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GeneE
10 sources retrieved Β· Most recent: April 2026 Β· Index updated 14 days ago
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OTOG
otogelin
Chromosome 11 Β· 11p15.1
NCBI Gene: 340990Ensembl: ENSG00000188162.12HGNC: HGNC:8516UniProt: H9KVB3
17PubMed Papers
21Diseases
0Drugs
131Pathogenic Variants
RESEARCH IMPACT
Variant-Rich
CLINICAL
OMIM Disease Gene
DATA QUALITY
βœ“ Experimental GO Evidenceβœ“ Swiss-Prot Reviewed
extracellular matrix structural constituentGO:0005615extracellular matrixL-arabinose metabolic processhearing loss, autosomal recessiveRare genetic deafnessdeafnessHearing impairment
✦AI Summary

OTOG encodes otogelin, a glycoprotein component of inner ear acellular membranes, particularly the tectorial and otolithic membranes 1. The protein functions as an extracellular matrix structural constituent [UniProt], with roles in anchoring otoconial membranes and cupulae to the underlying neuroepithelia in the vestibule, and in organizing the fibrillar network of the tectorial membrane in the cochlea. OTOG likely participates in mechanotransduction processes critical for auditory and vestibular function. Biallelic mutations in OTOG cause autosomal recessive non-syndromic hearing loss designated DFNB18B 2. Clinical characterization of 26 probands with OTOG variants revealed predominantly congenital or childhood-onset, non-progressive mild-to-moderate hearing loss without accompanying symptoms 2. However, rare homozygous missense variants can associate with severe-to-profound hearing loss, likely through disruption of disulfide bonds affecting protein stability 1. Beyond isolated deafness, OTOG has emerged as a candidate gene in Meniere's disease pathogenesis. Multiplex rare missense variants in OTOG were identified in 33% of familial Meniere's disease cases 3, and exome sequencing identified OTOG variants in multiple families, suggesting possible digenic inheritance patterns 45. These findings implicate OTOG in both primary hearing loss and complex inner ear disorders involving vestibular dysfunction.

Sources cited
1
OTOG-associated DFNB18B hearing loss characterized by non-progressive mild-to-moderate congenital or childhood-onset hearing loss without accompanying symptoms
PMID: 39858607
2
OTOG encodes otogelin component of tectorial membrane; rare homozygous missense variants can cause severe-to-profound hearing loss through disruption of protein disulfide bonds
PMID: 34118384
3
Multiplex rare missense variants in OTOG reported in 33% of familial Meniere's disease cases, suggesting multiallelic inheritance
PMID: 31874721
4
OTOG identified through exome sequencing as carrying rare missense variants in multiple families with Meniere's disease
PMID: 37865853
5
OTOG mutations in same families with TECTA and MYO7A genes suggest integrity of stereocilia and their interaction with tectorial and otolithic membranes involved in Meniere's disease pathophysiology
PMID: 36565421
Disease Associationsβ“˜21
hearing loss, autosomal recessiveOpen Targets
0.71Strong
Rare genetic deafnessOpen Targets
0.53Moderate
deafnessOpen Targets
0.46Moderate
Hearing impairmentOpen Targets
0.44Moderate
nonsyndromic genetic hearing lossOpen Targets
0.44Moderate
Non-syndromic genetic deafnessOpen Targets
0.37Weak
Meniere diseaseOpen Targets
0.37Weak
VertigoOpen Targets
0.35Weak
central nervous system origin vertigoOpen Targets
0.34Weak
peripheral vertigoOpen Targets
0.34Weak
vestibular diseaseOpen Targets
0.34Weak
autosomal dominant nonsyndromic hearing lossOpen Targets
0.28Weak
trauma complicationOpen Targets
0.28Weak
inner ear diseaseOpen Targets
0.27Weak
Intellectual disabilityOpen Targets
0.27Weak
SeizureOpen Targets
0.27Weak
peripheral vascular diseaseOpen Targets
0.24Weak
hypertrophic cardiomyopathyOpen Targets
0.22Weak
gastric ulcerOpen Targets
0.20Weak
autosomal recessive diseaseOpen Targets
0.15Weak
Deafness, autosomal recessive, 18BUniProt
Pathogenic Variants131
NM_001292063.2(OTOG):c.4985del (p.Gly1662fs)Pathogenic
not provided
β˜…β˜…β˜†β˜†2026β†’ Residue 1662
NM_001292063.2(OTOG):c.3664C>T (p.Arg1222Ter)Pathogenic
not provided|Autosomal recessive nonsyndromic hearing loss 18B
β˜…β˜…β˜†β˜†2026β†’ Residue 1222
NM_001292063.2(OTOG):c.2464C>T (p.Gln822Ter)Pathogenic
Autosomal recessive nonsyndromic hearing loss 18B|Seizure;Intellectual disability|not provided|Rare genetic deafness|Monogenic hearing loss
β˜…β˜…β˜†β˜†2026β†’ Residue 822
NM_001292063.2(OTOG):c.5926dup (p.Gln1976fs)Pathogenic
Rare genetic deafness|not provided
β˜…β˜…β˜†β˜†2025β†’ Residue 1976
NM_001292063.2(OTOG):c.499del (p.Val167fs)Pathogenic
Rare genetic deafness|not provided
β˜…β˜…β˜†β˜†2025β†’ Residue 167
NM_001292063.2(OTOG):c.996+1G>TPathogenic
not provided|Monogenic hearing loss
β˜…β˜…β˜†β˜†2025
NM_001292063.2(OTOG):c.5935del (p.Met1979fs)Pathogenic
Autosomal recessive nonsyndromic hearing loss 18B|not provided
β˜…β˜…β˜†β˜†2025β†’ Residue 1979
NM_001292063.2(OTOG):c.3187C>T (p.Arg1063Ter)Pathogenic
not provided|Rare genetic deafness|Autosomal recessive nonsyndromic hearing loss 18B
β˜…β˜…β˜†β˜†2025β†’ Residue 1063
NM_001292063.2(OTOG):c.2453_2454insACTGGACACCCA (p.Tyr818Ter)Pathogenic
Rare genetic deafness|not provided|Autosomal recessive nonsyndromic hearing loss 18B
β˜…β˜…β˜†β˜†2025β†’ Residue 818
NM_001292063.2(OTOG):c.3186G>A (p.Trp1062Ter)Pathogenic
not provided
β˜…β˜…β˜†β˜†2025β†’ Residue 1062
NM_001292063.2(OTOG):c.1666C>T (p.Gln556Ter)Pathogenic
not provided|Autosomal recessive nonsyndromic hearing loss 18B
β˜…β˜…β˜†β˜†2025β†’ Residue 556
NM_001292063.2(OTOG):c.6721del (p.Asp2241fs)Pathogenic
Autosomal recessive nonsyndromic hearing loss 18B|not provided
β˜…β˜…β˜†β˜†2025β†’ Residue 2241
NM_001292063.2(OTOG):c.2561+1delLikely pathogenic
Autosomal recessive nonsyndromic hearing loss 18B|not provided
β˜…β˜…β˜†β˜†2025
NM_001292063.2(OTOG):c.3457C>T (p.Arg1153Ter)Pathogenic
Rare genetic deafness|not provided|Autosomal recessive nonsyndromic hearing loss 18B
β˜…β˜…β˜†β˜†2025β†’ Residue 1153
NM_001292063.2(OTOG):c.6523C>T (p.Arg2175Ter)Pathogenic
Autosomal recessive nonsyndromic hearing loss 18B|not provided
β˜…β˜…β˜†β˜†2025β†’ Residue 2175
NM_001292063.2(OTOG):c.7418del (p.Arg2473fs)Pathogenic
Autosomal recessive nonsyndromic hearing loss 18B|not provided|OTOG-related disorder|Rare genetic deafness
β˜…β˜…β˜†β˜†2025β†’ Residue 2473
NM_001292063.2(OTOG):c.7417C>T (p.Arg2473Ter)Pathogenic
Autosomal recessive nonsyndromic hearing loss 18B|not provided
β˜…β˜…β˜†β˜†2025β†’ Residue 2473
NM_001292063.2(OTOG):c.5747_5750del (p.Gln1916fs)Pathogenic
not provided
β˜…β˜…β˜†β˜†2025β†’ Residue 1916
NM_001292063.2(OTOG):c.755del (p.Asp252fs)Pathogenic
not provided
β˜…β˜…β˜†β˜†2024β†’ Residue 252
NM_001292063.2(OTOG):c.3546C>A (p.Tyr1182Ter)Pathogenic
Autosomal recessive nonsyndromic hearing loss 18B|not provided
β˜…β˜…β˜†β˜†2024β†’ Residue 1182
View on ClinVar β†—
Related Genes
HOXB2Shared pathway100%MOBPShared pathway100%SCRG1Shared pathway100%IRF2BPLShared pathway100%NRSN2Shared pathway100%GNG8Shared pathway100%
Tissue Expression6 tissues
Brain
100%
Ovary
3%
Liver
2%
Bone Marrow
1%
Lung
1%
Heart
0%
Gene Interaction Network
Click a node to explore
OTOGHOXB2MOBPSCRG1IRF2BPLNRSN2GNG8
PROTEIN STRUCTURE
Preparing viewer…
AlphaFoldAI-predicted Β· UniProt Q6ZRI0
View on AlphaFold β†—
Constraintβ“˜
LOEUFβ“˜
1.09LoF Tolerant
pLIβ“˜
0.00Tolerant
Observed/Expected LoF0.99 [0.90–1.09]
RankingsWhere OTOG stands among ~20K protein-coding genes
  • #15,082of 20,598
    Most Researched17
  • #594of 5,498
    Most Pathogenic Variants131 Β· top quartile
  • #11,117of 17,882
    Most Constrained (LOEUF)1.09
Genes detectedOTOG
Sources retrieved10 papers
Response timeβ€”
πŸ“„ Sources
10β–Ό
1
Epidemiology and genetics of Meniere's disease.
PMID: 37865853
Curr Opin Neurol Β· 2024
1.00
2
Bacteroides uniformis-generated hexadecanedioic acid ameliorates metabolic-associated fatty liver disease.
PMID: 40413726
Gut Microbes Β· 2025
0.90
3
Novel
PMID: 39858607
Genes (Basel) Β· 2025
0.80
4
Genetic advances in Meniere Disease.
PMID: 36565421
Mol Biol Rep Β· 2023
0.70
5
Mutation spectrum of hearing loss patients in Northwest China: Identification of 20 novel variants.
PMID: 38860500
Mol Genet Genomic Med Β· 2024
0.60