Defective HEXB does not cleave the terminal GalNAc from keratan sulfate

Stable Identifier
Reaction [transition]
Homo sapiens
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There are two forms of HEX; HEXA and B. The A form is a trimer of the subunits alpha, beta A and beta B. The B form is a tetramer of 2 beta A and 2 beta B subunits. Beta-hexosaminidase B (HEXB) cleaves the terminal N-acetyl galactosamine (GalNAc) from glucosaminoglycans (GAGs) and any other molecules containing a terminal GalNAc. Defects in the beta subunits are the cause of GM2-gangliosidosis type 2 (GM2G2) (MIM:268800), also known as Sandhoff disease (Banerjee et al. 1991). HEXB mutations can result in either infantile-, juvenile-, adult- or chronic-onset forms of Sandhoff disease, with the infantile form being the most severe. A common HEXB mutation causing the infantile-onset form of Sandhoff disease is a 16kb deletion of the HEXB promoter, exons 1 to 5, and part of intron 5 and accounts for ~27% of Sandhoff alleles examined (not annotated here) (Bikker et al. 1989, Neote et al. 1990). Other, less common mutations causing the infantile form are S62L, R284*, M26Cfs*5 and I322Kfs*5 (Zhang et al. 1995, Zampieri et al. 2009, Drousiotou et al. 2000).
Literature References
PubMed ID Title Journal Year
1720305 Molecular basis of an adult form of beta-hexosaminidase B deficiency with motor neuron disease

Boyers, MJ, Siciliano, L, Banerjee, P, Oliveri, D, Horwitz, AL, Li, SC, McCabe, NR, Dawson, G

Biochem Biophys Res Commun 1991
2921040 Demonstration of a Sandhoff disease-associated autosomal 50-kb deletion by field inversion gel electrophoresis

Bolhuis, PA, de Vijlder, JJ, Wolterman, RA, van den Berg, FM, Bikker, H

Hum. Genet. 1989
7633435 A second, large deletion in the HEXB gene in a patient with infantile Sandhoff disease

Gravel, RA, Mules, EH, Zhang, ZX, Wakamatsu, N, Akerman, BR, Thomas, GH

Hum. Mol. Genet. 1995
2147027 Structure and distribution of an Alu-type deletion mutation in Sandhoff disease

Gravel, RA, McInnes, B, Neote, K, Mahuran, DJ

J. Clin. Invest. 1990
10982028 Sandhoff disease in Cyprus: population screening by biochemical and DNA analysis indicates a high frequency of carriers in the Maronite community

Oladimeji, A, Furihata, K, Anastasiadou, V, Kalakoutis, G, Suzuki, K, Christopoulos, G, Drousiotou, A, Hara, Y, Ioannou, PA, Ueno, I, Stylianidou, G, Mavrikiou, E, Fensom, AH, Georgiou, T

Hum. Genet. 2000
18758829 Molecular and functional analysis of the HEXB gene in Italian patients affected with Sandhoff disease: identification of six novel alleles

Stroppiano, M, Filocamo, M, Regis, S, Zampieri, S, Bembi, B, Carnevale, F, Bignulin, E, Rosso, N, Vlahovicek, K, Buratti, E, Dardis, A

Neurogenetics 2009
Catalyst Activity

beta-N-acetylhexosaminidase activity of HEXB mutants [lysosomal lumen]

Normal reaction
Functional status

Loss of function of HEXB mutants [lysosomal lumen]

Name Identifier Synonyms
gangliosidosis GM2 DOID:3321 GM>2< gangliosidosis (disorder)
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