ATG12

Chr 5

autophagy related 12

Also known as: APG12, APG12L, FBR93, HAPG12

NCBI Gene: 9140ENSG00000145782UniProt: O94817

Autophagy is a process of bulk protein degradation in which cytoplasmic components, including organelles, are enclosed in double-membrane structures called autophagosomes and delivered to lysosomes or vacuoles for degradation. ATG12 is the human homolog of a yeast protein involved in autophagy (Mizushima et al., 1998 [PubMed 9852036]).[supplied by OMIM, Mar 2008]

56
ClinVar variants
28
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— ATG12
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
28 Pathogenic / Likely Pathogenic· 25 VUS of 56 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.
1.74LOEUF
pLI 0.000
Z-score -0.06
OE 1.02 (0.60–1.74)
Tolerant

Highly tolerant — LoF variants common in population

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 1.45 (1.24–1.70)
106 obs / 73.1 exp
Tolerant

Tolerant to missense variation

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.1.02 (0.60–1.74)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.1.45 (1.24–1.70)
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.1.47
0≤1.21.6
LoF obs/exp: 8 / 7.8Missense obs/exp: 106 / 73.1Syn Z: -1.97

ClinVar Variant Classifications

56 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic23
Likely Pathogenic5
VUS25
Likely Benign2
Conflicting1
23
Pathogenic
5
Likely Pathogenic
25
VUS
2
Likely Benign
1
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
23
0
23
Likely Pathogenic
0
2
3
0
5
VUS
0
23
2
0
25
Likely Benign
0
1
1
0
2
Benign
0
0
0
0
0
Conflicting
—1
Total02629056

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

View in ClinVar →

Protein Context — Lollipop Plot

ATG12 · 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
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Autophagy in the physiological endometrium and cancer.
Devis-Jauregui L et al.·Autophagy
2021Review
Trehalose induces autophagy via lysosomal-mediated TFEB activation in models of motoneuron degeneration.
Rusmini P et al.·Autophagy
2019Functional
ATG7 safeguards human neural integrity.
Collier JJ et al.·Autophagy
2021
Functional Relationships between L1CAM, LC3, ATG12, and Aβ.
Loers G et al.·Int J Mol Sci
2024Functional
Integrated multi-omics and machine learning elucidate the pathogenic role of mitophagy in osteoarthritis and identify novel therapeutic strategies.
Dong Q et al.·Int Immunopharmacol
2026
LncRNA DDX11-AS1 Promotes Chemoresistance through LIN28A-Mediated ATG12 mRNA Stabilization in Breast Cancer.
Si X et al.·Pharmacology
2023
Blocking LC3 lipidation and ATG12 conjugation reactions by ATG7 mutant protein containing C572S.
Nitta A et al.·Biochem Biophys Res Commun
2019
Independent and interactive roles of hirudin and HMGB1 interference in protecting renal function by regulating autophagy, apoptosis, and kidney injury in chronic kidney disease.
Li Y et al.·Eur J Histochem
2025
Adaptor SH3BGRL drives autophagy-mediated chemoresistance through promoting PIK3C3 translation and ATG12 stability in breast cancers.
Zhang S et al.·Autophagy
2022
The role of HIF-1α-mediated autophagy in ionizing radiation-induced testicular injury.
Xu R et al.·J Mol Histol
2023
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Phosphorylation of Atg12 for optimal autophagy in yeast Komagataella phaffii.
Kobe M et al.·J Biochem
2026
5-hydroxymethylfurfural as an important component of cigarette smoke impairs the blood-testis barrier via mTOR/Atg12-mediated autophagy in Sertoli cells in mice.
Yu Y et al.·Ecotoxicol Environ Saf
2026
In Silico Study of Molecular Docking Between Lactoferrin and Autophagy-apoptosis Genes ATG3, ATG5, and ATG12 and In Vitro Study of Lactoferrin Effect on These Gene Expressions in Breast Cancer.
Noorani SF et al.·J Cell Biochem
2025
Targeting the ATG12-ATG3 protein-protein interaction: From structural insights to therapeutic opportunities in autophagy modulation.
Kamel EM et al.·Pathol Res Pract
2025
The TECPR1:ATG5-ATG12 complex conjugates LC3/ATG8 to damaged lysosomes that expose luminal glycans in response to osmotic imbalance.
Wang Y et al.·Autophagy Rep
2025🔓 Open Access
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