ATG3

Chr 3

autophagy related 3

Also known as: APG3, APG3-LIKE, APG3L, PC3-96, hApg3

NCBI Gene: 64422 ENSG00000144848 UniProt: Q9NT62 OMIM: 609606

This gene encodes an E2 conjugating enzyme that catalyzes the lipidation of ATG8-like proteins to phosphatidylethanolamine in membranes, a critical step in autophagosome formation during autophagy. Mutations cause ATG3-related developmental and epileptic encephalopathy, characterized by early-onset seizures, severe developmental delay, and neurodegeneration with autosomal recessive inheritance. The gene shows tolerance to loss-of-function variants in the general population, suggesting that pathogenic variants likely have specific functional consequences.

OMIM ResearchSummary from RefSeq, UniProt

This gene encodes a ubiquitin-like-conjugating enzyme and is a component of ubiquitination-like systems involved in autophagy, the process of degradation, turnover and recycling of cytoplasmic constituents in eukaryotic cells. This protein is known to play a role in regulation of autophagy during cell death. A pseudogene of this gene is located on chromosome 20. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jul 2013]

OMIM ResearchGenerating clinical summary…

DNmechanismLOEUF 0.72

Clinical Summary— ATG3

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.72LOEUF

pLI 0.001

Z-score 2.55

OE 0.41 (0.25–0.72)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

1.76Z-score

OE missense 0.61 (0.52–0.72)

101 obs / 164.6 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.41 (0.25–0.72)

0≤0.351.4

Missense OE?0.61 (0.52–0.72)

0≤0.61.4

Synonymous OE?0.96

0≤1.21.6

LoF obs/exp: 9 / 21.9Missense obs/exp: 101 / 164.6Syn Z: 0.24

This gene — mechanism propensity

0.6745th %ile

GOF

0.5758th %ile

LOF

0.2971th %ile

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.