ESPNL

Chr 2

espin like

NCBI Gene: 339768ENSG00000144488UniProt: Q6ZVH7

The protein binds actin and is required for the formation and maintenance of inner ear hair cell stereocilia, which are essential for normal hearing. Mutations cause autosomal recessive nonsyndromic hearing loss. The gene shows minimal constraint against loss-of-function variants, consistent with a recessive inheritance pattern.

Summary from RefSeq, UniProt
Research Assistant →
0
Active trials
0
Pubs (1 yr)
83
P/LP submissions
0%
P/LP missense
0.94
LOEUF
Multiple*
Mechanism· predicted
Clinical Summary— ESPNL
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
81 unique Pathogenic / Likely Pathogenic· 250 VUS of 353 total submissions
Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint
0.94LOEUF
pLI 0.000
Z-score 1.83
OE 0.65 (0.45–0.94)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
0.49Z-score
OE missense 0.95 (0.88–1.01)
614 obs / 649.5 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.65 (0.45–0.94)
0≤0.351.4
Missense OE0.95 (0.88–1.01)
0≤0.61.4
Synonymous OE0.99
0≤1.21.6
LoF obs/exp: 20 / 31.0Missense obs/exp: 614 / 649.5Syn Z: 0.12
DN
0.6258th %ile
GOF
0.77top 25%
LOF
0.3745th %ile

This gene has evidence for multiple mechanisms of pathogenicity (gain-of-function and dominant-negative). Both the Badonyi & Marsh prediction and the broader genomic evidence point to gain-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

GOFprediction above median
DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

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

ClinVar Variant Classifications

353 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic79
Likely Pathogenic2
VUS250
Likely Benign13
Benign2
79
Pathogenic
2
Likely Pathogenic
250
VUS
13
Likely Benign
2
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
79
0
79
Likely Pathogenic
0
0
2
0
2
VUS
0
240
10
0
250
Likely Benign
0
10
1
2
13
Benign
0
2
0
0
2
Total0252922346

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

View in ClinVar →

Protein Context — Lollipop Plot

ESPNL · 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

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 1 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC

No open access results found

Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients