ANO5

Chr 11ADAR

anoctamin 5

NCBI Gene: 203859ENSG00000171714UniProt: Q75V66

Plays a role in plasma membrane repair in a process involving annexins (PubMed:33496727). Does not exhibit calcium-activated chloride channel (CaCC) activity

Primary Disease Associations & Inheritance

Gnathodiaphyseal dysplasiaMIM #166260
AD
Miyoshi muscular dystrophy 3MIM #613319
AR
Muscular dystrophy, limb-girdle, autosomal recessive 12MIM #611307
AR
1576
ClinVar variants
53
Pathogenic / LP
0.00
pLI score
2
Active trials
Clinical Summary— ANO5
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
53 Pathogenic / Likely Pathogenic· 291 VUS of 1576 total submissions
💊
Clinical Trials
2 active or recruiting trials — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.95LOEUF
pLI 0.000
Z-score 1.86
OE 0.73 (0.57–0.95)
Tolerant

Typical tolerance to LoF variation

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
0.12Z-score
OE missense 0.98 (0.91–1.06)
467 obs / 474.2 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.73 (0.57–0.95)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.98 (0.91–1.06)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.18
0≤1.21.6
LoF obs/exp: 42 / 57.2Missense obs/exp: 467 / 474.2Syn Z: -1.80

ClinVar Variant Classifications

1576 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic25
Likely Pathogenic28
VUS291
Likely Benign143
Benign2
Conflicting3
25
Pathogenic
28
Likely Pathogenic
291
VUS
143
Likely Benign
2
Benign
3
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
8
1
16
0
25
Likely Pathogenic
15
5
8
0
28
VUS
8
246
34
3
291
Likely Benign
1
2
81
59
143
Benign
0
0
2
0
2
Conflicting
—3
Total3225414162492

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View 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.

Gene2Phenotype Curations

ANO5-related gnathodiaphyseal dysplasia

moderate
ADGain Of FunctionAltered Gene Product Structure
Dev. DisordersSkeletal
G2P ↗

ANO5-related limb-girdle muscular dystrophy

limited
ARLoss Of FunctionAbsent Gene Product
Dev. Disorders
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
ANOCTAMIN 5; ANO5
MIM #608662 · *

Gnathodiaphyseal dysplasia

MIM #166260

Molecular basis of disorder known

Autosomal dominant

Miyoshi muscular dystrophy 3

MIM #613319

Molecular basis of disorder known

Autosomal recessive

Muscular dystrophy, limb-girdle, autosomal recessive 12

MIM #611307

Molecular basis of disorder known

Autosomal recessive
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Sequential targeted exome sequencing of 1001 patients affected by unexplained limb-girdle weakness.
Töpf A et al.·Genet Med
2020Cohort
Panorama of the distal myopathies.
Savarese M et al.·Acta Myol
2020Review
Autosomal recessive limb-girdle and Miyoshi muscular dystrophies in the Netherlands: The clinical and molecular spectrum of 244 patients.
Ten Dam L et al.·Clin Genet
2019Cohort
Anoctamin-5 related muscle disease: clinical and genetic findings in a large European cohort.
de Bruyn A et al.·Brain
2023Cohort
Novel Variant in ANO5 Muscular Dystrophy: Identification by Whole Genome Sequencing and Quad Analysis.
Ćuk M et al.·Genes (Basel)
2024
Clinical and molecular findings in a cohort of ANO5-related myopathy.
Silva AMS et al.·Ann Clin Transl Neurol
2019Cohort
Familial gigantiform cementoma with recurrent ANO5 p.Cys356Tyr mutations: Clinicopathological and genetic study with literature review.
Zhou Z et al.·Mol Genet Genomic Med
2024Review
A novel ANO5 splicing variant in a LGMD2L patient leads to production of a truncated aggregation-prone Ano5 peptide.
Xu J et al.·J Pathol Clin Res
2018
ANO5 ensures trafficking of annexins in wounded myofibers.
Foltz SJ et al.·J Cell Biol
2021
Diagnostic anoctamin-5 protein defect in patients with ANO5-mutated muscular dystrophy.
Vihola A et al.·Neuropathol Appl Neurobiol
2018Cohort
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov
Neuromuscular DiseasesLimb Girdle Muscular Dystrophy

3 Year Follow up on ANO5 Patients

ACTIVE NOT RECRUITING
NCT05206617Rigshospitalet, DenmarkStarted 2018-01-01
No intervention - pure observational study
Limb Girdle Muscular Dystrophy

MRI-phenotyping of Patients With Pathogenic Anoctamin 5 Variants

RECRUITING
NCT05102799Rigshospitalet, DenmarkStarted 2021-04-01
No intervention

External Resources

Links to major genomics databases and tools