EPS15
protein-codingepidermal growth factor receptor pathway substrate 15, the group of EF-hand domain containing
Gene summary
This gene encodes a protein that is part of the EGFR pathway. The protein is present at clatherin-coated pits and is involved in receptor-mediated endocytosis of EGF. Notably, this gene is rearranged with the HRX/ALL/MLL gene in acute myelogeneous leukemias. Alternative splicing results in multiple transcript variants encoding distinct isoforms. [provided by RefSeq, May 2009]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~165.1 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 EPS15 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_001981.3. 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 | 109 | 2 | 111 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 10 | 10 | ||||
| Total | 0 | 0 | 121 | 2 | 0 | 123 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_001972.1 | 25 | MANE Select | |
| Ensembl | ENSP00000360798.3 | 25 | MANE Select | |
| RefSeq | NP_001153441.1 | 13 | Standard | |
| RefSeq | NP_001397725.1 | 24 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Endocytosis - Homo sapiens (human)
- VEGFA-VEGFR2 Signaling Pathway
- Ebola Virus Pathway on Host
- Ebola Virus Pathway on Host
- EGF-EGFR Signaling Pathway
Biological Process
- positive regulation of receptor recycling
- Golgi to endosome transport
- epidermal growth factor receptor signaling pathway
- cell population proliferation
- vesicle organization
Molecular Function
- calcium ion binding
- protein binding
- SH3 domain binding
- polyubiquitin modification-dependent protein binding
- cargo receptor activity
Cellular Component
- cytosol
- plasma membrane
- clathrin-coated pit
- basal plasma membrane
- membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000371733
- Coding exons
- 25
- Length
- 165066
- Individuals with no LoFs
- 125719
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 28
- Defined
- 125747
- p
- 0.000111
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.781 | 402 | 449 | 0.896 | 0.0000213 | 5930 |
| Missense (PolyPhen) | 110 | 152.55 | 0.72108 | 2081 | ||
| Synonymous | 0.369 | 157 | 163 | 0.963 | 0.00000847 | 1635 |
| Loss of Function | 4.56 | 14 | 48.2 | 0.291 | 0.00000214 | 629 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.000062 | 0.000062 | rare |
| Latino/Admixed American | 0.00012 | 0.00012 | rare |
| Ashkenazi Jewish | 0.000099 | 0.000099 | rare |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.00017 | 0.00015 | rare |
| South Asian | 0.00014 | 0.00013 | rare |
| Other | 0.00016 | 0.00016 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Involved in cell growth regulation. May be involved in the regulation of mitogenic signals and control of cell proliferation. Involved in the internalization of ligand-inducible receptors of the receptor tyrosine kinase (RTK) type, in particular EGFR. Plays a role in the assembly of clathrin-coated pits (CCPs). Acts as a clathrin adapter required for post-Golgi trafficking. Seems to be involved in CCPs maturation including invagination or budding. Involved in endocytosis of integrin beta- 1 (ITGB1) and transferrin receptor (TFR); internalization of ITGB1 as DAB2-dependent cargo but not TFR seems to require association with DAB2. {ECO:0000269|PubMed:16903783, ECO:0000269|PubMed:18362181, ECO:0000269|PubMed:19458185, ECO:0000269|PubMed:22648170}.;
- Disease
- DISEASE: Note=A chromosomal aberration involving EPS15 is found in acute leukemias. Translocation t(1;11)(p32;q23) with KMT2A/MLL1. The result is a rogue activator protein.;
Recessive Scores
- pRec
- 0.434
Intolerance Scores
- LoFtool
- 0.667
- RVIS EVS
- 0.47
- RVIS percentile EVS
- 78.83
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- K
- Indispensability pred.
- E
- Indispensability score
- 0.704
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |