The world's first wiki where authorship really matters (Nature Genetics, 2008). Due credit and reputation for authors. Imagine a global collaborative knowledge base for original thoughts. Search thousands of articles and collaborate with scientists around the globe.

wikigene or wiki gene protein drug chemical gene disease author authorship tracking collaborative publishing evolutionary knowledge reputation system wiki2.0 global collaboration genes proteins drugs chemicals diseases compound
Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)



Gene Review

HEXA  -  hexosaminidase A (alpha polypeptide)

Homo sapiens

Synonyms: Beta-N-acetylhexosaminidase subunit alpha, Beta-hexosaminidase subunit alpha, Hexosaminidase subunit A, N-acetyl-beta-glucosaminidase subunit alpha
Welcome! If you are familiar with the subject of this article, you can contribute to this open access knowledge base by deleting incorrect information, restructuring or completely rewriting any text. Read more.

Disease relevance of HEXA


Psychiatry related information on HEXA

  • In many reptile species, sexual differentiation of gonads is sensitive to temperature (temperature-dependent sex determination, TSD) during a critical period of embryonic development (thermosensitive period, TSP) [6].
  • Hexosaminidase A deficiency should be considered in unexplained progressive neurologic disorders of childhood and adolescence, including isolated dementia [7].
  • Subjects were submitted to partial (PSD) (n = 6) or total (TSD) (n = 6) sleep deprivation for 40 hours before placebo or ethanol conditions [8].
  • Urinary levels of N-acetyl-beta-glucosaminidase (NAG) were measured in 58 patients with panic disorder [9].
  • Elevated levels of N-acetyl-beta-glucosaminidase in affective disorders and chemical dependence [10].

High impact information on HEXA

  • The GM2 gangliosidoses, Tay-Sachs and Sandhoff diseases, are caused by mutations in the HEXA (alpha-subunit) and HEXB (beta-subunit) genes, respectively [11].
  • We developed methods to detect the three mutations in the HEXA gene that occur with high frequency among Ashkenazi Jews: two mutations cause infantile Tay-Sachs disease, and the third causes the adult-onset form of the disease [12].
  • In 23 of 27 cases of the common form of childhood acute lymphoblastic leukemia, the activity of hexosaminidase component I was greatly increased; the activity ratio of hexosaminidase I to hexosaminidase A was greater than 0.5 in 18 of these cases, whereas for other types of leukemia and for all normal cells tested, the ratio was less than 0 [13].
  • We report a 57-year-old patient with a very mild phenotype, although residual hexosaminidase A activity in his cultured fibroblasts was less than 3% of normal activity, a level observed in juvenile onset patients [14].
  • The genotype and the low level of residual hexosaminidase A activity would be expected to produce a juvenile Sandhoff phenotype in this patient, as well as in four of his six clinically normal siblings [14].

Chemical compound and disease context of HEXA


Biological context of HEXA

  • Sequence of DNA flanking the exons of the HEXA gene, and identification of mutations in Tay-Sachs disease [20].
  • These data suggest a common origin of the HEXA and HEXB genes and account for the similar substrate specificities of the alpha-dimer subunit, hexosaminidase S, and hexosaminidase B [21].
  • Analysis of the HEXA gene showed that they were compound heterozygotes for the functionally silent 4-bp insertion in exon 11, typical of the infantile form of the disease and for a novel mutation, T538-->C, resulting in the missense Tyr180-->His [22].
  • Of the 13 introns, 12 interrupt the coding sequences at homologous positions in the HEXA and HEXB genes [23].
  • A "HEXA-like" band segregated with chromosome 15 (or X/15) but independently of chromosome 5 [24].

Anatomical context of HEXA


Associations of HEXA with chemical compounds


Regulatory relationships of HEXA


Other interactions of HEXA


Analytical, diagnostic and therapeutic context of HEXA

  • The HEXA exons were PCR amplified, and the products were analyzed for mutations by using restriction-enzyme digestion or single-strand gel electrophoresis [39].
  • CONCLUSIONS: Multiple mutation detection and analysis within the Tay-Sachs disease gene (HEXA) is possible using single cells for clinical preimplantation genetic diagnosis [40].
  • The polypeptide chains of hexosaminidase A (30 mg) were digested with trypsin, and peptides were isolated by reverse phase high pressure liquid chromatography and their amino acid sequences determined [21].
  • beta-N-Acetylhexosaminidase (hexosaminidase) I, which has an intermediate charge character between those of hexosaminidases A(alpha beta 2) and B[beta beta)2), was purified 1,500-fold from human placenta by procedures including chromatographies on concanavalin A (Con A)-Sepharose and an immunoadsorbent column [41].
  • This isoenzyme was determined by an immunological procedure, radial immunodiffusion, by which hexosaminidase A can be directly and specifically detected, even in the presence of excess amounts of hexosaminidase B [28].


  1. Mutational analyses of Tay-Sachs disease: studies on Tay-Sachs carriers of French Canadian background living in New England. Triggs-Raine, B., Richard, M., Wasel, N., Prence, E.M., Natowicz, M.R. Am. J. Hum. Genet. (1995) [Pubmed]
  2. The molecular basis of HEXA mRNA deficiency caused by the most common Tay-Sachs disease mutation. Boles, D.J., Proia, R.L. Am. J. Hum. Genet. (1995) [Pubmed]
  3. Identification of candidate active site residues in lysosomal beta-hexosaminidase A. Fernandes, M.J., Yew, S., Leclerc, D., Henrissat, B., Vorgias, C.E., Gravel, R.A., Hechtman, P., Kaplan, F. J. Biol. Chem. (1997) [Pubmed]
  4. A new mutation in the HEXA gene associated with a spinal muscular atrophy phenotype. Navon, R., Khosravi, R., Korczyn, T., Masson, M., Sonnino, S., Fardeau, M., Eymard, B., Lefevre, M., Turpin, J.C., Rondot, P. Neurology (1995) [Pubmed]
  5. The X-ray crystal structure of human beta-hexosaminidase B provides new insights into Sandhoff disease. Maier, T., Strater, N., Schuette, C.G., Klingenstein, R., Sandhoff, K., Saenger, W. J. Mol. Biol. (2003) [Pubmed]
  6. Temperature-dependent sex determination and gonadal differentiation in reptiles. Pieau, C., Dorizzi, M., Richard-Mercier, N. EXS. (2001) [Pubmed]
  7. The juvenile and chronic forms of GM2 gangliosidosis: clinical and enzymatic heterogeneity. Specola, N., Vanier, M.T., Goutières, F., Mikol, J., Aicardi, J. Neurology (1990) [Pubmed]
  8. Effects of alcohol on sleep parameters of sleep-deprived healthy volunteers. Lobo, L.L., Tufik, S. Sleep. (1997) [Pubmed]
  9. Association of levels of N-acetyl-beta-glucosaminidase with severity of psychiatric symptoms in panic disorder. Garvey, M.J., Noyes, R. Psychiatry research. (1996) [Pubmed]
  10. Elevated levels of N-acetyl-beta-glucosaminidase in affective disorders and chemical dependence. Garvey, M., Noyes, R., Cook, B., Barrickman, L., Noel, M., Ghosheh, R. Journal of affective disorders. (1990) [Pubmed]
  11. Mice lacking both subunits of lysosomal beta-hexosaminidase display gangliosidosis and mucopolysaccharidosis. Sango, K., McDonald, M.P., Crawley, J.N., Mack, M.L., Tifft, C.J., Skop, E., Starr, C.M., Hoffmann, A., Sandhoff, K., Suzuki, K., Proia, R.L. Nat. Genet. (1996) [Pubmed]
  12. Screening for carriers of Tay-Sachs disease among Ashkenazi Jews. A comparison of DNA-based and enzyme-based tests. Triggs-Raine, B.L., Feigenbaum, A.S., Natowicz, M., Skomorowski, M.A., Schuster, S.M., Clarke, J.T., Mahuran, D.J., Kolodny, E.H., Gravel, R.A. N. Engl. J. Med. (1990) [Pubmed]
  13. Expression of hexosaminidase isoenzymes in childhood leukemia. Ellis, R.B., Rapson, N.T., Patrick, A.D., Greaves, M.F. N. Engl. J. Med. (1978) [Pubmed]
  14. An unusual splicing mutation in the HEXB gene is associated with dramatically different phenotypes in patients from different racial backgrounds. McInnes, B., Potier, M., Wakamatsu, N., Melancon, S.B., Klavins, M.H., Tsuji, S., Mahuran, D.J. J. Clin. Invest. (1992) [Pubmed]
  15. A glycine250--> aspartate substitution in the alpha-subunit of hexosaminidase A causes juvenile-onset Tay-Sachs disease in a Lebanese-Canadian family. Trop, I., Kaplan, F., Brown, C., Mahuran, D., Hechtman, P. Hum. Mutat. (1992) [Pubmed]
  16. The excretion of N-acetyl-beta-glucosaminidase in glomerulonephritis. Hultberg, B., Ravnskov, U. Clin. Nephrol. (1981) [Pubmed]
  17. Randomised trial comparing two combination chemotherapy regimens (Hexa-CAF vs CHAP-5) in advanced ovarian carcinoma. Neijt, J.P., ten Bokkel Huinink, W.W., van der Burg, M.E., van Oosterom, A.T., Vriesendorp, R., Kooyman, C.D., van Lindert, A.C., Hamerlynck, J.V., van Lent, M., van Houwelingen, J.C. Lancet (1984) [Pubmed]
  18. Isolation and molecular characterization of hepatitis B virus X-protein from a baculovirus expression system. Urban, S., Hildt, E., Eckerskorn, C., Sirma, H., Kekulé, A., Hofschneider, P.H. Hepatology (1997) [Pubmed]
  19. Plasma lysosomal enzyme activity in acute myocardial infarction. Welman, E., Selwyn, A.P., Peters, T.J., Colbeck, J.F., Fox, K.M. Cardiovasc. Res. (1978) [Pubmed]
  20. Sequence of DNA flanking the exons of the HEXA gene, and identification of mutations in Tay-Sachs disease. Triggs-Raine, B.L., Akerman, B.R., Clarke, J.T., Gravel, R.A. Am. J. Hum. Genet. (1991) [Pubmed]
  21. Isolation of cDNA clones coding for the alpha-subunit of human beta-hexosaminidase. Extensive homology between the alpha- and beta-subunits and studies on Tay-Sachs disease. Korneluk, R.G., Mahuran, D.J., Neote, K., Klavins, M.H., O'Dowd, B.F., Tropak, M., Willard, H.F., Anderson, M.J., Lowden, J.A., Gravel, R.A. J. Biol. Chem. (1986) [Pubmed]
  22. Late-onset GM2 gangliosidosis: Ashkenazi Jewish family with an exon 5 mutation (Tyr180-->His) in the Hex A alpha-chain gene. De Gasperi, R., Gama Sosa, M.A., Battistini, S., Yeretsian, J., Raghavan, S., Zelnik, N., Leshinsky, E., Kolodny, E.H. Neurology (1996) [Pubmed]
  23. Characterization of the human HEXB gene encoding lysosomal beta-hexosaminidase. Neote, K., Bapat, B., Dumbrille-Ross, A., Troxel, C., Schuster, S.M., Mahuran, D.J., Gravel, R.A. Genomics (1988) [Pubmed]
  24. Immunochemical analysis of the N-acetyl hexosaminidases in human-mouse hybrids made using a double selective system. Swallow, D.M., Solomon, E., Pajunen, L. Cytogenet. Cell Genet. (1977) [Pubmed]
  25. Bicistronic lentiviral vector corrects beta-hexosaminidase deficiency in transduced and cross-corrected human Sandhoff fibroblasts. Arfi, A., Bourgoin, C., Basso, L., Emiliani, C., Tancini, B., Chigorno, V., Li, Y.T., Orlacchio, A., Poenaru, L., Sonnino, S., Caillaud, C. Neurobiol. Dis. (2005) [Pubmed]
  26. Proteolytic processing of pro-alpha and pro-beta precursors from human beta-hexosaminidase. Generation of the mature alpha and beta a beta b subunits. Mahuran, D.J., Neote, K., Klavins, M.H., Leung, A., Gravel, R.A. J. Biol. Chem. (1988) [Pubmed]
  27. Genetic variation of hexosaminidase A and arylsulfatase A activity. Correlation study in amnio-maternal pairs of cultured cells. Harzer, K., Hayashi, K. Hum. Genet. (1981) [Pubmed]
  28. Hexosaminidase A in amniotic fluid of Tay-Sachs fetuses. Geiger, B., Navon, R., Arnon, R. Clin. Chem. (1978) [Pubmed]
  29. Specific mutations in the HEXA gene among Iraqi Jewish Tay-Sachs disease carriers: dating of founder ancestor. Karpati, M., Gazit, E., Goldman, B., Frisch, A., Colombo, R., Peleg, L. Neurogenetics (2004) [Pubmed]
  30. Interrelationship of hexosaminidases A and B: conformation of the common and the unique subunit theory. Srivastava, S.K., Wiktorowicz, J.E., Awasthi, Y.C. Proc. Natl. Acad. Sci. U.S.A. (1976) [Pubmed]
  31. Six novel deleterious and three neutral mutations in the gene encoding the alpha-subunit of hexosaminidase A in non-Jewish individuals. Mules, E.H., Hayflick, S., Miller, C.S., Reynolds, L.W., Thomas, G.H. Am. J. Hum. Genet. (1992) [Pubmed]
  32. Two new mutations in a late infantile Tay-Sachs patient are both in exon 1 of the beta-hexosaminidase alpha subunit gene. Harmon, D.L., Gardner-Medwin, D., Stirling, J.L. J. Med. Genet. (1993) [Pubmed]
  33. Chemical characterization and subunit structure of human N-acetylhexosaminidases A and B. Geiger, B., Arnon, R. Biochemistry (1976) [Pubmed]
  34. Characterization of an activating factor required for hydrolysis of Gm2 ganglioside catalyzed by hexosaminidase A. Hechtman, P. Can. J. Biochem. (1977) [Pubmed]
  35. Complete localization of disulfide bonds in GM2 activator protein. Schütte, C.G., Lemm, T., Glombitza, G.J., Sandhoff, K. Protein Sci. (1998) [Pubmed]
  36. Amino acid utilization and urine protein excretion in children treated with succinylated Acinetobacter glutaminase-asparaginase. Kien, C.L., Holcenberg, J.S. Cancer Res. (1981) [Pubmed]
  37. Clinical implications of the genetics of ALS and other motor neuron diseases. Orrell, R.W., Figlewicz, D.A. Neurology (2001) [Pubmed]
  38. A method for analysing fertility of heterozygotes for autosomal recessive disorders, with special reference to cystic fibrosis, Tay-Sachs disease and phenylketonuria. Ten Kate, L.P. Ann. Hum. Genet. (1977) [Pubmed]
  39. A second mutation associated with apparent beta-hexosaminidase A pseudodeficiency: identification and frequency estimation. Cao, Z., Natowicz, M.R., Kaback, M.M., Lim-Steele, J.S., Prence, E.M., Brown, D., Chabot, T., Triggs-Raine, B.L. Am. J. Hum. Genet. (1993) [Pubmed]
  40. Primer system for single cell detection of double mutation for Tay-Sachs disease. Liu, M.C., Drury, K.C., Kipersztok, S., Zheng, W., Williams, R.S. J. Assist. Reprod. Genet. (2000) [Pubmed]
  41. Purification and characterization of beta-N-acetylhexosaminidase I from human placenta. Kinoshita, K., Taniguchi, N., Makita, A., Narita, M., Oikawa, K. J. Biochem. (1988) [Pubmed]
WikiGenes - Universities