ATG5

Chr 6AR

autophagy related 5

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

NCBI Gene: 9474ENSG00000057663UniProt: Q9H1Y0

The protein encoded by this gene, in combination with autophagy protein 12, functions as an E1-like activating enzyme in a ubiquitin-like conjugating system. The encoded protein is involved in several cellular processes, including autophagic vesicle formation, mitochondrial quality control after oxidative damage, negative regulation of the innate antiviral immune response, lymphocyte development and proliferation, MHC II antigen presentation, adipocyte differentiation, and apoptosis. Several transcript variants encoding different protein isoforms have been found for this gene. [provided by RefSeq, Sep 2015]

Primary Disease Associations & Inheritance

?Spinocerebellar ataxia, autosomal recessive 25MIM #617584
AR
45
ClinVar variants
15
Pathogenic / LP
0.98
pLI score· haploinsufficient
0
Active trials
Clinical Summary— ATG5
🧬
Gene-Disease Validity (ClinGen)
spinocerebellar ataxia, autosomal recessive 25 · ARLimited

Limited evidence — not for standalone diagnostic reporting

⚡
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.
📋
ClinVar Variants
15 Pathogenic / Likely Pathogenic· 24 VUS of 45 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
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?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
1.82Z-score
OE missense 0.57 (0.48–0.69)
81 obs / 142.0 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.06 (0.02–0.29)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.57 (0.48–0.69)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.83
0≤1.21.6
LoF obs/exp: 1 / 16.1Missense obs/exp: 81 / 142.0Syn Z: 0.89

ClinVar Variant Classifications

45 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
1
12
11
0
24
Likely Benign
0
1
0
0
1
Benign
0
2
1
2
5
Total11527245

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.

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

?Spinocerebellar ataxia, autosomal recessive 25

MIM #617584

Molecular basis of disorder known

Autosomal recessive
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Copper metabolism in cell death and autophagy.
Xue Q et al.·Autophagy
2023Review
TRIM45 aggravates microglia pyroptosis via Atg5/NLRP3 axis in septic encephalopathy.
Huang X et al.·J Neuroinflammation
2023
Autophagy in the physiological endometrium and cancer.
Devis-Jauregui L et al.·Autophagy
2021Review
Periplocin suppresses the growth of colorectal cancer cells by triggering LGALS3 (galectin 3)-mediated lysophagy.
Wang K et al.·Autophagy
2023
HMBOX1 reverses autophagy mediated 5-fluorouracil resistance through promoting HACE1-induced ubiquitination and degradation of ATG5 in colorectal cancer.
Gao Y et al.·Autophagy
2025
Autophagy modulates endothelial junctions to restrain neutrophil diapedesis during inflammation.
Reglero-Real N et al.·Immunity
2021
Pathogenicity and virulence of Japanese encephalitis virus: Neuroinflammation and neuronal cell damage.
Ashraf U et al.·Virulence
2021Review
MIR106A-5p upregulation suppresses autophagy and accelerates malignant phenotype in nasopharyngeal carcinoma.
Zhu Q et al.·Autophagy
2021
Inhibition of ACSS2 triggers glycolysis inhibition and nuclear translocation to activate SIRT1/ATG5/ATG2B deacetylation axis, promoting autophagy and reducing malignancy and chemoresistance in ovarian cancer.
Yang J et al.·Metabolism
2025
USP19 potentiates autophagic cell death via inhibiting mTOR pathway through deubiquitinating NEK9 in pancreatic cancer.
Wang G et al.·Cell Death Differ
2025
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools