ANO3

Chr 11AD

anoctamin 3

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

The protein is a transmembrane calcium-activated chloride channel that belongs to the anoctamin family and modulates calcium signaling pathways. Mutations cause autosomal dominant craniocervical dystonia (dystonia 24) through a gain-of-function mechanism that disrupts endoplasmic reticulum-dependent calcium signaling. The inheritance pattern is autosomal dominant.

GeneReviewsOMIMResearchSummary from RefSeq, OMIM, UniProt, Mechanism
MultiplemechanismADLOEUF 0.771 OMIM phenotype
Clinical SummaryANO3
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
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GeneReview available — ANO3
Authoritative clinical overview · Recommended first read
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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
0.77LOEUF
pLI 0.000
Z-score 3.11
OE 0.58 (0.450.77)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
2.46Z-score
OE missense 0.70 (0.650.76)
378 obs / 538.4 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios
LoF OE0.58 (0.450.77)
00.351.4
Missense OE0.70 (0.650.76)
00.61.4
Synonymous OE1.01
01.21.6
LoF obs/exp: 38 / 65.0Missense obs/exp: 378 / 538.4Syn Z: -0.15
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
limitedANO3-related dystoniaOTHERAD
DN
0.80top 25%
GOF
0.79top 25%
LOF
0.2386th %ile

This gene has evidence for multiple mechanisms of pathogenicity (dominant-negative and gain-of-function). Both the Badonyi & Marsh prediction and the broader genomic evidence point to dominant-negative as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

DNprediction above median
GOFprediction above median

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.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

0 submitted variants 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.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Genetics and Pathogenesis of Dystonia.
Thomsen M et al.·Annu Rev Pathol
2024Review
The Clinical Spectrum of ANO3-Report of a New Family and Literature Review.
Percetti M et al.·Mov Disord Clin Pract
2024Review
Genetic Update and Treatment for Dystonia.
Koptielow J et al.·Int J Mol Sci
2024Review
Isolated dystonia: clinical and genetic updates.
Domingo A et al.·J Neural Transm (Vienna)
2021Review
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC