ANO5 — anoctamin 5

16 sources retrieved · Most recent: April 2026 · Index updated 3 months ago

68PubMed Papers

#6,955 · top 36% of 19K genes

23Diseases

top 2%

0Drugs

187Pathogenic Variants

top 7%

OMIM Disease GeneVariant-RichExperimental GO EvidenceSwiss-Prot Reviewed

intracellularly calcium-gated chloride channel activityplasma membranechloride transmembrane transportplasma membrane repairautosomal recessive limb-girdle muscular dystrophy type 2Lgnathodiaphyseal dysplasiaMiyoshi muscular dystrophy 3autosomal recessive limb-girdle muscular dystrophy

AI Summary

ANO5 (anoctamin 5) is a multi-pass membrane protein localized to the sarcolemma and sarcoplasmic reticulum that plays a crucial role in plasma membrane repair through a process involving annexins 1. Unlike other anoctamins, ANO5 does not exhibit calcium-activated chloride channel activity but instead functions in membrane repair mechanisms. Mutations in ANO5 cause autosomal recessive limb-girdle muscular dystrophy R12 (LGMD-R12) and Miyoshi muscular dystrophy 3 (MMD3), representing a significant portion of muscular dystrophy cases 2 3. ANO5-related myopathy accounts for 7-26% of LGMD cases across different populations, making it one of the major contributing genes to LGMD phenotypes 2 4. The disease exhibits notable sex differences, with males more frequently presenting with moderate to severe skeletal muscle pathology and elevated creatine kinase levels, while females may develop cardiomyopathy features 5. Clinical presentation includes progressive muscle weakness, with wide variation in age of onset (0-72 years) and cardiac abnormalities occurring in approximately 17% of patients 4. The estimated minimum prevalence is 14.4 × 10-6 in the Netherlands 4. ANO5 myopathy represents part of a clinical continuum with varying degrees of muscle cell pathologies, and no clear genotype-phenotype correlation exists 1.

Sources cited

ANO5 is a multi-pass membrane protein localized to sarcolemma and sarcoplasmic reticulum involved in plasma membrane repair

PMID: 36157496

ANO5 accounts for 7% of LGMD cases and is one of the major contributing genes to LGMD phenotypes

PMID: 30564623

ANO5 is among the genes collectively accounting for over half of solved muscle disease cases

PMID: 32528171

ANO5 mutations cause 26% of LGMD cases in Netherlands cohort with wide age of onset variation and 17% cardiac involvement

PMID: 30919934

ANO5 myopathy exhibits sex differences with males more frequently presenting severe pathology and females developing cardiomyopathy

PMID: 35020501

Disease Associations23

autosomal recessive limb-girdle muscular dystrophy type 2LOpen Targets

0.84Strong

gnathodiaphyseal dysplasiaOpen Targets

0.82Strong

Miyoshi muscular dystrophy 3Open Targets

0.78Strong

autosomal recessive limb-girdle muscular dystrophyOpen Targets

0.71Strong

limb-girdle muscular dystrophyOpen Targets

0.67Moderate

Distal anoctaminopathyOpen Targets

0.64Moderate

isolated asymptomatic elevation of creatine phosphokinaseOpen Targets

0.57Moderate

Elevated circulating creatine kinase concentrationOpen Targets

0.49Moderate

atrial fibrillationOpen Targets

0.48Moderate

myopathyOpen Targets

0.46Moderate

Abnormality of the musculatureOpen Targets

0.44Moderate

muscular dystrophyOpen Targets

0.42Moderate

COVID-19Open Targets

0.37Weak

Disproportionate short statureOpen Targets

0.37Weak

Distal muscle weaknessOpen Targets

0.37Weak

Fatty replacement of skeletal muscleOpen Targets

0.37Weak

skeletal dysplasiaOpen Targets

0.37Weak

hereditary fructose intoleranceOpen Targets

0.34Weak

Lower limb muscle weaknessOpen Targets

0.34Weak

Meckel syndromeOpen Targets

0.34Weak

Gnathodiaphyseal dysplasiaUniProt

Miyoshi muscular dystrophy 3UniProt

Muscular dystrophy, limb-girdle, autosomal recessive 12UniProt

Pathogenic Variants187

NM_213599.3(ANO5):c.1450C>T (p.Arg484Cys)Likely pathogenic

not provided|ANO5-Related Muscle Diseases|Autosomal recessive limb-girdle muscular dystrophy type 2L;Gnathodiaphyseal dysplasia|not specified|Autosomal recessive limb-girdle muscular dystrophy

★★★☆2026→ Residue 484

NM_213599.3(ANO5):c.41-1G>APathogenic

not provided|Autosomal recessive limb-girdle muscular dystrophy type 2L|Gnathodiaphyseal dysplasia;Autosomal recessive limb-girdle muscular dystrophy type 2L|Autosomal recessive limb-girdle muscular dystrophy

★★★☆2026

NM_213599.3(ANO5):c.692G>T (p.Gly231Val)Likely pathogenic

Autosomal recessive limb-girdle muscular dystrophy type 2L|not provided|ANO5-related disorder|Autosomal recessive limb-girdle muscular dystrophy type 2L;Gnathodiaphyseal dysplasia|Autosomal recessive limb-girdle muscular dystrophy type 2L;Gnathodiaphyseal dysplasia;Miyoshi muscular dystrophy 3|Hereditary fructosuria|Autosomal recessive limb-girdle muscular dystrophy|Miyoshi muscular dystrophy 3|Ovarian serous cystadenocarcinoma|Acute rhabdomyolysis|Nonpapillary renal cell carcinoma

★★★☆2026→ Residue 231

NM_213599.3(ANO5):c.1733T>C (p.Phe578Ser)Pathogenic

not provided|Autosomal recessive limb-girdle muscular dystrophy type 2L;Gnathodiaphyseal dysplasia|Abnormality of the musculature|Autosomal recessive limb-girdle muscular dystrophy type 2L|Miyoshi muscular dystrophy 3|Autosomal recessive limb-girdle muscular dystrophy type 2L;Miyoshi muscular dystrophy 3;Gnathodiaphyseal dysplasia|Autosomal recessive limb-girdle muscular dystrophy

★★★☆2026→ Residue 578

NM_213599.3(ANO5):c.242A>G (p.Asp81Gly)Pathogenic

not provided|Gnathodiaphyseal dysplasia;Autosomal recessive limb-girdle muscular dystrophy type 2L|Autosomal recessive limb-girdle muscular dystrophy

★★★☆2026→ Residue 81

NM_213599.3(ANO5):c.1295C>G (p.Ala432Gly)Pathogenic

Autosomal recessive limb-girdle muscular dystrophy type 2L|not provided|Autosomal recessive limb-girdle muscular dystrophy type 2L;Miyoshi muscular dystrophy 3;Gnathodiaphyseal dysplasia|Autosomal recessive limb-girdle muscular dystrophy type 2L;Gnathodiaphyseal dysplasia|Autosomal recessive limb-girdle muscular dystrophy|ANO5-related disorder

★★★☆2026→ Residue 432

NM_213599.3(ANO5):c.1898+1G>APathogenic

not provided|Autosomal recessive limb-girdle muscular dystrophy type 2L;Gnathodiaphyseal dysplasia|Miyoshi muscular dystrophy 3;Autosomal recessive limb-girdle muscular dystrophy type 2L;Gnathodiaphyseal dysplasia|Autosomal recessive limb-girdle muscular dystrophy type 2L|Autosomal recessive limb-girdle muscular dystrophy|Miyoshi muscular dystrophy 3;Autosomal recessive limb-girdle muscular dystrophy type 2L

★★★☆2025

NM_213599.3(ANO5):c.172C>T (p.Arg58Trp)Pathogenic

Autosomal recessive limb-girdle muscular dystrophy type 2L|not provided|Autosomal recessive limb-girdle muscular dystrophy type 2L;Gnathodiaphyseal dysplasia|Miyoshi muscular dystrophy 3|Abnormality of the musculature|Autosomal recessive limb-girdle muscular dystrophy|ANO5-related disorder|Autosomal recessive limb-girdle muscular dystrophy type 2L;Miyoshi muscular dystrophy 3;Gnathodiaphyseal dysplasia

★★★☆2025→ Residue 58

NM_213599.3(ANO5):c.108_109del (p.Glu36fs)Pathogenic

not provided|Gnathodiaphyseal dysplasia;Autosomal recessive limb-girdle muscular dystrophy type 2L|Autosomal recessive limb-girdle muscular dystrophy

★★★☆2025→ Residue 36

NM_213599.3(ANO5):c.191dup (p.Asn64fs)Pathogenic

Miyoshi muscular dystrophy 3|Autosomal recessive limb-girdle muscular dystrophy type 2L|not provided|Myopathy|Gnathodiaphyseal dysplasia;Autosomal recessive limb-girdle muscular dystrophy type 2L|Polycystic kidney disease;Achilles tendon contracture;Elevated circulating creatine kinase concentration;Lower limb muscle weakness;Lower limb amyotrophy|ANO5-related disorder|Gnathodiaphyseal dysplasia|Intellectual disability|Autosomal recessive limb-girdle muscular dystrophy|Gnathodiaphyseal dysplasia;Miyoshi muscular dystrophy 3;Autosomal recessive limb-girdle muscular dystrophy type 2L|ANO5-related muscular dystrophy|Miyoshi muscular dystrophy 3;Autosomal recessive limb-girdle muscular dystrophy type 2L

★★★☆2025→ Residue 64

NM_213599.3(ANO5):c.304_308del (p.Lys102fs)Pathogenic

not provided|Autosomal recessive limb-girdle muscular dystrophy type 2L;Gnathodiaphyseal dysplasia;Miyoshi muscular dystrophy 3|Autosomal recessive limb-girdle muscular dystrophy type 2L;Gnathodiaphyseal dysplasia|Abnormality of the musculature|Autosomal recessive limb-girdle muscular dystrophy

★★★☆2025→ Residue 102

NM_213599.3(ANO5):c.148C>T (p.Arg50Ter)Pathogenic

Gnathodiaphyseal dysplasia;Autosomal recessive limb-girdle muscular dystrophy type 2L|Miyoshi muscular dystrophy 3;Gnathodiaphyseal dysplasia;Autosomal recessive limb-girdle muscular dystrophy type 2L|Autosomal recessive limb-girdle muscular dystrophy

★★★☆2025→ Residue 50

NM_213599.3(ANO5):c.2272C>T (p.Arg758Cys)Pathogenic

Miyoshi muscular dystrophy 3|Autosomal recessive limb-girdle muscular dystrophy type 2L|not provided|Autosomal recessive limb-girdle muscular dystrophy type 2L;Gnathodiaphyseal dysplasia|ANO5 Muscle Disease|Autosomal recessive limb-girdle muscular dystrophy

★★★☆2025→ Residue 758

NM_213599.3(ANO5):c.2018A>G (p.Tyr673Cys)Pathogenic

not provided|Autosomal recessive limb-girdle muscular dystrophy type 2L;Gnathodiaphyseal dysplasia|Autosomal recessive limb-girdle muscular dystrophy|Autosomal recessive limb-girdle muscular dystrophy type 2L

★★★☆2025→ Residue 673

NM_213599.3(ANO5):c.2503_2505del (p.Phe835del)Likely pathogenic

not provided|Autosomal recessive limb-girdle muscular dystrophy type 2L;Gnathodiaphyseal dysplasia|Autosomal recessive limb-girdle muscular dystrophy

★★★☆2025→ Residue 835

NM_213599.3(ANO5):c.989dup (p.Leu330fs)Pathogenic

not provided|Gnathodiaphyseal dysplasia;Miyoshi muscular dystrophy 3;Autosomal recessive limb-girdle muscular dystrophy type 2L|Gnathodiaphyseal dysplasia;Autosomal recessive limb-girdle muscular dystrophy type 2L|Autosomal recessive limb-girdle muscular dystrophy

★★★☆2025→ Residue 330

NM_213599.3(ANO5):c.1359C>G (p.Tyr453Ter)Pathogenic

Autosomal recessive limb-girdle muscular dystrophy type 2L|not provided|Gnathodiaphyseal dysplasia;Autosomal recessive limb-girdle muscular dystrophy type 2L|Autosomal recessive limb-girdle muscular dystrophy type 2L;Miyoshi muscular dystrophy 3

★★☆☆2026→ Residue 453

NM_213599.3(ANO5):c.1520del (p.Phe507fs)Pathogenic

not provided|Gnathodiaphyseal dysplasia;Autosomal recessive limb-girdle muscular dystrophy type 2L|Autosomal recessive limb-girdle muscular dystrophy type 2L|Autosomal recessive limb-girdle muscular dystrophy|Miyoshi muscular dystrophy 3;Autosomal recessive limb-girdle muscular dystrophy type 2L

★★☆☆2026→ Residue 507

NM_213599.3(ANO5):c.813C>G (p.Tyr271Ter)Pathogenic

Autosomal recessive limb-girdle muscular dystrophy type 2L|not provided|Gnathodiaphyseal dysplasia;Autosomal recessive limb-girdle muscular dystrophy type 2L

★★☆☆2026→ Residue 271

NM_213599.3(ANO5):c.1213C>T (p.Gln405Ter)Pathogenic

not provided|Muscular dystrophy|Autosomal recessive limb-girdle muscular dystrophy type 2L;Gnathodiaphyseal dysplasia|Autosomal recessive limb-girdle muscular dystrophy type 2L

★★☆☆2026→ Residue 405

Tissue Expression6 tissues

Heart

100%

Brain

17%

Liver

Lung

Ovary

Bone Marrow

Gene Interaction Network6 neighbors

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StructureAlphaFold

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AlphaFoldAI-predicted · UniProt Q75V66

View on AlphaFold

ConstraintgnomAD v4.1

LOEUFⓘ

1.03LoF Tolerant

pLIⓘ

0.00Tolerant

Observed/Expected LoF0.87 [0.73–1.03]

Rankings3 dim

Where ANO5 stands among ~20K protein-coding genes

#6,875of 20,598
Most Researched68
#380of 5,509
Most Pathogenic Variants187 · top 10%
#10,257of 17,882
Most Constrained (LOEUF)1.03