EPS8

Chr 12AR

EGFR pathway substrate 8, signaling adaptor

Also known as: DFNB102

The EPS8 protein regulates actin cytoskeleton dynamics and architecture, controlling cellular protrusions and serving as a signaling adapter in processes including axonal filopodia formation and stereocilia elongation in hair cells. Mutations cause autosomal recessive deafness (DFNB102), affecting the auditory system. This gene is highly constrained against loss-of-function mutations (pLI = 0.97), indicating that biallelic variants are likely required for disease manifestation.

Summary from RefSeq, OMIM, UniProt
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Primary Disease Associations & Inheritance

?Deafness, autosomal recessive 102MIM #615974
AR
0
Active trials
8
Pubs (1 yr)
12
P/LP submissions
0%
P/LP missense
0.31
LOEUF· LoF intol.
Mechanism
Clinical SummaryEPS8
🧬
Gene-Disease Validity (ClinGen)
autosomal recessive nonsyndromic hearing loss 102 · ARModerate

Moderate evidence — consider for supplementary testing

Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.97). One damaged copy is likely sufficient to cause disease.
📋
ClinVar Variants
12 unique Pathogenic / Likely Pathogenic· 105 VUS of 200 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

LoF intolerant — likely haploinsufficient
LoF Constraint
0.31LOEUF
pLI 0.973
Z-score 5.23
OE 0.17 (0.100.31)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint
0.81Z-score
OE missense 0.89 (0.820.97)
402 obs / 450.4 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.17 (0.100.31)
00.351.4
Missense OE0.89 (0.820.97)
00.61.4
Synonymous OE0.95
01.21.6
LoF obs/exp: 8 / 46.4Missense obs/exp: 402 / 450.4Syn Z: 0.48

ClinVar Variant Classifications

200 submitted variants in ClinVar

Classification Summary

Pathogenic9
Likely Pathogenic3
VUS105
Likely Benign48
Conflicting1
9
Pathogenic
3
Likely Pathogenic
105
VUS
48
Likely Benign
1
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
2
0
7
0
9
Likely Pathogenic
1
0
2
0
3
VUS
0
101
3
1
105
Likely Benign
0
3
20
25
48
Benign
0
0
0
0
0
Conflicting
1
Total31043226166

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

View in ClinVar →

Protein Context — Lollipop Plot

EPS8 · protein map & ClinVar variants

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

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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