This gene, which is one of the largest in the human genome, encodes a member of the N-acetylglucosaminyltransferase gene family. The exact function of LARGE, a golgi protein, remains uncertain. It encodes a glycosyltransferase which participates in glycosylation of alpha-dystroglycan, and may carry out the synthesis of glycoprotein and glycosphingolipid sugar chains. It may also be involved in the addition of a repeated disaccharide unit. Mutations in this gene cause MDC1D, a novel form of congenital muscular dystrophy with severe mental retardation and abnormal glycosylation of alpha-dystroglycan. Alternative splicing of this gene results in two transcript variants that encode the same protein.
LARGE may also play a role in tumor-specific genomic rearrangements. Mutations in this gene may be involved in the development and progression of meningioma through modification of ganglioside composition and other glycosylated molecules in tumor cells.
^Dunham I, Shimizu N, Roe BA, Chissoe S, Hunt AR, Collins JE, Bruskiewich R, Beare DM, Clamp M, Smink LJ, Ainscough R, Almeida JP, Babbage A, Bagguley C, Bailey J, Barlow K, Bates KN, Beasley O, Bird CP, Blakey S, Bridgeman AM, Buck D, Burgess J, Burrill WD, O'Brien KP, et al. (Dec 1999). "The DNA sequence of human chromosome 22". Nature. 402 (6761): 489–95. doi:10.1038/990031. PMID10591208.
^ abcLongman C, Brockington M, Torelli S, Jimenez-Mallebrera C, Kennedy C, Khalil N, Feng L, Saran RK, Voit T, Merlini L, Sewry CA, Brown SC, Muntoni F (Oct 2003). "Mutations in the human LARGE gene cause MDC1D, a novel form of congenital muscular dystrophy with severe mental retardation and abnormal glycosylation of alpha-dystroglycan". Hum Mol Genet. 12 (21): 2853–61. doi:10.1093/hmg/ddg307. PMID12966029.
Nagase T, Ishikawa K, Miyajima N, et al. (1998). "Prediction of the coding sequences of unidentified human genes. IX. The complete sequences of 100 new cDNA clones from brain which can code for large proteins in vitro". DNA Res. 5 (1): 31–9. doi:10.1093/dnares/5.1.31. PMID9628581.
Brockington M, Torelli S, Prandini P, et al. (2005). "Localization and functional analysis of the LARGE family of glycosyltransferases: significance for muscular dystrophy". Hum. Mol. Genet. 14 (5): 657–65. doi:10.1093/hmg/ddi062. PMID15661757.
Fujimura K, Sawaki H, Sakai T, et al. (2005). "LARGE2 facilitates the maturation of alpha-dystroglycan more effectively than LARGE". Biochem. Biophys. Res. Commun. 329 (3): 1162–71. doi:10.1016/j.bbrc.2005.02.082. PMID15752776.
Grewal PK, McLaughlan JM, Moore CJ, et al. (2006). "Characterization of the LARGE family of putative glycosyltransferases associated with dystroglycanopathies". Glycobiology. 15 (10): 912–23. doi:10.1093/glycob/cwi094. PMID15958417.