ATL3

Chr 11

atlastin GTPase 3

Also known as: AT3, ATL-3, HSN1F

NCBI Gene: 25923 ENSG00000184743 UniProt: Q6DD88

Atlastin-3 is a membrane-anchored GTPase that mediates GTP-dependent fusion of endoplasmic reticulum membranes to maintain the continuous ER network. Mutations cause hereditary sensory neuropathy type IF, which primarily affects the peripheral sensory nervous system. This gene follows autosomal recessive inheritance and is not highly constrained against loss-of-function variants.

ResearchSummary from RefSeq, UniProt

This gene encodes a member of a family of dynamin-like, integral membrane GTPases. The encoded protein is required for the proper formation of the network of interconnected tubules of the endoplasmic reticulum. Mutations in this gene may be associated with hereditary sensory neuropathy type IF. Alternatively spliced transcript variants that encode distinct isoforms have been described. [provided by RefSeq, Feb 2014]

ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtNeuropathy, hereditary sensory, 1F

Clinical highlights

Gene–disease validity (ClinGen)

Moderate · neuropathy, hereditary sensory, type 1F · AD · ClinGen 2026

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.90

LOEUF

Multiple*

Mechanism· predicted

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?

0.90LOEUF

pLI 0.000

Z-score 1.98

OE 0.62 (0.43–0.90)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

1.15Z-score

OE missense 0.81 (0.73–0.90)

232 obs / 286.7 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.62 (0.43–0.90)

0≤0.351.4

Missense OE?0.81 (0.73–0.90)

0≤0.61.4

Synonymous OE?1.08

0≤1.21.6

LoF obs/exp: 19 / 30.9Missense obs/exp: 232 / 286.7Syn Z: -0.68

Background carrier burden — how many people carry a rare variant somewhere in ATL3?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 110

765 rare PASS variants

Rare truncating (LoF)

1 in 1,400

133 rare PASS variants

Rare synonymous (reference)

1 in 200

286 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for ATL3. 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 160	1 in 1,900
South Asian	~43k	1 in 92	1 in 350
Remaining (unassigned)	~30k	1 in 68	1 in 1,400
European (Finnish)	~27k	1 in 830	≈ 1 in 26,000
Admixed American	~22k	1 in 99	1 in 1,400
African / African American	~21k	1 in 50	1 in 880
East Asian	~20k	1 in 130	1 in 1,500
Ashkenazi Jewish	~13k	1 in 1,400	≈ 1 in 6,500
Middle Eastern	~2,884	1 in 76	1 in 560

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): 12 of 13 coding exons well covered in gnomAD exomes; exon 6 marginal. Genomes: all 13.? see exons ↓