VPS26A: VPS26 Retromer Complex Component A
A key component of the retromer complex involved in endosomal protein sorting and implicated in neurodegenerative and developmental disorders.
Gene Information Card
| Symbol | VPS26A |
|---|---|
| Full Name | VPS26 retromer complex component A |
| Gene Type | protein-coding |
| Chromosomal Location | 10q22.1 |
| NCBI Gene ID | 9559 ncbi.nlm.nih.gov/gene/9559 |
| Ensembl ID | ENSG00000120071 |
| UniProt ID | O75436 |
| OMIM ID | 605506 |
| HGNC ID | 12713 |
| Aliases | VPS26, Hβ58, HB58 |
Description
VPS26A encodes a core component of the retromer complex, which is essential for endosomal protein sorting and recycling of transmembrane receptors. The retromer complex, composed of VPS26A, VPS29, and VPS35, mediates retrograde transport from endosomes to the trans-Golgi network. VPS26A directly interacts with VPS35 and is required for complex stability and cargo recognition. Dysregulation of retromer function is linked to neurodegenerative diseases such as Parkinson and Alzheimer disease, as well as developmental disorders.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Parkinson disease | Impaired retromer-mediated trafficking of autophagy-related proteins and lysosomal enzymes leads to alpha-synuclein accumulation. | PMID: 24607389; ClinVar |
| Alzheimer disease | Reduced retromer function disrupts amyloid precursor protein (APP) trafficking, increasing amyloid-beta production. | PMID: 18511905; NCBI Gene |
| Developmental and epileptic encephalopathy | Loss-of-function mutations in VPS26A cause early-onset seizures and intellectual disability due to defective neuronal endosomal sorting. | PMID: 32004446; ClinVar |
| Retinitis pigmentosa | Retromer dysfunction in photoreceptor cells impairs rhodopsin recycling, leading to retinal degeneration. | PMID: 30026314; OMIM |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 12.5 | Medium |
| Testis | 10.2 | Medium |
| Adrenal gland | 9.8 | Medium |
| Thyroid | 8.5 | Medium |
| Liver | 6.3 | Low |
| Heart | 5.1 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| SH-SY5Y (neuroblastoma) | 14.2 | High expression; used in retromer studies |
| HeLa (cervical carcinoma) | 11.0 | Moderate expression |
| HEK293 (embryonic kidney) | 9.5 | Moderate expression |
| HepG2 (hepatocellular carcinoma) | 6.8 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.497G>A (p.Arg166Gln) | Missense | Rare | Impaired VPS35 binding and retromer complex assembly |
| c.1A>G (p.Met1Val) | Start loss | Rare | Loss of protein expression; associated with developmental encephalopathy |
| c.769C>T (p.Arg257Trp) | Missense | Rare | Reduced retromer stability and endosomal trafficking defects |
Mutation functional classification
Loss of Function (LOF)
Missense and start-loss mutations that disrupt VPS26A protein expression or interaction with VPS35, leading to retromer complex instability and impaired endosomal sorting.
Gain of Function (GOF)
No gain-of-function mutations reported for VPS26A.
Dominant Negative (DN)
Heterozygous missense mutations (e.g., p.Arg166Gln) may exert dominant-negative effects by incorporating into the retromer complex and disrupting its function.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Retromer-mediated retrograde transport (Reactome: R-HSA-6811434)
• Endosomal sorting and recycling (KEGG: hsa04144)
Protein Summary
VPS26A is a 337-amino-acid protein (UniProt O75436) that forms a stable subcomplex with VPS35 and VPS29. It contains a VPS26 domain that mediates cargo recognition and membrane recruitment. The protein is ubiquitously expressed, with highest levels in brain and testis. VPS26A is essential for retromer-dependent sorting of transmembrane receptors such as sortilin, CI-MPR, and Wntless. Mutations in VPS26A cause retromer dysfunction, contributing to neurodegeneration and developmental epilepsy.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| VPS26A Knockout HEK293 Cell Line | EDJ-KQ6639 | Human | 9559 | Details Get a Quote |
| VPS26A Knockout A-549 Cell Line | EDJ-KQ30901 | Human | 9559 | Details Get a Quote |
| VPS26A Knockout HCT 116 Cell Line | EDJ-KQ30902 | Human | 9559 | Details Get a Quote |
| VPS26A Knockout HeLa Cell Line | EDJ-KQ30903 | Human | 9559 | Details Get a Quote |
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