EPN2
protein-codingepsin 2
Gene summary
This gene encodes a protein which interacts with clathrin and adaptor-related protein complex 2, alpha 1 subunit. The protein is found in a brain-derived clathrin-coated vesicle fraction and localizes to the peri-Golgi region and the cell periphery. The protein is thought to be involved in clathrin-mediated endocytosis. Alternate splicing of this gene results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jul 2008]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~121.1 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 EPN2 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_014964.5. 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 | 2 | 2 | ||||
| missense | 68 | 2 | 70 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 1 | 1 | ||||
| Total | 0 | 0 | 71 | 2 | 0 | 73 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_055779.2 | 9 | MANE Select | |
| Ensembl | ENSP00000320543.5 | 9 | MANE Select | |
| RefSeq | NP_001096134.1 | 7 | Standard | |
| RefSeq | NP_683723.2 | 8 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Endocytosis - Homo sapiens (human)
- Vesicle-mediated transport
- Membrane Trafficking
- Clathrin-mediated endocytosis
- EGFR1
Biological Process
- endocytosis
- negative regulation of vascular endothelial growth factor receptor signaling pathway
- positive regulation of Notch signaling pathway
- membrane organization
- negative regulation of sprouting angiogenesis
Molecular Function
- protein binding
- lipid binding
- cadherin binding
Cellular Component
- cytosol
- clathrin coat of endocytic vesicle
- intracellular membrane-bounded organelle
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000314728
- Coding exons
- 9
- Length
- 121101
- Individuals with no LoFs
- 125726
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 22
- Defined
- 125748
- p
- 0.0000875
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 1.39 | 301 | 377 | 0.799 | 0.0000230 | 4078 |
| Missense (PolyPhen) | 69 | 117.95 | 0.58499 | 1254 | ||
| Synonymous | 1.45 | 141 | 165 | 0.857 | 0.0000107 | 1380 |
| Loss of Function | 3.87 | 5 | 26.5 | 0.189 | 0.00000139 | 277 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.000062 | 0.000062 | rare |
| Latino/Admixed American | 0 | 0.0 | absent |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.000059 | 0.000054 | rare |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.00011 | 0.00011 | rare |
| South Asian | 0.00023 | 0.00023 | rare |
| Other | 0.00016 | 0.00016 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Plays a role in the formation of clathrin-coated invaginations and endocytosis. {ECO:0000269|PubMed:10567358}.;
Recessive Scores
- pRec
- 0.102
Intolerance Scores
- LoFtool
- 0.521
- RVIS EVS
- -0.38
- RVIS percentile EVS
- 28.11
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.756
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |