Defective HGSNAT does not acetylate Heparan chain(1)

Stable Identifier
Reaction [transition]
Homo sapiens
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Enzyme misfolding due to missense mutations results in incorrect glycosylation therefore HGSNAT is not targeted to the lysosome and stays in the ER (Feldhammer et al. 2009). This, together with mutations giving rise to nonsense-mediated mRNA decay (Fedele & Hopwood 2010), appear to be the major molecular mechanisms underlying MPSIIIC. More than 50 mutations are known in the HGSNAT gene. Some of them drastically reduce enzyme activity; W403C/A615T double mutant (Fedele & Hopwood 2010), R344C, S518F and R384X (Fedele et al. 2007, Ruijter et al.2008).
Literature References
PubMed ID Title Journal Year
20583299 Functional analysis of the HGSNAT gene in patients with mucopolysaccharidosis IIIC (Sanfilippo C Syndrome)

Hopwood, JJ, Fedele, AO

Hum Mutat 2010
18024218 Clinical and genetic spectrum of Sanfilippo type C (MPS IIIC) disease in The Netherlands

Pshezhetsky, AV, Valstar, MJ, Van Diggelen, OP, van der Helm, RM, van de Kamp, JM, Ruijter, GJ, Wevers, RA, Durand, S, Wijburg, FA, Poorthuis, BJ

Mol Genet Metab 2008
19823584 Protein misfolding as an underlying molecular defect in mucopolysaccharidosis III type C

Pshezhetsky, AV, Feldhammer, M, Durand, S

PLoS One 2009
17397050 Mutational analysis of the HGSNAT gene in Italian patients with mucopolysaccharidosis IIIC (Sanfilippo C syndrome). Mutation in brief #959. Online

Filocamo, M, Di Rocco, M, L├╝bke, T, Sersale, G, Cosma, MP, Fedele, AO, Di Natale, P, Ballabio, A

Hum Mutat 2007
Catalyst Activity

heparan-alpha-glucosaminide N-acetyltransferase activity of HGSNAT mutants [lysosomal membrane]

Normal reaction
Functional status

Loss of function of HGSNAT mutants [lysosomal membrane]

Name Identifier Synonyms
mucopolysaccharidosis III DOID:12801 Sanfilippo's syndrome, SANFILIPPO SYNDROME B, N-sulphoglucosamine sulphohydrolase deficiency, Sanfilippo's syndrome, mucopolysaccharidosis type IIIB, NAGLU DEFICIENCY, mucopolysaccharidosis type IIIA, Mucopolysaccharidosis, MPS-III, Mucopolysaccharidosis, MPS-III-B (disorder), mucopolysaccharidosis III, SANFILIPPO SYNDROME A, N-ACETYL-ALPHA-D-GLUCOSAMINIDASE DEFICIENCY, HEPARAN SULFATE SULFATASE DEFICIENCY, mucopolysaccharidosis type III
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