PJVK

Summary

PJVK (pejvakin, HGNC:29502) is a protein-coding gene on chromosome 2q31.2, encoding Pejvakin (Q0ZLH3). Peroxisome-associated protein required to protect auditory hair cells against noise-induced damage.

The protein encoded by this gene is a member of the gasdermin family, a family which is found only in vertebrates. The encoded protein is required for the proper function of auditory pathway neurons. Defects in this gene are a cause of non-syndromic sensorineural deafness autosomal recessive type 59 (DFNB59).

Source: NCBI Gene 494513 — RefSeq curated summary.

At a glance

• Gene–disease (curated): nonsyndromic genetic hearing loss (Definitive, ClinGen) — +2 more curated relationships
• GWAS associations: 1
• Clinical variants (ClinVar): 298 total — 30 pathogenic, 8 likely-pathogenic
• Phenotypes (HPO): 2
• MANE Select transcript: NM_001042702

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:29502
Approved symbol	PJVK
Name	pejvakin
Location	2q31.2
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000204311
Ensembl biotype	protein_coding
OMIM	610219
Entrez	494513

Gene structure

Transcript identifiers

Ensembl transcripts: 17 — 13 protein_coding, 2 retained_intron, 1 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

ENST00000375129, ENST00000437056, ENST00000442710, ENST00000444615, ENST00000642192, ENST00000642492, ENST00000642762, ENST00000643738, ENST00000643768, ENST00000644554, ENST00000644580, ENST00000645572, ENST00000645762, ENST00000645817, ENST00000647226, ENST00000970493, ENST00000970494

RefSeq mRNA: 6 — MANE Select: NM_001042702 NM_001042702, NM_001353775, NM_001353776, NM_001353777, NM_001353778, NM_001369912

CCDS: CCDS42787, CCDS86897

Canonical transcript exons

ENST00000644580 — 7 exons

Exon	Start	End
ENSE00000000289	178460982	178462102
ENSE00001527133	178454332	178454527
ENSE00001587788	178453388	178453620
ENSE00003555742	178458510	178458627
ENSE00003563813	178460348	178460446
ENSE00003683044	178456010	178456151
ENSE00003828815	178451378	178451769

Expression profiles

Bgee: expression breadth ubiquitous, 188 present calls, max score 96.96.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.1182 / max 21.2010, expressed in 40 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
23934	0.1182	40

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
sperm	CL:0000019	96.96	gold quality
right testis	UBERON:0004534	93.30	gold quality
left testis	UBERON:0004533	93.03	gold quality
testis	UBERON:0000473	90.93	gold quality
left ovary	UBERON:0002119	83.21	gold quality
adenohypophysis	UBERON:0002196	83.07	gold quality
pituitary gland	UBERON:0000007	82.44	gold quality
right ovary	UBERON:0002118	81.95	gold quality
right lobe of liver	UBERON:0001114	81.20	gold quality
Brodmann (1909) area 9	UBERON:0013540	80.50	gold quality
metanephros cortex	UBERON:0010533	80.32	gold quality
lower esophagus mucosa	UBERON:0035834	80.12	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	79.61	gold quality
ovary	UBERON:0000992	79.44	gold quality
left lobe of thyroid gland	UBERON:0001120	79.01	gold quality
mucosa of stomach	UBERON:0001199	78.62	gold quality
body of uterus	UBERON:0009853	78.62	gold quality
right uterine tube	UBERON:0001302	78.61	gold quality
oviduct epithelium	UBERON:0004804	78.56	gold quality
right frontal lobe	UBERON:0002810	78.44	gold quality
right adrenal gland cortex	UBERON:0035827	78.44	gold quality
endocervix	UBERON:0000458	78.43	gold quality
thyroid gland	UBERON:0002046	78.43	gold quality
right lobe of thyroid gland	UBERON:0001119	78.35	gold quality
tibial nerve	UBERON:0001323	78.22	gold quality
right adrenal gland	UBERON:0001233	77.84	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	77.78	gold quality
anterior cingulate cortex	UBERON:0009835	77.57	gold quality
lower esophagus muscularis layer	UBERON:0035833	77.49	gold quality
lower esophagus	UBERON:0013473	77.48	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	4.31

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

15 targeting PJVK, 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-4747-5P	100.00	67.90	2681
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-4760-3P	99.93	70.50	2385
HSA-MIR-6885-3P	99.75	70.36	3187
HSA-MIR-330-3P	99.41	69.95	2521
HSA-MIR-32-3P	99.36	68.20	2517
HSA-MIR-122B-3P	99.21	68.90	1333
HSA-MIR-21-3P	99.21	68.95	1312
HSA-MIR-3688-5P	99.12	69.67	1091
HSA-MIR-9500	98.62	66.54	1845
HSA-MIR-10395-3P	98.10	66.70	1726
HSA-MIR-891A-3P	98.05	67.99	970
HSA-MIR-4474-3P	96.97	65.87	870
HSA-MIR-7108-5P	96.42	66.17	598
HSA-MIR-3130-3P	94.98	66.97	574

Literature-anchored findings (GeneRIF, showing 14)

• DFNB59, a newly identified gene on chromosome 2q31.1-q31.3 mutated in four families segregating autosomal recessive auditory neuropathy (PMID:16804542)
• We have identified a consanguineous family segregating autosomal recessive congenital progressive hearing loss (ARNSHL) and retinal degeneration with central vestibular dysfunction having homozygosity for a DFNB59 mutation. (PMID:17301963)
• data indicate that nonsense mutations in DFNB59 cause nonsyndromic hearing loss, but that mutations in DFNB59 are not a major cause of nonsyndromic hearing impairment in the Turkish and Dutch population (PMID:17373699)
• Mutations in DFNB59 are associated with autosomal recessive non-syndromic hearing loss in about 6.7% of GJB2-negative families. (PMID:17718865)
• failed to detect the presence either of mutations T54I and R183W in the exon 2 and exon 4 or any other deafness-associated mutations in the whole DFNB59 gene in this family (PMID:19160860)
• a c.406C>T (p.R136X) nonsense mutation in the DFNB59 gene hearing loss in an isolated Arab population (PMID:21696384)
• OTOF and PJVK gene variants have a role in auditory neuropathy spectrum disorder in Chinese patients (PMID:21935370)
• Missense mutation in PJVK causes progressive hearing loss. (PMID:22617256)
• p.C312W fsX19 mutation causative of autosomal recessive, non-syndromic, prelingual sensorineural hearing impairment (PMID:25631766)
• 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)
• Study describes a genetic form of noise-induced hearing loss , by showing that pejvakin deficiency in mice and DFNB59 patients leads to hypervulnerability to sound, due to a peroxisomal deficiency. (PMID:26544938)
• We identified in Moroccan deaf patients two mutations in PJVK and one mutation in MYO15A described for the first time in association with non-syndromic recessive hearing loss (PMID:28964305)
• two mutations, one in MYO6 (c.554-1 G > A) gene and another in PJVK (c.547C > T) are responsible for 1% each of the Iranian ARNSHL patients (PMID:30582396)
• Novel Pathogenic Variants in PJVK, the Gene Encoding Pejvakin, in Subjects with Autosomal Recessive Non-Syndromic Hearing Impairment and Auditory Neuropathy Spectrum Disorder. (PMID:35052489)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Pjvk	ENSMUSG00000075267
rattus_norvegicus	Pjvk	ENSRNOG00000038165

Paralogs (4): GSDMB (ENSG00000073605), GSDMD (ENSG00000104518), GSDMC (ENSG00000147697), GSDMA (ENSG00000167914)

Protein

Protein identifiers

Pejvakin — Q0ZLH3 (reviewed: Q0ZLH3)

Alternative names: Autosomal recessive deafness type 59 protein

All UniProt accessions (7): A0A2R8Y564, A0A2R8Y7D2, A0A2R8YD96, A0PK15, Q0ZLH3, H7C1C3, H7C3A9

UniProt curated annotations — full annotation on UniProt →

Function. Peroxisome-associated protein required to protect auditory hair cells against noise-induced damage. Acts by regulating noise-induced peroxisome proliferation in auditory hair cells and neurons, and promoting autophagic degradation of damaged peroxisomes (pexophagy). Noise overexposure increases reactive oxygen species (ROS) levels, causing oxidative damage to auditory hair cells and resulting in hearing loss. PJVK acts as a ROS sensor that recruits the autophagy machinery to trigger pexophagy of peroxisomes damaged by oxidative stress. In addition to pexophagy, also required to promote peroxisome proliferation in response to sound overstimulation.

Subunit / interactions. Interacts with MAP1LC3B; interaction is direct. Interacts with IQGAP1. Interacts with ROCK2. Interacts with TRIOBP.

Subcellular location. Peroxisome membrane. Cell projection. Cilium.

Disease relevance. Deafness, autosomal recessive, 59 (DFNB59) [MIM:610220] A form of sensorineural hearing impairment with absent or severely abnormal auditory brainstem response but normal otoacoustic emissions (auditory neuropathy or auditory dys-synchrony). Auditory neuropathies result from a lesion in the area including the inner hair cells, connections between the inner hair cells and the cochlear branch of the auditory nerve, the auditory nerve itself and auditory pathways of the brainstem. The disease is caused by variants affecting the gene represented in this entry.

Miscellaneous. ‘Pejvakin’ means ’echo’ in Persian.

Similarity. Belongs to the gasdermin family.

RefSeq proteins (6): NP_001036167, NP_001340704, NP_001340705, NP_001340706, NP_001340707, NP_001356841 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR040460	Gasdermin_pore	Domain
IPR042377	GSDME	Family

Pfam: PF04598

UniProt features (10 total): sequence variant 9, chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q0ZLH3-F1	68.16	0.33

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: 83 (showing top): GOBP_SENSORY_PERCEPTION_OF_MECHANICAL_STIMULUS, GOBP_DETECTION_OF_MECHANICAL_STIMULUS_INVOLVED_IN_SENSORY_PERCEPTION, GOBP_CELLULAR_COMPONENT_MAINTENANCE, GOBP_NEUROGENESIS, GOBP_CELLULAR_RESPONSE_TO_OXYGEN_CONTAINING_COMPOUND, GOBP_MACROAUTOPHAGY, GOBP_DETECTION_OF_MECHANICAL_STIMULUS, GOBP_EAR_DEVELOPMENT, GOBP_RESPONSE_TO_OXYGEN_CONTAINING_COMPOUND, GOBP_RESPONSE_TO_ABIOTIC_STIMULUS, GOBP_MECHANORECEPTOR_DIFFERENTIATION, GOBP_DETECTION_OF_MECHANICAL_STIMULUS_INVOLVED_IN_SENSORY_PERCEPTION_OF_SOUND, GOBP_DETECTION_OF_ABIOTIC_STIMULUS, GOBP_DETECTION_OF_STIMULUS, GOBP_SENSORY_PERCEPTION

GO Biological Process (8): response to reactive oxygen species (GO:0000302), pexophagy (GO:0000425), sensory perception of sound (GO:0007605), detection of mechanical stimulus involved in sensory perception of sound (GO:0050910), programmed cell death in response to reactive oxygen species (GO:0097468), stereocilium maintenance (GO:0120045), regulation of peroxisome organization (GO:1900063), programmed cell death (GO:0012501)

GO Molecular Function (0):

GO Cellular Component (11): cytoplasm (GO:0005737), peroxisomal membrane (GO:0005778), cortical actin cytoskeleton (GO:0030864), ciliary rootlet (GO:0035253), neuronal cell body (GO:0043025), stereocilium base (GO:0120044), peroxisome (GO:0005777), cilium (GO:0005929), endomembrane system (GO:0012505), membrane (GO:0016020), cell projection (GO:0042995)

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	6
response to oxidative stress	1
response to oxygen-containing compound	1
macroautophagy	1
autophagy of peroxisome	1
sensory perception of mechanical stimulus	1
sensory perception of sound	1
nervous system process	1
detection of mechanical stimulus involved in sensory perception	1
programmed cell death	1
cellular response to reactive oxygen species	1
cellular component maintenance	1
inner ear receptor cell stereocilium organization	1
peroxisome organization	1
regulation of organelle organization	1
signal transduction	1
cell death	1
intracellular anatomical structure	1
peroxisome	1
microbody membrane	1
actin cytoskeleton	1
cortical cytoskeleton	1
cytoskeleton	1
cilium	1
somatodendritic compartment	1
cell body	1
stereocilium	1
microbody	1
intraciliary transport particle	1
membrane-bounded organelle	1
plasma membrane bounded cell projection	1
vacuole	1
plasma membrane	1

Protein interactions and networks

STRING

598 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PJVK	GSDMC	Q9BYG8	840
PJVK	GSDMB	Q8TAX9	827
PJVK	TMPRSS3	P57727	794
PJVK	TMPRSS4	Q9NRS4	738
PJVK	OTOF	Q9HC10	734
PJVK	MAP1LC3B	Q9GZQ8	703
PJVK	NLRP1	Q9C000	694
PJVK	MERTK	Q12866	688
PJVK	TMC1	Q8TDI8	683
PJVK	MYO15A	Q9UKN7	641
PJVK	NOD1	Q9Y239	634
PJVK	PCDH15	Q96QU1	633
PJVK	SLC26A4	O43511	633
PJVK	CDH23	Q9H251	627
PJVK	LHFPL5	Q8TAF8	626

IntAct

2 interactions, top by confidence:

A	B	Type	Score
DCAF4	IGLL5	psi-mi:“MI:0914”(association)	0.350

BioGRID (1): DFNB59 (Affinity Capture-MS)

ESM2 similar proteins: A2CJ06, O15050, P57764, P85967, Q0ZLH2, Q0ZLH3, Q12769, Q2HJH8, Q2KHK6, Q2NL11, Q32M21, Q32NG6, Q3MHH2, Q3TR54, Q3UIR3, Q402B2, Q5E9L4, Q5EB20, Q5PNP6, Q5RB52, Q5TGP6, Q5U228, Q5Y4Y6, Q5ZL79, Q61194, Q63517, Q6AYK4, Q6DRL4, Q6IQY5, Q6NU51, Q6ZUG5, Q7Z2Y8, Q7Z2Z1, Q80SU7, Q80ZQ3, Q8BJW5, Q8BQ33, Q8CB12, Q8CC70, Q8K1K4

Diamond homologs: O60443, Q0ZLH2, Q0ZLH3, Q7YS54, Q9Z2D3

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	30
Likely pathogenic	8
Uncertain significance	94
Likely benign	124
Benign	14

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1047877	GRCh37/hg19 2q31.1-31.3(chr2:171999572-182774361)	Pathogenic
1298	NM_001042702.5(PJVK):c.161C>T (p.Thr54Ile)	Pathogenic
1299	NM_001042702.5(PJVK):c.113dup (p.Lys41fs)	Pathogenic
1301	NM_001042702.5(PJVK):c.726del (p.Phe242fs)	Pathogenic
1302	NM_001042702.5(PJVK):c.988del (p.Val330fs)	Pathogenic
1303	NM_001042702.5(PJVK):c.122del (p.Lys41fs)	Pathogenic
1329504	NM_001042702.5(PJVK):c.671T>G (p.Leu224Arg)	Pathogenic
1329505	NM_001042702.5(PJVK):c.880del (p.His294fs)	Pathogenic
1329507	NM_001042702.5(PJVK):c.950del (p.Phe317fs)	Pathogenic
1935986	NM_001042702.5(PJVK):c.391_392insTA (p.Lys131fs)	Pathogenic
2092124	NM_001042702.5(PJVK):c.886C>T (p.Arg296Ter)	Pathogenic
2718001	NM_001042702.5(PJVK):c.93T>G (p.Tyr31Ter)	Pathogenic
2719460	NM_001042702.5(PJVK):c.56T>G (p.Leu19Ter)	Pathogenic
2720001	NM_001042702.5(PJVK):c.1028G>C (p.Cys343Ser)	Pathogenic
2734336	NM_001042702.5(PJVK):c.274C>T (p.Arg92Ter)	Pathogenic
2762251	NM_001042702.5(PJVK):c.716del (p.Thr239fs)	Pathogenic
2803977	NM_001042702.5(PJVK):c.206C>G (p.Ser69Ter)	Pathogenic
2807695	NM_001042702.5(PJVK):c.131_134del (p.Phe44fs)	Pathogenic
2831368	NM_001042702.5(PJVK):c.190_194del (p.Gly64fs)	Pathogenic
2844584	NM_001042702.5(PJVK):c.723del (p.Phe242fs)	Pathogenic
2868197	NM_001042702.5(PJVK):c.766+2T>G	Pathogenic
2905652	NM_001042702.5(PJVK):c.811_814del (p.Asp271fs)	Pathogenic
3001211	NM_001042702.5(PJVK):c.709dup (p.Glu237fs)	Pathogenic
3601636	NM_001042702.5(PJVK):c.199_200del (p.Glu67fs)	Pathogenic
3601637	NM_001042702.5(PJVK):c.226C>T (p.Gln76Ter)	Pathogenic
3601638	NM_001042702.5(PJVK):c.408-2A>G	Pathogenic
3677633	NM_001042702.5(PJVK):c.823del (p.Ser275fs)	Pathogenic
4727826	NM_001042702.5(PJVK):c.962_963del (p.Thr321fs)	Pathogenic
497396	NM_001042702.5(PJVK):c.515_516del (p.Ser172fs)	Pathogenic
560905	NM_001042702.5(PJVK):c.406C>T (p.Arg136Ter)	Pathogenic

SpliceAI

1536 predictions. Top by Δscore:

Variant	Effect	Δscore
2:178453411:T:G	acceptor_gain	1.0000
2:178453418:T:A	acceptor_gain	1.0000
2:178454353:T:A	acceptor_gain	1.0000
2:178460444:G:GT	donor_gain	1.0000
2:178460444:GAA:G	donor_gain	1.0000
2:178460447:G:GG	donor_gain	1.0000
2:178460977:TTTA:T	acceptor_loss	1.0000
2:178460979:TA:T	acceptor_loss	1.0000
2:178460980:A:AC	acceptor_loss	1.0000
2:178460980:A:AG	acceptor_gain	1.0000
2:178460981:G:GG	acceptor_gain	1.0000
2:178453361:A:AG	acceptor_gain	0.9900
2:178453362:A:G	acceptor_gain	0.9900
2:178453415:T:TA	acceptor_gain	0.9900
2:178453421:T:A	acceptor_gain	0.9900
2:178454077:A:AG	acceptor_gain	0.9900
2:178454347:A:AG	acceptor_gain	0.9900
2:178454351:ACT:A	acceptor_gain	0.9900
2:178456140:G:GT	donor_gain	0.9900
2:178456140:G:T	donor_gain	0.9900
2:178460461:GA:G	donor_gain	0.9900
2:178460981:GAT:G	acceptor_gain	0.9900
2:178460981:GATA:G	acceptor_gain	0.9900
2:178453366:T:TA	acceptor_gain	0.9800
2:178454351:A:AG	acceptor_gain	0.9800
2:178458508:A:AG	acceptor_gain	0.9800
2:178458509:G:GG	acceptor_gain	0.9800
2:178460422:T:G	donor_gain	0.9800
2:178460462:A:AG	donor_gain	0.9800
2:178460463:G:GG	donor_gain	0.9800

AlphaMissense

2297 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:178454483:A:C	K121N	1.000
2:178454483:A:T	K121N	1.000
2:178456078:T:A	V159D	1.000
2:178456093:G:C	R164P	1.000
2:178458583:C:A	A208D	1.000
2:178461140:T:C	C309R	1.000
2:178453413:T:C	F2L	0.999
2:178453414:T:C	F2S	0.999
2:178453414:T:G	F2C	0.999
2:178453415:T:A	F2L	0.999
2:178453415:T:G	F2L	0.999
2:178453423:C:A	A5D	0.999
2:178453435:T:C	F9S	0.999
2:178453474:T:A	V22D	0.999
2:178453594:T:C	L62P	0.999
2:178454350:T:C	L77S	0.999
2:178454470:G:T	G117V	0.999
2:178454476:T:A	V119E	0.999
2:178454481:A:G	K121E	0.999
2:178456086:A:C	S162R	0.999
2:178456088:C:A	S162R	0.999
2:178456088:C:G	S162R	0.999
2:178456090:T:A	I163N	0.999
2:178458580:T:A	I207K	0.999
2:178458580:T:G	I207R	0.999
2:178458582:G:C	A208P	0.999
2:178458585:T:C	F209L	0.999
2:178458587:C:A	F209L	0.999
2:178458587:C:G	F209L	0.999
2:178458601:T:C	L214P	0.999

dbSNP variants (sampled 300 via entrez): RS1000208344 (2:178452579 AT>A,ATT), RS1000239298 (2:178452769 G>A), RS1000277615 (2:178449465 T>A), RS1000389659 (2:178454670 A>G), RS1000415039 (2:178458166 G>A,C,T), RS1000598511 (2:178458570 C>T), RS1000891945 (2:178462076 A>C,G), RS1001008706 (2:178450821 G>A,C), RS1001368786 (2:178462183 A>G), RS1001633991 (2:178450572 G>A), RS1002021690 (2:178451178 C>A,G), RS1002126191 (2:178452503 A>T), RS1002155641 (2:178457064 G>A), RS1002371174 (2:178451335 A>C), RS1002992947 (2:178456915 G>A)

Disease associations

OMIM: gene MIM:610219 | disease phenotypes: MIM:610220, MIM:128600, MIM:220290, MIM:607197

GenCC curated gene-disease

Disease	Classification	Inheritance
nonsyndromic genetic hearing loss	Definitive	Autosomal recessive
autosomal recessive nonsyndromic hearing loss 59	Definitive	Autosomal recessive
hearing loss, autosomal recessive	Supportive	Autosomal recessive

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
nonsyndromic genetic hearing loss	Definitive	AR

Mondo (5): hearing loss disorder (MONDO:0005365), autosomal recessive nonsyndromic hearing loss 59 (MONDO:0012445), ear malformation (MONDO:0007500), hearing loss, autosomal recessive (MONDO:0019588), nonsyndromic genetic hearing loss (MONDO:0019497)

Orphanet (3): Rare autosomal recessive non-syndromic sensorineural deafness type DFNB (Orphanet:90636), Rare genetic deafness (Orphanet:96210), Rare autosomal dominant non-syndromic sensorineural deafness type DFNA (Orphanet:90635)

HPO phenotypes

2 total (2 of 2 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000407	Sensorineural hearing impairment

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST003332_1	Rapid functional decline in sporadic amyotrophic lateral sclerosis	2.000000e-08

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0007784	functional decline measurement

MeSH disease descriptors (4)

Descriptor	Name	Tree numbers
D034381	Hearing Loss	C09.218.458.341; C10.597.751.418.341; C23.888.592.763.393.341
C564609	Deafness, Autosomal Recessive (supp.)
C565698	Deafness, Autosomal Recessive 59 (supp.)
C580334	Nonsyndromic Deafness (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

16 total (human), top 16 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Nickel	decreases expression	2
Aflatoxin B1	increases expression, increases methylation	2
trichostatin A	increases expression	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
butyraldehyde	decreases expression	1
ferrous chloride	decreases expression	1
jinfukang	affects cotreatment, increases expression	1
Cisplatin	affects cotreatment, increases expression	1
Dimethyl Sulfoxide	affects expression	1
Oxygen	increases expression	1
Sodium Dodecyl Sulfate	increases expression	1
Tobacco Smoke Pollution	decreases expression	1
Valproic Acid	increases methylation	1
Cyclosporine	decreases expression	1
Okadaic Acid	decreases expression	1
Acrylamide	increases expression	1

Clinical trials (associated diseases)

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

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