BRIP1

Chr 17ADSomatic

BRCA1 interacting DNA helicase 1

Also known as: BACH1, FANCJ, OF

The BRIP1 protein is a DNA helicase that maintains chromosomal stability through DNA double-strand break repair and functions in the Fanconi anemia pathway. Mutations cause Fanconi anemia complementation group J and increase susceptibility to early-onset breast cancer. BRIP1 is inherited in an autosomal dominant pattern and is extremely intolerant to loss-of-function variants (pLI near 1.0), indicating that heterozygous mutations are likely pathogenic.

GeneReviewsOMIMResearchSummary from RefSeq, OMIM, UniProt
LOFmechanismAD/SomaticLOEUF 0.792 OMIM phenotypes
Clinical SummaryBRIP1
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Gene-Disease Validity (ClinGen)
Fanconi anemia complementation group J · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

3 total gene-disease associations curated

Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
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Clinical Trials
12 active or recruiting trials — potential therapeutic options may be available
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GeneReview available — BRIP1
Authoritative clinical overview · Recommended first read
Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
0.79LOEUF
pLI 0.000
Z-score 2.92
OE 0.59 (0.460.79)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
1.20Z-score
OE missense 0.87 (0.810.93)
553 obs / 638.3 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.59 (0.460.79)
00.351.4
Missense OE0.87 (0.810.93)
00.61.4
Synonymous OE0.94
01.21.6
LoF obs/exp: 36 / 60.5Missense obs/exp: 553 / 638.3Syn Z: 0.65
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
definitiveBRIP1-related Fanconi anemiaLOFAR

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

DN
0.6841th %ile
GOF
0.3590th %ile
LOF
0.3552th %ile

The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.

Literature Evidence

DNDominant-negative pathogenic variant BRIP1 c.1045G>C is a high-risk allele for non-mucinous epithelial ovarian cancer: A case-control study.PMID:34585738
LOFWeber-Lassale et al. 2018 - study of 6341 patients with breast cancer and 706 patients with ovarian cancer, with 2189 matched female controls. Found LoF mutations (including nonsense mutations, splicing mutations, small intragenic deletions) in BRIP1 confer an increased risk for ovarian cancer, but PMID:29368626

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

BRIP1 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

Advanced Solid TumorsEwing SarcomaHepatocellular Carcinoma (HCC)

A Phase 1/1B Study of ST-01156, a Small Molecule RBM39 Degrader, in Patients With Advanced Solid Malignancies

RECRUITING
NCT07197554Phase PHASE1SEED Therapeutics, Inc.Started 2025-12-01
ST-01156
Polycythemia VeraEssential ThrombocythaemiaMyelofibrosis

Prevalence Of Germline Gene Mutations In Patients With Myeloproliferative Neoplasms With Family History

NOT YET RECRUITING
NCT06923670Phase NAFondazione Policlinico Universitario Agostino Gemelli IRCCSStarted 2025-05-21
NGS testingNGS analysis for mutations in genes involved in familial predisposition to hematological malignancies
Ovarian CancerBreast Cancer

A Bidirectional Cohort Study on Prophylactic Resection Surgery in Populations at Moderate-to-High Risk for Hereditary Ovarian Cancer

RECRUITING
NCT07532434Peking University Third HospitalStarted 2025-09-30
BRCA1 Gene MutationBRCA2 Gene MutationRAD51C Gene Mutation

TUBectomy With Delayed Oophorectomy in High Risk Women to Assess the Safety of Prevention

RECRUITING
NCT04294927Phase NAUniversity Medical Center NijmegenStarted 2020-03-01
Risk-reducing salpingectomy with delayed oophorectomyRisk-reducing salpingo-oophorectomy
Metastatic Breast CancerInvasive Breast CancerSomatic Mutation Breast Cancer (BRCA1)

Olaparib In Metastatic Breast Cancer

ACTIVE NOT RECRUITING
NCT03344965Phase PHASE2Beth Israel Deaconess Medical CenterStarted 2018-04-01
Olaparib
BRCA1 MutationPOLD1 Gene MutationCDKN2A Mutation

An Intervention to Increase Genetic Testing in Families Who May Share a Gene Mutation Related to Cancer Risk and An Intervention to Help Patients and Their Primary Care Providers Stay Up-to-date About Uncertain Genetic Test Results

RECRUITING
NCT05420064Phase NAMemorial Sloan Kettering Cancer CenterStarted 2022-12-01
Intervention Arm At-risk Relative/ARR ContactsMyGene PortalStandard of Care
Breast Cancer RiskOvarian Cancer RiskCancer Gene Mutation

Population Based Germline Testing for Early Detection and Prevention of Cancer

RECRUITING
NCT07498829Phase NAQueen Mary University of LondonStarted 2025-12-18
Genetic testing for Cancer Susceptibility Genes (CSGs) (BRCA1, BRCA2, RAD51C, RAD51D, BRIP1, PALB2, MLH1, MSH2, MSH6) and personalised breast and ovarian cancer risk
Deleterious BARD1 Gene MutationDeleterious BRCA1 Gene MutationDeleterious BRCA2 Gene Mutation

Surgery in Preventing Ovarian Cancer in Patients With Genetic Mutations

ACTIVE NOT RECRUITING
NCT02760849Phase NAM.D. Anderson Cancer CenterStarted 2016-05-02
Laboratory Biomarker AnalysisOophorectomyQuality-of-Life Assessment
Malignant Solid Neoplasms

Adapting Treatment to the Tumor Molecular Alterations for Patients With Advanced Solid Tumors: MyOwnSpecificTreatment

RECRUITING
NCT02029001Phase PHASE2Centre Leon BerardStarted 2014-03
Nilotinib (400 mg BID)Everolimus (10 mg QD)Sorafenib (400 mg BID)
Triple Negative Breast CancerBreast Cancer

Serial Circulating Tumor DNA (ctDNA) Monitoring During Adjuvant Capecitabine in Early Triple-negative Breast Cancer

RECRUITING
NCT04768426Phase PHASE2Stanford UniversityStarted 2021-02-03
Capecitabine
Prostate Cancer Metastatic Castration-ResistantAbnormal DNA RepairMetastatic Prostate Carcinoma

Abiraterone/Prednisone, Olaparib, or Abiraterone/Prednisone + Olaparib in Patients With Metastatic Castration-Resistant Prostate Cancer With DNA Repair Defects

ACTIVE NOT RECRUITING
NCT03012321Phase PHASE2Northwestern UniversityStarted 2017-01-12
OlaparibAbiraterone AcetatePrednisone
BRCA-Mutated Ovarian CarcinomaBRIP1 Gene MutationMSH2 A636P

Cascade Testing in Families With Newly Diagnosed Hereditary Breast and Ovarian Cancer Syndrome

ACTIVE NOT RECRUITING
NCT04009148NYU Langone HealthStarted 2019-03-01
CASCADE genetic screening
Clinical Literature
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