ANO2

Chr 12

anoctamin 2

Also known as: C12orf3, TMEM16B

NCBI Gene: 57101 ENSG00000047617 UniProt: Q9NQ90 OMIM: 610109

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.

OMIM ResearchSummary from RefSeq, UniProt

ANO2 belongs to a family of calcium-activated chloride channels (CaCCs) (reviewed by Hartzell et al., 2009 [PubMed 19015192]).[supplied by OMIM, Jan 2011]

OMIM ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.96

LOEUF

Multiple*

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.96LOEUF

pLI 0.000

Z-score 1.79

OE 0.74 (0.58–0.96)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

-0.01Z-score

OE missense 1.00 (0.93–1.07)

568 obs / 567.1 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.74 (0.58–0.96)

0≤0.351.4

Missense OE?1.00 (0.93–1.07)

0≤0.61.4

Synonymous OE?0.97

0≤1.21.6

LoF obs/exp: 42 / 56.5Missense obs/exp: 568 / 567.1Syn Z: 0.41

Background carrier burden — how many people carry a rare variant somewhere in ANO2?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 34

1,404 rare PASS variants

Rare truncating (LoF)

1 in 310

232 rare PASS variants

Rare synonymous (reference)

1 in 75

519 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for ANO2. 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 38	1 in 360
South Asian	~43k	1 in 30	1 in 390
Remaining (unassigned)	~30k	1 in 27	1 in 270
European (Finnish)	~27k	1 in 180	1 in 1,800
Admixed American	~22k	1 in 30	1 in 240
African / African American	~21k	1 in 27	1 in 200
East Asian	~20k	1 in 44	1 in 280
Ashkenazi Jewish	~13k	1 in 57	≈ 1 in 4,300
Middle Eastern	~2,884	1 in 38	≈ 1 in 700

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