OTOGL

Summary

OTOGL (otogelin like, HGNC:26901) is a protein-coding gene on chromosome 12q21.31, encoding Otogelin-like protein (Q3ZCN5).

The protein encoded by this gene belongs to the otogelin family. This gene is expressed in the inner ear of vertebrates with the highest level of expression seen at the embryonic stage and lowest in adult. Knockdown studies in zebrafish suggest that this gene is essential for normal inner ear function. Mutations in this gene are associated with autosomal recessive deafness.

Source: NCBI Gene 283310 — 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): 1,260 total — 50 pathogenic, 44 likely-pathogenic
• Phenotypes (HPO): 4
• Dosage sensitivity (ClinGen): haploinsufficiency autosomal recessive, triplosensitivity no evidence
• MANE Select transcript: NM_001378609

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:26901
Approved symbol	OTOGL
Name	otogelin like
Location	12q21.31
Locus type	gene with protein product
Status	Approved
Aliases	FLJ90579
Ensembl gene	ENSG00000165899
Ensembl biotype	protein_coding
OMIM	614925
Entrez	283310

Gene structure

Transcript identifiers

Ensembl transcripts: 8 — 4 protein_coding, 2 retained_intron, 2 nonsense_mediated_decay

ENST00000298820, ENST00000546620, ENST00000547103, ENST00000550182, ENST00000551340, ENST00000642294, ENST00000643417, ENST00000646859

RefSeq mRNA: 4 — MANE Select: NM_001378609 NM_001368062, NM_001378609, NM_001378610, NM_173591

CCDS: CCDS91730, CCDS91731

Canonical transcript exons

ENST00000547103 — 59 exons

Exon	Start	End
ENSE00001259590	80356416	80356520
ENSE00001548124	80267253	80267327
ENSE00001549907	80314305	80314331
ENSE00001550765	80254524	80254570
ENSE00001551735	80252076	80252201
ENSE00001552020	80336912	80337004
ENSE00001553313	80339075	80339264
ENSE00001554691	80265001	80265210
ENSE00001556151	80251693	80251799
ENSE00001556720	80353325	80353510
ENSE00001557937	80355736	80355948
ENSE00001558543	80352295	80352436
ENSE00001558841	80341948	80342162
ENSE00001559315	80329051	80329119
ENSE00001559410	80318546	80318713
ENSE00001560506	80253466	80253574
ENSE00001560764	80270102	80270154
ENSE00001561907	80271648	80271810
ENSE00001563704	80320422	80320700
ENSE00001564078	80266451	80266616
ENSE00001564115	80328665	80328744
ENSE00001564187	80323723	80323840
ENSE00001603158	80336797	80336820
ENSE00002210608	80261969	80262093
ENSE00002213206	80279028	80279166
ENSE00002216449	80278168	80278275
ENSE00002218161	80310611	80310727
ENSE00002219724	80232892	80233097
ENSE00002221966	80210847	80210886
ENSE00002231578	80257825	80258002
ENSE00002235715	80238851	80238978
ENSE00002235775	80217598	80217664
ENSE00002237616	80335963	80336140
ENSE00002239814	80255040	80255185
ENSE00002242147	80239333	80239439
ENSE00002259235	80313476	80313632
ENSE00002267288	80333005	80333078
ENSE00002281326	80296827	80296961
ENSE00002282991	80302634	80302783
ENSE00002284217	80211949	80211997
ENSE00002288006	80305576	80305695
ENSE00002289309	80222091	80222245
ENSE00002292709	80336413	80336555
ENSE00002293662	80219814	80219912
ENSE00002298694	80256337	80256460
ENSE00002310029	80229257	80229378
ENSE00003486997	80367561	80367739
ENSE00003514534	80370570	80370689
ENSE00003530794	80372019	80372064
ENSE00003570572	80377123	80377202
ENSE00003647856	80368205	80368309
ENSE00003687623	80356807	80356914
ENSE00003713410	80358860	80358900
ENSE00003725411	80366574	80366637
ENSE00003729953	80358248	80358349
ENSE00003752109	80358671	80358775
ENSE00003821415	80209413	80209510
ENSE00003829191	80099537	80099605
ENSE00003829652	80377848	80380880

Expression profiles

Bgee: expression breadth ubiquitous, 152 present calls, max score 82.35.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.1261 / max 32.8343, expressed in 44 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
127087	0.0972	38
127088	0.0289	6

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	82.35	gold quality
right atrium auricular region	UBERON:0006631	81.94	gold quality
cardiac atrium	UBERON:0002081	81.62	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	77.52	gold quality
secondary oocyte	CL:0000655	77.51	gold quality
Brodmann (1909) area 9	UBERON:0013540	69.82	gold quality
right frontal lobe	UBERON:0002810	67.69	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	67.36	gold quality
prefrontal cortex	UBERON:0000451	67.18	gold quality
islet of Langerhans	UBERON:0000006	66.59	gold quality
endothelial cell	CL:0000115	66.30	gold quality
frontal cortex	UBERON:0001870	65.10	gold quality
lower esophagus	UBERON:0013473	65.07	gold quality
lower esophagus muscularis layer	UBERON:0035833	65.05	gold quality
anterior cingulate cortex	UBERON:0009835	64.77	gold quality
neocortex	UBERON:0001950	63.98	gold quality
lower esophagus mucosa	UBERON:0035834	63.21	gold quality
muscle layer of sigmoid colon	UBERON:0035805	62.76	gold quality
cerebral cortex	UBERON:0000956	61.67	gold quality
hindlimb stylopod muscle	UBERON:0004252	61.48	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	61.43	gold quality
pituitary gland	UBERON:0000007	61.04	gold quality
Brodmann (1909) area 23	UBERON:0013554	60.42	gold quality
heart	UBERON:0000948	59.26	gold quality
adenohypophysis	UBERON:0002196	58.92	gold quality
tibial artery	UBERON:0007610	58.70	gold quality
popliteal artery	UBERON:0002250	58.69	gold quality
superior frontal gyrus	UBERON:0002661	58.40	gold quality
mucosa of stomach	UBERON:0001199	58.39	gold quality
oocyte	CL:0000023	58.07	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	7.39

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

63 targeting OTOGL, 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-4262	100.00	73.26	3931
HSA-MIR-1252-5P	100.00	69.80	2774
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-181A-5P	99.99	72.96	2995
HSA-MIR-181B-5P	99.99	72.97	2996
HSA-MIR-181C-5P	99.99	72.95	2996
HSA-MIR-181D-5P	99.99	73.04	2997
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-3692-3P	99.98	70.27	2139
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-1468-3P	99.96	72.74	3797
HSA-LET-7C-3P	99.95	73.42	2862
HSA-MIR-144-3P	99.94	73.98	2698
HSA-MIR-450B-5P	99.92	71.48	3175
HSA-MIR-3671	99.90	73.04	3897
HSA-MIR-95-5P	99.89	72.17	3973
HSA-MIR-137-3P	99.87	74.74	2401
HSA-MIR-548AZ-5P	99.83	69.94	3230
HSA-MIR-548T-5P	99.83	69.91	3220
HSA-MIR-3934-3P	99.76	65.51	1351
HSA-MIR-4679	99.76	69.19	1229
HSA-MIR-6505-5P	99.73	69.25	1595
HSA-MIR-132-3P	99.73	70.56	1424
HSA-MIR-212-3P	99.73	70.65	1424
HSA-MIR-4524A-3P	99.72	66.85	2406
HSA-MIR-4699-3P	99.71	70.15	3142
HSA-MIR-518A-5P	99.70	69.01	2209

Functional genomics

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

Literature-anchored findings (GeneRIF, showing 4)

• OTOGL mutations affect the production and/or function of acellular structures of the inner ear, which ultimately leads to sensorineural hearing loss. (PMID:23122586)
• Patients with OTOGL mutation show a flat to downsloping configuration of the audiogram with mild to moderate sensorineural hearing loss. Speech recognition scores remain good and vestibular hyporeflexia is present. (PMID:24378291)
• We identified novel biallelic OTOGL mutations in a Chinese autosomal recessive non-syndromic hearing loss family. (PMID:25829320)
• [Phenotype and genotype analysis of recessive hereditary moderate sensorineural hearing loss caused by new mutations in OTOGL gene]. (PMID:33455126)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	otogl	ENSDARG00000088750
mus_musculus	Otogl	ENSMUSG00000091455
rattus_norvegicus	Otogl	ENSRNOG00000030316

Paralogs (19): CHRDL2 (ENSG00000054938), CHRD (ENSG00000090539), CHRDL1 (ENSG00000101938), TECTA (ENSG00000109927), VWF (ENSG00000110799), MUC5B (ENSG00000117983), KCP (ENSG00000135253), ZAN (ENSG00000146839), CRIM1 (ENSG00000150938), BMPER (ENSG00000164619), VWCE (ENSG00000167992), VWC2L (ENSG00000174453), MUC6 (ENSG00000184956), OTOG (ENSG00000188162), VWC2 (ENSG00000188730), MUC2 (ENSG00000198788), MUC19 (ENSG00000205592), MUC5AC (ENSG00000215182), FCGBP (ENSG00000275395)

Protein

Protein identifiers

Otogelin-like protein — Q3ZCN5 (reviewed: Q3ZCN5)

All UniProt accessions (6): A0A2R8YCH1, A0A2R8YF04, Q3ZCN5, H0YIF7, H0YIL4, H7BXL6

UniProt curated annotations — full annotation on UniProt →

Subcellular location. Secreted.

Tissue specificity. Expressed at high levels in fetal inner ear and heart. Low levels in fetal skeletal muscle, kidney, spleen and colon. Not detected in fetal liver, lung, brain, nor in fetal stomach. In adult tissues, highest levels in brain, kidney, heart and retina. Relatively low levels in lung, spleen and duodenum. Not detected in adult skeletal muscle, liver, nor testis.

Disease relevance. Deafness, autosomal recessive, 84B (DFNB84B) [MIM:614944] A form of non-syndromic deafness characterized by congenital, non-progressive, sensorineural, symmetric hearing loss. Vestibular hypofunction is rarely observed. The disease is caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the otogelin family.

RefSeq proteins (4): NP_001354991, NP_001365538, NP_001365539, NP_775862 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001007	VWF_dom	Domain
IPR001846	VWF_type-D	Domain
IPR002919	TIL_dom	Domain
IPR006207	Cys_knot_C	Domain
IPR007934	AbfB_ABD	Domain
IPR014853	VWF/SSPO/ZAN-like_Cys-rich_dom	Domain
IPR036084	Ser_inhib-like_sf	Homologous_superfamily
IPR036195	AbfB_ABD_sf	Homologous_superfamily
IPR050780	Mucin_vWF_Thrombospondin_sf	Family
IPR058753	TIL_OTOGL_Mucin	Domain
IPR058754	OTOGL-like_N	Domain
IPR058755	Fn1-VW_OTOGL	Domain

Pfam: PF00094, PF01826, PF05270, PF08742, PF25960, PF25961, PF25962

UniProt features (35 total): disulfide bond 12, glycosylation site 8, domain 7, sequence conflict 4, sequence variant 2, signal peptide 1, chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q3ZCN5-F1	72.19	0.07

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 (12): 123–257, 145–296, 483–618, 505–653, 527–535, 948–1078, 992–999, 1536–1683, 2261–2317, 2282–2331, 2293–2348, 2297–2350

Glycosylation sites (8): 434, 473, 826, 876, 1289, 1604, 2198, 144

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-9662361	Sensory processing of sound by outer hair cells of the cochlea

MSigDB gene sets: 75 (showing top): TGCTGCT_MIR15A_MIR16_MIR15B_MIR195_MIR424_MIR497, GOBP_SENSORY_PERCEPTION_OF_MECHANICAL_STIMULUS, GOBP_NEUROGENESIS, GOBP_EAR_DEVELOPMENT, AML_Q6, GOMF_EXTRACELLULAR_MATRIX_STRUCTURAL_CONSTITUENT, chr12q21, WTGAAAT_UNKNOWN, GOBP_CARBOHYDRATE_METABOLIC_PROCESS, GOBP_MECHANORECEPTOR_DIFFERENTIATION, GOBP_SENSORY_PERCEPTION, GOBP_SENSORY_ORGAN_DEVELOPMENT, GOBP_CELL_PROJECTION_ORGANIZATION, AML1_01, GOBP_MONOSACCHARIDE_METABOLIC_PROCESS

GO Biological Process (5): intracellular protein localization (GO:0008104), L-arabinose metabolic process (GO:0046373), vibrational conductance of sound to the inner ear (GO:0055127), inner ear receptor cell stereocilium organization (GO:0060122), sensory perception of sound (GO:0007605)

GO Molecular Function (3): extracellular matrix structural constituent (GO:0005201), alpha-L-arabinofuranosidase activity (GO:0046556), protein binding (GO:0005515)

GO Cellular Component (3): obsolete extracellular space (GO:0005615), extracellular matrix (GO:0031012), extracellular region (GO:0005576)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Sensory processing of sound	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
macromolecule localization	1
arabinose metabolic process	1
sensory perception of sound	1
multicellular organismal process	1
neuron projection development	1
inner ear receptor cell development	1
sensory perception of mechanical stimulus	1
structural molecule activity	1
extracellular matrix	1
hydrolase activity, hydrolyzing O-glycosyl compounds	1
binding	1
external encapsulating structure	1
cellular anatomical structure	1

Protein interactions and networks

STRING

1326 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
OTOGL	STRC	Q7RTU9	774
OTOGL	CEACAM16	Q2WEN9	742
OTOGL	TECTB	Q96PL2	715
OTOGL	OTOL1	A6NHN0	656
OTOGL	TSPEAR	Q8WU66	549
OTOGL	KCNQ4	P56696	532
OTOGL	TECTA	O75443	529
OTOGL	MYO15A	Q9UKN7	527
OTOGL	OTOG	Q6ZRI0	516
OTOGL	ADGRV1	Q8WXG9	512
OTOGL	TMC1	Q8TDI8	471
OTOGL	SLC17A8	Q8NDX2	468
OTOGL	MYO7A	P78427	465
OTOGL	CDH23	Q9H251	459
OTOGL	OTOF	Q9HC10	459

IntAct

4 interactions, top by confidence:

A	B	Type	Score
HTT	OTOGL	psi-mi:“MI:0915”(physical association)	0.560

ESM2 similar proteins: A0A292G9J6, A0A8M9PFP2, A1L2K1, A2A863, A7E2Z9, B0S5G3, B5MFE9, F1R520, F7A4A7, F8VQ03, O93449, O94985, P16144, P35447, P53813, P98089, Q08761, Q0V9V5, Q0VCN6, Q28483, Q3ZCN5, Q5R9Q9, Q5RCW9, Q5RD64, Q61592, Q63772, Q64632, Q6DDW2, Q6DFV8, Q6PZE0, Q6Q0N0, Q8BH34, Q8BJD1, Q8CFM6, Q8CIZ8, Q8CJ69, Q8K410, Q8N2E2, Q8N8U9, Q8R553

Diamond homologs: F1NBL0, F7A4A7, P0DM55, P98088, P98091, P98092, Q02817, Q28295, Q28833, Q2PC93, Q3ZCN5, Q62635, Q6PZE0, Q6W4X9, Q7Z5P9, Q80T03, Q80Z19, Q8T0W0, Q98UI9, Q9HC84, O55225, P04275, P80012, Q5RCW9, Q6ZRI0, Q8CIZ8, Q9U8M0, Q9V496, A2VEC9, P98167, Q3U492, Q700K0, Q8CG65, P0DM56, P18614, P56199, Q3V0T4, Q3V3R4, Q62469, Q62935

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

1260 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	50
Likely pathogenic	44
Uncertain significance	549
Likely benign	324
Benign	174

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1071395	NM_001378609.3(OTOGL):c.5742del (p.Glu1914fs)	Pathogenic
1176602	NM_001378609.3(OTOGL):c.4273C>T (p.Arg1425Ter)	Pathogenic
1254654	NM_001378609.3(OTOGL):c.3501C>A (p.Cys1167Ter)	Pathogenic
1298551	NM_001378609.3(OTOGL):c.1834A>T (p.Arg612Ter)	Pathogenic
1323400	NM_001378609.3(OTOGL):c.2391-2A>G	Pathogenic
1323401	NM_001378609.3(OTOGL):c.6064G>T (p.Glu2022Ter)	Pathogenic
1386809	NM_001378609.3(OTOGL):c.6427G>T (p.Glu2143Ter)	Pathogenic
1424442	NM_001378609.3(OTOGL):c.3210G>A (p.Trp1070Ter)	Pathogenic
1451847	NM_001378609.3(OTOGL):c.4353G>A (p.Trp1451Ter)	Pathogenic
1456193	NM_001378609.3(OTOGL):c.6271G>T (p.Glu2091Ter)	Pathogenic
1457939	NM_001378609.3(OTOGL):c.6703_6706dup (p.Pro2236fs)	Pathogenic
1526105	NM_001378609.3(OTOGL):c.6355C>T (p.Gln2119Ter)	Pathogenic
1693320	NM_001378609.3(OTOGL):c.5632del (p.Glu1878fs)	Pathogenic
2427503	NC_000012.11:g.(?80714182)(80714500_?)del	Pathogenic
2578689	NM_001378609.3(OTOGL):c.3675del (p.Ser1226fs)	Pathogenic
2697187	NM_001378609.3(OTOGL):c.2939del (p.Asp980fs)	Pathogenic
2697188	NM_001378609.3(OTOGL):c.4805del (p.Lys1602fs)	Pathogenic
2744059	NM_001378609.3(OTOGL):c.5826T>A (p.Cys1942Ter)	Pathogenic
2790641	NM_001378609.3(OTOGL):c.3593del (p.Ser1198fs)	Pathogenic
2850746	NM_001378609.3(OTOGL):c.3363del (p.Cys1122fs)	Pathogenic
2874493	NM_001378609.3(OTOGL):c.3555C>A (p.Tyr1185Ter)	Pathogenic
2877973	NC_000012.12:g.80254523GT[4]	Pathogenic
2889105	NM_001378609.3(OTOGL):c.1489C>T (p.Arg497Ter)	Pathogenic
291087	NM_001378609.3(OTOGL):c.3103C>T (p.Gln1035Ter)	Pathogenic
2991531	NM_001378609.3(OTOGL):c.5297G>A (p.Trp1766Ter)	Pathogenic
2999764	NM_001378609.3(OTOGL):c.1349T>G (p.Leu450Ter)	Pathogenic
3244447	NC_000012.11:g.(?80704371)(80708131_?)del	Pathogenic
3244448	NC_000012.11:g.(?80750567)(80752700_?)del	Pathogenic
3383056	NM_001378609.3(OTOGL):c.6501dup (p.Cys2168fs)	Pathogenic
3601567	NM_001378609.3(OTOGL):c.6436G>T (p.Glu2146Ter)	Pathogenic

SpliceAI

8047 predictions. Top by Δscore:

Variant	Effect	Δscore
12:80217594:A:AG	acceptor_gain	1.0000
12:80217595:A:G	acceptor_gain	1.0000
12:80219808:CCTCA:C	acceptor_loss	1.0000
12:80219809:CTCA:C	acceptor_loss	1.0000
12:80219810:TCA:T	acceptor_loss	1.0000
12:80219811:CAG:C	acceptor_loss	1.0000
12:80219812:A:T	acceptor_loss	1.0000
12:80219813:G:GA	acceptor_loss	1.0000
12:80219908:GATCA:G	donor_gain	1.0000
12:80219909:A:G	donor_gain	1.0000
12:80219909:ATCA:A	donor_gain	1.0000
12:80219910:TCA:T	donor_gain	1.0000
12:80219911:CAGT:C	donor_loss	1.0000
12:80219912:AG:A	donor_loss	1.0000
12:80219913:G:GG	donor_gain	1.0000
12:80219914:TAA:T	donor_loss	1.0000
12:80222089:A:AG	acceptor_gain	1.0000
12:80222090:G:GG	acceptor_gain	1.0000
12:80222090:GT:G	acceptor_gain	1.0000
12:80222090:GTCC:G	acceptor_gain	1.0000
12:80222090:GTCCC:G	acceptor_gain	1.0000
12:80232889:A:AG	acceptor_gain	1.0000
12:80232890:A:G	acceptor_gain	1.0000
12:80232891:G:GG	acceptor_gain	1.0000
12:80233093:GCAAG:G	donor_gain	1.0000
12:80233095:AAGG:A	donor_loss	1.0000
12:80233096:AGG:A	donor_loss	1.0000
12:80233097:GGTA:G	donor_loss	1.0000
12:80233099:T:A	donor_loss	1.0000
12:80251684:A:AG	acceptor_gain	1.0000

AlphaMissense

15702 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000011328 (12:80304264 A>G,T), RS1000011806 (12:80168355 T>A), RS1000043924 (12:80169471 G>A), RS1000078464 (12:80279223 C>G,T), RS1000087129 (12:80366503 T>G), RS1000096175 (12:80287108 A>C), RS1000098353 (12:80117134 T>A,C), RS1000101624 (12:80346871 G>T), RS1000102713 (12:80127276 T>G), RS1000114506 (12:80191299 G>A), RS1000120273 (12:80192942 G>A), RS1000142907 (12:80151980 G>A), RS1000192399 (12:80235505 G>A), RS1000208555 (12:80148016 C>T), RS1000210855 (12:80205718 A>G)

Disease associations

OMIM: gene MIM:614925 | disease phenotypes: MIM:614944, MIM:156000, MIM:220290, MIM:607197

GenCC curated gene-disease

Disease	Classification	Inheritance
nonsyndromic genetic hearing loss	Definitive	Autosomal recessive
autosomal recessive nonsyndromic hearing loss 84B	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 (6): autosomal recessive nonsyndromic hearing loss 84B (MONDO:0013984), hearing loss disorder (MONDO:0005365), Meniere disease (MONDO:0007972), nonsyndromic genetic hearing loss (MONDO:0019497), hearing loss, autosomal recessive (MONDO:0019588), megacolon (MONDO:0001273)

Orphanet (5): Rare autosomal recessive non-syndromic sensorineural deafness type DFNB (Orphanet:90636), Rare genetic deafness (Orphanet:96210), Rare non-syndromic genetic deafness (Orphanet:87884), Rare autosomal dominant non-syndromic sensorineural deafness type DFNA (Orphanet:90635), NON RARE IN EUROPE: Menière disease (Orphanet:45360)

HPO phenotypes

4 total (4 of 4 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000407	Sensorineural hearing impairment
HP:0001756	Vestibular hyporeflexia
HP:0003577	Congenital onset

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST006813_3	End stage renal disease x APOL1 genotype interaction	9.000000e-07

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0009324	APOL1 risk genotype carrier status

MeSH disease descriptors (5)

Descriptor	Name	Tree numbers
D034381	Hearing Loss	C09.218.458.341; C10.597.751.418.341; C23.888.592.763.393.341
D008531	Megacolon	C06.405.469.158.701
D008575	Meniere Disease	C09.218.568.217.500
C564609	Deafness, Autosomal Recessive (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

17 total (human), top 17 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression	3
(+)-JQ1 compound	decreases expression	2
sodium arsenite	increases expression	1
benzo(e)pyrene	decreases methylation	1
aflatoxin B2	decreases methylation	1
triadimefon	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
dorsomorphin	affects cotreatment, increases expression	1
bisphenol S	decreases expression	1
2,6-dichloro-(1,4)benzoquinone	increases expression	1
Sunitinib	decreases expression	1
Vorinostat	increases expression	1
Benzo(a)pyrene	affects methylation	1
Doxorubicin	increases expression	1
Estradiol	decreases expression	1
Methapyrilene	decreases methylation	1
Tobacco Smoke Pollution	affects 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