ESPN

Chr 1

espin

Also known as: DFNA91, DFNB36, LP2654, USH1M

NCBI Gene: 83715 ENSG00000187017 UniProt: B1AK53

This protein is a multifunctional actin-bundling protein that regulates the organization and dynamics of stereocilia in inner ear hair cells, which are essential for hearing and balance. Mutations cause autosomal recessive deafness (DFNB36), autosomal dominant deafness (DFNA91), and possibly Usher syndrome type 1M, which combines congenital deafness with progressive vision loss. The gene shows very low constraint against loss-of-function variants, and both recessive and dominant inheritance patterns are observed depending on the specific mutation.

GeneReviews ResearchSummary from RefSeq, OMIM, UniProt

This gene encodes a multifunctional actin-bundling protein. It plays a major role in regulating the organization, dimensions, dynamics, and signaling capacities of the actin filament-rich, microvillus-type specializations that mediate sensory transduction in various mechanosensory and chemosensory cells. Mutations in this gene are associated with autosomal recessive neurosensory deafness, and autosomal dominant sensorineural deafness without vestibular involvement. [provided by RefSeq, Nov 2009]

GeneReviews ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtDeafness, autosomal recessive, 36, with or without vestibular involvement

UniProtDeafness, autosomal dominant, 91

UniProtUsher syndrome 1M

Clinical highlights

Gene-disease validity (ClinGen)

nonsyndromic genetic hearing loss · ARDefinitivesufficient evidence for diagnostic panels2 gene-disease associations curated in total

Interpreting a novel variant

Loss of function is the curated mechanism (Gene2Phenotype), though the gene is not strongly LoF-constrained in the population — weigh truncating variants against that tolerance.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.93

LOEUF

LOF

Mechanism· G2P

📖

GeneReview available — ESPN