ATG5

Chr 6AR

autophagy related 5

Also known as: APG5, APG5-LIKE, APG5L, ASP, SCAR25, hAPG5

NCBI Gene: 9474ENSG00000057663UniProt: Q9H1Y0OMIM: 604261

ATG5 encodes a protein that functions as an E1-like activating enzyme in autophagy, essential for autophagic vesicle formation, mitochondrial quality control, lymphocyte development, and axon maintenance. Mutations cause autosomal recessive spinocerebellar ataxia (SCAR25). The gene is highly constrained against loss-of-function variants (pLI 0.98, LOEUF 0.30), indicating that complete loss of ATG5 function is likely detrimental.

OMIMResearchSummary from RefSeq, OMIM, UniProt
LOFmechanismARLOEUF 0.291 OMIM phenotype
Clinical Summary— ATG5
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Gene-Disease Validity (ClinGen)
spinocerebellar ataxia, autosomal recessive 25 · ARLimited

Limited evidence — not for standalone diagnostic reporting

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Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.98). One damaged copy is likely sufficient to cause disease.
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ClinVar Variants
15 unique Pathogenic / Likely Pathogenic· 24 VUS of 53 total submissions
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Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available
Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
LoF Constraint
0.29LOEUF
pLI 0.978
Z-score 3.48
OE 0.06 (0.02–0.29)
Highly constrained

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

Missense Constraint
1.82Z-score
OE missense 0.57 (0.48–0.69)
81 obs / 142.0 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.06 (0.02–0.29)
0≤0.351.4
Missense OE0.57 (0.48–0.69)
0≤0.61.4
Synonymous OE0.83
0≤1.21.6
LoF obs/exp: 1 / 16.1Missense obs/exp: 81 / 142.0Syn Z: 0.89
DN
0.3694th %ile
GOF
0.3887th %ile
LOF
0.67top 25%

The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).

LOFprediction above median · LOEUF 0.29

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

53 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic15
VUS24
Likely Benign1
Benign5
15
Pathogenic
24
VUS
1
Likely Benign
5
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
15
0
15
Likely Pathogenic
0
0
0
0
0
VUS
2
11
11
0
24
Likely Benign
0
1
0
0
1
Benign
0
2
1
2
5
Total21427245

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

ATG5 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

3D Protein StructureAlphaFold
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
ATG7 vs. ATG5: Distinct autophagy pathways shaping TGF-β signaling and endothelial function.
Singh A et al.·PLoS One
2026
ATG5 overexpression enhances the therapeutic efficacy of mesenchymal stem cells in a mouse colitis model by augmenting anti-inflammatory and antioxidative mechanisms.
Sun Y et al.·Stem Cell Res Ther
2026Functional
Suppression of fibroblastic activity prolongs cardiac transplant survival through targeting their ATG5 expression.
Wu Z et al.·J Thorac Cardiovasc Surg
2026
Urinary mRNA profiling of autophagy-related genes ATG5, ATG7, MAP1LC3B, and mTOR in non-muscle invasive bladder cancer (NMIBC).
Chamgordani PR et al.·Cancer Treat Res Commun
2026
Restoring cardiolipin homeostasis mitigates cerebral ischemia-reperfusion injury by suppressing ATG5-mediated neuronal autophagy-dependent ferroptosis.
Dong W et al.·J Adv Res
2026
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients