ATG2A

Chr 11

autophagy related 2A

Also known as: BLTP4A

NCBI Gene: 23130 ENSG00000110046 UniProt: Q2TAZ0 OMIM: 616225

ATG2A encodes a lipid transfer protein that mediates autophagosome assembly by transferring phospholipids from the endoplasmic reticulum to expanding isolation membranes during autophagy. Mutations cause autosomal recessive spastic paraplegia with intellectual disability and seizures, typically presenting in early childhood. The gene is highly constrained against loss-of-function variants (LOEUF 0.346), reflecting its essential role in cellular autophagy.

OMIM ResearchSummary from RefSeq, UniProt

Enables lipid transfer activity. Involved in autophagosome assembly and positive regulation of autophagosome assembly. Is active in organelle membrane contact site. [provided by Alliance of Genome Resources, Jul 2025]

OMIM ResearchGenerating clinical summary…

Clinical highlights

Interpreting a novel variant

This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Based on population constraint only.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.35

LOEUF· LoF intol.

—

Mechanism

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

LoF intolerant — likely haploinsufficient

LoF Constraint?

0.35LOEUF

pLI 0.054

Z-score 6.70

OE 0.24 (0.17–0.35)

Highly constrained

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

Missense Constraint?

1.81Z-score

OE missense 0.85 (0.81–0.90)

1027 obs / 1204.2 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.24 (0.17–0.35)

0≤0.351.4

Missense OE?0.85 (0.81–0.90)

0≤0.61.4

Synonymous OE?0.98

0≤1.21.6

LoF obs/exp: 22 / 90.9Missense obs/exp: 1027 / 1204.2Syn Z: 0.41

Background carrier burden — how many people carry a rare variant somewhere in ATG2A?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 22

2,519 rare PASS variants

Rare truncating (LoF)

1 in 1,100

264 rare PASS variants

Rare synonymous (reference)

1 in 32

1,147 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for ATG2A. 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 27	1 in 1,100
South Asian	~43k	1 in 21	1 in 770
Remaining (unassigned)	~30k	1 in 19	1 in 2,100
European (Finnish)	~27k	1 in 85	1 in 1,300
Admixed American	~22k	1 in 21	1 in 810
African / African American	~21k	1 in 18	1 in 750
East Asian	~20k	1 in 21	1 in 950
Ashkenazi Jewish	~13k	1 in 66	≈ 1 in 6,200
Middle Eastern	~2,884	1 in 17	1 in 510

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): All 41 coding exons well covered in gnomAD exomes and genomes.? see exons ↓