Function
EYA4 is a tyrosine phosphatase that specifically dephosphorylates 'Tyr-142' of histone H2AX (H2AXY142ph). Phosphorylation of 'Tyr-142' on histone H2AX plays a critical role in DNA repair and serves as a marker distinguishing between apoptotic and repair responses to genotoxic stress. EYA4 promotes efficient DNA repair by dephosphorylating H2AX, thereby facilitating the recruitment of DNA repair complexes containing MDC1. Its function as a histone phosphatase likely explains its role in transcription regulation during organogenesis. EYA4 may also be involved in eye development.
Gene References Into Functions
- Overexpression of EYA4 enhanced glioma cell proliferation and suppressed the expression of p27Kip1 directly in these cells. PMID: 30231237
- While the clinical outcome of our 38 Colorectal Cancer patients was not associated with EYA4 promoter hypermethylation, the high frequency of this methylation and its high sensitivity and specificity to neoplastic cells may qualify EYA4 promoter methylation as a potential candidate screening marker in the Iranian population and could aid in improving early detection of CRC. PMID: 29436791
- Eyes absent homolog 4 (Drosophila) protein (EYA4) is frequently hypermethylated in esophageal squamous cell carcinoma (ESCC) and may function as a tumor suppressor gene in the development of ESCC. PMID: 29660222
- A novel EYA4 mutation identified may be responsible for the hearing loss observed in the proband and her father, while a dual molecular diagnosis was reached in the relatives co-segregating the EYA4 and the PAX3 mutations. PMID: 29287889
- EYA4 hypermethylation is associated with colorectal cancer. PMID: 28351398
- EYA4 functions as a tumor suppressor gene in pancreatic ductal adenocarcinoma via repressing beta-catenin/ID2 activation and was an independent prognostic factor in PDAC. PMID: 27378242
- Low expression of EYA4 is associated with oral cancer. PMID: 27015871
- Two genome-wide significant SNPs were discovered. The first was novel and near ISG20. The second was in TRIOBP, a gene previously associated with prelingual nonsyndromic hearing loss. Based on the TRIOBP findings, exons in known hearing loss genes were examined, identifying two additional SNPs, rs2877561 in ILDR1 and rs9493672 in EYA4 (at a significance threshold adjusted for the number of SNPs in those regions). PMID: 27764096
- Locus polymorphism of rs3813346 was associated with the risk of developing noise-induced hearing loss in the dominance, codominance, and additive models. Generalized multiple dimensionality reduction indicated that the combined interaction of the 2 loci-rs3813346 and rs9493627-significantly affected the incidence of noise-induced hearing loss. PMID: 27613755
- To date, only 7 loci have been linked to mid-frequency hearing loss. Only four genetic mid-frequency deafness genes, namely, DFNA10 (EYA4), DFNA8/12 (TECTA), DFNA13 (COL11A2), DFNA44 (CCDC50), have been reported. [review] PMID: 27142990
- This study identified EYA4 gene as targets for AML1-ETO and indicated it as a novel tumor suppressor gene. Additionally, evidence was provided that EYA4 gene might be a novel therapeutic target and a potential candidate for treating AML1-ETO+ t (8;21) AML. PMID: 27231175
- Loss of EYA4 expression is associated with intrahepatic cholangiocarcinoma. PMID: 27469137
- The identification of a novel EYA4 truncation mutation associated with DFNA10, rather than syndromic hearing loss, supports a previously reported genotype-phenotype correlation in this gene. PMID: 26015337
- These results implicate Eya4/Six1 in regulating normal cardiac function via p27/casein kinase-2alpha/histone deacetylase 2 and indicate that mutations within this transcriptional complex and signaling cascade lead to the development of cardiomyopathy. PMID: 26499333
- In a Dutch family with c.464del EYA4 mutation, hearing impairment begins as a mid-frequency hearing impairment in childhood and develops into a high-frequency, moderate hearing impairment later in life. PMID: 26331839
- Genetic variations in the EYA4, GRHL2, and DFNA5 genes and their interactions with occupational noise exposure may play a significant role in the incidence of noise-induced hearing loss (NIHL). PMID: 26400775
- Analysis of an EYA4 mutation causing hearing loss in a Chinese DFNA family. PMID: 25963406
- A novel missense mutation c.1643C>G (p.T548R) in EYA4 may cause autosomal dominant non-syndromic hearing impairment. PMID: 25809937
- EYA4 mutations are associated with autosomal dominant non-syndromic hearing loss. PMID: 25781927
- Exome Sequencing Identifies a Mutation in EYA4 as a Novel Cause of Autosomal Dominant Non-Syndromic Hearing Loss PMID: 25961296
- EYA4 methylation may be identified in stool samples. PMID: 25620232
- Results provide molecular and clinical information to gain a better understanding of the pathogenesis of DFNA10 protein EYA4 mutations and the genotype-phenotype correlations of DFNA10 hearing loss. PMID: 25242383
- Autosomal dominant hearing impairment due to a novel EYA4 frameshift mutation: a novel heterozygous frame-shift mutation (c.579_580insTACC, p.(Asp194Tyrfs*52)) in EYA4 was identified that truncates the so-called variable region of the protein. PMID: 25681523
- Low EYA4 expression is associated with hepatocellular carcinoma. PMID: 24306662
- This work shows a clear role for EYA4 as a putative tumor suppressor gene in non-small-cell lung cancer. PMID: 24096489
- High methylation of the EYA4 gene is associated with ulcerative colitis with colorectal cancer. PMID: 23867875
- Serum methylation levels of TAC1, SEPT9, and EYA4 were significant discriminants between stage I colorectal cancer and healthy controls. PMID: 23862763
- Observational study and genome-wide association study of gene-disease association, gene-environment interaction, and pharmacogenomic / toxicogenomic. (HuGE Navigator) PMID: 21061259
- Clinical trial of gene-disease association and gene-environment interaction. (HuGE Navigator) PMID: 20379614
- EYA4 and hTERT mRNA expression increased with the severity of esophageal pathological changes and may be useful for identifying high-risk endoscopy candidates or for monitoring changes in premalignant esophageal lesions. PMID: 19939248
- Findings identify a role of EYA4 and possibly interacting SIX and DACH proteins in MPNSTs and suggest the EYA4 pathway as a rational therapeutic target. PMID: 19901965
- Mutation analysis of the EYA4 gene, which maps to 6q22.3, revealed an insertion of 4 bp (1558insTTTG) in affected family members with hereditary hearing impairment. PMID: 12477971
- Mutation in the transcriptional coactivator EYA4 causes dilated cardiomyopathy and sensorineural hearing loss. PMID: 15735644
- Results show the first definitive cardiac evaluations of DFNA10 hearing loss to support a correlation of EYA4 mutation with/without the of dilated cardiomyopathy, and will facilitate the counseling of patients with these phenotypes and EYA4 mutations. PMID: 17567890
- This study is the first report of a point mutation in EYA4 that is hypothesized to lead to aberrant pre-mRNA splicing and human disease. PMID: 17568404
- Mice lacking the orthologous gene have severe hearing deficits, suggesting that some human otitis media susceptibility reflects underlying genetic predisposition in genes such as this one. PMID: 18219393
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Involvement In Disease
Deafness, autosomal dominant, 10 (DFNA10); Cardiomyopathy, dilated 1J (CMD1J)
Protein Families
HAD-like hydrolase superfamily, EYA family
Subcellular Location
Cytoplasm. Nucleus.
Tissue Specificity
Highly expressed in heart and skeletal muscle.