EYA4

Chr 6AD

EYA transcriptional coactivator and phosphatase 4

EYA4 encodes a tyrosine phosphatase that dephosphorylates histone H2AX to promote DNA repair and regulate transcription during organogenesis. Mutations cause autosomal dominant non-syndromic sensorineural hearing loss (DFNA10) with postlingual, progressive onset and dilated cardiomyopathy. The gene is highly constrained against loss-of-function variants (LOEUF 0.45), reflecting its essential cellular functions.

OMIMResearchSummary from RefSeq, UniProt
LOFmechanismADLOEUF 0.452 OMIM phenotypes
Clinical SummaryEYA4
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Gene-Disease Validity (ClinGen)
nonsyndromic genetic hearing loss · ADDefinitive

Definitive — sufficient evidence for diagnostic panels

2 total gene-disease associations curated

Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.27) despite low pLI — interpret in context.
Some data sources returned errors (1)

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Moderate LoF intolerance
LoF Constraint
0.45LOEUF
pLI 0.049
Z-score 4.18
OE 0.27 (0.160.45)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
1.12Z-score
OE missense 0.83 (0.750.92)
276 obs / 333.4 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.27 (0.160.45)
00.351.4
Missense OE0.83 (0.750.92)
00.61.4
Synonymous OE0.84
01.21.6
LoF obs/exp: 10 / 37.7Missense obs/exp: 276 / 333.4Syn Z: 1.38
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
limitedEYA4-related dilated cardiomyopathyOTHERAD
definitiveEYA4-related deafnessLOFAD
DN
0.6064th %ile
GOF
0.3392th %ile
LOF
0.49top 25%

The Badonyi & Marsh model scores dominant-negative highest, but genomic evidence most strongly supports loss-of-function (haploinsufficiency) as the primary mechanism.

LOF1 literature citation · LOEUF 0.45

Literature Evidence

LOFMutations in the transcriptional activator EYA4 cause late-onset deafness at the DFNA10 locusPMID:11159937

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

EYA4 · 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.

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Clinical Literature
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