EYA4

Chr 6

EYA transcriptional coactivator and phosphatase 4

Also known as: CMD1J, DFNA10

NCBI Gene: 2070ENSG00000112319UniProt: O95677

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]

GeneReviewsResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtDeafness, autosomal dominant, 10
UniProtCardiomyopathy, dilated, 1J

Clinical highlights

Gene-disease validity (ClinGen)
nonsyndromic genetic hearing loss · ADDefinitivesufficient evidence for diagnostic panels2 gene-disease associations curated in total
Interpreting a novel variant
Loss of function is the curated mechanism (Gene2Phenotype) and the gene is intolerant of it in the population — truncating, frameshift and canonical splice variants carry more prior weight here than missense.Curated gene-level mechanism — a prior for triage, not a per-variant call.
0
Active trials
15
Pubs (1 yr)
—
P/LP submissions
—
P/LP missense
0.45
LOEUF
LOF
Mechanism· G2P
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GeneReview available — EYA4
Authoritative clinical overview · Recommended first read
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Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Moderate LoF intolerance
LoF Constraint?
0.45LOEUF
pLI 0.049
Z-score 4.18
OE 0.27 (0.16–0.45)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?
1.12Z-score
OE missense 0.83 (0.75–0.92)
276 obs / 333.4 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?
LoF OE?0.27 (0.16–0.45)
0≤0.351.4
Missense OE?0.83 (0.75–0.92)
0≤0.61.4
Synonymous OE?0.84
0≤1.21.6
LoF obs/exp: 10 / 37.7Missense obs/exp: 276 / 333.4Syn Z: 1.38

ClinVar Variant Classifications

0 submitted variants in ClinVar

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

ClinicalTrials.gov

No active trials found for this gene.

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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