Defective EXT2 (in EXT1:EXT2) does not transfer GlcNAc to the heparan chain

Stable Identifier
Reaction [transition]
Homo sapiens
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Exostosin 1 and 2 (EXT1 and 2) are dual-specific glycosyltransferases required to form heparan sulfate (HS) which is involved in regulating various body functions during development, homeostasis and pathology including blood clotting, angiogenesis and metastasis of cancer cells. They are able to transfer N-acetylglucosamine (GlcNAc) and glucuronate (GlcA) to HS during its synthesis. Defects in EXT2 cause exostoses 2 (MIM:133701), an autosomal dominant disorder characterised by multiple projections of bone capped by cartilage resulting in deformed legs, forearms and hands. Mutations causing exostoses 2 are V187Pfs*115, A361Pfs*44, D227N, G172*, Q258* and Y222* (Stickens et al. 1996, Wyuts et al. 1996, Philippe et al. 1997, Heinritz et al. 2009).
Literature References
PubMed ID Title Journal Year
8894688 Positional cloning of a gene involved in hereditary multiple exostoses

Willems, PJ, Wauters, J, Mallet, L, Fransen, E, Halley, DJ, De Boulle, K, Reyniers, E, Shows, TB, Balemans, W, Herrygers, I, de Vries, BB, Coucke, P, Nowak, NJ, Bossuyt, P, van den Ouweland, AM, Vits, L, Van Hul, EV, Van Hul, W, Hendrickx, J, Wuyts, W, Nemtsova, M, McGaughran, J

Hum. Mol. Genet. 1996
8782816 The EXT2 multiple exostoses gene defines a family of putative tumour suppressor genes

Hogue, D, Hecht, JT, Evans, GA, Ramos, P, Burbee, D, Stickens, D, Lovett, M, Thomas, S, Clines, G

Nat. Genet. 1996
19344451 New mutations of EXT1 and EXT2 genes in German patients with Multiple Osteochondromas

Strenge, S, Zweier, C, Bohring, A, Froster, UG, Leinung, S, Miterski, B, Heinritz, W, Mitulla, B, H├╝ffmeier, U, Peters, U

Ann. Hum. Genet. 2009
9326317 Mutation screening of the EXT1 and EXT2 genes in patients with hereditary multiple exostoses

Emerton, ME, Philippe, C, Wells, DE, Monaco, AP, Simpson, AH, Porter, DE

Am. J. Hum. Genet. 1997
Catalyst Activity

glucuronosyl-N-acetylglucosaminyl-proteoglycan 4-alpha-N-acetylglucosaminyltransferase activity of EXT1:EXT2 mutants [Golgi membrane]

Normal reaction
Functional status

Loss of function of EXT1:EXT2 mutants [Golgi membrane]

Name Identifier Synonyms
hereditary multiple exostoses DOID:206 Osteochondromatosis syndrome (disorder) [Ambiguous], Multiple exostosis syndromes, Multiple congenital exostosis
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