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Genetics Home Reference: your guide to understanding genetic conditions
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MFN2

Reviewed January 2010

What is the official name of the MFN2 gene?

The official name of this gene is “mitofusin 2.”

MFN2 is the gene's official symbol. The MFN2 gene is also known by other names, listed below.

What is the normal function of the MFN2 gene?

The MFN2 gene provides instructions for making a protein called mitofusin 2. This protein helps determine the shape and structure (morphology) of mitochondria, the energy-producing centers within cells. Mitofusin 2 is made in many types of cells and tissues, including muscles, the spinal cord, and nerves that connect the brain and spinal cord to muscles (peripheral nerves). Within cells, mitofusin 2 is found in the outer membrane that surrounds mitochondria.

Mitochondria are dynamic structures that undergo changes in morphology through processes called fission (splitting into smaller pieces) and fusion (combining pieces). These changes in morphology are necessary for mitochondria to function properly. Mitofusin 2 helps to regulate the morphology of mitochondria by controlling the fusion process.

How are changes in the MFN2 gene related to health conditions?

Charcot-Marie-Tooth disease - caused by mutations in the MFN2 gene

Researchers have identified approximately 50 MFN2 gene mutations that cause a form of Charcot-Marie-Tooth disease known as type 2A. Almost all of these mutations change single protein building blocks (amino acids) in mitofusin 2. These genetic changes alter a critical region in mitofusin 2, and the protein cannot function properly. A few mutations create a premature stop signal in the instructions for making mitofusin 2. As a result, no protein is produced, or an abnormally small protein is made.

Several MFN2 gene mutations cause a variant of type 2A Charcot-Marie-Tooth disease that affects vision. (This variant is also called hereditary motor and sensory neuropathy VI.) Vision loss is caused by the degeneration of the nerves that carry information from the eyes to the brain (optic atrophy). People with this variant usually experience severe symptoms of Charcot-Marie-Tooth disease that begin before age 10.

It is unclear how MFN2 gene mutations lead to the nerve problems characteristic of type 2A Charcot-Marie-Tooth disease. Researchers suggest that mitochondria cannot fuse properly or move normally within the cell without functional mitofusin 2, which may disrupt the cell's energy supply. Nerve cells may be particularly sensitive to an interrupted supply of energy.

Where is the MFN2 gene located?

Cytogenetic Location: 1p36.22

Molecular Location on chromosome 1: base pairs 11,980,180 to 12,013,514

The MFN2 gene is located on the short (p) arm of chromosome 1 at position 36.22.

The MFN2 gene is located on the short (p) arm of chromosome 1 at position 36.22.

More precisely, the MFN2 gene is located from base pair 11,980,180 to base pair 12,013,514 on chromosome 1.

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 MFN2?

You and your healthcare professional may find the following resources about MFN2 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 MFN2 gene or gene products?

  • CMT2A2
  • CPRP1
  • KIAA0214
  • MARF
  • MFN2_HUMAN
  • mitochondrial assembly regulatory factor

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 MFN2?

acids ; atrophy ; cell ; critical region ; gene ; hereditary ; mitochondria ; morphology ; motor ; neuropathy ; optic atrophy ; peripheral ; peripheral nerves ; peripheral neuropathy ; protein ; sensory neuropathy

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

References

  • Amiott EA, Lott P, Soto J, Kang PB, McCaffery JM, DiMauro S, Abel ED, Flanigan KM, Lawson VH, Shaw JM. Mitochondrial fusion and function in Charcot-Marie-Tooth type 2A patient fibroblasts with mitofusin 2 mutations. Exp Neurol. 2008 May;211(1):115-27. doi: 10.1016/j.expneurol.2008.01.010. Epub 2008 Jan 26. (http://www.ncbi.nlm.nih.gov/pubmed/18316077?dopt=Abstract)
  • Baloh RH, Schmidt RE, Pestronk A, Milbrandt J. Altered axonal mitochondrial transport in the pathogenesis of Charcot-Marie-Tooth disease from mitofusin 2 mutations. J Neurosci. 2007 Jan 10;27(2):422-30. (http://www.ncbi.nlm.nih.gov/pubmed/17215403?dopt=Abstract)
  • Ben-Asher E, Lancet D. A new gene for the Charcot-Marie-Tooth disorder. Isr Med Assoc J. 2004 Jun;6(6):376-7. (http://www.ncbi.nlm.nih.gov/pubmed/15214472?dopt=Abstract)
  • Bradbury J. Mitochondrial fusion protein mutated in CMT2A. Lancet Neurol. 2004 Jun;3(6):326. (http://www.ncbi.nlm.nih.gov/pubmed/15176403?dopt=Abstract)
  • Cho HJ, Sung DH, Kim BJ, Ki CS. Mitochondrial GTPase mitofusin 2 mutations in Korean patients with Charcot-Marie-Tooth neuropathy type 2. Clin Genet. 2007 Mar;71(3):267-72. (http://www.ncbi.nlm.nih.gov/pubmed/17309650?dopt=Abstract)
  • Chung KW, Kim SB, Park KD, Choi KG, Lee JH, Eun HW, Suh JS, Hwang JH, Kim WK, Seo BC, Kim SH, Son IH, Kim SM, Sunwoo IN, Choi BO. Early onset severe and late-onset mild Charcot-Marie-Tooth disease with mitofusin 2 (MFN2) mutations. Brain. 2006 Aug;129(Pt 8):2103-18. Epub 2006 Jul 10. (http://www.ncbi.nlm.nih.gov/pubmed/16835246?dopt=Abstract)
  • Kijima K, Numakura C, Izumino H, Umetsu K, Nezu A, Shiiki T, Ogawa M, Ishizaki Y, Kitamura T, Shozawa Y, Hayasaka K. Mitochondrial GTPase mitofusin 2 mutation in Charcot-Marie-Tooth neuropathy type 2A. Hum Genet. 2005 Jan;116(1-2):23-7. Epub 2004 Nov 11. (http://www.ncbi.nlm.nih.gov/pubmed/15549395?dopt=Abstract)
  • NCBI Gene (http://www.ncbi.nlm.nih.gov/gene/9927)
  • Neuspiel M, Zunino R, Gangaraju S, Rippstein P, McBride H. Activated mitofusin 2 signals mitochondrial fusion, interferes with Bax activation, and reduces susceptibility to radical induced depolarization. J Biol Chem. 2005 Jul 1;280(26):25060-70. Epub 2005 May 4. (http://www.ncbi.nlm.nih.gov/pubmed/15878861?dopt=Abstract)
  • Niemann A, Berger P, Suter U. Pathomechanisms of mutant proteins in Charcot-Marie-Tooth disease. Neuromolecular Med. 2006;8(1-2):217-42. Review. (http://www.ncbi.nlm.nih.gov/pubmed/16775378?dopt=Abstract)
  • OMIM: MITOFUSIN 2 (http://omim.org/entry/608507)
  • Verhoeven K, Claeys KG, Züchner S, Schröder JM, Weis J, Ceuterick C, Jordanova A, Nelis E, De Vriendt E, Van Hul M, Seeman P, Mazanec R, Saifi GM, Szigeti K, Mancias P, Butler IJ, Kochanski A, Ryniewicz B, De Bleecker J, Van den Bergh P, Verellen C, Van Coster R, Goemans N, Auer-Grumbach M, Robberecht W, Milic Rasic V, Nevo Y, Tournev I, Guergueltcheva V, Roelens F, Vieregge P, Vinci P, Moreno MT, Christen HJ, Shy ME, Lupski JR, Vance JM, De Jonghe P, Timmerman V. MFN2 mutation distribution and genotype/phenotype correlation in Charcot-Marie-Tooth type 2. Brain. 2006 Aug;129(Pt 8):2093-102. Epub 2006 May 19. (http://www.ncbi.nlm.nih.gov/pubmed/16714318?dopt=Abstract)
  • Züchner S, De Jonghe P, Jordanova A, Claeys KG, Guergueltcheva V, Cherninkova S, Hamilton SR, Van Stavern G, Krajewski KM, Stajich J, Tournev I, Verhoeven K, Langerhorst CT, de Visser M, Baas F, Bird T, Timmerman V, Shy M, Vance JM. Axonal neuropathy with optic atrophy is caused by mutations in mitofusin 2. Ann Neurol. 2006 Feb;59(2):276-81. (http://www.ncbi.nlm.nih.gov/pubmed/16437557?dopt=Abstract)
  • Züchner S, Mersiyanova IV, Muglia M, Bissar-Tadmouri N, Rochelle J, Dadali EL, Zappia M, Nelis E, Patitucci A, Senderek J, Parman Y, Evgrafov O, Jonghe PD, Takahashi Y, Tsuji S, Pericak-Vance MA, Quattrone A, Battaloglu E, Polyakov AV, Timmerman V, Schröder JM, Vance JM. Mutations in the mitochondrial GTPase mitofusin 2 cause Charcot-Marie-Tooth neuropathy type 2A. Nat Genet. 2004 May;36(5):449-51. Epub 2004 Apr 4. Erratum in: Nat Genet. 2004 Jun;36(6):660. Battologlu E [corrected to Battaloglu E]. (http://www.ncbi.nlm.nih.gov/pubmed/15064763?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: January 2010
Published: July 28, 2014