CDH23

Summary

CDH23 (cadherin related 23, HGNC:13733) is a protein-coding gene on chromosome 10q22.1, encoding Cadherin-23 (Q9H251). Cadherins are calcium-dependent cell adhesion proteins.

This gene is a member of the cadherin superfamily, whose genes encode calcium dependent cell-cell adhesion glycoproteins. The encoded protein is thought to be involved in stereocilia organization and hair bundle formation. The gene is located in a region containing the human deafness loci DFNB12 and USH1D. Usher syndrome 1D and nonsyndromic autosomal recessive deafness DFNB12 are caused by allelic mutations of this cadherin-like gene. Upregulation of this gene may also be associated with breast cancer. Alternative splice variants encoding different isoforms have been described.

Source: NCBI Gene 64072 — RefSeq curated summary.

At a glance

• Gene–disease (curated): Usher syndrome type 1 (Definitive, ClinGen) — +4 more curated relationships
• GWAS associations: 21
• Clinical variants (ClinVar): 5,717 total — 295 pathogenic, 295 likely-pathogenic
• Phenotypes (HPO): 153
• Dosage sensitivity (ClinGen): haploinsufficiency autosomal recessive, triplosensitivity unscored
• MANE Select transcript: NM_022124

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:13733
Approved symbol	CDH23
Name	cadherin related 23
Location	10q22.1
Locus type	gene with protein product
Status	Approved
Aliases	CDHR23
Ensembl gene	ENSG00000107736
Ensembl biotype	protein_coding
OMIM	605516
Entrez	64072

Gene structure

Transcript identifiers

Ensembl transcripts: 15 — 10 protein_coding, 2 retained_intron, 2 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

ENST00000224721, ENST00000299366, ENST00000398792, ENST00000398809, ENST00000442677, ENST00000461841, ENST00000466757, ENST00000470494, ENST00000475158, ENST00000616684, ENST00000642965, ENST00000643732, ENST00000644511, ENST00000646131, ENST00000647092

RefSeq mRNA: 7 — MANE Select: NM_022124 NM_001171930, NM_001171931, NM_001171932, NM_001171933, NM_001171934, NM_022124, NM_052836

CCDS: CCDS44429, CCDS81472, CCDS81473, CCDS86100

Canonical transcript exons

ENST00000224721 — 70 exons

Exon	Start	End
ENSE00000986868	71778189	71778308
ENSE00000986869	71779267	71779447
ENSE00000986871	71784287	71784420
ENSE00000986873	71785631	71785738
ENSE00000986874	71788940	71789042
ENSE00000986875	71790288	71790413
ENSE00000986876	71791132	71791335
ENSE00001185490	71725372	71725520
ENSE00001247641	71813244	71813348
ENSE00001247809	71793182	71793640
ENSE00001247854	71784891	71785100
ENSE00001247870	71777680	71777901
ENSE00001248267	71741694	71741921
ENSE00001710046	71712665	71712813
ENSE00001806487	71511120	71511212
ENSE00002434793	71643861	71643866
ENSE00002530035	71734656	71734658
ENSE00003240224	71677456	71677693
ENSE00003247526	71814952	71815947
ENSE00003251328	71570790	71570918
ENSE00003255225	71577914	71577992
ENSE00003255342	71695418	71695525
ENSE00003258202	71706897	71707049
ENSE00003281990	71687647	71687719
ENSE00003292133	71709098	71709211
ENSE00003297753	71615504	71615616
ENSE00003303308	71675112	71675176
ENSE00003326446	71690468	71690584
ENSE00003342406	71566742	71566936
ENSE00003353514	71704911	71705130
ENSE00003354801	71702022	71702211
ENSE00003366913	71679387	71679492
ENSE00003370016	71446318	71446395
ENSE00003384567	71510954	71511001
ENSE00003393272	71682445	71682572
ENSE00003403664	71694147	71694259
ENSE00003442884	71702549	71702694
ENSE00003443802	71617205	71617393
ENSE00003458662	71798354	71798578
ENSE00003465950	71806168	71806281
ENSE00003467826	71807516	71807767
ENSE00003467895	71807277	71807406
ENSE00003474708	71811315	71811435
ENSE00003487270	71805806	71805997
ENSE00003494739	71807846	71808007
ENSE00003500541	71802898	71803075
ENSE00003500988	71724045	71724105
ENSE00003516620	71811713	71811753
ENSE00003520926	71797104	71797220
ENSE00003529570	71739644	71739772
ENSE00003531821	71809820	71810076
ENSE00003534803	71799111	71799280
ENSE00003540881	71812480	71812609
ENSE00003543906	71810472	71810569
ENSE00003544841	71803209	71803420
ENSE00003545618	71812768	71812890
ENSE00003568091	71730469	71730604
ENSE00003574527	71645831	71645980
ENSE00003579161	71799492	71799629
ENSE00003648788	71740822	71740950
ENSE00003652114	71734240	71734341
ENSE00003653430	71811955	71812015
ENSE00003669097	71439827	71439898
ENSE00003676166	71811511	71811590
ENSE00003676587	71800636	71800755
ENSE00003691957	71738498	71738647
ENSE00003692112	71731987	71732375
ENSE00003720683	71510082	71510224
ENSE00003732465	71646459	71646617
ENSE00003893363	71396920	71397318

Expression profiles

Bgee: expression breadth ubiquitous, 161 present calls, max score 92.78.

FANTOM5 (CAGE): breadth broad, TPM avg 3.0277 / max 106.2591, expressed in 640 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
105420	2.9290	603
105427	0.0562	24
105425	0.0295	18
105428	0.0130	5

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
ventricular zone	UBERON:0003053	92.78	gold quality
left ovary	UBERON:0002119	90.91	gold quality
right ovary	UBERON:0002118	89.08	gold quality
right hemisphere of cerebellum	UBERON:0014890	88.23	gold quality
cerebellar hemisphere	UBERON:0002245	87.65	gold quality
cerebellar cortex	UBERON:0002129	87.62	gold quality
granulocyte	CL:0000094	86.27	gold quality
cerebellum	UBERON:0002037	86.02	gold quality
lower esophagus muscularis layer	UBERON:0035833	86.02	gold quality
right lobe of liver	UBERON:0001114	85.77	gold quality
lower esophagus	UBERON:0013473	85.77	gold quality
monocyte	CL:0000576	85.49	gold quality
leukocyte	CL:0000738	85.08	gold quality
ovary	UBERON:0000992	82.53	gold quality
sural nerve	UBERON:0015488	82.24	gold quality
omental fat pad	UBERON:0010414	82.10	gold quality
peritoneum	UBERON:0002358	82.05	gold quality
apex of heart	UBERON:0002098	81.62	gold quality
left uterine tube	UBERON:0001303	81.27	gold quality
adipose tissue of abdominal region	UBERON:0007808	81.12	gold quality
blood	UBERON:0000178	80.86	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	80.80	gold quality
right lung	UBERON:0002167	79.69	gold quality
ganglionic eminence	UBERON:0004023	79.53	gold quality
right testis	UBERON:0004534	79.10	gold quality
buccal mucosa cell	CL:0002336	79.01	silver quality
body of pancreas	UBERON:0001150	78.96	gold quality
left testis	UBERON:0004533	78.94	gold quality
upper lobe of left lung	UBERON:0008952	78.64	gold quality
hypothalamus	UBERON:0001898	77.17	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): NR1I2, TAL1

miRNA regulators (miRDB)

16 targeting CDH23, 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-9983-3P	99.94	71.48	3631
HSA-MIR-129-5P	99.88	70.26	3273
HSA-MIR-3660	99.68	67.33	1149
HSA-MIR-4526	99.68	67.07	1136
HSA-MIR-587	99.64	70.86	2611
HSA-MIR-4761-5P	99.51	66.69	804
HSA-MIR-513C-5P	99.50	68.42	1730
HSA-MIR-514B-5P	99.50	68.19	1766
HSA-MIR-4717-3P	99.06	66.34	1072
HSA-MIR-1178-3P	98.57	67.09	890
HSA-MIR-7158-3P	98.46	66.45	728
HSA-MIR-1910-3P	98.44	67.51	1695
HSA-MIR-6511A-5P	98.13	67.47	1770
HSA-MIR-4659B-5P	98.03	66.84	979
HSA-MIR-4659A-5P	98.03	66.42	819
HSA-MIR-6886-3P	96.96	66.36	844

Functional genomics

ClinGen dosage: haploinsufficiency 30 (autosomal recessive), triplosensitivity Not yet evaluated (unscored). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 40)

• Three novel CDH23 mutations have been identified in patients with Usher syndrome type 1D. (PMID:11857743)
• patients with mutations in CDH23 display a wide range of hearing loss and retinitis pigmentosa phenotypes (PMID:12075507)
• the shaping of the hair bundle relies on a functional unit composed of myosin VIIa, harmonin b and cadherin 23 that is essential to ensure the cohesion of the stereocilia (PMID:12485990)
• Mutations in the calcium-binding motifs of CDH23 and the 35delG mutation in GJB2 cause hearing loss in one family (PMID:12522556)
• CDH23 and PCDH15 play an essential long-term role in maintaining the normal organization of the stereocilia bundle. (PMID:15537665)
• Describes cloning of human and mouse isoforms B1, B2, C1 and C2. (PMID:15882574)
• Missense mutations in CDH23 have been associated with presbycusis and nonsyndromic prelingual hearing loss (DFNB12), whereas null alleles cause the majority of Usher syndrome (Usher 1D). (PMID:16550584)
• individuals with the rs1227049 CC genotype, rs3802711 TT genotype and GG genotype in the terminal position of exon 7 of CDH23 might be more susceptible to noise induced hearing loss. (PMID:16598924)
• Disease causing mutations were identified in 31 of the 34 families referred: 17 in MYO7A, 6 in CDH23, 6 in PCDH15, and 2 in USH1C. (PMID:16679490)
• the apparent occurrence of an unusual TG 3’ splice site in intron 11 is discussed (PMID:17672918)
• analysis of CDH23 mutations in Japanese patients with non-syndromic hearing loss (PMID:17850630)
• Four missense mutations have been described in USH1 patients in a homozygous state. (PMID:18273900)
• Molecular genetic analysis was performed in 11 patients and pathogenic mutations were identified in all cases: (mutation in cadherin 23 gene in 6 cases). Two new mutations in the CDH23 gene never reported were found. (PMID:18323324)
• 35 SNP-s were identified. The nonsynonymous SNPs localized to the part of the gene encoding the extracellular domain of Cadherin 23, (ectodomains 5, 13, 14, 15, 16, 17, 19, and 22). One amino acid change occurred at a conserved position in ectodomain 5. (PMID:18348277)
• Screening revealed that in Japanese, mutation in CDH23 is the major causes of hearing loss. (PMID:18368581)
• Based on our results it is estimated that about 20% of patients with Usher syndrome type I have CDH23 mutations. (PMID:18429043)
• The structures of the harmonin N-domain alone and in complex with the cadherin 23 internal peptide fragment uncovered the detailed binding mechanism of this interaction between harmonin and cadherin 23. (PMID:19297620)
• determined the structure of the extracellular cadherin (EC)1-EC2 domains of cadherin 23, which binds to protocadherin 15 to form tip links of mechanosensory hair cells. (PMID:20498078)
• Five mutations (three in MYO7A and two in CDH23) were identified in four of five unrelated patients with Usher syndrome type 1. (PMID:20844544)
• One non-syndromic deafness allele (DFNB12) in trans configuration to an Usher syndrome allele (USH1D) of CDH23 preserves vision and balance in deaf individuals, indicating that the DFNB12 allele is phenotypically dominant to an USH1D allele. (PMID:21940737)
• cadherin-23 is up-regulated in breast cancer tissue versus normal tissue and we propose that cadherin-23-mediated heterotypic adhesion between invading tumor cells and stromal fibroblasts may play a role in the metastatic cascade. (PMID:22413011)
• Despite that the Ahl allele of Cdh23 had been implicated with ARHI in mice, we found no positive association of the CDH23 tag SNP in intron 7 with ARHI in Han Chinese. (PMID:22581638)
• Large protein assemblies formed by multivalent interactions between cadherin23 and harmonin suggest a stable anchorage structure at the tip link of stereocilia (PMID:22879593)
• mutations of the CDH23 gene are an important cause of non-syndromic hearing loss. (PMID:22899989)
• Hearing loss was found to co-segregate with locus-specific STR markers for CDH23 in 1 Pakistani family. (PMID:23770805)
• Description of the spectrum of mutations in CDH23 in 374 families with autosomal recessive, non-syndromic hearing loss from India. (PMID:24416283)
• The results of this study confirm that CDH23 genetic variant may modify the susceptibility to noise-induced hearing loss development in humans (PMID:24448297)
• mutations in the CDH23 gene are one of the most important causes of non-syndromic hearing loss in East Asians. (PMID:24767429)
• possible role in the deterioration of kidney function [meta-analysis] (PMID:25493955)
• The results revealed that CDH23 mutations are highly prevalent in patients with congenital high-frequency sporadic or recessively inherited hearing loss (PMID:25963016)
• Four (3.1 %) of 128 children carried two CDH23 mutant alleles, and SLC26A4 and GJB2 accounted for 18.0 and 17.2 %, respectively and showed profound nonsyndromic sensorineural hearing loss with minimal residual hearing. (PMID:26264712)
• A new diagnosis of sector retinitis pigmentosa was found to have two novel compound heterozygous mutations in CDH23, including one missense (c.8530C > A; p.Pro2844Thr) and one splice-site (c.5820 + 5G > A) mutation. (PMID:26878454)
• data suggest that CDH23-C is a CAMSAP3/Marshalin-binding protein that can modify MT networks indirectly through its interaction with CAMSAP3/Marshalin. (PMID:27349180)
• an important contribution of CDH23 mutations to poslingual Sensorineural Hearing Loss (PMID:27792758)
• We have identified CDH23 mutations as a genetic risk factor for both familial and sporadic pituitary adenoma. (PMID:28413019)
• 19 variants including 6 pathogenic missense mutations were identified among South Indian assortative mating hearing-impaired individuals (PMID:29148562)
• Crystal structures showing 18 CDH23 extracellular cadherin (EC) repeats, including the most and least conserved, a fragment carrying disease mutations, and EC repeats with non-canonical Ca(2+)-binding motif sequences and unusual secondary structure. Deafness mutations’ effects on stability and affinity for Ca(2+). Additionally, contiguous CDH23 EC repeats reveals helicity and potential parallel dimerization faces. (PMID:30033219)
• data indicate the role of Cdh23 as a suppressor of cell migration. (PMID:30747484)
• High-Throughput Sequencing Identifies 3 Novel Susceptibility Genes for Hereditary Melanoma. (PMID:32276436)
• Gene polymorphisms in CDH23 might associate significantly with the risk of noise-induced hearing loss (PMID:32306668)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	cdh23	ENSDARG00000007561
mus_musculus	Cdh23	ENSMUSG00000012819
rattus_norvegicus	Cdh23	ENSRNOG00000033087

Paralogs (33): CDH1 (ENSG00000039068), CDH10 (ENSG00000040731), CDH3 (ENSG00000062038), CDH19 (ENSG00000071991), CDHR2 (ENSG00000074276), CDH17 (ENSG00000079112), CDH7 (ENSG00000081138), PCDH11Y (ENSG00000099715), CDHR5 (ENSG00000099834), CDH20 (ENSG00000101542), PCDH11X (ENSG00000102290), CDH9 (ENSG00000113100), CDH6 (ENSG00000113361), CDH26 (ENSG00000124215), CDHR3 (ENSG00000128536), CDH15 (ENSG00000129910), CDH24 (ENSG00000139880), CDH11 (ENSG00000140937), CDH13 (ENSG00000140945), CDH18 (ENSG00000145526), CDHR1 (ENSG00000148600), CDH22 (ENSG00000149654), CDH8 (ENSG00000150394), CDH12 (ENSG00000154162), PCDH1 (ENSG00000156453), DCHS1 (ENSG00000166341), PCDH7 (ENSG00000169851), CDH2 (ENSG00000170558), CDH4 (ENSG00000179242), CDH5 (ENSG00000179776), PCDH9 (ENSG00000184226), DCHS2 (ENSG00000197410), PCDH20 (ENSG00000280165)

Protein

Protein identifiers

Cadherin-23 — Q9H251 (reviewed: Q9H251)

Alternative names: Otocadherin

All UniProt accessions (10): Q9H251, A0A087WWD9, A0A087WYR8, A0A0A0MS94, A0A2R8Y663, A0A2R8Y6D5, A0A2R8YEM1, B1AVV0, Q8N5B3, R4GN92

UniProt curated annotations — full annotation on UniProt →

Function. Cadherins are calcium-dependent cell adhesion proteins. They preferentially interact with themselves in a homophilic manner in connecting cells. CDH23 is required for establishing and/or maintaining the proper organization of the stereocilia bundle of hair cells in the cochlea and the vestibule during late embryonic/early postnatal development. It is part of the functional network formed by USH1C, USH1G, CDH23 and MYO7A that mediates mechanotransduction in cochlear hair cells. Required for normal hearing.

Subunit / interactions. antiparallel heterodimer with PCDH15. Interacts with USH1C and USH1G.

Subcellular location. Cell membrane.

Tissue specificity. Particularly strong expression in the retina. Found also in the cochlea.

Disease relevance. Usher syndrome 1D (USH1D) [MIM:601067] USH is a genetically heterogeneous condition characterized by the association of retinitis pigmentosa with sensorineural deafness. Age at onset and differences in auditory and vestibular function distinguish Usher syndrome type 1 (USH1), Usher syndrome type 2 (USH2) and Usher syndrome type 3 (USH3). USH1 is characterized by profound congenital sensorineural deafness, absent vestibular function and prepubertal onset of progressive retinitis pigmentosa leading to blindness. The disease is caused by variants affecting the gene represented in this entry. Usher syndrome 1D/F (USH1DF) [MIM:601067] A digenic recessive form of Usher syndrome, a genetically heterogeneous condition characterized by the association of retinitis pigmentosa with sensorineural deafness. Age at onset and differences in auditory and vestibular function distinguish Usher syndrome type 1 (USH1), Usher syndrome type 2 (USH2) and Usher syndrome type 3 (USH3). USH1 is characterized by profound congenital sensorineural deafness, absent vestibular function and prepubertal onset of progressive retinitis pigmentosa leading to blindness. The disease is caused by variants affecting distinct genetic loci, including the gene represented in this entry. Deafness, autosomal recessive, 12 (DFNB12) [MIM:601386] 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. Pituitary adenoma 5, multiple types (PITA5) [MIM:617540] A form of pituitary adenoma, a neoplasm of the pituitary gland and one of the most common neuroendocrine tumors. Pituitary adenomas are clinically classified as functional and non-functional tumors, and manifest with a variety of features, including local invasion of surrounding structures and excessive hormone secretion. Functional pituitary adenomas are further classified by the type of hormone they secrete: growth hormone (GH)-secreting, prolactin (PRL)-secreting, adrenocorticotropin (ACTH)-secreting, thyroid-stimulating hormone (TSH)-secreting, and plurihormonal (GH and TSH) tumors. Familial and sporadic forms have been reported. The transmission pattern of familial PITA5 is consistent with autosomal dominant inheritance with reduced penetrance. Disease susceptibility is associated with variants affecting the gene represented in this entry.

Domain organisation. Three calcium ions are usually bound at the interface of each cadherin domain and rigidify the connections, imparting a strong curvature to the full-length ectodomain. Cadherin repeats 1 and 2 mediate calcium-dependent heterophilic interaction with PCDH15.

Isoforms (11)

UniProt ID	Names	Canonical?
Q9H251-1	1	yes
Q9H251-2	2
Q9H251-3	3
Q9H251-4	4
Q9H251-5	5
Q9H251-6	6
Q9H251-7	7, B1
Q9H251-8	8
Q9H251-9	9, B2
Q9H251-10	10, C1
Q9H251-11	11, C2

RefSeq proteins (7): NP_001165401, NP_001165402, NP_001165403, NP_001165404, NP_001165405, NP_071407, NP_443068 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002126	Cadherin-like_dom	Domain
IPR015919	Cadherin-like_sf	Homologous_superfamily
IPR020894	Cadherin_CS	Conserved_site

Pfam: PF00028

UniProt features (274 total): sequence variant 126, strand 41, glycosylation site 41, domain 27, helix 12, splice variant 11, turn 8, sequence conflict 3, topological domain 2, signal peptide 1, chain 1, transmembrane region 1

Structure

Experimental structures (PDB)

6 structures.

PDB	Method	Resolution (Å)
5WJ8	X-RAY DIFFRACTION	1.86
5TFM	X-RAY DIFFRACTION	2.92
5VVM	X-RAY DIFFRACTION	3.54
2KBR	SOLUTION NMR
2KBS	SOLUTION NMR
2LSR	SOLUTION NMR

Predicted structure (AlphaFold)

No AlphaFold model available for Q9H251 — AlphaFold DB does not currently provide models for proteins above ~3000 aa.

Functional residue map

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

Glycosylation sites (41): 155, 206, 349, 393, 434, 466, 472, 652, 694, 765, 810, 827, 941, 1001, 1018, 1171, 1282, 1315, 1473, 1534 …

Function

Pathways and Gene Ontology

Reactome pathways

4 pathways

ID	Pathway
R-HSA-9662360	Sensory processing of sound by inner hair cells of the cochlea
R-HSA-9662361	Sensory processing of sound by outer hair cells of the cochlea
R-HSA-9659379	Sensory processing of sound
R-HSA-9709957	Sensory Perception

MSigDB gene sets: 445 (showing top): GSE45365_NK_CELL_VS_CD8A_DC_DN, GSE45365_NK_CELL_VS_CD11B_DC_UP, AP1_01, GOBP_EPITHELIUM_DEVELOPMENT, BENPORATH_ES_WITH_H3K27ME3, GOBP_BEHAVIOR, GOBP_SENSORY_PERCEPTION_OF_MECHANICAL_STIMULUS, GOBP_NEUROGENESIS, TAL1ALPHAE47_01, GOCC_MICROTUBULE_ORGANIZING_CENTER, GOBP_NEUROMUSCULAR_PROCESS_CONTROLLING_BALANCE, GOBP_MONOATOMIC_CATION_TRANSPORT, GOBP_CALCIUM_DEPENDENT_CELL_CELL_ADHESION, GOBP_CELL_CELL_ADHESION, GOBP_EPIDERMAL_CELL_DIFFERENTIATION

GO Biological Process (21): calcium ion transport (GO:0006816), homophilic cell-cell adhesion (GO:0007156), visual perception (GO:0007601), sensory perception of sound (GO:0007605), locomotory behavior (GO:0007626), calcium-dependent cell-cell adhesion (GO:0016339), cell migration (GO:0016477), neuron projection development (GO:0031175), photoreceptor cell maintenance (GO:0045494), sensory perception of light stimulus (GO:0050953), equilibrioception (GO:0050957), regulation of cytosolic calcium ion concentration (GO:0051480), auditory receptor cell stereocilium organization (GO:0060088), cochlea development (GO:0090102), obsolete cell-cell adhesion via plasma-membrane adhesion molecules (GO:0098742), cell adhesion (GO:0007155), inner ear morphogenesis (GO:0042472), inner ear auditory receptor cell differentiation (GO:0042491), inner ear development (GO:0048839), inner ear receptor cell stereocilium organization (GO:0060122), cell-cell adhesion (GO:0098609)

GO Molecular Function (5): calcium ion binding (GO:0005509), beta-catenin binding (GO:0008013), cadherin binding (GO:0045296), protein binding (GO:0005515), metal ion binding (GO:0046872)

GO Cellular Component (11): photoreceptor inner segment (GO:0001917), centrosome (GO:0005813), membrane (GO:0016020), catenin complex (GO:0016342), stereocilium (GO:0032420), stereocilium tip (GO:0032426), kinocilium (GO:0060091), cochlear hair cell ribbon synapse (GO:0098683), photoreceptor ribbon synapse (GO:0098684), plasma membrane (GO:0005886), synapse (GO:0045202)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Sensory processing of sound	2
Sensory Perception	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
cell-cell adhesion	2
sensory perception	2
inner ear development	2
anatomical structure development	2
stereocilium bundle	2
neuron projection	2
ribbon synapse	2
metal ion transport	1
sensory perception of light stimulus	1
sensory perception of mechanical stimulus	1
behavior	1
cell motility	1
neuron development	1
plasma membrane bounded cell projection organization	1
retina homeostasis	1
multicellular organismal process	1
neuromuscular process controlling balance	1
intracellular calcium ion homeostasis	1
auditory receptor cell morphogenesis	1
inner ear receptor cell stereocilium organization	1
cellular process	1
ear morphogenesis	1
embryonic morphogenesis	1
hair cell differentiation	1
inner ear receptor cell differentiation	1
ear development	1
neuron projection development	1
inner ear receptor cell development	1
metal ion binding	1
protein binding	1
cell adhesion molecule binding	1
binding	1
cation binding	1
centriole	1
microtubule organizing center	1
extrinsic component of plasma membrane	1
plasma membrane protein complex	1
actin-based cell projection	1
stereocilium	1

Protein interactions and networks

STRING

1478 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CDH23	E9PNW1	E9PNW1	999
CDH23	MYO7A	P78427	998
CDH23	USH1G	Q495M9	992
CDH23	PCDH15	Q96QU1	992
CDH23	ADGRV1	Q8WXG9	970
CDH23	USH2A	O75445	947
CDH23	WHRN	Q9P202	943
CDH23	ATP2B2	Q01814	897
CDH23	TMC2	Q8TDI7	870
CDH23	CLRN1	P58418	849
CDH23	CIB2	O75838	841
CDH23	TMC1	Q8TDI8	834
CDH23	MYO15A	Q9UKN7	825
CDH23	OTOF	Q9HC10	815
CDH23	ATP2B4	P23634	798

IntAct

26 interactions, top by confidence:

A	B	Type	Score
USH1C	CDH23	psi-mi:“MI:0407”(direct interaction)	0.650
CDH23	USH1C	psi-mi:“MI:0407”(direct interaction)	0.650
CDH23	CDH23	psi-mi:“MI:0407”(direct interaction)	0.560
CDH23	Dlg4	psi-mi:“MI:0407”(direct interaction)	0.440
GHRH	CDH23	psi-mi:“MI:0915”(physical association)	0.400
DCAF4	IGLL5	psi-mi:“MI:0914”(association)	0.350
CDH23	GTPBP10	psi-mi:“MI:0914”(association)	0.350
CDH23	SGTA	psi-mi:“MI:0914”(association)	0.350
LIG3	POLR1A	psi-mi:“MI:0914”(association)	0.350
CDH23	NHERF2	psi-mi:“MI:0915”(physical association)	0.000
CDH23	NXN	psi-mi:“MI:0915”(physical association)	0.000
CDH23	CYFIP1	psi-mi:“MI:0915”(physical association)	0.000
CDH23	ABI1	psi-mi:“MI:0915”(physical association)	0.000
WASF1	CDH23	psi-mi:“MI:0915”(physical association)	0.000
CDH23	GOPC	psi-mi:“MI:0915”(physical association)	0.000
CDH23	NCKAP1	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (71): CDH23 (Biochemical Activity), CDH23 (Affinity Capture-MS), GOPC (Affinity Capture-MS), NCKAP1 (Affinity Capture-MS), ABI1 (Affinity Capture-MS), NXN (Affinity Capture-MS), CDH23 (Affinity Capture-MS), CYFIP1 (Affinity Capture-MS), SLC9A3R2 (Affinity Capture-MS), CDH23 (Affinity Capture-MS), CDH23 (Affinity Capture-MS), USH1C (Two-hybrid), USH1C (Reconstituted Complex), YEATS2 (Affinity Capture-MS), PCSK5 (Affinity Capture-MS)

ESM2 similar proteins: B0KW95, B2KI42, B4USZ0, O00222, O18926, O55075, O60245, O94779, P10288, P15116, P19022, P19534, P24503, P33145, P33150, P35400, P39038, P47743, P55283, P55290, P58365, P68500, P70579, P97527, Q07409, Q0E9H9, Q0ZM14, Q14831, Q3B7N0, Q5H8C1, Q5R5W6, Q5R9X1, Q5RDQ8, Q62682, Q62845, Q63149, Q68ED2, Q69Z26, Q8IWV2, Q90275

Diamond homologs: B2KI42, E9Q7P9, O18926, O54800, O55075, O93319, P08641, P20310, P30944, P33147, P55280, P55284, P55286, P55287, P55288, P58365, P97291, P97326, Q2PZL6, Q3SWX5, Q63418, Q6B457, Q6PB90, Q6PFX6, Q767I8, Q86UP0, Q8AYD0, Q8UVJ7, Q8VHP6, Q8WN91, Q90762, Q90Z37, Q91XU7, Q91XZ4, Q96JP9, Q99PF4, Q9BYE9, Q9H251, Q9QYP2, B4USZ0

SIGNOR signaling

3 interactions.

A	Effect	B	Mechanism
calcium(2+)	“up-regulates activity”	CDH23	“chemical activation”
CDH23	“up-regulates activity”	CTNNB1	binding
CDH23	“form complex”	“TIP-LINK complex”	binding

Disease & clinical

Clinical variants and AI predictions

ClinVar

5717 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	295
Likely pathogenic	295
Uncertain significance	1900
Likely benign	2487
Benign	215

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1027559	NM_022124.6(CDH23):c.7872+1G>A	Pathogenic
1027560	NM_022124.6(CDH23):c.271C>T (p.Gln91Ter)	Pathogenic
1064608	NM_022124.6(CDH23):c.1291-1G>A	Pathogenic
1066040	NM_022124.6(CDH23):c.9319+1G>C	Pathogenic
1066661	NM_022124.6(CDH23):c.9278+2T>G	Pathogenic
1067318	NM_022124.6(CDH23):c.6049+1G>T	Pathogenic
1067877	NC_000010.10:g.(?73544034)(73556987_?)del	Pathogenic
1070107	NM_022124.6(CDH23):c.5201del (p.Val1734fs)	Pathogenic
1070249	NM_022124.6(CDH23):c.8106C>G (p.Tyr2702Ter)	Pathogenic
1071246	NM_022124.6(CDH23):c.4299del (p.Val1434fs)	Pathogenic
1071392	NC_000010.10:g.(?73442182)(73442349_?)del	Pathogenic
1071750	NM_022124.6(CDH23):c.65G>A (p.Trp22Ter)	Pathogenic
1071894	NM_022124.6(CDH23):c.7221C>A (p.Tyr2407Ter)	Pathogenic
1071895	NM_022124.6(CDH23):c.8432G>A (p.Trp2811Ter)	Pathogenic
1071896	NM_022124.6(CDH23):c.9389_9390del (p.Pro3130fs)	Pathogenic
1072139	NM_022124.6(CDH23):c.7921G>A (p.Asp2641Asn)	Pathogenic
1072143	NM_022124.6(CDH23):c.2719dup (p.Val907fs)	Pathogenic
1073301	NC_000010.10:g.(?73269819)(73270989_?)del	Pathogenic
1073475	NM_022124.6(CDH23):c.9167del (p.Val3056fs)	Pathogenic
1074713	NM_022124.6(CDH23):c.214G>T (p.Glu72Ter)	Pathogenic
1076701	NM_022124.6(CDH23):c.227_233dup (p.Phe78fs)	Pathogenic
1076702	NM_022124.6(CDH23):c.1446_1447insTT (p.Leu483fs)	Pathogenic
1185586	NM_022124.5(CDH23):c.337del	Pathogenic
1322047	NM_022124.6(CDH23):c.9296del (p.Lys3099fs)	Pathogenic
1341497	NM_022124.6(CDH23):c.5535C>A (p.Asn1845Lys)	Pathogenic
1352013	NM_022124.6(CDH23):c.5306_5307del (p.His1769fs)	Pathogenic
1352849	NM_022124.6(CDH23):c.4274del (p.Ala1425fs)	Pathogenic
1353385	NM_022124.6(CDH23):c.1521_1542del (p.Leu508fs)	Pathogenic
1355793	NM_022124.6(CDH23):c.2853_2865del (p.Glu952fs)	Pathogenic
1359389	NM_022124.6(CDH23):c.9466_9500del (p.Leu3156fs)	Pathogenic

SpliceAI

16145 predictions. Top by Δscore:

Variant	Effect	Δscore
10:71510070:T:TA	acceptor_gain	1.0000
10:71510071:G:A	acceptor_gain	1.0000
10:71510075:A:AG	acceptor_gain	1.0000
10:71510080:A:AG	acceptor_gain	1.0000
10:71510081:G:GA	acceptor_gain	1.0000
10:71510081:GGT:G	acceptor_gain	1.0000
10:71510081:GGTTC:G	acceptor_gain	1.0000
10:71510220:GAGAG:G	donor_gain	1.0000
10:71510222:GAG:G	donor_gain	1.0000
10:71510224:GGT:G	donor_loss	1.0000
10:71510225:G:GG	donor_gain	1.0000
10:71510225:GTAT:G	donor_loss	1.0000
10:71510942:C:G	acceptor_gain	1.0000
10:71510952:A:AG	acceptor_gain	1.0000
10:71510953:G:GA	acceptor_gain	1.0000
10:71510998:GGGG:G	donor_gain	1.0000
10:71510999:GGG:G	donor_gain	1.0000
10:71510999:GGGG:G	donor_gain	1.0000
10:71511000:GG:G	donor_gain	1.0000
10:71511000:GGG:G	donor_gain	1.0000
10:71511001:GG:G	donor_gain	1.0000
10:71511002:G:GC	donor_loss	1.0000
10:71511002:G:GG	donor_gain	1.0000
10:71511114:T:TA	acceptor_gain	1.0000
10:71511117:CAGGT:C	acceptor_loss	1.0000
10:71511118:A:AG	acceptor_gain	1.0000
10:71511118:AG:A	acceptor_gain	1.0000
10:71511118:AGGT:A	acceptor_gain	1.0000
10:71511119:G:GA	acceptor_gain	1.0000
10:71511119:GG:G	acceptor_gain	1.0000

AlphaMissense

22091 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
10:71510979:T:C	F105S	0.999
10:71510985:T:A	V107D	0.999
10:71617296:C:A	P346Q	0.999
10:71617302:T:C	F348S	0.999
10:71645883:T:C	F398S	0.999
10:71646460:T:C	L431P	0.999
10:71646466:C:A	A433D	0.999
10:71677617:C:A	P559H	0.999
10:71687666:C:A	P669H	0.999
10:71694201:T:C	L744P	0.999
10:71695494:A:T	E789V	0.999
10:71702116:G:A	G831D	0.999
10:71702615:A:C	D885A	0.999
10:71702624:C:A	P888H	0.999
10:71709119:T:C	F1043S	0.999
10:71712743:C:A	P1100H	0.999
10:71799255:C:A	P2400H	0.999
10:71800667:G:C	R2465P	0.999
10:71800703:C:A	A2477D	0.999
10:71803373:C:T	P2609S	0.999
10:71803374:C:A	P2609H	0.999
10:71803380:T:C	F2611S	0.999
10:71803380:T:G	F2611C	0.999
10:71805843:C:A	A2637D	0.999
10:71805945:G:A	G2671D	0.999
10:71805951:T:A	I2673N	0.999
10:71806181:C:A	A2693D	0.999
10:71806226:T:C	L2708P	0.999
10:71446381:A:T	E44V	0.998
10:71510100:T:C	L55S	0.998

dbSNP variants (sampled 300 via entrez): RS1000011908 (10:71625836 G>A), RS1000012790 (10:71663926 A>G), RS1000025762 (10:71812528 C>G,T), RS1000029742 (10:71402121 A>G), RS1000032660 (10:71635699 G>A), RS1000036954 (10:71596430 G>C), RS1000043803 (10:71545549 A>G), RS1000050253 (10:71736681 C>T), RS1000056940 (10:71463191 G>A), RS1000059128 (10:71512455 T>A), RS1000062564 (10:71703535 A>G), RS1000071679 (10:71534792 T>C), RS1000075022 (10:71809663 G>A), RS1000077187 (10:71585949 C>T), RS1000077474 (10:71703790 T>G)

Disease associations

OMIM: gene MIM:605516 | disease phenotypes: MIM:601067, MIM:601386, MIM:617540, MIM:108300, MIM:276900, MIM:156000, MIM:128600, MIM:120970, MIM:249900, MIM:220290, MIM:607197, MIM:192350, MIM:611721, MIM:610539, MIM:611722, MIM:248510, MIM:500004, MIM:268000, MIM:276901, MIM:613391

GenCC curated gene-disease

Disease	Classification	Inheritance
Usher syndrome type 1	Definitive	Unknown
nonsyndromic genetic hearing loss	Definitive	Autosomal recessive
Usher syndrome type 1D	Definitive	Autosomal recessive
autosomal recessive nonsyndromic hearing loss 12	Definitive	Autosomal recessive
hearing loss, autosomal recessive	Supportive	Autosomal recessive

ClinGen Gene-Disease Validity (2)

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

Disease	Classification	Inheritance
Usher syndrome type 1	Definitive	AR
nonsyndromic genetic hearing loss	Definitive	AR

Mondo (29): Usher syndrome type 1 (MONDO:0010168), Usher syndrome type 1D (MONDO:0010984), autosomal recessive nonsyndromic hearing loss 12 (MONDO:0011067), pituitary adenoma 5, multiple types (MONDO:0054601), nonsyndromic genetic hearing loss (MONDO:0019497), hearing loss disorder (MONDO:0005365), Stickler syndrome (MONDO:0019354), inherited retinal dystrophy (MONDO:0019118), Usher syndrome (MONDO:0019501), Meniere disease (MONDO:0007972), ear malformation (MONDO:0007500), optic atrophy (MONDO:0003608), cone-rod dystrophy (MONDO:0015993), metachromatic leukodystrophy due to saposin B deficiency (MONDO:0009590), intellectual disability (MONDO:0001071)

Orphanet (22): Usher syndrome type 1 (Orphanet:231169), Usher syndrome (Orphanet:886), Rare autosomal recessive non-syndromic sensorineural deafness type DFNB (Orphanet:90636), Rare non-syndromic genetic deafness (Orphanet:87884), Stickler syndrome (Orphanet:828), OBSOLETE: Inherited retinal disorder (Orphanet:71862), Cone rod dystrophy (Orphanet:1872), Metachromatic leukodystrophy (Orphanet:512), Rare genetic deafness (Orphanet:96210), Rare autosomal dominant non-syndromic sensorineural deafness type DFNA (Orphanet:90635), VACTERL/VATER association (Orphanet:887), Encephalopathy due to prosaposin deficiency (Orphanet:139406), Atypical Gaucher disease due to saposin C deficiency (Orphanet:309252), Gaucher disease (Orphanet:355), Krabbe disease (Orphanet:487)

HPO phenotypes

153 total (30 of 153 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000007	Autosomal recessive inheritance
HP:0000026	Male hypogonadism
HP:0000044	Hypogonadotropic hypogonadism
HP:0000134	Female hypogonadism
HP:0000135	Hypogonadism
HP:0000140	Abnormality of the menstrual cycle
HP:0000141	Amenorrhea
HP:0000365	Hearing impairment
HP:0000375	Abnormal cochlea morphology
HP:0000399	Prelingual sensorineural hearing impairment
HP:0000407	Sensorineural hearing impairment
HP:0000508	Ptosis
HP:0000510	Rod-cone dystrophy
HP:0000512	Abnormal electroretinogram
HP:0000518	Cataract
HP:0000529	Progressive visual loss
HP:0000572	Visual loss
HP:0000575	Scotoma
HP:0000618	Blindness
HP:0000651	Diplopia
HP:0000662	Nyctalopia
HP:0000708	Atypical behavior
HP:0000709	Psychosis
HP:0000712	Emotional lability
HP:0000716	Depression
HP:0000725	Psychotic episodes
HP:0000726	Dementia
HP:0000739	Anxiety
HP:0000750	Delayed speech and language development

GWAS associations

21 associations (top):

Study	Trait	p-value
GCST001113_21	Age at smoking initiation in chronic obstructive pulmonary disease	9.000000e-06
GCST001670_3	Vitiligo	2.000000e-08
GCST002306_20	Bipolar disorder (body mass index interaction)	3.000000e-06
GCST002720_2	Kidney function decline traits	5.000000e-06
GCST002875_50	Diisocyanate-induced asthma	7.000000e-06
GCST003814_14	Selective IgA deficiency	2.000000e-06
GCST004625_180	Monocyte count	2.000000e-09
GCST005109_2	Progranulin levels	2.000000e-12
GCST005714_3	Cerebrospinal fluid beta-site APP cleaving enzyme levels	9.000000e-06
GCST006473_1	Diffusing capacity of the lung for carbon monoxide traits	3.000000e-07
GCST006632_8	Decline in glucose metabolism in posterior cingulate cortex	5.000000e-08
GCST006810_23	Self-reported risk-taking behaviour	4.000000e-08
GCST008891_11	Cognitive performance (processing speed)	7.000000e-06
GCST009144_2	Disease progression in age-related macular degeneration (adjusted for baseline)	9.000000e-06
GCST011096_3	Systemic lupus erythematosus	5.000000e-08
GCST011956_43	Systemic lupus erythematosus	1.000000e-09
GCST012442_13	Age-related hearing impairment	6.000000e-09
GCST90002393_356	Monocyte count	1.000000e-20
GCST90002393_357	Monocyte count	2.000000e-09
GCST90002394_346	Monocyte percentage of white cells	3.000000e-10
GCST90011866_17	Systemic lupus erythematosus	1.000000e-07

EFO canonical traits (13, from GWAS)

EFO ID	Trait name
EFO:0005670	smoking initiation
EFO:0004340	body mass index
EFO:0006829	GFR change measurement
EFO:0006995	response to diisocyanate
EFO:0005091	monocyte count
EFO:0004625	progranulin measurement
EFO:0009179	beta-secretase 1 measurement
EFO:0009369	diffusing capacity of the lung for carbon monoxide
EFO:0009392	glucose metabolism decline measurement
EFO:0008579	risk-taking behaviour
EFO:0004363	information processing speed
EFO:0008336	disease progression measurement
EFO:0007989	monocyte percentage of leukocytes

MeSH disease descriptors (18)

Descriptor	Name	Tree numbers
D000071700	Cone-Rod Dystrophies	C11.270.152; C11.768.585.658.250; C16.320.290.152
D034381	Hearing Loss	C09.218.458.341; C10.597.751.418.341; C23.888.592.763.393.341
D008607	Intellectual Disability	C10.597.606.360; C23.888.592.604.646; F01.700.687; F03.625.539
D008575	Meniere Disease	C09.218.568.217.500
D009896	Optic Atrophy	C10.292.700.225; C11.640.451
D012164	Retinal Diseases	C11.768
D058499	Retinal Dystrophies	C11.768.585.658
D012174	Retinitis Pigmentosa	C11.270.684; C11.768.585.658.500; C16.320.290.684
D052245	Usher Syndromes	C09.218.458.341.186.500.500; C09.218.458.341.887.886; C10.597.751.418.341.186.500.500; C10.597.751.418.341.887.886; C10.597.751.941.162.625.500; C11.768.585.658.500.813; C11.966.075.375.500; C16.131.077.299.500; C16.320.290.684.500; C23.888.592.763.393.341.887.886
D044905	beta-Mannosidosis	C16.320.565.202.607.750; C16.320.565.595.577.750; C18.452.648.202.607.750; C18.452.648.595.577.750
C567125	Combined Saposin Deficiency (supp.)
C564609	Deafness, Autosomal Recessive (supp.)
C563327	Deafness, Autosomal Recessive 12 (supp.)
C566435	Gaucher Disease, Atypical, Due To Saposin C Deficiency (supp.)
C567097	Krabbe Disease, Atypical, due to Saposin A Deficiency (supp.)
C562609	Metachromatic Leukodystrophy due to Saposin B Deficiency (supp.)
C580334	Nonsyndromic Deafness (supp.)
C536490	Usher syndrome, type 2A (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
rs17712523	Efficacy	3	methylphenidate	Attention Deficit Disorder with Hyperactivity

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs17712523	CDH23	3	0.00	1	methylphenidate

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, decreases expression, increases methylation	4
Valproic Acid	affects cotreatment, increases expression, increases methylation	3
Aflatoxin B1	decreases expression, increases methylation	3
bisphenol A	increases expression, affects methylation	2
Diethylhexyl Phthalate	decreases expression, increases abundance, increases methylation	2
Methapyrilene	affects methylation, decreases expression, increases methylation	2
Phenylmercuric Acetate	decreases expression, affects cotreatment	2
Tobacco Smoke Pollution	affects expression, decreases methylation	2
aristolochic acid I	increases expression	1
triphenyl phosphate	affects expression	1
propionaldehyde	increases expression	1
trichostatin A	increases expression	1
mono-(2-ethylhexyl)phthalate	increases abundance, increases methylation	1
sodium arsenite	increases expression	1
benzo(e)pyrene	affects methylation, increases methylation	1
aflatoxin B2	affects methylation	1
di-n-butylphosphoric acid	affects expression	1
tebuconazole	decreases expression	1
CGP 52608	affects binding, increases reaction	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	increases expression, affects cotreatment, decreases expression	1
dorsomorphin	affects cotreatment, decreases expression, increases expression	1
licochalcone B	increases expression	1
bisphenol S	decreases methylation	1
jinfukang	increases expression	1
Resveratrol	increases expression	1
Arsenic Trioxide	increases expression	1
Vehicle Emissions	decreases methylation	1
Citrulline	decreases expression	1
Clorgyline	increases expression	1
Doxorubicin	decreases expression	1

Cellosaurus cell lines

3 cell lines: 3 induced pluripotent stem cell

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

Cellosaurus	Name	Category	Sex
CVCL_C9H9	RCMGi011-A	Induced pluripotent stem cell	Male
CVCL_C9HA	RCMGi011-B	Induced pluripotent stem cell	Male
CVCL_D0GZ	JUFMDOi008-A	Induced pluripotent stem cell	Female

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
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