VPS50
protein-codingVPS50 subunit of EARP/GARPII complex, the group of Endosome-associated recycling protein (EARP) complex
Gene summary
Enables SNARE binding activity. Acts upstream of or within endocytic recycling. Located in recycling endosome. Part of EARP complex. [provided by Alliance of Genome Resources, Jul 2025]
- CCDC132
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~128.8 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AR
Disease ID:MONDO:0001150
Submitter: LiferaOmics
Genetic evidence – Published PMID: 37644014 – Family 1 – one affected fetus. Case-level (AR homozygous; predicted null nonsense; default = 1.5; no consanguinity information provided; no deduction applied) = 1.5; Segregation = 0; Case-control = 0 Published genetic evidence total = 1.5 Genetic evidence – Our cases Family 1 – one proband. Case-level (AR homozygous; predicted null nonsense; default = 1.5; consanguineous family; −0.5 consanguinity deduction applied) = 1.0; Segregation = 0; Case-control = 0 Family 2 – one proband. Case-level (AR homozygous; predicted null nonsense; default = 1.5; no consanguinity reported; no deduction applied) = 1.5; Segregation = 0; Case-control = 0 Family 3 – one proband. Case-level (AR homozygous; predicted null nonsense; default = 1.5; consanguineous family; −0.5 consanguinity deduction applied) = 1.0; Segregation = 0; Case-control = 0 Our cases genetic evidence total = 3.5 Total genetic evidence (Published + Our cases) 5.0 / 12 Experimental evidence – Published No experimental evidence supporting a VPS50-related autosomal recessive congenital hydrocephalus phenotype was identified. Experimental evidence total = 0 / 6 Overall score Genetic evidence = 5.0 Experimental evidence = 0 Total = 5.0
Inheritance Pattern: AR
Disease ID:MONDO:0859216
Submitter: Ambry Genetics
Inheritance Pattern: AR
Disease ID:MONDO:0859216
Submitter: PanelApp Australia
Clinical Genomic Database (CGD)
Manifestation: Gastrointestinal; Neurologic
Intervention: General
Rationale: Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to VPS50 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_017667.4. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 1 | 7 | 1 | 9 | ||
| missense | 98 | 3 | 1 | 102 | ||
| nonsense | 1 | 2 | 2 | 5 | ||
| start loss | 0 | |||||
| frameshift | 1 | 1 | ||||
| splice donor/acceptor (+/-2bp) | 1 | 2 | 6 | 9 | ||
| Total | 2 | 5 | 107 | 10 | 2 | 126 |
Highest pathogenic variant AF is 0.0000013758016
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_060137.2 | 28 | MANE Select | |
| Ensembl | ENSP00000307666.5 | 28 | MANE Select | |
| RefSeq | NP_001244927.1 | 27 | Standard | |
| RefSeq | NP_078829.1 | 12 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Biological Process
- protein transport
- endocytic recycling
- retrograde transport, endosome to Golgi
Molecular Function
- SNARE binding
- protein binding
Cellular Component
- cytosol
- membrane
- recycling endosome
- extracellular exosome
- EARP complex
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000305866
- Coding exons
- 28
- Length
- 126686
- Individuals with no LoFs
- 125727
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 21
- Defined
- 125748
- p
- 0.0000835
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 2.50 | 325 | 479 | 0.678 | 0.0000233 | 6352 |
| Missense (PolyPhen) | 80 | 144.4 | 0.55401 | 1968 | ||
| Synonymous | -0.246 | 167 | 163 | 1.02 | 0.00000782 | 1719 |
| Loss of Function | 5.63 | 12 | 58.4 | 0.205 | 0.00000281 | 755 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00013 | 0.00012 | rare |
| Latino/Admixed American | 0 | 0.0 | absent |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.00015 | 0.00014 | rare |
| South Asian | 0.00010 | 0.000098 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Acts as component of the EARP complex that is involved in endocytic recycling. The EARP complex associates with Rab4- positive endosomes and promotes recycling of internalized transferrin receptor (TFRC) to the plasma membrane. Within the EARP complex, required to tether the complex to recycling endosomes. Not involved in retrograde transport from early and late endosomes to the trans-Golgi network (TGN). {ECO:0000269|PubMed:25799061}.;
Intolerance Scores
- RVIS EVS
- -0.18
- RVIS percentile EVS
- 40.56
Essentials
- Essential (gene trap)
- N