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Genetics Home Reference: your guide to understanding genetic conditions
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GNE

Reviewed December 2008

What is the official name of the GNE gene?

The official name of this gene is “glucosamine (UDP-N-acetyl)-2-epimerase/N-acetylmannosamine kinase.”

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

What is the normal function of the GNE gene?

The GNE gene provides instructions for making an enzyme that is found in cells and tissues throughout the body. This enzyme plays a key role in a chemical pathway that produces sialic acid, which is a simple sugar that attaches to the ends of more complex molecules on the surface of cells. By modifying these molecules, sialic acid influences a wide variety of cellular functions including cell movement (migration), attaching cells to one another (adhesion), signaling between cells, and inflammation.

The enzyme produced from the GNE gene is responsible for two steps in the formation of sialic acid. It first converts a molecule known as UDP-GlcNAc to a similar molecule called ManNAc. In the next step, the enzyme transfers a cluster of oxygen and phosphorus atoms (a phosphate group) to ManNAc to create ManNAc-6-phosphate. Other enzymes then convert ManNAc-6-phosphate to sialic acid.

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

inclusion body myopathy 2 - caused by mutations in the GNE gene

More than 40 mutations in the GNE gene have been identified in people with inclusion body myopathy 2. Most of these mutations change single protein building blocks (amino acids) in several regions of the enzyme. A few mutations delete a piece of the enzyme or otherwise alter its structure.

Different GNE mutations cause inclusion body myopathy 2 in different populations. One mutation causes the disorder in people of Iranian Jewish heritage; this genetic change replaces the amino acid methionine with the amino acid threonine at position 712 in a region of the enzyme known as the kinase domain (written as Met712Thr or M712T). In the Japanese population, where the condition is called Nonaka myopathy, the most common GNE mutation replaces the amino acid valine with the amino acid leucine at position 572 in the enzyme's kinase domain (written as Val572Leu or V572L).

The mutations responsible for inclusion body myopathy 2 reduce the activity of the enzyme produced from the GNE gene, which decreases the production of sialic acid. As a result, less of this simple sugar is available to attach to cell surface molecules. Researchers are working to determine how a shortage of sialic acid leads to progressive muscle weakness in people with inclusion body myopathy 2. Sialic acid is important for the normal function of many different cells and tissues, so it is unclear why the signs and symptoms of this disorder appear to be limited to the skeletal muscles.

sialuria - caused by mutations in the GNE gene

Several mutations in the GNE gene have been found to cause sialuria. Each of these mutations changes a single amino acid in a region of the enzyme known as the allosteric site. This region is critical for the normal regulation of the enzyme.

The enzyme produced from the GNE gene is carefully controlled to ensure that cells produce an appropriate amount of sialic acid. A feedback system shuts off the enzyme when no more sialic acid is needed. Mutations in the allosteric site disrupt this feedback mechanism, resulting in an overproduction of sialic acid. This simple sugar builds up within cells and is excreted in urine. Researchers are working to determine how an accumulation of sialic acid in the body interferes with normal development in people with sialuria.

Where is the GNE gene located?

Cytogenetic Location: 9p13.3

Molecular Location on chromosome 9: base pairs 36,214,440 to 36,277,055

The GNE gene is located on the short (p) arm of chromosome 9 at position 13.3.

The GNE gene is located on the short (p) arm of chromosome 9 at position 13.3.

More precisely, the GNE gene is located from base pair 36,214,440 to base pair 36,277,055 on chromosome 9.

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 GNE?

You and your healthcare professional may find the following resources about GNE 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 GNE gene or gene products?

  • Bifunctional UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase
  • DMRV
  • GLCNE
  • GLCNE_HUMAN
  • IBM2
  • N-acylmannosamine kinase
  • Uae1
  • UDP-GlcNAc-2-epimerase/ManAc kinase
  • UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase

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 GNE?

acids ; amino acid ; cell ; domain ; enzyme ; gene ; glycolipids ; glycoproteins ; inclusion body ; inflammation ; kinase ; leucine ; methionine ; molecule ; mutation ; oxygen ; phosphate ; phosphorus ; population ; protein ; sialic acid ; simple sugar ; threonine ; valine

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

References

  • Argov Z, Eisenberg I, Grabov-Nardini G, Sadeh M, Wirguin I, Soffer D, Mitrani-Rosenbaum S. Hereditary inclusion body myopathy: the Middle Eastern genetic cluster. Neurology. 2003 May 13;60(9):1519-23. (http://www.ncbi.nlm.nih.gov/pubmed/12743242?dopt=Abstract)
  • Eisenberg I, Avidan N, Potikha T, Hochner H, Chen M, Olender T, Barash M, Shemesh M, Sadeh M, Grabov-Nardini G, Shmilevich I, Friedmann A, Karpati G, Bradley WG, Baumbach L, Lancet D, Asher EB, Beckmann JS, Argov Z, Mitrani-Rosenbaum S. The UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase gene is mutated in recessive hereditary inclusion body myopathy. Nat Genet. 2001 Sep;29(1):83-7. (http://www.ncbi.nlm.nih.gov/pubmed/11528398?dopt=Abstract)
  • Eisenberg I, Grabov-Nardini G, Hochner H, Korner M, Sadeh M, Bertorini T, Bushby K, Castellan C, Felice K, Mendell J, Merlini L, Shilling C, Wirguin I, Argov Z, Mitrani-Rosenbaum S. Mutations spectrum of GNE in hereditary inclusion body myopathy sparing the quadriceps. Hum Mutat. 2003 Jan;21(1):99. (http://www.ncbi.nlm.nih.gov/pubmed/12497639?dopt=Abstract)
  • Kayashima T, Matsuo H, Satoh A, Ohta T, Yoshiura K, Matsumoto N, Nakane Y, Niikawa N, Kishino T. Nonaka myopathy is caused by mutations in the UDP-N-acetylglucosamine-2-epimerase/N-acetylmannosamine kinase gene (GNE). J Hum Genet. 2002;47(2):77-9. (http://www.ncbi.nlm.nih.gov/pubmed/11916006?dopt=Abstract)
  • Keppler OT, Hinderlich S, Langner J, Schwartz-Albiez R, Reutter W, Pawlita M. UDP-GlcNAc 2-epimerase: a regulator of cell surface sialylation. Science. 1999 May 21;284(5418):1372-6. (http://www.ncbi.nlm.nih.gov/pubmed/10334995?dopt=Abstract)
  • Klootwijk RD, Savelkoul PJ, Ciccone C, Manoli I, Caplen NJ, Krasnewich DM, Gahl WA, Huizing M. Allele-specific silencing of the dominant disease allele in sialuria by RNA interference. FASEB J. 2008 Nov;22(11):3846-52. doi: 10.1096/fj.08-110890. Epub 2008 Jul 24. (http://www.ncbi.nlm.nih.gov/pubmed/18653764?dopt=Abstract)
  • Krause S, Aleo A, Hinderlich S, Merlini L, Tournev I, Walter MC, Argov Z, Mitrani-Rosenbaum S, Lochmüller H. GNE protein expression and subcellular distribution are unaltered in HIBM. Neurology. 2007 Aug 14;69(7):655-9. (http://www.ncbi.nlm.nih.gov/pubmed/17698786?dopt=Abstract)
  • Malicdan MC, Noguchi S, Nishino I. Recent advances in distal myopathy with rimmed vacuoles (DMRV) or hIBM: treatment perspectives. Curr Opin Neurol. 2008 Oct;21(5):596-600. doi: 10.1097/WCO.0b013e32830dd595. Review. (http://www.ncbi.nlm.nih.gov/pubmed/18769255?dopt=Abstract)
  • NCBI Gene (http://www.ncbi.nlm.nih.gov/gene/10020)
  • Nishino I, Malicdan MC, Murayama K, Nonaka I, Hayashi YK, Noguchi S. Molecular pathomechanism of distal myopathy with rimmed vacuoles. Acta Myol. 2005 Oct;24(2):80-3. Review. (http://www.ncbi.nlm.nih.gov/pubmed/16550921?dopt=Abstract)
  • Noguchi S, Keira Y, Murayama K, Ogawa M, Fujita M, Kawahara G, Oya Y, Imazawa M, Goto Y, Hayashi YK, Nonaka I, Nishino I. Reduction of UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase activity and sialylation in distal myopathy with rimmed vacuoles. J Biol Chem. 2004 Mar 19;279(12):11402-7. Epub 2004 Jan 5. (http://www.ncbi.nlm.nih.gov/pubmed/14707127?dopt=Abstract)
  • Penner J, Mantey LR, Elgavish S, Ghaderi D, Cirak S, Berger M, Krause S, Lucka L, Voit T, Mitrani-Rosenbaum S, Hinderlich S. Influence of UDP-GlcNAc 2-epimerase/ManNAc kinase mutant proteins on hereditary inclusion body myopathy. Biochemistry. 2006 Mar 7;45(9):2968-77. (http://www.ncbi.nlm.nih.gov/pubmed/16503651?dopt=Abstract)
  • Seppala R, Lehto VP, Gahl WA. Mutations in the human UDP-N-acetylglucosamine 2-epimerase gene define the disease sialuria and the allosteric site of the enzyme. Am J Hum Genet. 1999 Jun;64(6):1563-9. (http://www.ncbi.nlm.nih.gov/pubmed/10330343?dopt=Abstract)
  • Tomimitsu H, Shimizu J, Ishikawa K, Ohkoshi N, Kanazawa I, Mizusawa H. Distal myopathy with rimmed vacuoles (DMRV): new GNE mutations and splice variant. Neurology. 2004 May 11;62(9):1607-10. (http://www.ncbi.nlm.nih.gov/pubmed/15136692?dopt=Abstract)
  • Wopereis S, Abd Hamid UM, Critchley A, Royle L, Dwek RA, Morava E, Leroy JG, Wilcken B, Lagerwerf AJ, Huijben KM, Lefeber DJ, Rudd PM, Wevers RA. Abnormal glycosylation with hypersialylated O-glycans in patients with Sialuria. Biochim Biophys Acta. 2006 Jun;1762(6):598-607. (http://www.ncbi.nlm.nih.gov/pubmed/16769205?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: December 2008
Published: July 21, 2014