EYA4

Summary

Gene Symbol: EYA4
Description: EYA transcriptional coactivator and phosphatase 4
Alias: CMD1J, DFNA10, eyes absent homolog 4, dJ78N10.1 (eyes absent), eyes absent-like protein 4
Species: human
Products:     EYA4

Top Publications

  1. Borsani G, DeGrandi A, Ballabio A, Bulfone A, Bernard L, Banfi S, et al. EYA4, a novel vertebrate gene related to Drosophila eyes absent. Hum Mol Genet. 1999;8:11-23 pubmed
    ..Here we present the detailed characterization of the EYA4 gene in human and mouse...
  2. Wayne S, Robertson N, Declau F, Chen N, Verhoeven K, Prasad S, et al. Mutations in the transcriptional activator EYA4 cause late-onset deafness at the DFNA10 locus. Hum Mol Genet. 2001;10:195-200 pubmed
    ..activators, as the causative gene of postlingual, progressive, autosomal dominant hearing loss at the DFNA10 locus...
  3. Tan M, Shen X, Yao J, Wei Q, Lu Y, Cao X, et al. Identification of I411K, a novel missense EYA4 mutation causing autosomal dominant non‑syndromic hearing loss. Int J Mol Med. 2014;34:1467-72 pubmed publisher
    ..Our results provide additional molecular and clinical information in order to gain improved understanding of the pathogenesis of EYA4 mutations and the genotype‑phenotype correlations of DFNA10 hearing loss.
  4. Schönberger J, Wang L, Shin J, Kim S, Depreux F, Zhu H, et al. Mutation in the transcriptional coactivator EYA4 causes dilated cardiomyopathy and sensorineural hearing loss. Nat Genet. 2005;37:418-22 pubmed
    ..that affect structural proteins, this mutation deletes 4,846 bp of the human transcriptional coactivator gene EYA4. To elucidate the roles of eya4 in heart function, we studied zebrafish embryos injected with antisense morpholino ..
  5. Makishima T, Madeo A, Brewer C, Zalewski C, Butman J, Sachdev V, et al. Nonsyndromic hearing loss DFNA10 and a novel mutation of EYA4: evidence for correlation of normal cardiac phenotype with truncating mutations of the Eya domain. Am J Med Genet A. 2007;143A:1592-8 pubmed
    ..Dominant, truncating mutations of eyes absent 4 (EYA4) on chromosome 6q23 can cause either nonsyndromic hearing loss DFNA10 or hearing loss with dilated cardiomyopathy (DCM)...
  6. O Neill M, Marietta J, Nishimura D, Wayne S, Van Camp G, Van Laer L, et al. A gene for autosomal dominant late-onset progressive non-syndromic hearing loss, DFNA10, maps to chromosome 6. Hum Mol Genet. 1996;5:853-6 pubmed
    ..Using an extended American family in which a gene for autosomal dominant late-onset non-syndromic hearing impairment is segregating, we have identified a new locus, DFNA10, on chromosome 6.
  7. Pfister M, Toth T, Thiele H, Haack B, Blin N, Zenner H, et al. A 4-bp insertion in the eya-homologous region (eyaHR) of EYA4 causes hearing impairment in a Hungarian family linked to DFNA10. Mol Med. 2002;8:607-11 pubmed
    ..Mutations in the EYA4 gene are responsible for postlingual, progressive, autosomal dominant hearing loss at the DFNA10 locus. EYA4 is orthologous to the Drosophila gene eya ("eyes absent"), a key regulator of eye formation...
  8. Hildebrand M, Coman D, Yang T, Gardner R, Rose E, Smith R, et al. A novel splice site mutation in EYA4 causes DFNA10 hearing loss. Am J Med Genet A. 2007;143A:1599-604 pubmed
    Nonsyndromic autosomal dominant sensorineural hearing loss (SNHL) at the DFNA10 locus was described in two families in 2001. Causative mutations that affect the EyaHR domain of the 'Eyes absent 4' (EYA4) protein were identified...
  9. Abe Y, Oka A, Mizuguchi M, Igarashi T, Ishikawa S, Aburatani H, et al. EYA4, deleted in a case with middle interhemispheric variant of holoprosencephaly, interacts with SIX3 both physically and functionally. Hum Mutat. 2009;30:E946-55 pubmed publisher
    ..4 Mb at 6q22.31-q23.2, which includes the EYA4 gene. EYA4 is one of four vertebrate orthologs of the Drosophila melanogaster gene, eyes absent...

More Information

Publications51

  1. Zhang X, Ni Y, Liu Y, Zhang L, Zhang M, Fang X, et al. Screening of noise-induced hearing loss (NIHL)-associated SNPs and the assessment of its genetic susceptibility. Environ Health. 2019;18:30 pubmed publisher
    ..The results were validated using a prospective cohort population. Seven SNPs in the CDH23, PCDH15, EYA4, MYO1A, KCNMA1, and OTOG genes were significantly (P < 0...
  2. Chen K, Liu M, Wu X, Zong L, Jiang H. Targeted next generation sequencing reveals OTOF mutations in auditory neuropathy spectrum disorder. Int J Pediatr Otorhinolaryngol. 2018;115:19-23 pubmed publisher
    ..In the proband, the targeted NGS panel revealed five suspected variants in four genes (OTOF, EYA4, PCDH15, and GIPC3), of which two mutations-c.5098G > C (p.Glu1700Gln) and c.1702C > T (p...
  3. Li Z, Qiu R, Qiu X, Tian T. EYA4 Promotes Cell Proliferation Through Downregulation of p27Kip1 in Glioma. Cell Physiol Biochem. 2018;49:1856-1869 pubmed publisher
    Accumulating evidence suggests that Eyes Absent Homologue 4 (EYA4) plays an important role in tumorigenesis and progression of various cancers. However, the role of EYA4 in glioma development is still unclear...
  4. Mo S, Hou X, Hao X, Cai J, Liu X, Chen W, et al. EYA4 inhibits hepatocellular carcinoma growth and invasion by suppressing NF-κB-dependent RAP1 transactivation. Cancer Commun (Lond). 2018;38:9 pubmed publisher
    Our previous studies demonstrated that eyes absent homolog 4 (EYA4), a member of the eye development-related EYA family in Drosophila, is frequently methylated and silenced in hepatocellular carcinoma (HCC) specimens and associated with ..
  5. Fan Y, Zhang Y, Wu R, Chen X, Zhang Y, Chen X, et al. miR-431 is involved in regulating cochlear function by targeting Eya4. Biochim Biophys Acta. 2016;1862:2119-2126 pubmed publisher
    ..A bioinformatics analysis predicted that the mRNA target of miR-431 was Eya4, a finding confirmed by luciferase reporter assays and western blotting...
  6. Lopez J, Angulo J, Martin A, Sanchez Chapado M, González Corpas A, Colás B, et al. A DNA hypermethylation profile reveals new potential biomarkers for the evaluation of prognosis in urothelial bladder cancer. APMIS. 2017;125:787-796 pubmed publisher
    ..02) or grade (p = 0.02) was demonstrated. Hypermethylation of JAK3 and absence of hypermethylation of EYA4, GAT6, and SOX1 were associated with low-grade non-invasive disease...
  7. Li Q, Chen C, Ren X, Sun W. DNA methylation profiling identifies the HOXA11 gene as an early diagnostic and prognostic molecular marker in human lung adenocarcinoma. Oncotarget. 2017;8:33100-33109 pubmed publisher
    ..NL) tissues, we found that, among the six genes identified with hypermethylation, the HOXA11, CDKN2A-EX2 and EYA4 genes showed highly promising DNA hypermethylation diagnostic markers in the lung AD tissues...
  8. Li M, Li Y, Weeks O, Mijatovic V, Teumer A, Huffman J, et al. SOS2 and ACP1 Loci Identified through Large-Scale Exome Chip Analysis Regulate Kidney Development and Function. J Am Soc Nephrol. 2017;28:981-994 pubmed publisher
    ..single nucleotide polymorphisms at seven new loci associated with eGFRcrea (PPM1J, EDEM3, ACP1, SPEG, EYA4, CYP1A1, and ATXN2L; PStage1<3...
  9. Hata T, Dal Molin M, Hong S, Tamura K, Suenaga M, Yu J, et al. Predicting the Grade of Dysplasia of Pancreatic Cystic Neoplasms Using Cyst Fluid DNA Methylation Markers. Clin Cancer Res. 2017;23:3935-3944 pubmed publisher
    ..after surgical resection were analyzed for methylated DNA at selected genes (SOX17, BNIP3, FOXE1, PTCHD2, SLIT2, EYA4, and SFRP1) using methylation-specific droplet-digital PCR (dd-QMSP)...
  10. Frykholm C, Klar J, Arnesson H, Rehnman A, Lodahl M, Wedén U, et al. Phenotypic variability in a seven-generation Swedish family segregating autosomal dominant hearing impairment due to a novel EYA4 frameshift mutation. Gene. 2015;563:10-6 pubmed publisher
    Linkage to an interval overlapping the DFNA10 locus on chromosome 6q22-23 was found through genome wide linkage analysis in a seven-generation Swedish family segregating postlingual, autosomal dominant nonsyndromic sensorineural hearing ..
  11. Xia W, Liu F, Ma D. Research progress in pathogenic genes of hereditary non-syndromic mid-frequency deafness. Front Med. 2016;10:137-42 pubmed publisher
    ..Only four genetic midfrequency deafness genes, namely, DFNA10 (EYA4), DFNA8/12 (TECTA), DFNA13 (COL11A2), DFNA44 (CCDC50), have been reported to date...
  12. van Beelen E, Oonk A, Leijendeckers J, Hoefsloot E, Pennings R, Feenstra I, et al. Audiometric Characteristics of a Dutch DFNA10 Family With Mid-Frequency Hearing Impairment. Ear Hear. 2016;37:103-11 pubmed publisher
    Mutations in EYA4 can cause nonsyndromic autosomal dominant sensorineural hearing impairment (DFNA10) or a syndromic variant with hearing impairment and dilated cardiomyopathy...
  13. Hao X, Cai J, Liu X, Chen W, Hou X, Chen D, et al. EYA4 gene functions as a prognostic marker and inhibits the growth of intrahepatic cholangiocarcinoma. Chin J Cancer. 2016;35:70 pubmed publisher
    ..The purpose of this study was to investigate the prognostic value of the eyes absent homolog 4 (EYA4) gene in ICC and its biological effects on ICC growth in vitro and in vivo...
  14. Huang A, Yuan Y, Liu Y, Zhu Q, Dai P. A novel EYA4 mutation causing hearing loss in a Chinese DFNA family and genotype-phenotype review of EYA4 in deafness. J Transl Med. 2015;13:154 pubmed publisher
    ..Mutations in the EYA4 gene are responsible for postlingual, progressive, autosomal dominant hearing loss at the DFNA10 locus. We report on a Chinese family with sensorineural, progressive hearing loss...
  15. Hoffmann T, Keats B, Yoshikawa N, Schaefer C, Risch N, Lustig L. A Large Genome-Wide Association Study of Age-Related Hearing Impairment Using Electronic Health Records. PLoS Genet. 2016;12:e1006371 pubmed publisher
    ..00019) and speech discrimination score (SDS; p = 0.0019); and rs9493627 (missense change in EYA4, p = 0.00011) which replicated in the UK Biobank (p = 0.0095), other GERA groups (p = 0...
  16. Matsuzaki S, Hosoya M, Okano H, Fujioka M, Ogawa K. Expression pattern of EYA4 in the common marmoset (Callithrix jacchus) cochlea. Neurosci Lett. 2018;662:185-188 pubmed publisher
    ..b>EYA4, one of the vertebrate genes of Eya family, is reported to be causative for late-onset mid-frequency sensorineural ..
  17. Zhang Y, Knosp B, Maconochie M, Friedman R, Smith R. A comparative study of Eya1 and Eya4 protein function and its implication in branchio-oto-renal syndrome and DFNA10. J Assoc Res Otolaryngol. 2004;5:295-304 pubmed
    ..vertebrate Eya gene family, underlie two types of inherited human deafness, branchio-oto-renal (BOR) syndrome and DFNA10, respectively...
  18. Kemp J, Medina Gomez C, Estrada K, St Pourcain B, Heppe D, Warrington N, et al. Phenotypic dissection of bone mineral density reveals skeletal site specificity and facilitates the identification of novel loci in the genetic regulation of bone mass attainment. PLoS Genet. 2014;10:e1004423 pubmed publisher
    ..Allowing for these differences by performing genome-wide association at different skeletal sites may help uncover new genetic influences on BMD. ..
  19. Wan Y, Rogers M, Szabo Rogers H. A six-gene expression toolbox for the glands, epithelium and chondrocytes in the mouse nasal cavity. Gene Expr Patterns. 2018;27:46-55 pubmed publisher
    ..Here, using in situ hybridization expression experiments, we report that Alx1, Ap-2?, Crispld1, Eya4, Moxd1, and Penk have tissue specific expression during murine nasal development. At E11...
  20. Wilson I, Vucic E, Enfield K, Thu K, Zhang Y, Chari R, et al. EYA4 is inactivated biallelically at a high frequency in sporadic lung cancer and is associated with familial lung cancer risk. Oncogene. 2014;33:4464-73 pubmed publisher
    ..of disruption in tumors across multiple cohorts, we have identified a putative lung cancer TSG, Eyes Absent 4 (EYA4)...
  21. Yang Q, Xu X, Jiao J, Zheng Y, He L, Yu S, et al. Genetic variation in EYA4 on the risk of noise-induced hearing loss in Chinese steelworks firm sample. Occup Environ Med. 2016;73:823-828 pubmed publisher
    ..of this study was to examine the association between the genetic susceptibility of the eye absent homolog 4 (EYA4) gene and the risk of developing noise-induced hearing loss in China...
  22. Mo S, Liu X, Hao X, Chen W, Zhang K, Cai J, et al. EYA4 functions as tumor suppressor gene and prognostic marker in pancreatic ductal adenocarcinoma through ?-catenin/ID2 pathway. Cancer Lett. 2016;380:403-12 pubmed publisher
    Eye absent homolog 4 (EYA4) was initially found as key gene in controlling eye development in Drosophila. We recently found that EYA4 was an independent prognostic factor in hepatocellular carcinoma...
  23. Zhang X, Liu Y, Zhang L, Yang Z, Yang L, Wang X, et al. Associations of genetic variations in EYA4, GRHL2 and DFNA5 with noise-induced hearing loss in Chinese population: a case- control study. Environ Health. 2015;14:77 pubmed publisher
    ..The purpose of this study was to examine the associations between genetic variations in the EYA4, GRHL2 and DFNA5 genes and the risk to noise-induced hearing loss (NIHL) in a Chinese population...
  24. Choi H, Kim A, Kim S, Choi B. Identification of a novel truncation mutation of EYA4 in moderate degree hearing loss by targeted exome sequencing. Eur Arch Otorhinolaryngol. 2016;273:1123-9 pubmed publisher
    ..of this gene are known to cause postlingual and progressive sensorineural hearing loss, either as non-syndromic (DFNA10) or syndromic hearing loss, depending on the location of truncation of the mutant protein...
  25. Liu F, Hu J, Xia W, Hao L, Ma J, Ma D, et al. Exome Sequencing Identifies a Mutation in EYA4 as a Novel Cause of Autosomal Dominant Non-Syndromic Hearing Loss. PLoS ONE. 2015;10:e0126602 pubmed publisher
    Autosomal dominant non-syndromic hearing loss is highly heterogeneous, and eyes absent 4 (EYA4) is a disease-causing gene...
  26. Kim Y, Kim M, Sagong B, Bae S, Lee H, Kim H, et al. Evaluation of the contribution of the EYA4 and GRHL2 genes in Korean patients with autosomal dominant non-syndromic hearing loss. PLoS ONE. 2015;10:e0119443 pubmed publisher
    ..Since EYA4 and GRHL2 were identified as the transcription factors for the DFNA10 and DFNA28, 8 EYA4 mutations and 2 GRHL2 mutations have been reported worldwide...
  27. Kim S, Tae C, Hong S, Min B, Chang D, Rhee P, et al. EYA4 Acts as a New Tumor Suppressor Gene in Colorectal Cancer. Mol Carcinog. 2015;54:1748-57 pubmed publisher
    ..methylation array for colorectal cancer (CRC) identified aberrant promoter methylation of eyes absent 4 (EYA4)...
  28. Liu Y, Tham C, Ong S, Ho K, Lim J, Chew M, et al. Serum methylation levels of TAC1. SEPT9 and EYA4 as diagnostic markers for early colorectal cancers: a pilot study. Biomarkers. 2013;18:399-405 pubmed publisher
    ..Serum methylation levels of TAC1, SEPT9, and EYA4 were significant discriminants between stage I CRC and healthy controls. Combination of TAC1 and SEPT9 rendered 73...
  29. Plant D, Bowes J, Potter C, Hyrich K, Morgan A, Wilson A, et al. Genome-wide association study of genetic predictors of anti-tumor necrosis factor treatment efficacy in rheumatoid arthritis identifies associations with polymorphisms at seven loci. Arthritis Rheum. 2011;63:645-53 pubmed publisher
    ..The strongest effect was at rs17301249, mapping to the EYA4 gene on chromosome 6: the minor allele conferred improved response to treatment (coefficient -0.27, P = 5.67(-05) )...
  30. Li H, Diao T, Zhou Z, Yang F, Ma Q, Li Q. Relationship between the expression of hTERT and EYA4 mRNA in peripheral blood mononuclear cells with the progressive stages of carcinogenesis of the esophagus. J Exp Clin Cancer Res. 2009;28:145 pubmed publisher
    ..squamous cell diseases and the expression of human telomerase reverse transcriptase (hTERT) and Eyes absent 4 (EYA4) mRNA in peripheral blood mononuclear cells...
  31. Williams T, Hundertmark M, Nordbeck P, Voll S, Arias Loza P, Oppelt D, et al. Eya4 Induces Hypertrophy via Regulation of p27kip1. Circ Cardiovasc Genet. 2015;8:752-64 pubmed publisher
    E193, a heterozygous truncating mutation in the human transcription cofactor Eyes absent 4 (Eya4), causes hearing impairment followed by dilative cardiomyopathy...
  32. Huang S, Jiang M, Chen G, Qian K, Gao H, Guan W, et al. Epigenetic Silencing of Eyes Absent 4 Gene by Acute Myeloid Leukemia 1-Eight-twenty-one Oncoprotein Contributes to Leukemogenesis in t(8;21) Acute Myeloid Leukemia. Chin Med J (Engl). 2016;129:1355-62 pubmed publisher
    ..By focusing on the anti-leukemia effects of eyes absent 4 (EYA4) gene on AML cells, we investigated the biologic and molecular mechanism associated with AML1-ETO expressed in t(8;..
  33. Sun Y, Zhang Z, Cheng J, Lu Y, Yang C, Luo Y, et al. A novel mutation of EYA4 in a large Chinese family with autosomal dominant middle-frequency sensorineural hearing loss by targeted exome sequencing. J Hum Genet. 2015;60:299-304 pubmed publisher
    ..To date, only three genes are reported to be associated with MFSNHL, including TECTA, EYA4 and COL11A2...
  34. Kisiel J, Garrity Park M, Taylor W, Smyrk T, Ahlquist D. Methylated eyes absent 4 (EYA4) gene promotor in non-neoplastic mucosa of ulcerative colitis patients with colorectal cancer: evidence for a field effect. Inflamm Bowel Dis. 2013;19:2079-83 pubmed publisher
    Aberrant methylation of the EYA4 gene (mEYA4) highly discriminates ulcerative colitis (UC) cases with colorectal neoplasia from UC controls in both tissue and stool...
  35. McInnes T, Zou D, Rao D, Munro F, Phillips V, McCall J, et al. Genome-wide methylation analysis identifies a core set of hypermethylated genes in CIMP-H colorectal cancer. BMC Cancer. 2017;17:228 pubmed publisher
    ..b>EYA4, TFPI2 and TLX1 were hypermethylated in more than 90% of all tumours examined...
  36. Turner S, Bailey K, Schwartz G, Chapman A, Chai H, Boerwinkle E. Genomic association analysis identifies multiple loci influencing antihypertensive response to an angiotensin II receptor blocker. Hypertension. 2012;59:1204-11 pubmed publisher
  37. Cesca F, Bettella E, Polli R, Cama E, Scimemi P, Santarelli R, et al. 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. Int J Pediatr Otorhinolaryngol. 2018;104:88-93 pubmed publisher
    ..In these two subjects the DFNA10 phenotype was masked by Waardenburg syndrome...
  38. Schonberger J, Levy H, Grunig E, Sangwatanaroj S, Fatkin D, MacRae C, et al. Dilated cardiomyopathy and sensorineural hearing loss: a heritable syndrome that maps to 6q23-24. Circulation. 2000;101:1812-8 pubmed
    ..8 cM interval between loci D6S975 and D6S292, a location that overlaps an SNHL disease locus (DFNA10). However, DFNA10 does not cause cardiomyopathy...
  39. Depreux F, Darrow K, Conner D, Eavey R, Liberman M, Seidman C, et al. Eya4-deficient mice are a model for heritable otitis media. J Clin Invest. 2008;118:651-8 pubmed publisher
    ..As EYA4 mutations cause sensorineural hearing loss in humans, we produced and characterized Eya4-deficient (Eya4(-/-)) mice,..
  40. Towle R, Truong D, Garnis C. Epigenetic mediated silencing of EYA4 contributes to tumorigenesis in oral dysplastic cells. Genes Chromosomes Cancer. 2016;55:568-76 pubmed publisher
    ..We previously identified EYA4 as frequently hypermethylated and silenced in premalignant disease based on an analysis of lesion-adjacent normal, ..
  41. Hou X, Peng J, Hao X, Cai J, Liang L, Zhai J, et al. DNA methylation profiling identifies EYA4 gene as a prognostic molecular marker in hepatocellular carcinoma. Ann Surg Oncol. 2014;21:3891-9 pubmed publisher
    ..050), and methylation levels of EYA4 were inversely related to DFS and OS (both P < 0.050)...
  42. Miller S, Lan Z, Hardiman A, Wu J, Kordich J, Patmore D, et al. Inhibition of Eyes Absent Homolog 4 expression induces malignant peripheral nerve sheath tumor necrosis. Oncogene. 2010;29:368-79 pubmed publisher
    ..We identified a decrease in DACH1 expression, and increases in the expressions of PAX6, EYA1, EYA2, EYA4, and SIX1-4 genes...