ANO1

Chr 11ARAD

anoctamin 1

Also known as: DOG1, INDMS, MYMY7, ORAOV2, TAOS2, TMEM16A

NCBI Gene: 55107ENSG00000131620UniProt: Q5XXA6

Enables identical protein binding activity; iodide transmembrane transporter activity; and ligand-gated monoatomic ion channel activity. Involved in several processes, including monoatomic anion transport; mucus secretion; and positive regulation of insulin secretion involved in cellular response to glucose stimulus. Located in apical plasma membrane and nucleoplasm. Implicated in Moyamoya disease. [provided by Alliance of Genome Resources, Jul 2025]

Primary Disease Associations & Inheritance

?Intestinal dysmotility syndromeMIM #620045
AR
Moyamoya disease 7MIM #620687
ADAR
215
ClinVar variants
11
Pathogenic / LP
0.87
pLI score
0
Active trials
Clinical Summary— ANO1
⚡
Population Constraint (gnomAD)
Moderately constrained gene (pLI 0.87) — some intolerance to loss-of-function variants.
📋
ClinVar Variants
11 Pathogenic / Likely Pathogenic· 134 VUS of 215 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
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.
0.33LOEUF
pLI 0.874
Z-score 5.52
OE 0.20 (0.12–0.33)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

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.
2.77Z-score
OE missense 0.68 (0.63–0.74)
413 obs / 604.7 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.0.20 (0.12–0.33)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.68 (0.63–0.74)
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.0.90
0≤1.21.6
LoF obs/exp: 11 / 55.2Missense obs/exp: 413 / 604.7Syn Z: 1.23

ClinVar Variant Classifications

215 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic8
Likely Pathogenic3
VUS134
Likely Benign32
Benign4
8
Pathogenic
3
Likely Pathogenic
134
VUS
32
Likely Benign
4
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
2
6
0
8
Likely Pathogenic
0
0
3
0
3
VUS
2
129
3
0
134
Likely Benign
0
10
4
18
32
Benign
0
0
1
3
4
Total21411721181

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

View in ClinVar →

Protein Context — Lollipop Plot

ANO1 · protein map & ClinVar variants

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

Gene2Phenotype Curations

ANO1-related intestinal disease

limited
ARLoss Of FunctionAbsent Gene Product
Dev. Disorders
G2P ↗

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

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

?Intestinal dysmotility syndrome

MIM #620045

Molecular basis of disorder known

Autosomal recessive

Moyamoya disease 7

MIM #620687

Molecular basis of disorder known

Autosomal dominantAutosomal recessive
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
ANO1-Mediated Inhibition of Cancer Ferroptosis Confers Immunotherapeutic Resistance through Recruiting Cancer-Associated Fibroblasts.
Jiang F et al.·Adv Sci (Weinh)
2023
Pendred syndrome.
Wémeau JL et al.·Best Pract Res Clin Endocrinol Metab
2017Review
ANO1: central role and clinical significance in non-neoplastic and neoplastic diseases.
Hu Y et al.·Front Immunol
2025Review
Blockade of calcium-activated chloride channel ANO1 ameliorates ionizing radiation-induced intestinal injury.
Guo Y et al.·J Adv Res
2026
Role of ANO1 in tumors and tumor immunity.
Li H et al.·J Cancer Res Clin Oncol
2022Review
TMEM16A/ANO1: Current Strategies and Novel Drug Approaches for Cystic Fibrosis.
Mitri C et al.·Cells
2021Review
IL-13-induced STAT3-dependent signaling networks regulate esophageal epithelial proliferation in eosinophilic esophagitis.
Marella S et al.·J Allergy Clin Immunol
2023
Pooled ctDNA analysis of MONALEESA phase III advanced breast cancer trials.
André F et al.·Ann Oncol
2023
Pathogenic Relationships in Cystic Fibrosis and Renal Diseases: CFTR, SLC26A9 and Anoctamins.
Kunzelmann K et al.·Int J Mol Sci
2023Review
Eosinophilic esophagitis: Immune mechanisms and therapeutic targets.
Khokhar D et al.·Clin Exp Allergy
2022Review
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
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