OTOG

Chr 11

otogelin

Also known as: DFNB18B, MLEMP, OTGN

NCBI Gene: 340990 ENSG00000188162 UniProt: Q6ZRI0

The protein encoded by OTOG is a glycoprotein component of the acellular membranes of the inner ear that anchors otoconial membranes and cupulae to underlying neuroepithelia and organizes the fibrillar network of the tectorial membrane in the cochlea. Mutations cause autosomal recessive nonsyndromic deafness type 18B, affecting hearing without other associated features. This gene shows tolerance to loss-of-function variants (low pLI score) and follows autosomal recessive inheritance.

ResearchSummary from RefSeq, OMIM, UniProt

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]

ResearchGenerating clinical summary…

DNmechanismLOEUF 0.75

Clinical Summary— OTOG

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Gene-Disease Validity (ClinGen)

nonsyndromic genetic hearing loss · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

136 unique Pathogenic / Likely Pathogenic· 572 VUS of 1518 total submissions

Explore recent and relevant literature in Research Assistant →

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.75LOEUF

pLI 0.000

Z-score 3.96

OE 0.62 (0.52–0.75)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

1.92Z-score

OE missense 0.87 (0.83–0.91)

1413 obs / 1630.8 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.62 (0.52–0.75)

0≤0.351.4

Missense OE?0.87 (0.83–0.91)

0≤0.61.4

Synonymous OE?0.87

0≤1.21.6

LoF obs/exp: 79 / 127.1Missense obs/exp: 1413 / 1630.8Syn Z: 2.64

This gene — mechanism propensity

0.6550th %ile

GOF

0.6346th %ile

LOF

0.2777th %ile

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

1518 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic53

Likely Pathogenic83

VUS572

Likely Benign525

Benign196

Conflicting86

Pathogenic

Likely Pathogenic

572

VUS

525

Likely Benign

196

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	52	1	0	0	53
Likely Pathogenic	76	5	2	0	83
VUS	6	534	21	11	572
Likely Benign	0	38	200	287	525
Benign	0	28	143	25	196
Conflicting	—				86
Total	134	606	366	323	1,515

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

View in ClinVar →

12 pathogenic / likely-pathogenic (of 22) ClinVar copy-number / structural variants overlap OTOG — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →