ATG3
Chr 3autophagy related 3
Also known as: APG3, APG3-LIKE, APG3L, PC3-96, hApg3
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.
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Typical tolerance to LoF variation
Mild missense constraint
The highest-scoring mechanism for this gene is dominant-negative.
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.
ClinVar Variant Classifications
88 submitted variants in ClinVar
Classification Summary
Curated Variants Distribution
Classified variants from ClinVar · 5 ACMG categories
| Classification | LoF | Missense + Inframe | Non-coding | Synonymous | Total |
|---|---|---|---|---|---|
Pathogenic | 0 | 0 | 25 | 0 | 25 |
Likely Pathogenic | 0 | 0 | 1 | 0 | 1 |
VUS | 0 | 31 | 5 | 0 | 36 |
Likely Benign | 0 | 0 | 0 | 0 | 0 |
Benign | 0 | 0 | 0 | 0 | 0 |
| Total | 0 | 31 | 31 | 0 | 62 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
ATG3 · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
3D Protein StructureAlphaFold
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
No active trials found for this gene.
Search ClinicalTrials.gov →External Resources
Links to major genomics databases and tools