EPS15

Chr 1

epidermal growth factor receptor pathway substrate 15

Also known as: AF-1P, AF1P, MLLT5

NCBI Gene: 2060ENSG00000085832UniProt: P42566

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]

123
ClinVar variants
9
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— EPS15
⚡
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.29) despite low pLI — interpret in context.
📋
ClinVar Variants
9 Pathogenic / Likely Pathogenic· 112 VUS of 123 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Moderate LoF intolerance
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.46LOEUF
pLI 0.003
Z-score 4.56
OE 0.29 (0.19–0.46)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
0.78Z-score
OE missense 0.90 (0.82–0.97)
402 obs / 448.6 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.29 (0.19–0.46)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.90 (0.82–0.97)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.96
0≤1.21.6
LoF obs/exp: 14 / 48.2Missense obs/exp: 402 / 448.6Syn Z: 0.37

ClinVar Variant Classifications

123 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic6
Likely Pathogenic3
VUS112
Likely Benign2
6
Pathogenic
3
Likely Pathogenic
112
VUS
2
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
6
0
6
Likely Pathogenic
0
0
3
0
3
VUS
0
107
5
0
112
Likely Benign
0
2
0
0
2
Benign
0
0
0
0
0
Total0109140123

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

EPS15 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
STRIPAK complexes: structure, biological function, and involvement in human diseases.
Hwang J et al.·Int J Biochem Cell Biol
2014Review
Over-expression of EPS15 is a favorable prognostic factor in breast cancer.
Dai X et al.·Mol Biosyst
2015
The endocytic adaptor proteins of pathogenic fungi: charting new and familiar pathways.
Wang P et al.·Med Mycol
2011Review
Increased Eps15 homology domain 1 and RAB11FIP3 expression regulate breast cancer progression via promoting epithelial growth factor receptor recycling.
Tong D et al.·Tumour Biol
2017
SGIP1alpha is an endocytic protein that directly interacts with phospholipids and Eps15.
Uezu A et al.·J Biol Chem
2007
PHD3 regulates EGFR internalization and signalling in tumours.
Garvalov BK et al.·Nat Commun
2014
EHD2-mediated restriction of caveolar dynamics regulates cellular fatty acid uptake.
Matthaeus C et al.·Proc Natl Acad Sci U S A
2020
Reps2: a cellular signaling and molecular trafficking nexus.
Badway JA et al.·Int J Biochem Cell Biol
2011Review
A novel EHD1/CD44/Hippo/SP1 positive feedback loop potentiates stemness and metastasis in lung adenocarcinoma.
Liu Y et al.·Clin Transl Med
2022
NF-κB-driven improvement of EHD1 contributes to erlotinib resistance in EGFR-mutant lung cancers.
Wang X et al.·Cell Death Dis
2018
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools