PCDH15

Summary

PCDH15 (protocadherin related 15, HGNC:14674) is a protein-coding gene on chromosome 10q21.1, encoding Protocadherin-15 (Q96QU1). Calcium-dependent cell-adhesion protein.

This gene is a member of the cadherin superfamily. Family members encode integral membrane proteins that mediate calcium-dependent cell-cell adhesion. It plays an essential role in maintenance of normal retinal and cochlear function. Mutations in this gene result in hearing loss and Usher Syndrome Type IF (USH1F). Extensive alternative splicing resulting in multiple isoforms has been observed in the mouse ortholog. Similar alternatively spliced transcripts are inferred to occur in human, and additional variants are likely to occur.

Source: NCBI Gene 65217 — RefSeq curated summary.

At a glance

• Gene–disease (curated): Usher syndrome type 1 (Definitive, ClinGen) — +4 more curated relationships
• GWAS associations: 30
• Clinical variants (ClinVar): 3,862 total — 243 pathogenic, 264 likely-pathogenic
• Phenotypes (HPO): 22
• Druggable target: yes
• Dosage sensitivity (ClinGen): haploinsufficiency autosomal recessive, triplosensitivity no evidence
• MANE Select transcript: NM_001384140

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:14674
Approved symbol	PCDH15
Name	protocadherin related 15
Location	10q21.1
Locus type	gene with protein product
Status	Approved
Aliases	CDHR15
Ensembl gene	ENSG00000150275
Ensembl biotype	protein_coding
OMIM	605514
Entrez	65217

Gene structure

Transcript identifiers

Ensembl transcripts: 29 — 24 protein_coding, 3 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined, 1 retained_intron

ENST00000320301, ENST00000361849, ENST00000373955, ENST00000373956, ENST00000373957, ENST00000373965, ENST00000395430, ENST00000395433, ENST00000395440, ENST00000395442, ENST00000395445, ENST00000395446, ENST00000409834, ENST00000414367, ENST00000437009, ENST00000448885, ENST00000458638, ENST00000463095, ENST00000476074, ENST00000495484, ENST00000613346, ENST00000613657, ENST00000615043, ENST00000616114, ENST00000617271, ENST00000618301, ENST00000621708, ENST00000642496, ENST00000644397

RefSeq mRNA: 18 — MANE Select: NM_001384140 NM_001142763, NM_001142764, NM_001142765, NM_001142766, NM_001142767, NM_001142768, NM_001142769, NM_001142770, NM_001142771, NM_001142772, NM_001142773, NM_001354404, NM_001354411, NM_001354420, NM_001354429, NM_001354430, NM_001384140, NM_033056

CCDS: CCDS44400, CCDS44401, CCDS44403, CCDS44404, CCDS7248, CCDS73134, CCDS73135, CCDS73136, CCDS73137, CCDS73138, CCDS86093, CCDS86094, CCDS86095, CCDS91245

Canonical transcript exons

ENST00000644397 — 38 exons

Exon	Start	End
ENSE00001095682	54236823	54236931
ENSE00001095686	54369120	54369275
ENSE00001095689	54317271	54317441
ENSE00001095722	54153100	54153293
ENSE00001095727	54329596	54329706
ENSE00001095729	54378782	54378942
ENSE00001192999	54185134	54185268
ENSE00001221423	54527812	54527877
ENSE00001221521	54183444	54183593
ENSE00001221588	54213936	54214048
ENSE00001330164	54346365	54346484
ENSE00001462024	53802771	53807130
ENSE00002491684	53817995	53818013
ENSE00003466405	54022892	54023197
ENSE00003470824	54020192	54020416
ENSE00003485133	54066757	54066885
ENSE00003491122	54079331	54079424
ENSE00003520483	53940866	53940975
ENSE00003522061	53840320	53840496
ENSE00003533152	54089984	54090063
ENSE00003545608	54195683	54195889
ENSE00003549622	53903243	53903370
ENSE00003549696	53959732	53959844
ENSE00003604358	53827393	53827548
ENSE00003621879	53961752	53961892
ENSE00003635683	53810556	53810664
ENSE00003639412	53828565	53828573
ENSE00003644204	53831315	53831533
ENSE00003647421	53995649	53995765
ENSE00003672188	53938815	53938955
ENSE00003684295	54664172	54664290
ENSE00003688173	53866642	53866857
ENSE00003691563	53857175	53857263
ENSE00003714459	54132875	54133007
ENSE00003735901	53816239	53816277
ENSE00003747726	53811549	53811619
ENSE00003829683	53820165	53820230
ENSE00003908782	54800925	54801231

Expression profiles

Bgee: expression breadth ubiquitous, 130 present calls, max score 82.63.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.9899 / max 64.9079, expressed in 168 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
109416	0.4476	127
109415	0.3741	114
109414	0.0724	53
109417	0.0500	34
109419	0.0458	23

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
left adrenal gland cortex	UBERON:0035825	82.63	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	82.55	gold quality
adrenal tissue	UBERON:0018303	82.21	gold quality
right adrenal gland cortex	UBERON:0035827	81.33	gold quality
left adrenal gland	UBERON:0001234	81.31	gold quality
amygdala	UBERON:0001876	81.15	gold quality
right adrenal gland	UBERON:0001233	79.69	gold quality
adrenal gland	UBERON:0002369	79.55	gold quality
adrenal cortex	UBERON:0001235	79.44	gold quality
hypothalamus	UBERON:0001898	78.60	gold quality
anterior cingulate cortex	UBERON:0009835	78.31	gold quality
right frontal lobe	UBERON:0002810	74.45	gold quality
nucleus accumbens	UBERON:0001882	73.77	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	73.70	gold quality
adenohypophysis	UBERON:0002196	72.31	gold quality
caudate nucleus	UBERON:0001873	72.04	gold quality
Brodmann (1909) area 9	UBERON:0013540	71.92	gold quality
substantia nigra	UBERON:0002038	71.71	gold quality
putamen	UBERON:0001874	71.68	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	71.48	gold quality
spinal cord	UBERON:0002240	70.68	gold quality
prefrontal cortex	UBERON:0000451	70.16	gold quality
corpus callosum	UBERON:0002336	69.52	gold quality
pituitary gland	UBERON:0000007	69.32	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	68.67	gold quality
midbrain	UBERON:0001891	67.95	gold quality
forebrain	UBERON:0001890	67.64	gold quality
neocortex	UBERON:0001950	67.59	gold quality
Ammon’s horn	UBERON:0001954	66.85	gold quality
brain	UBERON:0000955	66.36	gold quality

Single-cell (SCXA)

Detected in 9 experiment(s), a significant marker in 9.

Experiment	Marker?	Max mean expression
E-HCAD-35	yes	5084.84
E-HCAD-30	yes	5001.39
E-GEOD-180759	yes	3756.50
E-HCAD-25	yes	3687.57
E-GEOD-131882	yes	2179.20
E-CURD-119	yes	2038.38
E-GEOD-84465	yes	26.96
E-ANND-3	yes	7.73
E-GEOD-93593	yes	6.03

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

53 targeting PCDH15, 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-340-5P	100.00	72.50	4437
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-548J-3P	99.94	72.61	4881
HSA-MIR-539-5P	99.93	70.30	2855
HSA-MIR-335-3P	99.93	73.36	4958
HSA-MIR-6835-3P	99.93	70.49	2904
HSA-MIR-548AE-3P	99.93	72.66	4867
HSA-MIR-548AH-3P	99.93	72.54	4872
HSA-MIR-548AM-3P	99.93	72.54	4872
HSA-MIR-548AQ-3P	99.93	72.66	4867
HSA-MIR-3671	99.90	73.04	3897
HSA-MIR-548E-5P	99.89	72.73	4486
HSA-MIR-5003-3P	99.85	69.29	2517
HSA-MIR-548AR-3P	99.85	71.26	3889
HSA-MIR-6739-5P	99.80	67.87	2806
HSA-MIR-548AG	99.77	69.25	1492
HSA-MIR-3156-3P	99.76	66.72	939
HSA-MIR-6733-5P	99.74	67.94	2759
HSA-MIR-4677-5P	99.70	70.09	1940
HSA-MIR-548AI	99.69	69.24	1494
HSA-MIR-548BA	99.69	69.14	1514
HSA-MIR-570-5P	99.69	69.24	1494
HSA-MIR-4328	99.57	71.06	4094
HSA-MIR-3153	99.55	67.59	2337
HSA-MIR-543	99.52	69.03	2595
HSA-MIR-217-5P	99.49	69.93	1419

Functional genomics

ClinGen dosage: haploinsufficiency 30 (autosomal recessive), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 40)

• Mutations cause Usher syndrome type 1F. Protocadherins are essential for maintenance of normal retinal and cochlear function. (PMID:11487575)
• A founder mutation, R245X, of the PCDH15 gene among Ashkenazi Jews is a cause of Type 1 Usher Syndrome. (PMID:12711741)
• Here we report that non-syndromic recessive hearing loss (DFNB23) is caused by missense mutations of PCDH15. (PMID:14570705)
• CDH23 and PCDH15 play an essential long-term role in maintaining the normal organization of the stereocilia bundle. (PMID:15537665)
• 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)
• characterizeation of a new allele of the protocadherin 15 gene (designatedPcdh15(av-6J); Young Pcdh15(av-6J) mice are unresponsive to auditory stimulation and show circling behavior indicative of vestibular dysfunction (PMID:16887306)
• Analysis of three large deletions revealed that all six breakpoints are different. Breakpoint junction was identified in one patient and four other breakpoints were mapped to 4 kb. (PMID:17277737)
• Both mouse and human protocadherin 15 genes have complex genomic structures and transcription control mechanisms. (PMID:17706913)
• Humans with PCDH15 (USH1F), USH2A or GPR98 (USH2C) had a similar retinal phenotype to MYO7A (PMID:18463160)
• study of PCDH15 mutations in nonsyndromic deafness DFNB23 and type 1 Usher syndrome (PMID:18719945)
• missense mutations in conserved motifs of PCDH15 cause nonsyndromic hearing loss (PMID:19107147)
• One SNP in PCDH15 (rs7095441) and two SNPs in MYH14 (rs667907 and rs588035), resulted in significant associations in the Polish sample set and significant interactions with noise exposure level in the Swedish sample set. (PMID:19183343)
• Study suggests that PCDH15 is associated with lipid abnormalities. (PMID:19816713)
• a combination of PCR-based mutation screening, together with deletion and duplication analysis, is mandatory for the accurate screening of the PCDH15 gene in Usher patients. (PMID:20538994)
• Alberta Hutterites with Usher syndrome type I do not carry the exon 10 mutation in the PCDH15 gene. (PMID:22690115)
• Seven different point mutations, five novel, were detected in PCDH15 gene in Spanish patients with Usher syndrome type I. (PMID:22815625)
• Single nucleotide polymorphisms spanning a 9-kb region centered on exon 11 of the protocadherin 15 ( PCDH15 ) gene were found to be associated with irritable bowel syndrome in Australian, United States, and Swedish populations. (PMID:24797007)
• Patients lacking PCDH15-CD2 isoform are profoundly deaf. (PMID:24940003)
• PCDH15 has several alternate cytoplasmic domain exons and differentially spliced isoforms may function redundantly (PMID:25307757)
• Genetic variations of PCDH15 and their interactions with occupational noise exposure are associated with genetic susceptibility t onoise-induced hearing loss. (PMID:25462672)
• The novel homozygous mutation in a family segregating non-syndromic hearing loss family supports previous reported observations that PCDH15 does not only causes Usher syndrome type 1F, but also DFNB23. (PMID:25930172)
• PCDH15 or DFNB59 variants are associated with poor CI performance, yet children with PCDH15 or DFNB59 variants might show clinical features indistinguishable from those of other typical pediatric cochlear implant recipients. (PMID:26166082)
• PCDH15 p.Asp1010Gly variant probably modified the phenotypic expression of the 7511T>C mutation in MT-TS1 (PMID:26279247)
• Results uncovered a novel interaction between MYO3A and PCDH15 shedding new light on the function of myosin IIIA at stereocilia tips. (PMID:26841241)
• no statistically significant association between any rare, heterozygous PCDH15 point variants and schizophrenia or autism spectrum disorders was found (PMID:27058588)
• We found a remarkable genetic heterogeneity in the studied families with USH1 with a variety of mutations, among which three were novel. These novel mutations will be included in the NADf mutation screening chip that will allow a higher diagnosis efficiency of this extremely genetically heterogeneous disease. (PMID:27440999)
• PCDH15 polymorphism is associated with extraversion. (PMID:27918536)
• Results present structures of a protocadherin-15 fragment featuring a non-canonical linker region that exhibits increased flexibility without compromising mechanical strength. (PMID:28238533)
• This study confirms that genetic variations in PCDH15 modify the susceptibility to noise-induced hearing loss development in humans. (PMID:28292353)
• rs2045145 associated with more European female facial profile (PMID:29301965)
• Novel 4658delT PCDH15 mutation was identified in a family with nonsyndromic hearing loss. (PMID:29692870)
• The protein products of PCDH15 and USH1G function together at the stereocilia tips in the hair cells. (PMID:30029624)
• PCDH15 molecules form double-helical assemblies through cis-dimerization in the extracellular cadherin domain region and in a membrane-proximal domain. (PMID:30057206)
• Whole-exome sequencing for ocular adnexal sebaceous carcinoma suggests PCDH15 as a novel mutation associated with metastasis. (PMID:31937901)
• A novel missense mutation locus of cadherin 23 and the interaction of cadherin 23 and protocadherin 15 in a patient with usher syndrome. (PMID:32835555)
• Structural determinants of protocadherin-15 mechanics and function in hearing and balance perception. (PMID:32963095)
• Protocadherin 15 suppresses oligodendrocyte progenitor cell proliferation and promotes motility through distinct signalling pathways. (PMID:35637313)
• The association of genetic polymorphisms in protocadherin 15 with sudden sensorineural hearing loss in a Chinese population. (PMID:37198144)
• A novel compound heterozygous PCDH15 variants is associated with arRP in a Chinese pedigree. (PMID:39187782)
• Nanomechanics of wild-type and mutant dimers of the inner-ear tip-link protein protocadherin 15. (PMID:39298473)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	pcdh15b	ENSDARG00000008127
danio_rerio	pcdh15a	ENSDARG00000098257
mus_musculus	Pcdh15	ENSMUSG00000052613
rattus_norvegicus	Pcdh15	ENSRNOG00000000606

Paralogs (61): PCDHB4 (ENSG00000081818), PCDHA6 (ENSG00000081842), PCDHGA2 (ENSG00000081853), PCDHB2 (ENSG00000112852), PCDHB3 (ENSG00000113205), PCDHB5 (ENSG00000113209), PCDHB6 (ENSG00000113211), PCDHB7 (ENSG00000113212), PCDHB15 (ENSG00000113248), PCDH12 (ENSG00000113555), PCDH17 (ENSG00000118946), PCDHB8 (ENSG00000120322), PCDHB10 (ENSG00000120324), PCDHB14 (ENSG00000120327), PCDHB12 (ENSG00000120328), PCDH8 (ENSG00000136099), PCDH10 (ENSG00000138650), PCDH19 (ENSG00000165194), CDH16 (ENSG00000166589), PCDHB1 (ENSG00000171815), PCDHB9 (ENSG00000177839), PCDHB13 (ENSG00000187372), CDHR4 (ENSG00000187492), PCDH18 (ENSG00000189184), PCDHB11 (ENSG00000197479), PCDHGA1 (ENSG00000204956), PCDHA9 (ENSG00000204961), PCDHA8 (ENSG00000204962), PCDHA7 (ENSG00000204963), PCDHA5 (ENSG00000204965), PCDHA4 (ENSG00000204967), PCDHA2 (ENSG00000204969), PCDHA1 (ENSG00000204970), PCDHA13 (ENSG00000239389), PCDHGC3 (ENSG00000240184), PCDHGC5 (ENSG00000240764), PCDHGC4 (ENSG00000242419), PCDHAC2 (ENSG00000243232), PCDHAC1 (ENSG00000248383), PCDHA11 (ENSG00000249158)

Protein

Protein identifiers

Protocadherin-15 — Q96QU1 (reviewed: Q96QU1)

All UniProt accessions (22): Q96QU1, A0A087WTR6, A0A087WUC7, A0A087WX70, A0A087WXQ6, A0A087WZN4, A0A087WZN9, A0A087X1T6, A0A2R8YEV2, A2A3D8, A2A3D9, A2A3E1, A2A3E4, A2A3E5, A2A3E6, A2A3E7, A2A3E8, A9Z1W1, B7ZBT8, E7EM53, E7EM97, E7EMG8

UniProt curated annotations — full annotation on UniProt →

Function. Calcium-dependent cell-adhesion protein. Essential for maintenance of normal retinal and cochlear function.

Subunit / interactions. Antiparallel heterodimer with CDH23. Found in a complex with TMIE and LHFPL5. Interacts with LHFPL5/TMHS; this interaction is required for efficient localization to hair bundles. Interacts with MYO7A. Interacts with USH1G; this interaction may recruit USH1G to the plasma membrane. Interacts with TOMT. Isoforms CD1 and CD3 interact with TMC1 (via N-terminus) and TMC2 (via N-terminus).

Subcellular location. Cell membrane Secreted.

Tissue specificity. Expressed in brain, lung, kidney, spleen and testis. Found also in the inner and outer synaptic layers, and the nerve fiber layer in adult and fetal retinas. Found in the supporting cells, outer sulcus cells and spiral ganglion of fetal cochlea. Expressed in cytotoxic tumor-derived T- and NK-cell lines as well as biopsies of nasal NK/T-cell lymphomas. Not detected in normal or in vitro activated peripheral blood cells, CD4 or CD8 lymphocytes or NK cells. Isoform 3 is expressed in brain, heart, cerebellum and kidney. CD1 isoforms, such as isoform 1, have a limited pattern of expression and is detected in testis, retina and cochlea. CD2 isoforms, such as isoforms 4 and 5, are expressed in heart, kidney, thymus, spleen, testis, retina and cochlea. CD3 isoforms, such as isoform 6, are widely expressed.

Disease relevance. Usher syndrome 1F (USH1F) [MIM:602083] 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, 23 (DFNB23) [MIM:609533] 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.

Domain organisation. Cadherin repeats 1 and 2 mediate calcium-dependent heterophilic interaction with CDH23. 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.

Isoforms (6)

UniProt ID	Names	Canonical?
Q96QU1-1	1, A, CD1-1	yes
Q96QU1-2	2, B
Q96QU1-3	3, C
Q96QU1-4	4, CD2-1
Q96QU1-6	5, CD3-1
Q96QU1-7	7

RefSeq proteins (18): NP_001136235, NP_001136236, NP_001136237, NP_001136238, NP_001136239, NP_001136240, NP_001136241, NP_001136242, NP_001136243, NP_001136244, NP_001136245, NP_001341333, NP_001341340, NP_001341349, NP_001341358, NP_001341359, NP_001371069, NP_149045 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002126	Cadherin-like_dom	Domain
IPR015919	Cadherin-like_sf	Homologous_superfamily
IPR020894	Cadherin_CS	Conserved_site
IPR030718	EC_dom_sf	Homologous_superfamily
IPR041149	EC_dom	Domain
IPR050971	Cadherin-domain_protein	Family
IPR056989	PCDH15_12th_dom	Domain

Pfam: PF00028, PF18432, PF23206

UniProt features (168 total): strand 71, turn 20, sequence variant 14, helix 13, glycosylation site 13, domain 11, splice variant 11, region of interest 4, sequence conflict 3, topological domain 2, compositionally biased region 2, signal peptide 1, chain 1, transmembrane region 1, disulfide bond 1

Structure

Experimental structures (PDB)

8 structures.

PDB	Method	Resolution (Å)
5T4M	X-RAY DIFFRACTION	2.24
6EB5	X-RAY DIFFRACTION	2.6
5ULY	X-RAY DIFFRACTION	2.64
5T4N	X-RAY DIFFRACTION	2.7
4XHZ	X-RAY DIFFRACTION	2.8
6N2E	X-RAY DIFFRACTION	2.9
6E8F	X-RAY DIFFRACTION	2.99
6MFO	X-RAY DIFFRACTION	3.15

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96QU1-F1	66.05	0.09

Functional residue map

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

Disulfide bonds (1): 32–120

Glycosylation sites (13): 52, 97, 201, 419, 559, 662, 724, 768, 821, 851, 1064, 1084, 1175

Function

Pathways and Gene Ontology

Reactome pathways

2 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

MSigDB gene sets: 158 (showing top): GOBP_SENSORY_PERCEPTION_OF_MECHANICAL_STIMULUS, GCANCTGNY_MYOD_Q6, chr10q21, GOBP_NEUROMUSCULAR_PROCESS_CONTROLLING_BALANCE, GOBP_CELL_CELL_ADHESION, GOBP_EAR_DEVELOPMENT, GOBP_PHOTORECEPTOR_CELL_MAINTENANCE, GOBP_SENSORY_PERCEPTION_OF_LIGHT_STIMULUS, GOBP_MULTICELLULAR_ORGANISMAL_LEVEL_HOMEOSTASIS, GOBP_SENSORY_PERCEPTION, GOCC_NEURON_PROJECTION, E12_Q6, GOBP_SENSORY_ORGAN_DEVELOPMENT, GOBP_RETINA_HOMEOSTASIS, GOBP_NEUROMUSCULAR_PROCESS

GO Biological Process (7): cell adhesion (GO:0007155), homophilic cell-cell adhesion (GO:0007156), sensory perception of sound (GO:0007605), photoreceptor cell maintenance (GO:0045494), inner ear development (GO:0048839), sensory perception of light stimulus (GO:0050953), equilibrioception (GO:0050957)

GO Molecular Function (2): calcium ion binding (GO:0005509), cell adhesion molecule binding (GO:0050839)

GO Cellular Component (7): photoreceptor outer segment (GO:0001750), extracellular region (GO:0005576), obsolete extracellular space (GO:0005615), plasma membrane (GO:0005886), stereocilium (GO:0032420), synapse (GO:0045202), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Sensory processing of sound	2

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
sensory perception	2
cellular process	1
cell-cell adhesion	1
sensory perception of mechanical stimulus	1
retina homeostasis	1
multicellular organismal process	1
ear development	1
anatomical structure development	1
neuromuscular process controlling balance	1
metal ion binding	1
protein binding	1
photoreceptor cell cilium	1
membrane	1
cell periphery	1
stereocilium bundle	1
neuron projection	1
actin-based cell projection	1
cell junction	1

Protein interactions and networks

STRING

1724 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PCDH15	MYO7A	P78427	996
PCDH15	CDH23	Q9H251	992
PCDH15	E9PNW1	E9PNW1	989
PCDH15	USH1G	Q495M9	985
PCDH15	LHFPL5	Q8TAF8	954
PCDH15	ADGRV1	Q8WXG9	929
PCDH15	USH2A	O75445	922
PCDH15	WHRN	Q9P202	892
PCDH15	TMC1	Q8TDI8	885
PCDH15	CIB2	O75838	879
PCDH15	TMC2	Q8TDI7	869
PCDH15	CLRN1	P58418	868
PCDH15	ATP2B2	Q01814	800
PCDH15	TMIE	Q8NEW7	790
PCDH15	NDST2	P52849	767

IntAct

2 interactions, top by confidence:

A	B	Type	Score
Dlg4	PCDH15	psi-mi:“MI:0407”(direct interaction)	0.440

BioGRID (6): PCDH15 (Affinity Capture-MS), PCDH15 (Affinity Capture-MS), PCDH15 (Affinity Capture-MS), PCDH15 (Proximity Label-MS), PCDH15 (Co-fractionation), PCDH15 (Proximity Label-MS)

ESM2 similar proteins: A0A1L8F5J9, A0JN27, F1NBL0, O15294, O89050, P35438, P35439, P56558, P69849, P81436, Q03555, Q05586, Q0ZM14, Q12841, Q13888, Q15155, Q15303, Q27HV0, Q2TBV5, Q3ZCW2, Q58D84, Q5JPE7, Q5R1P0, Q5R5K6, Q5R9Y1, Q5RB35, Q5RFN0, Q5VV63, Q5ZHQ2, Q61527, Q62632, Q62956, Q6A051, Q6P1K8, Q6PIU2, Q6UXG2, Q8BUV3, Q8CGY8, Q8VED9, Q90610

Diamond homologs: A0A8M2BIB6, B0KW95, B2KI42, B4USZ0, F1PAA9, H2EQR6, O02840, O18926, O35902, O55075, O55111, O88278, O88689, P08641, P09803, P10287, P10288, P12830, P15116, P19022, P19534, P20310, P22223, P24503, P30944, P32926, P33145, P33146, P33147, P33148, P33150, P33152, P33450, P33545, P39038, P55283, P55290, P55291, P55292, P55850

SIGNOR signaling

4 interactions.

A	Effect	B	Mechanism
PCDH15	“up-regulates activity”	TMC1	binding
PCDH15	“up-regulates activity”	TMC2	binding
FGFR1	“up-regulates activity”	PCDH15	phosphorylation
PCDH15	“form complex”	“TIP-LINK complex”	binding

Disease & clinical

Clinical variants and AI predictions

ClinVar

3862 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	243
Likely pathogenic	264
Uncertain significance	1324
Likely benign	1528
Benign	187

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1012779	NM_001384140.1(PCDH15):c.3757del (p.Ser1253fs)	Pathogenic
1027565	NM_001384140.1(PCDH15):c.3667_3668del (p.Ile1223fs)	Pathogenic
1068955	NM_033056.4(PCDH15):c.4369_4372dup (p.Phe1458fs)	Pathogenic
1069601	NM_001384140.1(PCDH15):c.4240C>T (p.Arg1414Ter)	Pathogenic
1070734	NC_000010.10:g.(?56077031)(56106244_?)del	Pathogenic
1071756	NM_033056.4(PCDH15):c.4685_4688dup (p.Arg1564fs)	Pathogenic
1073349	NM_001384140.1(PCDH15):c.3600T>G (p.Tyr1200Ter)	Pathogenic
1073474	NM_001384140.1(PCDH15):c.4128dup (p.Leu1378fs)	Pathogenic
1074677	NC_000010.10:g.(?55849724)(55849843_?)del	Pathogenic
1074678	NC_000010.10:g.(?55849744)(55955649_?)del	Pathogenic
1074873	NM_001384140.1(PCDH15):c.2321del (p.Ala774fs)	Pathogenic
1076111	NM_001384140.1(PCDH15):c.84dup (p.Asp29Ter)	Pathogenic
1076709	NM_001384140.1(PCDH15):c.2088_2089insA (p.Gly697fs)	Pathogenic
1185088	NM_001384140.1(PCDH15):c.2756del (p.Met919fs)	Pathogenic
1339715	NM_001384140.1(PCDH15):c.3495_3496del (p.Arg1165fs)	Pathogenic
1343721	NM_001384140.1(PCDH15):c.423_430dup (p.Ser144fs)	Pathogenic
1357705	NM_001384140.1(PCDH15):c.1313del (p.Asp438fs)	Pathogenic
1360574	NM_001384140.1(PCDH15):c.2156del (p.Pro719fs)	Pathogenic
1371565	NM_033056.4(PCDH15):c.4616_4647dup (p.Asp1550delinsIleGlnThrPheHisArgGluGlnIleLeuTer)	Pathogenic
1384879	NM_001384140.1(PCDH15):c.3441del (p.Lys1147fs)	Pathogenic
1391199	NM_001384140.1(PCDH15):c.617_618del (p.Ile206fs)	Pathogenic
1393361	NM_001384140.1(PCDH15):c.1357_1358del (p.Thr453fs)	Pathogenic
1394146	NM_001384140.1(PCDH15):c.996_999del (p.Glu332fs)	Pathogenic
1395619	NM_001384140.1(PCDH15):c.2651del (p.Ala884fs)	Pathogenic
1419765	NM_001384140.1(PCDH15):c.2267del (p.Leu756fs)	Pathogenic
1420760	NM_001384140.1(PCDH15):c.3789del (p.Lys1263_Ile1264insTer)	Pathogenic
1422787	NM_001384140.1(PCDH15):c.3981_3982insTTTTTTTTTTTTTTTTTTTTNNNNNNNNNNAGGTATATCTCCCAATGCTATCCCTCCCCCCTCCCCCGACCCCACCACAGTCCCCAGAAATGAGCTTTTT (p.Lys1328delinsPhePhePhePhePhePheXaaXaaXaaXaaArgTyrIleSerGlnCysTyrProSerProLeuProArgProHisHisSerProGlnLysTer)	Pathogenic
1428307	NC_000010.10:g.(?55616925)(55782967_?)del	Pathogenic
1428344	NC_000010.10:g.(?55566339)(56288162_?)del	Pathogenic
1428365	NC_000010.10:g.(?55996563)(56089486_?)del	Pathogenic

SpliceAI

10906 predictions. Top by Δscore:

Variant	Effect	Δscore
10:53810551:ATTAC:A	donor_loss	1.0000
10:53810553:TACCT:T	donor_loss	1.0000
10:53810555:C:CT	donor_loss	1.0000
10:53810555:CCT:C	donor_gain	1.0000
10:53810560:T:TA	donor_gain	1.0000
10:53811560:A:C	donor_gain	1.0000
10:53827391:A:AC	donor_gain	1.0000
10:53827392:C:CC	donor_gain	1.0000
10:53827550:T:C	acceptor_gain	1.0000
10:53831539:T:TC	acceptor_gain	1.0000
10:53840313:CACTT:C	donor_loss	1.0000
10:53840314:ACTTA:A	donor_loss	1.0000
10:53840316:TTA:T	donor_loss	1.0000
10:53840317:TA:T	donor_loss	1.0000
10:53840318:A:AC	donor_gain	1.0000
10:53840318:AC:A	donor_loss	1.0000
10:53840319:C:CC	donor_gain	1.0000
10:53840319:CT:C	donor_gain	1.0000
10:53840319:CTT:C	donor_gain	1.0000
10:53840319:CTTA:C	donor_gain	1.0000
10:53840319:CTTAA:C	donor_gain	1.0000
10:53840492:AGATC:A	acceptor_gain	1.0000
10:53840493:GATC:G	acceptor_gain	1.0000
10:53840495:TC:T	acceptor_gain	1.0000
10:53840496:CC:C	acceptor_gain	1.0000
10:53840497:C:CA	acceptor_loss	1.0000
10:53840497:C:CC	acceptor_gain	1.0000
10:53840505:C:CT	acceptor_gain	1.0000
10:53857173:A:AC	donor_gain	1.0000
10:53857174:C:CC	donor_gain	1.0000

AlphaMissense

11427 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
10:54020208:A:T	V912D	1.000
10:54079353:G:T	A690D	1.000
10:54079365:A:G	L686P	1.000
10:54079413:A:G	L670P	1.000
10:54317395:A:G	L251P	1.000
10:54317440:T:G	D236A	1.000
10:54369160:G:T	P145H	1.000
10:54369169:T:G	D142A	1.000
10:54369178:T:A	D139V	1.000
10:54369178:T:G	D139A	1.000
10:54369179:C:G	D139H	1.000
10:54369190:A:C	I135R	1.000
10:54369190:A:T	I135K	1.000
10:54369234:G:C	C120W	1.000
10:54369235:C:G	C120S	1.000
10:54369235:C:T	C120Y	1.000
10:54369236:A:G	C120R	1.000
10:54369236:A:T	C120S	1.000
10:54378813:A:G	L96P	1.000
10:54378819:A:G	L94P	1.000
10:53831348:G:C	P1390R	0.999
10:53831355:A:G	C1388R	0.999
10:53831358:A:G	C1387R	0.999
10:53831378:A:T	L1380Q	0.999
10:53831528:A:G	L1330S	0.999
10:53840326:A:G	L1326P	0.999
10:53840368:G:T	A1312E	0.999
10:53840374:A:T	V1310D	0.999
10:53840479:A:T	V1275D	0.999
10:53857226:A:T	V1252D	0.999

dbSNP variants (sampled 300 via entrez): RS1000002847 (10:54475312 T>C), RS1000006074 (10:53955267 C>T), RS1000006770 (10:55218593 A>G), RS1000009561 (10:54326709 T>C), RS1000011315 (10:54050108 A>G), RS1000012151 (10:55420947 C>T), RS1000012467 (10:55343549 A>G), RS1000013422 (10:54380340 C>T), RS1000014950 (10:54454853 T>A,G), RS1000015364 (10:54300699 A>T), RS1000017189 (10:54835145 T>A,C), RS1000021929 (10:53894047 ATAAAC>A), RS1000024457 (10:54408093 G>A,T), RS1000025721 (10:54786409 A>G), RS1000025772 (10:55011780 T>G)

Disease associations

OMIM: gene MIM:605514 | disease phenotypes: MIM:602083, MIM:601067, MIM:609533, MIM:220290, MIM:607197, MIM:128600, MIM:181500, MIM:276900, MIM:268000, MIM:606943, MIM:209850, MIM:156000

GenCC curated gene-disease

Disease	Classification	Inheritance
Usher syndrome type 1	Definitive	Unknown
Usher syndrome type 1F	Definitive	Autosomal recessive
autosomal recessive nonsyndromic hearing loss 23	Definitive	Autosomal recessive
hearing loss, autosomal recessive	Supportive	Autosomal recessive
nonsyndromic genetic hearing loss	Limited	Autosomal recessive

ClinGen Gene-Disease Validity (2)

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

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

Mondo (16): Usher syndrome type 1F (MONDO:0011186), Usher syndrome type 1D (MONDO:0010984), autosomal recessive nonsyndromic hearing loss 23 (MONDO:0012293), hearing loss disorder (MONDO:0005365), hearing loss, autosomal recessive (MONDO:0019588), ear malformation (MONDO:0007500), Usher syndrome type 1 (MONDO:0010168), optic atrophy (MONDO:0003608), schizophrenia (MONDO:0005090), inherited retinal dystrophy (MONDO:0019118), Usher syndrome (MONDO:0019501), retinitis pigmentosa (MONDO:0019200), Usher syndrome type 1G (MONDO:0011748), autism (MONDO:0005260), Meniere disease (MONDO:0007972)

Orphanet (9): Usher syndrome type 1 (Orphanet:231169), Usher syndrome (Orphanet:886), Rare autosomal recessive non-syndromic sensorineural deafness type DFNB (Orphanet:90636), Rare autosomal dominant non-syndromic sensorineural deafness type DFNA (Orphanet:90635), Rare genetic deafness (Orphanet:96210), OBSOLETE: Inherited retinal disorder (Orphanet:71862), Retinitis pigmentosa (Orphanet:791), NON RARE IN EUROPE: Schizophrenia (Orphanet:3140), NON RARE IN EUROPE: Menière disease (Orphanet:45360)

HPO phenotypes

22 total (25 of 22 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000365	Hearing impairment
HP:0000375	Abnormal cochlea morphology
HP:0000407	Sensorineural hearing impairment
HP:0000505	Visual impairment
HP:0000510	Rod-cone dystrophy
HP:0000512	Abnormal electroretinogram
HP:0000518	Cataract
HP:0000572	Visual loss
HP:0000575	Scotoma
HP:0000662	Nyctalopia
HP:0000716	Depression
HP:0000739	Anxiety
HP:0000750	Delayed speech and language development
HP:0001270	Motor delay
HP:0001751	Abnormal vestibular function
HP:0002141	Gait imbalance
HP:0003577	Congenital onset
HP:0007663	Reduced visual acuity
HP:0007994	Peripheral visual field loss
HP:0008527	Congenital sensorineural hearing impairment
HP:0031629	Impaired tandem gait
HP:0100753	Schizophrenia
HP:0000556	Retinal dystrophy
HP:0000717	Autism

GWAS associations

30 associations (top):

Study	Trait	p-value
GCST000837_7	Weight	5.000000e-06
GCST001491_15	Immune response to smallpox vaccine (IL-6)	2.000000e-10
GCST001859_41	Thiazide-induced adverse metabolic effects in hypertensive patients	5.000000e-07
GCST002181_3	Adverse response to chemotherapy in breast cancer (alopecia)	3.000000e-07
GCST002436_1	Irritable bowel syndrome	5.000000e-06
GCST002724_9	Airway responsiveness in chronic obstructive pulmonary disease	6.000000e-08
GCST002847_2	Disease-free survival in breast cancer	4.000000e-07
GCST002940_3	Sporadic pituitary adenoma	7.000000e-10
GCST003101_6	Bone mineral density (spine) and age at menarche	6.000000e-08
GCST003102_1	Bone mineral density (hip) and age at menarche	6.000000e-08
GCST003114_2	Carotid intima media thickness	7.000000e-09
GCST003265_318	Post bronchodilator FEV1/FVC ratio in COPD	3.000000e-06
GCST003980_4	Sleep duration	4.000000e-07
GCST004015_3	Extraversion	5.000000e-10
GCST004735_27	Epstein-Barr virus copy number in lymphoblastoid cell lines	2.000000e-06
GCST005790_18	Rosacea symptom severity	5.000000e-06
GCST006633_23	Initial alcohol sensitivity	7.000000e-06
GCST007576_226	Chronotype	4.000000e-08
GCST007576_435	Chronotype	4.000000e-08
GCST008156_112	Hip circumference adjusted for BMI	2.000000e-06
GCST008951_1	Chromosomal aberration frequency (total)	3.000000e-06
GCST009240_368	Serum metabolite levels (CMS)	1.000000e-10
GCST009240_373	Serum metabolite levels (CMS)	7.000000e-10
GCST009240_377	Serum metabolite levels (CMS)	7.000000e-10
GCST009240_380	Serum metabolite levels (CMS)	4.000000e-10
GCST009530_3	Childhood body mass index	6.000000e-08
GCST010244_360	Triglyceride levels	5.000000e-08
GCST010724_19	HOMA-B (corrected for HOMA-IR)	2.000000e-07
GCST011768_7	Schizophrenia	2.000000e-08
GCST90000015_22	Parkinson’s disease motor subtype (tremor to postural instability/gait difficulty score ratio)	8.000000e-06

EFO canonical traits (17, from GWAS)

EFO ID	Trait name
EFO:0004338	body weight
EFO:0004645	response to vaccine
EFO:0006897	airway responsiveness measurement
EFO:0000409	disease free survival
EFO:0004703	age at menarche
EFO:0007701	spine bone mineral density
EFO:0007702	hip bone mineral density
EFO:0004713	FEV/FVC ratio
EFO:0004317	extraversion
EFO:0009180	rosacea severity measurement
EFO:0008328	chronotype measurement
EFO:0008039	BMI-adjusted hip circumference
EFO:0009860	chromosomal aberration frequency
EFO:0004340	body mass index
EFO:0004530	triglyceride measurement
EFO:0004469	HOMA-B
EFO:0600011	Parkinson’s disease symptom measurement

MeSH disease descriptors (11)

Descriptor	Name	Tree numbers
D001321	Autistic Disorder	F03.625.164.113.500
D034381	Hearing Loss	C09.218.458.341; C10.597.751.418.341; C23.888.592.763.393.341
D008575	Meniere Disease	C09.218.568.217.500
D009896	Optic Atrophy	C10.292.700.225; C11.640.451
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
C564609	Deafness, Autosomal Recessive (supp.)
C563705	Deafness, Autosomal Recessive 23 (supp.)
C580334	Nonsyndromic Deafness (supp.)
C564643	Usher Syndrome, Type IG (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6112 (SINGLE PROTEIN)

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

CTD chemical–gene interactions

20 total (human), top 20 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Aflatoxin B1	decreases methylation, increases methylation	2
bisphenol F	affects cotreatment, decreases methylation	1
bisphenol A	affects methylation	1
sodium arsenite	decreases expression	1
benzo(e)pyrene	decreases methylation	1
coumarin	increases phosphorylation	1
abrine	decreases expression	1
Fulvestrant	affects cotreatment, decreases methylation	1
Arsenic	affects methylation	1
Benzo(a)pyrene	increases methylation	1
Hydralazine	affects cotreatment, increases expression	1
Malathion	decreases expression	1
Methapyrilene	decreases methylation	1
Triclosan	increases expression	1
Valproic Acid	increases expression, affects cotreatment	1
Asbestos, Crocidolite	decreases methylation	1
Asbestos, Amosite	decreases methylation	1
Antirheumatic Agents	decreases expression	1
Okadaic Acid	decreases expression	1
Permethrin	decreases expression	1

ChEMBL screening assays

9 unique, capped per target: 9 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL909565	Binding	Suppression of human PCDH15 R3X mutation at 30 ug/ml	Redesign of aminoglycosides for treatment of human genetic diseases caused by premature stop mutations. — Bioorg Med Chem Lett

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
NCT03655223	Not specified	ENROLLING_BY_INVITATION	Early Check: Expanded Screening in Newborns
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