EPS15L1
protein-codingepidermal growth factor receptor pathway substrate 15 like 1, the group of EF-hand domain containing
Gene summary
Enables cadherin binding activity. Predicted to be involved in endocytosis and endosomal transport. Located in membrane. [provided by Alliance of Genome Resources, Jun 2026]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~116.9 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AD
Disease ID:MONDO:0016576
Submitter: Orphanet
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to EPS15L1 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_001258374.3. 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 | 3 | 3 | ||||
| missense | 100 | 5 | 105 | |||
| nonsense | 2 | 2 | ||||
| start loss | 0 | |||||
| frameshift | 1 | 1 | ||||
| splice donor/acceptor (+/-2bp) | 7 | 7 | ||||
| Total | 0 | 0 | 113 | 5 | 0 | 118 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_001245303.1 | 24 | MANE Select | |
| Ensembl | ENSP00000393313.1 | 24 | MANE Select | |
| RefSeq | NP_001245304.1 | 22 | Standard | |
| RefSeq | NP_001245305.1 | 16 | Standard |
Model Organisms & Knockout Phenotypes
Observed phenotypic effects in mouse and zebrafish models
| Gene / Model | Organism | Observed Phenotype |
|---|---|---|
| eps15l1b | Danio rerio | Structure: T cell differentiation in thymus Quality: disrupted abnormal |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Endocytosis - Homo sapiens (human)
- EGF-EGFR Signaling Pathway
- Signal Transduction
- Vesicle-mediated transport
- Membrane Trafficking
Biological Process
- endocytosis
- negative regulation of epidermal growth factor receptor signaling pathway
- membrane organization
Molecular Function
- calcium ion binding
- protein binding
- cadherin binding
Cellular Component
- nucleus
- cytosol
- plasma membrane
- membrane
- clathrin coat of coated pit
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000455140
- Coding exons
- 24
- Length
- 116847
- Individuals with no LoFs
- 125734
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 14
- Defined
- 125748
- p
- 0.0000557
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 1.90 | 417 | 542 | 0.770 | 0.0000322 | 6002 |
| Missense (PolyPhen) | 111 | 182.89 | 0.60691 | 2116 | ||
| Synonymous | 0.746 | 220 | 235 | 0.938 | 0.0000164 | 1739 |
| Loss of Function | 5.90 | 7 | 53.6 | 0.131 | 0.00000293 | 579 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0.000029 | 0.000029 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.00011 | 0.00011 | rare |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.000097 | 0.000088 | rare |
| South Asian | 0.000033 | 0.000033 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Seems to be a constitutive component of clathrin-coated pits that is required for receptor-mediated endocytosis. 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:22648170, ECO:0000269|PubMed:9407958}.;
Recessive Scores
- pRec
- 0.127
Intolerance Scores
- LoFtool
- 0.269
- RVIS EVS
- -2.13
- RVIS percentile EVS
- 1.51
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- S
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.603
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |