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ANO5
anoctamin 5
The ANO5 gene provides instructions for producing the anoctamin-5 protein, which is primarily involved in muscle function and has been linked to several muscular disorders. 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 is responsible for making the anoctamin-5 protein, which belongs to a larger family of proteins known as anoctamins. These proteins are generally involved in transporting charged chloride atoms across cell membranes, influencing electrical signals within cells. Ano-5 is particularly abundant in skeletal muscles, playing a role in their normal contraction and relaxation processes.
What the gene does
The anoctamin-5 protein, encoded by the ANO5 gene, is understood to function as a calcium-activated chloride channel. These channels facilitate the movement of negatively charged chloride ions in and out of cells, which is essential for generating and transmitting electrical signals. Beyond its channel activity, anoctamin-5 is also thought to contribute to maintaining the integrity of cell membranes and assisting in their repair following damage. In muscle cells, the precise regulation of chloride flow, mediated by proteins like anoctamin-5, is critical for coordinated muscle contraction and relaxation. The protein is also found in cardiac muscle cells and bone cells, suggesting a broader role in tissue development before birth.
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Chromosome location
The ANO5 gene is situated on the short arm of chromosome 11, specifically at position 11p14.3. This genomic location indicates its place within the human genome.
Protein structure
Domain architecture has not been experimentally characterised in detail for this protein.
Key variants
Genetic variations, or alterations, within the ANO5 gene can lead to changes in the anoctamin-5 protein. These changes may affect the protein's ability to function correctly, potentially disrupting cellular processes, particularly those in muscle and bone tissue. Different types of variations, including single amino acid changes, have been identified.
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.2520+1G>A | - | Pathogenic/Likely pathogenic | ★★☆☆ | ANO5-related disorder |
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 |
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
Variations in the ANO5 gene are linked to several inherited conditions, primarily affecting muscles and bones. These include limb-girdle muscular dystrophy, which causes progressive weakness, and Miyoshi myopathy, characterised by weakness in muscles further from the body's centre. It is also associated with gnathodiaphyseal dysplasia, a bone disorder leading to fragile bones and jaw issues.
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
The ANO5 gene is included on several NHS Genomic Medicine Service national panels in the UK. These panels cover conditions such as Acute rhabdomyolysis, Distal myopathies, Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies (R82), Rhabdomyolysis and metabolic muscle disorders, and Skeletal dysplasia (R104). Its inclusion indicates clinical relevance for diagnostic testing within the UK healthcare system.
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 acts as a calcium-activated chloride channel. This protein helps regulate chloride ion movement across cell membranes, vital for electrical signalling and muscle function.
Which conditions are associated with variations in the ANO5 gene?
Variations in the ANO5 gene are associated with inherited conditions such as limb-girdle muscular dystrophy, Miyoshi myopathy (also known as distal anoctaminopathy), and gnathodiaphyseal dysplasia, affecting both muscles and bones.
Is ANO5 considered in UK clinical genetic testing?
Yes, the ANO5 gene is part of several NHS Genomic Medicine Service national panels in the UK, including those for rhabdomyolysis, muscular dystrophies, and skeletal dysplasias, highlighting its clinical importance.
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