ANO2

Chr 12

anoctamin 2

Also known as: C12orf3, TMEM16B

ANO2 encodes a calcium-activated chloride channel that functions in olfactory signal transduction and may contribute to light perception amplification in the retina. This gene is not highly constrained against loss-of-function variation and currently has no well-established disease associations in pediatric neurogenetics. Further research is needed to determine if ANO2 mutations cause human disease.

Summary from RefSeq, UniProt
Research Assistant →
0
Active trials
8
Pubs (1 yr)
52
P/LP submissions
P/LP missense
0.96
LOEUF
Multiple*
Mechanism· predicted
Clinical SummaryANO2
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
52 unique Pathogenic / Likely Pathogenic· 8 VUS of 85 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
0.96LOEUF
pLI 0.000
Z-score 1.79
OE 0.74 (0.580.96)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
-0.01Z-score
OE missense 1.00 (0.931.07)
568 obs / 567.1 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE0.74 (0.580.96)
00.351.4
Missense OE1.00 (0.931.07)
00.61.4
Synonymous OE0.97
01.21.6
LoF obs/exp: 42 / 56.5Missense obs/exp: 568 / 567.1Syn Z: 0.41
DN
0.7034th %ile
GOF
0.79top 25%
LOF
0.2971th %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

85 submitted variants in ClinVar

Classification Summary

Pathogenic49
Likely Pathogenic3
VUS8
Likely Benign4
Benign2
49
Pathogenic
3
Likely Pathogenic
8
VUS
4
Likely Benign
2
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories· variant type breakdown unavailable

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
49
Likely Pathogenic
3
VUS
8
Likely Benign
4
Benign
2
Total66

Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

ANO2 · protein map & ClinVar variants

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

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
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