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10 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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ATG9A
autophagy related 9A
Chromosome 2 · 2q35
NCBI Gene: 79065Ensembl: ENSG00000198925.13HGNC: HGNC:22408UniProt: Q7Z3C6
125PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
FUNCTIONAL ROLE
Highly ConstrainedTransporter
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
autophagosome membraneautophagosome assemblyprotein bindingphospholipid scramblase activityneurodegenerative diseaselysosomal storage diseasecancerneoplasm
✦AI Summary

ATG9A is a ubiquitously expressed transmembrane phospholipid scramblase essential for autophagosome biogenesis 1. Its primary function involves mediating autophagosomal membrane expansion by cycling between the phagophore assembly site and cytoplasmic vesicles, supplying phospholipids for autophagosome growth 1. ATG9A's lipid scramblase activity distributes phospholipids across the bilayer to drive membrane expansion, while also recruiting phosphatidylinositol 4-kinase beta via ARFIP2 to supply phosphatidylinositol 4-phosphate for autophagosome initiation 1. Beyond autophagy, ATG9A has emerged with multiple non-canonical functions: it protects plasma membrane integrity through ESCRT cooperation 2, delivers PI4K2A to damaged lysosomes for repair via ARFIP2 interaction 3, and independently mediates galectin-9 secretion through specialized vesicle carriers 4. ATG9A deficiency causes severe cellular and organismal defects, including impaired oligodendrocyte differentiation and mitochondrial dynamics 5. In diabetes pathogenesis, dysregulated ATG9A expression contributes to pathological autophagy overload in pancreatic β-cells under glucolipotoxic stress 6. ATG9A's multi-functional roles position it as a critical regulator of cellular homeostasis beyond classical autophagy.

Sources cited
1
ATG9A is ubiquitously expressed, its deficiency causes severe cellular and organismal defects, and it functions in autophagosomal membrane expansion and phagophore expansion
PMID: 39099167
2
ATG9A protects plasma membrane integrity through cooperation with IQGAP1 and ESCRT components
PMID: 34257406
3
ATG9A and ARFIP2 cooperate to deliver PI4K2A to damaged lysosomes for repair by controlling PI4P levels
PMID: 40460835
4
ATG9A functions independently of autophagy to mediate galectin-9 secretion as a specialized vesicle carrier
PMID: 40335523
5
ATG9A knockdown significantly reduces oligodendrocyte progenitor cell proliferation and survival, and is involved in mitophagy during oligodendrocyte differentiation
PMID: 33404293
6
ATG9A expression is upregulated in pancreatic β-cells under glucolipotoxic stress via the NR3C1-FTO-m6A modifications axis, contributing to pathological autophagy overload and diabetes
PMID: 37039556
Disease Associationsⓘ20
neurodegenerative diseaseOpen Targets
0.52Moderate
lysosomal storage diseaseOpen Targets
0.37Weak
cancerOpen Targets
0.09Suggestive
neoplasmOpen Targets
0.09Suggestive
triple-negative breast cancerOpen Targets
0.08Suggestive
infectionOpen Targets
0.05Suggestive
glioblastoma multiformeOpen Targets
0.05Suggestive
hepatocellular carcinomaOpen Targets
0.04Suggestive
hereditary spastic paraplegiaOpen Targets
0.04Suggestive
breast cancerOpen Targets
0.03Suggestive
benign prostatic hyperplasiaOpen Targets
0.03Suggestive
asthmaOpen Targets
0.02Suggestive
cardiac hypertrophyOpen Targets
0.02Suggestive
in situ carcinomaOpen Targets
0.02Suggestive
punctate palmoplantar keratoderma type IIIOpen Targets
0.02Suggestive
lumbar disc degenerationOpen Targets
0.02Suggestive
Parkinson diseaseOpen Targets
0.02Suggestive
Alzheimer diseaseOpen Targets
0.02Suggestive
colorectal carcinomaOpen Targets
0.02Suggestive
Chlamydia trachomatis infectious diseaseOpen Targets
0.02Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
BECN1Protein interaction100%PIK3C3Protein interaction99%ATG5Protein interaction97%OPTNProtein interaction97%GABARAPL1Protein interaction97%SUPT20HProtein interaction97%
Tissue Expression6 tissues
Liver
100%
Lung
99%
Brain
78%
Ovary
68%
Heart
67%
Bone Marrow
34%
Gene Interaction Network
Click a node to explore
ATG9ABECN1PIK3C3ATG5OPTNGABARAPL1SUPT20H
PROTEIN STRUCTURE
Preparing viewer…
PDB6WQZ · 2.80 Å · EM
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
0.33Highly Constrained
pLIⓘ
1.00Intolerant
Observed/Expected LoF0.23 [0.16–0.33]
RankingsWhere ATG9A stands among ~20K protein-coding genes
  • #3,753of 20,598
    Most Researched125 · top quartile
  • #1,407of 17,882
    Most Constrained (LOEUF)0.33 · top 10%
Genes detectedATG9A
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
Autophagy and autophagy-related proteins in cancer.
PMID: 31969156
Mol Cancer · 2020
1.00
2
Emerging roles of ATG9/ATG9A in autophagy: implications for cell and neurobiology.
PMID: 39099167
Autophagy · 2024
0.90
3
BNIP3L-mediated mitophagy is required for mitochondrial remodeling during the differentiation of optic nerve oligodendrocytes.
PMID: 33404293
Autophagy · 2021
0.80
4
STING directly activates autophagy to tune the innate immune response.
PMID: 30568238
Cell Death Differ · 2019
0.70
5
Autophagy-independent role of ATG9A vesicles as carriers for galectin-9 secretion.
PMID: 40335523
Nat Commun · 2025
0.60