EYA1

Chr 8AD

EYA transcriptional coactivator and phosphatase 1

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

NCBI Gene: 2138ENSG00000104313UniProt: Q99502

This gene encodes a member of the eyes absent (EYA) family of proteins. The encoded protein may play a role in the developing kidney, branchial arches, eye, and ear. Mutations of this gene have been associated with branchiootorenal dysplasia syndrome, branchiootic syndrome, and sporadic cases of congenital cataracts and ocular anterior segment anomalies. A similar protein in mice can act as a transcriptional activator. Alternatively spliced transcript variants have been identified for this gene. [provided by RefSeq, Dec 2013]

Primary Disease Associations & Inheritance

?Otofaciocervical syndromeMIM #166780
AD
Anterior segment anomalies with or without cataractMIM #602588
AD
Branchiootic syndrome 1MIM #602588
AD
Branchiootorenal syndrome 1, with or without cataractsMIM #113650
AD
559
ClinVar variants
186
Pathogenic / LP
0.95
pLI score· haploinsufficient
0
Active trials
Clinical Summary— EYA1
🧬
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.
📋
ClinVar Variants
186 Pathogenic / Likely Pathogenic· 174 VUS of 559 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.33LOEUF
pLI 0.946
Z-score 4.60
OE 0.17 (0.09–0.33)
Highly constrained

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

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
1.02Z-score
OE missense 0.84 (0.76–0.93)
273 obs / 324.7 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.17 (0.09–0.33)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.84 (0.76–0.93)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.99
0≤1.21.6
LoF obs/exp: 6 / 35.7Missense obs/exp: 273 / 324.7Syn Z: 0.08

ClinVar Variant Classifications

559 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic139
Likely Pathogenic47
VUS174
Likely Benign109
Benign57
Conflicting33
139
Pathogenic
47
Likely Pathogenic
174
VUS
109
Likely Benign
57
Benign
33
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
56
5
78
0
139
Likely Pathogenic
20
11
16
0
47
VUS
1
112
53
8
174
Likely Benign
0
15
59
35
109
Benign
0
2
48
7
57
Conflicting
—33
Total7714525450559

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

View 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.

Gene2Phenotype Curations

EYA1-related branchiootorenal syndrome

definitive
ADLoss Of FunctionAbsent Gene Product
Dev. DisordersEyeEar
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

?Otofaciocervical syndrome

MIM #166780

Molecular basis of disorder known

Autosomal dominant

Anterior segment anomalies with or without cataract

MIM #602588

Molecular basis of disorder known

Autosomal dominant

Branchiootic syndrome 1

MIM #602588

Molecular basis of disorder known

Autosomal dominant

Branchiootorenal syndrome 1, with or without cataracts

MIM #113650

Molecular basis of disorder known

Autosomal dominant
📖
GeneReview available — EYA1
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Prenatal whole-exome sequencing for fetal structural anomalies: a retrospective analysis of 145 Chinese cases.
Qin Y et al.·BMC Med Genomics
2023Cohort
Branchio-oto-renal syndrome.
Kochhar A et al.·Am J Med Genet A
2007Review
Prenatal Phenotypic Analysis of Branchio-Oto-Renal Spectrum Disorder Attributable to EYA1 Gene Pathogenic Variants and Systematic Literature Review.
Tian Y et al.·Prenat Diagn
2024Review
EYA1-related disorders: two clinical cases and a literature review.
Castiglione A et al.·Int J Pediatr Otorhinolaryngol
2014Review
[Clinical phenotypic and genetic analysis of syndrome families with EYA1 gene variants].
Shao H et al.·Lin Chuang Er Bi Yan Hou Tou Jing Wai Ke Za Zhi
2024
A monoallelic variant in EYA1 is associated with Branchio-Otic syndrome in a Malian family.
Yalcouyé A et al.·Mol Genet Genomic Med
2022
Identification of thyroid cancer biomarkers using WGCNA and machine learning.
Hu G et al.·Eur J Med Res
2025
Otofaciocervical Syndrome and Its Overlap with Branchiootorenal Spectrum: An Integrated Literature Analysis of EYA1-Related Disorders, Including a Novel Case with an 8q13.2q13.3 Deletion.
Graziani L et al.·Genes (Basel)
2025Review
Novel EYA1 variants causing Branchio-oto-renal syndrome.
Klingbeil KD et al.·Int J Pediatr Otorhinolaryngol
2017
Whole genome sequencing identifies candidate genes for familial essential tremor and reveals biological pathways implicated in essential tremor aetiology.
Clark LN et al.·EBioMedicine
2022
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools