SNX27: Sorting Nexin 27 – Endosomal Trafficking and PDZ Domain Signaling
A key regulator of endosome-to-plasma membrane recycling, linked to Down syndrome, Alzheimer disease, and viral infection.
Gene Information Card
| Symbol | SNX27 |
|---|---|
| Full Name | Sorting Nexin 27 |
| Gene Type | Protein-coding |
| Chromosomal Location | 1q21.3 |
| NCBI Gene ID | 81609 ncbi.nlm.nih.gov/gene/81609 |
| Ensembl ID | ENSG00000143376 |
| UniProt ID | Q96L92 |
| OMIM ID | 611541 |
| HGNC ID | 14573 |
| Aliases | MGC20410, MGC23908, MGC26130 |
Description
SNX27 encodes sorting nexin 27, a member of the sorting nexin family characterized by a Phox homology (PX) domain and a PDZ domain. SNX27 functions as a cargo adaptor in endosomal trafficking, specifically mediating the recycling of internalized receptors (e.g., β2-adrenergic receptor, AMPA receptor, GLUT1) from endosomes back to the plasma membrane. It interacts with the retromer complex and is essential for maintaining cell surface receptor homeostasis. Loss of SNX27 is implicated in Down syndrome (due to trisomy 21-mediated repression), Alzheimer disease, and susceptibility to viral entry (e.g., SARS-CoV-2).
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Down syndrome | Reduced SNX27 expression due to trisomy 21 leads to impaired endosomal recycling and synaptic dysfunction. | PMID: 23452853, 25100654 |
| Alzheimer disease | SNX27 deficiency accelerates amyloid-β accumulation and impairs AMPA receptor trafficking, contributing to cognitive decline. | PMID: 25100654, 28459430 |
| Viral infection (SARS-CoV-2) | SNX27 facilitates endosomal trafficking of ACE2, modulating viral entry. | PMID: 32697943 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain (cerebral cortex) | 12.5 | Medium |
| Brain (hippocampus) | 11.8 | Medium |
| Heart | 8.2 | Low |
| Liver | 6.1 | Low |
| Kidney | 9.4 | Low |
| Lung | 7.3 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| SH-SY5Y (neuroblastoma) | 14.2 | Neuronal model |
| HEK293 (embryonic kidney) | 11.5 | Common overexpression system |
| HeLa (cervical carcinoma) | 9.8 | Epithelial model |
| HepG2 (hepatocellular carcinoma) | 6.7 | Hepatic model |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1A>G (p.Met1?) | Missense | Rare | Loss of start codon; predicted loss of function |
| c.286C>T (p.Arg96Trp) | Missense | Rare | PDZ domain variant; reduced binding to cargo |
| c.487G>A (p.Gly163Arg) | Missense | Rare | PX domain variant; impaired membrane association |
Mutation functional classification
Loss of Function (LOF)
Missense variants in the PDZ or PX domain that disrupt cargo binding or endosomal localization lead to loss of SNX27 recycling function.
Gain of Function (GOF)
No gain-of-function mutations have been reported for SNX27.
Dominant Negative (DN)
Heterozygous missense variants may act in a dominant-negative manner by competing with wild-type SNX27 for retromer binding.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Endosomal recycling (retromer-dependent)
• Neurotransmitter receptor recycling (AMPA receptor)
• GLUT1 glucose transporter recycling
• β2-adrenergic receptor recycling
Protein Summary
SNX27 is a 542-amino-acid protein containing an N-terminal PDZ domain and a central PX domain. The PDZ domain binds to PDZ-binding motifs (e.g., type I PDZ ligands) on cargo proteins, while the PX domain binds phosphatidylinositol-3-phosphate (PI3P) on endosomal membranes. SNX27 forms a complex with the retromer (VPS26-VPS29-VPS35) to sort cargo into recycling tubules. It is highly expressed in the brain and is critical for synaptic plasticity. Downregulation of SNX27 in Down syndrome contributes to cognitive impairment, and its loss exacerbates Alzheimer-related pathology.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| SNX27 Knockout HEK293 Cell Line | EDJ-KQ9724 | Human | 81609 | Details Get a Quote |
| SNX27 Knockout A-549 Cell Line | EDJ-KQ36538 | Human | 81609 | Details Get a Quote |
| SNX27 Knockout HCT 116 Cell Line | EDJ-KQ36539 | Human | 81609 | Details Get a Quote |
| SNX27 Knockout HeLa Cell Line | EDJ-KQ36540 | Human | 81609 | Details Get a Quote |
