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GeneE
7 sources retrieved Β· Most recent: April 2026 Β· Index updated 14 days ago
β“˜GeneE is for informational purposes only. It is not a substitute for professional medical advice, diagnosis, or treatment.
VPS50
VPS50 subunit of EARP/GARPII complex
Chromosome 7 Β· 7q21.2-q21.3
NCBI Gene: 55610Ensembl: ENSG00000004766.18HGNC: HGNC:25956UniProt: Q96JG6
51PubMed Papers
21Diseases
0Drugs
7Pathogenic Variants
FUNCTIONAL ROLE
Transporter
CLINICAL
OMIM Disease Gene
DATA QUALITY
βœ“ Experimental GO Evidenceβœ“ Swiss-Prot Reviewed
EARP complexendocytic recyclingSNARE bindingprotein bindingneurodevelopmental disorder with microcephaly, seizures, and neonatal cholestasisnutritional deficiency diseaseplacenta praeviamacular degeneration
✦AI Summary

VPS50 is a unique subunit of the EARP (endosome-associated recycling protein) complex, a heterotetrameric membrane-tethering protein located at recycling endosomes 1. The EARP complex, which shares three subunits (VPS51, VPS52, VPS53) with the related GARP complex, mediates endocytic recycling by promoting the recycling of internalized transferrin receptors back to the plasma membrane 2. VPS50 is required to tether the EARP complex to recycling endosomes and functions distinctly from retrograde transport pathways 1. Biallelic VPS50 variants cause a severe neurodevelopmental disorder characterized by developmental delay, postnatal microcephaly, corpus callosum hypoplasia, seizures, neonatal cholestasis, and failure to thrive 13. Loss-of-function mutations impair transferrin receptor recycling and destabilize associated EARP subunits 1. Beyond endocytic recycling, VPS50 dysfunction affects hepatocyte polarity, causing mislocalization of bile canalicular proteins to basolateral membranes and abnormal tight junctions 1. Additionally, genetic variants in human VPS50 are associated with depression traits, suggesting roles in hippocampal neural network function 4. The disease, termed GARP/EARP deficiency when involving shared subunits, is potentially fatal in early childhood 3.

Sources cited
1
VPS50 is required for recycling of internalized transferrin receptors to the cell surface and its mutations cause neurodevelopmental disorders
PMID: 30828385
2
Biallelic VPS50 variants cause neurodevelopmental disorder with microcephaly, seizures, neonatal cholestasis; VPS50 is unique to EARP complex and required for endocytic recycling and hepatocyte polarity
PMID: 34037727
3
VPS50 deficiency core phenotype includes severe developmental delay, microcephaly, hypoplastic corpus callosum, neonatal cholestasis, and is potentially fatal in early childhood
PMID: 38876772
4
Human VPS50 genetic variants are significantly associated with depression traits from genomic studies
PMID: 36163151
⚠Limited data available β€” This gene has 4 indexed publications. Summary and analysis may be incomplete.
Disease Associationsβ“˜21
neurodevelopmental disorder with microcephaly, seizures, and neonatal cholestasisOpen Targets
0.51Moderate
nutritional deficiency diseaseOpen Targets
0.29Weak
placenta praeviaOpen Targets
0.29Weak
macular degenerationOpen Targets
0.27Weak
Abnormal corpus callosum morphologyOpen Targets
0.27Weak
Failure to thriveOpen Targets
0.27Weak
Profound global developmental delayOpen Targets
0.27Weak
Secondary microcephalyOpen Targets
0.27Weak
SeizureOpen Targets
0.27Weak
glomerulonephritisOpen Targets
0.24Weak
ArthropathyOpen Targets
0.23Weak
gastric cancerOpen Targets
0.07Suggestive
liver diseaseOpen Targets
0.05Suggestive
Abnormality of the skeletal systemOpen Targets
0.05Suggestive
hemangiomaOpen Targets
0.03Suggestive
lymphangiomaOpen Targets
0.03Suggestive
corneal dystrophyOpen Targets
0.02Suggestive
brain compressionOpen Targets
0.02Suggestive
neoplasmOpen Targets
0.02Suggestive
edemaOpen Targets
0.02Suggestive
Neurodevelopmental disorder with microcephaly, seizures, and neonatal cholestasisUniProt
Pathogenic Variants7
NM_017667.4(VPS50):c.1739del (p.Pro580fs)Likely pathogenic
not provided
β˜…β˜†β˜†β˜†2025β†’ Residue 580
NM_017667.4(VPS50):c.2464-1G>CLikely pathogenic
not provided
β˜…β˜†β˜†β˜†2024
NM_017667.4(VPS50):c.2208-2A>GLikely pathogenic
not provided
β˜…β˜†β˜†β˜†2024
NM_017667.4(VPS50):c.1705C>T (p.Arg569Ter)Likely pathogenic
Neurodevelopmental disorder with microcephaly, seizures, and neonatal cholestasis
β˜…β˜†β˜†β˜†2024β†’ Residue 569
NM_017667.4(VPS50):c.1723C>T (p.Gln575Ter)Likely pathogenic
Neurodevelopmental disorder with microcephaly, seizures, and neonatal cholestasis
β˜…β˜†β˜†β˜†2022β†’ Residue 575
NM_017667.4(VPS50):c.1978-1G>TPathogenic
Neurodevelopmental disorder with microcephaly, seizures, and neonatal cholestasis
β˜†β˜†β˜†β˜†2022
NM_017667.4(VPS50):c.1823_1825del (p.Thr608del)Pathogenic
Neurodevelopmental disorder with microcephaly, seizures, and neonatal cholestasis
β˜†β˜†β˜†β˜†2022β†’ Residue 608
View on ClinVar β†—
Related Genes
EIPR1Protein interaction97%VPS54Protein interaction97%VPS53Protein interaction73%VPS51Protein interaction69%VPS29Shared pathway67%VPS52Protein interaction64%
Tissue Expression6 tissues
Brain
100%
Heart
91%
Bone Marrow
71%
Ovary
70%
Lung
59%
Liver
55%
Gene Interaction Network
Click a node to explore
VPS50EIPR1VPS54VPS53VPS51VPS29VPS52
PROTEIN STRUCTURE
Preparing viewer…
AlphaFoldAI-predicted Β· UniProt Q96JG6
View on AlphaFold β†—
Constraintβ“˜
LOEUFβ“˜
0.78LoF Tolerant
pLIβ“˜
0.11Tolerant
Observed/Expected LoF0.46 [0.28–0.78]
RankingsWhere VPS50 stands among ~20K protein-coding genes
  • #8,756of 20,598
    Most Researched51
  • #3,222of 5,498
    Most Pathogenic Variants7
  • #6,397of 17,882
    Most Constrained (LOEUF)0.78
Genes detectedVPS50
Sources retrieved7 papers
Response timeβ€”
πŸ“„ Sources
7β–Ό
1
The rare mutation in the endosome-associated recycling protein gene
PMID: 30828385
Mol Cytogenet Β· 2019
1.00
2
Biallelic variants in VPS50 cause a neurodevelopmental disorder with neonatal cholestasis.
PMID: 34037727
Brain Β· 2021
0.86
3
Involvement of a BH3-only apoptosis sensitizer gene Blm-s in hippocampus-mediated mood control.
PMID: 36163151
Transl Psychiatry Β· 2022
0.71
4
A neurodevelopmental disorder caused by mutations in the VPS51 subunit of the GARP and EARP complexes.
PMID: 30624672
Hum Mol Genet Β· 2019
0.57
5
Complex structural variation and nonsense variant
PMID: 38876772
J Med Genet Β· 2024
0.43