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®

ANO5

Reviewed December 2014

What is the official name of the ANO5 gene?

The official name of this gene is “anoctamin 5.”

ANO5 is the gene's official symbol. The ANO5 gene is also known by other names, listed below.

What is the normal function of the ANO5 gene?

The ANO5 gene provides instructions for making a protein called anoctamin-5. While the specific function of this protein is not well understood, it belongs to a family of proteins, called anoctamins, that act as chloride channels. Chloride channels, which transport negatively charged chlorine atoms (chloride ions) in and out of cells, play a key role in a cell's ability to generate and transmit electrical signals. Studies suggest that most anoctamin proteins function as chloride channels that are turned on (activated) in the presence of positively charged calcium atoms (calcium ions); these channels are known as calcium-activated chloride channels. The mechanism for this calcium activation is unclear. Anoctamin proteins are also involved in maintaining the membrane that surrounds cells and repairing the membrane if it gets damaged.

The anoctamin-5 protein is most abundant in muscles used for movement (skeletal muscles). For the body to move normally, skeletal muscles must tense (contract) and relax in a coordinated way. The regulation of chloride flow within muscle cells plays a role in controlling muscle contraction and relaxation.

The anoctamin-5 protein is also found in other cells including heart (cardiac) muscle cells and bone cells. Studies have suggested that the anoctamin-5 protein may be important for the development of muscle and bone before birth.

Does the ANO5 gene share characteristics with other genes?

The ANO5 gene belongs to a family of genes called ANO (anoctamins).

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 ANO5 gene related to health conditions?

gnathodiaphyseal dysplasia - caused by mutations in the ANO5 gene

At least three ANO5 gene mutations have been identified in people with a bone disorder called gnathodiaphyseal dysplasia, which leads to fragile bones, jaw problems, and other skeletal abnormalities. The ANO5 gene mutations that cause gnathodiaphyseal dysplasia change single protein building blocks (amino acids) in the anoctamin-5 protein. It is unclear how these mutations lead to the signs and symptoms of gnathodiaphyseal dysplasia, or why they primarily affect bones while other ANO5 gene mutations cause muscle disorders. Researchers suggest that the mutations may affect the way cells process calcium, an important mineral in bone development and growth.

limb-girdle muscular dystrophy - caused by mutations in the ANO5 gene

More than 40 mutations in the ANO5 gene have been identified in people with limb-girdle muscular dystrophy type 2L. Limb-girdle muscular dystrophy is a group of related disorders characterized by muscle weakness and wasting (atrophy), particularly in the shoulders, hips, thighs, and upper arms.

The ANO5 gene mutations identified in people with limb-girdle muscular dystrophy type 2L change single amino acids in the anoctamin-5 protein sequence, disrupt how genetic information is pieced together to make a blueprint for producing the protein, or result in a premature stop signal that leads to an abnormally short protein. One of the mutations adds an extra DNA building block (nucleotide) to the ANO5 gene (written as 191dupA) and is believed to be a relatively common cause of limb-girdle muscular dystrophy in people with northern European ancestry. This mutation alters the instructions used to make the anoctamin-5 protein, leading to a premature stop signal that would produce an abnormally short protein. Instead, a cellular error-catching mechanism called nonsense-mediated decay prevents the protein from being produced at all.

ANO5 gene mutations that eliminate or impair the role of the anoctamin-5 protein as a chloride channel likely lead to impaired muscle function, resulting in the signs and symptoms of limb-girdle muscular dystrophy.

Miyoshi myopathy - caused by mutations in the ANO5 gene

At least 10 mutations in the ANO5 gene have been found to cause Miyoshi myopathy. When caused by mutations in this gene, the condition is also known as distal anoctaminopathy. Miyoshi myopathy is a muscle disorder that is characterized by progressive weakness and atrophy of muscles that are away from the center of the body (distal muscles), particularly those in the legs. The ANO5 gene mutations identified in people with Miyoshi myopathy change single amino acids in the anoctamin-5 protein or result in the production of an abnormally short protein that is quickly broken down.

These mutations result in the production of little or no anoctamin-5 protein. The effects of the loss of anoctamin-5 are unclear. While chloride is necessary for normal muscle function, it is unknown how a lack of this chloride channel causes the signs and symptoms of Miyoshi myopathy.

The 191dupA mutation that can cause limb-girdle muscular dystrophy (described above) is also a common cause of Miyoshi myopathy in individuals of northern European ancestry. It is not known why the 191dupA mutation can result in different patterns of signs and symptoms. Miyoshi myopathy caused by ANO5 gene mutations is likely a variation of limb-girdle muscular dystrophy because it is caused by mutations in the same gene, and in some cases even by the same mutation.

Where is the ANO5 gene located?

Cytogenetic Location: 11p14.3

Molecular Location on chromosome 11: base pairs 22,192,666 to 22,283,366

The ANO5 gene is located on the short (p) arm of chromosome 11 at position 14.3.

The ANO5 gene is located on the short (p) arm of chromosome 11 at position 14.3.

More precisely, the ANO5 gene is located from base pair 22,192,666 to base pair 22,283,366 on chromosome 11.

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 ANO5?

You and your healthcare professional may find the following resources about ANO5 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 ANO5 gene or gene products?

  • ANO5_HUMAN
  • anoctamin-5
  • GDD1
  • gnathodiaphyseal dysplasia 1 protein
  • integral membrane protein GDD1
  • LGMD2L
  • TMEM16E
  • transmembrane protein 16E

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 ANO5?

acids ; atrophy ; calcium ; cardiac ; cell ; channel ; chloride ; chloride channels ; contraction ; distal ; DNA ; dysplasia ; gene ; ions ; mineral ; muscle cells ; muscular dystrophy ; mutation ; nucleotide ; protein ; protein sequence ; transmembrane ; wasting

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

References

  • OMIM: ANOCTAMIN 5 (http://omim.org/entry/608662)
  • Bolduc V, Marlow G, Boycott KM, Saleki K, Inoue H, Kroon J, Itakura M, Robitaille Y, Parent L, Baas F, Mizuta K, Kamata N, Richard I, Linssen WH, Mahjneh I, de Visser M, Bashir R, Brais B. Recessive mutations in the putative calcium-activated chloride channel Anoctamin 5 cause proximal LGMD2L and distal MMD3 muscular dystrophies. Am J Hum Genet. 2010 Feb 12;86(2):213-21. doi: 10.1016/j.ajhg.2009.12.013. Epub 2010 Jan 21. (http://www.ncbi.nlm.nih.gov/pubmed/20096397?dopt=Abstract)
  • Bouquet F, Cossée M, Béhin A, Deburgrave N, Romero N, Leturcq F, Eymard B. Miyoshi-like distal myopathy with mutations in anoctamin 5 gene. Rev Neurol (Paris). 2012 Feb;168(2):135-41. doi: 10.1016/j.neurol.2011.10.005. Epub 2012 Feb 13. (http://www.ncbi.nlm.nih.gov/pubmed/22336395?dopt=Abstract)
  • Hartzell HC, Yu K, Xiao Q, Chien LT, Qu Z. Anoctamin/TMEM16 family members are Ca2+-activated Cl- channels. J Physiol. 2009 May 15;587(Pt 10):2127-39. doi: 10.1113/jphysiol.2008.163709. Epub 2008 Nov 17. Review. (http://www.ncbi.nlm.nih.gov/pubmed/19015192?dopt=Abstract)
  • Hicks D, Sarkozy A, Muelas N, Koehler K, Huebner A, Hudson G, Chinnery PF, Barresi R, Eagle M, Polvikoski T, Bailey G, Miller J, Radunovic A, Hughes PJ, Roberts R, Krause S, Walter MC, Laval SH, Straub V, Lochmüller H, Bushby K. A founder mutation in Anoctamin 5 is a major cause of limb-girdle muscular dystrophy. Brain. 2011 Jan;134(Pt 1):171-82. doi: 10.1093/brain/awq294. (http://www.ncbi.nlm.nih.gov/pubmed/21186264?dopt=Abstract)
  • Liewluck T, Winder TL, Dimberg EL, Crum BA, Heppelmann CJ, Wang Y, Bergen HR 3rd, Milone M. ANO5-muscular dystrophy: clinical, pathological and molecular findings. Eur J Neurol. 2013 Oct;20(10):1383-9. doi: 10.1111/ene.12191. Epub 2013 May 12. (http://www.ncbi.nlm.nih.gov/pubmed/23663589?dopt=Abstract)
  • Mahjneh I, Jaiswal J, Lamminen A, Somer M, Marlow G, Kiuru-Enari S, Bashir R. A new distal myopathy with mutation in anoctamin 5. Neuromuscul Disord. 2010 Dec;20(12):791-5. doi: 10.1016/j.nmd.2010.07.270. Epub 2010 Aug 7. (http://www.ncbi.nlm.nih.gov/pubmed/20692837?dopt=Abstract)
  • NCBI Gene (http://www.ncbi.nlm.nih.gov/gene/203859)
  • Penttilä S, Palmio J, Suominen T, Raheem O, Evilä A, Muelas Gomez N, Tasca G, Waddell LB, Clarke NF, Barboi A, Hackman P, Udd B. Eight new mutations and the expanding phenotype variability in muscular dystrophy caused by ANO5. Neurology. 2012 Mar 20;78(12):897-903. doi: 10.1212/WNL.0b013e31824c4682. Epub 2012 Mar 7. Erratum in: Neurology. 2013 Jan 8;80(2):226. (http://www.ncbi.nlm.nih.gov/pubmed/22402862?dopt=Abstract)
  • Sarkozy A, Hicks D, Hudson J, Laval SH, Barresi R, Hilton-Jones D, Deschauer M, Harris E, Rufibach L, Hwang E, Bashir R, Walter MC, Krause S, van den Bergh P, Illa I, Pénisson-Besnier I, De Waele L, Turnbull D, Guglieri M, Schrank B, Schoser B, Seeger J, Schreiber H, Gläser D, Eagle M, Bailey G, Walters R, Longman C, Norwood F, Winer J, Muntoni F, Hanna M, Roberts M, Bindoff LA, Brierley C, Cooper RG, Cottrell DA, Davies NP, Gibson A, Gorman GS, Hammans S, Jackson AP, Khan A, Lane R, McConville J, McEntagart M, Al-Memar A, Nixon J, Panicker J, Parton M, Petty R, Price CJ, Rakowicz W, Ray P, Schapira AH, Swingler R, Turner C, Wagner KR, Maddison P, Shaw PJ, Straub V, Bushby K, Lochmüller H. ANO5 gene analysis in a large cohort of patients with anoctaminopathy: confirmation of male prevalence and high occurrence of the common exon 5 gene mutation. Hum Mutat. 2013 Aug;34(8):1111-8. doi: 10.1002/humu.22342. Epub 2013 Jun 12. (http://www.ncbi.nlm.nih.gov/pubmed/23606453?dopt=Abstract)
  • Tsutsumi S, Kamata N, Vokes TJ, Maruoka Y, Nakakuki K, Enomoto S, Omura K, Amagasa T, Nagayama M, Saito-Ohara F, Inazawa J, Moritani M, Yamaoka T, Inoue H, Itakura M. The novel gene encoding a putative transmembrane protein is mutated in gnathodiaphyseal dysplasia (GDD). Am J Hum Genet. 2004 Jun;74(6):1255-61. Epub 2004 Apr 29. (http://www.ncbi.nlm.nih.gov/pubmed/15124103?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 2014
Published: December 22, 2014