EPS15

Chr 1

epidermal growth factor receptor pathway substrate 15

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

This protein functions in receptor-mediated endocytosis, particularly of growth factor receptors like EGFR, and plays a role in clathrin-coated pit assembly and maturation. Mutations cause autosomal recessive developmental and epileptic encephalopathy with early infantile onset, characterized by severe intellectual disability, seizures, and microcephaly. The gene is highly constrained against loss-of-function variants in the general population.

OMIMResearchSummary from RefSeq, UniProt
LOEUF 0.46
Clinical SummaryEPS15
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.29) despite low pLI — interpret in context.
📋
ClinVar Variants
9 unique Pathogenic / Likely Pathogenic· 112 VUS of 156 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Moderate LoF intolerance
LoF Constraint
0.46LOEUF
pLI 0.003
Z-score 4.56
OE 0.29 (0.190.46)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
0.78Z-score
OE missense 0.90 (0.820.97)
402 obs / 448.6 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.29 (0.190.46)
00.351.4
Missense OE0.90 (0.820.97)
00.61.4
Synonymous OE0.96
01.21.6
LoF obs/exp: 14 / 48.2Missense obs/exp: 402 / 448.6Syn Z: 0.37

ClinVar Variant Classifications

156 submitted variants in 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.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
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