ATG7

Chr 3AR

autophagy related 7

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

NCBI Gene: 10533 ENSG00000197548 UniProt: O95352 OMIM: 608760

ATG7 encodes an E1-like activating enzyme essential for autophagy, activating ATG12 and ATG8 family proteins for conjugation reactions required for autophagosome formation and cytoplasm-to-vacuole transport. Mutations cause spinocerebellar ataxia, autosomal recessive 31, which follows autosomal recessive inheritance. The gene is not highly constrained against loss-of-function variants and plays critical roles in axonal homeostasis and mitochondrial quality control.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

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]

OMIM ResearchGenerating clinical summary…

LOFmechanismARLOEUF 0.941 OMIM phenotype

Clinical Summary— ATG7

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Gene-Disease Validity (ClinGen)

spinocerebellar ataxia, autosomal recessive 31 · ARStrong

Strong evidence — appropriate for clinical testing

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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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ClinVar Variants

9 unique Pathogenic / Likely Pathogenic· 125 VUS of 189 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

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.94LOEUF

pLI 0.000

Z-score 1.86

OE 0.66 (0.47–0.94)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

1.37Z-score

OE missense 0.80 (0.73–0.88)

313 obs / 388.9 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.66 (0.47–0.94)

0≤0.351.4

Missense OE?0.80 (0.73–0.88)

0≤0.61.4

Synonymous OE?0.99

0≤1.21.6

LoF obs/exp: 23 / 34.8Missense obs/exp: 313 / 388.9Syn Z: 0.11

Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗

strongATG7-related intellectual disability and ataxiaLOFAR

This gene — mechanism propensity

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

0.6549th %ile

GOF

0.4974th %ile

LOF

0.3164th %ile

The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.

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

ClinVar Variant Classifications

189 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic7

Likely Pathogenic2

VUS125

Likely Benign18

Benign4

Conflicting2

Pathogenic

Likely Pathogenic

125

VUS

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	2	4	1	0	7
Likely Pathogenic	2	0	0	0	2
VUS	0	124	1	0	125
Likely Benign	0	9	2	7	18
Benign	0	0	2	2	4
Conflicting	—				2
Total	4	137	6	9	158

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

View in ClinVar →

34 pathogenic / likely-pathogenic (of 39) ClinVar copy-number / structural variants overlap ATG7 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →