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Genetics Home Reference: your guide to understanding genetic conditions
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GAN

Reviewed October 2007

What is the official name of the GAN gene?

The official name of this gene is “gigaxonin.”

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

What is the normal function of the GAN gene?

The GAN gene provides instructions for making a protein called gigaxonin. Gigaxonin is involved in a cellular function that destroys and gets rid of excess or damaged proteins using a mechanism called the ubiquitin-proteasome system. The ubiquitin-proteasome system is a multi-step process that begins with the activation of a protein called ubiquitin. With the assistance of other proteins called ubiquitin-conjugating enzymes and ubiquitin ligases, the ubiquitin attaches to a targeted protein. When a chain of ubiquitin proteins is attached to the targeted protein, the protein is recognized and destroyed by a complex of enzymes called a proteasome.

Researchers believe that gigaxonin belongs to a group of ubiquitin ligases called the BTB/kelch superfamily. These ubiquitin ligases help ubiquitin target specific proteins for destruction. Gigaxonin targets proteins that must be broken down in order for the cytoskeleton, the framework that gives structure to cells, to develop properly.

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

giant axonal neuropathy - caused by mutations in the GAN gene

Several mutations in the GAN gene have been identified in people with giant axonal neuropathy. Some mutations change or remove one of the protein building blocks (amino acids) used to make gigaxonin. This type of alteration affects the shape of the gigaxonin protein, preventing it from binding to other proteins properly to help organize the structure of neurons. Other mutations result in the absence of any functional gigaxonin.

Absence of functional gigaxonin leads to accumulation of proteins that should have been destroyed by the ubiquitin-proteasome system. This accumulation of proteins results in disorganization of the cytoskeleton.

In nerve cells (neurons), the absence of functional gigaxonin results in abnormally large, densely packed accumulations of neurofilaments, an important part of the cytoskeleton. Neurofilaments are particularly abundant in axons, the long nerve cell extensions that transmit signals to other cells.

The excess neurofilaments that build up in the axon as a result of a deficiency of functional gigaxonin result in distended or giant axons that do not transmit signals properly. Affected axons eventually deteriorate, causing problems with movement and sensation. The giant axons are commonly seen in the peripheral nerves, which carry signals between the brain and spinal cord (central nervous system) and other areas of the body. However, neurons in the central nervous system can be affected as well.

Where is the GAN gene located?

Cytogenetic Location: 16q24.1

Molecular Location on chromosome 16: base pairs 81,314,965 to 81,380,197

The GAN gene is located on the long (q) arm of chromosome 16 at position 24.1.

The GAN gene is located on the long (q) arm of chromosome 16 at position 24.1.

More precisely, the GAN gene is located from base pair 81,314,965 to base pair 81,380,197 on chromosome 16.

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 GAN?

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

  • GAN1
  • GAN_HUMAN
  • giant axonal neuropathy (gigaxonin)
  • KLHL16

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 GAN?

acids ; axons ; cell ; central nervous system ; cytoskeleton ; deficiency ; distended ; gene ; nerve cell ; nervous system ; neuropathy ; peripheral ; peripheral nerves ; proteasome ; protein ; ubiquitin

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

References

  • Allen E, Ding J, Wang W, Pramanik S, Chou J, Yau V, Yang Y. Gigaxonin-controlled degradation of MAP1B light chain is critical to neuronal survival. Nature. 2005 Nov 10;438(7065):224-8. Epub 2005 Oct 16. (http://www.ncbi.nlm.nih.gov/pubmed/16227972?dopt=Abstract)
  • Ben Hamida C, Cavalier L, Belal S, Sanhaji H, Nadal N, Barhoumi C, M'Rissa N, Marzouki N, Mandel JL, Ben Hamida M, Koenig M, Hentati F. Homozygosity mapping of giant axonal neuropathy gene to chromosome 16q24.1. Neurogenetics. 1997 Sep;1(2):129-33. (http://www.ncbi.nlm.nih.gov/pubmed/10732815?dopt=Abstract)
  • Bomont P, Cavalier L, Blondeau F, Ben Hamida C, Belal S, Tazir M, Demir E, Topaloglu H, Korinthenberg R, Tüysüz B, Landrieu P, Hentati F, Koenig M. The gene encoding gigaxonin, a new member of the cytoskeletal BTB/kelch repeat family, is mutated in giant axonal neuropathy. Nat Genet. 2000 Nov;26(3):370-4. (http://www.ncbi.nlm.nih.gov/pubmed/11062483?dopt=Abstract)
  • Bomont P, Ioos C, Yalcinkaya C, Korinthenberg R, Vallat JM, Assami S, Munnich A, Chabrol B, Kurlemann G, Tazir M, Koenig M. Identification of seven novel mutations in the GAN gene. Hum Mutat. 2003 Apr;21(4):446. (http://www.ncbi.nlm.nih.gov/pubmed/12655563?dopt=Abstract)
  • Cullen VC, Brownlees J, Banner S, Anderton BH, Leigh PN, Shaw CE, Miller CC. Gigaxonin is associated with the Golgi and dimerises via its BTB domain. Neuroreport. 2004 Apr 9;15(5):873-6. (http://www.ncbi.nlm.nih.gov/pubmed/15073534?dopt=Abstract)
  • Ding J, Allen E, Wang W, Valle A, Wu C, Nardine T, Cui B, Yi J, Taylor A, Jeon NL, Chu S, So Y, Vogel H, Tolwani R, Mobley W, Yang Y. Gene targeting of GAN in mouse causes a toxic accumulation of microtubule-associated protein 8 and impaired retrograde axonal transport. Hum Mol Genet. 2006 May 1;15(9):1451-63. Epub 2006 Mar 24. (http://www.ncbi.nlm.nih.gov/pubmed/16565160?dopt=Abstract)
  • Ding J, Liu JJ, Kowal AS, Nardine T, Bhattacharya P, Lee A, Yang Y. Microtubule-associated protein 1B: a neuronal binding partner for gigaxonin. J Cell Biol. 2002 Aug 5;158(3):427-33. Epub 2002 Jul 29. Erratum in: J Cell Biol. 2003 Oct 13;163(1):189. (http://www.ncbi.nlm.nih.gov/pubmed/12147674?dopt=Abstract)
  • Flanigan KM, Crawford TO, Griffin JW, Goebel HH, Kohlschütter A, Ranells J, Camfield PR, Ptácek LJ. Localization of the giant axonal neuropathy gene to chromosome 16q24. Ann Neurol. 1998 Jan;43(1):143-8. (http://www.ncbi.nlm.nih.gov/pubmed/9450783?dopt=Abstract)
  • Gene Review: Giant Axonal Neuropathy (http://www.ncbi.nlm.nih.gov/books/NBK1136/)
  • NCBI Gene (http://www.ncbi.nlm.nih.gov/gene/8139)
  • OMIM: GAN GENE (http://omim.org/entry/605379)
  • Pintard L, Willems A, Peter M. Cullin-based ubiquitin ligases: Cul3-BTB complexes join the family. EMBO J. 2004 Apr 21;23(8):1681-7. Epub 2004 Apr 8. Review. Erratum in: EMBO J. 2005 Mar 9;24(5):1092. (http://www.ncbi.nlm.nih.gov/pubmed/15071497?dopt=Abstract)
  • Wang W, Ding J, Allen E, Zhu P, Zhang L, Vogel H, Yang Y. Gigaxonin interacts with tubulin folding cofactor B and controls its degradation through the ubiquitin-proteasome pathway. Curr Biol. 2005 Nov 22;15(22):2050-5. (http://www.ncbi.nlm.nih.gov/pubmed/16303566?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: October 2007
Published: July 28, 2014