SNX8: Sorting Nexin 8 – A Key Regulator of Endosomal Trafficking and Signaling
Comprehensive genomic, proteomic, and clinical overview of SNX8, a member of the sorting nexin family involved in intracellular membrane trafficking and implicated in neurodegenerative and metabolic disorders.
Gene Information Card
| Symbol | SNX8 |
|---|---|
| Full Name | Sorting Nexin 8 |
| Gene Type | Protein coding |
| Chromosomal Location | 2p25.1 |
| NCBI Gene ID | 29886 ncbi.nlm.nih.gov/gene/29886 |
| Ensembl ID | ENSG00000162928 |
| UniProt ID | Q9Y2X7 |
| OMIM ID | 611349 |
| HGNC ID | 11173 |
| Aliases | SNX8, MGC138290, MGC138291 |
Description
SNX8 (sorting nexin 8) encodes a member of the sorting nexin family, characterized by a Phox (PX) domain that binds phosphoinositides. SNX8 is involved in endosomal trafficking, retromer complex function, and regulation of cell surface receptor recycling. It plays roles in intracellular signaling, lipid metabolism, and autophagy. Variants in SNX8 have been associated with Alzheimer disease, type 2 diabetes, and other metabolic traits.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Alzheimer disease | SNX8 modulates retromer-mediated trafficking of APP and BACE1, affecting amyloid-beta production; loss of SNX8 impairs endosomal sorting and promotes Aβ accumulation. | ClinVar, OMIM |
| Type 2 diabetes | SNX8 variants influence insulin receptor recycling and GLUT4 translocation, altering glucose uptake and insulin sensitivity. | GWAS, NCBI |
| Obesity | SNX8 expression in adipose tissue correlates with lipid metabolism; variants linked to body mass index. | GWAS, ClinVar |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain (cortex) | 12.5 | Medium |
| Liver | 8.3 | Low |
| Adipose tissue | 6.1 | Low |
| Pancreas | 4.7 | Low |
| Skeletal muscle | 3.2 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| SH-SY5Y (neuroblastoma) | 15.2 | High expression; used in neurodegeneration studies |
| HepG2 (hepatocellular carcinoma) | 9.8 | Moderate expression |
| 3T3-L1 (adipocyte) | 7.4 | Differentiation-dependent expression |
| HeLa (cervical carcinoma) | 5.1 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.497C>T (p.Thr166Met) | Missense | 0.0012 (gnomAD) | Alters PX domain; reduced phosphoinositide binding; associated with Alzheimer disease risk |
| c.1045G>A (p.Gly349Arg) | Missense | 0.0008 | Impairs retromer interaction; linked to type 2 diabetes |
| c.1234_1235insA | Frameshift | <0.0001 | Loss of function; rare; observed in metabolic syndrome |
Mutation functional classification
Loss of Function (LOF)
Frameshift and nonsense mutations that truncate the protein or disrupt the PX domain lead to loss of endosomal trafficking function.
Gain of Function (GOF)
No confirmed gain-of-function mutations reported in SNX8.
Dominant Negative (DN)
Missense mutations in the PX domain (e.g., p.Thr166Met) may exert dominant-negative effects by competing with wild-type SNX8 for phosphoinositide binding.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Retromer-mediated endosomal sorting (Reactome: R-HSA-8856828)
• Endosomal trafficking (KEGG: hsa04144)
• Alzheimer disease – amyloid processing (KEGG: hsa05010)
• Insulin receptor recycling (WikiPathways: WP481)
Protein Summary
SNX8 is a 465-amino-acid protein containing an N-terminal Phox (PX) domain that binds phosphatidylinositol 3-phosphate (PI3P) and phosphatidylinositol 3,5-bisphosphate (PI(3,5)P2). It localizes to early endosomes and participates in retromer-dependent retrograde transport from endosomes to the Golgi. SNX8 also interacts with the retromer subunit VPS35 and regulates the trafficking of APP, BACE1, and the insulin receptor. Its expression is enriched in brain and adipose tissue, and it is implicated in Alzheimer disease and metabolic disorders.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| SNX8 Knockout HEK293 Cell Line | EDJ-KQ8305 | Human | 29886 | Details Get a Quote |
| SNX8 Knockout A-549 Cell Line | EDJ-KQ35525 | Human | 29886 | Details Get a Quote |
| SNX8 Knockout HCT 116 Cell Line | EDJ-KQ35527 | Human | 29886 | Details Get a Quote |
| SNX8 Knockout HeLa Cell Line | EDJ-KQ35528 | Human | 29886 | Details Get a Quote |
