Skip Navigation
Genetics Home Reference: your guide to understanding genetic conditions
http://ghr.nlm.nih.gov/     A service of the U.S. National Library of Medicine®

GNPTAB

Reviewed August 2009

What is the official name of the GNPTAB gene?

The official name of this gene is “N-acetylglucosamine-1-phosphate transferase, alpha and beta subunits.”

GNPTAB is the gene's official symbol. The GNPTAB gene is also known by other names, listed below.

What is the normal function of the GNPTAB gene?

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.

Does the GNPTAB gene share characteristics with other genes?

The GNPTAB gene belongs to a family of genes called EF-hand domain containing (EF-hand domain containing).

A gene family is a group of genes that share important characteristics. Classifying individual genes into families helps researchers describe how genes are related to each other. For more information, see What are gene families? (http://ghr.nlm.nih.gov/handbook/howgeneswork/genefamilies) in the Handbook.

How are changes in the GNPTAB gene related to health conditions?

mucolipidosis II alpha/beta - caused by mutations in the GNPTAB gene

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.

mucolipidosis III alpha/beta - caused by mutations in the GNPTAB gene

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.

Where is the GNPTAB gene located?

Cytogenetic Location: 12q23.2

Molecular Location on chromosome 12: base pairs 101,745,496 to 101,830,866

The GNPTAB gene is located on the long (q) arm of chromosome 12 at position 23.2.

The GNPTAB gene is located on the long (q) arm of chromosome 12 at position 23.2.

More precisely, the GNPTAB gene is located from base pair 101,745,496 to base pair 101,830,866 on chromosome 12.

See How do geneticists indicate the location of a gene? (http://ghr.nlm.nih.gov/handbook/howgeneswork/genelocation) in the Handbook.

Where can I find additional information about GNPTAB?

You and your healthcare professional may find the following resources about GNPTAB helpful.

You may also be interested in these resources, which are designed for genetics professionals and researchers.

What other names do people use for the GNPTAB gene or gene products?

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

See How are genetic conditions and genes named? (http://ghr.nlm.nih.gov/handbook/mutationsanddisorders/naming) in the Handbook.

What glossary definitions help with understanding GNPTAB?

cell ; digestive ; enzyme ; gene ; hydrolase ; lysosome ; mannose ; molecule ; phosphate ; subunit ; transferase

You may find definitions for these and many other terms in the Genetics Home Reference Glossary (http://www.ghr.nlm.nih.gov/glossary).

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. (http://www.ncbi.nlm.nih.gov/pubmed/16630736?dopt=Abstract)
  • 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. (http://www.ncbi.nlm.nih.gov/pubmed/18425436?dopt=Abstract)
  • 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. (http://www.ncbi.nlm.nih.gov/pubmed/19617216?dopt=Abstract)
  • Gene Review: Mucolipidosis II (http://www.ncbi.nlm.nih.gov/books/NBK1828)
  • Gene Review: Mucolipidosis III Alpha/Beta (http://www.ncbi.nlm.nih.gov/books/NBK1875)
  • 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. (http://www.ncbi.nlm.nih.gov/pubmed/16465621?dopt=Abstract)
  • OMIM: N-ACETYLGLUCOSAMINE-1-PHOSPHOTRANSFERASE, ALPHA/BETA SUBUNITS (http://omim.org/entry/607840)
  • NCBI Gene (http://www.ncbi.nlm.nih.gov/gene/79158)
  • 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. (http://www.ncbi.nlm.nih.gov/pubmed/19197337?dopt=Abstract)
  • 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. (http://www.ncbi.nlm.nih.gov/pubmed/18190596?dopt=Abstract)
  • 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. (http://www.ncbi.nlm.nih.gov/pubmed/15633164?dopt=Abstract)
  • 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. (http://www.ncbi.nlm.nih.gov/pubmed/16094673?dopt=Abstract)
  • 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. (http://www.ncbi.nlm.nih.gov/pubmed/16200072?dopt=Abstract)

 

The resources on this site should not be used as a substitute for professional medical care or advice. Users seeking information about a personal genetic disease, syndrome, or condition should consult with a qualified healthcare professional. See How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.

 
Reviewed: August 2009
Published: December 22, 2014