EVPL
protein-codingenvoplakin, the group of Plakins
Gene summary
This gene encodes a member of the plakin family of proteins that forms a component of desmosomes and the epidermal cornified envelope. This gene is located in the tylosis oesophageal cancer locus on chromosome 17q25, and its deletion is associated with both familial and sporadic forms of oesophageal squamous cell carcinoma. Patients suffering from the autoimmune mucocutaneous disorder, paraneoplastic pemphigus, develop antibodies against the encoded protein. [provided by RefSeq, Jul 2016]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~22.8 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: Unknown
Disease ID:MONDO:0007661
Submitter: Labcorp Genetics (formerly Invitae)
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to EVPL variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_001988.4. 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 | 3 | 7 | 10 | |||
| missense | 377 | 27 | 3 | 407 | ||
| nonsense | 1 | 1 | ||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 6 | 6 | ||||
| Total | 0 | 0 | 387 | 34 | 3 | 424 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_001979.2 | 22 | MANE Select | |
| Ensembl | ENSP00000301607.3 | 22 | MANE Select | |
| RefSeq | NP_001307676.1 | 22 | Standard | |
| Ensembl | ENSP00000465630.1 | 22 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Keratinization
- Developmental Biology
- Validated transcriptional targets of TAp63 isoforms
- Formation of the cornified envelope
Biological Process
- epidermis development
- peptide cross-linking
- keratinocyte differentiation
- wound healing
- intermediate filament cytoskeleton organization
Molecular Function
- structural molecule activity
- intermediate filament binding
- protein binding, bridging
- cadherin binding
Cellular Component
- cornified envelope
- cytoplasm
- cytosol
- intermediate filament
- membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000301607
- Coding exons
- 22
- Length
- 22951
- Individuals with no LoFs
- 125463
- Homozygous LoFs
- 1
- Heterozygous LoFs
- 284
- Defined
- 125748
- p
- 0.00113
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | -0.307 | 1302 | 1.27e+3 | 1.02 | 0.0000924 | 13012 |
| Missense (PolyPhen) | 347 | 357.22 | 0.97139 | 3803 | ||
| Synonymous | -0.340 | 574 | 564 | 1.02 | 0.0000402 | 4154 |
| Loss of Function | 3.55 | 54 | 90.4 | 0.597 | 0.00000460 | 974 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.0028 | 0.0022 | notable |
| Latino/Admixed American | 0.00056 | 0.00055 | rare |
| Ashkenazi Jewish | 0.00030 | 0.00030 | rare |
| East Asian | 0.0013 | 0.0013 | notable |
| Finnish | 0.00041 | 0.00037 | rare |
| European (Non-Finnish) | 0.0013 | 0.0012 | notable |
| South Asian | 0.0016 | 0.0016 | notable |
| Other | 0.0016 | 0.0013 | notable |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Component of the cornified envelope of keratinocytes. May link the cornified envelope to desmosomes and intermediate filaments.;
Recessive Scores
- pRec
- 0.260
Intolerance Scores
- LoFtool
- 0.859
- RVIS EVS
- 0.77
- RVIS percentile EVS
- 86.9
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.731
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |