ANO5

Chr 11

anoctamin 5

Also known as: GDD1, LGMD2L, LGMDR12, TMEM16E

NCBI Gene: 203859 ENSG00000171714 UniProt: Q75V66

The protein functions in plasma membrane repair through interaction with annexins and localizes to the endoplasmic reticulum membrane. Mutations cause autosomal recessive limb-girdle muscular dystrophy type 12 and Miyoshi muscular dystrophy 3, as well as autosomal dominant gnathodiaphyseal dysplasia through a predicted gain-of-function mechanism. The muscular dystrophies result from impaired membrane repair, while the bone dysplasia represents a distinct dominant phenotype.

GeneReviews ResearchSummary from RefSeq, OMIM, UniProt, Mechanism

This gene encodes a member of the anoctamin family of transmembrane proteins. The encoded protein is likely a calcium activated chloride channel. Mutations in this gene have been associated with gnathodiaphyseal dysplasia. Alternatively spliced transcript variants have been described. [provided by RefSeq, Nov 2009]

GeneReviews ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtGnathodiaphyseal dysplasia

UniProtMuscular dystrophy, limb-girdle, autosomal recessive 12

UniProtMiyoshi muscular dystrophy 3

Clinical highlights

Gene–disease validity (ClinGen)

Interpreting a novel variant

Gain of function is the curated mechanism (Gene2Phenotype), so a variant that simply removes the protein may not be the pathogenic class here — missense variants in functional domains often carry more weight.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

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Pubs (1 yr)

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P/LP submissions

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P/LP missense

0.95

LOEUF

GOF

Mechanism· G2P

📖

GeneReview available — ANO5

Authoritative clinical overview · Recommended first read

Open GeneReview ↗

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.95LOEUF

pLI 0.000

Z-score 1.86

OE 0.73 (0.57–0.95)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

0.12Z-score

OE missense 0.98 (0.91–1.06)

467 obs / 474.2 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.73 (0.57–0.95)

0≤0.351.4

Missense OE?0.98 (0.91–1.06)

0≤0.61.4

Synonymous OE?1.18

0≤1.21.6

LoF obs/exp: 42 / 57.2Missense obs/exp: 467 / 474.2Syn Z: -1.80

Background carrier burden — how many people carry a rare variant somewhere in ANO5?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 47

1,131 rare PASS variants

Rare truncating (LoF)

1 in 520

236 rare PASS variants

Rare synonymous (reference)

1 in 150

423 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for ANO5. 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 76	1 in 530
South Asian	~43k	1 in 52	1 in 760
Remaining (unassigned)	~30k	1 in 45	1 in 530
European (Finnish)	~27k	1 in 180	1 in 530
Admixed American	~22k	1 in 50	1 in 360
African / African American	~21k	1 in 51	1 in 380
East Asian	~20k	1 in 51	1 in 520
Ashkenazi Jewish	~13k	1 in 180	1 in 650
Middle Eastern	~2,884	1 in 76	1 in 410

Each group is summed over the variants that are rare in that group. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): 18 of 22 coding exons well covered in gnomAD exomes; exons 2, 5, 6, 14 marginal. Genomes: all 22.? see exons ↓