EYA4 eyes absent homolog 4 (Drosophila) [Homo sapiens (human)] - Gene

Summary

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Official Symbol: EYA4provided by HGNC
Official Full Name: eyes absent homolog 4 (Drosophila)provided by HGNC
Primary source: HGNC:3522
Locus tag: RP11-704J17.4
See related: Ensembl:ENSG00000112319; HPRD:04648; MIM:603550; Vega:OTTHUMG00000015602
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: CMD1J; DFNA10
Summary: This gene encodes a member of the eyes absent (EYA) family of proteins. The encoded protein may act as a transcriptional activator through its protein phosphatase activity, and it may be important for eye development, and for continued function of the mature organ of Corti. Mutations in this gene are associated with postlingual, progressive, autosomal dominant hearing loss at the deafness, autosomal dominant nonsyndromic sensorineural 10 locus. Defects in this gene are also associated with dilated cardiomyopathy 1J. Three transcript variants encoding distinct isoforms have been identified for this gene. [provided by RefSeq, Jul 2008]

Genomic context

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Location :: 6q23

Sequence :: Chromosome: 6; NC_000006.11 (133562495..133853258)

See EYA4 in Epigenomics, MapViewer

Chromosome 6 - NC_000006.11 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Genomic Sequence

Go to nucleotideGraphics FASTA GenBank

Go to reference sequence details

Bibliography

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GeneRIFs: Gene References Into Functions What's a GeneRIF?

Observational study and genome-wide association study of gene-disease association, gene-environment interaction, and pharmacogenomic / toxicogenomic. (HuGE Navigator)
Title: Genome-wide association study of genetic predictors of anti-tumor necrosis factor treatment efficacy in rheumatoid arthritis identifies associations with polymorphisms at seven loci.
Clinical trial of gene-disease association and gene-environment interaction. (HuGE Navigator)
Title: Personalized smoking cessation: interactions between nicotine dose, dependence and quit-success genotype score.
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.
Title: Relationship between the expression of hTERT and EYA4 mRNA in peripheral blood mononuclear cells with the progressive stages of carcinogenesis of the esophagus.
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.
Title: Inhibition of Eyes Absent Homolog 4 expression induces malignant peripheral nerve sheath tumor necrosis.
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.
Title: Eya4-deficient mice are a model for heritable otitis media.
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.
Title: Nonsyndromic hearing loss DFNA10 and a novel mutation of EYA4: evidence for correlation of normal cardiac phenotype with truncating mutations of the Eya domain.
Study is the first report of a point mutation in EYA4 that is hypothesized to lead to aberrant pre-mRNA splicing and human disease.
Title: A novel splice site mutation in EYA4 causes DFNA10 hearing loss.
Mutation in the transcriptional coactivator EYA4 causes dilated cardiomyopathy and sensorineural hearing loss
Title: Mutation in the transcriptional coactivator EYA4 causes dilated cardiomyopathy and sensorineural hearing loss.
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
Title: A 4-bp insertion in the eya-homologous region (eyaHR) of EYA4 causes hearing impairment in a Hungarian family linked to DFNA10.

Submit: New GeneRIF Correction

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Deafness, autosomal dominant 10

MIM: 601316

Genetic Testing Registry

Summary from GeneReviews: Deafness and Hereditary Hearing Loss Overview

Hereditary hearing loss and deafness may be conductive, sensorineural, or a combination of both; syndromic (associated with malformations of the external ear or other organs or with medical problems involving other organ systems) or nonsyndromic (no associated visible abnormalities of the external ear or any related medical problems); and prelingual (before language develops) or postlingual (after language develops).

Diagnosis Testing

Genetic forms of hearing loss must be distinguished from acquired (non-genetic) causes of hearing loss. The genetic forms of hearing loss are diagnosed by otologic, audiologic, and physical examination, family history, ancillary testing (e.g., CT examination of the temporal bone), and molecular genetic testing. Molecular genetic testing, possible for many types of syndromic and nonsyndromic deafness, plays a prominent role in diagnosis and genetic counseling.

Genetic Counseling

Hereditary hearing loss can be inherited in an autosomal dominant, autosomal recessive, or X-linked recessive manner, as well as by mitochondrial inheritance. Genetic counseling and risk assessment depend on accurate determination of the specific genetic diagnosis. In the absence of a specific diagnosis, empiric recurrence risk figures, coupled with GJB2 and GJB6 molecular genetic testing results, can be used for genetic counseling.

References

PMID: 20301607

Dilated cardiomyopathy 1J

MIM: 605362

Genetic Testing Registry

Summary from GeneReviews: Dilated Cardiomyopathy Overview

Disease Characteristics

Nonsyndromic isolated dilated cardiomyopathy (DCM) is characterized by left ventricular enlargement and systolic dysfunction, a reduction in the myocardial force of contraction. DCM usually presents with any one of the following: Heart failure with symptoms of congestion (edema, orthopnea, paroxysmal dyspnea) and/or reduced cardiac output (fatigue, dyspnea on exertion). Arrhythmias and/or conduction system disease. Thromboembolic disease (from left ventricular mural thrombus) including stroke .

Diagnosis Testing

Genetic forms of DCM must be distinguished from other identifiable causes. After exclusion of all identifiable non-genetic causes, DCM is traditionally referred to as idiopathic dilated cardiomyopathy. When two or more closely related family members meet a formal diagnostic standard for idiopathic dilated cardiomyopathy, the diagnosis of familial dilated cardiomyopathy (FDC) is made. The genetic forms of DCM are diagnosed by family history and molecular genetic testing.

Genetic Counseling

Genetic DCM can be inherited in an autosomal dominant, autosomal recessive, or X-linked manner. Maternal mitochondrial inheritance has also been reported; however, mitochondrial forms of DCM, although highly variable in presentation (including mild adult-onset forms), are usually syndromic and thus outside the scope of this review. Genetic counseling and risk assessment depend on determination of the specific DCM subtype in an individual.

References

PMID: 20301486

Primary dilated cardiomyopathy

Genetic Testing Registry

Summary from GeneReviews: Dilated Cardiomyopathy Overview

Disease Characteristics

Nonsyndromic isolated dilated cardiomyopathy (DCM) is characterized by left ventricular enlargement and systolic dysfunction, a reduction in the myocardial force of contraction. DCM usually presents with any one of the following: Heart failure with symptoms of congestion (edema, orthopnea, paroxysmal dyspnea) and/or reduced cardiac output (fatigue, dyspnea on exertion). Arrhythmias and/or conduction system disease. Thromboembolic disease (from left ventricular mural thrombus) including stroke .

Diagnosis Testing

Genetic forms of DCM must be distinguished from other identifiable causes. After exclusion of all identifiable non-genetic causes, DCM is traditionally referred to as idiopathic dilated cardiomyopathy. When two or more closely related family members meet a formal diagnostic standard for idiopathic dilated cardiomyopathy, the diagnosis of familial dilated cardiomyopathy (FDC) is made. The genetic forms of DCM are diagnosed by family history and molecular genetic testing.

Genetic Counseling

Genetic DCM can be inherited in an autosomal dominant, autosomal recessive, or X-linked manner. Maternal mitochondrial inheritance has also been reported; however, mitochondrial forms of DCM, although highly variable in presentation (including mild adult-onset forms), are usually syndromic and thus outside the scope of this review. Genetic counseling and risk assessment depend on determination of the specific DCM subtype in an individual.

References

PMID: 20301486

NHGRI GWAS Catalog

A genome-wide association study identifies protein quantitative trait loci (pQTLs).

Genome-wide association for abdominal subcutaneous and visceral adipose reveals a novel locus for visceral fat in women.

Genomic association analysis identifies multiple loci influencing antihypertensive response to an angiotensin II receptor blocker.

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description
O95677	Q15475	SIX1		HPRD	PubMed

General gene information

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Markers

RH16384 (e-PCR)
- UniSTS:14103

SHGC-68688 (e-PCR)
- UniSTS:95549

D6S975 (e-PCR)
- UniSTS:58429

D6S2411 (e-PCR)
- UniSTS:574

RH47434 (e-PCR)
- UniSTS:7243

D6S292 (e-PCR)
- UniSTS:6486

EYA4__7614 (e-PCR)
- UniSTS:468055

RH91846 (e-PCR)
- UniSTS:89218

RH122244 (e-PCR)
- UniSTS:134792

RH36228 (e-PCR)
- UniSTS:10125

SGC35210 (e-PCR)
- UniSTS:64676

G49694 (e-PCR)
- UniSTS:109259

AL008749 (e-PCR)
- UniSTS:94687

Genotypes

See EYA4 SNP Geneview Report
See EYA4 SNP Genotype Report
See EYA4 SNP Variation Viewer Report

Homology

Homologs of the EYA4 gene: The EYA4 gene is conserved in chimpanzee, Rhesus monkey, dog, cow, mouse, rat, and chicken.
Map Viewer (Mouse, Rat)
OrthoDB: The Hierarchical Catalog of Eukaryotic Orthologs

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
metal ion binding	IEA Inferred from Electronic Annotation more info
protein tyrosine phosphatase activity	IEA Inferred from Electronic Annotation more info

Process	Evidence Code	Pubs
DNA repair	IEA Inferred from Electronic Annotation more info
anatomical structure morphogenesis	TAS Traceable Author Statement more info	PubMed
chromatin modification	IEA Inferred from Electronic Annotation more info
middle ear morphogenesis	IEA Inferred from Electronic Annotation more info
regulation of transcription, DNA-dependent	IEA Inferred from Electronic Annotation more info
sensory perception of sound	IEA Inferred from Electronic Annotation more info
transcription, DNA-dependent	IEA Inferred from Electronic Annotation more info
visual perception	TAS Traceable Author Statement more info	PubMed

Component	Evidence Code	Pubs
cytoplasm	IEA Inferred from Electronic Annotation more info
nucleus	IEA Inferred from Electronic Annotation more info

General protein information

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Preferred Names: eyes absent homolog 4

Names: eyes absent homolog 4; dJ78N10.1 (eyes absent)

NP_004091.3

EC 3.1.3.48

NP_742101.2

EC 3.1.3.48

NP_742103.1

EC 3.1.3.48

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

NG_011596.1 RefSeqGene

Range

5001..295764

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_004100.4 → NP_004091.3 eyes absent homolog 4 isoform a

Status: REVIEWED

Description

Transcript Variant: This variant (1) encodes isoform a, which is more abundant in adult brain.

Source sequence(s)

AL450270, AW613879, BC014193, BX490250, DA760903, Y17114

Consensus CDS

CCDS5165.1

UniProtKB/Swiss-Prot

O95677

UniProtKB/TrEMBL

Q96CJ7

Related

ENSP00000356870, OTTHUMP00000017235, ENST00000367895, OTTHUMT00000042282

Conserved Domains (1) summary

TIGR01658
Location:368 – 639
Blast Score: 1011

EYA-cons_domain; eyes absent protein conserved domain
NM_172103.3 → NP_742101.2 eyes absent homolog 4 isoform b

Status: REVIEWED

Description

Transcript Variant: This variant (2) lacks an in-frame segment of the 5' coding region, compared to variant 1. The resulting isoform (b) is shorter than isoform a.

Source sequence(s)

AL450270, AW613879, BC014193, BC041063, BX490250, Y17114

Consensus CDS

CCDS43506.1

UniProtKB/Swiss-Prot

O95677

UniProtKB/TrEMBL

Q96CJ7

Conserved Domains (1) summary

TIGR01658
Location:345 – 616
Blast Score: 1011

EYA-cons_domain; eyes absent protein conserved domain
NM_172105.3 → NP_742103.1 eyes absent homolog 4 isoform d

Status: REVIEWED

Description

Transcript Variant: This variant (4) contains an alternate in-frame exon in the 3' coding region, compared to variant 1. The resulting isoform (d) is the same size but has a region of difference in the C-terminal, compared to isoform a.

Source sequence(s)

AJ007994, AL450270, AW613879, BC014193, BX490250, DA760903, Y17114

Consensus CDS

CCDS5166.1

UniProtKB/Swiss-Prot

O95677

UniProtKB/TrEMBL

Q96CJ7

Related

ENSP00000347294, ENST00000355167

Conserved Domains (1) summary

TIGR01658
Location:368 – 639
Blast Score: 1017

EYA-cons_domain; eyes absent protein conserved domain

RefSeqs of Annotated Genomes: Homo sapiens Annotation Release 104

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh37.p10 Primary Assembly

Genomic

NC_000006.11 Reference GRCh37.p10 Primary Assembly

Range

133562495..133853258

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Alternate HuRef

Genomic

AC_000138.1 Alternate HuRef

Range

131131517..131422316

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Alternate CHM1_1.0

Genomic

NC_018917.1 Alternate CHM1_1.0

Range

133563644..133854458

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Suppressed Reference Sequence(s)

The following Reference Sequences have been suppressed. Explain

NM_172104.1: Suppressed sequence

Description

NM_172104.1: This RefSeq was permanently suppressed because it is a nonsense-mediated mRNA decay (NMD) candidate.

Nucleotide		Protein
Heading	Accession and Version	Protein
genomic	ABBA01025870.1 (45023..54973)	None
genomic	ABBA01025871.1	None
genomic	ABBA01025872.1	None
genomic	ABBA01025873.1	None
genomic	AL024497.5	None
genomic	AL121959.15 (81545..136377)	None
genomic	AL356242.17 (101..65933)	None
genomic	AL450270.7 (101..29616)	None
genomic	AMYH01016681.1 (214578..316781)	None
genomic	AMYH01016682.1	None
genomic	AMYH01016683.1	None
genomic	CH471051.2	EAW48004.1
		EAW48005.1
		EAW48006.1
genomic	Y17847.1	CAA76891.1
mRNA	AJ007993.1	CAA07816.1
mRNA	AJ007994.1	CAA07817.1
mRNA	AK295798.1	BAG58618.1
mRNA	AK299378.1	BAG61368.1
mRNA	AK301950.1	BAH13593.1
mRNA	AW613879.1	None
mRNA	BC014193.2	AAH14193.2
mRNA	BC030588.2	None
mRNA	BC041063.1	AAH41063.1
mRNA	BX490250.1	None
mRNA	DA760903.1	None
mRNA	Y17114.1	CAA76636.1
other-genetic	EU446856.1	ABZ92385.1