ANO10

Chr 3AR

anoctamin 10

Also known as: SCAR10, TMEM16K

NCBI Gene: 55129 ENSG00000160746 UniProt: Q9NW15 OMIM: 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.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt, Mechanism

The transmembrane protein encoded by this gene belongs to the anoctamin family of calcium-activated chloride channels, also known as the transmembrane 16 family. The encoded protein contains eight transmembrane domains with cytosolic N- and C-termini. Defects in this gene may cause autosomal recessive spinocerebellar ataxia-10. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Oct 2016]

GeneReviews OMIM ResearchGenerating clinical summary…

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

89 unique Pathogenic / Likely Pathogenic· 174 VUS of 617 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 OE?0.81 (0.59–1.13)

0≤0.351.4

Missense OE?0.95 (0.87–1.04)

0≤0.61.4

Synonymous OE?1.11

0≤1.21.6

LoF obs/exp: 25 / 30.9Missense obs/exp: 327 / 343.5Syn Z: -0.95

This gene — mechanism propensity

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

617 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic55

Likely Pathogenic34

VUS174

Likely Benign247

Benign52

Conflicting39

Pathogenic

Likely Pathogenic

174

VUS

247

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	45	1	9	0	55
Likely Pathogenic	25	4	5	0	34
VUS	1	146	25	2	174
Likely Benign	0	9	100	138	247
Benign	0	5	44	3	52
Conflicting	—				39
Total	71	165	183	143	601

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

View in ClinVar →

8 pathogenic / likely-pathogenic (of 13) ClinVar copy-number / structural variants overlap ANO10 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →