EPS8

Chr 12AR

EGFR pathway substrate 8, signaling adaptor

Also known as: DFNB102

NCBI Gene: 2059 ENSG00000151491 UniProt: Q12929 OMIM: 600206

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.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

This gene encodes a member of the EPS8 family. This protein contains one PH domain and one SH3 domain. It functions as part of the EGFR pathway, though its exact role has not been determined. Highly similar proteins in other organisms are involved in the transduction of signals from Ras to Rac and growth factor-mediated actin remodeling. Alternate transcriptional splice variants of this gene have been observed but have not been thoroughly characterized. [provided by RefSeq, Jul 2008]

OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

?Deafness, autosomal recessive 102MIM #615974

Clinical highlights

Gene-disease validity (ClinGen)

autosomal recessive nonsyndromic hearing loss 102 · ARModerateconsider for supplementary testing

Interpreting a novel variant

This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Based on population constraint only.

Active trials

Pubs (1 yr)

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P/LP submissions

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P/LP missense

0.31

LOEUF· LoF intol.

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Mechanism