The HEXB gene provides instructions for making a protein that is a part (subunit) of two related enzymes, beta-hexosaminidase A and beta-hexosaminidase B. Each of these enzymes is made up of two subunits. Beta-hexosaminidase A includes one alpha subunit (produced from the HEXA gene) and one beta subunit (produced from the HEXB gene). Beta-hexosaminidase B is composed of two beta subunits, which are produced from the HEXB gene.
Beta-hexosaminidase A and beta-hexosaminidase B play a critical role in the brain and spinal cord (central nervous system). These enzymes are found in lysosomes, which are structures in cells that break down toxic substances and act as recycling centers. Within lysosomes, the enzymes break down fatty compounds called sphingolipids, complex sugars called oligosaccharides, and molecules that are linked to sugars (such as glycoproteins). In particular, beta-hexosaminidase A forms part of a complex that breaks down a fatty substance called GM2 ganglioside.
Health Conditions Related to Genetic Changes
About 30 mutations that cause Sandhoff disease have been identified in the HEXB gene. These mutations reduce or eliminate the activity of both beta-hexosaminidase A and beta-hexosaminidase B. The malfunctioning or missing enzymes are unable to break down GM2 ganglioside and other molecules, which allows these compounds to accumulate within cells. Increased levels of GM2 ganglioside are particularly toxic to nerve cells in the central nervous system. Excess GM2 ganglioside leads to the progressive destruction of these cells, which causes many of the characteristic features of Sandhoff disease.
Most of the known mutations in the HEXB gene cause the severe form of Sandhoff disease, which becomes apparent in infancy. These mutations prevent cells from making any beta-hexosaminidase A or beta-hexosaminidase B, or lead to the production of completely nonfunctional versions of these enzymes. The most common mutation deletes a large segment of DNA near the beginning of the HEXB gene, which results in a total loss of enzyme activity. Other mutations reduce but do not eliminate the activity of the enzymes; these genetic changes are responsible for the less severe forms of Sandhoff disease, which appear later in life.More About This Health Condition
Other Names for This Gene
- beta-N-acetylhexosaminidase B
- Hex B
- hexosaminidase B
- hexosaminidase B (beta polypeptide)
Additional Information & Resources
Tests Listed in the Genetic Testing Registry
Scientific Articles on PubMed
Catalog of Genes and Diseases from OMIM
- Lemieux MJ, Mark BL, Cherney MM, Withers SG, Mahuran DJ, James MN. Crystallographic structure of human beta-hexosaminidase A: interpretation of Tay-Sachs mutations and loss of GM2 ganglioside hydrolysis. J Mol Biol. 2006 Jun 16;359(4):913-29. Epub 2006 Apr 27. Citation on PubMed or Free article on PubMed Central
- Mahuran DJ. Biochemical consequences of mutations causing the GM2 gangliosidoses. Biochim Biophys Acta. 1999 Oct 8;1455(2-3):105-38. Review. Citation on PubMed
- Maier T, Strater N, Schuette CG, Klingenstein R, Sandhoff K, Saenger W. The X-ray crystal structure of human beta-hexosaminidase B provides new insights into Sandhoff disease. J Mol Biol. 2003 May 2;328(3):669-81. Citation on PubMed
- Mark BL, Mahuran DJ, Cherney MM, Zhao D, Knapp S, James MN. Crystal structure of human beta-hexosaminidase B: understanding the molecular basis of Sandhoff and Tay-Sachs disease. J Mol Biol. 2003 Apr 11;327(5):1093-109. Citation on PubMed or Free article on PubMed Central
- Myerowitz R, Lawson D, Mizukami H, Mi Y, Tifft CJ, Proia RL. Molecular pathophysiology in Tay-Sachs and Sandhoff diseases as revealed by gene expression profiling. Hum Mol Genet. 2002 May 15;11(11):1343-50. Citation on PubMed