The HEXA gene provides instructions for making one part (subunit) of an enzyme called beta-hexosaminidase A. Specifically, the protein produced from the HEXA gene forms the alpha subunit of this enzyme. One alpha subunit joins with one beta subunit (produced from the HEXB gene) to form a functioning enzyme.
Beta-hexosaminidase A plays a critical role in the brain and spinal cord (central nervous system). This enzyme is found in lysosomes, which are structures in cells that break down toxic substances and act as recycling centers. Within lysosomes, beta-hexosaminidase A forms part of a complex that breaks down a fatty substance called GM2 ganglioside.
Health Conditions Related to Genetic Changes
More than 120 mutations that cause Tay-Sachs disease have been identified in the HEXA gene. These mutations reduce or eliminate the activity of the enzyme beta-hexosaminidase A, which prevents the enzyme from breaking down GM2 ganglioside. As a result, this substance builds up to toxic levels, particularly in nerve cells in the brain and spinal cord. Progressive damage caused by the buildup of GM2 ganglioside leads to the destruction of these cells, which causes the signs and symptoms of Tay-Sachs disease.
Most of the known HEXA mutations result in a completely nonfunctional version of beta-hexosaminidase A. These mutations cause the severe form of Tay-Sachs disease, which appears in infancy. Other mutations reduce but do not eliminate the activity of beta-hexosaminidase A; these genetic changes are responsible for the less severe forms of Tay-Sachs disease, which appear later in life.More About This Health Condition
Other Names for This Gene
- Beta-hexosaminidase A
- beta-N-Acetylhexosaminidase A
- Hex A
- hexosaminidase A (alpha polypeptide)
Additional Information & Resources
Tests Listed in the Genetic Testing Registry
Scientific Articles on PubMed
Catalog of Genes and Diseases from OMIM
- Chavany C, Jendoubi M. Biology and potential strategies for the treatment of GM2 gangliosidoses. Mol Med Today. 1998 Apr;4(4):158-65. Review. Citation on PubMed
- 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
- Matsuzawa F, Aikawa S, Sakuraba H, Lan HT, Tanaka A, Ohno K, Sugimoto Y, Ninomiya H, Doi H. Structural basis of the GM2 gangliosidosis B variant. J Hum Genet. 2003;48(11):582-9. Epub 2003 Oct 24. Citation on PubMed
- Montalvo AL, Filocamo M, Vlahovicek K, Dardis A, Lualdi S, Corsolini F, Bembi B, Pittis MG. Molecular analysis of the HEXA gene in Italian patients with infantile and late onset Tay-Sachs disease: detection of fourteen novel alleles. Hum Mutat. 2005 Sep;26(3):282. Citation on PubMed
- 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
- Toro C, Shirvan L, Tifft C. HEXA Disorders. 1999 Mar 11 [updated 2020 Oct 1]. In: Adam MP, Ardinger HH, Pagon RA, Wallace SE, Bean LJH, Mirzaa G, Amemiya A, editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2021. Available from http://www.ncbi.nlm.nih.gov/books/NBK1218/ Citation on PubMed