Gene: BRCA1

Alternate names for this Gene: BRCAI|BRCC1|BROVCA1|FANCS|IRIS|PNCA4|PPP1R53|PSCP|RNF53

Gene Summary: 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.

Gene is located in Chromosome: 17

Location in Chromosome : 17q21.31

Description of this Gene: BRCA1 DNA repair associated

Type of Gene: protein-coding

Gene: NBR2

Alternate names for this Gene: NCRNA00192

Gene Summary: This gene was identified by its close proximity on chromosome 17 to tumor suppressor gene BRCA1. Experimental evidence indicates that the two genes share a bi-directional promoter. Transcription for either gene is controlled individually by distinct transcriptional repressor factors. A short (112 amino acid) open reading frame is observed which includes a region derived from a LINE1 element. A strong Kozak signal is not observed for the putative ORF and the stop codon is more than 55 nucleotides upstream of the last splice site for the transcript, suggesting that the transcript is subject to nonsense-mediated decay. Therefore, this gene does not appear to encode a protein. Glucose starvation induces the expression of this gene and the long non-coding RNA transcribed by it functions with AMP-activated protein kinase in mediating the energy stress response.

Gene is located in Chromosome: 17

Location in Chromosome : 17q21.31

Description of this Gene: neighbor of BRCA1 lncRNA 2

Type of Gene: ncRNA

rs80356929 in BRCA1;NBR2 gene and BREAST-OVARIAN CANCER, FAMILIAL, SUSCEPTIBILITY TO, 1 PMID 10528853 1999 A highly accurate, low cost test for BRCA1 mutations.

PMID 23867111 2013 A high-throughput functional complementation assay for classification of BRCA1 missense variants.

PMID 21725363 2012 Functional differences among BRCA1 missense mutations in the control of centrosome duplication.

PMID 21922593 2011 Assessment of human Nter and Cter BRCA1 mutations using growth and localization assays in yeast.

PMID 11320250 2001 Cancer-predisposing mutations within the RING domain of BRCA1: loss of ubiquitin protein ligase activity and protection from radiation hypersensitivity.

PMID 10717622 2000 Frequency of BRCA1/BRCA2 mutations in a population-based sample of young breast carcinoma cases.

PMID 9523200 1998 Identification of missense and truncating mutations in the BRCA1 gene in sporadic and familial breast and ovarian cancer.

PMID 25893891 2015 Validation of an NGS Approach for Diagnostic BRCA1/BRCA2 Mutation Testing.

PMID 31131967 2019 Large scale multifactorial likelihood quantitative analysis of BRCA1 and BRCA2 variants: An ENIGMA resource to support clinical variant classification.

PMID 17924331 2007 A systematic genetic assessment of 1,433 sequence variants of unknown clinical significance in the BRCA1 and BRCA2 breast cancer-predisposition genes.

PMID 20103620 2010 Identification of breast tumor mutations in BRCA1 that abolish its function in homologous DNA recombination.

PMID 19563646 2009 A simple method for co-segregation analysis to evaluate the pathogenicity of unclassified variants; BRCA1 and BRCA2 as an example.

PMID 8531967 1996 BRCA1 mutations in a population-based sample of young women with breast cancer.

PMID 21990134 2012 A review of a multifactorial probability-based model for classification of BRCA1 and BRCA2 variants of uncertain significance (VUS).

PMID 15385441 2004 Evolution of the tumor suppressor BRCA1 locus in primates: implications for cancer predisposition.

PMID 10851077 2000 Initiation of translation from a downstream in-frame AUG codon on BRCA1 can generate the novel isoform protein DeltaBRCA1(17aa).

PMID 15235020 2004 Analysis of missense variation in human BRCA1 in the context of interspecific sequence variation.

PMID 25682074 2015 Prevalence of BRCA1 and BRCA2 germline mutations in patients with triple-negative breast cancer.

PMID 7837387 1995 A collaborative survey of 80 mutations in the BRCA1 breast and ovarian cancer susceptibility gene. Implications for presymptomatic testing and screening.

PMID 10498392 1999 Population-based estimate of the average age-specific cumulative risk of breast cancer for a defined set of protein-truncating mutations in BRCA1 and BRCA2. Australian Breast Cancer Family Study.

PMID 8651293 1996 Two distinct origins of a common BRCA1 mutation in breast-ovarian cancer families: a genetic study of 15 185delAG-mutation kindreds.

PMID 7545954 1994 A strong candidate for the breast and ovarian cancer susceptibility gene BRCA1.

PMID 11352856 2001 The lifetime risks of breast cancer in Ashkenazi Jewish carriers of BRCA1 and BRCA2 mutations.

PMID 24764757 2014 Prevalence and impact of founder mutations in hereditary breast cancer in Latin America.

PMID 7550349 1995 The carrier frequency of the BRCA1 185delAG mutation is approximately 1 percent in Ashkenazi Jewish individuals.

PMID 8531968 1996 Germ-line BRCA1 mutations in Jewish and non-Jewish women with early-onset breast cancer.

PMID 18034184 2007 Breast cancer risk associated with BRCA1 and BRCA2 in diverse populations.

PMID 15994883 2005 Breast and ovarian cancer risks to carriers of the BRCA1 5382insC and 185delAG and BRCA2 6174delT mutations: a combined analysis of 22 population based studies.

PMID 21324516 2011 Frequencies of BRCA1 and BRCA2 mutations among 1,342 unselected patients with invasive ovarian cancer.

PMID 23233716 2013 Prevalence and type of BRCA mutations in Hispanics undergoing genetic cancer risk assessment in the southwestern United States: a report from the Clinical Cancer Genetics Community Research Network.

PMID 17307836 2007 Cancer risks in carriers of the BRCA1/2 Ashkenazi founder mutations.

PMID 12473589 2002 Ovarian cancer risk in Ashkenazi Jewish carriers of BRCA1 and BRCA2 mutations.

rs1567823254 in BRCA1;NBR2 gene and Hereditary Breast and Ovarian Cancer Syndrome PMID 16683254 2006 A DGGE system for comprehensive mutation screening of BRCA1 and BRCA2: application in a Dutch cancer clinic setting.

PMID 21725363 2012 Functional differences among BRCA1 missense mutations in the control of centrosome duplication.

PMID 15385441 2004 Evolution of the tumor suppressor BRCA1 locus in primates: implications for cancer predisposition.

PMID 25823446 2015 Massively Parallel Functional Analysis of BRCA1 RING Domain Variants.

PMID 16403807 2006 Genetic analysis of BRCA1 ubiquitin ligase activity and its relationship to breast cancer susceptibility.

PMID 20103620 2010 Identification of breast tumor mutations in BRCA1 that abolish its function in homologous DNA recombination.

PMID 23161852 2013 Analysis of BRCA1 variants in double-strand break repair by homologous recombination and single-strand annealing.

PMID 12827452 2003 A mutation analysis of the BRCA1 gene in 140 families from southeast France with a history of breast and/or ovarian cancer.

PMID 10923033 2000 The breast cancer information core: database design, structure, and scope.

PMID 11802209 2002 Comprehensive analysis of 989 patients with breast or ovarian cancer provides BRCA1 and BRCA2 mutation profiles and frequencies for the German population.

PMID 11595708 2001 Mutational analysis of BRCA1 and BRCA2 and clinicopathologic analysis of ovarian cancer in 82 ovarian cancer families: two common founder mutations of BRCA1 in Japanese population.

PMID 22006311 2011 Mutations in 12 genes for inherited ovarian, fallopian tube, and peritoneal carcinoma identified by massively parallel sequencing.

PMID 21922593 2011 Assessment of human Nter and Cter BRCA1 mutations using growth and localization assays in yeast.

PMID 9145677 1997 BRCA1 mutations in women attending clinics that evaluate the risk of breast cancer.

PMID 24504028 2014 Clinical characteristics of ovarian cancer classified by BRCA1, BRCA2, and RAD51C status.

PMID 21120943 2011 EMMA, a cost- and time-effective diagnostic method for simultaneous detection of point mutations and large-scale genomic rearrangements: application to BRCA1 and BRCA2 in 1,525 patients.

PMID 2246425 1990 Postoperative respiratory failure due to acute eosinophilic pneumonia.

PMID 25682074 2015 Prevalence of BRCA1 and BRCA2 germline mutations in patients with triple-negative breast cancer.

PMID 26543556 2015 Addressing health disparities in Hispanic breast cancer: accurate and inexpensive sequencing of BRCA1 and BRCA2.

PMID 22711857 2012 BRCA mutation frequency and patterns of treatment response in BRCA mutation-positive women with ovarian cancer: a report from the Australian Ovarian Cancer Study Group.

PMID 7837387 1995 A collaborative survey of 80 mutations in the BRCA1 breast and ovarian cancer susceptibility gene. Implications for presymptomatic testing and screening.

PMID 10498392 1999 Population-based estimate of the average age-specific cumulative risk of breast cancer for a defined set of protein-truncating mutations in BRCA1 and BRCA2. Australian Breast Cancer Family Study.

PMID 22763381 2013 Haplotype analysis of the 185delAG BRCA1 mutation in ethnically diverse populations.

PMID 20104584 2010 Characterization of BRCA1 and BRCA2 deleterious mutations and variants of unknown clinical significance in unilateral and bilateral breast cancer: the WECARE study.

PMID 20924075 2011 Double heterozygosity in the BRCA1 and BRCA2 genes in the Jewish population.

PMID 9145676 1997 The risk of cancer associated with specific mutations of BRCA1 and BRCA2 among Ashkenazi Jews.

PMID 9921907 1998 Identification of the 185delAG BRCA1 mutation in a Spanish Gypsy population.

PMID 9042909 1997 The founder mutations 185delAG and 5382insC in BRCA1 and 6174delT in BRCA2 appear in 60% of ovarian cancer and 30% of early-onset breast cancer patients among Ashkenazi women.

PMID 24737347 2014 BRCA1 and BRCA2 germline mutations are frequently demonstrated in both high-risk pancreatic cancer screening and pancreatic cancer cohorts.

PMID 7894492 1994 Common origins of BRCA1 mutations in Canadian breast and ovarian cancer families.

PMID 30262796 2018 Comprehensive Analysis of Germline Variants in Mexican Patients with Hereditary Breast and Ovarian Cancer Susceptibility.

PMID 15994883 2005 Breast and ovarian cancer risks to carriers of the BRCA1 5382insC and 185delAG and BRCA2 6174delT mutations: a combined analysis of 22 population based studies.

PMID 23658460 2013 High prevalence of BRCA1 and BRCA2 germline mutations with loss of heterozygosity in a series of resected pancreatic adenocarcinoma and other neoplastic lesions.

PMID 22430266 2012 Breast and ovarian cancer risk and risk reduction in Jewish BRCA1/2 mutation carriers.

PMID 16267036 2005 Application of embryonic lethal or other obvious phenotypes to characterize the clinical significance of genetic variants found in trans with known deleterious mutations.

PMID 12566964 2003 Mutations of the BRCA1 gene in hereditary breast and ovarian cancer in the Czech Republic.

PMID 8651293 1996 Two distinct origins of a common BRCA1 mutation in breast-ovarian cancer families: a genetic study of 15 185delAG-mutation kindreds.

PMID 21643751 2012 Common BRCA1 and BRCA2 mutations in breast cancer families: a meta-analysis from systematic review.

PMID 8571953 1996 Haplotype and phenotype analysis of six recurrent BRCA1 mutations in 61 families: results of an international study.

PMID 23788959 2013 Prevalence of the BRCA1 c.68_69delAG (BIC: 185delAG) mutation in women with breast cancer from north-central Poland and a review of the literature on other regions of the country.

PMID 8642955 1996 Germline BRCA1 185delAG mutations in Jewish women with breast cancer.

PMID 23867111 2013 A high-throughput functional complementation assay for classification of BRCA1 missense variants.

PMID 25863477 2015 The prevalence and spectrum of BRCA1 and BRCA2 mutations in Korean population: recent update of the Korean Hereditary Breast Cancer (KOHBRA) study.

rs786203152 in BRCA1;NBR2 gene and Malignant neoplasm of breast PMID 7939630 1994 BRCA1 mutations in primary breast and ovarian carcinomas.

PMID 8776600 1996 Comparison of BRCA1 polymorphisms, rare sequence variants and/or missense mutations in unaffected and breast/ovarian cancer populations.

PMID 9760198 1998 A high proportion of mutations in the BRCA1 gene in German breast/ovarian cancer families with clustering of mutations in the 3' third of the gene.

PMID 8723683 1996 Mutations in the BRCA1 gene in Japanese breast cancer patients.

PMID 7894491 1994 Mutations in the BRCA1 gene in families with early-onset breast and ovarian cancer.

PMID 7894493 1994 Confirmation of BRCA1 by analysis of germline mutations linked to breast and ovarian cancer in ten families.

PMID 7545954 1994 A strong candidate for the breast and ovarian cancer susceptibility gene BRCA1.

PMID 10323242 1999 Molecular characterization of germline mutations in the BRCA1 and BRCA2 genes from breast cancer families in Taiwan.

PMID 9482581 1998 Constant denaturant gel electrophoresis (CDGE) in BRCA1 mutation screening.

PMID 15133502 2004 Structure and mechanism of BRCA1 BRCT domain recognition of phosphorylated BACH1 with implications for cancer.

PMID 11114888 2000 Functional interactions between BRCA1 and the checkpoint kinase ATR during genotoxic stress.

PMID 12938098 2003 Twenty-three novel BRCA1 and BRCA2 sequence alterations in breast and/or ovarian cancer families in Southern Germany.

PMID 11301010 2001 BACH1, a novel helicase-like protein, interacts directly with BRCA1 and contributes to its DNA repair function.

PMID 28364669 2017 Suggestion of BRCA1 c.5339T>C (p.L1780P) variant confer from 'unknown significance' to 'Likely pathogenic' based on clinical evidence in Korea.

PMID 12442275 2002 BRCA1 and BRCA2 mutation analysis of early-onset and familial breast cancer cases in Mexico.

PMID 14722926 2004 Novel germline mutations in the BRCA1 and BRCA2 genes in Indian breast and breast-ovarian cancer families.

PMID 21473589 2011 Impact of BRCA1 BRCT domain missense substitutions on phosphopeptide recognition.

PMID 18285836 2008 Pathogenicity of the BRCA1 missense variant M1775K is determined by the disruption of the BRCT phosphopeptide-binding pocket: a multi-modal approach.

PMID 23867111 2013 A high-throughput functional complementation assay for classification of BRCA1 missense variants.

PMID 12427738 2003 Structural consequences of a cancer-causing BRCA1-BRCT missense mutation.

rs80356929 in BRCA1;NBR2 gene and Neoplastic Syndromes, Hereditary PMID 23867111 2013 A high-throughput functional complementation assay for classification of BRCA1 missense variants.

PMID 9523200 1998 Identification of missense and truncating mutations in the BRCA1 gene in sporadic and familial breast and ovarian cancer.

PMID 8531967 1996 BRCA1 mutations in a population-based sample of young women with breast cancer.

PMID 9544766 1998 BRCA1 mutations and breast cancer in the general population: analyses in women before age 35 years and in women before age 45 years with first-degree family history.

PMID 25823446 2015 Massively Parallel Functional Analysis of BRCA1 RING Domain Variants.

PMID 21372787 2011 Identifying the effects of BRCA1 mutations on homologous recombination using cells that express endogenous wild-type BRCA1.

PMID 27272900 2016 Functional Assessment of Genetic Variants with Outcomes Adapted to Clinical Decision-Making.

PMID 23161852 2013 Analysis of BRCA1 variants in double-strand break repair by homologous recombination and single-strand annealing.

PMID 22753008 2012 A guide for functional analysis of BRCA1 variants of uncertain significance.

PMID 12732733 2003 Binding and recognition in the assembly of an active BRCA1/BARD1 ubiquitin-ligase complex.

PMID 8807330 1996 Mutations and polymorphisms in the familial early-onset breast cancer (BRCA1) gene. Breast Cancer Information Core.

PMID 11844822 2002 BRCA1 and BRCA2 mutation frequency in women evaluated in a breast cancer risk evaluation clinic.

PMID 22006311 2011 Mutations in 12 genes for inherited ovarian, fallopian tube, and peritoneal carcinoma identified by massively parallel sequencing.

PMID 11573085 2001 Structure of a BRCA1-BARD1 heterodimeric RING-RING complex.

PMID 11526114 2001 BRCA1 RING domain cancer-predisposing mutations. Structural consequences and effects on protein-protein interactions.

PMID 26287763 2015 A high frequency of BRCA mutations in young black women with breast cancer residing in Florida.

PMID 15235020 2004 Analysis of missense variation in human BRCA1 in the context of interspecific sequence variation.

PMID 11896095 2002 Clinical characteristics of individuals with germline mutations in BRCA1 and BRCA2: analysis of 10,000 individuals.

PMID 7837387 1995 A collaborative survey of 80 mutations in the BRCA1 breast and ovarian cancer susceptibility gene. Implications for presymptomatic testing and screening.

PMID 8651293 1996 Two distinct origins of a common BRCA1 mutation in breast-ovarian cancer families: a genetic study of 15 185delAG-mutation kindreds.

PMID 9042909 1997 The founder mutations 185delAG and 5382insC in BRCA1 and 6174delT in BRCA2 appear in 60% of ovarian cancer and 30% of early-onset breast cancer patients among Ashkenazi women.

PMID 18779604 2008 Performance of BRCA1/2 mutation prediction models in Asian Americans.

PMID 23658460 2013 High prevalence of BRCA1 and BRCA2 germline mutations with loss of heterozygosity in a series of resected pancreatic adenocarcinoma and other neoplastic lesions.

PMID 19906413 2010 BRCA1 185delAG mutant protein, BRAt, up-regulates maspin in ovarian epithelial cells.

PMID 23633455 2013 Nonequivalent gene expression and copy number alterations in high-grade serous ovarian cancers with BRCA1 and BRCA2 mutations.

PMID 20104584 2010 Characterization of BRCA1 and BRCA2 deleterious mutations and variants of unknown clinical significance in unilateral and bilateral breast cancer: the WECARE study.

PMID 10090881 1999 The prevalence of common BRCA1 and BRCA2 mutations among Ashkenazi Jews.

PMID 23086583 2013 Absence of loss of heterozygosity of BRCA1 in a renal tumor from a BRCA1 germline mutation carrier.

PMID 22703879 2012 Secondary variants in individuals undergoing exome sequencing: screening of 572 individuals identifies high-penetrance mutations in cancer-susceptibility genes.

PMID 22763381 2013 Haplotype analysis of the 185delAG BRCA1 mutation in ethnically diverse populations.

PMID 22535016 2012 Double heterozygosity for mutations in BRCA1 and BRCA2 in German breast cancer patients: implications on test strategies and clinical management.

PMID 22009639 2012 Predictive factors for BRCA1/BRCA2 mutations in women with ductal carcinoma in situ.

PMID 22516946 2012 Germline BRCA1 mutations increase prostate cancer risk.

PMID 7550349 1995 The carrier frequency of the BRCA1 185delAG mutation is approximately 1 percent in Ashkenazi Jewish individuals.

PMID 28390335 2017 A case series of three Sri Lankan families with hereditary breast and ovarian cancer syndrome due to pathogenic germline mutations in the BRCA1 gene

PMID 26543556 2015 Addressing health disparities in Hispanic breast cancer: accurate and inexpensive sequencing of BRCA1 and BRCA2.

PMID 7611277 1995 Detection of eight BRCA1 mutations in 10 breast/ovarian cancer families, including 1 family with male breast cancer.

PMID 15994883 2005 Breast and ovarian cancer risks to carriers of the BRCA1 5382insC and 185delAG and BRCA2 6174delT mutations: a combined analysis of 22 population based studies.

PMID 24737347 2014 BRCA1 and BRCA2 germline mutations are frequently demonstrated in both high-risk pancreatic cancer screening and pancreatic cancer cohorts.

PMID 28477318 2017 Molecular characterization and clinical interpretation of BRCA1/BRCA2 variants in families from Murcia (south-eastern Spain) with hereditary breast and ovarian cancer: clinical-pathological features in BRCA carriers and non-carriers.

PMID 28324225 2017 Spectrum of genetic variants of BRCA1 and BRCA2 in a German single center study.

PMID 26440929 2015 Identification of germline genetic mutations in patients with pancreatic cancer.

PMID 27553291 2016 High prevalence and predominance of BRCA1 germline mutations in Pakistani triple-negative breast cancer patients.

PMID 17011978 2006 RNA-based analysis of BRCA1 and BRCA2 gene alterations.

PMID 24667779 2014 Functional characterization of BRCA1 gene variants by mini-gene splicing assay.

PMID 23942203 2014 Streamlined ion torrent PGM-based diagnostics: BRCA1 and BRCA2 genes as a model.

PMID 22762150 2012 Variation in breast cancer risk associated with factors related to pregnancies according to truncating mutation location, in the French National BRCA1 and BRCA2 mutations carrier cohort (GENEPSO).

PMID 21120943 2011 EMMA, a cost- and time-effective diagnostic method for simultaneous detection of point mutations and large-scale genomic rearrangements: application to BRCA1 and BRCA2 in 1,525 patients.

rs80358010 in BRCA1;NBR2 gene and ovarian neoplasm PMID 15145354 2004 Nonsense-mediated mRNA decay: terminating erroneous gene expression.