Variant position:  1775

Type of variant:  LP/P [Disclaimer: Variants classification is intended for research purposes only, not for clinical and diagnostic use. The label disease variant is assigned according to literature reports on probable disease-association that can be based on theoretical reasons. This label must not be considered as a definitive proof for the pathogenic role of a variant.]

Residue change:  From Methionine (M) to Arginine (R) at position 1775 (M1775R, p.Met1775Arg).

Physico-chemical properties:  Change from medium size and hydrophobic (M) to large size and basic (R)

BLOSUM score:  -1

Variant description:  In BC; alters protein stability and abolishes ACACA and BRIP1 binding.

Other resources:  

• Variant rs41293463 [ dbSNP | Ensembl ]

Variant position:  1775

Protein sequence length:  1863

Location on the sequence:   SQDRKIFRGLEICCYGPFTN  M PTDQLEWMVQLCGASVVKEL

Residue conservation: 

Human                         SQDRKIFRGLEICCYGPFTNMPTDQLEWMVQL---CGASVVKEL

Gorilla                       SQDRKIFRGLDICCYGPFTNMPTDQLEWMVQL---CGASVV

Rhesus macaque                SPDRKIFRGLEICCYGPFTNMPTDQLEWMVQL---CGASVV

Chimpanzee                    SQDRKIFRGLEICCYGPFTNMPTDQLEWMVQL---CGASVV

Mouse                         SRE-KLFKGLQVYCCEPFTNMPKDELERMLQL---CGASVV

Rat                           SQE-KLFEGLQIYCCEPFTNMPKDELERMLQL---CGASVV

Bovine                        SRDKKIFKGLEICCYGPFTNMPTDQLEWMVQL---CGASVV

Caenorhabditis elegans        DEHGKLFAGRRFMILRKFTMNPYFDYKQLIELVQQCGGEIL

Sequence annotation in neighborhood:  

A strong candidate for the breast and ovarian cancer susceptibility gene BRCA1.
Miki Y.; Swensen J.; Shattuck-Eidens D.; Futreal P.A.; Harshman K.; Tavtigian S.; Liu Q.; Cochran C.; Bennett L.M.; Ding W.; Bell R.; Rosenthal J.; Hussey C.; Tran T.; McClure M.; Frye C.; Hattier T.; Phelps R.; Haugen-Strano A.; Katcher H.; Yakumo K.; Gholami Z.; Shaffer D.; Stone S.; Bayer S.; Wray C.; Bogden R.; Dayananth P.; Ward J.; Tonin P.; Narod S.; Bristow P.K.; Norris F.H.; Helvering L.; Morrison P.; Rosteck P.; Lai M.; Barrett J.C.; Lewis C.; Neuhausen S.; Cannon-Albright L.; Godlgar D.; Wiseman R.; Kamb A.; Skolnick M.H.;
Science 266:66-71(1994)
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1); VARIANT BC ARG-1775;

BACH1, a novel helicase-like protein, interacts directly with BRCA1 and contributes to its DNA repair function.
Cantor S.B.; Bell D.W.; Ganesan S.; Kass E.M.; Drapkin R.; Grossman S.; Wahrer D.C.R.; Sgroi D.C.; Lane W.S.; Haber D.A.; Livingston D.M.;
Cell 105:149-160(2001)
Cited for: INTERACTION WITH BRIP1; CHARACTERIZATION OF VARIANT OVARIAN CANCER ARG-1749; CHARACTERIZATION OF VARIANT BC ARG-1775;

Structural consequences of a cancer-causing BRCA1-BRCT missense mutation.
Williams R.S.; Glover J.N.;
J. Biol. Chem. 278:2630-2635(2003)
Cited for: X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) OF 1646-1859 OF VARIANT BC ARG-1775; CHARACTERIZATION OF VARIANT BC ARG-1775; CIRCULAR DICHROISM;

Structure and mechanism of BRCA1 BRCT domain recognition of phosphorylated BACH1 with implications for cancer.
Clapperton J.A.; Manke I.A.; Lowery D.M.; Ho T.; Haire L.F.; Yaffe M.B.; Smerdon S.J.;
Nat. Struct. Mol. Biol. 11:512-518(2004)
Cited for: X-RAY CRYSTALLOGRAPHY (1.85 ANGSTROMS) OF 1649-1859 IN COMPLEX WITH PHOSPHORYLATED BRIP1 PEPTIDE; MUTAGENESIS OF SER-1655; LYS-1702 AND GLY-1738; CHARACTERIZATION OF VARIANT OVARIAN CANCER ARG-1749; CHARACTERIZATION OF VARIANT BC ARG-1775; SUBCELLULAR LOCATION; INTERACTION WITH PHOSPHORYLATED BRIP1;

BRCA1 mutations in primary breast and ovarian carcinomas.
Futreal P.A.; Liu Q.; Shattuck-Eidens D.; Cochran C.; Harshman K.; Tavtigian S.; Bennett L.M.; Haugen-Strano A.; Swensen J.; Miki Y.; Eddington K.; McClure M.; Frye C.; Weaver-Felhaus J.; Ding W.; Gholami Z.; Soederkvist P.; Terry L.; Jhanwar S.; Berchuk A.; Iglehart J.D.; Marks J.; Ballinger D.G.; Barrett J.C.; Skolnick M.H.; Kamb A.; Wiseman R.;
Science 266:120-122(1994)
Cited for: VARIANT BC ARG-1775; VARIANTS LEU-1637 AND GLU-1708;