Affinage

EYA4

Protein phosphatase EYA4 · UniProt O95677

Length
639 aa
Mass
69.5 kDa
Annotated
2026-04-28
64 papers in source corpus 21 papers cited in narrative 21 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

EYA4 is a dual-function protein that acts both as a transcriptional coactivator in partnership with SIX-family homeodomain proteins and as an intrinsic tyrosine and serine/threonine phosphatase, coupling gene regulation to cell cycle control, DNA repair, and organ maintenance. As a coactivator, EYA4 is recruited to the nucleus by SIX1, SIX2, or SIX3, where it regulates targets including p27Kip1 (via the p27/CK2α/HDAC2 cascade in cardiomyocytes) and p21/CDKN1A (in a p53-dependent senescence program) (PMID:26499333, PMID:41991886, PMID:15492887). Its tyrosine phosphatase activity dephosphorylates PLK1 at pY445 to enable centrosome maturation and mitotic entry, and RAD51 at pY315 to promote homologous recombination, while its serine/threonine phosphatase activity dephosphorylates β-catenin at Ser552 to restrain Wnt signaling and maintains replication fork stability (PMID:38360978, PMID:38084915, PMID:31385398, PMID:37777742). Haploinsufficiency caused by truncating mutations underlies DFNA10 progressive sensorineural hearing loss, and more severe N-terminal truncations that abolish SIX-binding cause dilated cardiomyopathy (PMID:11159937, PMID:15735644).

Mechanistic history

Synthesis pass · year-by-year structured walk · 14 steps
  1. 1999 Medium

    Identification of EYA4 as a member of the EYA gene family with a conserved C-terminal Eya-homologous region (eya-HR) established the structural framework for subsequent functional studies.

    Evidence Molecular cloning and sequence analysis of human and mouse EYA4

    PMID:9887327

    Open questions at the time
    • No functional activity was demonstrated for the protein at this stage
    • Expression pattern in specific tissues not fully resolved
  2. 2001 High

    Demonstration that EYA4 haploinsufficiency causes DFNA10 sensorineural hearing loss established a post-developmental, maintenance role for EYA4 in the organ of Corti — the first disease link.

    Evidence Mutation identification in two unrelated DFNA10 families with premature stop codons

    PMID:11159937

    Open questions at the time
    • Molecular targets of EYA4 in cochlear maintenance unknown
    • Whether residual protein is produced from truncating alleles was not tested
  3. 2004 Medium

    Showing that EYA4 interacts with SIX1 and requires SIX1 for nuclear translocation resolved how EYA4 reaches transcriptional targets, establishing the SIX-dependent shuttling mechanism.

    Evidence Yeast two-hybrid and immunofluorescence in mammalian cells

    PMID:15492887

    Open questions at the time
    • DACH1 interaction was negative but other DACH family members untested
    • Endogenous interaction not confirmed
  4. 2005 High

    Correlation of mutation severity with disease spectrum — C-terminal truncations preserving SIX-binding cause hearing loss alone, whereas the short 193-aa peptide losing SIX-binding causes dilated cardiomyopathy — established SIX-EYA interaction as the critical determinant of cardiac function, validated by zebrafish morphant heart failure.

    Evidence Biochemical binding assays of EYA4 mutant peptides; morpholino knockdown in zebrafish with hemodynamic analysis

    PMID:15735644

    Open questions at the time
    • Downstream cardiac transcriptional targets of EYA4-SIX unidentified
    • Mammalian in vivo cardiac model not yet available
  5. 2008 High

    Identification of Na+/K+-ATPase β2b subunit (atp1b2b) as a downstream effector whose overexpression rescues eya4-morphant hair cell loss and heart failure provided the first defined transcriptional target linking EYA4 to ion homeostasis.

    Evidence Morpholino knockdown and rescue overexpression in zebrafish

    PMID:18799547

    Open questions at the time
    • Whether EYA4 directly binds the atp1b2b promoter was not tested
    • Relevance to mammalian hearing not confirmed
  6. 2009 Medium

    EYA4 interaction with SIX3 broadened the coactivator partnership beyond SIX1, showing that EYA4 uses multiple SIX family members for nuclear recruitment and transcriptional activation.

    Evidence Co-immunoprecipitation, confocal microscopy, and luciferase reporter assays

    PMID:19606496

    Open questions at the time
    • Endogenous tissue context for EYA4-SIX3 cooperation not defined
    • SIX3 target genes regulated by EYA4 not identified
  7. 2015 High

    ChIP demonstration that EYA4 binds the p27Kip1 promoter and drives p27/CK2α/HDAC2 signaling in the heart, with transgenic mice showing dose-dependent cardiac pathology (hypertrophy vs. dilated cardiomyopathy), provided the first defined mammalian transcriptional cascade and in vivo cardiac model.

    Evidence ChIP, luciferase reporter, cardiac-specific transgenic mouse overexpression with MRI and hemodynamics

    PMID:26499333

    Open questions at the time
    • Whether phosphatase activity contributes to cardiac phenotype was not tested
    • Direct vs. indirect regulation of p27 promoter not resolved
  8. 2018 Medium

    Discovery of EYA4's serine/threonine phosphatase activity toward IκBα (blocking NF-κB signaling) and β-catenin Ser552 (suppressing Wnt signaling) established EYA4 as a dual-specificity phosphatase with tumor-suppressive roles in hepatocellular carcinoma.

    Evidence EYA4 overexpression/KO with phosphatase inhibitor treatment, ubiquitination assays, western blots for phospho-substrates, and xenograft models

    PMID:29764501 PMID:31385398

    Open questions at the time
    • In vitro phosphatase reconstitution on IκBα not performed
    • Whether EYA4 directly dephosphorylates IκBα or acts upstream is ambiguous
  9. 2020 Medium

    Confirmation that truncating EYA4 mutations produce no detectable protein (consistent with nonsense-mediated decay) formally established haploinsufficiency as the universal DFNA10 disease mechanism.

    Evidence Transient expression of tagged EYA4 mutants in COS7 cells with western blot and immunofluorescence

    PMID:32277154

    Open questions at the time
    • Patient-derived cells not examined
    • Residual mRNA levels not quantified in human cochlear tissue
  10. 2023 High

    Identification of the ERK2-TRIM69 axis that phosphorylates EYA4 at Ser37 and drives its polyubiquitylation and proteasomal degradation revealed how EYA4 protein levels are post-translationally controlled.

    Evidence In vitro kinase assay, GST-pulldown, CHX pulse-chase, ubiquitination assay, and xenograft in pancreatic cancer

    PMID:36741265

    Open questions at the time
    • Physiological contexts beyond pancreatic cancer not explored
    • Whether Ser37 phosphorylation affects EYA4 phosphatase or coactivator activity is unknown
  11. 2023 Medium

    EYA4's serine/threonine phosphatase activity was shown to promote replication fork progression and prevent ATR-dependent replication stress, extending its phosphatase role to S-phase genome integrity.

    Evidence EYA4 knockdown/overexpression with hydroxyurea sensitivity, γH2AX immunofluorescence, ATR activation assays, and xenograft

    PMID:37777742

    Open questions at the time
    • Direct replication fork substrate(s) not identified
    • Separation of S/T vs. tyrosine phosphatase contributions not fully resolved
  12. 2024 High

    In vitro reconstitution proved EYA4 is a tyrosine phosphatase for PLK1 pY445, and that this dephosphorylation is required for centrosome maturation, PLK1 centrosomal localization, and mitotic entry — establishing a cell-cycle-essential catalytic function.

    Evidence In vitro phosphatase assay, molecular dynamics simulation, EYA4 depletion with centrosome imaging, chemical inhibitor validation

    PMID:38360978

    Open questions at the time
    • Crystal structure of EYA4-PLK1 complex not available
    • Relative contributions of EYA4 vs. EYA1 in different tissues unknown
  13. 2024 High

    Reconstitution of EYA4 tyrosine phosphatase activity on RAD51 pY315 showed it promotes presynaptic filament formation and homologous recombination, with the novel finding that DNA binding stimulates EYA4's phosphatase activity.

    Evidence In vitro phosphatase assay on RAD51, HR reporter assay, RAD51 foci formation, ssDNA accumulation assay

    PMID:38084915

    Open questions at the time
    • Structural basis for DNA-stimulated phosphatase activity unknown
    • Whether EYA4 acts on RAD51 before or after loading onto ssDNA is unclear
  14. 2024 Medium

    EYA4 interaction with SIX2 and phosphatase-independent transcriptional activation of p21/CDKN1A in a p53-dependent manner established a role for EYA4 in cellular senescence, functionally separating its coactivator and phosphatase activities.

    Evidence Co-IP (EYA4-SIX2), p21 promoter reporter, phosphatase-dead mutant, p53 knockdown epistasis, senescence assays

    PMID:41991886

    Open questions at the time
    • Physiological tissue context for EYA4-driven senescence not defined
    • Whether EYA4-SIX2 binds the p21 promoter directly (ChIP) was not shown

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key open questions include: the structural basis of EYA4's dual phosphatase specificity, the tissue-specific division of labor between its coactivator and phosphatase functions, and the identity of replication-fork substrates mediating its role in S-phase genome stability.
  • No crystal structure of EYA4 catalytic domain available
  • Relative contribution of EYA4 vs. other EYA family members in each tissue context unclear
  • Replication fork substrate(s) for S/T phosphatase activity unidentified

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 4 GO:0003677 DNA binding 1
Localization
GO:0005634 nucleus 4 GO:0005829 cytosol 2 GO:0005815 microtubule organizing center 1
Pathway
R-HSA-162582 Signal Transduction 3 R-HSA-74160 Gene expression (Transcription) 3 R-HSA-1643685 Disease 2 R-HSA-73894 DNA Repair 2 R-HSA-1640170 Cell Cycle 1 R-HSA-69306 DNA Replication 1
Partners
ERK2H2AXPLK1RAD51SIX1SIX2SIX3TRIM69

Evidence

Reading pass · 21 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1999 EYA4 encodes a protein containing a highly conserved C-terminal Eya homologous domain (eya-HR) of 271 amino acids, which in Drosophila eya mediates developmentally important protein-protein interactions. Molecular cloning and sequence analysis of human and mouse EYA4 Human molecular genetics Medium 9887327
2001 EYA4 functions as a transcriptional activator and its haploinsufficiency (via premature stop codons) causes late-onset progressive sensorineural hearing loss (DFNA10), demonstrating a post-developmental role in maintenance of the organ of Corti. Mutation identification in two unrelated families; genetic linkage and sequencing Human molecular genetics High 11159937
2004 EYA4 Eya-homologous region (Eya4HR) interacts with SIX1 (but not DACH1) in yeast two-hybrid assays; Eya4HR localizes to the cytoplasm alone but is translocated to the nucleus upon co-expression with SIX1. Yeast two-hybrid system; immunofluorescence staining; coexpression in mammalian cells Journal of the Association for Research in Otolaryngology : JARO Medium 15492887
2005 EYA4 peptides associated with sensorineural hearing loss (C-terminal Eya domain truncations) bind wild-type EYA4 and SIX proteins, whereas the shortened 193-amino acid peptide associated with dilated cardiomyopathy does not; zebrafish eya4 morphants display heart failure phenotype, and eya4 regulates cardiac function via EYA4-SIX-mediated transcriptional regulation. Biochemical interaction assays of mutant EYA4 peptides; antisense morpholino knockdown in zebrafish; hemodynamic analysis Nature genetics High 15735644
2008 Eya4 regulates expression of Na+/K+-ATPase (atp1b2b beta2b subunit) in zebrafish; loss of eya4 reduces atp1b2b levels and causes hair cell loss and heart failure, and atp1b2b overexpression rescues these eya4 morphant phenotypes. Morpholino knockdown of eya4 and atp1b2b in zebrafish; rescue experiments with atp1b2b overexpression; sensory response assays 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 in reporter gene assays. Co-immunoprecipitation; confocal microscopy; luciferase reporter assays Human mutation Medium 19606496
2015 EYA4 and its truncation mutant E193 regulate p27Kip1 expression by binding and regulating the p27 promoter (ChIP assay); cardiac-specific overexpression of Eya4 in mice causes age-dependent hypertrophy via p27/casein kinase-2α/HDAC2 signaling, whereas E193 overexpression causes dilated cardiomyopathy. Luciferase reporter assays; chromatin immunoprecipitation; transgenic mouse overexpression; MRI and hemodynamic analysis Circulation. Cardiovascular genetics High 26499333
2016 miR-431 directly targets Eya4 mRNA in cochlear spiral ganglion neurons; overexpression of miR-431 in transgenic mice inhibits EYA4 translation, reduces spiral ganglion neuron density, and causes hearing loss. Luciferase reporter assay; western blotting; transgenic mouse model; ABR testing; primary SGN culture Biochimica et biophysica acta Medium 27545760
2018 EYA4 suppresses HCC proliferation and invasion by antagonizing TNF-α-induced NF-κB activation: EYA4's serine/threonine phosphatase activity blocks phosphorylation and ubiquitination of IκBα, inhibiting p65 nuclear translocation and RAP1A transactivation. Stable transfection; ChIP; immunofluorescence; ubiquitination assay; calyculin A (phosphatase inhibitor) treatment; xenograft Cancer communications (London, England) Medium 29764501
2018 EYA4 overexpression reduces phosphorylation of AKT and GSK-3β, leading to inactivation of Slug and suppression of TGF-β1-induced epithelial-mesenchymal transition in esophageal squamous cell carcinoma cells. EYA4 overexpression and knockdown; western blotting for phospho-AKT, phospho-GSK-3β, Slug; migration/invasion assays Cancer science Medium 29660222
2018 EYA4 promotes glioma cell proliferation by suppressing p27Kip1 expression in a SIX1-dependent manner. EYA4 overexpression in glioma cells; CCK-8, BrdU proliferation assays; western blotting for p27Kip1; SIX1 co-expression experiments Cellular physiology and biochemistry Low 30231237
2019 EYA4 dephosphorylates β-catenin at Ser552 (using its serine/threonine phosphatase activity), reducing nuclear translocation of β-catenin and thereby suppressing β-catenin/LEF1-driven transcription of MYCBP, inhibiting HCC proliferation. EYA4 overexpression/KO; rescue with MYCBP siRNA or overexpression; western blot for p-β-catenin S552; gene microarray Cancer science Medium 31385398
2020 Truncating EYA4 mutations lead to absence of mutant protein expression (consistent with nonsense-mediated decay), and haploinsufficiency is the common disease mechanism for DFNA10; nuclear translocation of missense EYA4 mutant p.Glu369Asp requires SIX1 co-expression, as for wild-type EYA4. Transient expression of c-myc-tagged EYA4 mutants in COS7 cells; western blot; immunofluorescence; minigene splicing assays in NIH3T3 cells Scientific reports Medium 32277154
2023 TRIM69 (an E3 ubiquitin ligase) promotes EYA4 polyubiquitylation and proteasomal degradation; ERK2 directly binds a D-site docking groove in EYA4 (Leu512/514) and phosphorylates EYA4 at Ser37, which is required for TRIM69-mediated ubiquitylation and turnover of EYA4 in pancreatic cancer. Co-immunoprecipitation; GST-pulldown; in vitro kinase assay; CHX pulse-chase; cellular ubiquitination assay; ChIP; luciferase reporter assay; xenograft Journal of Cancer High 36741265
2023 EYA4 serine/threonine phosphatase activity promotes replication fork progression and prevents replication stress; depletion of EYA4 activates the ATR pathway, causes endoreplication and polyploidy, and reduces breast cancer cell tumorigenic properties in vitro and in vivo. EYA4 knockdown/overexpression; hydroxyurea sensitivity assay; γH2AX immunofluorescence; ATR pathway activation assays; in vivo xenograft Molecular cancer Medium 37777742
2024 EYA4 (and EYA1) are tyrosine phosphatases that dephosphorylate PLK1 at pY445 during G2 phase; dephosphorylation of pY445 is required for centrosome maturation, PLK1 localization to centrosomes, polo-box domain (PBD)-dependent interactions with PLK1-activation complexes, and successful mitosis. Chemical inhibition of EYA phosphatase activity reduces PLK1 activation and causes mitotic defects and cell death. Co-immunoprecipitation; in vitro phosphatase assay; molecular dynamics simulation; EYA4/EYA1 depletion; centrosome maturation and PLK1 localization imaging; chemical inhibitor studies Nature communications High 38360978
2024 EYA4 tyrosine phosphatase activity dephosphorylates RAD51 at Tyr315, promoting RAD51 localization, presynaptic filament formation, foci formation, and homologous recombination at DNA double-strand breaks; DNA binding stimulates EYA4 phosphatase activity. In vitro phosphatase assay with RAD51; RAD51 foci formation assay; HR reporter assay; EYA4 overexpression/depletion; single-stranded DNA accumulation assay Nucleic acids research High 38084915
2024 EYA4 directly interacts with histone H2AX and facilitates DNA double-strand break repair, reducing osteosarcoma sensitivity to doxorubicin. Co-immunoprecipitation (EYA4-H2AX); EYA4 knockdown/overexpression; in vitro and in vivo doxorubicin sensitivity assays Biochemical pharmacology Low 38876260
2024 EYA4 interacts with SIX2 and promotes transcription of p21 (CDKN1A) in a p53-dependent manner to drive cellular senescence; this function requires transcriptional activation activity but is independent of EYA4's phosphatase activity. EYA4 knockdown; co-immunoprecipitation (EYA4-SIX2); luciferase reporter for p21 promoter; phosphatase-deficient mutant; p53 knockdown epistasis; replicative and stress-induced senescence assays Advanced biotechnology Medium 41991886
2024 lncRNA EYA4-au1 recruits the mediator subunit Med11 to the EYA4 promoter to activate EYA4 transcription, subsequently activating the EYA4/p27Kip1/CK2α/HDAC2 cascade to drive cardiomyocyte hypertrophy. AngII-induced in vitro hypertrophy model; EYA4-au1 knockdown/overexpression; ChIP for Med11 at EYA4 promoter; pathway component analysis Ecotoxicology and environmental safety Medium 39471666
2025 Combined inhibition of EYA phosphatase activity and PLK1 shows synergistic lethality in neuroblastoma and glioblastoma cells overexpressing EYA1/EYA4, mediated by decreased PLK1 activity, reduced RAD51 foci, and mitotic arrest. Chemical inhibitor combination studies in cancer cell lines and glioblastoma stem cell models; PLK1 activity assay; RAD51 foci quantification; multi-omic correlational analysis bioRxivpreprint Low bio_10.1101_2025.01.19.633804

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 153 15735644
2019 Circular RNA ACVR2A suppresses bladder cancer cells proliferation and metastasis through miR-626/EYA4 axis. Molecular cancer 133 31101108
1999 EYA4, a novel vertebrate gene related to Drosophila eyes absent. Human molecular genetics 129 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
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 EYA4 inhibits hepatocellular carcinoma growth and invasion by suppressing NF-κB-dependent RAP1 transactivation. Cancer communications (London, England) 29 29764501
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
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
2019 EYA4 inhibits hepatocellular carcinoma by repressing MYCBP by dephosphorylating β-catenin at Ser552. Cancer science 19 31385398
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
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
2023 EYA4 promotes breast cancer progression and metastasis through its role in replication stress avoidance. Molecular cancer 10 37777742
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
2024 The Eyes Absent family members EYA4 and EYA1 promote PLK1 activation and successful mitosis through tyrosine dephosphorylation. Nature communications 9 38360978
2019 Familial Interstitial 6q23.2 Deletion Including Eya4 Associated With Otofaciocervical Syndrome. Frontiers in genetics 9 31379922
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
2024 The protein phosphatase EYA4 promotes homologous recombination (HR) through dephosphorylation of tyrosine 315 on RAD51. Nucleic acids research 7 38084915
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
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
2023 Delineating the tumour-regulatory roles of EYA4. Biochemical pharmacology 5 36849065
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 3 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