EYA1

Chr 8AD

EYA transcriptional coactivator and phosphatase 1

Also known as: BOP, BOR, BOS1, OFC1, OTFCS

The EYA1 protein functions as both a tyrosine phosphatase that dephosphorylates histone H2AX to promote DNA repair and as a transcriptional coactivator for SIX family proteins during organogenesis. Mutations cause branchiootorenal syndrome, branchiootic syndrome, and anterior segment eye anomalies with or without cataracts, affecting development of the kidneys, ears, branchial arches, and eyes. The gene follows autosomal dominant inheritance and is highly constrained against loss-of-function variants.

OMIMResearchSummary from RefSeq, OMIM, UniProt
LOFmechanismADLOEUF 0.334 OMIM phenotypes
Clinical SummaryEYA1
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Gene-Disease Validity (ClinGen)
branchio-oto-renal syndrome · ADDefinitive

Definitive — sufficient evidence for diagnostic panels

Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.95). One damaged copy is likely sufficient to cause disease.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

LoF intolerant — likely haploinsufficient
LoF Constraint
0.33LOEUF
pLI 0.946
Z-score 4.60
OE 0.17 (0.090.33)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint
1.02Z-score
OE missense 0.84 (0.760.93)
273 obs / 324.7 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.17 (0.090.33)
00.351.4
Missense OE0.84 (0.760.93)
00.61.4
Synonymous OE0.99
01.21.6
LoF obs/exp: 6 / 35.7Missense obs/exp: 273 / 324.7Syn Z: 0.08
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
definitiveEYA1-related branchiootorenal syndromeLOFAD
DN
0.3594th %ile
GOF
0.2397th %ile
LOF
0.76top 10%

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

LOFprediction above median · 1 literature citation · LOEUF 0.33
DN1 literature citation
GOF1 literature citation

Literature Evidence

DNThese studies lend support to the hypothesis that dominant-negative effects of EYA1 mutations may have a role in the pathogenesis of BOR.PMID:19951260
GOFWesuggest that the pathogenesis of BOR syndrome involves a compo-nent of dominant-negative gain-of-function effects, in addition to the previously reported haploinsuficiency model.PMID:19206155
LOFA novel mutation in EYA1 in a Chinese family with Branchio-oto-renal syndromePMID:30086703

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

EYA1 · 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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