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10 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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SNX4
sorting nexin 4
Chromosome 3 · 3q21.2
NCBI Gene: 8723Ensembl: ENSG00000114520.12HGNC: HGNC:11175UniProt: O95219
60PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
FUNCTIONAL ROLE
Transporter
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
epidermal growth factor receptor bindinginsulin receptor bindingprotein bindingphosphatidylinositol-3-phosphate bindingHirsutismAlzheimer diseasenonpapillary renal cell carcinomabronchopneumonia
✦AI Summary

SNX4 (sorting nexin 4) is a phosphatidylinositol 3-phosphate-binding protein that plays critical roles in endosomal recycling and autophagy regulation 1. The protein functions as part of the recycler complex, composed of SNX4, SNX5, and SNX17, which mediates autophagosomal components recycling (ACR) by facilitating the retrieval of autophagosome outer membrane components from autolysosomes 2 3. SNX4 specifically controls the recycling of ATG9A, a lipid scramblase essential for autophagosome membrane expansion, from endolysosomes to early endosomes, thereby sustaining autophagic flux 1. The protein also regulates transferrin receptor recycling and forms complexes with clathrin and dynein to mediate endosome-to-Golgi transport 4 5. In neurons, SNX4 functions as a negative regulator of synaptic vesicle docking and release, affecting synapse ultrastructure by controlling vesicle density at active zones 6. Clinically, SNX4 expression is downregulated in clear cell renal cell carcinoma, correlating with poor prognosis and altered immune infiltration 7. The protein's recycling activities are regulated by mTORC1 through SNX16 phosphorylation and Rab32 family proteins 8 3.

Sources cited
1
SNX4 is a PI3P-binding protein that mediates ATG9A recycling from endolysosomes and is required for autophagic flux
PMID: 33468622
2
SNX4 is part of the recycler complex (SNX4-SNX5-SNX17) that mediates autophagosomal components recycling
PMID: 35840484
3
The recycler complex cooperates with dynein-dynactin and is regulated by Rab32 family proteins
PMID: 38323995
4
SNX4 forms complexes with clathrin and dynein for endosome-to-Golgi transport
PMID: 19529763
5
SNX4 interacts with Rab11a and functions in transferrin receptor recycling
PMID: 23825023
6
SNX4 negatively regulates synaptic vesicle docking and release in neurons
PMID: 39699951
7
SNX4 is downregulated in clear cell renal cell carcinoma and correlates with poor prognosis
PMID: 39328330
8
mTORC1 regulates autophagosomal components recycling through SNX16 phosphorylation in the recycler complex
PMID: 41237209
Disease Associationsⓘ20
HirsutismOpen Targets
0.30Weak
Alzheimer diseaseOpen Targets
0.08Suggestive
nonpapillary renal cell carcinomaOpen Targets
0.07Suggestive
bronchopneumoniaOpen Targets
0.04Suggestive
Lung AbscessOpen Targets
0.04Suggestive
COVID-19Open Targets
0.03Suggestive
severe acute respiratory syndromeOpen Targets
0.03Suggestive
neoplasmOpen Targets
0.03Suggestive
circadian rhythm sleep disorderOpen Targets
0.02Suggestive
seborrheic keratosisOpen Targets
0.02Suggestive
cancerOpen Targets
0.02Suggestive
clear cell renal carcinomaOpen Targets
0.01Suggestive
COVID-19–associated multisystem inflammatory syndrome in adultsOpen Targets
0.01Suggestive
kidney oncocytomaOpen Targets
0.01Suggestive
IGA glomerulonephritisOpen Targets
0.01Suggestive
infectionOpen Targets
0.00Suggestive
neuromyelitis opticaOpen Targets
0.00Suggestive
Salmonella InfectionsOpen Targets
0.00Suggestive
Townes-Brocks syndromeOpen Targets
0.00Suggestive
Parkinson diseaseOpen Targets
0.00Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
SNAP23Protein interaction100%STX6Protein interaction100%VPS26AProtein interaction100%VPS35Protein interaction100%STX12Protein interaction99%VPS29Protein interaction99%
Tissue Expression6 tissues
Bone Marrow
100%
Liver
97%
Brain
84%
Heart
73%
Ovary
48%
Lung
47%
Gene Interaction Network
Click a node to explore
SNX4SNAP23STX6VPS26AVPS35STX12VPS29
PROTEIN STRUCTURE
Preparing viewer…
AlphaFoldAI-predicted · UniProt O95219
View on AlphaFold ↗
Constraintⓘ
LOEUFⓘ
1.08LoF Tolerant
pLIⓘ
0.00Tolerant
Observed/Expected LoF0.78 [0.57–1.08]
RankingsWhere SNX4 stands among ~20K protein-coding genes
  • #7,709of 20,598
    Most Researched60
  • #10,899of 17,882
    Most Constrained (LOEUF)1.08
Genes detectedSNX4
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
Rab32 family proteins regulate autophagosomal components recycling.
PMID: 38323995
J Cell Biol · 2024
1.00
2
Endosomal sorting protein SNX4 limits synaptic vesicle docking and release.
PMID: 39699951
Elife · 2024
0.90
3
mTORC1 regulates autophagosomal components recycling through SNX16 phosphorylation.
PMID: 41237209
Proc Natl Acad Sci U S A · 2025
0.80
4
SNX4 Is Correlated With Immune Infiltration and Prognosis in Clear Cell Renal Cell Carcinoma.
PMID: 39328330
World J Oncol · 2024
0.70
5
Autophagosomal components recycling on autolysosomes.
PMID: 35840484
Trends Cell Biol · 2022
0.60