BRIP1

Chr 17ADSomatic

BRCA1 interacting DNA helicase 1

Also known as: BACH1, FANCJ, OF

The protein encoded by this gene is a member of the RecQ DEAH helicase family and interacts with the BRCT repeats of breast cancer, type 1 (BRCA1). The bound complex is important in the normal double-strand break repair function of breast cancer, type 1 (BRCA1). This gene may be a target of germline cancer-inducing mutations. [provided by RefSeq, Jul 2008]

Primary Disease Associations & Inheritance

{Breast cancer, early-onset, susceptibility to}MIM #114480

ADSomatic

Fanconi anemia, complementation group JMIM #609054

UniProtFanconi anemia complementation group J

491

ClinVar variants

Pathogenic / LP

0.00

pLI score

Active trials

Clinical Summary— BRIP1

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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.

📋

ClinVar Variants

79 Pathogenic / Likely Pathogenic· 297 VUS of 491 total submissions

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Clinical Trials

12 active or recruiting trials — potential therapeutic options may be available

Some data sources returned errors (2)

ensembl: Error: Ensembl fetch failed: 500 for https://rest.ensembl.org/lookup/symbol/homo_sapiens/BRIP1?content-type=application/json&expand=1

clinvar: Error: NCBI fetch failed: 429 https://eutils.ncbi.nlm.nih.gov/entrez/eutils/esearch.fcgi

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.

0.79LOEUF

pLI 0.000

Z-score 2.92

OE 0.59 (0.46–0.79)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.

1.20Z-score

OE missense 0.87 (0.81–0.93)

553 obs / 638.3 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.

LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.59 (0.46–0.79)

0≤0.351.4

Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.87 (0.81–0.93)

0≤0.61.4

Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.94

0≤1.21.6

LoF obs/exp: 36 / 60.5Missense obs/exp: 553 / 638.3Syn Z: 0.65

ClinVar Variant Classifications

491 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic57

Likely Pathogenic22

VUS297

Likely Benign113

Benign1

Conflicting1

Pathogenic

Likely Pathogenic

297

VUS

113

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	40	0	17	0	57
Likely Pathogenic	20	0	1	1	22
VUS	16	247	33	1	297
Likely Benign	1	13	45	54	113
Benign	0	0	0	1	1
Conflicting	—				1
Total	77	260	96	57	491

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View 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.

Gene2Phenotype Curations

BRIP1-related Fanconi anemia

definitive

ARLoss Of FunctionAbsent Gene Product

Dev. DisordersCancer

G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

BRCA1-INTERACTING PROTEIN 1; BRIP1

MIM #605882 · *

{Breast cancer, early-onset, susceptibility to}

MIM #114480

Molecular basis of disorder known

Autosomal dominantSomatic mutation

Fanconi anemia, complementation group J

MIM #609054

Molecular basis of disorder known

External Resources

Links to major genomics databases and tools

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GeneReview available — BRIP1

Authoritative clinical overview · NCBI Bookshelf · Recommended first read

Open GeneReview ↗

Clinical Literature

Landmark / reviewRecent case evidence

Key Publications

Landmark & review papers · by relevance

PubMed

Pathogenic and likely pathogenic variant prevalence among the first 10,000 patients referred for next-generation cancer panel testing.

Susswein LR et al.·Genet Med

2016Cohort

Hereditary cancer variants and homologous recombination deficiency in biliary tract cancer.

Okawa Y et al.·J Hepatol

2023

Homologous Recombination Deficiencies and Hereditary Tumors.

Yamamoto H et al.·Int J Mol Sci

2021Review

Population-based Screening for Hereditary Colorectal Cancer Variants in Japan.

Fujita M et al.·Clin Gastroenterol Hepatol

2022

Frequency of mutations in a large series of clinically ascertained ovarian cancer cases tested on multi-gene panels compared to reference controls.

Lilyquist J et al.·Gynecol Oncol

2017Cohort

Germline Mutations in the BRIP1, BARD1, PALB2, and NBN Genes in Women With Ovarian Cancer.

Ramus SJ et al.·J Natl Cancer Inst

2015

Inherited Mutations in Women With Ovarian Carcinoma.

Norquist BM et al.·JAMA Oncol

2016

Breast cancer genes: beyond BRCA1 and BRCA2.

Filippini SE et al.·Front Biosci (Landmark Ed)

2013Review

Understanding genetic variations associated with familial breast cancer.

Pal M et al.·World J Surg Oncol

2024Review

Prevalence of Germline Sequence Variations Among Patients With Pancreatic Cancer in China.

Yin L et al.·JAMA Netw Open

2022Cohort

Top 10 resultsSearch PubMed ↗

Recent Gene-Specific Literature

Gene in title · MEDLINE · newest first

Europe PMC

BRIP1-mediated RINT1 acetylation and NF-κB activation promote DNA repair and immunosuppressive microenvironment in lung adenocarcinoma.

Wu H et al.·Cancer Lett

2026

The Genetic and Molecular Analyses of Rare Candidate Germline BRIP1/FANCJ Variants Implicated in Hereditary Breast and Ovarian Cancers.

Alenezi WM et al.·Int J Mol Sci

2026🔓 Open Access

Clinical and Prognostic Relevance of BRIP1 Expression in Colorectal Cancer: Evidence from TCGA and Korean Cohorts.

Park D et al.·Medicina (Kaunas)

2025🔓 Open AccessCohort

Long-Term Survival With Olaparib Maintenance Therapy in Metastatic Pancreatic Carcinoma of a Patient Harboring Germline BRIP1 and ATM Mutations.

Birhiray RE et al.·Case Rep Oncol Med

2025🔓 Open Access

Exploration of possible association of BRIP1 pathogenic variants with central nervous system cancers in an institutional cohort.

Cappadocia J et al.·J Med Genet

2025Cohort

Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

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

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

Renal Cell CarcinomaMetastatic Renal Cell CarcinomaKidney Cancer

Study of Olaparib in Metastatic Renal Cell Carcinoma Patients With DNA Repair Gene Mutations

RECRUITING

NCT03786796Phase PHASE2Sidney Kimmel Comprehensive Cancer Center at Johns HopkinsStarted 2019-06-03

Olaparib

Gastric CancerGastroEsophageal Cancer

Study of SBRT/Olaparib Followed by Pembrolizumab/Olaparib in Gastric Cancers

ACTIVE NOT RECRUITING

NCT05379972Phase PHASE2University of Colorado, DenverStarted 2023-01-12

PembrolizumabOlaparibStereotactic Body Radiation Therapy

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

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

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

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

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)

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