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ANO5
anoctamin 5
The ANO5 gene provides instructions for the anoctamin-5 protein, which plays a role in skeletal muscle function, cell membrane maintenance, and repair, and is implicated in various muscular dystrophies. The ANO5 gene encodes the anoctamin-5 protein, a member of the anoctamin family of proteins.
ANO5 is located on the short (p) arm of chromosome 11, at band 11p14.3. Arm ratio per GRCh38 - banding schematic.
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Overview
The ANO5 gene, also known as anoctamin 5, contains the genetic blueprint for a protein called anoctamin-5. This protein is predominantly found in skeletal muscles, which are essential for movement, but it is also present in cardiac muscle and bone cells. Research indicates that ANO5 is involved in critical cellular processes, including ion transport, cell membrane maintenance, and repair.
What the gene does
The anoctamin-5 protein is part of a larger family of proteins called anoctamins, many of which function as chloride channels. These channels facilitate the movement of negatively charged chloride ions across cell membranes, which is vital for electrical signalling within cells. Although the exact mechanisms for anoctamin-5 are not fully understood, it is believed to contribute to the regulation of chloride flow, particularly in muscle cells, which is important for coordinated muscle contraction and relaxation. Additionally, anoctamin proteins, including anoctamin-5, are thought to be involved in maintaining and repairing the integrity of cell membranes. Some studies suggest a role for anoctamin-5 in the development of muscle and bone before birth.
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Chromosome location
The ANO5 gene is located on the long arm (q) of chromosome 11, specifically at position 11p14.3. This position indicates its precise address within the human genome.
Protein structure
The anoctamin-5 protein consists of 913 amino acids. Domain architecture has not been experimentally characterised in detail for this protein.
Key variants
Variants within the ANO5 gene can lead to alterations in the anoctamin-5 protein, which may impair its normal function. These genetic changes can range from single nucleotide substitutions to more complex rearrangements, impacting the protein's role in muscle function and cell membrane processes.
Sample of pathogenic variants
10 pathogenic / likely-pathogenic variants from ClinVar, ranked by review status (expert-panel-reviewed first). This is a sample; recurrent founder variants in a specific population may not appear here - see the full ClinVar listing via the link above.
| Variant (HGVS) | Protein change | Classification | Evidence | Associated condition |
|---|---|---|---|---|
c.1067G>A | p.Cys356Tyr | Pathogenic | ★★☆☆ | Autosomal recessive limb-girdle muscular dystrophy type 2L |
c.1553G>A | p.Gly518Glu | Pathogenic/Likely pathogenic | ★★☆☆ | Autosomal recessive limb-girdle muscular dystrophy type 2L |
c.1965G>A | p.Trp655Ter | Pathogenic/Likely pathogenic | ★★☆☆ | Gnathodiaphyseal dysplasia |
c.2032dup | p.Thr678fs | Pathogenic/Likely pathogenic | ★★☆☆ | Gnathodiaphyseal dysplasia |
c.2236-2_2238dup | - | Pathogenic/Likely pathogenic | ★★☆☆ | Gnathodiaphyseal dysplasia |
c.258C>A | p.Tyr86Ter | Pathogenic | ★★☆☆ | Autosomal recessive limb-girdle muscular dystrophy type 2L |
c.431_432del | p.Ala144fs | Pathogenic | ★★☆☆ | Autosomal recessive limb-girdle muscular dystrophy |
c.774G>A | p.Trp258Ter | Pathogenic/Likely pathogenic | ★★☆☆ | Gnathodiaphyseal dysplasia |
c.846T>G | p.Tyr282Ter | Pathogenic/Likely pathogenic | ★★☆☆ | Autosomal recessive limb-girdle muscular dystrophy type 2L |
c.970del | p.Cys324fs | Pathogenic/Likely pathogenic | ★★☆☆ | Autosomal recessive limb-girdle muscular dystrophy type 2L |
Evidence stars indicate ClinVar review status. Individual variant interpretation should always be performed by a qualified clinical laboratory - many variants remain classified as Variants of Uncertain Significance (VUS) pending more research.
Associated conditions
Pathogenic variants in the ANO5 gene are linked to several inherited conditions, primarily affecting muscles and bones. These include various forms of limb-girdle muscular dystrophy, Miyoshi myopathy (also known as distal anoctaminopathy), and gnathodiaphyseal dysplasia, a rare bone disorder characterised by fragile bones and jaw abnormalities. These conditions typically follow an autosomal recessive inheritance pattern.
No disease links recorded for this gene in our reference set.
Inheritance pattern
Conditions caused by pathogenic ANO5 variants typically follow autosomal recessive inheritance.
When both parents are carriers, each child has a 25% chance of being affected, 50% of being a carrier, and 25% of being unaffected.
UK clinical status
In the UK, the ANO5 gene is included on several NHS Genomic Medicine Service national test panels. These panels cover conditions such as Acute rhabdomyolysis (R419), DDG2P, Distal myopathies, Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies (R82), Rhabdomyolysis and metabolic muscle disorders, and Skeletal dysplasia (R104), indicating its clinical relevance for genetic testing in the UK.
Sources: NHS GMS PanelApp · Genomics England PanelApp · NHS National Genomic Test Directory
Frequently asked questions
What is the primary function of the ANO5 gene?
The ANO5 gene provides instructions for the anoctamin-5 protein, which is believed to function as a chloride channel. It plays a key role in regulating chloride flow within muscle cells, which is important for coordinated muscle contraction and relaxation, and is also involved in maintaining and repairing cell membranes.
Which conditions are associated with variants in the ANO5 gene?
Variants in the ANO5 gene are associated with several conditions, including limb-girdle muscular dystrophy, Miyoshi myopathy (a type of distal muscular dystrophy), and gnathodiaphyseal dysplasia, which affects bone development.
How is ANO5 relevant to genetic testing in the UK?
In the UK, ANO5 is part of several NHS Genomic Medicine Service national test panels. This indicates its importance for diagnostic genetic testing for conditions such as muscular dystrophies, rhabdomyolysis, and skeletal dysplasias.
References
- Sarkozy A, Hicks D, Hudson J. 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. Human mutation. 2013. PMID: 23606453
- Liewluck T, Winder TL, Dimberg EL. ANO5-muscular dystrophy: clinical, pathological and molecular findings. European journal of neurology. 2013. PMID: 23663589
- Bouquet F, Cossée M, Béhin A. Miyoshi-like distal myopathy with mutations in anoctamin 5 gene. Revue neurologique. 2012. PMID: 22336395
- Penttilä S, Palmio J, Suominen T. Eight new mutations and the expanding phenotype variability in muscular dystrophy caused by ANO5. Neurology. 2012. PMID: 22402862
- Hicks D, Sarkozy A, Muelas N. A founder mutation in Anoctamin 5 is a major cause of limb-girdle muscular dystrophy. Brain : a journal of neurology. 2011. PMID: 21186264
- Bolduc V, Marlow G, Boycott KM. Recessive mutations in the putative calcium-activated chloride channel Anoctamin 5 cause proximal LGMD2L and distal MMD3 muscular dystrophies. American journal of human genetics. 2010. PMID: 20096397
- Mahjneh I, Jaiswal J, Lamminen A. A new distal myopathy with mutation in anoctamin 5. Neuromuscular disorders : NMD. 2010. PMID: 20692837
- Hartzell HC, Yu K, Xiao Q. Anoctamin/TMEM16 family members are Ca2+-activated Cl- channels. The Journal of physiology. 2009. PMID: 19015192
- Tsutsumi S, Kamata N, Vokes TJ. The novel gene encoding a putative transmembrane protein is mutated in gnathodiaphyseal dysplasia (GDD). American journal of human genetics. 2004. PMID: 15124103