Target intelligence / Profile preview

BRCA1 interacting protein C-terminal helicase 1 (BRIP1)

Target: BRIP1
Molecular classification: Enzyme, Helicase (DEAH helicase family), DNA repair protein, Fanconi anemia (FA) pathway protein

Overview

BRCA1 interacting protein C-terminal helicase 1 (BRIP1) is a DNA-dependent ATPase and a 5′–3′ DNA helicase from the DEAH helicase family that plays a vital role in DNA double-strand break repair via homologous recombination, operates in concert with BRCA1 and the Fanconi anemia pathway, and maintains genome stability[2][3][5]. Germline mutations cause Fanconi anemia (complementation group J) and increase susceptibility to ovarian, breast, and other cancers, where BRIP1 may act as a tumor suppressor or oncogenic factor depending on context[1][2][3][4][5]. BRIP1 is both a biomarker and emerging therapeutic target, especially where PARP inhibitors are used in precision oncology for DNA repair-defective tumors[1][5].

Other names: BRIP1BACH1FANCJFanconi anemia group J proteinBRCA1-associated C-terminal helicase-1

Mechanism of action

Synthetic lethality (e.g., inhibition of PARP in cells with defective BRIP1-mediated DNA repair)[1]; Inhibition of homologous recombination repair pathways causing tumor cell death

Biological functions

DNA repair (homologous recombination)Genome stability maintenanceDNA replication stress responseCell cycle checkpoint regulation (G2–M phase)Tumor suppressionRegulation of cell proliferation and invasion

Disease associations

Cancer (notably ovarian, breast, pancreatic)Fanconi anemiaTumor suppression and cancer predispositionPossibly neurodegenerative disorders (due to roles in neuronal DNA repair)

Safety considerations

Risk of myelosuppression and secondary malignancies (with DNA repair pathway inhibition)Potential for anemia, bone marrow failure (in germline mutations, Fanconi anemia context)Genomic instability leading to cancer predisposition in BRIP1-deficient individuals

Interacting drugs

PARP inhibitors (approved; e.g., olaparib, niraparib, rucaparib for BRIP1-mutated tumors)[1]

1 more in the full profile.

Biomarkers

BRIP1 gene mutation (germline or somatic) as a predictive biomarker for PARP inhibitor therapy in ovarian cancer[1][5]BRIP1 expression or methylation patterns in cancer prognosis and response prediction[5]Loss-of-function mutations as diagnostic for Fanconi anemia complementation group J

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