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10 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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SNX1
sorting nexin 1
Chromosome 15 · 15q22.31
NCBI Gene: 6642Ensembl: ENSG00000028528.16HGNC: HGNC:11172UniProt: Q13596
144PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
FUNCTIONAL ROLE
Transporter
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
epidermal growth factor receptor bindinginsulin receptor bindingprotein bindingphosphatidylinositol bindingplacenta praeviaIGA glomerulonephritisalcohol drinkingeye disease
✦AI Summary

SNX1 (sorting nexin 1) is a membrane-trafficking protein located on chromosome 15 that functions as a key component of the retromer complex 1. SNX1 contains PX and BAR domains that bind phosphatidylinositol 3-phosphate (PtdIns(3P))-enriched, highly curved endosomal membranes and mediates retrograde transport of cargo proteins from endosomes to the trans-Golgi network 1. The protein forms heterodimeric complexes (with SNX2, SNX5, or SNX6) and functions in membrane deformation and tubulation to facilitate endosome-to-TGN transport carrier formation 2. SNX1 regulates recycling of multiple receptors including IGF2R, M6PR, and EGFR, directing ligand-activated EGFR to lysosomes for degradation [UniProt data]. SNX1 expression is controlled through alternative splicing mechanisms that may be developmentally regulated, particularly in liver tissues 3. Clinically, SNX1 dysfunction has emerged as relevant to neurodegenerative diseases; genome-wide association studies identified SNX1 variants associated with both Alzheimer's disease risk and human longevity, with enrichment in microglial and oligodendrocytic gene networks 4. SNX1 polymorphisms also distinguish amyloid-β predominant Alzheimer's neuropathologic change from classical disease 5. In cancer contexts, SNX1 acts as a tumor suppressor; downregulation correlates with colorectal and ovarian cancer progression, while SNX1 restoration induces ferroptosis and inhibits proliferation, suggesting therapeutic potential 67.

Sources cited
1
SNX1 is a component of the retromer complex that mediates retrograde transport from endosomes to TGN; contains PX and BAR domains for binding curved PI(3)P-enriched membranes
PMID: 18472259
2
SNX1 gene is located on chromosome 15q22 with 15 exons; undergoes developmentally-regulated alternative splicing, particularly in liver; has housekeeping-type promoter
PMID: 11410165
3
SNX1 forms 1:1 heterodimers with SNX6 and mediates endosome-to-TGN transport through cargo selection and membrane remodeling
PMID: 29908913
4
SNX1 genetic variants are enriched in microglia and oligodendrocyte networks associated with Alzheimer's disease risk and human longevity
PMID: 39778705
5
SNX1 polymorphisms distinguish amyloid-β predominant Alzheimer's neuropathologic change from classical ADNC
PMID: 39417691
6
SNX1 is downregulated in colorectal cancer; low expression correlates with advanced stages and poor outcomes; SNX1 restoration induces ferroptosis via PPARs-ACSL1/4 pathway
PMID: 40095264
7
SNX1 is downregulated in ovarian cancer; acts as tumor suppressor by inhibiting proliferation, blocking G1/S transition, promoting apoptosis, and suppressing migration
PMID: 41487280
Disease Associationsⓘ20
placenta praeviaOpen Targets
0.23Weak
IGA glomerulonephritisOpen Targets
0.22Weak
alcohol drinkingOpen Targets
0.11Weak
eye diseaseOpen Targets
0.09Suggestive
gastric cancerOpen Targets
0.08Suggestive
ovarian cancerOpen Targets
0.07Suggestive
Abruptio PlacentaeOpen Targets
0.06Suggestive
neoplasmOpen Targets
0.05Suggestive
gastric ulcerOpen Targets
0.05Suggestive
hemorrhageOpen Targets
0.05Suggestive
colorectal carcinomaOpen Targets
0.03Suggestive
Parkinson diseaseOpen Targets
0.02Suggestive
non-small cell lung carcinomaOpen Targets
0.02Suggestive
chronic obstructive pulmonary diseaseOpen Targets
0.02Suggestive
hypertensionOpen Targets
0.02Suggestive
gliomaOpen Targets
0.02Suggestive
infectionOpen Targets
0.01Suggestive
colorectal cancerOpen Targets
0.01Suggestive
lung cancerOpen Targets
0.01Suggestive
Salmonella InfectionsOpen Targets
0.01Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
LEPRProtein interaction98%VPS26BProtein interaction96%SNX12Protein interaction94%DNAJC13Protein interaction94%SNX27Protein interaction91%TBC1D5Protein interaction90%
Tissue Expression6 tissues
Lung
100%
Heart
87%
Liver
83%
Ovary
79%
Brain
63%
Bone Marrow
45%
Gene Interaction Network
Click a node to explore
SNX1LEPRVPS26BSNX12DNAJC13SNX27TBC1D5
PROTEIN STRUCTURE
Preparing viewer…
PDB8A1G · 2.50 Å · X-ray
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
0.67LoF Tolerant
pLIⓘ
0.01Tolerant
Observed/Expected LoF0.47 [0.34–0.67]
RankingsWhere SNX1 stands among ~20K protein-coding genes
  • #3,180of 20,598
    Most Researched144 · top quartile
  • #4,898of 17,882
    Most Constrained (LOEUF)0.67
Genes detectedSNX1
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
Retromer.
PMID: 18472259
Curr Opin Cell Biol · 2008
1.00
2
Structural and functional characterization of the human gene for sorting nexin 1 (SNX1).
PMID: 11410165
DNA Cell Biol · 2001
0.90
3
Human longevity and Alzheimer's disease variants act via microglia and oligodendrocyte gene networks.
PMID: 39778705
Brain · 2025
0.80
4
Amyloid-β predominant Alzheimer's disease neuropathologic change.
PMID: 39417691
Brain · 2025
0.70
5
Nutrient deficiency-induced downregulation of SNX1 inhibits ferroptosis through PPARs-ACSL1/4 axis in colorectal cancer.
PMID: 40095264
Apoptosis · 2025
0.60