GeneID: 230

Description:
LARGE1 is a member of the N-acetylglucosaminyltransferase gene family. It encodes a glycosyltransferase that is involved in O-linked glycosylation. It is a bifunctional enzyme that alternately transfers xylose and glucuronic acid to α-dystroglycan (transmembrane protein that links the extracellular matrix to the cytoskeleton, NCBI: 1605), facilitating the synthesis of O-mannosyl glycans that are required for binding to laminin-G domain-containing extracellular matrix ligands. Therefore, the LARGE modification of α-dystroglycan confers its ligand-binding activity and is involved in the maintenance of skeletal muscle membrane integrity and the structure and function of the central nervous system. Mutations in this gene cause MDC1D, a form of congenital muscular dystrophy with severe mental retardation and abnormal glycosylation of α-dystroglycan. A polymorphism in this gene associated with fetal haemoglobin levels in patients with sickle cell disease. Alternative splicing of this gene results in two transcript variants that encode the same protein.

Synonyms: LARGE , MDC1D , MDDGA6 , MDDGB6

Comments:
N/A

Number of entries/variants: 1

1. Inamori K, Yoshida-Moriguchi T, Hara Y, Anderson ME, Yu L, Campbell KP, Dystroglycan function requires xylosyl- and glucuronyltransferase activities of LARGE., Science , 335(6064), 93-6, 2012 PubMed
2. Inamori K, Willer T, Hara Y, Venzke D, Anderson ME, Clarke NF, Guicheney P, Bönnemann CG, Moore SA, Campbell KP, Endogenous glucuronyltransferase activity of LARGE or LARGE2 required for functional modification of α-dystroglycan in cells and tissues., J. Biol. Chem. , 289(41), 28138-48, 2014 PubMed
3. Shaikho EM, Farrell JJ, Alsultan A, Sebastiani P, Steinberg MH, Genetic Determinants of HbF in Saudi Arabian and African Benin Haplotype Sickle Cell Anemia., Am. J. Hematol. , 2017 PubMed