ATG2A

Chr 11

autophagy related 2A

Also known as: BLTP4A

NCBI Gene: 23130ENSG00000110046UniProt: Q2TAZ0

Enables lipid transfer activity. Involved in autophagosome assembly and positive regulation of autophagosome assembly. Is active in organelle membrane contact site. [provided by Alliance of Genome Resources, Jul 2025]

384
ClinVar variants
8
Pathogenic / LP
0.05
pLI score
0
Active trials
Clinical Summary— ATG2A
⚡
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.24) despite low pLI — interpret in context.
📋
ClinVar Variants
8 Pathogenic / Likely Pathogenic· 300 VUS of 384 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.
0.35LOEUF
pLI 0.054
Z-score 6.70
OE 0.24 (0.17–0.35)
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.
1.81Z-score
OE missense 0.85 (0.81–0.90)
1027 obs / 1204.2 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.0.24 (0.17–0.35)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.85 (0.81–0.90)
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.0.98
0≤1.21.6
LoF obs/exp: 22 / 90.9Missense obs/exp: 1027 / 1204.2Syn Z: 0.41

ClinVar Variant Classifications

384 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic6
Likely Pathogenic2
VUS300
Likely Benign24
Benign5
Conflicting1
6
Pathogenic
2
Likely Pathogenic
300
VUS
24
Likely Benign
5
Benign
1
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
6
0
6
Likely Pathogenic
0
0
2
0
2
VUS
0
295
5
0
300
Likely Benign
0
20
1
3
24
Benign
0
3
0
2
5
Conflicting
—1
Total0318145338

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

View in ClinVar →

Protein Context — Lollipop Plot

ATG2A · 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
Therapeutic targeting of the USP2-E2F4 axis inhibits autophagic machinery essential for zinc homeostasis in cancer progression.
Xiao W et al.·Autophagy
2022
An Unstable ATG2A Variant Causes a Neurodegenerative Disorder via Impaired Autophagy and Proteotoxic Stress in Brain Atrophy.
Rehan Ahmad S et al.·Clin Genet
2026Case report
Fine particulate matter inhibits phagocytosis of macrophages by disturbing autophagy.
Li Y et al.·FASEB J
2020
circPGAM1 enhances autophagy signaling during laryngocarcinoma drug resistance by regulating miR-376a.
Feng B et al.·Biochem Biophys Res Commun
2021
YF343, A Novel Histone Deacetylase Inhibitor, Combined with CQ to Inhibit- Autophagy, Contributes to Increased Apoptosis in Triple- Negative Breast Cancer.
Liu N et al.·Curr Med Chem
2023
Linkage of Metabolic Defects to Activated PIK3CA Alleles in Endothelial Cells Derived from Lymphatic Malformation.
Glaser K et al.·Lymphat Res Biol
2018
A methodology for gene level omics-WAS integration identifies genes influencing traits associated with cardiovascular risks: the Long Life Family Study.
Acharya S et al.·Hum Genet
2024
Genetic variants in autophagy-related genes and granuloma formation in a cohort of surgically treated Crohn's disease patients.
Brinar M et al.·J Crohns Colitis
2012Cohort
Association of ATG5 Gene Polymorphisms With Behçet's Disease and ATG10 Gene Polymorphisms With VKH Syndrome in a Chinese Han Population.
Zheng M et al.·Invest Ophthalmol Vis Sci
2015
Generation R birth cohort study shows that specific enamel defects were not associated with elevated serum transglutaminase type 2 antibodies.
Beth SA et al.·Acta Paediatr
2016Cohort
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