ESPN

Chr 1ARAD

espin

Also known as: DFNA91, DFNB36, LP2654, USH1M

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.

OMIMResearchSummary from RefSeq, OMIM, UniProt
LOFmechanismAR/ADLOEUF 0.933 OMIM phenotypes
Clinical SummaryESPN
🧬
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.

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 OE0.63 (0.430.93)
00.351.4
Missense OE1.01 (0.931.09)
00.61.4
Synonymous OE0.93
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

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.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →