EYA4

EYA transcriptional coactivator and phosphatase 4, the group of EYA transcriptional coactivator and phosphatases

Basic information

Region (hg38): 6:133240514-133532128

Previous symbols: [ "DFNA10", "CMD1J" ]

Links

ENSG00000112319 ∙ NCBI:2070 ∙ OMIM:603550 ∙ HGNC:3522 ∙ Uniprot:O95677 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• autosomal dominant nonsyndromic hearing loss 10 (Strong), mode of inheritance: AD
• autosomal dominant nonsyndromic hearing loss (Supportive), mode of inheritance: AD
• dilated cardiomyopathy 1J (Supportive), mode of inheritance: AD
• autosomal dominant nonsyndromic hearing loss 10 (Strong), mode of inheritance: AD
• nonsyndromic genetic hearing loss (Definitive), mode of inheritance: AD
• dilated cardiomyopathy 1J (Limited), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Cardiomyopathy, dilated, 1J	AD	Cardiovascular	Related to cardiomyopathy, preventive measures and medical management may be helpful to help decrease morbidity	Audiologic/Otolaryngologic; Cardiovascular	10769282; 10982027; 11159937; 15735644; 17568404; 17567890
The condition may also include childhood-onset sensorineural hearing loss

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the EYA4 gene.

• Dilated cardiomyopathy 1J (14 variants)
• not provided (9 variants)
• Autosomal dominant nonsyndromic hearing loss 10 (4 variants)
• Nonsyndromic genetic hearing loss (1 variants)
• Inborn genetic diseases (1 variants)
• EYA4-related disorder (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the EYA4 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			6	151	1	158
missense	1	1	394	4		400
nonsense	14	6	1			21
start loss			1			1
frameshift	12	3	1			16
inframe indel			5			5
splice donor/acceptor (+/-2bp)	1	12	1			14
splice region		1	31	21		53
non coding			59	113	57	229
Total	28	22	468	268	58

Variants in EYA4

This is a list of pathogenic ClinVar variants found in the EYA4 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
6-133241370-C-T		Dilated cardiomyopathy 1J • Autosomal dominant nonsyndromic hearing loss 10	Benign/Likely benign (Jan 13, 2018)
6-133241385-T-C		Dilated cardiomyopathy 1J • Autosomal dominant nonsyndromic hearing loss 10	Uncertain significance (Jan 12, 2018)
6-133241407-G-T		Dilated cardiomyopathy 1J • Autosomal dominant nonsyndromic hearing loss 10	Uncertain significance (Jan 12, 2018)
6-133241459-T-C		Dilated cardiomyopathy 1J • Autosomal dominant nonsyndromic hearing loss 10	Benign/Likely benign (Jan 13, 2018)
6-133241489-C-G		Dilated cardiomyopathy 1J • Autosomal dominant nonsyndromic hearing loss 10	Benign/Likely benign (Jan 12, 2018)
6-133241559-C-T		Dilated cardiomyopathy 1J • Autosomal dominant nonsyndromic hearing loss 10	Uncertain significance (Jan 13, 2018)
6-133241571-C-G		Dilated cardiomyopathy 1J • Autosomal dominant nonsyndromic hearing loss 10	Benign/Likely benign (Jan 13, 2018)
6-133241585-A-AT		Dilated Cardiomyopathy, Dominant • Nonsyndromic Hearing Loss, Dominant	Likely benign (Jun 14, 2016)
6-133241691-C-T		Autosomal dominant nonsyndromic hearing loss 10 • Dilated cardiomyopathy 1J	Uncertain significance (Jan 13, 2018)
6-133241739-C-T		Autosomal dominant nonsyndromic hearing loss 10 • Dilated cardiomyopathy 1J	Benign (Jan 12, 2018)
6-133274433-G-A			Benign (Sep 18, 2018)
6-133274546-C-A			Benign (Sep 04, 2018)
6-133274767-A-G		not specified	Uncertain significance (Mar 02, 2020)
6-133274782-T-C		Dilated cardiomyopathy 1J • Cardiovascular phenotype	Uncertain significance (May 15, 2023)
6-133274785-A-G		Dilated cardiomyopathy 1J • Cardiovascular phenotype	Uncertain significance (Nov 17, 2023)
6-133274787-G-A		Dilated cardiomyopathy 1J • Cardiovascular phenotype	Uncertain significance (Jun 05, 2023)
6-133274789-C-T		not specified • Cardiovascular phenotype • Dilated cardiomyopathy 1J	Likely benign (Jan 22, 2024)
6-133274792-C-T		Cardiovascular phenotype	Likely benign (May 22, 2019)
6-133274796-G-A		Cardiovascular phenotype • Dilated cardiomyopathy 1J	Uncertain significance (Nov 24, 2023)
6-133274803-A-G		Dilated cardiomyopathy 1J	Uncertain significance (Aug 11, 2023)
6-133274804-T-G		Dilated cardiomyopathy 1J	Uncertain significance (Dec 20, 2022)
6-133274806-A-C		Dilated cardiomyopathy 1J	Uncertain significance (May 10, 2019)
6-133274810-A-G		Dilated cardiomyopathy 1J	Uncertain significance (Nov 22, 2016)
6-133274812-C-T		Dilated cardiomyopathy 1J • Autosomal dominant nonsyndromic hearing loss 10;Dilated cardiomyopathy 1J	Uncertain significance (Aug 11, 2021)
6-133274813-A-G		Dilated cardiomyopathy 1J	Uncertain significance (Dec 24, 2021)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
EYA4	protein_coding	protein_coding	ENST00000367895	19	291523

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.0487	0.951	125736	0	11	125747	0.0000437

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.12	276	333	0.828	0.0000168	4153
Missense in Polyphen		92	135.82	0.67738		1741
Synonymous	1.38	103	122	0.841	0.00000668	1223
Loss of Function	4.18	10	37.7	0.265	0.00000173	467

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000181	0.000181
Ashkenazi Jewish	0.00	0.00
East Asian	0.0000544	0.0000544
Finnish	0.00	0.00
European (Non-Finnish)	0.0000352	0.0000352
Middle Eastern	0.0000544	0.0000544
South Asian	0.0000653	0.0000653
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Tyrosine phosphatase that specifically dephosphorylates 'Tyr-142' of histone H2AX (H2AXY142ph). 'Tyr-142' phosphorylation of histone H2AX plays a central role in DNA repair and acts as a mark that distinguishes between apoptotic and repair responses to genotoxic stress. Promotes efficient DNA repair by dephosphorylating H2AX, promoting the recruitment of DNA repair complexes containing MDC1. Its function as histone phosphatase probably explains its role in transcription regulation during organogenesis. May be involved in development of the eye (By similarity). {ECO:0000250|UniProtKB:Q99502}.
• Disease: DISEASE: Cardiomyopathy, dilated 1J (CMD1J) [MIM:605362]: A disorder characterized by ventricular dilation and impaired systolic function, resulting in congestive heart failure and arrhythmia. Patients are at risk of premature death. CMD1J is characterized by the association of sensorineural hearing loss and dilated cardiomyopathy in the absence of other anomalies. {ECO:0000269|PubMed:15735644}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: DNA Repair;DNA Double-Strand Break Repair;Recruitment and ATM-mediated phosphorylation of repair and signaling proteins at DNA double strand breaks;DNA Double Strand Break Response (Consensus)

Recessive Scores

• pRec: 0.160

Intolerance Scores

• loftool: 0.0973
• rvis_EVS: -0.42
• rvis_percentile_EVS: 25.56

Haploinsufficiency Scores

• pHI: 0.748
• hipred: Y
• hipred_score: 0.604
• ghis: 0.552

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.269

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	High	Medium	High
Primary Immunodeficiency	High	High	High
Cancer	High	High	High

Mouse Genome Informatics

• Gene name: Eya4
• Phenotype: growth/size/body region phenotype; adipose tissue phenotype (the observable morphological and physiological characteristics of mammalian fat tissue that are manifested through development and lifespan); endocrine/exocrine gland phenotype; homeostasis/metabolism phenotype; craniofacial phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); reproductive system phenotype; embryo phenotype; immune system phenotype; digestive/alimentary phenotype; hearing/vestibular/ear phenotype

Zebrafish Information Network

• Gene name: eya4
• Affected structure: pillar of the posterior semicircular canal
• Phenotype tag: abnormal
• Phenotype quality: malformed

Gene ontology

• Biological process: DNA repair;multicellular organism development;visual perception;sensory perception of sound;anatomical structure morphogenesis;histone dephosphorylation;peptidyl-tyrosine dephosphorylation;positive regulation of DNA repair;anatomical structure development;negative regulation of extrinsic apoptotic signaling pathway in absence of ligand
• Cellular component: nucleus;cytoplasm
• Molecular function: protein tyrosine phosphatase activity;protein binding;metal ion binding