OTOG

Summary

OTOG (otogelin, HGNC:8516) is a protein-coding gene on chromosome 11p15.1, encoding Otogelin (Q6ZRI0). Glycoprotein specific to acellular membranes of the inner ear.

The protein encoded by this gene is a component of the acellular membranes of the inner ear. Disruption of the orthologous mouse gene shows that it plays a role in auditory and vestibular functions. It is involved in fibrillar network organization, the anchoring of otoconial membranes and cupulae to the neuroepithelia, and likely in sound stimulation resistance. Mutations in this gene cause autosomal recessive nonsyndromic deafness, type 18B. Alternative splicing of this gene results in multiple transcript variants.

Source: NCBI Gene 340990 — RefSeq curated summary.

At a glance

• Gene–disease (curated): nonsyndromic genetic hearing loss (Definitive, ClinGen) — +2 more curated relationships
• GWAS associations: 2
• Clinical variants (ClinVar): 1,515 total — 54 pathogenic, 59 likely-pathogenic
• Phenotypes (HPO): 5
• MANE Select transcript: NM_001292063

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:8516
Approved symbol	OTOG
Name	otogelin
Location	11p15.1
Locus type	gene with protein product
Status	Approved
Aliases	mlemp, OTGN, FLJ46346
Ensembl gene	ENSG00000188162
Ensembl biotype	protein_coding
OMIM	604487
Entrez	340990

Gene structure

Transcript identifiers

Ensembl transcripts: 6 — 3 retained_intron, 3 protein_coding

ENST00000342528, ENST00000399391, ENST00000399397, ENST00000428619, ENST00000485669, ENST00000498332

RefSeq mRNA: 2 — MANE Select: NM_001292063 NM_001277269, NM_001292063

CCDS: CCDS59225, CCDS76390

Canonical transcript exons

ENST00000399397 — 56 exons

Exon	Start	End
ENSE00001365196	17612620	17612765
ENSE00001366319	17596038	17596154
ENSE00001367237	17605857	17606135
ENSE00001367866	17609655	17611423
ENSE00001371602	17596851	17597007
ENSE00001372219	17593610	17593756
ENSE00001373439	17631702	17631922
ENSE00001374281	17633680	17633874
ENSE00001378491	17612162	17612330
ENSE00001378629	17608296	17608413
ENSE00001378956	17629133	17629316
ENSE00001380078	17638451	17638549
ENSE00001380404	17602210	17602377
ENSE00001381894	17594047	17594166
ENSE00001382176	17613612	17613701
ENSE00001384720	17635610	17635711
ENSE00001385410	17632088	17632226
ENSE00001390199	17609130	17609209
ENSE00001390315	17593193	17593327
ENSE00001537950	17645744	17646044
ENSE00001537953	17645564	17645643
ENSE00001537954	17643461	17643506
ENSE00001537956	17642127	17642246
ENSE00001537958	17641847	17641951
ENSE00001537961	17640913	17641091
ENSE00001537962	17640745	17640820
ENSE00001537964	17639423	17639463
ENSE00001537974	17635080	17635187
ENSE00001537977	17634844	17634948
ENSE00001537979	17634069	17634281
ENSE00001537995	17599671	17599697
ENSE00001538005	17591450	17591588
ENSE00001538007	17578373	17578526
ENSE00001538008	17576868	17576911
ENSE00001538009	17576556	17576630
ENSE00001538014	17574720	17574912
ENSE00001538018	17573078	17573290
ENSE00001538040	17572080	17572204
ENSE00001538041	17570213	17570390
ENSE00001538059	17547927	17547987
ENSE00003473013	17560709	17560817
ENSE00003477968	17558538	17558644
ENSE00003521557	17558185	17558315
ENSE00003525669	17553365	17553519
ENSE00003525684	17559052	17559161
ENSE00003547872	17555779	17555897
ENSE00003568530	17569156	17569288
ENSE00003577477	17548152	17548212
ENSE00003595599	17559534	17559662
ENSE00003632643	17561091	17561137
ENSE00003641134	17586474	17586581
ENSE00003652347	17561662	17561807
ENSE00003688156	17553119	17553211
ENSE00003689620	17552000	17552075
ENSE00003689999	17557118	17557323
ENSE00003763445	17547259	17547466

Expression profiles

Bgee: expression breadth broad, 25 present calls, max score 76.04.

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	76.04	gold quality
ventricular zone	UBERON:0003053	57.99	silver quality
ganglionic eminence	UBERON:0004023	54.77	gold quality
right testis	UBERON:0004534	53.37	gold quality
left testis	UBERON:0004533	52.69	gold quality
testis	UBERON:0000473	52.34	gold quality
pituitary gland	UBERON:0000007	52.18	gold quality
granulocyte	CL:0000094	49.79	silver quality
adenohypophysis	UBERON:0002196	49.17	gold quality
colonic epithelium	UBERON:0000397	44.89	gold quality
superior frontal gyrus	UBERON:0002661	44.15	gold quality
prefrontal cortex	UBERON:0000451	42.29	gold quality
primary visual cortex	UBERON:0002436	41.31	gold quality
monocyte	CL:0000576	40.26	gold quality
bone marrow cell	CL:0002092	40.18	gold quality
sural nerve	UBERON:0015488	39.49	gold quality
frontal cortex	UBERON:0001870	39.03	gold quality
stromal cell of endometrium	CL:0002255	38.50	gold quality
putamen	UBERON:0001874	37.12	gold quality
duodenum	UBERON:0002114	36.58	gold quality
cortical plate	UBERON:0005343	36.47	gold quality
cerebral cortex	UBERON:0000956	35.99	gold quality
caudate nucleus	UBERON:0001873	35.62	silver quality
brain	UBERON:0000955	35.44	gold quality
hindlimb stylopod muscle	UBERON:0004252	35.28	gold quality
Ammon’s horn	UBERON:0001954	35.24	silver quality
Brodmann (1909) area 9	UBERON:0013540	35.24	gold quality
apex of heart	UBERON:0002098	34.63	gold quality
right frontal lobe	UBERON:0002810	33.85	gold quality
muscle tissue	UBERON:0002385	33.84	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.89

Regulation

Is transcription factor: no

Literature-anchored findings (GeneRIF, showing 6)

• study reports the identification of mutations in OTOG as a cause of moderate nonsyndromic hearing loss (PMID:23122587)
• Patients with OTOG 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)
• A novel truncation mutation in OTOG gene is associated with prelingual mild hearing loss without vestibular dysfunction. (PMID:29800624)
• Burden of Rare Variants in the OTOG Gene in Familial Meniere’s Disease. (PMID:33136635)
• Prediction and interpretation of rare missense variant in OTOG associated with hearing loss. (PMID:34118384)
• An overload of missense variants in the OTOG gene may drive a higher prevalence of familial Meniere disease in the European population. (PMID:38519595)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	otog	ENSDARG00000068460
mus_musculus	Otog	ENSMUSG00000009487
rattus_norvegicus	Otog	ENSRNOG00000010983

Paralogs (19): CHRDL2 (ENSG00000054938), CHRD (ENSG00000090539), CHRDL1 (ENSG00000101938), TECTA (ENSG00000109927), VWF (ENSG00000110799), MUC5B (ENSG00000117983), KCP (ENSG00000135253), ZAN (ENSG00000146839), CRIM1 (ENSG00000150938), BMPER (ENSG00000164619), OTOGL (ENSG00000165899), VWCE (ENSG00000167992), VWC2L (ENSG00000174453), MUC6 (ENSG00000184956), VWC2 (ENSG00000188730), MUC2 (ENSG00000198788), MUC19 (ENSG00000205592), MUC5AC (ENSG00000215182), FCGBP (ENSG00000275395)

Protein

Protein identifiers

Otogelin — Q6ZRI0 (reviewed: Q6ZRI0)

All UniProt accessions (3): C9IZ84, Q6ZRI0, H9KVB3

UniProt curated annotations — full annotation on UniProt →

Function. Glycoprotein specific to acellular membranes of the inner ear. May be required for the anchoring of the otoconial membranes and cupulae to the underlying neuroepithelia in the vestibule. May be involved in the organization and/or stabilization of the fibrillar network that compose the tectorial membrane in the cochlea. May play a role in mechanotransduction processes.

Subcellular location. Apical cell membrane. Secreted. Extracellular space.

Post-translational modifications. N-glycosylated. Not O-glycosylated.

Disease relevance. Deafness, autosomal recessive, 18B (DFNB18B) [MIM:614945] A form of non-syndromic deafness characterized by a moderate hearing impairment, which can be associated with vestibular dysfunction, and a flat to shallow ‘U’ or slightly downsloping shaped audiograms. The disease is caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the otogelin family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q6ZRI0-1	1	yes
Q6ZRI0-2	2

RefSeq proteins (2): NP_001264198, NP_001278992* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000742	EGF	Domain
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, PF23244, PF25960, PF25961, PF25962

UniProt features (64 total): sequence variant 17, disulfide bond 15, domain 7, region of interest 6, compositionally biased region 6, splice variant 6, glycosylation site 3, sequence conflict 2, signal peptide 1, chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

No AlphaFold model available for Q6ZRI0 — AlphaFold DB does not currently provide models for proteins above ~3000 aa.

Functional residue map

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

Disulfide bonds (15): 106–120, 114–126, 128–138, 152–285, 199–206, 514–652, 536–687, 558–566, 986–1115, 1030–1037, 2112–2249, 2840–2889, 2854–2903, 2865–2920, 2869–2922

Glycosylation sites (3): 914, 1478, 1612

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: 51 (showing top): GOMF_EXTRACELLULAR_MATRIX_STRUCTURAL_CONSTITUENT, GOBP_CARBOHYDRATE_METABOLIC_PROCESS, GOCC_APICAL_PLASMA_MEMBRANE, GOBP_MONOSACCHARIDE_METABOLIC_PROCESS, GOBP_PENTOSE_METABOLIC_PROCESS, GOCC_APICAL_PART_OF_CELL, GOCC_PLASMA_MEMBRANE_REGION, GOMF_HYDROLASE_ACTIVITY_ACTING_ON_GLYCOSYL_BONDS, GOMF_HYDROLASE_ACTIVITY_HYDROLYZING_O_GLYCOSYL_COMPOUNDS, GOMF_STRUCTURAL_MOLECULE_ACTIVITY, MARTENS_TRETINOIN_RESPONSE_UP, FOSTER_KDM1A_TARGETS_UP, GOCC_EXTERNAL_ENCAPSULATING_STRUCTURE, NABA_ECM_GLYCOPROTEINS, NME2_TARGET_GENES

GO Biological Process (7): nervous system development (GO:0007399), L-arabinose metabolic process (GO:0046373), sensory perception of sound (GO:0007605), intracellular protein localization (GO:0008104), adult locomotory behavior (GO:0008344), vibrational conductance of sound to the inner ear (GO:0055127), inner ear receptor cell stereocilium organization (GO:0060122)

GO Molecular Function (4): extracellular matrix structural constituent (GO:0005201), alpha-L-arabinofuranosidase activity (GO:0046556), structural molecule activity (GO:0005198), protein binding (GO:0005515)

GO Cellular Component (7): obsolete extracellular space (GO:0005615), apical plasma membrane (GO:0016324), extracellular matrix (GO:0031012), extracellular region (GO:0005576), cytosol (GO:0005829), plasma membrane (GO:0005886), membrane (GO:0016020)

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
cellular anatomical structure	3
system development	1
arabinose metabolic process	1
sensory perception of mechanical stimulus	1
macromolecule localization	1
locomotory behavior	1
adult behavior	1
sensory perception of sound	1
multicellular organismal process	1
neuron projection development	1
inner ear receptor cell development	1
structural molecule activity	1
extracellular matrix	1
hydrolase activity, hydrolyzing O-glycosyl compounds	1
molecular_function	1
binding	1
apical part of cell	1
plasma membrane region	1
external encapsulating structure	1
cytoplasm	1
membrane	1
cell periphery	1

Protein interactions and networks

STRING

1286 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
OTOG	TECTB	Q96PL2	974
OTOG	OTOA	Q7RTW8	955
OTOG	STRC	Q7RTU9	860
OTOG	E9PNW1	E9PNW1	843
OTOG	CEACAM16	Q2WEN9	753
OTOG	OTOL1	A6NHN0	704
OTOG	OTOF	Q9HC10	666
OTOG	MYO15A	Q9UKN7	641
OTOG	KCNQ4	P56696	627
OTOG	MYO7A	P78427	597
OTOG	MYO6	Q9UM54	595
OTOG	ADGRV1	Q8WXG9	591
OTOG	SLC26A5	P58743	590
OTOG	CDH23	Q9H251	589
OTOG	OC90	Q02509	587

IntAct

8 interactions, top by confidence:

A	B	Type	Score
YWHAB	PIK3C2A	psi-mi:“MI:0914”(association)	0.800
YWHAG	BLTP3B	psi-mi:“MI:0914”(association)	0.640
YWHAE	PIK3C2A	psi-mi:“MI:0914”(association)	0.570
YWHAH	BLTP3B	psi-mi:“MI:0914”(association)	0.570
YWHAZ	PIK3C2A	psi-mi:“MI:0914”(association)	0.570
YWHAQ	MCRIP1	psi-mi:“MI:0914”(association)	0.350
EPHA1	PIK3R2	psi-mi:“MI:2364”(proximity)	0.270

BioGRID (9): OTOG (Proximity Label-MS), OTOG (Affinity Capture-MS), OTOG (Affinity Capture-MS), OTOG (Affinity Capture-MS), OTOG (Affinity Capture-MS), OTOG (Affinity Capture-MS), OTOG (Affinity Capture-MS), OTOG (Affinity Capture-MS), OTOG (Reconstituted Complex)

ESM2 similar proteins: A0A0R4IKU3, A1A5Y0, A2ASQ1, A2VCU8, A6QR11, O42182, O55225, P01130, P01131, P01132, P01133, P07522, P20063, P25304, P31696, P35950, P35951, P35952, P97607, Q00968, Q14393, Q28832, Q501P1, Q53RD9, Q5R3Z7, Q61220, Q61592, Q62918, Q62919, Q63772, Q66PY1, Q6ZRI0, Q75N90, Q7T3Q2, Q7ZXL5, Q8AWW5, Q8CJ69, Q8IX30, Q8N8U9, Q8R4Y4

Diamond homologs: A2VEC9, A6QNY1, B3EWZ3, B3EWZ8, C0HL12, C5IAW9, D3YXG0, D3ZTD8, F1LW30, O08721, O08722, O08747, O14514, O15072, O55225, O60241, O60242, O75173, O88783, O95185, O95450, P04275, P07358, P07996, P27918, P35441, P35442, P35448, P55314, P57110, P58397, P58459, P59384, P79331, P80012, P97857, P98088, P98092, P98160, P98164

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 11 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Activation of BAD and translocation to mitochondria	6	415.3×	7e-14
Chk1/Chk2(Cds1) mediated inactivation of Cyclin B:Cdk1 complex	6	366.4×	8e-14
SARS-CoV-1 targets host intracellular signalling and regulatory pathways	6	366.4×	8e-14
Activation of BH3-only proteins	6	270.8×	5e-13
RHO GTPases activate PKNs	6	173.0×	8e-12
Intrinsic Pathway for Apoptosis	6	159.7×	1e-11
SARS-CoV-1-host interactions	6	95.8×	3e-10
Apoptosis	6	91.6×	3e-10

GO biological processes:

GO term	Partners	Fold	FDR
protein targeting	5	166.5×	6e-09
intracellular protein localization	6	57.1×	2e-08

Disease & clinical

Clinical variants and AI predictions

ClinVar

1515 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	54
Likely pathogenic	59
Uncertain significance	572
Likely benign	477
Benign	196

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1069694	NM_001292063.2(OTOG):c.4037del (p.Val1346fs)	Pathogenic
1074443	NM_001292063.2(OTOG):c.5707C>T (p.Arg1903Ter)	Pathogenic
1220328	NM_001292063.2(OTOG):c.4985del (p.Gly1662fs)	Pathogenic
1298383	NM_001292063.2(OTOG):c.1198C>T (p.Gln400Ter)	Pathogenic
1323392	NM_001292063.2(OTOG):c.4309C>T (p.Gln1437Ter)	Pathogenic
1323395	NM_001292063.2(OTOG):c.1410_1411del (p.Tyr471fs)	Pathogenic
1323397	NM_001292063.2(OTOG):c.6068del (p.Gly2023fs)	Pathogenic
1323398	NM_001292063.2(OTOG):c.6721del (p.Asp2241fs)	Pathogenic
1323399	NM_001292063.2(OTOG):c.4380del (p.Thr1461fs)	Pathogenic
1375022	NM_001292063.2(OTOG):c.3186G>A (p.Trp1062Ter)	Pathogenic
1375656	NM_001292063.2(OTOG):c.6637C>T (p.Gln2213Ter)	Pathogenic
1389922	NM_001292063.2(OTOG):c.2080+2_2080+12del	Pathogenic
1413462	NM_001292063.2(OTOG):c.7268-2A>T	Pathogenic
1451286	NM_001292063.2(OTOG):c.7781_7784dup (p.Tyr2596fs)	Pathogenic
1451999	NM_001292063.2(OTOG):c.7630C>T (p.Arg2544Ter)	Pathogenic
1452273	NM_001292063.2(OTOG):c.3284G>A (p.Trp1095Ter)	Pathogenic
1454855	NM_001292063.2(OTOG):c.996+1G>T	Pathogenic
1456319	NM_001292063.2(OTOG):c.925C>T (p.Gln309Ter)	Pathogenic
1456548	NM_001292063.2(OTOG):c.7180C>T (p.Gln2394Ter)	Pathogenic
1456906	NM_001292063.2(OTOG):c.7422del (p.Phe2474fs)	Pathogenic
1805713	NM_001292063.2(OTOG):c.2523T>A (p.Tyr841Ter)	Pathogenic
1956821	NM_001292063.2(OTOG):c.3967C>T (p.Gln1323Ter)	Pathogenic
2034964	NM_001292063.2(OTOG):c.6694C>T (p.Gln2232Ter)	Pathogenic
2051588	NM_001292063.2(OTOG):c.6330del (p.Phe2111fs)	Pathogenic
2083432	NM_001292063.2(OTOG):c.4507del (p.Ala1503fs)	Pathogenic
2445642	NM_001292063.2(OTOG):c.3546C>A (p.Tyr1182Ter)	Pathogenic
2445643	NM_001292063.2(OTOG):c.6469del (p.Leu2156_Val2157insTer)	Pathogenic
2445644	NM_001292063.2(OTOG):c.7686C>G (p.Tyr2562Ter)	Pathogenic
2570796	NM_001292063.2(OTOG):c.2214C>A (p.Cys738Ter)	Pathogenic
2702302	NM_001292063.2(OTOG):c.5435dup (p.Val1813fs)	Pathogenic

SpliceAI

9879 predictions. Top by Δscore:

Variant	Effect	Δscore
11:17553207:GATGG:G	donor_gain	1.0000
11:17553360:CTCAG:C	acceptor_loss	1.0000
11:17553361:TCAG:T	acceptor_loss	1.0000
11:17553362:CA:C	acceptor_loss	1.0000
11:17553363:A:AG	acceptor_gain	1.0000
11:17553363:A:G	acceptor_loss	1.0000
11:17553363:AGT:A	acceptor_gain	1.0000
11:17553364:G:GA	acceptor_gain	1.0000
11:17553364:GT:G	acceptor_gain	1.0000
11:17553364:GTG:G	acceptor_gain	1.0000
11:17553364:GTGT:G	acceptor_gain	1.0000
11:17553364:GTGTA:G	acceptor_gain	1.0000
11:17553516:CCAG:C	donor_loss	1.0000
11:17553517:CAG:C	donor_loss	1.0000
11:17553518:AGG:A	donor_loss	1.0000
11:17553519:GG:G	donor_loss	1.0000
11:17553520:G:GA	donor_loss	1.0000
11:17553521:T:A	donor_loss	1.0000
11:17557302:G:GT	donor_gain	1.0000
11:17558645:G:GG	donor_gain	1.0000
11:17559159:GCA:G	donor_gain	1.0000
11:17559162:G:GG	donor_gain	1.0000
11:17560801:G:GT	donor_gain	1.0000
11:17569154:A:AG	acceptor_gain	1.0000
11:17569155:G:GG	acceptor_gain	1.0000
11:17569285:GATG:G	donor_gain	1.0000
11:17570206:T:TA	acceptor_gain	1.0000
11:17570211:A:AG	acceptor_gain	1.0000
11:17570211:A:G	acceptor_loss	1.0000
11:17570212:G:GA	acceptor_loss	1.0000

AlphaMissense

18917 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
11:17632207:G:C	W2363C	1.000
11:17632207:G:T	W2363C	1.000
11:17645938:G:C	W2924C	1.000
11:17645938:G:T	W2924C	1.000
11:17559139:G:C	W409C	0.999
11:17559139:G:T	W409C	0.999
11:17631903:T:G	F2317C	0.999
11:17632205:T:A	W2363R	0.999
11:17632205:T:C	W2363R	0.999
11:17645584:T:A	C2840S	0.999
11:17645585:G:C	C2840S	0.999
11:17645771:T:A	C2869S	0.999
11:17645771:T:C	C2869R	0.999
11:17645772:G:C	C2869S	0.999
11:17553202:T:A	C138S	0.998
11:17553203:G:C	C138S	0.998
11:17561667:T:C	C514R	0.998
11:17596988:G:C	W1233C	0.998
11:17596988:G:T	W1233C	0.998
11:17632104:T:G	F2329C	0.998
11:17634115:G:C	W2450C	0.998
11:17634115:G:T	W2450C	0.998
11:17640927:T:A	C2688S	0.998
11:17640927:T:C	C2688R	0.998
11:17640928:G:C	C2688S	0.998
11:17641011:T:A	C2716S	0.998
11:17641012:G:C	C2716S	0.998
11:17642141:G:C	W2782C	0.998
11:17642141:G:T	W2782C	0.998
11:17645626:T:A	C2854S	0.998

dbSNP variants (sampled 300 via entrez): RS1000037228 (11:17547916 C>T), RS1000042737 (11:17643626 TGA>T), RS1000084004 (11:17632754 G>A), RS1000088649 (11:17559720 C>T), RS1000098301 (11:17565833 GC>G), RS1000117385 (11:17575275 C>A,T), RS1000190883 (11:17627255 T>A), RS1000223285 (11:17550130 A>G), RS1000251680 (11:17602914 AG>A), RS1000280205 (11:17621211 T>G), RS1000288211 (11:17590210 T>C), RS1000295258 (11:17554619 G>C), RS1000339895 (11:17564878 A>G), RS1000341678 (11:17560644 G>A), RS1000368270 (11:17578717 G>C)

Disease associations

OMIM: gene MIM:604487 | disease phenotypes: MIM:614945, MIM:156000, MIM:220290, MIM:607197

GenCC curated gene-disease

Disease	Classification	Inheritance
autosomal recessive nonsyndromic hearing loss 18B	Definitive	Autosomal recessive
nonsyndromic genetic hearing loss	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 (7): autosomal recessive nonsyndromic hearing loss 18B (MONDO:0013985), hearing loss disorder (MONDO:0005365), nonsyndromic genetic hearing loss (MONDO:0019497), autosomal recessive disease (MONDO:0006025), Meniere disease (MONDO:0007972), hearing loss, autosomal recessive (MONDO:0019588), intellectual disability (MONDO:0001071)

Orphanet (6): Rare autosomal recessive non-syndromic sensorineural deafness type DFNB (Orphanet:90636), Rare non-syndromic genetic deafness (Orphanet:87884), Rare genetic deafness (Orphanet:96210), Rare autosomal dominant non-syndromic sensorineural deafness type DFNA (Orphanet:90635), NON RARE IN EUROPE: Menière disease (Orphanet:45360), NON RARE IN EUROPE: Unexplained intellectual disability (Orphanet:319658)

HPO phenotypes

5 total (5 of 5 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000407	Sensorineural hearing impairment
HP:0000750	Delayed speech and language development
HP:0001756	Vestibular hyporeflexia
HP:0003577	Congenital onset

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST003264_121	Post bronchodilator FEV1/FVC ratio	2.000000e-06
GCST003542_112	Night sleep phenotypes	2.000000e-06

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004713	FEV/FVC ratio

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
D008607	Intellectual Disability	C10.597.606.360; C23.888.592.604.646; F01.700.687; F03.625.539
D008575	Meniere Disease	C09.218.568.217.500
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

11 total (human), top 11 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
bufotalin	decreases expression	1
propionaldehyde	decreases expression	1
dimethylselenide	increases expression, increases oxidation	1
CGP 52608	affects binding, increases reaction	1
Resveratrol	affects cotreatment, decreases expression	1
Leflunomide	increases expression	1
Benzo(a)pyrene	affects methylation	1
Phthalic Acids	increases methylation	1
Plant Extracts	affects cotreatment, decreases expression	1
Reactive Oxygen Species	increases expression, increases oxidation	1
S-Nitrosoglutathione	decreases 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