VPS45
protein-codingvacuolar protein sorting 45 homolog
Gene summary
Vesicle mediated protein sorting plays an important role in segregation of intracellular molecules into distinct organelles. Genetic studies in yeast have identified more than 40 vacuolar protein sorting (VPS) genes involved in vesicle transport to vacuoles. This gene is a member of the Sec1 domain family, and shows a high degree of sequence similarity to mouse, rat and yeast Vps45. The exact function of this gene is not known, but its high expression in peripheral blood mononuclear cells suggests a role in trafficking proteins, including inflammatory mediators. Multiple alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Jul 2013]
- VPS45B
- VPS45A
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~78.1 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AR
Disease ID:MONDO:0014118
Submitter: Labcorp Genetics (formerly Invitae)
Inheritance Pattern: AR
Disease ID:MONDO:0014118
Submitter: Orphanet
Inheritance Pattern: AR
Disease ID:MONDO:0014118
Submitter: PanelApp Australia
Inheritance Pattern: AR
Disease ID:MONDO:0014118
Submitter: Natera
Clinical Genomic Database (CGD)
Manifestation: Allergy/Immunology/Infectious
Intervention: Allergy/Immunology/Infectious
Rationale: Individuals have been described with frequent and severe infections, and awareness may allow prophylactic measures (including treatment with G-CSF), as well as early and aggressive treatment of infections; HSCT has been described
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to VPS45 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_007259.5. 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 | 10 | 237 | 2 | 249 | ||
| missense | 1 | 5 | 185 | 7 | 198 | |
| nonsense | 9 | 9 | ||||
| start loss | 0 | |||||
| frameshift | 8 | 2 | 1 | 11 | ||
| splice donor/acceptor (+/-2bp) | 3 | 1 | 4 | |||
| Total | 1 | 22 | 200 | 245 | 3 | 471 |
Highest pathogenic variant AF is 0.000035936366
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_009190.2 | 15 | MANE Select | |
| Ensembl | ENSP00000495563.1 | 15 | MANE Select | |
| RefSeq | NP_001266282.1 | 13 | Standard | |
| RefSeq | NP_001266283.1 | 14 | Standard |
Model Organisms & Knockout Phenotypes
Observed phenotypic effects in mouse and zebrafish models
| Gene / Model | Organism | Observed Phenotype |
|---|---|---|
| vps45 | Danio rerio | Structure: neutrophil Quality: decreased amount abnormal |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Endocytosis - Homo sapiens (human)
- Vesicle-mediated transport
- Membrane Trafficking
- Factors involved in megakaryocyte development and platelet production
- Hemostasis
Biological Process
- intracellular protein transport
- vesicle docking involved in exocytosis
- blood coagulation
Molecular Function
- molecular_function
- protein binding
Cellular Component
- Golgi membrane
- cellular_component
- Golgi apparatus
- synaptic vesicle
- endosome membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000369130
- Coding exons
- 15
- Length
- 78137
- Individuals with no LoFs
- 125705
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 42
- Defined
- 125747
- p
- 0.000167
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 1.63 | 229 | 309 | 0.740 | 0.0000161 | 3731 |
| Missense (PolyPhen) | 65 | 112.74 | 0.57652 | 1371 | ||
| Synonymous | 1.67 | 85 | 107 | 0.795 | 0.00000513 | 1095 |
| Loss of Function | 3.14 | 15 | 35.1 | 0.427 | 0.00000208 | 394 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.000062 | 0.000062 | rare |
| Latino/Admixed American | 0.00015 | 0.00014 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.00028 | 0.00027 | rare |
| Finnish | 0.000093 | 0.000092 | rare |
| European (Non-Finnish) | 0.00016 | 0.00016 | rare |
| South Asian | 0.00033 | 0.00033 | rare |
| Other | 0.00017 | 0.00016 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: May play a role in vesicle-mediated protein trafficking from the Golgi stack through the trans-Golgi network.;
Recessive Scores
- pRec
- 0.118
Intolerance Scores
- LoFtool
- 0.830
- RVIS EVS
- -0.54
- RVIS percentile EVS
- 20.54
Essentials
- Essential (CRISPR)
- E
- Essential (CRISPR2)
- S
- Essential (gene trap)
- K
- Indispensability pred.
- E
- Indispensability score
- 0.829
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |