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10 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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SNX6
sorting nexin 6
Chromosome 14 · 14q13.1
NCBI Gene: 58533Ensembl: ENSG00000129515.20HGNC: HGNC:14970UniProt: A0A0A0MRI2
103PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
FUNCTIONAL ROLE
Transporter
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
protein homodimerization activitycellular response to amyloid-betaendosomeintracellular protein transportneurodegenerative diseaseCOVID-19hypertriglyceridemia 2familial hypercholesterolemia
✦AI Summary

SNX6 (sorting nexin 6) is a PX and BAR domain-containing protein that functions as a transient component of the retromer complex, mediating retrograde endosome-to-trans-Golgi network (TGN) transport 1. SNX6 forms heterodimeric complexes with SNX1 and participates in cargo selection and membrane remodeling to generate endosome-to-TGN transport carriers 2. The protein binds phosphoinositide-enriched endosomal membranes and coordinates with the retromer cargo-recognition trimer (Vps26/Vps29/Vps35) to retrieve cargoes including the cation-independent mannose-6-phosphate receptor 3. SNX6 negatively regulates BACE1 retrograde transport, thereby suppressing amyloid-beta production relevant to Alzheimer's disease pathogenesis 4. Additionally, SNX6 modulates E-cadherin sorting and interacts with GIT1 to promote EGFR lysosomal degradation 5. Beyond trafficking functions, SNX6 regulates PD-L1 expression by modulating Cullin3-mediated ubiquitination, influencing cancer immune evasion 6. SNX6 expression correlates with poor prognosis in pancreatic cancer and promotes epithelial-mesenchymal transition 7. SNX6 also interacts with Rab32 to affect retromer-dependent Golgi trafficking, potentially linking this protein to Parkinson's disease-associated pathways 8.

Sources cited
1
SNX6 is a transient subunit of the retromer complex mediating retrograde endosome-to-TGN transport
PMID: 18472259
2
SNX6 forms heterodimeric complexes with SNX1 for cargo selection and membrane remodeling
PMID: 29908913
3
SNX6 (as part of ESCPE-1) deforms membranes with bis-phosphoinositides and CI-MPR cargo
PMID: 39937906
4
SNX6 negatively regulates BACE1 retrograde transport and amyloid-beta production
PMID: 20354142
5
SNX6 associates with GIT1 in EGFR lysosomal degradation
PMID: 39073202
6
SNX6 regulates PD-L1 expression by modulating Cullin3-mediated ubiquitination
PMID: 34510437
7
SNX6 expression predicts poor prognosis and promotes epithelial-mesenchymal transition in pancreatic cancer
PMID: 30307473
8
SNX6 directly interacts with Rab32 affecting retromer-dependent Golgi trafficking
PMID: 30640902
Disease Associationsⓘ20
neurodegenerative diseaseOpen Targets
0.25Weak
COVID-19Open Targets
0.24Weak
hypertriglyceridemia 2Open Targets
0.05Suggestive
familial hypercholesterolemiaOpen Targets
0.05Suggestive
Combined hyperlipidemiaOpen Targets
0.04Suggestive
thyroid hormone metabolism, abnormal, 2Open Targets
0.04Suggestive
sitosterolemia 2Open Targets
0.04Suggestive
homozygous familial hypercholesterolemiaOpen Targets
0.04Suggestive
hypercholesterolemia, autosomal dominant, 3Open Targets
0.04Suggestive
hyperlipidemia due to hepatic triglyceride lipase deficiencyOpen Targets
0.04Suggestive
hypercholesterolemia, autosomal dominant, type BOpen Targets
0.03Suggestive
pancreatic triacylglycerol lipase deficiencyOpen Targets
0.03Suggestive
Abnormality of the skeletal systemOpen Targets
0.03Suggestive
poisoningOpen Targets
0.03Suggestive
familial apolipoprotein C-II deficiencyOpen Targets
0.03Suggestive
Hyperlipoproteinemia type 1Open Targets
0.03Suggestive
Ataxia with vitamin E deficiencyOpen Targets
0.03Suggestive
familial isolated deficiency of vitamin EOpen Targets
0.03Suggestive
open-angle glaucomaOpen Targets
0.03Suggestive
response to antihypertensive drugOpen Targets
0.03Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
IGF2RProtein interaction99%SERPINE2Protein interaction98%SNX4Protein interaction98%TBC1D5Protein interaction98%SNX12Protein interaction98%IFT122Protein interaction98%
Tissue Expression6 tissues
Heart
100%
Brain
96%
Bone Marrow
63%
Lung
58%
Ovary
49%
Liver
37%
Gene Interaction Network
Click a node to explore
SNX6IGF2RSERPINE2SNX4TBC1D5SNX12IFT122
PROTEIN STRUCTURE
Preparing viewer…
AlphaFoldAI-predicted · UniProt Q9UNH7
View on AlphaFold ↗
Constraintⓘ
LOEUFⓘ
0.81LoF Tolerant
pLIⓘ
0.01Tolerant
Observed/Expected LoF0.52 [0.34–0.81]
RankingsWhere SNX6 stands among ~20K protein-coding genes
  • #4,663of 20,598
    Most Researched103 · top quartile
  • #6,810of 17,882
    Most Constrained (LOEUF)0.81
Genes detectedSNX6
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
Retromer.
PMID: 18472259
Curr Opin Cell Biol · 2008
1.00
2
SNX32 Regulates Sorting and Trafficking of Activated EGFR to the Lysosomal Degradation Pathway.
PMID: 39073202
Traffic · 2024
0.90
3
Expression and purification of the SNX1/SNX6 complex.
PMID: 29908913
Protein Expr Purif · 2018
0.80
4
VARP binds SNX27 to promote endosomal supercomplex formation on membranes.
PMID: 39937906
Sci Adv · 2025
0.70
5
Rab32 interacts with SNX6 and affects retromer-dependent Golgi trafficking.
PMID: 30640902
PLoS One · 2019
0.60