VEPH1
protein-codingventricular zone expressed PH domain containing 1, the group of Armadillo like helical domain containing|Pleckstrin homology domain containing
Gene summary
Predicted to enable phosphatidylinositol-5-phosphate binding activity. Involved in negative regulation of SMAD protein signal transduction and negative regulation of transforming growth factor beta receptor signaling pathway. Predicted to be located in endomembrane system. Predicted to be active in plasma membrane. [provided by Alliance of Genome Resources, Apr 2025]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~273.9 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
No GenCC data available for this gene.
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to VEPH1 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_001167912.2. 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 | 2 | ||||
| missense | 94 | 6 | 100 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 4 | 4 | ||||
| Total | 0 | 0 | 100 | 6 | 0 | 106 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_001161384.1 | 13 | MANE Select | |
| Ensembl | ENSP00000354919.2 | 13 | MANE Select | |
| RefSeq | NP_001161383.1 | 12 | Standard | |
| RefSeq | NP_001161387.1 | 3 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Molecular Function
- protein binding
Cellular Component
- plasma membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000362010
- Coding exons
- 13
- Length
- 273878
- Individuals with no LoFs
- 125624
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 124
- Defined
- 125748
- p
- 0.000493
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | -0.213 | 446 | 434 | 1.03 | 0.0000210 | 5535 |
| Missense (PolyPhen) | 145 | 133.47 | 1.0864 | 1762 | ||
| Synonymous | 1.15 | 142 | 161 | 0.884 | 0.00000847 | 1550 |
| Loss of Function | 0.449 | 35 | 38.0 | 0.921 | 0.00000188 | 465 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00025 | 0.00025 | rare |
| Latino/Admixed American | 0.00038 | 0.00038 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.00033 | 0.00033 | rare |
| Finnish | 0.000046 | 0.000046 | rare |
| European (Non-Finnish) | 0.00071 | 0.00071 | rare |
| South Asian | 0.00042 | 0.00039 | rare |
| Other | 0.0011 | 0.0011 | notable |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Interacts with TGF-beta receptor type-1 (TGFBR1) and inhibits dissociation of activated SMAD2 from TGFBR1, impeding its nuclear accumulation and resulting in impaired TGF-beta signaling. May also affect FOXO, Hippo and Wnt signaling. {ECO:0000269|PubMed:26039994}.;
Recessive Scores
- pRec
- 0.0970
Intolerance Scores
- LoFtool
- 0.961
- RVIS EVS
- 1.07
- RVIS percentile EVS
- 91.69
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.305
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | High |
| Cancer | Medium | Medium | Medium |