ANO10

Chr 3AR

anoctamin 10

Also known as: SCAR10, TMEM16K

NCBI Gene: 55129ENSG00000160746UniProt: Q9NW15OMIM: 613726

The protein encoded by ANO10 is a transmembrane protein belonging to the anoctamin family of calcium-activated chloride channels that inhibits the activity of ANO1, though it does not itself exhibit calcium-activated chloride channel activity. Mutations cause autosomal recessive spinocerebellar ataxia-10 through a predicted gain-of-function mechanism. The inheritance pattern is autosomal recessive.

GeneReviewsOMIMResearchSummary from RefSeq, OMIM, UniProt, Mechanism
MultiplemechanismARLOEUF 1.131 OMIM phenotype
Clinical Summary— ANO10
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Gene-Disease Validity (ClinGen)
autosomal recessive spinocerebellar ataxia 10 · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

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Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
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ClinVar Variants
12 unique Pathogenic / Likely Pathogenic· 50 VUS of 100 total submissions
Explore recent and relevant literature in Research Assistant →
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GeneReview available — ANO10
Authoritative clinical overview · Recommended first read
Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint
1.13LOEUF
pLI 0.000
Z-score 0.99
OE 0.81 (0.59–1.13)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
0.32Z-score
OE missense 0.95 (0.87–1.04)
327 obs / 343.5 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.81 (0.59–1.13)
0≤0.351.4
Missense OE0.95 (0.87–1.04)
0≤0.61.4
Synonymous OE1.11
0≤1.21.6
LoF obs/exp: 25 / 30.9Missense obs/exp: 327 / 343.5Syn Z: -0.95
DN
0.6746th %ile
GOF
0.76top 25%
LOF
0.2678th %ile

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.

GOFprediction above median
DNprediction 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

100 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic7
Likely Pathogenic5
VUS50
Likely Benign22
7
Pathogenic
5
Likely Pathogenic
50
VUS
22
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
4
0
3
0
7
Likely Pathogenic
5
0
0
0
5
VUS
0
49
1
0
50
Likely Benign
0
0
6
16
22
Benign
0
0
0
0
0
Total949101684

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

View in ClinVar →

Protein Context — Lollipop Plot

ANO10 · 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

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
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
ANO10-Related Spinocerebellar Ataxia: MDSGene Systematic Literature Review and a Romani Case Series.
Milovanović A et al.·Mov Disord
2024Review
A Coding Variant of ANO10, Affecting Volume Regulation of Macrophages, Is Associated with Borrelia Seropositivity.
Hammer C et al.·Mol Med
2015
[Rare forms of autosomal recessive spinocerebellar ataxia associated with mutations in the ANO10 (ATX-ANO10) and SYNE1 (ATX-SYNE1) genes].
Nuzhnyi EP et al.·Zh Nevrol Psikhiatr Im S S Korsakova
2024
Executive and Attentional Disorders, Epilepsy and Porencephalic Cyst in Autosomal Recessive Cerebellar Ataxia Type 3 Due to ANO10 Mutation.
Chamard L et al.·Eur Neurol
2016Case report
Autosomal recessive spino-cerebellar ataxia type 10 (SCAR10): clinical presentation associated with c.289delA ANO10 gene variant.
Norata D et al.·Neurol Sci
2024
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients