VPS51
protein-codingVPS51 subunit of GARP complex, the group of Golgi associated retrograde protein (GARP) complex|Endosome-associated recycling protein (EARP) complex
Gene summary
This gene encodes a member of the vacuolar protein sorting-associated protein 51 family. The encoded protein is a component of the Golgi-associated retrograde protein complex which acts as a tethering factor for carriers in retrograde transport from the early and late endosomes to the trans-Golgi network. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2012]
- C11orf3
- C11orf2
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~22.5 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AR
Disease ID:MONDO:0032831
Submitter: PanelApp Australia
Inheritance Pattern: Unknown
Disease ID:MONDO:0032831
Submitter: Labcorp Genetics (formerly Invitae)
Inheritance Pattern: AR
Disease ID:MONDO:0032831
Submitter: Ambry Genetics
Clinical Genomic Database (CGD)
Manifestation: Craniofacial; Neurologic; Ophthalmologic
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 VPS51 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_013265.4. 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 | 2 | 11 | 13 | |||
| missense | 1 | 138 | 3 | 142 | ||
| nonsense | 1 | 1 | 2 | |||
| start loss | 0 | |||||
| frameshift | 1 | 1 | 3 | 5 | ||
| splice donor/acceptor (+/-2bp) | 2 | 2 | ||||
| Total | 2 | 2 | 146 | 14 | 0 | 164 |
Highest pathogenic variant AF is 0.000007441076
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_037397.2 | 10 | MANE Select | |
| Ensembl | ENSP00000279281.3 | 10 | MANE Select | |
| Ensembl | ENSP00000431188.1 | 3 | Standard | |
| Ensembl | ENSP00000435629.1 | 4 | Standard |
Model Organisms & Knockout Phenotypes
Observed phenotypic effects in mouse and zebrafish models
| Gene / Model | Organism | Observed Phenotype |
|---|---|---|
| vps51 | Danio rerio | Structure: cholangiocyte Quality: dilated abnormal |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Vesicle-mediated transport
- Membrane Trafficking
- Retrograde transport at the Trans-Golgi-Network
- Intra-Golgi and retrograde Golgi-to-ER traffic
Biological Process
- lipid transport
- autophagy
- Golgi organization
- lysosomal transport
- protein transport
Molecular Function
- molecular_function
- protein binding
Cellular Component
- GARP complex
- nucleolus
- Golgi apparatus
- trans-Golgi network
- cytosol
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000279281
- Coding exons
- 10
- Length
- 22537
- Individuals with no LoFs
- 125685
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 63
- Defined
- 125748
- p
- 0.000251
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 2.66 | 347 | 518 | 0.670 | 0.0000364 | 4920 |
| Missense (PolyPhen) | 99 | 170.61 | 0.58026 | 1602 | ||
| Synonymous | 1.79 | 200 | 235 | 0.851 | 0.0000173 | 1699 |
| Loss of Function | 1.87 | 17 | 27.6 | 0.616 | 0.00000126 | 312 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00012 | 0.00012 | rare |
| Latino/Admixed American | 0.00024 | 0.00017 | rare |
| Ashkenazi Jewish | 0.00052 | 0.00040 | rare |
| East Asian | 0.00011 | 0.00011 | rare |
| Finnish | 0.00083 | 0.00074 | rare |
| European (Non-Finnish) | 0.00020 | 0.00019 | rare |
| South Asian | 0.00016 | 0.00016 | rare |
| Other | 0.0010 | 0.00098 | notable |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Acts as component of the GARP complex that is involved in retrograde transport from early and late endosomes to the trans-Golgi network (TGN). The GARP complex is required for the maintenance of protein retrieval from endosomes to the TGN, acid hydrolase sorting, lysosome function, endosomal cholesterol traffic and autophagy. VPS51 participates in retrograde transport of acid hydrolase receptors, likely by promoting tethering and SNARE-dependent fusion of endosome-derived carriers to the TGN (PubMed:20685960). 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 (PubMed:25799061). {ECO:0000269|PubMed:20685960, ECO:0000269|PubMed:25799061}.;
Recessive Scores
- pRec
- 0.183
Intolerance Scores
- RVIS EVS
- -0.64
- RVIS percentile EVS
- 16.53
Essentials
- Essential (CRISPR)
- E
- Essential (CRISPR2)
- S
- Essential (gene trap)
- E
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |