mutation	Cisplatin + Oxaliplatin	Pancreatic Cancer	Sensitivity/Response	CIViC B	EID5915
BRCA1 Mutation	Cisplatin + Gemcitabine + Veliparib	Pancreatic Cancer	Sensitivity/Response	CIViC B	EID5932
BRCA1 Mutation	Veliparib	Pancreatic Cancer	Sensitivity/Response	CIViC B	EID5934
BRCA1 Mutation	Olaparib	Ovarian Serous Carcinoma	Sensitivity/Response	CIViC B	EID6333
BRCA1 Mutation	Olaparib	Breast Cancer	Sensitivity/Response	CIViC B	EID9019

+13 more predictive associations (showing top 30 by evidence level).

PharmGKB: 1 entry (VIP=true, CPIC=false)

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs799917	BRCA1		0.00	0

ChEMBL bioactivities

107 potent at pChembl≥5 of 358 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
7.40	Ki	40	nM	CHEMBL2017822
7.10	Ki	80	nM	CHEMBL2017821
7.00	Ki	100	nM	CHEMBL2017816
6.90	Potency	125.9	nM	CHEMBL1606751
6.90	Potency	125.9	nM	CHEMBL374632
6.89	Ki	130	nM	CHEMBL2017815
6.80	Potency	158.5	nM	CHEMBL212242
6.72	Kd	190	nM	CHEMBL1784784
6.70	Ki	200	nM	CHEMBL1784785
6.57	Ki	270	nM	CHEMBL1784784
6.52	Kd	300	nM	CHEMBL5723350
6.51	IC50	310	nM	CHEMBL5723350
6.50	Potency	316.2	nM	CHEMBL516616
6.39	Kd	410	nM	CHEMBL1784787
6.36	Kd	440	nM	CHEMBL1784786
6.30	Ki	500	nM	CHEMBL2017817
6.27	Ki	540	nM	CHEMBL2017814
6.20	Potency	631	nM	CHEMBL1313353
6.20	Potency	631	nM	CHEMBL1379677
6.20	Potency	631	nM	CHEMBL1253351
6.20	Potency	631	nM	CHEMBL1606751
6.10	Potency	794.3	nM	CHEMBL1379677
6.10	Potency	794.3	nM	CHEMBL1604052
6.00	Potency	1000	nM	CHEMBL516616
6.00	Potency	1000	nM	CHEMBL1336008
6.00	Potency	1000	nM	CHEMBL1487801
6.00	IC50	1000	nM	CHEMBL1784784
5.91	Ki	1240	nM	CHEMBL2017812
5.90	Potency	1259	nM	EUFLAVINE
5.90	Potency	1259	nM	CHEMBL1602532
5.90	Potency	1259	nM	CHEMBL1564313
5.80	Potency	1585	nM	CHEMBL1724937
5.80	Potency	1585	nM	CHEMBL1604052
5.80	IC50	1600	nM	CHEMBL1784785
5.73	Ki	1850	nM	CHEMBL1784774
5.71	Ki	1960	nM	CHEMBL1784703
5.70	Potency	1995	nM	CHEMBL1531429
5.60	Potency	2512	nM	CHEMBL1566406
5.60	Potency	2512	nM	CHEMBL1333758
5.60	Potency	2512	nM	CHEMBL1580759
5.50	Potency	3162	nM	CHEMBL1527008
5.50	Potency	3162	nM	CHEMBL3207650
5.50	Potency	3162	nM	CHEMBL1361000
5.50	Potency	3162	nM	CHEMBL1317415
5.50	Potency	3162	nM	JUGLONE
5.50	IC50	3200	nM	CHEMBL1784703
5.40	Potency	3981	nM	CHEMBL1556008
5.40	Potency	3981	nM	CHEMBL1370169
5.40	Potency	3981	nM	CHEMBL1459360
5.40	Potency	3981	nM	CHEMBL1526658

PubChem BioAssay actives

20 with measured affinity, of 47 total; 15 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
(2S)-2-[[(2S)-3-methyl-2-[[(2S)-1-[(2S)-2-[[(E)-4-phenylbut-3-enoyl]amino]-3-phosphonooxypropanoyl]pyrrolidine-2-carbonyl]amino]butanoyl]amino]-3-phenylpropanoic acid	655661: Inhibition of BRCT domain of His-tagged BRCA1 after 1 min by competitive fluorescence polarization assay	ki	0.0400	uM
(2S)-2-[[(2S)-3-methyl-2-[[(2S)-1-[(2S)-2-[(3-phenylbenzoyl)amino]-3-phosphonooxypropanoyl]pyrrolidine-2-carbonyl]amino]butanoyl]amino]-3-phenylpropanoic acid	655661: Inhibition of BRCT domain of His-tagged BRCA1 after 1 min by competitive fluorescence polarization assay	ki	0.0800	uM
(2S)-2-[[(2S)-3-methyl-2-[[(2S)-1-[(2S)-2-(3-phenylpropanoylamino)-3-phosphonooxypropanoyl]pyrrolidine-2-carbonyl]amino]butanoyl]amino]-3-phenylpropanoic acid	655661: Inhibition of BRCT domain of His-tagged BRCA1 after 1 min by competitive fluorescence polarization assay	ki	0.1000	uM
(2S)-2-[[(2S)-2-[[(2S)-1-[(2S)-2-[[(2S)-2-acetamido-3-naphthalen-2-ylpropanoyl]amino]-3-phosphonooxypropanoyl]pyrrolidine-2-carbonyl]amino]-3-methylbutanoyl]amino]-3-phenylpropanoic acid	655661: Inhibition of BRCT domain of His-tagged BRCA1 after 1 min by competitive fluorescence polarization assay	ki	0.1300	uM
(2S)-2-[[(2S,3R)-2-[[(2S)-1-[(2S)-2-acetamido-3-phosphonooxypropanoyl]pyrrolidine-2-carbonyl]amino]-3-hydroxybutanoyl]amino]-3-phenylpropanoic acid	602102: Binding affinity to BRCA1 by isothermal titration calorimetric assay	kd	0.1900	uM
(2S)-2-[[(2S)-2-[[(2S)-1-[(2S)-2-acetamido-3-phosphonooxypropanoyl]pyrrolidine-2-carbonyl]amino]-3-methylbutanoyl]amino]-3-phenylpropanoic acid	655661: Inhibition of BRCT domain of His-tagged BRCA1 after 1 min by competitive fluorescence polarization assay	ki	0.2000	uM
(2S,3R)-2-[[(2S)-5-amino-2-[[(2S)-6-amino-2-[[(2S)-4-amino-2-[[(2S)-2-[[(2S,3R)-2-[[(2S)-1-[(2S)-2-[[(2S,3R)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S,3S)-2-amino-3-methylpentanoyl]amino]-3-hydroxypropanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]amino]-3-hydroxypropanoyl]amino]-3-hydroxybutanoyl]amino]-3-phosphonooxypropanoyl]pyrrolidine-2-carbonyl]amino]-3-hydroxybutanoyl]amino]-3-phenylpropanoyl]amino]-4-oxobutanoyl]amino]hexanoyl]amino]-5-oxopentanoyl]amino]-3-hydroxybutanoic acid	602102: Binding affinity to BRCA1 by isothermal titration calorimetric assay	kd	0.4100	uM
[(2S)-2-[[(2S,3R)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-acetamido-3-hydroxypropanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]amino]-3-hydroxypropanoyl]amino]-3-hydroxybutanoyl]amino]-3-[(2S)-2-[[(2S,3R)-1-[[(2S)-1-[[(2S)-4-amino-1-[[(2S)-1,6-diamino-1-oxohexan-2-yl]amino]-1,4-dioxobutan-2-yl]amino]-1-oxo-3-phenylpropan-2-yl]amino]-3-hydroxy-1-oxobutan-2-yl]carbamoyl]pyrrolidin-1-yl]-3-oxopropyl] dihydrogen phosphate	602102: Binding affinity to BRCA1 by isothermal titration calorimetric assay	kd	0.4400	uM
(2S)-2-[[(2S)-3-methyl-2-[[(2S)-1-[(2S)-2-(4-phenylbutanoylamino)-3-phosphonooxypropanoyl]pyrrolidine-2-carbonyl]amino]butanoyl]amino]-3-phenylpropanoic acid	655661: Inhibition of BRCT domain of His-tagged BRCA1 after 1 min by competitive fluorescence polarization assay	ki	0.5000	uM
[(2S)-2-[[(2S)-2-acetamido-3-naphthalen-2-ylpropanoyl]amino]-3-[(2S)-2-[[(2S)-1-[[(2S)-1-amino-1-oxo-3-phenylpropan-2-yl]amino]-3-methyl-1-oxobutan-2-yl]carbamoyl]pyrrolidin-1-yl]-3-oxopropyl] dihydrogen phosphate	655661: Inhibition of BRCT domain of His-tagged BRCA1 after 1 min by competitive fluorescence polarization assay	ki	0.5400	uM
[(2S)-2-[[(2S)-2-acetamido-3-naphthalen-2-ylpropanoyl]amino]-3-[(2S)-2-[[(2S,3R)-1-[[(2S)-1-amino-1-oxo-3-phenylpropan-2-yl]amino]-3-hydroxy-1-oxobutan-2-yl]carbamoyl]pyrrolidin-1-yl]-3-oxopropyl] dihydrogen phosphate	655661: Inhibition of BRCT domain of His-tagged BRCA1 after 1 min by competitive fluorescence polarization assay	ki	1.2400	uM
[(2S)-2-acetamido-3-[(2S)-2-[[(2S,3R)-1-[[(2S)-1-amino-1-oxo-3-phenylpropan-2-yl]amino]-3-hydroxy-1-oxobutan-2-yl]carbamoyl]pyrrolidin-1-yl]-3-oxopropyl] dihydrogen phosphate	655661: Inhibition of BRCT domain of His-tagged BRCA1 after 1 min by competitive fluorescence polarization assay	ki	1.8500	uM
[(2S)-2-acetamido-3-[(2S)-2-[[(2S)-1-[[(2S)-1-amino-1-oxo-3-phenylpropan-2-yl]amino]-3-methyl-1-oxobutan-2-yl]carbamoyl]pyrrolidin-1-yl]-3-oxopropyl] dihydrogen phosphate	655661: Inhibition of BRCT domain of His-tagged BRCA1 after 1 min by competitive fluorescence polarization assay	ki	1.9600	uM
(2S)-2-[[(2S)-2-[[(2S)-1-[(2S)-2-[3-(3,4-dimethoxyphenyl)propanoylamino]-3-phosphonooxypropanoyl]pyrrolidine-2-carbonyl]amino]-3-methylbutanoyl]amino]-3-phenylpropanoic acid	655661: Inhibition of BRCT domain of His-tagged BRCA1 after 1 min by competitive fluorescence polarization assay	ki	4.0400	uM
[(2S)-2-acetamido-3-[(2S)-2-[[(2S,3S)-1-[[(2S)-1-amino-1-oxo-3-phenylpropan-2-yl]amino]-3-methyl-1-oxopentan-2-yl]carbamoyl]pyrrolidin-1-yl]-3-oxopropyl] dihydrogen phosphate	602101: Inhibition of BRCA1 by fluorescence polarization assay	ic50	7.1000	uM

CTD chemical–gene interactions

191 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Estradiol	affects reaction, affects binding, increases activity, increases phosphorylation, affects cotreatment (+5 more)	15
Benzo(a)pyrene	increases expression, increases reaction, increases abundance, affects reaction, decreases reaction (+4 more)	11
Tetrachlorodibenzodioxin	increases expression, decreases expression, increases methylation, decreases reaction, affects binding (+5 more)	9
sodium arsenite	decreases reaction, affects cotreatment, increases reaction, decreases expression, increases expression (+5 more)	8
Cisplatin	increases activity, increases phosphorylation, increases reaction, increases response to substance, decreases reaction (+3 more)	8
bisphenol A	increases expression, increases activity, increases reaction, increases methylation, affects reaction (+3 more)	7
Resveratrol	affects reaction, affects expression, affects localization, increases methylation, affects binding (+6 more)	7
Doxorubicin	affects binding, decreases reaction, increases expression, decreases expression	6
lasiocarpine	affects cotreatment, affects expression, decreases expression, increases metabolic processing, increases expression	4
Fulvestrant	affects cotreatment, increases methylation, decreases reaction, increases expression, decreases expression	4
Cannabidiol	decreases expression, affects cotreatment, increases expression	4
Fluorouracil	increases expression, decreases reaction, decreases expression	4
indole-3-carbinol	decreases reaction, increases activity, increases reaction, affects cotreatment, increases expression (+1 more)	3
(+)-JQ1 compound	decreases expression, increases response to substance	3
Arsenic	affects methylation, increases expression, affects cotreatment, decreases expression, increases abundance	3
Cadmium	decreases expression, decreases phosphorylation	3
Etoposide	affects localization, decreases reaction, increases expression, decreases expression	3
Methotrexate	increases expression, increases reaction, increases response to substance, affects cotreatment, decreases expression	3
Oxygen	decreases expression	3
Quercetin	decreases expression, increases expression	3
Tamoxifen	affects binding, affects reaction, decreases expression, increases response to substance, decreases reaction (+4 more)	3
Tretinoin	decreases expression, increases expression	3
Valproic Acid	decreases expression, increases methylation	3
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	affects expression, decreases expression, increases reaction	3
Cadmium Chloride	decreases expression, decreases phosphorylation, increases expression, increases reaction	3
Genistein	decreases reaction, increases expression, affects cotreatment	3
4-biphenylamine	decreases expression, decreases reaction	2
alpha-naphthoflavone	increases activity, decreases reaction, increases expression, affects binding	2
trichostatin A	decreases expression, affects cotreatment, affects expression	2
epigallocatechin gallate	increases expression, affects cotreatment, decreases expression	2

ChEMBL screening assays

13 unique, capped per target: 9 binding, 4 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1613817	Functional	PUBCHEM_BIOASSAY: qHTS Assay for Inhibitors of BRCT-Phosphoprotein Interaction (Green Fluorophore). (Class of assay: confirmatory)	PubChem BioAssay data set
CHEMBL1785941	Binding	Inhibition of BRCA1 by fluorescence polarization assay	Structure-activity relationship studies to probe the phosphoprotein binding site on the carboxy terminal domains of the breast cancer susceptibility gene 1. — J Med Chem

Cellosaurus cell lines

108 cell lines: 51 cancer cell line, 33 transformed cell line, 19 induced pluripotent stem cell, 2 embryonic stem cell, 1 spontaneously immortalized cell line, 1 finite cell line, 1 telomerase immortalized cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_0290	HCC1937	Cancer cell line	Female
CVCL_0623	MDA-MB-436	Cancer cell line	Female
CVCL_1304	IGROV-1	Cancer cell line	Female
CVCL_1781	UACC-812	Cancer cell line	Female
CVCL_2420	COV362	Cancer cell line	Female
CVCL_2421	COV362.4	Cancer cell line	Female
CVCL_3281	HCC1937 BL	Transformed cell line	Female
CVCL_3377	HCC3153	Cancer cell line	Female
CVCL_3422	SUM149PT	Cancer cell line	Female
CVCL_4V48	IGROV(T100r)	Cancer cell line	Female

Clinical trials (associated diseases)

382 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT02562170	PHASE4	COMPLETED	Protexa® Versus TiLoopBra® in Immediate Breast Reconstruction- A Pilot Study
NCT00014638	PHASE4	COMPLETED	Letrozole in Treating Postmenopausal Women With Metastatic Breast Cancer
NCT00022386	PHASE4	COMPLETED	Epoetin Alfa in Treating Chemotherapy-Related Anemia in Women With Stage I, Stage II, or Stage III Breast Cancer
NCT00029224	PHASE4	COMPLETED	Treatment With Zoledronic Acid in Patients With Breast Cancer, Multiple Myeloma, and Prostate Cancer With Cancer Related Bone Lesions
NCT00030758	PHASE4	UNKNOWN	Filgrastim or Pegfilgrastim in Preventing Neutropenia in Women Receiving Chemotherapy Following Surgery for Breast Cancer
NCT00082277	PHASE4	COMPLETED	Anastrozole Biphosphonate Study in Postmenopausal Women With Hormone-Receptor-Positive Early Breast Cancer
NCT00087620	PHASE4	TERMINATED	A Study of Capecitabine In Combination With Docetaxel vs Capecitabine Followed by Docetaxel As First-Line Treatment For Metastatic Breast Cancer
NCT00121836	PHASE4	COMPLETED	A Study of Xeloda (Capecitabine) in Women With HER2-Negative Metastatic Breast Cancer
NCT00126360	PHASE4	UNKNOWN	STARS Breast Trial (Study of Anastrozole and Radiotherapy Sequencing Pilot)
NCT00127933	PHASE4	COMPLETED	XeNA Study - A Study of Xeloda (Capecitabine) in Patients With Invasive Breast Cancer
NCT00128297	PHASE4	COMPLETED	Pamidronate Administration in Breast Cancer Patients With Bone Metastases
NCT00129597	PHASE4	UNKNOWN	Effect of Ketalar to Prevent Postoperative Chronic Pain After Mastectomy
NCT00131170	PHASE4	COMPLETED	Paravertebral Block for Breast Surgery
NCT00156039	PHASE4	COMPLETED	Randomized Trial of Follow-up Strategies in Breast Cancer
NCT00160901	PHASE4	COMPLETED	Complementary Therapies for the Reduction of Side Effects During Chemotherapy for Breast Cancer
NCT00171847	PHASE4	TERMINATED	Study of the Efficacy and Safety of Letrozole Combined With Trastuzumab in Patients With Metastatic Breast Cancer
NCT00176046	PHASE4	COMPLETED	Mistletoe Extract in Early or Advanced Breast Cancer, A Feasibility Study
NCT00190697	PHASE4	COMPLETED	A Study of LY353381 (Arzoxifene) for Patients Who Benefitted From This Drug in Other Oncology Trials and Wished to Continue Treatment
NCT00234195	PHASE4	COMPLETED	Wellbutrin XL, Major Depressive Disorder and Breast Cancer
NCT00237133	PHASE4	COMPLETED	Treatment of Locally Advanced Breast Cancer With Letrozole in Postmenopausal Women
NCT00237224	PHASE4	COMPLETED	Open Label Study of Postmenopausal Women With ER and /or PgR Positive Breast Cancer Treated With Letrozole
NCT00241046	PHASE4	TERMINATED	Letrozole in the Treatment of 1st and 2nd Line Hormone Receptor Positive Breast Cancer: Pre-therapeutic Risk Assessment
NCT00277160	PHASE4	COMPLETED	A Study of Primary Prophylaxis With Neulasta (Pegfilgrastim) Versus Secondary Prophylaxis After Chemotherapy in Elderly Subjects (>/= 65 Years Old) With Cancer
NCT00323479	PHASE4	COMPLETED	Arthralgia During Anastrozole Therapy for Breast Cancer
NCT00334139	PHASE4	COMPLETED	Effect of Zoledronic Acid on Bone Metabolism in Patients With Bone Metastasis and Prostate or Breast Cancer
NCT00356148	PHASE4	COMPLETED	The Efficacy of Prophylactic Antibiotic Administration During Breast Cancer Surgery in Overweight Patients.
NCT00372476	PHASE4	COMPLETED	Efficacy and Safety of Imatinib and Vinorelbine in Patients With Advanced Breast Cancer
NCT00413491	PHASE4	UNKNOWN	National Screening in Denmark With MR Versus Mammography and Ultrasound of Women With BRCA1 or BRCA2 Mutations
NCT00484614	PHASE4	UNKNOWN	Study the Role of Positron Emission Mammography in Pre-surgical Planning for Breast Cancer
NCT00485953	PHASE4	COMPLETED	Effect of Bisphosphonate on Bone Loss in Postmenopausal Women With Breast Cancer Initiating Aromatase Inhibitor Therapy
NCT00496678	PHASE4	COMPLETED	Trial of Patient Navigation-Activation
NCT00531973	PHASE4	UNKNOWN	A Study of Liposomal Doxorubicin in Women With Breast Cancer Exploiting Tissue Doppler Imaging
NCT00537771	PHASE4	COMPLETED	Liver Safety Under Upfront Arimidex vs Tamoxifen
NCT00544986	PHASE4	COMPLETED	A Prospective,Open-label Study of Anastrozole in Post-menopausal Women With Hormone Sensitive Advanced Breast Cancer
NCT00613275	PHASE4	COMPLETED	Patient Navigation in the Safety Net:CONNECTeDD
NCT00638599	PHASE4	COMPLETED	Comparison of Laryngeal Mask Airway (LMA®) and Tracheal Tube in Modified Radical Mastectomy on Breast Cancer
NCT00647075	PHASE4	UNKNOWN	Yunzhi as Dietary Supplement in Breast Cancer
NCT00688909	PHASE4	COMPLETED	Rheumatological Evaluation of Anastrozole and Letrozole as Adjuvant Treatment in Post-menopausal Women With Breast Cancer
NCT00699101	PHASE4	TERMINATED	Using the Conture® Multi-Lumen Balloon to Deliver Accelerated Partial Breast Brachytherapy
NCT00742222	PHASE4	COMPLETED	Electronic Xoft Intersociety Brachytherapy Trial: Electronic Brachytherapy (EBT) For Treatment of Early Stage Breast Cancer

Associated diseases: breast-ovarian cancer, familial, susceptibility to, 1, Fanconi anemia, complementation group S, BRCA1-related cancer predisposition, pancreatic cancer, susceptibility to, 4, hereditary breast ovarian cancer syndrome, Fanconi anemia, ovarian carcinoma, prostate carcinoma, Her2-receptor negative breast cancer, triple-negative breast carcinoma, pancreatic adenocarcinoma, castration-resistant prostate carcinoma, peritoneal carcinoma, fallopian tube carcinoma, malignant pancreatic neoplasm, breast carcinoma, malignant mesothelioma, cancer, ovarian serous adenocarcinoma
Biomarker drugs (CIViC) (drugs whose response is associated with variants in this gene — CIViC predictive evidence, not targeting): Rucaparib, Olaparib, Niraparib, Talazoparib, Veliparib
Disease cohort memberships (association, not causation — diseases whose associated-gene cohort lists this gene; a subset are also under Associated diseases): biliary tract cancer, BRCA1-related cancer predisposition, breast cancer, breast carcinoma, breast ductal adenocarcinoma, breast neoplasm, breast-ovarian cancer, familial, susceptibility to, 1, breast-ovarian cancer, familial, susceptibility to, 2, Burkitt lymphoma, cancer, castration-resistant prostate carcinoma, colon carcinoma, colorectal cancer, susceptibility to, 1, dysgerminoma, endometrial carcinoma, exocrine pancreatic carcinoma, fallopian tube carcinoma, familial pancreatic carcinoma, Fanconi anemia, Fanconi anemia complementation group A, Fanconi anemia, complementation group S, female reproductive system disorder, gastric cancer, Her2-receptor negative breast cancer, hereditary breast carcinoma, hereditary breast ovarian cancer syndrome, hereditary neoplastic syndrome, infant-type hemispheric glioma, invasive ductal breast carcinoma, low grade glioma, lung cancer, lung carcinoma, Lynch syndrome 1, malignant mesothelioma, malignant pancreatic neoplasm, ovarian cancer, ovarian carcinoma, ovarian disorder, ovarian endometrioid adenocarcinoma, ovarian neoplasm, ovarian serous adenocarcinoma, ovarian serous surface papillary adenocarcinoma, pancreatic adenocarcinoma, pancreatic cancer, susceptibility to, 4, peritoneal carcinoma, peritoneum cancer, periventricular nodular heterotopia, pilocytic astrocytoma, polyposis syndrome, hereditary mixed, 1, prostate cancer, prostate cancer, hereditary, prostate carcinoma, punctate palmoplantar keratoderma type 2, rhabdomyosarcoma, triple-negative breast carcinoma, urinary bladder cancer, uterine cancer, uterine corpus cancer