EYA1

Summary

EYA1 (EYA transcriptional coactivator and phosphatase 1, HGNC:3519) is a protein-coding gene on chromosome 8q13.3, encoding Protein phosphatase EYA1 (Q99502). Functions both as protein phosphatase and as transcriptional coactivator for SIX1, and probably also for SIX2, SIX4 and SIX5. It is haploinsufficient (ClinGen: sufficient evidence).

This gene encodes a member of the eyes absent (EYA) family of proteins. The encoded protein may play a role in the developing kidney, branchial arches, eye, and ear. Mutations of this gene have been associated with branchiootorenal dysplasia syndrome, branchiootic syndrome, and sporadic cases of congenital cataracts and ocular anterior segment anomalies. A similar protein in mice can act as a transcriptional activator. Alternatively spliced transcript variants have been identified for this gene.

Source: NCBI Gene 2138 — RefSeq curated summary.

At a glance

• Gene–disease (curated): branchio-oto-renal syndrome (Definitive, ClinGen) — +2 more curated relationships
• GWAS associations: 30
• Clinical variants (ClinVar): 749 total — 146 pathogenic, 63 likely-pathogenic
• Phenotypes (HPO): 90
• Dosage sensitivity (ClinGen): haploinsufficiency sufficient evidence, triplosensitivity no evidence
• MANE Select transcript: NM_000503

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:3519
Approved symbol	EYA1
Name	EYA transcriptional coactivator and phosphatase 1
Location	8q13.3
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000104313
Ensembl biotype	protein_coding
OMIM	601653
Entrez	2138

Gene structure

Transcript identifiers

Ensembl transcripts: 31 — 20 protein_coding, 4 retained_intron, 4 protein_coding_CDS_not_defined, 3 nonsense_mediated_decay

ENST00000303824, ENST00000340726, ENST00000388740, ENST00000388741, ENST00000388742, ENST00000388743, ENST00000419131, ENST00000422295, ENST00000465115, ENST00000493349, ENST00000496494, ENST00000518177, ENST00000519927, ENST00000521794, ENST00000523327, ENST00000523987, ENST00000642391, ENST00000643681, ENST00000644229, ENST00000644424, ENST00000644712, ENST00000645451, ENST00000645793, ENST00000647540, ENST00000862515, ENST00000862516, ENST00000862517, ENST00000862518, ENST00000964980, ENST00000964981, ENST00000964982

RefSeq mRNA: 11 — MANE Select: NM_000503 NM_000503, NM_001288574, NM_001288575, NM_001370333, NM_001370334, NM_001370335, NM_001370336, NM_001411797, NM_172058, NM_172059, NM_172060

CCDS: CCDS34906, CCDS34907, CCDS47873, CCDS75750, CCDS94312, CCDS94313

Canonical transcript exons

ENST00000340726 — 18 exons

Exon	Start	End
ENSE00001371724	71361647	71362069
ENSE00001622503	71322199	71322268
ENSE00003458429	71334097	71334174
ENSE00003475632	71215614	71215728
ENSE00003476223	71215387	71215508
ENSE00003480021	71356462	71356511
ENSE00003480509	71317552	71317689
ENSE00003481860	71216965	71217023
ENSE00003521318	71354782	71354909
ENSE00003530837	71299047	71299233
ENSE00003544031	71197433	71199420
ENSE00003547586	71269740	71269823
ENSE00003564816	71299638	71299720
ENSE00003565963	71271758	71271897
ENSE00003591173	71211156	71211256
ENSE00003637241	71321734	71321879
ENSE00003642688	71244603	71244692
ENSE00003672874	71216692	71216852

Expression profiles

Bgee: expression breadth ubiquitous, 205 present calls, max score 94.48.

FANTOM5 (CAGE): breadth broad, TPM avg 3.2899 / max 124.9230, expressed in 612 samples.

FANTOM5 promoters (17 alternative TSS)

Promoter ID	TPM avg	Samples expressed
93540	0.8922	376
93534	0.7658	219
93547	0.2564	134
93538	0.2319	129
93543	0.2086	118
93548	0.1985	66
93537	0.1974	115
93541	0.1361	67
93536	0.1026	41
93535	0.0766	34

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
choroid plexus epithelium	UBERON:0003911	94.48	gold quality
urethra	UBERON:0000057	88.96	gold quality
mucosa of paranasal sinus	UBERON:0005030	88.75	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	87.82	gold quality
putamen	UBERON:0001874	87.22	gold quality
pituitary gland	UBERON:0000007	86.01	gold quality
bronchial epithelial cell	CL:0002328	85.42	gold quality
epithelium of bronchus	UBERON:0002031	85.26	gold quality
caudate nucleus	UBERON:0001873	84.88	gold quality
adenohypophysis	UBERON:0002196	84.83	gold quality
bronchus	UBERON:0002185	84.40	gold quality
periodontal ligament	UBERON:0008266	81.07	silver quality
nasal cavity epithelium	UBERON:0005384	81.06	gold quality
nucleus accumbens	UBERON:0001882	80.58	gold quality
nasal cavity mucosa	UBERON:0001826	80.25	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	80.02	gold quality
prostate gland	UBERON:0002367	79.00	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	78.45	gold quality
secondary oocyte	CL:0000655	77.87	gold quality
heart right ventricle	UBERON:0002080	77.14	gold quality
right uterine tube	UBERON:0001302	76.37	gold quality
heart left ventricle	UBERON:0002084	75.44	gold quality
cardiac ventricle	UBERON:0002082	75.35	gold quality
epithelium of nasopharynx	UBERON:0001951	74.82	gold quality
nasopharynx	UBERON:0001728	74.81	gold quality
hindlimb stylopod muscle	UBERON:0004252	74.78	gold quality
vagina	UBERON:0000996	73.89	gold quality
ectocervix	UBERON:0012249	73.69	gold quality
biceps brachii	UBERON:0001507	72.87	gold quality
endothelial cell	CL:0000115	72.61	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-HCAD-10	yes	40.99
E-ANND-3	yes	6.72
E-GEOD-124858	no	1.29

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

3 targets.

Target	Regulation
GLI1	Activation
NRP1	Activation
NRP2	Activation

Upstream regulators (CollecTRI, top): ATF2, ATF3, ATF5, CEBPB, CEBPD, CEBPG, ETS2, HIF1A, HNF4A, HNRNPK, HR, HSF1, JUN, MYB, MYC, NFKB, NR2F2, PAX1, PAX3, PAX6, PROX1, REL, RORA, SIX1, SP1, STAT5A, TBX1, TP63, ZBTB17

miRNA regulators (miRDB)

203 targeting EYA1, 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-513A-5P	100.00	69.77	2465
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-4673	100.00	66.64	1490
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-4668-3P	100.00	68.74	2635
HSA-MIR-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-4776-3P	100.00	68.73	1340
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-3185	99.99	68.12	1959
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-4282	99.99	75.36	6408
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-12136	99.98	72.81	5713
HSA-MIR-8068	99.98	73.85	2376
HSA-MIR-19A-3P	99.98	75.33	2762
HSA-MIR-19B-3P	99.98	75.44	2754
HSA-LET-7F-2-3P	99.98	70.98	2588
HSA-MIR-1185-1-3P	99.98	71.04	2593
HSA-MIR-1185-2-3P	99.98	71.04	2593
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882

Functional genomics

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

Literature-anchored findings (GeneRIF, showing 40)

• Mutations in the EYA1 gene have been identified in both branchio-oto and branchio-oto-renal syndromes. (PMID:11683347)
• Defective protein-protein interactions of mutations in the EYA domain underlie brachio-oto-renal syndrome. (PMID:11950062)
• These results suggest that the S189G mutation is a candidate mutation for Branchio-Oto syndrome. (PMID:12701758)
• three Six1 mutations are crucial for Eya1-Six1 interaction, and the two mutations within the homeodomain region are essential for specific Six1-DNA binding (PMID:15141091)
• EYA1 mutation represents a previously undescribed cause of cardiofacial syndrome. (PMID:15493068)
• Mutations in the EYA1 gene on the chromosome band 8q13.3, have been identified to be the underlying genetic defects. We found a Korean family with BOR syndrome and identified a novel insertion mutation (c.1474_1475insC; R492PfsX40) in the EYA1 gene. (PMID:16005355)
• Point mutations altering the EYA1 reading frame, can be found in patients with oto-facio-cervical syndrome. (PMID:16441263)
• A novel EYA1 mutation was identified in a newborn with laryngomalacia, glossoptosis, retrognathism, and funnel chest. (PMID:16691597)
• We report a second Korean family with branchio-oto-renal syndrome with a novel nonsense EYA1 mutation (PMID:17049623)
• Four EYA1 mutations provide a molecular diagnosis of branchio-oto-renal syndrome in five out of six Danish families. (PMID:17637804)
• results indicate that mutations in EYA1 and TCF2 rarely result in an isolated Congenital anomalies of the kidney and urinary tract (CAKUT) phenotype. (PMID:18065799)
• EYA1 mutations were found in 31% of families fitting established clinical criteria for branchio-oto-renal syndrome (BOR) and 7% of families with questionable BOR phenotype (PMID:18220287)
• A mutation suggests that certain transcripts of EYA1 escape nonsense-mediated decay and encode truncated EYA proteins that may be capable of dominant-negative interactions producing distinct phenotypic features within the BOR spectrum. (PMID:19206155)
• Familial transmission of Goldenhar syndrome is not due to mutations in EYA1. (PMID:19213029)
• A novel one-base-pair deletion in the EYA1 gene, resulting in a truncated protein (c.321delT; p.Ala107fs), was found in Korean males with Branchio-oto-renal syndrome. (PMID:19667416)
• miR-562 expression is reduced in Wilms’ tumor and may contribute to tumorigenesis by deregulating target gene EYA1. (PMID:19789318)
• Hypomethylation of EYA1 in microtia may be related to the pathogenesis of the disease. (PMID:20209935)
• Data report the identification of the related proteins Sipl1 (Shank-interacting protein-like 1) and Rbck1 (RBCC protein interacting with PKC1) as novel interaction partners of Eya1. (PMID:20956555)
• This report describes the expanded phenotype of individuals, resulting from contiguous gene deletion involving the EYA1 gene and provides a molecular description of the genomic rearrangements involving this gene in branchio-oto-renal syndrome. (PMID:20979191)
• Study reports a screening of 140 patients from 124 families with Branchio-oto-renal and identified 36 EYA1 mutations in 42 unrelated patients, 2 mutations, and 1 change of unknown significance in SIX1 in 3 unrelated patients, but no mutation in SIX5. (PMID:21280147)
• A 23 year old woman with Branchio-oto-renal syndrome presented with a novel heterozygous mutation 1420-1421delCC in exon 14 of EYA-1 gene. (PMID:21955869)
• Two novel EYA1 mutations (c.466C>T and c.1735delG) were identified in two families with BOR syndrome. (PMID:22447252)
• EYA1 is efficiently degraded during mitotic exit in a ANAPC1-dependent manner and these two proteins physically interact. (PMID:23263983)
• A novel EYA1 splice site mutation was found to be associated with Branchio-Oto-Renal Syndrome and focal glomerulosclerosis. (PMID:23506628)
• results showed evidence of weak association between the two SNPs of EYA1 (rs13260349 and rs2380716) and nonsyndromic orofacial clefts. (PMID:23601008)
• The EYA1 phosphatase regulates cell-cycle control via transcriptional complex formation at the cyclin D1 promoter. (PMID:23636126)
• Novel EYA1 mutations may add to the genotypic and phenotypic spectrum of BOR syndrome in the East Asian population. (PMID:23840632)
• Low EYA1 expression is associated with gastric carcinoma. (PMID:24729159)
• Three causative genes for BOR syndrome have been reported thus far: EYA1, SIX1, and SIX5, but the causative genes for approximately half of all BOR patients remain unknown.[review] (PMID:24730701)
• PI3K/Akt signaling enhances Eya1 transcription activity, which largely attributes to the phosphorylation-induced reduction of Eya1 SUMOylation. (PMID:24954506)
• Association between EYA1 three SNPs and NSOCs and suggested that maternal environmental tobacco smoke, common cold history, and alcohol consumption. (PMID:25640282)
• we proved that the branchiooto (BO) syndrome in these cases was caused by germinal mosaicism of the EYA1 gene in either the mother or father. (PMID:25780253)
• Our findings implicate this EYA1 partial duplication segregating with branchiootic phenotype in a Brazilian pedigree and is the first description of a large duplication leading to the Branchiootorenal syndrome/BO syndrom (PMID:25926005)
• miR-101 is downregulated in breast cancer, and can inhibit cell proliferation and promote apoptosis by targeting EYA1 through the Notch signaling pathway. (PMID:27082308)
• Results found that EYA1 affects FBW7-Myc binding to regulate the FBW7-mediated Myc degradation machinery in breast cancer cells. (PMID:27795300)
• These results identify the conserved arginine residues of EYA1 that play an important role for its activity, thus implicating arginine methylation as a novel regulatory mechanism of EYA function. (PMID:28213359)
• A variety of DNA changes including large deletions underlie BOR syndrome in different populations, which can be detected with comprehensive genetic testing (PMID:28583505)
• SIX1/EYA1 mutations might be partially responsible for conotruncal heart defects. (PMID:29043394)
• Protein Eya1 is essential in regulating cancer cell-mediated angiogenesis and contributes to tumor growth. (PMID:29496520)
• The affected members harbored a novel heterozygous nonsense variation in exon 11 of EYA1. (PMID:30086703)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	eya1	ENSDARG00000014259
mus_musculus	Eya1	ENSMUSG00000025932
rattus_norvegicus	Eya1	ENSRNOG00000007590
drosophila_melanogaster	eya	FBGN0000320
caenorhabditis_elegans	eya-1	WBGENE00001377

Paralogs (3): EYA2 (ENSG00000064655), EYA4 (ENSG00000112319), EYA3 (ENSG00000158161)

Protein

Protein identifiers

Protein phosphatase EYA1 — Q99502 (reviewed: Q99502)

Alternative names: Eyes absent homolog 1

All UniProt accessions (11): A0A2R8Y6K4, A0A2R8YET7, A0A2R8YF73, A0A2R8YFS6, A0A2R8YGM9, A6NCB9, Q99502, E5RHZ7, E5RIQ7, E7EQM5, F8WB53

UniProt curated annotations — full annotation on UniProt →

Function. Functions both as protein phosphatase and as transcriptional coactivator for SIX1, and probably also for SIX2, SIX4 and SIX5. Tyrosine phosphatase that dephosphorylates ‘Tyr-142’ of histone H2AX (H2AXY142ph) and promotes efficient DNA repair via the recruitment of DNA repair complexes containing MDC1. ‘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. Its function as histone phosphatase may contribute to its function in transcription regulation during organogenesis. Also has phosphatase activity with proteins phosphorylated on Ser and Thr residues (in vitro). Required for normal embryonic development of the craniofacial and trunk skeleton, kidneys and ears. Together with SIX1, it plays an important role in hypaxial muscle development; in this it is functionally redundant with EYA2.

Subunit / interactions. Probably interacts with SIX2, SIX4 and SIX5. Interacts with H2AX in response to DNA damage. Interacts with SIX3; promotes EYA1 translocation to the nucleus.

Subcellular location. Cytoplasm. Nucleus.

Tissue specificity. In the embryo, highly expressed in kidney with lower levels in brain. Weakly expressed in lung. In the adult, highly expressed in heart and skeletal muscle. Weakly expressed in brain and liver. No expression in eye or kidney.

Post-translational modifications. Sumoylated with SUMO1.

Disease relevance. Branchiootorenal syndrome 1 (BOR1) [MIM:113650] A syndrome characterized by branchial cleft fistulas or cysts, sensorineural and/or conductive hearing loss, pre-auricular pits, structural defects of the outer, middle or inner ear, and renal malformations. The disease is caused by variants affecting the gene represented in this entry. Otofaciocervical syndrome 1 (OTFCS1) [MIM:166780] A disorder characterized by facial dysmorphism, cup-shaped low-set ears, preauricular fistulas, hearing loss, branchial defects, skeletal anomalies including vertebral defects, low-set clavicles, winged scapulae, sloping shoulders, and mild intellectual disability. The disease is caused by variants affecting the gene represented in this entry. Branchiootic syndrome 1 (BOS1) [MIM:602588] A syndrome characterized by usually bilateral branchial cleft fistulas or cysts, sensorineural and/or conductive hearing loss, pre-auricular pits, and structural defects of the outer, middle or inner ear. Otic defects include malformed and hypoplastic pinnae, a narrowed external ear canal, bulbous internal auditory canal, stapes fixation, malformed and hypoplastic cochlea. Branchial and otic anomalies overlap with those seen in individuals with the branchiootorenal syndrome. However renal anomalies are absent in branchiootic syndrome patients. The disease is caused by variants affecting the gene represented in this entry. Anterior segment anomalies with or without cataract (ASA) [MIM:602588] A disease characterized by various types of developmental eye anomalies, in the absence of other abnormalities. The phenotypic spectrum of anterior segment anomalies include central corneal opacity, Peters anomaly, and bilateral persistence of the pupillary membrane. Some patients have cataract. The disease is caused by variants affecting the gene represented in this entry.

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

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

Isoforms (3)

UniProt ID	Names	Canonical?
Q99502-1	EYA1A	yes
Q99502-2	EYA1B
Q99502-3	EYA1D

RefSeq proteins (11): NP_000494, NP_001275503, NP_001275504, NP_001357262, NP_001357263, NP_001357264, NP_001357265, NP_001398726, NP_742055, NP_742056, NP_742057 (=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), 3 shown:

• O-phospho-L-tyrosyl-[protein] + H2O = L-tyrosyl-[protein] + phosphate (RHEA:10684)
• O-phospho-L-seryl-[protein] + H2O = L-seryl-[protein] + phosphate (RHEA:20629)
• O-phospho-L-threonyl-[protein] + H2O = L-threonyl-[protein] + phosphate (RHEA:47004)

UniProt features (36 total): sequence variant 17, compositionally biased region 6, binding site 3, splice variant 3, region of interest 2, active site 2, chain 1, mutagenesis site 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q99502-F1	66.68	0.45

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): 330 (proton donor); 328 (nucleophile)

Ligand- & substrate-binding residues (3): 328; 330; 556

Mutagenesis-validated functional residues (1):

Position	Phenotype
328	loss of tyrosine phosphatase activity toward h2ax.

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-5693565	Recruitment and ATM-mediated phosphorylation of repair and signaling proteins at DNA double strand breaks
R-HSA-9830674	Formation of the ureteric bud

MSigDB gene sets: 596 (showing top): GSE45365_NK_CELL_VS_CD8_TCELL_DN, MORF_ITGA2, GOBP_MORPHOGENESIS_OF_AN_EPITHELIUM, AP1_01, GOBP_EMBRYO_DEVELOPMENT_ENDING_IN_BIRTH_OR_EGG_HATCHING, GOBP_RESPONSE_TO_IONIZING_RADIATION, GOBP_EPITHELIUM_DEVELOPMENT, YAATNRNNNYNATT_UNKNOWN, FREAC2_01, TAATAAT_MIR126, GOBP_MUSCLE_TISSUE_DEVELOPMENT, GOBP_METANEPHROS_DEVELOPMENT, GOBP_SKELETAL_SYSTEM_DEVELOPMENT, TGCTGCT_MIR15A_MIR16_MIR15B_MIR195_MIR424_MIR497, GOBP_FORMATION_OF_PRIMARY_GERM_LAYER

GO Biological Process (40): metanephros development (GO:0001656), branching involved in ureteric bud morphogenesis (GO:0001658), outflow tract morphogenesis (GO:0003151), double-strand break repair (GO:0006302), pattern specification process (GO:0007389), mesodermal cell fate specification (GO:0007501), sensory perception of sound (GO:0007605), anatomical structure morphogenesis (GO:0009653), response to ionizing radiation (GO:0010212), striated muscle tissue development (GO:0014706), protein sumoylation (GO:0016925), cell differentiation (GO:0030154), aorta morphogenesis (GO:0035909), outer ear morphogenesis (GO:0042473), middle ear morphogenesis (GO:0042474), regulation of neuron differentiation (GO:0045664), positive regulation of DNA repair (GO:0045739), positive regulation of transcription by RNA polymerase II (GO:0045944), neuron fate specification (GO:0048665), embryonic skeletal system morphogenesis (GO:0048704), semicircular canal morphogenesis (GO:0048752), epithelial cell proliferation (GO:0050673), positive regulation of epithelial cell proliferation (GO:0050679), pharyngeal system development (GO:0060037), otic vesicle morphogenesis (GO:0071600), positive regulation of secondary heart field cardioblast proliferation (GO:0072513), cochlea morphogenesis (GO:0090103), extrinsic apoptotic signaling pathway in absence of ligand (GO:0097192), negative regulation of extrinsic apoptotic signaling pathway in absence of ligand (GO:2001240), ureteric bud development (GO:0001657), DNA repair (GO:0006281), chromatin organization (GO:0006325), chromatin remodeling (GO:0006338), DNA damage response (GO:0006974), multicellular organism development (GO:0007275), animal organ morphogenesis (GO:0009887), inner ear morphogenesis (GO:0042472), cell fate commitment (GO:0045165), positive regulation of DNA-templated transcription (GO:0045893), otic vesicle development (GO:0071599)

GO Molecular Function (8): RNA binding (GO:0003723), protein serine/threonine phosphatase activity (GO:0004722), protein tyrosine phosphatase activity (GO:0004725), metal ion binding (GO:0046872), histone H2AXY142 phosphatase activity (GO:0140793), phosphoprotein phosphatase activity (GO:0004721), protein binding (GO:0005515), hydrolase activity (GO:0016787)

GO Cellular Component (6): nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), nuclear body (GO:0016604), protein-DNA complex (GO:0032993), protein-containing complex (GO:0032991)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
DNA Double Strand Break Response	1
Kidney development	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
DNA repair	2
cell fate specification	2
ear morphogenesis	2
embryonic morphogenesis	2
phosphoprotein phosphatase activity	2
cellular anatomical structure	2
kidney development	1
branching morphogenesis of an epithelial tube	1
ureteric bud morphogenesis	1
heart morphogenesis	1
anatomical structure morphogenesis	1
multicellular organism development	1
multicellular organismal process	1
mesodermal cell fate commitment	1
sensory perception of mechanical stimulus	1
developmental process	1
anatomical structure development	1
response to radiation	1
muscle tissue development	1
peptidyl-lysine modification	1
protein modification by small protein conjugation	1
cellular developmental process	1
aorta development	1
artery morphogenesis	1
neuron differentiation	1
regulation of cell differentiation	1
regulation of DNA repair	1
positive regulation of response to stimulus	1
positive regulation of DNA metabolic process	1
regulation of transcription by RNA polymerase II	1
transcription by RNA polymerase II	1
positive regulation of DNA-templated transcription	1
neuron fate commitment	1
embryonic organ morphogenesis	1
skeletal system morphogenesis	1
embryonic skeletal system development	1
nucleic acid binding	1
cation binding	1
histone phosphatase activity	1
phosphatase activity	1

Protein interactions and networks

STRING

1728 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
EYA1	SIX1	Q15475	986
EYA1	TLX1	P31314	948
EYA1	DACH1	Q9UI36	921
EYA1	SIX2	Q9NPC8	915
EYA1	SIX5	Q8N196	893
EYA1	PAX2	Q02962	872
EYA1	PAX3	P23760	851
EYA1	SALL1	Q9NSC2	832
EYA1	SIX4	Q9UIU6	772
EYA1	PAX1	P15863	768
EYA1	NDUFB9	Q9Y6M9	763
EYA1	MEIS1	O00470	715
EYA1	MYF5	P13349	694
EYA1	MYC	P01106	693
EYA1	HOXA11	P31270	662

IntAct

16 interactions, top by confidence:

A	B	Type	Score
SIX1	EYA1	psi-mi:“MI:0915”(physical association)	0.740
EYA1	PTPN9	psi-mi:“MI:0914”(association)	0.530
SIX2	EYA2	psi-mi:“MI:0914”(association)	0.530
H2AX	EYA1	psi-mi:“MI:0915”(physical association)	0.400
Eya3	EYA1	psi-mi:“MI:0915”(physical association)	0.400
EYA1	HSP90B1	psi-mi:“MI:0915”(physical association)	0.400
SIX2	EYA4	psi-mi:“MI:0914”(association)	0.350
SIX1	EYA4	psi-mi:“MI:0914”(association)	0.350
EYA1	SPAG9	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	EYA1	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (62): EYA1 (Affinity Capture-MS), H2AFX (Biochemical Activity), MYC (Biochemical Activity), EYA1 (Affinity Capture-Western), MYC (Affinity Capture-Western), FBXW7 (Affinity Capture-Western), ATP6V1B2 (Affinity Capture-MS), BANF1 (Affinity Capture-MS), DPYSL3 (Affinity Capture-MS), GRPEL1 (Affinity Capture-MS), RPA1 (Affinity Capture-MS), RPA2 (Affinity Capture-MS), RPA3 (Affinity Capture-MS), SIX2 (Affinity Capture-MS), SIX4 (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

1 interactions.

A	Effect	B	Mechanism
EYA1	down-regulates	H2AX	dephosphorylation

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	146
Likely pathogenic	63
Uncertain significance	277
Likely benign	119
Benign	58

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1069048	NM_000503.6(EYA1):c.1698+1G>T	Pathogenic
1069049	NM_000503.6(EYA1):c.1644del (p.Val549fs)	Pathogenic
1072507	NM_000503.6(EYA1):c.1476-2A>T	Pathogenic
1202644	NM_000503.6(EYA1):c.1425del (p.Asp476fs)	Pathogenic
1202645	NM_000503.6(EYA1):c.1140+1G>A	Pathogenic
1297081	NM_000503.6(EYA1):c.639+2T>G	Pathogenic
1328426	NM_000503.6(EYA1):c.1496_1499del (p.Ile498_Leu499insTer)	Pathogenic
1340774	GRCh37/hg19 8q13.2-13.3(chr8:69894553-72597645)x1	Pathogenic
1370990	NM_000503.6(EYA1):c.1315del (p.Arg439fs)	Pathogenic
1391097	NM_000503.6(EYA1):c.1619_1620del (p.Arg540fs)	Pathogenic
1422984	NM_000503.6(EYA1):c.1272dup (p.Arg425fs)	Pathogenic
1428718	NM_000503.6(EYA1):c.782del (p.Pro261fs)	Pathogenic
1433497	NM_000503.6(EYA1):c.355C>T (p.Gln119Ter)	Pathogenic
1452496	NC_000008.10:g.(?72111575)(72267140_?)del	Pathogenic
1453510	NM_000503.6(EYA1):c.490dup (p.Leu164fs)	Pathogenic
145425	GRCh38/hg38 8q13.2-13.3(chr8:68987881-71640028)x1	Pathogenic
1455041	NM_000503.6(EYA1):c.1182dup (p.Asn395Ter)	Pathogenic
1457237	NM_000503.6(EYA1):c.1051-2A>G	Pathogenic
1457573	NC_000008.10:g.(?72123371)(72123511_?)del	Pathogenic
1457990	NM_000503.6(EYA1):c.1325_1326del (p.Lys442fs)	Pathogenic
1458401	NM_000503.6(EYA1):c.1236dup (p.Ala413fs)	Pathogenic
1459746	NM_000503.6(EYA1):c.1487_1488del (p.Val496fs)	Pathogenic
145997	GRCh38/hg38 8q13.3(chr8:71186873-71428549)x1	Pathogenic
1460082	NM_000503.6(EYA1):c.654T>G (p.Tyr218Ter)	Pathogenic
149198	GRCh38/hg38 8q13.2-13.3(chr8:68987835-71663466)x1	Pathogenic
1527439	GRCh37/hg19 8q13.2-13.3(chr8:69899336-72597645)	Pathogenic
163426	NM_172058.2(EYA1):c.(?-66)(*76_?)del	Pathogenic
163427	NM_000503.6(EYA1):c.1475+1G>C	Pathogenic
1704965	NM_000503.6(EYA1):c.1597+1G>C	Pathogenic
178857	NM_000503.6(EYA1):c.428G>A (p.Trp143Ter)	Pathogenic

SpliceAI

2795 predictions. Top by Δscore:

Variant	Effect	Δscore
8:71215381:GCTCA:G	donor_loss	1.0000
8:71215382:CTCA:C	donor_loss	1.0000
8:71215383:TCA:T	donor_loss	1.0000
8:71215384:CA:C	donor_loss	1.0000
8:71215386:C:CT	donor_loss	1.0000
8:71215508:CC:C	acceptor_loss	1.0000
8:71215509:C:CA	acceptor_loss	1.0000
8:71215509:C:CC	acceptor_gain	1.0000
8:71215510:T:G	acceptor_loss	1.0000
8:71216857:T:C	acceptor_gain	1.0000
8:71216861:A:C	acceptor_gain	1.0000
8:71217019:CATTC:C	acceptor_gain	1.0000
8:71217021:TTC:T	acceptor_gain	1.0000
8:71217022:TCCTA:T	acceptor_loss	1.0000
8:71217024:C:CC	acceptor_gain	1.0000
8:71217025:T:C	acceptor_loss	1.0000
8:71244601:A:AC	donor_gain	1.0000
8:71244602:C:CC	donor_gain	1.0000
8:71244602:CTT:C	donor_gain	1.0000
8:71269738:AC:A	donor_gain	1.0000
8:71269739:CC:C	donor_gain	1.0000
8:71269739:CCCT:C	donor_gain	1.0000
8:71269820:CTCT:C	acceptor_gain	1.0000
8:71269822:CT:C	acceptor_gain	1.0000
8:71299042:ATTAC:A	donor_loss	1.0000
8:71299043:TTAC:T	donor_loss	1.0000
8:71299044:TACCT:T	donor_loss	1.0000
8:71299045:ACCT:A	donor_loss	1.0000
8:71299046:C:CT	donor_loss	1.0000
8:71299238:C:CT	acceptor_gain	1.0000

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000000511 (8:71236742 T>C,G), RS1000016247 (8:71381229 T>G), RS1000033467 (8:71384769 G>A), RS1000043600 (8:71419652 T>C), RS1000062265 (8:71378335 C>G), RS1000063626 (8:71368708 A>G), RS1000065301 (8:71236568 T>C,G), RS1000068045 (8:71438196 A>G), RS1000069521 (8:71253045 A>G), RS1000075248 (8:71210553 G>T), RS1000082374 (8:71484759 C>A,T), RS1000092888 (8:71253611 A>C), RS1000108852 (8:71425271 G>C), RS1000111787 (8:71465218 T>C), RS1000113639 (8:71313451 T>G)

Disease associations

OMIM: gene MIM:601653 | disease phenotypes: MIM:113650, MIM:602588, MIM:166780, MIM:113620, MIM:600886

GenCC curated gene-disease

Disease	Classification	Inheritance
branchio-oto-renal syndrome	Definitive	Autosomal dominant
branchiootorenal syndrome 1	Definitive	Autosomal dominant
branchiootic syndrome	Supportive	Autosomal dominant

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
branchio-oto-renal syndrome	Definitive	AD

Mondo (13): branchio-oto-renal syndrome (MONDO:0007029), hearing loss disorder (MONDO:0005365), branchiootorenal syndrome 1 (MONDO:0007236), branchiootic syndrome 1 (MONDO:0011258), otofaciocervical syndrome 1 (MONDO:0024532), bilateral renal agenesis (MONDO:0015986), branchiooculofacial syndrome (MONDO:0007235), prostate cancer (MONDO:0008315), renal hypoplasia (MONDO:0019637), hereditary ataxia (MONDO:0100309), hereditary hyperferritinemia with congenital cataracts (MONDO:0010952), focal segmental glomerulosclerosis (MONDO:0100313), branchiootic syndrome (MONDO:0018878)

Orphanet (8): BOR syndrome (Orphanet:107), Renal agenesis, bilateral (Orphanet:1848), Branchio-oculo-facial syndrome (Orphanet:1297), Familial prostate cancer (Orphanet:1331), Rare genetic deafness (Orphanet:96210), Renal hypoplasia (Orphanet:93101), Hereditary ataxia (Orphanet:183518), Hereditary hyperferritinemia-cataract syndrome (Orphanet:163)

HPO phenotypes

90 total (30 of 90 shown, HPO-id order):

HPO	Term
HP:0000003	Multicystic kidney dysplasia
HP:0000006	Autosomal dominant inheritance
HP:0000074	Ureteropelvic junction obstruction
HP:0000076	Vesicoureteral reflux
HP:0000083	Renal insufficiency
HP:0000110	Renal dysplasia
HP:0000113	Polycystic kidney dysplasia
HP:0000122	Unilateral renal agenesis
HP:0000126	Hydronephrosis
HP:0000175	Cleft palate
HP:0000193	Bifid uvula
HP:0000218	High palate
HP:0000275	Narrow face
HP:0000276	Long face
HP:0000278	Retrognathia
HP:0000293	Full cheeks
HP:0000324	Facial asymmetry
HP:0000347	Micrognathia
HP:0000356	Abnormality of the outer ear
HP:0000359	Abnormality of the inner ear
HP:0000365	Hearing impairment
HP:0000369	Low-set ears
HP:0000370	Abnormality of the middle ear
HP:0000376	Incomplete partition of the cochlea type II
HP:0000377	Abnormal pinna morphology
HP:0000378	Cupped ear
HP:0000384	Preauricular skin tag
HP:0000394	Lop ear
HP:0000400	Macrotia
HP:0000402	Stenosis of the external auditory canal

GWAS associations

30 associations (top):

Study	Trait	p-value
GCST000081_4	Sleep-related phenotypes	3.000000e-06
GCST001737_17	Chronic obstructive pulmonary disease-related biomarkers	5.000000e-06
GCST002403_3	Longevity (85 years and older)	1.000000e-06
GCST002563_12	Hypospadias	2.000000e-12
GCST003989_7	Chin dimples	8.000000e-34
GCST004251_7	Paneth cell defects in Crohn’s disease	3.000000e-06
GCST004567_25	Waist-to-hip ratio adjusted for BMI (joint analysis for main effect and physical activity interaction)	1.000000e-08
GCST004567_7	Waist-to-hip ratio adjusted for BMI (joint analysis for main effect and physical activity interaction)	8.000000e-06
GCST004576_23	Waist-to-hip ratio adjusted for body mass index	1.000000e-06
GCST004576_49	Waist-to-hip ratio adjusted for body mass index	1.000000e-10
GCST004578_100	Waist-to-hip ratio adjusted for BMI in active individuals	5.000000e-06
GCST005956_46	Waist-to-hip ratio adjusted for BMI	3.000000e-07
GCST005962_26	Waist-to-hip ratio adjusted for BMI x sex x age interaction (4df test)	6.000000e-07
GCST006288_124	Heel bone mineral density	1.000000e-12
GCST006288_660	Heel bone mineral density	4.000000e-18
GCST006288_737	Heel bone mineral density	4.000000e-07
GCST006902_8	Adolescent idiopathic scoliosis	9.000000e-08
GCST006979_459	Heel bone mineral density	2.000000e-46
GCST006979_460	Heel bone mineral density	8.000000e-15
GCST006979_461	Heel bone mineral density	9.000000e-47
GCST006979_462	Heel bone mineral density	2.000000e-09
GCST009723_16	Vertical cup-disc ratio (adjusted for vertical disc diameter)	2.000000e-09
GCST009723_93	Vertical cup-disc ratio (adjusted for vertical disc diameter)	9.000000e-06
GCST009724_13	Vertical cup-disc ratio (multi-trait analysis)	6.000000e-10
GCST009724_14	Vertical cup-disc ratio (multi-trait analysis)	7.000000e-10
GCST011354_28	Bell’s palsy	1.000000e-06
GCST90011898_113	Alanine aminotransferase levels	5.000000e-08
GCST90011899_18	Aspartate aminotransferase levels	4.000000e-10
GCST90013663_51	Alanine aminotransferase levels	1.000000e-12
GCST90013664_52	Aspartate aminotransferase levels	2.000000e-16

EFO canonical traits (9, from GWAS)

EFO ID	Trait name
EFO:0004811	interleukin-8 measurement
EFO:0007963	abnormal paneth cell measurement
EFO:0007788	BMI-adjusted waist-hip ratio
EFO:0008002	physical activity measurement
EFO:0008007	age at assessment
EFO:0008343	sex interaction measurement
EFO:0009270	heel bone mineral density
EFO:0006939	cup-to-disc ratio measurement
EFO:0004736	aspartate aminotransferase measurement

MeSH disease descriptors (7)

Descriptor	Name	Tree numbers
D019280	Branchio-Oto-Renal Syndrome	C16.131.077.208; C16.131.260.090; C16.320.180.090
D005923	Glomerulosclerosis, Focal Segmental	C12.050.351.968.419.570.363.640; C12.200.777.419.570.363.660; C12.950.419.570.363.640
D034381	Hearing Loss	C09.218.458.341; C10.597.751.418.341; C23.888.592.763.393.341
D011471	Prostatic Neoplasms	C04.588.945.440.770; C12.100.500.260.750; C12.100.500.565.625; C12.200.294.260.750; C12.200.294.565.625; C12.200.758.409.750; C12.900.619.750
C537104	Branchiootic syndrome (supp.)
C531684	Hereditary spinal ataxia (supp.)
C538137	Hyperferritinemia, hereditary, with congenital cataracts (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

PharmGKB clinical annotations

1 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs12678747	Toxicity	3	aspirin	Peptic Ulcer Disease

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs12678747	EYA1	3	2.00	1	aspirin

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	increases expression, decreases expression, affects cotreatment	6
Tretinoin	affects cotreatment, decreases reaction, increases expression, decreases expression	3
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression, decreases reaction	2
Air Pollutants	affects cotreatment, affects expression, increases abundance, decreases expression	2
Tobacco Smoke Pollution	decreases expression	2
Aflatoxin B1	decreases methylation, increases methylation	2
bisphenol F	affects cotreatment, decreases methylation	1
alpha-pinene	affects cotreatment, affects expression, increases abundance	1
N(4)-hydroxycytidine	decreases expression	1
trichostatin A	increases expression	1
arsenite	affects binding, decreases reaction	1
sodium arsenite	decreases expression	1
tobacco tar	decreases expression, decreases reaction	1
benzo(e)pyrene	increases methylation	1
potassium chromate(VI)	decreases expression	1
diallyl disulfide	decreases expression, decreases reaction	1
aflatoxin B2	decreases methylation	1
nickel sulfate	decreases expression	1
methacrylaldehyde	affects expression, increases abundance, affects cotreatment	1
CGP 52608	affects binding, increases reaction	1
Chir 99021	affects cotreatment, increases expression, decreases reaction	1
ramelteon	decreases expression	1
nilotinib	decreases expression	1
dorsomorphin	affects cotreatment, increases expression	1
incobotulinumtoxinA	increases expression	1
Dabigatran	decreases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Sunitinib	decreases expression	1
Fulvestrant	affects cotreatment, decreases methylation	1
Microplastics	increases abundance, increases expression	1

Cellosaurus cell lines

5 cell lines: 5 embryonic stem cell

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

Cellosaurus	Name	Category	Sex
CVCL_A1P9	SEES3-1V human EYA1, clone1	Embryonic stem cell	Male
CVCL_A1Q0	SEES3-1V human EYA1, clone2	Embryonic stem cell	Male
CVCL_A1Q1	SEES3-1V human EYA1, clone3	Embryonic stem cell	Male
CVCL_Y322	SZ-BOR1	Embryonic stem cell	Female
CVCL_YL04	SZ-BOR2	Embryonic stem cell	Sex unspecified

Clinical trials (associated diseases)

300 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
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
NCT01109576	EARLY_PHASE1	COMPLETED	Workshops for Veterans With Vision and Hearing Loss