EYA4

Summary

EYA4 (EYA transcriptional coactivator and phosphatase 4, HGNC:3522) is a protein-coding gene on chromosome 6q23.2, encoding Protein phosphatase EYA4 (O95677). 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. It is haploinsufficient (ClinGen: sufficient evidence).

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 non-syndromic sensorineural 10 locus. The encoded protein is also a putative oncogene that mediates DNA repair, apoptosis, and innate immunity following DNA damage, cellular damage, and viral attack. Defects in this gene are also associated with dilated cardiomyopathy 1J. Alternative splicing results in multiple transcript variants encoding distinct isoforms.

Source: NCBI Gene 2070 — RefSeq curated summary.

At a glance

• Gene–disease (curated): nonsyndromic genetic hearing loss (Definitive, ClinGen) — +3 more curated relationships
• GWAS associations: 49
• Clinical variants (ClinVar): 1,031 total — 48 pathogenic, 31 likely-pathogenic
• Phenotypes (HPO): 10
• Dosage sensitivity (ClinGen): haploinsufficiency sufficient evidence, triplosensitivity no evidence
• MANE Select transcript: NM_004100

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:3522
Approved symbol	EYA4
Name	EYA transcriptional coactivator and phosphatase 4
Location	6q23.2
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000112319
Ensembl biotype	protein_coding
OMIM	603550
Entrez	2070

Gene structure

Transcript identifiers

Ensembl transcripts: 42 — 22 protein_coding, 16 protein_coding_CDS_not_defined, 3 retained_intron, 1 nonsense_mediated_decay

ENST00000355167, ENST00000355286, ENST00000421413, ENST00000430974, ENST00000431403, ENST00000441015, ENST00000452339, ENST00000497350, ENST00000525614, ENST00000525849, ENST00000531861, ENST00000531901, ENST00000532518, ENST00000682730, ENST00000683175, ENST00000683325, ENST00000683361, ENST00000683421, ENST00000683422, ENST00000683580, ENST00000683664, ENST00000683674, ENST00000683832, ENST00000684040, ENST00000684097, ENST00000684425, ENST00000684513, ENST00000684773, ENST00000706301, ENST00000883053, ENST00000883054, ENST00000883055, ENST00000883056, ENST00000883057, ENST00000883058, ENST00000883059, ENST00000883060, ENST00000883061, ENST00000883062, ENST00000883063, ENST00000883064, ENST00000943593

RefSeq mRNA: 7 — MANE Select: NM_004100 NM_001301012, NM_001301013, NM_001370458, NM_001370459, NM_004100, NM_172103, NM_172105

CCDS: CCDS43506, CCDS5165, CCDS75521, CCDS75523, CCDS94004, CCDS94005

Canonical transcript exons

ENST00000355286 — 20 exons

Exon	Start	End
ENSE00000798773	133512878	133513038
ENSE00000798774	133515321	133515435
ENSE00001284413	133241357	133241749
ENSE00001284455	133274716	133274813
ENSE00001597576	133523056	133523177
ENSE00001711375	133525154	133525254
ENSE00001852704	133528725	133532128
ENSE00003464008	133506106	133506195
ENSE00003468302	133483032	133483115
ENSE00003468388	133448111	133448179
ENSE00003540255	133512721	133512779
ENSE00003564780	133456556	133456648
ENSE00003566031	133481463	133481599
ENSE00003582680	133462335	133462477
ENSE00003587571	133382392	133382441
ENSE00003590926	133462621	133462764
ENSE00003595413	133461114	133461180
ENSE00003628601	133446630	133446754
ENSE00003648898	133468566	133468731
ENSE00003689200	133464779	133464858

Expression profiles

Bgee: expression breadth ubiquitous, 208 present calls, max score 93.60.

FANTOM5 (CAGE): breadth broad, TPM avg 4.7838 / max 188.6831, expressed in 777 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
69842	3.3256	724
69841	0.5093	314
69843	0.3197	143
69844	0.3008	148
69840	0.1652	81
69839	0.1633	78

Top tissues by expression

279 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
biceps brachii	UBERON:0001507	93.60	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	92.82	gold quality
seminal vesicle	UBERON:0000998	91.81	gold quality
gastrocnemius	UBERON:0001388	91.50	gold quality
muscle of leg	UBERON:0001383	90.98	gold quality
calcaneal tendon	UBERON:0003701	89.24	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	89.08	gold quality
muscle organ	UBERON:0001630	88.93	gold quality
mucosa of paranasal sinus	UBERON:0005030	88.80	gold quality
hindlimb stylopod muscle	UBERON:0004252	88.51	gold quality
bronchial epithelial cell	CL:0002328	87.99	gold quality
heart right ventricle	UBERON:0002080	87.27	gold quality
skeletal muscle tissue	UBERON:0001134	86.35	gold quality
deltoid	UBERON:0001476	85.49	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	84.35	gold quality
tibialis anterior	UBERON:0001385	83.17	silver quality
muscle tissue	UBERON:0002385	82.55	gold quality
quadriceps femoris	UBERON:0001377	81.82	gold quality
epithelium of bronchus	UBERON:0002031	81.34	gold quality
vastus lateralis	UBERON:0001379	81.32	gold quality
right uterine tube	UBERON:0001302	81.08	gold quality
bronchus	UBERON:0002185	80.61	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	80.02	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	78.97	gold quality
right atrium auricular region	UBERON:0006631	78.81	gold quality
tendon	UBERON:0000043	78.72	gold quality
cardiac atrium	UBERON:0002081	78.29	gold quality
myocardium	UBERON:0002349	77.43	gold quality
cardiac ventricle	UBERON:0002082	77.41	gold quality
heart left ventricle	UBERON:0002084	77.28	gold quality

Single-cell (SCXA)

Detected in 5 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-ANND-2	yes	2911.96
E-CURD-119	yes	29.43
E-ANND-3	yes	6.09
E-MTAB-5061	no	3.81
E-GEOD-83139	no	2.91

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): E2F1, RUNX1

miRNA regulators (miRDB)

185 targeting EYA4, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-656-3P	100.00	72.15	2788
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-4776-3P	100.00	68.73	1340
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-6867-5P	100.00	82.21	3464
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-513A-5P	100.00	69.77	2465
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-511-3P	99.99	68.85	1467
HSA-MIR-4789-3P	99.99	70.75	2484
HSA-MIR-27A-3P	99.98	72.13	2955
HSA-MIR-27B-3P	99.98	72.13	2955
HSA-MIR-9985	99.98	72.11	2939
HSA-MIR-3692-3P	99.98	70.27	2139
HSA-MIR-499A-5P	99.98	70.79	1323
HSA-MIR-1185-1-3P	99.98	71.04	2593
HSA-MIR-1185-2-3P	99.98	71.04	2593
HSA-LET-7F-2-3P	99.98	70.98	2588
HSA-MIR-8068	99.98	73.85	2376
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-19A-3P	99.98	75.33	2762
HSA-MIR-19B-3P	99.98	75.44	2754
HSA-MIR-3688-3P	99.97	72.02	2834
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-548AT-5P	99.96	70.83	2666

Functional genomics

ClinGen dosage: haploinsufficiency 3 (sufficient evidence), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 40)

• 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)
• 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)
• 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)
• 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)
• Serum methylation levels of TAC1, SEPT9, and EYA4 were significant discriminants between stage I colorectal cancer and healthy controls. (PMID:23862763)
• High methylation of the EYA4 gene is associated with ulcerative colitis with colorectal cancer. (PMID:23867875)
• Work shows a clear role for EYA4 as a putative tumor suppressor genes in non-small-cell lung cancer. (PMID:24096489)
• Low EYA4 expression is associated with hepatocellular carcinoma. (PMID:24306662)
• Results provide molecular and clinical information in order to gain improved understanding of the pathogenesis of DFNA10 protein EYA4 mutations and the genotypephenotype correlations of DFNA10 hearing loss. (PMID:25242383)
• EYA4 methylation may be identified in stool samples. (PMID:25620232)
• 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)
• EYA4 mutations are associated with autosomal dominant non-syndromic hearing loss. (PMID:25781927)
• A novel missense mutation c.1643C>G (p.T548R) in EYA4 may cause autosomal dominant non-syndromic hearing impairment. (PMID:25809937)
• Exome Sequencing Identifies a Mutation in EYA4 as a Novel Cause of Autosomal Dominant Non-Syndromic Hearing Loss (PMID:25961296)
• analysis of an EYA4 mutation causing hearing loss in a Chinese DFNA family (PMID:25963406)
• 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)
• 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 an important role in the incidence of noise-induced hearing loss (NIHL). (PMID:26400775)
• results implicate Eya4/Six1 regulates 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)
• Low expression of EYA4 is associated with oral cancer. (PMID:27015871)
• Up to now, merely 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 to date. [review] (PMID:27142990)
• study identified EYA4 gene as targets for AML1-ETO and indicated it as a novel tumor suppressor gene. In addition, we provided evidence that EYA4 gene might be a novel therapeutic target and a potential candidate for treating AML1-ETO+ t (8;21) AML. (PMID:27231175)
• EYA4 functions as tumor suppressor gene in pancreatic ductal adenocarcinoma via repressing beta-catenin/ID2 activation, and was an independent prognostic factor in PDAC. (PMID:27378242)
• Loss of EYA4 expression is associated with intrahepatic cholangiocarcinoma. (PMID:27469137)
• Locus polymorphism of rs3813346 was associated with the risk of developing noise-induced hearing loss in the dominance model, the codominance model and the addictive model. 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)
• We discovered two genome-wide significant SNPs. The first was novel and near ISG20. The second was in TRIOBP, a gene previously associated with prelingual nonsyndromic hearing loss. Motivated by our TRIOBP results, we also looked at exons in known hearing loss genes, and identified two additional SNPs, rs2877561 in ILDR1 and rs9493672 in EYA4 (at a significance threshold adjusted for number of SNPs in those regions). (PMID:27764096)
• EYA4 hypermethylation is associated with colorectal cancer. (PMID:28351398)
• identified novel EYA4 mutation can be considered responsible of 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)
• Although the clinical patient 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 Iranian population and may help to improve 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)
• Findings identified eyes absent homolog 4 (EYA4) as a tumor suppressor that disrupts aberrant activation of the nuclear factor kappa B (NF-kappaB)/RAP1 protein signaling pathway and thus orchestrates a physiological impediment to hepatocellular carcinoma (HCC) growth and invasion. (PMID:29764501)
• Overexpression of EYA4 enhanced glioma cell proliferation, and EYA4 suppressed the expression of p27Kip1 directly in these cells. (PMID:30231237)
• the novel missense mutation c.1855T>G (p.W619G) in EYA4 causing autosomal dominant non-syndromic hearing impairment in the selected Chinese family, was identified. (PMID:30942159)
• EYA4 is a novel tumour suppressor in HCC and a new prognostic biomarker and therapeutic target in HCC. (PMID:30957411)
• Result show that EYA4 expression is regulated by miR626 which targets its 3’UTR in bladder cancer cells. (PMID:31101108)
• Study reports that EYA4 suppressed hepatocellular carcinoma (HCC) tumor cell growth by reducing the nuclear translocation of beta-catenin by dephosphorylation at Ser552, thereby suppressing the transcription of MYCBP which was induced by beta-catenin/LEF1 binding to the promoter of MYCBP. (PMID:31385398)
• Prevalence and clinical features of hearing loss caused by EYA4 variants. (PMID:32107406)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	eya4	ENSDARG00000012397
mus_musculus	Eya4	ENSMUSG00000010461
rattus_norvegicus	Eya4	ENSRNOG00000016627
drosophila_melanogaster	eya	FBGN0000320
caenorhabditis_elegans	eya-1	WBGENE00001377

Paralogs (3): EYA2 (ENSG00000064655), EYA1 (ENSG00000104313), EYA3 (ENSG00000158161)

Protein

Protein identifiers

Protein phosphatase EYA4 — O95677 (reviewed: O95677)

Alternative names: Eyes absent homolog 4

All UniProt accessions (9): O95677, A0A0S2Z3Q2, A0A0S2Z3V9, A0A804HHY3, A0A804HL00, A0A8C8KDW0, E7ESD5, E9PLN6, F2Z2Y1

UniProt curated annotations — full annotation on UniProt →

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.

Subunit / interactions. Interacts with SIX3; translocates EYA4 from the cytoplasm to the nucleus and promotes activation of their target genes.

Subcellular location. Cytoplasm. Nucleus.

Tissue specificity. Highly expressed in heart and skeletal muscle.

Disease relevance. Deafness, autosomal dominant, 10 (DFNA10) [MIM:601316] A form of non-syndromic sensorineural hearing loss. Sensorineural deafness results from damage to the neural receptors of the inner ear, the nerve pathways to the brain, or the area of the brain that receives sound information. The disease is caused by variants affecting the gene represented in this entry. 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. The disease is caused by variants affecting the gene represented in this entry.

Cofactor. Binds 1 Mg(2+) ion per subunit.

Miscellaneous. May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.

Similarity. Belongs to the HAD-like hydrolase superfamily. EYA family.

Isoforms (5)

UniProt ID	Names	Canonical?
O95677-1	1	yes
O95677-2	2
O95677-3	3
O95677-4	4
O95677-5	5

RefSeq proteins (7): NP_001287941, NP_001287942, NP_001357387, NP_001357388, NP_004091, NP_742101, NP_742103 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR006545	EYA_dom	Domain
IPR028472	EYA	Family
IPR038102	EYA_dom_sf	Homologous_superfamily
IPR042577	EYA_dom_metazoan	Domain

Pfam: PF00702

Catalyzed reactions (Rhea), 1 shown:

• O-phospho-L-tyrosyl-[protein] + H2O = L-tyrosyl-[protein] + phosphate (RHEA:10684)

UniProt features (29 total): splice variant 6, sequence variant 6, region of interest 3, binding site 3, compositionally biased region 3, modified residue 2, cross-link 2, active site 2, chain 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O95677-F1	63.79	0.41

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Catalytic / active sites (2): 375 (nucleophile); 377 (proton donor)

Ligand- & substrate-binding residues (3): 377; 603; 375

Post-translational modifications (4): 1, 361, 14, 52

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-5693565	Recruitment and ATM-mediated phosphorylation of repair and signaling proteins at DNA double strand breaks

MSigDB gene sets: 242 (showing top): BENPORATH_ES_WITH_H3K27ME3, GOBP_EXTRINSIC_APOPTOTIC_SIGNALING_PATHWAY, CERVERA_SDHB_TARGETS_1_DN, CHANDRAN_METASTASIS_DN, GOBP_REGULATION_OF_DNA_REPAIR, GTGCCTT_MIR506, GOBP_NEGATIVE_REGULATION_OF_EXTRINSIC_APOPTOTIC_SIGNALING_PATHWAY, GOBP_APOPTOTIC_SIGNALING_PATHWAY, GOBP_SENSORY_PERCEPTION_OF_LIGHT_STIMULUS, GOBP_REGULATION_OF_EXTRINSIC_APOPTOTIC_SIGNALING_PATHWAY, GOBP_REGULATION_OF_EXTRINSIC_APOPTOTIC_SIGNALING_PATHWAY_IN_ABSENCE_OF_LIGAND, TGTGTGA_MIR377, GOBP_REGULATION_OF_RESPONSE_TO_STRESS, GOBP_SIGNAL_TRANSDUCTION_IN_ABSENCE_OF_LIGAND, ZIC1_01

GO Biological Process (10): DNA repair (GO:0006281), chromatin organization (GO:0006325), visual perception (GO:0007601), anatomical structure morphogenesis (GO:0009653), cell differentiation (GO:0030154), positive regulation of DNA repair (GO:0045739), inner ear development (GO:0048839), negative regulation of extrinsic apoptotic signaling pathway in absence of ligand (GO:2001240), DNA damage response (GO:0006974), multicellular organism development (GO:0007275)

GO Molecular Function (5): protein tyrosine phosphatase activity (GO:0004725), metal ion binding (GO:0046872), phosphoprotein phosphatase activity (GO:0004721), protein binding (GO:0005515), hydrolase activity (GO:0016787)

GO Cellular Component (2): nucleus (GO:0005634), cytoplasm (GO:0005737)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
DNA Double Strand Break Response	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
anatomical structure development	3
DNA metabolic process	1
DNA damage response	1
cellular component organization	1
sensory perception of light stimulus	1
developmental process	1
cellular developmental process	1
DNA repair	1
regulation of DNA repair	1
positive regulation of response to stimulus	1
positive regulation of DNA metabolic process	1
ear development	1
extrinsic apoptotic signaling pathway in absence of ligand	1
negative regulation of signal transduction in absence of ligand	1
negative regulation of extrinsic apoptotic signaling pathway	1
regulation of extrinsic apoptotic signaling pathway in absence of ligand	1
cellular response to stress	1
multicellular organismal process	1
phosphoprotein phosphatase activity	1
cation binding	1
phosphatase activity	1
catalytic activity, acting on a protein	1
binding	1
catalytic activity	1
intracellular membrane-bounded organelle	1
intracellular anatomical structure	1
cellular anatomical structure	1

Protein interactions and networks

STRING

1382 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
EYA4	TCF21	O43680	806
EYA4	NLRX1	Q86UT6	789
EYA4	RBM20	Q5T481	739
EYA4	ABCC9	O60706	703
EYA4	TMPO	P08918	688
EYA4	NEXN	Q0ZGT2	655
EYA4	KCNQ4	P56696	646
EYA4	FKTN	O75072	622
EYA4	SIX4	Q9UIU6	609
EYA4	MYBPC3	Q14896	604
EYA4	DSG2	Q14126	602
EYA4	SIX1	Q15475	602
EYA4	CSRP3	P50461	592
EYA4	TCAP	O15273	589
EYA4	SGCD	Q92629	585
EYA4	SGK1	O00141	585

IntAct

24 interactions, top by confidence:

A	B	Type	Score
SIX2	EYA2	psi-mi:“MI:0914”(association)	0.530
PFDN2	CDC40	psi-mi:“MI:0914”(association)	0.530
EYA4	AATK	psi-mi:“MI:0915”(physical association)	0.370
EYA4	ERBB3	psi-mi:“MI:0915”(physical association)	0.370
FOXJ2	TCERG1	psi-mi:“MI:0914”(association)	0.350
PIP	RBM47	psi-mi:“MI:0914”(association)	0.350
SIX5	PPM1G	psi-mi:“MI:0914”(association)	0.350
SIX1	EYA4	psi-mi:“MI:0914”(association)	0.350
GATA2	BCL9	psi-mi:“MI:2364”(proximity)	0.270
HNF1B	BCL9	psi-mi:“MI:2364”(proximity)	0.270
SOX15	SMCHD1	psi-mi:“MI:2364”(proximity)	0.270
SP7	IGF2BP3	psi-mi:“MI:2364”(proximity)	0.270
TLX1	BCL9	psi-mi:“MI:2364”(proximity)	0.270
EYA4	PPIP5K2	psi-mi:“MI:0915”(physical association)	0.000
EYA4	SEC24B	psi-mi:“MI:0915”(physical association)	0.000
EYA4	UBE2D2	psi-mi:“MI:0915”(physical association)	0.000
EYA4	PLEC	psi-mi:“MI:0915”(physical association)	0.000
EYA4	QSER1	psi-mi:“MI:0915”(physical association)	0.000
EYA4	AAK1	psi-mi:“MI:0915”(physical association)	0.000
EYA4	CCDC88A	psi-mi:“MI:0915”(physical association)	0.000
EYA4	LUZP1	psi-mi:“MI:0915”(physical association)	0.000
EYA4	URGCP	psi-mi:“MI:0915”(physical association)	0.000
EYA4	DVL3	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (273): EYA4 (Affinity Capture-MS), EYA4 (Affinity Capture-MS), DCTPP1 (Affinity Capture-MS), ERC1 (Affinity Capture-MS), RPA2 (Affinity Capture-MS), RPA3 (Affinity Capture-MS), SIX2 (Affinity Capture-MS), SIX4 (Affinity Capture-MS), SUPT5H (Affinity Capture-MS), EYA4 (Affinity Capture-MS), DCTPP1 (Affinity Capture-MS), SCO1 (Affinity Capture-MS), EOGT (Affinity Capture-MS), SLC25A15 (Affinity Capture-MS), SCO2 (Affinity Capture-MS)

ESM2 similar proteins: A0A1P8AS03, A3LX75, A5DDB7, D5MCN2, F4IUY8, F4K1Z0, G4NID8, M2TGT8, M2U3Z7, O13987, O17670, O60167, O61708, O74345, O74412, O95677, P25644, P34643, P53297, P97767, Q05672, Q07998, Q08400, Q09750, Q09801, Q10655, Q10667, Q18273, Q20374, Q20870, Q2L4W6, Q3MK94, Q3S405, Q61X54, Q6E3D2, Q6E3D4, Q6FLG1, Q6FSQ6, Q75BK1, Q7ZT82

Diamond homologs: O00167, O08575, O82162, O95677, P97480, P97767, Q05201, Q58DB6, Q99502, Q99504, Q9YH98, Q9YH99, Q9YHA0, Q9YHA1, Q9Z191, O17670

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

1031 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	48
Likely pathogenic	31
Uncertain significance	533
Likely benign	301
Benign	52

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1185054	NM_004100.5(EYA4):c.964C>T (p.Gln322Ter)	Pathogenic
1185589	NM_004100.5(EYA4):c.580+2T>C	Pathogenic
1185629	NM_004100.5(EYA4):c.804+2T>A	Pathogenic
1185652	NM_004100.5(EYA4):c.804+2del	Pathogenic
1210331	NM_004100.5(EYA4):c.1154C>A (p.Ser385Ter)	Pathogenic
1322847	NM_004100.5(EYA4):c.1026_1027dup (p.Thr343fs)	Pathogenic
1322854	NM_004100.5(EYA4):c.1048_1049dup (p.Arg352fs)	Pathogenic
1380128	NM_004100.5(EYA4):c.832C>T (p.Gln278Ter)	Pathogenic
1419206	NM_004100.5(EYA4):c.67C>T (p.Gln23Ter)	Pathogenic
1808956	GRCh37/hg19 6q23.2(chr6:133522860-134541311)x1	Pathogenic
1916328	NM_004100.5(EYA4):c.223_224del (p.Val75fs)	Pathogenic
1965243	NM_004100.5(EYA4):c.242G>A (p.Trp81Ter)	Pathogenic
2112319	NM_004100.5(EYA4):c.1574G>A (p.Trp525Ter)	Pathogenic
2126137	NM_004100.5(EYA4):c.1472del (p.Leu491fs)	Pathogenic
236032	NM_004100.5(EYA4):c.441del (p.Tyr148fs)	Pathogenic
2425022	NC_000006.11:g.(?133782232)(133783922_?)del	Pathogenic
2445629	NM_004100.5(EYA4):c.992dup (p.Ser331fs)	Pathogenic
2446670	NM_004100.5(EYA4):c.988C>T (p.Gln330Ter)	Pathogenic
2743050	NM_004100.5(EYA4):c.211G>T (p.Glu71Ter)	Pathogenic
2783559	NM_004100.5(EYA4):c.579C>G (p.Tyr193Ter)	Pathogenic
2833829	NM_004100.5(EYA4):c.1776dup (p.Gly593fs)	Pathogenic
3239625	GRCh37/hg19 6q23.2(chr6:133782252-133804253)x1	Pathogenic
3246004	NC_000006.11:g.(?133595919)(133595971_?)del	Pathogenic
3511153	NM_004100.5(EYA4):c.279del (p.Met93fs)	Pathogenic
3630137	NM_004100.5(EYA4):c.222del (p.Val75fs)	Pathogenic
3655361	NM_004100.5(EYA4):c.13C>T (p.Gln5Ter)	Pathogenic
3657058	NM_004100.5(EYA4):c.646C>T (p.Gln216Ter)	Pathogenic
3668390	NM_004100.5(EYA4):c.337_350del (p.Thr112_Gly113insTer)	Pathogenic
3685913	NM_004100.5(EYA4):c.616_617del (p.Ser206fs)	Pathogenic
3772603	NM_004100.5(EYA4):c.1269dup (p.Asn424Ter)	Pathogenic

SpliceAI

4787 predictions. Top by Δscore:

Variant	Effect	Δscore
6:133241746:CGAGG:C	donor_loss	1.0000
6:133241747:GAG:G	donor_gain	1.0000
6:133241747:GAGGT:G	donor_loss	1.0000
6:133241748:AGG:A	donor_loss	1.0000
6:133241749:GGTG:G	donor_loss	1.0000
6:133241750:G:C	donor_loss	1.0000
6:133241750:G:GG	donor_gain	1.0000
6:133274702:T:G	acceptor_gain	1.0000
6:133274708:T:A	acceptor_gain	1.0000
6:133274711:TTTA:T	acceptor_loss	1.0000
6:133274713:TA:T	acceptor_loss	1.0000
6:133274714:A:AG	acceptor_gain	1.0000
6:133274715:G:GA	acceptor_gain	1.0000
6:133274715:G:T	acceptor_loss	1.0000
6:133274715:GAT:G	acceptor_gain	1.0000
6:133274715:GATA:G	acceptor_gain	1.0000
6:133274809:AATCA:A	donor_gain	1.0000
6:133274810:ATCA:A	donor_gain	1.0000
6:133274811:TCA:T	donor_gain	1.0000
6:133274813:AGTAA:A	donor_loss	1.0000
6:133274814:G:GG	donor_gain	1.0000
6:133274815:TA:T	donor_loss	1.0000
6:133274816:AAGTC:A	donor_loss	1.0000
6:133398644:T:G	acceptor_gain	1.0000
6:133446609:T:TA	acceptor_gain	1.0000
6:133446612:T:A	acceptor_gain	1.0000
6:133446619:T:A	acceptor_gain	1.0000
6:133446751:GGAG:G	donor_gain	1.0000
6:133446752:GAGG:G	donor_gain	1.0000
6:133446752:GAGGT:G	donor_loss	1.0000

AlphaMissense

4168 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
6:133483039:T:C	F372S	1.000
6:133483042:T:A	V373D	1.000
6:133483044:T:A	W374R	1.000
6:133483044:T:C	W374R	1.000
6:133483045:G:C	W374S	1.000
6:133483046:G:C	W374C	1.000
6:133483046:G:T	W374C	1.000
6:133483048:A:C	D375A	1.000
6:133483053:G:C	D377H	1.000
6:133483054:A:C	D377A	1.000
6:133483054:A:T	D377V	1.000
6:133483057:A:T	E378V	1.000
6:133483060:C:T	T379I	1.000
6:133483071:T:C	F383L	1.000
6:133483073:T:A	F383L	1.000
6:133483073:T:G	F383L	1.000
6:133483074:C:G	H384D	1.000
6:133483081:T:C	L386P	1.000
6:133483084:T:A	L387H	1.000
6:133483084:T:C	L387P	1.000
6:133506130:G:A	G406R	1.000
6:133506130:G:C	G406R	1.000
6:133506131:G:A	G406E	1.000
6:133506134:T:C	L407P	1.000
6:133506143:A:T	E410V	1.000
6:133506144:A:C	E410D	1.000
6:133506144:A:T	E410D	1.000
6:133506154:T:C	F414L	1.000
6:133506155:T:C	F414S	1.000
6:133506155:T:G	F414C	1.000

dbSNP variants (sampled 300 via entrez): RS1000002767 (6:133490882 T>C), RS1000023310 (6:133381327 T>G), RS1000027181 (6:133278872 A>G), RS1000031267 (6:133318038 G>A,C), RS1000048055 (6:133333961 A>C), RS1000051989 (6:133318060 C>T), RS1000059224 (6:133260033 A>T), RS1000064526 (6:133405498 A>T), RS1000064572 (6:133299637 G>A,T), RS1000067185 (6:133422850 C>T), RS1000079360 (6:133364644 G>A), RS1000094068 (6:133374729 G>A), RS1000096522 (6:133405799 T>A,C), RS1000098998 (6:133445577 CTTTTTTT>C,CTTT,CTTTT,CTTTTT,CTTTTTT,CTTTTTTTT,CTTTTTTTTT,CTTTTTTTTTT,CTTTTTTTTTTTTT,CTTTTTTTTTTTTTT,CTTTTTTTTTTTTTTT,CTTTTTTTTTTTTTTTTTTTTTTTGTTTGTTTTTATATTTTCTTTTTTTTTTTTTTTAGTTTTTTTTTCTAGTTTCCTTTCCTTTTTTTTTTTTT,CTTTTTTTTTTTTTTTTTT,CTTTTTTTTTTTTTTTTTTT,CTTTTTTTTTTTTTTTTTTTTTTT), RS1000110115 (6:133511838 A>G)

Disease associations

OMIM: gene MIM:603550 | disease phenotypes: MIM:605362, MIM:601316, MIM:192600, MIM:115200

GenCC curated gene-disease

Disease	Classification	Inheritance
nonsyndromic genetic hearing loss	Definitive	Autosomal dominant
autosomal dominant nonsyndromic hearing loss 10	Definitive	Autosomal dominant
dilated cardiomyopathy 1J	Moderate	Autosomal dominant
autosomal dominant nonsyndromic hearing loss	Supportive	Autosomal dominant

ClinGen Gene-Disease Validity (2)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
nonsyndromic genetic hearing loss	Definitive	AD
dilated cardiomyopathy 1J	Limited	AD

Mondo (12): dilated cardiomyopathy 1J (MONDO:0011541), autosomal dominant nonsyndromic hearing loss 10 (MONDO:0011031), hearing loss disorder (MONDO:0005365), nonsyndromic genetic hearing loss (MONDO:0019497), dilated cardiomyopathy (MONDO:0005021), hypertrophic cardiomyopathy (MONDO:0005045), familial hypertrophic cardiomyopathy (MONDO:0024573), myoepithelial tumor (MONDO:0002380), congestive heart failure (MONDO:0005009), ventricular tachycardia (MONDO:0005477), familial dilated cardiomyopathy (MONDO:0016333), autosomal dominant nonsyndromic hearing loss (MONDO:0019587)

Orphanet (9): Sensorineural deafness with dilated cardiomyopathy (Orphanet:217622), Rare autosomal dominant non-syndromic sensorineural deafness type DFNA (Orphanet:90635), Rare non-syndromic genetic deafness (Orphanet:87884), Dilated cardiomyopathy (Orphanet:217604), Rare genetic deafness (Orphanet:96210), Rare hypertrophic cardiomyopathy (Orphanet:217569), Rare familial disorder with hypertrophic cardiomyopathy (Orphanet:99739), Familial dilated cardiomyopathy (Orphanet:217607), NON RARE IN EUROPE: Familial isolated hypertrophic cardiomyopathy (Orphanet:155)

HPO phenotypes

10 total (11 of 10 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000365	Hearing impairment
HP:0000403	Recurrent otitis media
HP:0000407	Sensorineural hearing impairment
HP:0001635	Congestive heart failure
HP:0001644	Dilated cardiomyopathy
HP:0001645	Sudden cardiac death
HP:0001699	Sudden death
HP:0005162	Abnormal left ventricular function
HP:0030872	Abnormal cardiac ventricular function
HP:0001639	Hypertrophic cardiomyopathy

GWAS associations

49 associations (top):

Study	Trait	p-value
GCST000189_13	Protein quantitative trait loci	1.000000e-06
GCST001520_10	Response to angiotensin II receptor blocker therapy	6.000000e-06
GCST001525_40	Visceral fat	9.000000e-06
GCST002493_5	Bone mineral density (paediatric, skull)	2.000000e-12
GCST002493_6	Bone mineral density (paediatric, skull)	8.000000e-17
GCST004136_25	Methadone dose in opioid dependence	6.000000e-06
GCST004292_20	Glomerular filtration rate (creatinine)	4.000000e-09
GCST004505_40	Waist-to-hip ratio adjusted for BMI (adjusted for smoking behaviour)	1.000000e-07
GCST004508_42	Waist-to-hip ratio adjusted for BMI in non-smokers	2.000000e-09
GCST006061_215	Atrial fibrillation	2.000000e-08
GCST006288_135	Heel bone mineral density	2.000000e-32
GCST006288_136	Heel bone mineral density	2.000000e-14
GCST006288_464	Heel bone mineral density	2.000000e-36
GCST006288_465	Heel bone mineral density	2.000000e-12
GCST006288_559	Heel bone mineral density	9.000000e-67
GCST006288_560	Heel bone mineral density	2.000000e-24
GCST006979_394	Heel bone mineral density	1.000000e-112
GCST006979_395	Heel bone mineral density	3.000000e-13
GCST006979_396	Heel bone mineral density	8.000000e-33
GCST007876_89	Estimated glomerular filtration rate	7.000000e-10
GCST007989_9	Facial morphology traits (63 three-dimensional facial segments)	6.000000e-12
GCST008058_79	Estimated glomerular filtration rate	5.000000e-23
GCST008059_72	Estimated glomerular filtration rate	8.000000e-22
GCST008156_26	Hip circumference adjusted for BMI	4.000000e-07
GCST008162_107	Hip circumference	7.000000e-06
GCST009028_4	Adverse response to drug	8.000000e-07
GCST010173_134	Triglyceride levels	2.000000e-09
GCST010244_326	Triglyceride levels	2.000000e-14
GCST011457_18	Asthma with severe exacerbations	6.000000e-07
GCST012125_6	Chronic pain	3.000000e-06

EFO canonical traits (10, from GWAS)

EFO ID	Trait name
EFO:0004815	alpha macroglobulin measurement
EFO:0007907	methadone dose measurement
EFO:0004318	smoking behavior
EFO:0007788	BMI-adjusted waist-hip ratio
EFO:0009270	heel bone mineral density
EFO:0008039	BMI-adjusted hip circumference
EFO:0009658	adverse effect
EFO:0004530	triglyceride measurement
EFO:0004980	appendicular lean mass
EFO:0004833	neutrophil count

MeSH disease descriptors (10)

Descriptor	Name	Tree numbers
D002311	Cardiomyopathy, Dilated	C14.280.195.160; C14.280.238.070; C16.320.488.750
D002312	Cardiomyopathy, Hypertrophic	C14.280.238.100; C14.280.484.048.750.070.160
D024741	Cardiomyopathy, Hypertrophic, Familial	C14.280.238.100.500; C14.280.484.048.750.070.160.500; C16.320.160
D034381	Hearing Loss	C09.218.458.341; C10.597.751.418.341; C23.888.592.763.393.341
D009208	Myoepithelioma	C04.557.435.585
D017180	Tachycardia, Ventricular	C14.280.067.845.940; C14.280.123.875.940; C23.550.073.845.940
C565337	Cardiomyopathy, Dilated, 1J (supp.)
C563354	Deafness, Autosomal Dominant 10 (supp.)
C580334	Nonsyndromic Deafness (supp.)
C536231	familial dilated cardiomyopathy (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs17301249	EYA4		0.00	0

CTD chemical–gene interactions

44 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, affects expression	7
trichostatin A	affects cotreatment, increases expression	3
sodium arsenite	affects methylation, increases expression, affects acetylation	2
entinostat	decreases expression, affects cotreatment	2
Vorinostat	affects cotreatment, increases expression	2
Tobacco Smoke Pollution	decreases expression, increases expression	2
Tretinoin	decreases expression	2
aristolochic acid I	decreases expression	1
TAK-243	increases sumoylation	1
methylmercuric chloride	decreases expression	1
methyleugenol	decreases expression	1
bisphenol A	increases expression	1
terbufos	increases methylation	1
arsenite	affects binding, decreases reaction	1
butyraldehyde	decreases expression	1
perfluorooctanoic acid	increases expression	1
manganese chloride	decreases expression	1
potassium chromate(VI)	decreases expression	1
CGP 52608	affects binding, increases reaction	1
perfluoro-n-nonanoic acid	decreases expression	1
monomethylarsonous acid	affects acetylation, affects methylation	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression, increases expression	1
2,2’,4,4’-tetrabromodiphenyl ether	increases expression	1
dorsomorphin	affects cotreatment, decreases expression, increases expression	1
(+)-JQ1 compound	increases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Arsenic Trioxide	decreases expression	1
Arsenic	affects methylation	1
Benzo(a)pyrene	affects methylation, decreases methylation	1
Carbamazepine	affects expression	1

Cellosaurus cell lines

4 cell lines: 4 induced pluripotent stem cell

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_E4DX	KEIUi004-A	Induced pluripotent stem cell	Female
CVCL_E4DY	KEIUi005-A	Induced pluripotent stem cell	Male
CVCL_E4DZ	KEIUi006-A	Induced pluripotent stem cell	Female
CVCL_E4E0	KEIUi007-A	Induced pluripotent stem cell	Male

Clinical trials (associated diseases)

301 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT00205881	PHASE4	COMPLETED	Bilateral Benefit in Adult Users of the HiRes 90K Bionic Ear System
NCT00331539	PHASE4	UNKNOWN	Relationship Between Auto NRT and Behavioural T & C Levels With the Nucleus Freedom Cochlear Implant
NCT00424307	PHASE4	UNKNOWN	Bilateral Cochlear Implant Benefit in Young Children
NCT00765635	PHASE4	COMPLETED	Chlorobutanol, Potassium Carbonate, and Irrigation in Cerumen Removal
NCT03321006	PHASE4	COMPLETED	Treating Hearing Loss to Improve Mood and Cognition in Older Adults
NCT01499901	PHASE3	WITHDRAWN	Comparison of the Bilateral Sequential and Simultaneous Cochlear Implantation in the Deaf Children
NCT02561091	PHASE3	COMPLETED	AM-111 in the Treatment of Acute Inner Ear Hearing Loss
NCT03331627	PHASE3	COMPLETED	Safety and Efficacy of STR001-IT and STR001-ER in Patients With SSHL
NCT05532657	PHASE3	ACTIVE_NOT_RECRUITING	ACHIEVE Brain Health Follow-Up Study
NCT00013455	PHASE2	COMPLETED	Quantifying Auditory Perceptual Learning Following Hearing Aid Fitting
NCT00323427	PHASE2	COMPLETED	Clinical Trial of the Living Well With Hearing Loss Workshop
NCT00552786	PHASE2	COMPLETED	Antioxidation Medication for Noise-induced Hearing Loss
NCT00802425	PHASE2	COMPLETED	Efficacy of AM-111 in Patients With Acute Sensorineural Hearing Loss
NCT01139281	PHASE2	COMPLETED	The Protective Effect of Ginkgo Biloba Extract on Cisplatin-induced Ototoxicity in Humans
NCT01451853	PHASE2	UNKNOWN	SPI-1005 for Prevention and Treatment of Chemotherapy Induced Hearing Loss
NCT01588925	PHASE2	COMPLETED	Hearing Preservation Using Dexamethasone and Hyaluronic Acid for Cochlear Implantation
NCT01773278	PHASE2	RECRUITING	Cholesterol and Antioxidant Treatment in Patients With Smith-Lemli-Opitz Syndrome (SLOS)
NCT02832128	PHASE2	COMPLETED	Evaluating Possible Improvement in Speech and Hearing Tests After 28 Days of Dosing of the Study Drug AUT00063 Compared to Placebo (QuicKfire)
NCT04915183	PHASE2	RECRUITING	Atorvastatin to Reduce Cisplatin-Induced Hearing Loss Among Individuals With Head and Neck Cancer
NCT05258773	PHASE2	COMPLETED	Evaluation of the Presence of SENS-401 in the Perilymph
NCT06340633	PHASE2	RECRUITING	SPI-1005 in Adults Receiving Cochlear Implant
NCT00582946	PHASE1	COMPLETED	Wide-Bandwidth Open Canal Hearing Aid For Better Multitalker Speech Understanding
NCT00584155	PHASE1	WITHDRAWN	Protection From Cisplatin Ototoxicity by Lactated Ringers
NCT01206829	PHASE1	UNKNOWN	Hearing Impairment, Cognitive Therapy and Coping
NCT01256229	PHASE1	COMPLETED	Outcomes In Children With Developmental Delay And Deafness
NCT01343394	PHASE1	WITHDRAWN	Safety of Autologous Human Umbilical Cord Blood Mononuclear Fraction to Treat Acquired Hearing Loss in Children
NCT01452607	PHASE1	COMPLETED	Study to Evaluate the Safety and Pharmacokinetics of SPI-1005
NCT02259595	PHASE1	COMPLETED	Study to Determine the Safety, Tolerability, and Pharmacokinetic Profile of HPN-07 and HPN-07 Plus NAC
NCT04041440	PHASE1	COMPLETED	Speech Recognition Training in Children With Hearing Loss
NCT07218913	PHASE1	RECRUITING	Testing the Addition of Pedmark to Cisplatin Chemotherapy for Reducing Drug-Induced Ear Damage in Men With Stage II-III Metastatic Testicular Germ Cell Tumors
NCT01802190	Not specified	TERMINATED	Prevalence of POU4F3 and SLC17A8 Mutations
NCT00486577	PHASE2/PHASE3	COMPLETED	Chronic Electrical Stimulation of the Auditory Cortex for Intractable Tinnitus
NCT00789061	PHASE2/PHASE3	UNKNOWN	Applying Proton Pump Inhibitor to Prevent and Treat Acute Fluctuating Hearing Loss in Patients With SLC26A4 Mutation
NCT01423409	PHASE2/PHASE3	COMPLETED	Multicenter Trial Assessing an Innovative VAS of Pain Among Deaf People
NCT05786378	PHASE2/PHASE3	UNKNOWN	Assessment of The Efficacy of Intratympanic Platelet Rich Plasma for Treatment of Sensorineural Hearing Loss.
NCT01108601	PHASE1/PHASE2	UNKNOWN	Transtympanic Ringer’s Lactate for the Prevention of Cisplatin Ototoxicity
NCT01621256	PHASE1/PHASE2	COMPLETED	Efficacy, Safety, and Tolerability of Ancrod in Patients With Sudden Hearing Loss
NCT06370351	PHASE1/PHASE2	RECRUITING	A Phase I/II Clinical Trial with SENS-501 in Children Suffering from Severe to Profound Hearing Loss Due to Otoferlin (OTOF) Mutations
NCT06545175	PHASE1/PHASE2	RECRUITING	Intracochlear Application of VSF1.01 for the Reduction of Cochlear Implant Surgery Related Trauma
NCT07304024	PHASE1/PHASE2	RECRUITING	A Treatment for a Form of Age-Related Central Auditory Processing Disorder Consisting of Clemastine Fumarate Plus Engineered Sound