Normal Function
The GNS gene provides instructions for producing an enzyme called N-acetylglucosamine-6-sulfatase. This enzyme is located in lysosomes, compartments within cells that digest and recycle different types of molecules. N-acetylglucosamine-6-sulfatase is involved in the step-wise breakdown of large molecules called glycosaminoglycans (GAGs). GAGs are composed of sugar molecules that are linked together to form a long string. To break down these large molecules, individual sugars are removed one at a time from one end of the molecule. N-acetylglucosamine-6-sulfatase removes a chemical group known as a sulfate from a subset of GAGs called heparan sulfate when the sugar N-acetylglucosamine-6-sulfate is located at the end.
Health Conditions Related to Genetic Changes
Mucopolysaccharidosis type III
Mutations in the GNS gene cause mucopolysaccharidosis type IIID (MPS IIID). Most of these mutations change single DNA building blocks (nucleotides) in the gene. All of the mutations that cause MPS IIID reduce or eliminate the function of N-acetylglucosamine-6-sulfatase.
The lack of N-acetylglucosamine-6-sulfatase activity disrupts the breakdown of heparan sulfate. As a result, partially broken down GAGs accumulate within lysosomes. Researchers believe that the accumulation of GAGs interferes with the functions of other proteins inside the lysosomes and disrupts the normal functions of cells. It is unknown why the buildup of heparan sulfate mostly affects the central nervous system in MPS IIID.
More About This Health ConditionOther Names for This Gene
- G6S
- glucosamine-6-sulfatase
- GNS_HUMAN
- MGC21274
- N-acetylglucosamine-6-sulfatase
- N-acetylglucosamine-6-sulfatase precursor
Additional Information & Resources
Tests Listed in the Genetic Testing Registry
Scientific Articles on PubMed
Catalog of Genes and Diseases from OMIM
References
- Jansen AC, Cao H, Kaplan P, Silver K, Leonard G, De Meirleir L, Lissens W, Liebaers I, Veilleux M, Andermann F, Hegele RA, Andermann E. Sanfilippo syndrome type D: natural history and identification of 3 novel mutations in the GNS Gene. Arch Neurol. 2007 Nov;64(11):1629-34. doi: 10.1001/archneur.64.11.1629. Citation on PubMed
- Valstar MJ, Bertoli-Avella AM, Wessels MW, Ruijter GJ, de Graaf B, Olmer R, Elfferich P, Neijs S, Kariminejad R, Suheyl Ezgu F, Tokatli A, Czartoryska B, Bosschaart AN, van den Bos-Terpstra F, Puissant H, Burger F, Omran H, Eckert D, Filocamo M, Simeonov E, Willems PJ, Wevers RA, Niermeijer MF, Halley DJ, Poorthuis BJ, van Diggelen OP. Mucopolysaccharidosis type IIID: 12 new patients and 15 novel mutations. Hum Mutat. 2010 May;31(5):E1348-60. doi: 10.1002/humu.21234. Citation on PubMed
- Valstar MJ, Ruijter GJ, van Diggelen OP, Poorthuis BJ, Wijburg FA. Sanfilippo syndrome: a mini-review. J Inherit Metab Dis. 2008 Apr;31(2):240-52. doi: 10.1007/s10545-008-0838-5. Epub 2008 Apr 4. Citation on PubMed
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