EYA4

Chr 6AD

EYA transcriptional coactivator and phosphatase 4

Also known as: CMD1J, DFNA10

This gene encodes a member of the eyes absent (EYA) family of proteins. The encoded protein may act as a transcriptional activator through its protein phosphatase activity, and it may be important for eye development, and for continued function of the mature organ of Corti. Mutations in this gene are associated with postlingual, progressive, autosomal dominant hearing loss at the deafness, autosomal dominant non-syndromic sensorineural 10 locus. The encoded protein is also a putative oncogene that mediates DNA repair, apoptosis, and innate immunity following DNA damage, cellular damage, and viral attack. Defects in this gene are also associated with dilated cardiomyopathy 1J. Alternative splicing results in multiple transcript variants encoding distinct isoforms. [provided by RefSeq, Jul 2014]

GeneReviewsOMIMResearchGenerating clinical summary…
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.
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GeneReview available — EYA4
Authoritative clinical overview · Recommended first read
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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 OE?0.27 (0.160.45)
00.351.4
Missense OE?0.83 (0.750.92)
00.61.4
Synonymous OE?0.84
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

This gene — mechanism propensity

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 · ClinGen HI: Sufficient evidence for dosage pathogenicity

Literature Evidence

LOFMutations in the transcriptional activator EYA4 cause late-onset deafness at the DFNA10 locus1

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

References

  1. 1.PMID 11159937

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.

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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