Affinage

EYA4

Protein phosphatase EYA4 · UniProt O95677

Length
639 aa
Mass
69.5 kDa
Annotated
2026-06-09
64 papers in source corpus 19 papers cited in narrative 20 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

EYA4 is a dual-function protein that acts both as a SIX-dependent transcriptional coactivator and as a phosphatase, operating in developmental gene-regulatory networks and in genome-maintenance pathways (PMID:15492887, PMID:38360978). It is built around a conserved C-terminal Eya homologous region that mediates protein-protein interactions (PMID:9887327); through this domain EYA4 binds SIX family transcription factors (SIX1, SIX3), which recruit cytoplasmic EYA4 to the nucleus where the complex activates target gene transcription (PMID:15492887, PMID:19606496). As a tyrosine phosphatase, EYA4 dephosphorylates PLK1 at pY445 during G2 to drive centrosome maturation and PLK1 activation, and dephosphorylates RAD51 at pY315 to promote presynaptic filament formation and homologous recombination, with its phosphatase activity stimulated by DNA binding (PMID:38360978, PMID:38084915). Its serine/threonine phosphatase activity supports replication fork progression and prevents replication stress (PMID:37777742), suppresses NF-κB signaling by blocking IκBα phosphorylation and p65 nuclear translocation (PMID:29764501), and dephosphorylates β-catenin at Ser552 to restrain β-catenin/LEF1-driven MYCBP transcription (PMID:31385398). In the heart EYA4 regulates a p27kip1/CK2α/HDAC2 cascade required for normal cardiac function (PMID:26499333), and in development it controls Na+/K+-ATPase (atp1b2b) expression needed for sensory hair cell and cardiac formation (PMID:18799547). EYA4 protein levels are controlled post-transcriptionally and post-translationally, including ERK2-primed, TRIM69-mediated ubiquitylation and proteasomal turnover (PMID:36741265). Haploinsufficiency from truncating EYA4 mutations causes DFNA10 postlingual progressive autosomal dominant sensorineural hearing loss, and more N-terminal truncations that additionally abolish SIX binding cause dilated cardiomyopathy (PMID:11159937, PMID:15735644).

Mechanistic history

Synthesis pass · year-by-year structured walk · 18 steps
  1. 1999 Medium

    Defined EYA4 at the sequence level and identified a conserved C-terminal domain as the likely interaction module, establishing the structural basis for later functional studies.

    Evidence cDNA cloning and domain characterization of human and mouse genes

    PMID:9887327

    Open questions at the time
    • No interaction partner or biochemical activity demonstrated
    • Function inferred only from homology
  2. 2001 High

    Established EYA4 as a disease gene by linking truncating mutations to DFNA10 hearing loss, implicating haploinsufficiency as the mechanism.

    Evidence Candidate gene sequencing and co-segregation in two unrelated families

    PMID:11159937

    Open questions at the time
    • Molecular function of EYA4 in the cochlea not addressed
    • Did not test protein-level consequences of mutations
  3. 2004 Medium

    Connected EYA4 to the SIX-EYA network by showing its conserved domain binds SIX1 and is shuttled to the nucleus by SIX1, providing a mechanism for nuclear function.

    Evidence Yeast two-hybrid, immunofluorescence localization, dual Eya constructs

    PMID:15492887

    Open questions at the time
    • Direct transcriptional targets not identified
    • Did not address phosphatase activity
  4. 2005 High

    Showed that SIX-binding-disrupting truncations cause dilated cardiomyopathy in addition to hearing loss, mechanistically separating cardiac from cochlear phenotypes by interaction competence.

    Evidence Zebrafish morpholino knockdown and truncated-peptide binding assays

    PMID:15735644

    Open questions at the time
    • Cardiac transcriptional targets not defined
    • How SIX binding maintains cardiac function unresolved
  5. 2008 High

    Placed Na+/K+-ATPase subunit atp1b2b downstream of EYA4, identifying an effector for its developmental role in hair cell and cardiac formation.

    Evidence Zebrafish morpholino knockdown with rescue/epistasis and phenotypic readouts

    PMID:18799547

    Open questions at the time
    • Whether EYA4 directly regulates atp1b2b transcription not shown
    • Mammalian relevance not tested
  6. 2009 Medium

    Extended the SIX-EYA module to SIX3, demonstrating EYA4 acts as a transcriptional coactivator recruited to the nucleus by a second SIX partner.

    Evidence Co-immunoprecipitation, confocal localization, luciferase reporter

    PMID:19606496

    Open questions at the time
    • No endogenous target genes identified
    • Forebrain role inferred, not directly tested
  7. 2015 High

    Defined a cardiac transcriptional/signaling mechanism in which EYA4 binds the p27 promoter and acts through CK2α/HDAC2, explaining how dosage changes drive hypertrophy versus dilated cardiomyopathy.

    Evidence Cardiac-specific transgenic mice, ChIP, luciferase, hemodynamic/MRI analysis

    PMID:26499333

    Open questions at the time
    • Whether p27 suppression depends on phosphatase or coactivator activity not separated
    • Direct CK2α/HDAC2 substrate relationship not biochemically dissected
  8. 2016 Medium

    Identified post-transcriptional control of EYA4 by miR-431, showing reduced EYA4 protein causes spiral ganglion loss and hearing loss.

    Evidence Luciferase reporter, western blot, transgenic mice with ABR and SGN counts

    PMID:27545760

    Open questions at the time
    • Downstream cochlear effectors of EYA4 not defined
    • Single regulatory miRNA studied
  9. 2018 High

    Established EYA4 as a serine/threonine phosphatase that suppresses NF-κB by inhibiting IκBα phosphorylation/ubiquitination, defining a tumor-suppressive signaling role.

    Evidence Stable transfection, xenografts, ChIP, ubiquitination assay, NF-κB reporter, calyculin A inhibition

    PMID:29764501

    Open questions at the time
    • Whether EYA4 directly dephosphorylates IκBα not shown
    • Specific phospho-site not identified
  10. 2018 Medium

    Linked EYA4 to EMT suppression via Akt/GSK-3β/slug and identified TGF-β1/DNMT3A methylation as a route to EYA4 silencing in ESCC.

    Evidence shRNA/overexpression, migration/invasion assays, western blotting, demethylating agents

    PMID:29660222

    Open questions at the time
    • Direct phosphatase substrate in the Akt/GSK-3β axis not defined
    • Mechanism of pathway regulation correlative
  11. 2019 Medium

    Identified β-catenin Ser552 as a serine/threonine phosphatase substrate, connecting EYA4 to Wnt/MYCBP-driven proliferation control.

    Evidence Overexpression/KO in HCC lines, siRNA rescue, phospho-β-catenin blotting, nuclear fractionation

    PMID:31385398

    Open questions at the time
    • Direct dephosphorylation not shown with purified components
    • Single cancer context
  12. 2021 Low

    Reported that EYA4 suppresses p27Kip1 in glioma in a SIX1-dependent manner, extending the coactivator-cell cycle link to another tissue.

    Evidence Overexpression, viability/BrdU, flow cytometry, gene expression

    PMID:30231237

    Open questions at the time
    • No ChIP or direct promoter assay reported for direct p27 suppression claim
    • Single lab, limited mechanistic depth
  13. 2023 Medium

    Demonstrated a genome-maintenance role: EYA4 serine/threonine phosphatase activity supports replication fork progression and prevents replication stress.

    Evidence KD/OE in breast cancer cells/xenografts, γH2AX, ATR markers, HU sensitivity, DNA fiber assay, phosphatase mutant

    PMID:37777742

    Open questions at the time
    • Relevant fork-associated phosphatase substrate not identified
    • Single lab
  14. 2023 High

    Defined post-translational control of EYA4 stability through an ERK2-priming/TRIM69 ubiquitylation axis, linking MAPK signaling to EYA4 turnover and β-catenin/ID2 activation in PDAC.

    Evidence Co-IP, GST pulldown, in vitro kinase assay (Ser37), CHX chase, ubiquitination assay, ChIP, reporter

    PMID:36741265

    Open questions at the time
    • Physiological contexts of TRIM69 regulation beyond PDAC not tested
    • Whether turnover affects phosphatase versus coactivator pools unknown
  15. 2024 High

    Identified PLK1 pY445 as a tyrosine phosphatase substrate, establishing EYA4 as a regulator of centrosome maturation and PLK1 activation in G2.

    Evidence Co-IP, phosphatase substrate assay, molecular dynamics, depletion/inhibition, centrosome and mitosis imaging

    PMID:38360978

    Open questions at the time
    • Relative contributions of EYA4 versus EYA1 not fully separated
    • Upstream signals controlling this dephosphorylation unclear
  16. 2024 High

    Identified RAD51 pY315 as a tyrosine phosphatase substrate and showed DNA binding stimulates EYA4 activity, establishing a direct role in homologous recombination repair.

    Evidence In vitro phosphatase assay, HR reporter, RAD51 foci, DNA fiber, ssDNA measurement, KD/OE

    PMID:38084915

    Open questions at the time
    • How DNA recruits/stimulates EYA4 in cells not defined
    • Coordination with PLK1/replication functions unresolved
  17. 2024 Low

    Reported a direct EYA4-H2AX interaction promoting DSB repair and chemoresistance in osteosarcoma.

    Evidence Co-IP, KD/OE, doxorubicin sensitivity assays, γH2AX measurement

    PMID:38876260

    Open questions at the time
    • Single co-IP without reciprocal/structural validation
    • Limited mechanistic detail
  18. 2026 Medium

    Showed a phosphatase-independent coactivator function: EYA4-SIX2 activates p21 transcription in a p53-dependent manner to drive senescence, dissociating transcriptional and enzymatic activities.

    Evidence KD, co-IP (EYA4-SIX2), p21 reporter/expression, phosphatase-deficient mutant, p53 KO epistasis, senescence assays

    PMID:41991886

    Open questions at the time
    • Direct binding of EYA4-SIX2 to the p21 promoter not established
    • How phosphatase versus coactivator modes are partitioned in cells unclear

Open questions

Synthesis pass · forward-looking unresolved questions
  • How EYA4's distinct activities (tyrosine versus serine/threonine phosphatase, SIX-dependent coactivation) are coordinated, partitioned between cytoplasm and nucleus, and selectively deployed across developmental versus genome-maintenance contexts remains unresolved.
  • No structural model integrating phosphatase and coactivator functions
  • Substrate selectivity rules unknown
  • Mechanism switching EYA4 between developmental and DNA-repair roles undefined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140096 catalytic activity, acting on a protein 5 GO:0140110 transcription regulator activity 3 GO:0003677 DNA binding 2 GO:0016787 hydrolase activity 2 GO:0060089 molecular transducer activity 2
Localization
GO:0005634 nucleus 2 GO:0005815 microtubule organizing center 1 GO:0005829 cytosol 1
Pathway
R-HSA-1266738 Developmental Biology 2 R-HSA-162582 Signal Transduction 2 R-HSA-74160 Gene expression (Transcription) 2 R-HSA-1640170 Cell Cycle 1 R-HSA-69306 DNA Replication 1 R-HSA-73894 DNA Repair 1
Partners
H2AFXPLK1RAD51SIX1SIX2SIX3TRIM69

Evidence

Reading pass · 20 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1999 EYA4 encodes a 640 amino acid protein containing a highly conserved C-terminal domain of 271 amino acids (Eya homologous region) that mediates developmentally important protein-protein interactions, as established by characterization of the human and mouse gene. cDNA cloning, sequence analysis, domain characterization Human molecular genetics Medium 9887327
2001 EYA4 is the causative gene for postlingual progressive autosomal dominant hearing loss at the DFNA10 locus; mutations creating premature stop codons in two unrelated families established haploinsufficiency as the disease mechanism. Candidate gene sequencing, mutation identification, co-segregation analysis in two families Human molecular genetics High 11159937
2004 EYA4 Eya homologous region (Eya4HR) interacts with SIX1 (demonstrated by yeast two-hybrid), but not with DACH1. Eya4HR localizes to the cytoplasm and is translocated to the nucleus upon co-expression with SIX1. Mutant truncating alleles are not translated, consistent with haploinsufficiency as the mechanism for DFNA10. Yeast two-hybrid, alpha-galactosidase activity assay, immunofluorescence, dual Eya-containing constructs Journal of the Association for Research in Otolaryngology : JARO Medium 15492887
2005 EYA4 deletion causes dilated cardiomyopathy in addition to sensorineural hearing loss; eya4 morpholino knockdown in zebrafish produced heart failure. EYA4 peptides associated with SNHL-only mutations bound wild-type EYA4 and SIX proteins, whereas the cardiomyopathy-associated short peptide (193 aa) did not, indicating that SIX protein interaction is required for cardiac function. Zebrafish morpholino knockdown, biochemical interaction assays (co-immunoprecipitation), truncated peptide binding studies Nature genetics High 15735644
2008 EYA4 regulates Na+/K+-ATPase (specifically the atp1b2b subunit) in zebrafish; eya4 morphant fish had reduced atp1b2b levels, reduced hair cells, and heart failure. Morpholino knockdown of atp1b2b recapitulated eya4 deficiency phenotypes, and atp1b2b overexpression rescued eya4 morphant phenotypes, placing atp1b2b downstream of eya4 in sensory and cardiac development. Zebrafish morpholino knockdown, genetic epistasis (rescue by overexpression), hair cell counts, sensory response measurement Development (Cambridge, England) High 18799547
2009 EYA4 physically interacts with SIX3 (co-immunoprecipitation) and is recruited to the nucleus by SIX3. EYA4 cooperates functionally with SIX3 as a transcriptional coactivator (reporter gene assay), suggesting a role in forebrain development. Co-immunoprecipitation, confocal microscopy localization, luciferase reporter assay Human mutation Medium 19606496
2015 EYA4 overexpression in cardiac tissue induces hypertrophy via regulation of p27kip1 expression; chromatin immunoprecipitation and luciferase assays confirmed that EYA4 binds the p27 promoter and suppresses p27 expression. The downstream signaling involves casein kinase-2α and histone deacetylase 2 (HDAC2) phosphorylation. The truncating mutation E193 acts in an opposing manner, promoting dilated cardiomyopathy. Transgenic mice (cardiac-specific overexpression), luciferase reporter assay, chromatin immunoprecipitation, MRI/hemodynamic analysis, in vitro expression studies Circulation. Cardiovascular genetics High 26499333
2016 miR-431 directly targets Eya4 mRNA; luciferase reporter assay and western blotting confirmed that miR-431 inhibits Eya4 translation. Overexpression of miR-431 in transgenic mice led to reduced EYA4 protein in cochleae, decreased spiral ganglion neuron density, and hearing loss. Luciferase reporter assay, western blotting, transgenic mice, ABR measurement, SGN counting Biochimica et biophysica acta Medium 27545760
2018 EYA4 suppresses HCC cell growth and invasion by antagonizing NF-κB activity: EYA4 serine/threonine phosphatase activity inhibits phosphorylation and ubiquitination of IκBα, blocks nuclear translocation and transactivation of p65, thereby suppressing RAP1 transcription driven by NF-κB. Calyculin A (phosphatase inhibitor) abolished EYA4's suppression of NF-κB, confirming phosphatase-dependence. Stable transfection, xenograft, chromatin immunoprecipitation, immunofluorescence, cellular ubiquitination assay, NF-κB reporter, pharmacological inhibition Cancer communications (London, England) High 29764501
2018 EYA4 knockdown in ESCC cells increases migration and invasion; EYA4 overexpression promotes epithelial phenotype and reduces TGF-β1-induced EMT by reducing phosphorylation of Akt and GSK-3β, leading to inactivation of slug. TGF-β1 decreases EYA4 expression through DNMT3A-mediated DNA methylation. shRNA knockdown, overexpression, migration/invasion assays, western blotting for pAkt/pGSK3β/slug, treatment with 5-aza-dC/TSA Cancer science Medium 29660222
2019 EYA4 dephosphorylates β-catenin at Ser552 (serine/threonine phosphatase activity), reducing nuclear translocation of β-catenin and thereby suppressing β-catenin/LEF1-driven transcription of MYCBP. EYA4 KO increased MYCBP; siRNA of MYCBP in EYA4-overexpressing cells rescued proliferation and G2/M arrest phenotypes. EYA4 overexpression/KO in HCC cell lines, siRNA rescue, western blotting for phospho-β-catenin, qRT-PCR, nuclear fractionation Cancer science Medium 31385398
2020 EYA4 truncating mutations in the EYA-HR domain result in absence of protein expression (confirmed in mammalian COS7 cells), consistent with haploinsufficiency. Missense mutant p.Glu369Asp shows normal expression and nuclear translocation in presence of SIX1. Minigene assays confirmed that synonymous and splice-site variants cause exon skipping leading to frameshifts. Transient expression in COS7 cells, confocal microscopy, minigene splicing assays in NIH3T3 cells, in silico splicing analysis Scientific reports Medium 32277154
2021 EYA4 promotes glioma cell proliferation by directly suppressing expression of p27Kip1, and SIX1 is required for EYA4 to suppress p27Kip1. EYA4 overexpression, cell viability/BrdU assay, flow cytometry, gene expression analysis Cellular physiology and biochemistry Low 30231237
2023 EYA4 serine/threonine phosphatase domain prevents replication-associated DNA damage and is required for replication fork progression. EYA4 depletion causes spontaneous replication stress (ATR pathway activation, γH2AX accumulation, sensitivity to hydroxyurea, endoreplication/polyploidy). EYA4 overexpression promotes breast cancer cell proliferation, migration, and metastasis. EYA4 KD/OE in breast cancer cells and xenografts, γH2AX staining, ATR pathway markers, hydroxyurea sensitivity, DNA fiber assay (replication fork), phosphatase domain mutant Molecular cancer Medium 37777742
2024 EYA4 (and EYA1) are tyrosine phosphatases that dephosphorylate PLK1 at pY445 during G2 phase of the cell cycle. This dephosphorylation is required for centrosome maturation, PLK1 localization to centrosomes, and polo-box domain (PBD)-dependent interactions between PLK1 and PLK1-activation complexes. Depletion or chemical inhibition of EYA phosphatase activity reduces PLK1 activation, causing mitotic defects and cell death. Co-immunoprecipitation, phosphatase substrate assay, molecular dynamics simulation, EYA4/EYA1 depletion, chemical inhibition, immunofluorescence of centrosome maturation, mitosis assays Nature communications High 38360978
2024 EYA4 tyrosine phosphatase activity dephosphorylates RAD51 at Tyr315, which regulates RAD51 localization, presynaptic filament formation, foci formation, and homologous recombination (HR) at DNA double-strand breaks. DNA binding stimulates EYA4 phosphatase activity. EYA4 depletion decreases ssDNA accumulation after DNA damage and impairs HR; overexpression promotes RAD51 dephosphorylation and nucleoprotein filament formation. In vitro phosphatase assay, HR reporter assay, RAD51 foci formation, DNA fiber assay, ssDNA accumulation measurement, EYA4 KD/OE Nucleic acids research High 38084915
2023 TRIM69 E3 ligase promotes EYA4 polyubiquitylation and proteasomal turnover. ERK2 directly binds EYA4 at Leu512/514 (MAPK docking groove D-site) and phosphorylates EYA4 at Ser37, which is required for TRIM69-mediated EYA4 polyubiquitylation. Loss of EYA4 via this axis enables β-catenin/ID2 cascade activation promoting PDAC proliferation. Co-immunoprecipitation, GST pulldown, in vitro protein kinase assay, cycloheximide pulse-chase, cellular ubiquitination assay, chromatin immunoprecipitation, luciferase reporter, immunofluorescence Journal of Cancer High 36741265
2024 EYA4 interacts with histone H2AX directly and facilitates DNA double-strand break repair via DDR pathway activation, reducing osteosarcoma sensitivity to doxorubicin. Co-immunoprecipitation (EYA4-H2AX interaction), EYA4 KD/OE, in vitro and in vivo doxorubicin sensitivity assays, γH2AX measurement Biochemical pharmacology Low 38876260
2026 EYA4 interacts with transcription factor SIX2 to promote transcription of p21 (CDKN1A), thereby accelerating cellular senescence. This transcriptional activation function is independent of EYA4 phosphatase activity (shown using phosphatase-deficient mutants). EYA4-SIX2-mediated p21 upregulation is p53-dependent. EYA4 KD, co-immunoprecipitation (EYA4-SIX2), reporter/expression assays for p21, phosphatase-deficient mutant, p53 KO epistasis, replicative and stress-induced senescence assays Advanced biotechnology Medium 41991886
2025 EYA4 and EYA1 promote PLK1 activation and cell survival in neuroblastoma and glioblastoma; combined chemical inhibition of EYA phosphatase and PLK1 kinase produces synergistic cell death. Mechanism involves decreased PLK1 activity and RAD51 foci formation, mitotic arrest. NuRD complex and SOX9 expression levels correlate with combination sensitivity. Chemical inhibition (EYA inhibitors + PLK1 inhibitors), cancer cell line viability assays, PLK1 activity measurement, RAD51 foci, mitotic arrest quantification, multi-omic correlation bioRxivpreprint Low

Source papers

Stage 0 corpus · 64 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2001 Mutations in the transcriptional activator EYA4 cause late-onset deafness at the DFNA10 locus. Human molecular genetics 171 11159937
2005 Mutation in the transcriptional coactivator EYA4 causes dilated cardiomyopathy and sensorineural hearing loss. Nature genetics 154 15735644
2019 Circular RNA ACVR2A suppresses bladder cancer cells proliferation and metastasis through miR-626/EYA4 axis. Molecular cancer 135 31101108
1999 EYA4, a novel vertebrate gene related to Drosophila eyes absent. Human molecular genetics 130 9887327
1996 A gene for autosomal dominant late-onset progressive non-syndromic hearing loss, DFNA10, maps to chromosome 6. Human molecular genetics 53 8776603
2008 Eya4 regulation of Na+/K+-ATPase is required for sensory system development in zebrafish. Development (Cambridge, England) 52 18799547
2004 A comparative study of Eya1 and Eya4 protein function and its implication in branchio-oto-renal syndrome and DFNA10. Journal of the Association for Research in Otolaryngology : JARO 46 15492887
2002 A 4-bp insertion in the eya-homologous region (eyaHR) of EYA4 causes hearing impairment in a Hungarian family linked to DFNA10. Molecular medicine (Cambridge, Mass.) 45 12477971
2013 EYA4 is inactivated biallelically at a high frequency in sporadic lung cancer and is associated with familial lung cancer risk. Oncogene 37 24096489
2007 Nonsyndromic hearing loss DFNA10 and a novel mutation of EYA4: evidence for correlation of normal cardiac phenotype with truncating mutations of the Eya domain. American journal of medical genetics. Part A 37 17567890
2007 A novel splice site mutation in EYA4 causes DFNA10 hearing loss. American journal of medical genetics. Part A 36 17568404
2018 EYA4 inhibits hepatocellular carcinoma growth and invasion by suppressing NF-κB-dependent RAP1 transactivation. Cancer communications (London, England) 31 29764501
2015 Associations of genetic variations in EYA4, GRHL2 and DFNA5 with noise-induced hearing loss in Chinese population: a case- control study. Environmental health : a global access science source 31 26400775
2018 Aberrant methylation of EYA4 promotes epithelial-mesenchymal transition in esophageal squamous cell carcinoma. Cancer science 27 29660222
2015 EYA4 Acts as a New Tumor Suppressor Gene in Colorectal Cancer. Molecular carcinogenesis 26 25620232
2020 Prevalence and clinical features of hearing loss caused by EYA4 variants. Scientific reports 23 32107406
2018 Sensorineural hearing loss and mild cardiac phenotype caused by an EYA4 mutation. Human genome variation 21 30155266
2009 EYA4, deleted in a case with middle interhemispheric variant of holoprosencephaly, interacts with SIX3 both physically and functionally. Human mutation 21 19606496
2019 EYA4 inhibits hepatocellular carcinoma by repressing MYCBP by dephosphorylating β-catenin at Ser552. Cancer science 20 31385398
2015 Evaluation of the contribution of the EYA4 and GRHL2 genes in Korean patients with autosomal dominant non-syndromic hearing loss. PloS one 20 25781927
2020 Insights into the pathophysiology of DFNA10 hearing loss associated with novel EYA4 variants. Scientific reports 19 32277154
2018 EYA4 Promotes Cell Proliferation Through Downregulation of p27Kip1 in Glioma. Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology 19 30231237
2015 Exome Sequencing Identifies a Mutation in EYA4 as a Novel Cause of Autosomal Dominant Non-Syndromic Hearing Loss. PloS one 19 25961296
2014 Identification of I411K, a novel missense EYA4 mutation causing autosomal dominant non‑syndromic hearing loss. International journal of molecular medicine 18 25242383
2015 A novel mutation of EYA4 in a large Chinese family with autosomal dominant middle-frequency sensorineural hearing loss by targeted exome sequencing. Journal of human genetics 16 25809937
2013 Methylated eyes absent 4 (EYA4) gene promotor in non-neoplastic mucosa of ulcerative colitis patients with colorectal cancer: evidence for a field effect. Inflammatory bowel diseases 16 23867875
2012 Evolution of electrosensory ampullary organs: conservation of Eya4 expression during lateral line development in jawed vertebrates. Evolution & development 16 23017075
2015 Identification of a novel truncation mutation of EYA4 in moderate degree hearing loss by targeted exome sequencing. European archives of oto-rhino-laryngology : official journal of the European Federation of Oto-Rhino-Laryngological Societies (EUFOS) : affiliated with the German Society for Oto-Rhino-Laryngology - Head and Neck Surgery 15 26015337
2017 Expression pattern of EYA4 in the common marmoset (Callithrix jacchus) cochlea. Neuroscience letters 14 29054432
2016 Audiometric Characteristics of a Dutch DFNA10 Family With Mid-Frequency Hearing Impairment. Ear and hearing 14 26331839
2015 A novel EYA4 mutation causing hearing loss in a Chinese DFNA family and genotype-phenotype review of EYA4 in deafness. Journal of translational medicine 13 25963406
2016 miR-431 is involved in regulating cochlear function by targeting Eya4. Biochimica et biophysica acta 12 27545760
2009 De novo 9 Mb deletion of 6q23.2q24.1 disrupting the gene EYA4 in a patient with sensorineural hearing loss, cardiac malformation, and mental retardation. European journal of medical genetics 12 19576303
2001 The DFNA10 phenotype. The Annals of otology, rhinology, and laryngology 12 11558763
2023 EYA4 promotes breast cancer progression and metastasis through its role in replication stress avoidance. Molecular cancer 11 37777742
2019 Novel EYA4 variant in Slovak family with late onset autosomal dominant hearing loss: a case report. BMC medical genetics 11 31101089
2017 A novel mutation of the EYA4 gene associated with post-lingual hearing loss in a proband is co-segregating with a novel PAX3 mutation in two congenitally deaf family members. International journal of pediatric otorhinolaryngology 11 29287889
2009 Relationship between the expression of hTERT and EYA4 mRNA in peripheral blood mononuclear cells with the progressive stages of carcinogenesis of the esophagus. Journal of experimental & clinical cancer research : CR 11 19939248
2024 The Eyes Absent family members EYA4 and EYA1 promote PLK1 activation and successful mitosis through tyrosine dephosphorylation. Nature communications 10 38360978
2016 Genetic variation in EYA4 on the risk of noise-induced hearing loss in Chinese steelworks firm sample. Occupational and environmental medicine 10 27613755
2015 Phenotypic variability in a seven-generation Swedish family segregating autosomal dominant hearing impairment due to a novel EYA4 frameshift mutation. Gene 10 25681523
2015 Eya4 Induces Hypertrophy via Regulation of p27kip1. Circulation. Cardiovascular genetics 10 26499333
2019 Familial Interstitial 6q23.2 Deletion Including Eya4 Associated With Otofaciocervical Syndrome. Frontiers in genetics 9 31379922
2024 The protein phosphatase EYA4 promotes homologous recombination (HR) through dephosphorylation of tyrosine 315 on RAD51. Nucleic acids research 8 38084915
2021 Genome-first approach to rare EYA4 variants and cardio-auditory phenotypes in adults. Human genetics 8 33745059
2016 Epigenetic mediated silencing of EYA4 contributes to tumorigenesis in oral dysplastic cells. Genes, chromosomes & cancer 8 27015871
2020 Early truncation of the N-terminal variable region of EYA4 gene causes dominant hearing loss without cardiac phenotype. Molecular genetics & genomic medicine 7 33301229
2023 Delineating the tumour-regulatory roles of EYA4. Biochemical pharmacology 6 36849065
2019 Identification of a novel missense eya4 mutation causing autosomal dominant non‑syndromic hearing loss in a chinese family. Cellular and molecular biology (Noisy-le-Grand, France) 6 30942159
2000 Refined localization and two additional linked families for the DFNA10 locus for nonsyndromic hearing impairment. Human genetics 6 10982027
2022 Identification of a novel CNV at the EYA4 gene in a Chinese family with autosomal dominant nonsyndromic hearing loss. BMC medical genomics 5 35578334
2021 Identification of a Novel Copy Number Variation of EYA4 Causing Autosomal Dominant Non-syndromic Hearing Loss. Otology & neurotology : official publication of the American Otological Society, American Neurotology Society [and] European Academy of Otology and Neurotology 5 33859130
2024 Exercise in ozone-polluted air evokes pathological cardiac hypertrophy via up-regulation of nuclear lncRNA EYA4-au1 and recruiting Med11 to activating EYA4/p27kip1/CK2α/HDAC2 cascade. Ecotoxicology and environmental safety 4 39471666
2023 Identification of mutations on the EMD and EYA4 genes associated with Emery-Dreifuss muscular dystrophy and deafness: a case report. Frontiers in neurology 4 37251241
2023 Tripartite motif containing 69 elicits ERK2-dependent EYA4 turnover to impart pancreatic tumorigenesis. Journal of Cancer 2 36741265
2022 Cigarette Smoke Regulates the Expression of EYA4 via Alternation of DNA Methylation Status. BioMed research international 2 35607307
2022 Aberrant DNA methylation and expression of EYA4 in gastric cardia intestinal metaplasia. Saudi journal of gastroenterology : official journal of the Saudi Gastroenterology Association 2 36453428
2005 RT-PCR analysis of Tecta, Coch, Eya4 and Strc in mouse cochlear explants. Neuroreport 2 15729138
2026 EYA4 promotes cellular senescence by enhancing P21 transcription through interaction with SIX2. Advanced biotechnology 0 41991886
2024 Retracted: Cigarette Smoke Regulates the Expression of EYA4 via Alternation of DNA Methylation Status. BioMed research international 0 38230007
2024 EYA4 reduces chemosensitivity of osteosarcoma to doxorubicin through DNA damage repair. Biochemical pharmacology 0 38876260
2024 Generation of four induced pluripotent stem cell lines (KEIUi004-A, KEIUi005-A, KEIUi006-A, and KEIUi007-A) from patients with sensorineural hearing loss with mutation in EYA4 gene. Stem cell research 0 39002249
2024 Identification of a novel EYA4 likely pathogenic variant in a Chinese family with postlingual non-syndromic hearing loss and analysis of molecular epidemiology of EYA4 variants. BMC medical genomics 0 39358765
2023 EYA4 drives breast cancer progression and metastasis through its novel role in replication stress avoidance. Research square 0 37292941

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