ESPN

Chr 1ARAD

espin

Also known as: DFNA91, DFNB36, LP2654, USH1M

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]

GeneReviewsOMIMResearchGenerating clinical summary…
LOFmechanismAR/ADLOEUF 0.933 OMIM phenotypes
Clinical SummaryESPN
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Gene-Disease Validity (ClinGen)
nonsyndromic genetic hearing loss · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

2 total gene-disease associations curated

Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
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GeneReview available — ESPN
Authoritative clinical overview · Recommended first read
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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint?
0.93LOEUF
pLI 0.000
Z-score 1.83
OE 0.63 (0.430.93)
Tolerant

Typical tolerance to LoF variation

Missense Constraint?
-0.08Z-score
OE missense 1.01 (0.931.09)
440 obs / 435.4 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios?
LoF OE?0.63 (0.430.93)
00.351.4
Missense OE?1.01 (0.931.09)
00.61.4
Synonymous OE?0.93
01.21.6
LoF obs/exp: 18 / 28.6Missense obs/exp: 440 / 435.4Syn Z: 0.80
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
definitiveESPN-related deafness with or without vestibular involvementLOFAR
limitedESPN-related Usher syndromeOTHERAR

This gene — mechanism propensity

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

DN
0.6161th %ile
GOF
0.6737th %ile
LOF
0.3939th %ile

The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

ESPN · 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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