ANO1

Chr 11ARAD

anoctamin 1

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

NCBI Gene: 55107 ENSG00000131620 UniProt: Q5XXA6 OMIM: 610108

The protein functions as a calcium-activated chloride channel essential for transepithelial anion transport, smooth muscle contraction, mucus secretion in airways and intestine, and gastrointestinal pacemaker activity through interstitial cells of Cajal. Mutations cause Moyamoya disease with autosomal dominant inheritance. The gene is highly constrained against loss-of-function variants (pLI 0.87, LOEUF 0.33), indicating that complete protein loss is likely incompatible with normal development.

GeneReviews OMIM ResearchSummary from RefSeq, UniProt

Enables identical protein binding activity and monoatomic ion transmembrane transporter activity. Involved in monoatomic anion transport; mucus secretion; and protein localization to membrane. Located in apical plasma membrane. Implicated in Moyamoya disease. [provided by Alliance of Genome Resources, Jun 2026]

GeneReviews OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

?Intestinal dysmotility syndromeMIM #620045

Moyamoya disease 7MIM #620687

ADAR

Clinical highlights

Gene–disease validity

Not independently assessedOMIM lists Moyamoya disease 7; no ClinGen or GenCC tier

Interpreting a novel variant

Loss of function is the curated mechanism (Gene2Phenotype) and the gene is intolerant of it in the population — truncating, frameshift and canonical splice variants carry more prior weight here than missense.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

103

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.33

LOEUF· LoF intol.

LOF

Mechanism· G2P

📖

GeneReview available — ANO1

Authoritative clinical overview · Recommended first read

Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

LoF intolerant — likely haploinsufficient

LoF Constraint?

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?

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?

LoF OE?0.20 (0.12–0.33)

0≤0.351.4

Missense OE?0.68 (0.63–0.74)

0≤0.61.4

Synonymous OE?0.90

0≤1.21.6

LoF obs/exp: 11 / 55.2Missense obs/exp: 413 / 604.7Syn Z: 1.23

Background carrier burden — how many people carry a rare variant somewhere in ANO1?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 50

1,232 rare PASS variants

Rare truncating (LoF)

1 in 930

179 rare PASS variants

Rare synonymous (reference)

1 in 58

612 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for ANO1. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 68	1 in 1,400
South Asian	~43k	1 in 40	1 in 330
Remaining (unassigned)	~30k	1 in 43	1 in 1,200
European (Finnish)	~27k	1 in 110	1 in 2,500
Admixed American	~22k	1 in 38	1 in 1,600
African / African American	~21k	1 in 50	1 in 1,200
East Asian	~20k	1 in 51	1 in 580
Ashkenazi Jewish	~13k	1 in 220	≈ 1 in 4,300
Middle Eastern	~2,884	1 in 46	1 in 470

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): 25 of 26 coding exons well covered in gnomAD exomes; exon 1 marginal. Genomes: all 26.? see exons ↓