|Institutional Source||Beutler Lab|
|Gene Name||BRCA1 interacting protein C-terminal helicase 1|
|Synonyms||8030460J03Rik, 3110009N10Rik, BACH1|
|Is this an essential gene?||Non essential (E-score: 0.000)|
|Stock #||P0018 (G1)|
|Chromosomal Location||86058138-86201193 bp(-) (GRCm38)|
|Type of Mutation||missense|
|DNA Base Change (assembly)||C to T at 86108868 bp|
|Amino Acid Change||Valine to Isoleucine at position 763 (V763I)|
|Ref Sequence||ENSEMBL: ENSMUSP00000043108 (fasta)|
|Gene Model||predicted gene model for transcript(s): [ENSMUST00000044423]|
|Predicted Effect||possibly damaging
AA Change: V763I
PolyPhen 2 Score 0.511 (Sensitivity: 0.88; Specificity: 0.90)
AA Change: V763I
|Meta Mutation Damage Score||0.3820|
|Coding Region Coverage||
|Validation Efficiency||72% (76/106)|
FUNCTION: This gene encodes a member of the DEAH subfamily of DEAD box helicases. A similar protein in humans is both a DNA-dependent ATPase and a 5-prime-to-3-prime DNA helicase, and plays a role in the repair of DNA double stranded breaks through interaction with the breast cancer-associated tumor suppressor BRCA1. [provided by RefSeq, Feb 2011]
PHENOTYPE: Mice homozygous for a gene trapped allele exhibit gonadal atrophy, subfertility, germ cell attrition, epithelial tumor predisposition, increased cellular sensitivity to interstrand crosslink-inducing agents, hypersensitivity to replication inhibitors, and predisposition to lymphoma. [provided by MGI curators]
|Allele List at MGI|
|Other mutations in this stock||
|Other mutations in Brip1||
|Protein Function and Prediction|
BRIP1 directly binds to BRCA1 (1); it functions as a DNA-dependent ATPase and a 5’-to-3’ DNA helicase (2). The association of BRIP1 with BRCA1 is cell cycle regulated and is required for DNA damage-induced checkpoint control during the transition from G2 to M phase (3). Further studies propose that, through the association with BRCA1, Brip1 facilitates BRCA1 DNA repair and possibly the localization of BRCA1 to DNA damage foci (4). BRIP1 is necessary to promote homologous recombination after DNA double-stranded breaks (5).
Northern blot analysis determined that BRIP1 is ubiquitously expressed with highest levels in the testis (1).
Mutations in BRIP1 are linked to early-onset breast cancer [OMIM: #114480; (1;6)] and Fanconi anemia, complementation group J [FA-J; OMIM: #609054; (7)]. FA-J is a clinically and genetically heterogeneous disorder that causes genomic instability. FA-J causes developmental abnormalities in major organ systems, early-onset bone marrow failure, and a high predisposition to cancer.
1. Cantor, S. B., Bell, D. W., Ganesan, S., Kass, E. M., Drapkin, R., Grossman, S., Wahrer, D. C., Sgroi, D. C., Lane, W. S., Haber, D. A., and Livingston, D. M. (2001) BACH1, a Novel Helicase-Like Protein, Interacts Directly with BRCA1 and Contributes to its DNA Repair Function. Cell. 105, 149-160.
2. Cantor, S., Drapkin, R., Zhang, F., Lin, Y., Han, J., Pamidi, S., and Livingston, D. M. (2004) The BRCA1-Associated Protein BACH1 is a DNA Helicase Targeted by Clinically Relevant Inactivating Mutations. Proc Natl Acad Sci U S A. 101, 2357-2362.
3. Yu, X., Chini, C. C., He, M., Mer, G., and Chen, J. (2003) The BRCT Domain is a Phospho-Protein Binding Domain. Science. 302, 639-642.
4. Peng, M., Litman, R., Jin, Z., Fong, G., and Cantor, S. B. (2006) BACH1 is a DNA Repair Protein Supporting BRCA1 Damage Response. Oncogene. 25, 2245-2253.
5. Litman, R., Peng, M., Jin, Z., Zhang, F., Zhang, J., Powell, S., Andreassen, P. R., and Cantor, S. B. (2005) BACH1 is Critical for Homologous Recombination and Appears to be the Fanconi Anemia Gene Product FANCJ. Cancer Cell. 8, 255-265.
6. Seal, S., Thompson, D., Renwick, A., Elliott, A., Kelly, P., Barfoot, R., Chagtai, T., Jayatilake, H., Ahmed, M., Spanova, K., North, B., McGuffog, L., Evans, D. G., Eccles, D., Breast Cancer Susceptibility Collaboration (UK), Easton, D. F., Stratton, M. R., and Rahman, N. (2006) Truncating Mutations in the Fanconi Anemia J Gene BRIP1 are Low-Penetrance Breast Cancer Susceptibility Alleles. Nat Genet. 38, 1239-1241.
7. Levran, O., Attwooll, C., Henry, R. T., Milton, K. L., Neveling, K., Rio, P., Batish, S. D., Kalb, R., Velleuer, E., Barral, S., Ott, J., Petrini, J., Schindler, D., Hanenberg, H., and Auerbach, A. D. (2005) The BRCA1-Interacting Helicase BRIP1 is Deficient in Fanconi Anemia. Nat Genet. 37, 931-933.
|Science Writer||Anne Murray|