ANO5
Chr 11ADARanoctamin 5
Also known as: GDD1, LGMD2L, LGMDR12, TMEM16E
The protein functions in plasma membrane repair through interaction with annexins and localizes to the endoplasmic reticulum membrane. Mutations cause autosomal recessive limb-girdle muscular dystrophy type 12 and Miyoshi muscular dystrophy 3, as well as autosomal dominant gnathodiaphyseal dysplasia through a predicted gain-of-function mechanism. The muscular dystrophies result from impaired membrane repair, while the bone dysplasia represents a distinct dominant phenotype.
Definitive — sufficient evidence for diagnostic panels
2 total gene-disease associations curated
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Typical tolerance to LoF variation
Mild missense constraint
This gene has evidence for multiple mechanisms of pathogenicity (gain-of-function and dominant-negative). Both the Badonyi & Marsh prediction and the broader genomic evidence point to gain-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.
Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.
Literature Evidence
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.
ClinVar Variant Classifications
0 submitted variants in ClinVar
Protein Context — Lollipop Plot
ANO5 · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
3D Protein StructureAlphaFold
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
MRI-phenotyping of Patients With Pathogenic Anoctamin 5 Variants
RECRUITING3 Year Follow up on ANO5 Patients
ACTIVE NOT RECRUITINGExternal Resources
Links to major genomics databases and tools