ATG7

Chr 3AR

autophagy related 7

Also known as: APG7-LIKE, APG7L, GSA7, SCAR31

NCBI Gene: 10533ENSG00000197548UniProt: O95352

This gene encodes an E1-like activating enzyme that is essential for autophagy and cytoplasmic to vacuole transport. The encoded protein is also thought to modulate p53-dependent cell cycle pathways during prolonged metabolic stress. It has been associated with multiple functions, including axon membrane trafficking, axonal homeostasis, mitophagy, adipose differentiation, and hematopoietic stem cell maintenance. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Sep 2015]

Primary Disease Associations & Inheritance

Spinocerebellar ataxia, autosomal recessive 31MIM #619422
AR
223
ClinVar variants
42
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— ATG7
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
42 Pathogenic / Likely Pathogenic· 125 VUS of 223 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
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.
0.94LOEUF
pLI 0.000
Z-score 1.86
OE 0.66 (0.47–0.94)
Tolerant

Typical tolerance to LoF variation

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.
1.37Z-score
OE missense 0.80 (0.73–0.88)
313 obs / 388.9 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.0.66 (0.47–0.94)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.80 (0.73–0.88)
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.0.99
0≤1.21.6
LoF obs/exp: 23 / 34.8Missense obs/exp: 313 / 388.9Syn Z: 0.11

ClinVar Variant Classifications

223 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic39
Likely Pathogenic3
VUS125
Likely Benign18
Benign4
Conflicting2
39
Pathogenic
3
Likely Pathogenic
125
VUS
18
Likely Benign
4
Benign
2
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
1
4
34
0
39
Likely Pathogenic
1
0
2
0
3
VUS
0
120
5
0
125
Likely Benign
0
9
2
7
18
Benign
0
0
2
2
4
Conflicting
—2
Total2133459191

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

View in ClinVar →

Protein Context — Lollipop Plot

ATG7 · protein map & ClinVar variants

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

Gene2Phenotype Curations

ATG7-related intellectual disability and ataxia

strong
ARLoss Of FunctionAbsent Gene Product
Dev. Disorders
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Spinocerebellar ataxia, autosomal recessive 31

MIM #619422

Molecular basis of disorder known

Autosomal recessive
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
ROS-mediated lysosomal membrane permeabilization and autophagy inhibition regulate bleomycin-induced cellular senescence.
Qi Z et al.·Autophagy
2024
Tubular cells produce FGF2 via autophagy after acute kidney injury leading to fibroblast activation and renal fibrosis.
Livingston MJ et al.·Autophagy
2023
CKAP5 deficiency induces premature ovarian insufficiency.
Hu Z et al.·EBioMedicine
2025
Autophagy deficiency abolishes liver mitochondrial DNA segregation.
Tostes K et al.·Autophagy
2022
Autophagy in the physiological endometrium and cancer.
Devis-Jauregui L et al.·Autophagy
2021Review
Increased LCN2 (lipocalin 2) in the RPE decreases autophagy and activates inflammasome-ferroptosis processes in a mouse model of dry AMD.
Gupta U et al.·Autophagy
2023Functional
Periplocin suppresses the growth of colorectal cancer cells by triggering LGALS3 (galectin 3)-mediated lysophagy.
Wang K et al.·Autophagy
2023
METTL3-mediated m(6)A modification of ATG7 regulates autophagy-GATA4 axis to promote cellular senescence and osteoarthritis progression.
Chen X et al.·Ann Rheum Dis
2022
ATF3 Deficiency Exacerbates Ageing-Induced Atherosclerosis and Clinical Intervention Strategy.
Nie H et al.·Adv Sci (Weinh)
2025
Circumventing autophagy inhibition.
Towers CG et al.·Cell Cycle
2019Review
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Salvia plebeia R. Br. extract delays cellular senescence and promotes healthy aging via Atg7-dependent autophagy, with rosmarinic acid as a major bioactive constituent.
He YN et al.·J Nutr Biochem
2026
A multilayered integrated analysis of insomnia-related genes ATG7 and JAK2 in the autophagy-inflammation mechanism and clinical implications in major depressive disorder.
Yu J et al.·Comput Biol Chem
2026Functional
Enhanced insulin signaling via circulating ATG7: A potential therapeutic strategy for diabetes.
Guan Y et al.·Proc Natl Acad Sci U S A
2026
The dual role of core autophagy E1 enzyme ATG7: revealing a new negative feedback mechanism as a substrate for protein ATG8ylation.
Xie H et al.·Autophagy
2026Functional
ATG7 dysfunction in senescent melanocytes and hypopigmented skin: Reversal by metformin.
Kim JC et al.·Br J Dermatol
2025
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