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10 sources retrieved Β· Most recent: April 2026 Β· Index updated 15 days ago
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VPS26C
VPS26 endosomal protein sorting factor C
Chromosome 21 Β· 21q22.13
NCBI Gene: 10311Ensembl: ENSG00000157538.14HGNC: HGNC:3044UniProt: A8MTY9
35PubMed Papers
20Diseases
0Drugs
1Pathogenic Variants
DATA QUALITY
βœ“ Experimental GO Evidenceβœ“ Swiss-Prot Reviewed
protein bindingendocytic recyclingnucleusprotein-containing complexalcohol drinkingNeurodevelopmental disorderGriscelli diseaseFuchs endothelial corneal dystrophy
✦AI Summary

VPS26C is a core component of the Retriever complex, a trimeric assembly that includes VPS35L and VPS29, which functions as a major endosomal recycling machinery distinct from the retromer pathway 1. VPS26C integrates with the CCC complex (containing COMMD1-10, CCDC22, and CCDC93) to form the Commander complex, a 16-protein assembly critical for endosomal cargo recycling 2. Mechanistically, VPS26C participates in recycling diverse transmembrane proteins from endosomes back to the cell surface through interaction with the cargo adaptor SNX17, which binds to a conserved interface between VPS35L and VPS26C subunits 3. This interaction is regulated by cargo-binding and membrane phosphatidylinositol-3-phosphate recognition, enabling selective cargo recruitment 4. VPS26C mutations are associated with Ritscher-Schinzel syndrome, reflecting its essential role in endosomal trafficking 2. Beyond integrin and signaling receptor recycling, the Commander complex containing VPS26C has been implicated in cell cycle regulation, immune response, and cilium assembly 5. Cancer-associated mutations in VPS26C disrupt complex formation and impair membrane protein homeostasis 6, underscoring its clinical relevance in disease pathogenesis.

Sources cited
1
VPS26C is a component of the Retriever complex and Commander complex linked to Ritscher-Schinzel syndrome; structural organization of these complexes
PMID: 37172566
2
Retriever is a multiprotein complex distinct from retromer that recycles over 120 cell surface proteins including integrins and signaling receptors
PMID: 28892079
3
VPS26C forms a conserved interface with VPS35L that binds SNX17 C-terminal tail for endosomal cargo recycling
PMID: 39587083
4
SNX17 interaction with Retriever VPS35L-VPS26C interface is enhanced by cargo binding and membrane recognition
PMID: 39653850
5
VPS26C mutations in cancer disrupt Retriever-CCC complex formation and membrane protein homeostasis
PMID: 38062209
6
Commander complex containing VPS26C is associated with cilium assembly and centrosome functions
PMID: 38459129
7
Commander complex with VPS26C linked to Wilson's disease, atherosclerosis, and cancer
PMID: 34943955
Disease Associationsβ“˜20
alcohol drinkingOpen Targets
0.29Weak
Neurodevelopmental disorderOpen Targets
0.27Weak
Griscelli diseaseOpen Targets
0.06Suggestive
Fuchs endothelial corneal dystrophyOpen Targets
0.05Suggestive
Griscelli disease type 3Open Targets
0.05Suggestive
Griscelli syndrome type 3Open Targets
0.05Suggestive
Piebald trait - neurologic defectsOpen Targets
0.04Suggestive
piebald trait-neurologic defects syndromeOpen Targets
0.04Suggestive
Familial ocular anterior segment mesenchymal dysgenesisOpen Targets
0.04Suggestive
corneal-cerebellar syndromeOpen Targets
0.04Suggestive
Tietz syndromeOpen Targets
0.04Suggestive
Tietze syndromeOpen Targets
0.04Suggestive
isolated familial wooly hair disorderOpen Targets
0.04Suggestive
Woolly hairOpen Targets
0.04Suggestive
uncombable hair syndromeOpen Targets
0.04Suggestive
oculocutaneous albinism type 3Open Targets
0.04Suggestive
Griscelli disease type 1Open Targets
0.04Suggestive
Griscelli syndrome type 1Open Targets
0.04Suggestive
piebaldismOpen Targets
0.04Suggestive
ermine phenotypeOpen Targets
0.04Suggestive
Pathogenic Variants1
NM_006052.2(VPS26C):c.178G>T (p.Glu60Ter)Likely pathogenic
not provided|Neurodevelopmental disorder
β˜…β˜†β˜†β˜†2024β†’ Residue 60
View on ClinVar β†—
Related Genes
ARL4CShared pathway100%SNX31Shared pathway100%COMMD3Protein interaction91%DENND10Protein interaction87%VPS35Protein interaction82%STMN2Protein interaction82%
Tissue Expression6 tissues
Heart
100%
Lung
94%
Liver
84%
Bone Marrow
58%
Ovary
54%
Brain
53%
Gene Interaction Network
Click a node to explore
VPS26CARL4CSNX31COMMD3DENND10VPS35STMN2
PROTEIN STRUCTURE
Preparing viewer…
PDB8SYN Β· 2.94 Γ… Β· EM
View on RCSB β†—
Constraintβ“˜
LOEUFβ“˜
0.85LoF Tolerant
pLIβ“˜
0.00Tolerant
Observed/Expected LoF0.57 [0.40–0.85]
RankingsWhere VPS26C stands among ~20K protein-coding genes
  • #11,092of 20,598
    Most Researched35
  • #5,220of 5,498
    Most Pathogenic Variants1
  • #7,362of 17,882
    Most Constrained (LOEUF)0.85
Genes detectedVPS26C
Sources retrieved10 papers
Response timeβ€”
πŸ“„ Sources
10β–Ό
1
Structure of the endosomal Commander complex linked to Ritscher-Schinzel syndrome.
PMID: 37172566
Cell Β· 2023
1.00
2
Diversity of retromer-mediated vesicular trafficking pathways in plants.
PMID: 37409293
Front Plant Sci Β· 2023
0.90
3
Structural organization of the retriever-CCC endosomal recycling complex.
PMID: 38062209
Nat Struct Mol Biol Β· 2024
0.80
4
Structure and interactions of the endogenous human Commander complex.
PMID: 38459129
Nat Struct Mol Biol Β· 2024
0.70
5
Structural basis for Retriever-SNX17 assembly and endosomal sorting.
PMID: 39587083
Nat Commun Β· 2024
0.60