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GNPTAB gene

N-acetylglucosamine-1-phosphate transferase subunits alpha and beta
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Normal Function

The GNPTAB gene provides instructions for making two different parts, the alpha and beta subunits, of an enzyme called GlcNAc-1-phosphotransferase. This enzyme is made up of two alpha (α), two beta (β), and two gamma (γ) subunits. The gamma subunit is produced from a different gene, called GNPTG. GlcNAc-1-phosphotransferase helps prepare certain newly made enzymes for transport to lysosomes. Lysosomes are compartments within the cell that use digestive enzymes called hydrolases to break down large molecules into smaller ones that can be reused by cells.

GlcNAc-1-phosphotransferase is involved in the first step of making a molecule called mannose-6-phosphate (M6P). M6P acts as a tag that indicates a hydrolase should be transported to the lysosome. Specifically, GlcNAc-1-phosphotransferase transfers a molecule called GlcNAc-1-phosphate to a newly produced hydrolase. In the next step, a molecule is removed to reveal an M6P attached to the hydrolase. Once a hydrolase has an M6P tag, it can be transported to a lysosome.

Health Conditions Related to Genetic Changes

Mucolipidosis II alpha/beta

Around 50 mutations in the GNPTAB gene have been found to cause mucolipidosis II alpha/beta. These mutations prevent the production of any functional GlcNAc-1-phosphotransferase. Without this enzyme, hydrolases cannot be tagged with M6P and transported to lysosomes. Instead, hydrolases end up outside the cell and have increased digestive activity. The lack of hydrolases within lysosomes causes large molecules to accumulate there. Conditions that cause molecules to build up inside lysosomes, including mucolipidosis II alpha/beta, are called lysosomal storage disorders. The signs and symptoms of mucolipidosis II alpha/beta are most likely caused by the lack of hydrolases within lysosomes and the effects these enzymes have outside the cell.

More About This Health Condition

Mucolipidosis III alpha/beta

Mutations in the GNPTAB gene have also been found to cause mucolipidosis III alpha/beta. Affected individuals have mutations that result in reduced activity of GlcNAc-1-phosphotransferase, which disrupts tagging of hydrolases with M6P. Digestive enzymes that do not receive the M6P tag end up outside the cell, where they have increased activity. The shortage of these digestive enzymes within lysosomes causes large molecules to accumulate there. Mucolipidosis III alpha/beta is also considered to be a lysosomal storage disorder. The signs and symptoms of mucolipidosis III alpha/beta are most likely due to the shortage of hydrolases inside lysosomes and the effects these enzymes have outside the cell.

More About This Health Condition

Other Names for This Gene

  • alpha-beta GlcNAc-1-phosphotransferase
  • DKFZp762B226
  • GlcNAc phosphotransferase
  • GlcNAc-1-phosphotransferase
  • GNPTA
  • GNPTA_HUMAN
  • KIAA1208
  • MGC4170
  • N-acetylglucosamine-1-phosphate transferase
  • N-acetylglucosamine-1-phosphate transferase alpha and beta subunits
  • N-acetylglucosamine-1-phosphate transferase, alpha and beta subunits
  • UDP-N-acetylglucosamine-lysosomal-enzyme N-acetylglucosamine
  • uridine 5'-diphosphate-N-acetylglucosamine: lysosomal hydrolase N-acetyl-1-phosphotransferase

Additional Information & Resources

Tests Listed in the Genetic Testing Registry

Scientific Articles on PubMed

Catalog of Genes and Diseases from OMIM

Research Resources

References

  • Bargal R, Zeigler M, Abu-Libdeh B, Zuri V, Mandel H, Ben Neriah Z, Stewart F, Elcioglu N, Hindi T, Le Merrer M, Bach G, Raas-Rothschild A. When Mucolipidosis III meets Mucolipidosis II: GNPTA gene mutations in 24 patients. Mol Genet Metab. 2006 Aug;88(4):359-63. Epub 2006 Apr 21. Erratum in: Mol Genet Metab. 2007 Jul;91(3):299. Citation on PubMed
  • Braulke T, Pohl S, Storch S. Molecular analysis of the GlcNac-1-phosphotransferase. J Inherit Metab Dis. 2008 Apr;31(2):253-7. doi: 10.1007/s10545-008-0862-5. Epub 2008 Apr 15. Review. Citation on PubMed
  • Cathey SS, Leroy JG, Wood T, Eaves K, Simensen RJ, Kudo M, Stevenson RE, Friez MJ. Phenotype and genotype in mucolipidoses II and III alpha/beta: a study of 61 probands. J Med Genet. 2010 Jan;47(1):38-48. doi: 10.1136/jmg.2009.067736. Epub 2009 Jul 16. Citation on PubMed or Free article on PubMed Central
  • Kudo M, Brem MS, Canfield WM. Mucolipidosis II (I-cell disease) and mucolipidosis IIIA (classical pseudo-hurler polydystrophy) are caused by mutations in the GlcNAc-phosphotransferase alpha / beta -subunits precursor gene. Am J Hum Genet. 2006 Mar;78(3):451-63. Epub 2006 Jan 24. Citation on PubMed or Free article on PubMed Central
  • Leroy JG, Cathey SS, Friez MJ. GNPTAB-Related Disorders. 2008 Aug 26 [updated 2019 Aug 29]. In: Adam MP, Ardinger HH, Pagon RA, Wallace SE, Bean LJH, Stephens K, Amemiya A, editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2020. Available from http://www.ncbi.nlm.nih.gov/books/NBK1828/ Citation on PubMed
  • Otomo T, Muramatsu T, Yorifuji T, Okuyama T, Nakabayashi H, Fukao T, Ohura T, Yoshino M, Tanaka A, Okamoto N, Inui K, Ozono K, Sakai N. Mucolipidosis II and III alpha/beta: mutation analysis of 40 Japanese patients showed genotype-phenotype correlation. J Hum Genet. 2009 Mar;54(3):145-51. doi: 10.1038/jhg.2009.3. Epub 2009 Feb 6. Citation on PubMed
  • Plante M, Claveau S, Lepage P, Lavoie EM, Brunet S, Roquis D, Morin C, Vézina H, Laprise C. Mucolipidosis II: a single causal mutation in the N-acetylglucosamine-1-phosphotransferase gene (GNPTAB) in a French Canadian founder population. Clin Genet. 2008 Mar;73(3):236-44. doi: 10.1111/j.1399-0004.2007.00954.x. Epub 2008 Jan 7. Citation on PubMed
  • Steet RA, Hullin R, Kudo M, Martinelli M, Bosshard NU, Schaffner T, Kornfeld S, Steinmann B. A splicing mutation in the alpha/beta GlcNAc-1-phosphotransferase gene results in an adult onset form of mucolipidosis III associated with sensory neuropathy and cardiomyopathy. Am J Med Genet A. 2005 Feb 1;132A(4):369-75. Citation on PubMed
  • Tiede S, Muschol N, Reutter G, Cantz M, Ullrich K, Braulke T. Missense mutations in N-acetylglucosamine-1-phosphotransferase alpha/beta subunit gene in a patient with mucolipidosis III and a mild clinical phenotype. Am J Med Genet A. 2005 Sep 1;137A(3):235-40. Citation on PubMed
  • Tiede S, Storch S, Lübke T, Henrissat B, Bargal R, Raas-Rothschild A, Braulke T. Mucolipidosis II is caused by mutations in GNPTA encoding the alpha/beta GlcNAc-1-phosphotransferase. Nat Med. 2005 Oct;11(10):1109-12. Epub 2005 Oct 2. Citation on PubMed
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