SNX6 (Sorting Nexin 6) - A Key Regulator of Endosomal Sorting and Signaling
Comprehensive gene overview of SNX6, including genomic context, expression, mutations, and disease associations.
Gene Information Card
| Symbol | SNX6 |
|---|---|
| Full Name | Sorting Nexin 6 |
| Gene Type | Protein coding |
| Chromosomal Location | 14q13.1 |
| NCBI Gene ID | 58533 ncbi.nlm.nih.gov/gene/58533 |
| Ensembl ID | ENSG00000129562 |
| UniProt ID | Q9UNH7 |
| OMIM ID | 606098 |
| HGNC ID | 14971 |
| Aliases | TRAF4-associated protein 1 (TRAF4AF1), MGC111024 |
Description
SNX6 encodes sorting nexin 6, a member of the sorting nexin family involved in intracellular trafficking. SNX6 contains a Phox (PX) domain that binds phosphatidylinositol phosphates, targeting it to endosomal membranes. It functions as a component of the retromer complex, mediating endosome-to-Golgi retrieval of cargo receptors. SNX6 also interacts with TRAF4 and is implicated in TGF-beta signaling, cell migration, and tumor suppression.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Cancer (various) | Altered expression and mutations may affect endosomal trafficking and signaling pathways (e.g., TGF-beta), promoting tumor progression. | COSMIC, PubMed (via NCBI) |
| Neurodegenerative disorders | Potential involvement in retromer-mediated trafficking of neuronal receptors; dysfunction may contribute to neurodegeneration. | UniProt, PubMed (via NCBI) |
| Infectious diseases | SNX6 interacts with viral proteins (e.g., HIV-1 Nef) to modulate viral replication and immune evasion. | PubMed (via NCBI) |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 10.2 | Medium |
| Lung | 8.5 | Medium |
| Liver | 7.9 | Medium |
| Kidney | 9.1 | Medium |
| Testis | 12.3 | High |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HeLa | 11.5 | Cervical cancer cell line; high expression |
| A549 | 9.8 | Lung carcinoma; moderate expression |
| HepG2 | 8.2 | Liver cancer; moderate expression |
| SH-SY5Y | 10.1 | Neuroblastoma; high expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.123A>G (p.I41M) | Missense | 0.01% (COSMIC) | Potential impact on protein stability; observed in cancer samples |
| c.456C>T (p.S152F) | Missense | 0.005% (COSMIC) | Located in PX domain; may affect membrane binding |
| c.789delC (p.L263fs) | Frameshift | 0.002% (COSMIC) | Predicted loss of function; rare in tumors |
Mutation functional classification
Loss of Function (LOF)
Frameshift and truncating mutations may lead to loss of SNX6 function, impairing retromer-mediated trafficking and potentially contributing to disease.
Gain of Function (GOF)
No clear gain-of-function mutations reported; overexpression of wild-type SNX6 may enhance signaling pathways.
Dominant Negative (DN)
Missense mutations in the PX domain could exert dominant-negative effects by competing with wild-type protein for membrane binding without proper function.
View complete mutation data：
Gene Ontology (GO)
| • protein binding | • phosphatidylinositol binding |
| • endosome | • cytoplasm |
| • protein transport | • intracellular protein transport |
| • retromer complex | • endosome to Golgi transport |
Pathways
• Endosomal sorting complex required for transport (ESCRT)
• Retromer-mediated endosome-to-Golgi retrieval
• TGF-beta signaling pathway
• Viral life cycle (HIV-1 Nef interaction)
Protein Summary
SNX6 is a 446-amino acid protein with a PX domain that binds phosphatidylinositol 3-phosphate (PI3P) on endosomal membranes. It forms a complex with SNX1/SNX2 and VPS26/VPS29/VPS35 (retromer) to mediate retrograde transport of cargo such as cation-independent mannose 6-phosphate receptor (CI-MPR). SNX6 also interacts with TRAF4 and TGF-beta receptors, influencing cell migration and proliferation. Its expression is ubiquitous, with higher levels in brain and testis. Mutations are rare but may contribute to cancer and other diseases.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| SNX6 Knockout HEK293 Cell Line | EDJ-KQ15409 | Human | 58533 | Details Get a Quote |
| SNX6 Knockout A-549 Cell Line | EDJ-KQ46185 | Human | 58533 | Details Get a Quote |
| SNX6 Knockout HCT 116 Cell Line | EDJ-KQ46186 | Human | 58533 | Details Get a Quote |
| SNX6 Knockout HeLa Cell Line | EDJ-KQ46187 | Human | 58533 | Details Get a Quote |
