ANO3

Chr 11AD

anoctamin 3

Also known as: C11orf25, DYT23, DYT24, GENX-3947, TMEM16C

NCBI Gene: 63982ENSG00000134343UniProt: Q9BYT9

The protein encoded by this gene belongs to the TMEM16 family of predicted membrane proteins, that are also known as anoctamins. While little is known about the function of this gene, mutations in this gene have been associated with some cases of autosomal dominant craniocervical dystonia. Cells from individuals with a mutation in this gene exhibited abnormalities in endoplasmic reticulum-dependent calcium signaling. Studies in rat show that the rat ortholog of this protein interacts with, and modulates the activity of a sodium-activated potassium channel. Deletion of this gene caused increased pain sensitivity in the rat model system. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Aug 2015]

Primary Disease Associations & Inheritance

Dystonia 24MIM #615034
AD
745
ClinVar variants
7
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— ANO3
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
7 Pathogenic / Likely Pathogenic· 294 VUS of 745 total submissions

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.
0.77LOEUF
pLI 0.000
Z-score 3.11
OE 0.58 (0.45–0.77)
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.
2.46Z-score
OE missense 0.70 (0.65–0.76)
378 obs / 538.4 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

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.0.58 (0.45–0.77)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.70 (0.65–0.76)
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.1.01
0≤1.21.6
LoF obs/exp: 38 / 65.0Missense obs/exp: 378 / 538.4Syn Z: -0.15

ClinVar Variant Classifications

745 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic6
Likely Pathogenic1
VUS294
Likely Benign126
Benign54
Conflicting6
6
Pathogenic
1
Likely Pathogenic
294
VUS
126
Likely Benign
54
Benign
6
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
2
4
0
6
Likely Pathogenic
0
1
0
0
1
VUS
10
240
38
6
294
Likely Benign
1
10
62
53
126
Benign
0
1
50
3
54
Conflicting
—6
Total1125415462487

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

View in ClinVar →

Protein Context — Lollipop Plot

ANO3 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Gene2Phenotype Curations

ANO3-related dystonia

limited
ADUndeterminedAltered Gene Product Structure
Dev. Disorders
G2P ↗
missense variant

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

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
ANOCTAMIN 3; ANO3
MIM #610110 · *

Dystonia 24

MIM #615034

Molecular basis of disorder known

Autosomal dominant
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Genetics and Pathogenesis of Dystonia.
Thomsen M et al.·Annu Rev Pathol
2024Review
Genetic Update and Treatment for Dystonia.
Koptielow J et al.·Int J Mol Sci
2024Review
Dystonia.
Morgante F et al.·Continuum (Minneap Minn)
2013Review
Genetics in dystonia.
Klein C·Parkinsonism Relat Disord
2014Review
The Clinical Spectrum of ANO3-Report of a New Family and Literature Review.
Percetti M et al.·Mov Disord Clin Pract
2024Review
Isolated dystonia: clinical and genetic updates.
Domingo A et al.·J Neural Transm (Vienna)
2021Review
Update on the Genetics of Dystonia.
Lohmann K et al.·Curr Neurol Neurosci Rep
2017Review
ANO3 and early-onset dyskinetic encephalopathy.
Jiménez de Domingo A et al.·Eur J Med Genet
2020Case report
Genotype-Phenotype Relations for Isolated Dystonia Genes: MDSGene Systematic Review.
Lange LM et al.·Mov Disord
2021Review
The expanding clinical and genetic spectrum of ANO3 dystonia.
Jiang LT et al.·Neurosci Lett
2021Case report
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
ANO3-related tremulous dystonia: case report.
Altıntaş M et al.·Acta Neurol Belg
2025Case report
Dystonia caused by ANO3 variants is due to attenuated Ca2+ influx by ORAI1.
Ousingsawat J et al.·BMC Med
2025🔓 Open Access
Broadening the clinical spectrum: molecular mechanisms and new phenotypes of ANO3-dystonia.
Ousingsawat J et al.·Brain
2024Functional
A novel ANO3 variant in two siblings with different phenotypes.
Esposito M et al.·Parkinsonism Relat Disord
2023
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools