OTOG

Chr 11AR

otogelin

Also known as: DFNB18B, MLEMP, OTGN

NCBI Gene: 340990ENSG00000188162UniProt: Q6ZRI0

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. [provided by RefSeq, May 2014]

Primary Disease Associations & Inheritance

Deafness, autosomal recessive 18BMIM #614945
AR
498
ClinVar variants
68
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— OTOG
🧬
Gene-Disease Validity (ClinGen)
nonsyndromic genetic hearing loss · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
68 Pathogenic / Likely Pathogenic· 270 VUS of 498 total submissions
Some data sources returned errors (1)

clinvar: Error: NCBI fetch failed: 429 https://eutils.ncbi.nlm.nih.gov/entrez/eutils/esearch.fcgi

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.75LOEUF
pLI 0.000
Z-score 3.96
OE 0.62 (0.52–0.75)
Tolerant

Typical tolerance to LoF variation

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
1.92Z-score
OE missense 0.87 (0.83–0.91)
1413 obs / 1630.8 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.62 (0.52–0.75)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.87 (0.83–0.91)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.87
0≤1.21.6
LoF obs/exp: 79 / 127.1Missense obs/exp: 1413 / 1630.8Syn Z: 2.64

ClinVar Variant Classifications

498 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic29
Likely Pathogenic39
VUS270
Likely Benign121
Benign36
Conflicting3
29
Pathogenic
39
Likely Pathogenic
270
VUS
121
Likely Benign
36
Benign
3
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
10
0
19
0
29
Likely Pathogenic
25
1
13
0
39
VUS
4
247
13
6
270
Likely Benign
0
2
30
89
121
Benign
0
0
33
3
36
Conflicting
—3
Total3925010898498

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

OTOG · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
OTOGELIN; OTOG
MIM #604487 · *

Deafness, autosomal recessive 18B

MIM #614945

Molecular basis of disorder known

Autosomal recessive
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Novel OTOG Variants and Clinical Features of Hearing Loss in a Large Japanese Cohort.
Arai Y et al.·Genes (Basel)
2025Cohort
Prediction and interpretation of rare missense variant in OTOG associated with hearing loss.
Askari M et al.·Genomics
2021
Mutation spectrum of hearing loss patients in Northwest China: Identification of 20 novel variants.
Ma P et al.·Mol Genet Genomic Med
2024Cohort
Genetic architecture of Meniere's disease.
Gallego-Martinez A et al.·Hear Res
2020Review
Types of Inheritance and Genes Associated with Familial Meniere Disease.
Parra-Perez AM et al.·J Assoc Res Otolaryngol
2023Review
Burden of Rare Variants in the OTOG Gene in Familial Meniere's Disease.
Roman-Naranjo P et al.·Ear Hear
2020
Similar phenotypes caused by mutations in OTOG and OTOGL.
Oonk AM et al.·Ear Hear
2014
Novel variant in OTOG gene in consanguineous family with sensorineural hearing loss.
An Y et al.·BMJ Case Rep
2025
Systematic Review of Sequencing Studies and Gene Expression Profiling in Familial Meniere Disease.
Escalera-Balsera A et al.·Genes (Basel)
2020Review
Genetic Risk Factors in Normal Pressure Hydrocephalus: What We Know and What Is Next.
Piccinin CC et al.·Mov Disord
2025
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools