OTOA

Chr 16AR

otoancorin

Also known as: CT108, DFNB22

NCBI Gene: 146183 ENSG00000155719 UniProt: Q7RTW8 OMIM: 607038

The encoded protein functions as an adhesion molecule that attaches the acellular gels to the apical surface of inner ear sensory epithelia. Mutations cause autosomal recessive deafness type 22 (DFNB22), typically presenting as congenital or early-onset hearing loss. The gene shows very low constraint against loss-of-function variants (pLI near zero), consistent with its autosomal recessive inheritance pattern where heterozygous carriers are unaffected.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt

The protein encoded by this gene is specifically expressed in the inner ear, and is located at the interface between the apical surface of the inner ear sensory epithelia and their overlying acellular gels. It is prposed that this protein is involved in the attachment of the inner ear acellular gels to the apical surface of the underlying nonsensory cells. Mutations in this gene are associated with autosomal recessive deafness type 22 (DFNB22). Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2009]

GeneReviews OMIM ResearchGenerating clinical summary…

LOFmechanismARLOEUF 0.691 OMIM phenotype

Clinical Summary— OTOA

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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

98 unique Pathogenic / Likely Pathogenic· 223 VUS of 793 total submissions

Explore recent and relevant literature in Research Assistant →

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GeneReview available — OTOA

Authoritative clinical overview · Recommended first read

Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.69LOEUF

pLI 0.000

Z-score 3.29

OE 0.49 (0.35–0.69)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

0.28Z-score

OE missense 0.96 (0.89–1.04)

463 obs / 480.4 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.49 (0.35–0.69)

0≤0.351.4

Missense OE?0.96 (0.89–1.04)

0≤0.61.4

Synonymous OE?0.95

0≤1.21.6

LoF obs/exp: 24 / 48.8Missense obs/exp: 463 / 480.4Syn Z: 0.51

Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗

limitedOTOA-related deafnessLOFAR

This gene — mechanism propensity

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

0.6258th %ile

GOF

0.6637th %ile

LOF

0.2775th %ile

The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.

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

ClinVar Variant Classifications

793 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic56

Likely Pathogenic42

VUS223

Likely Benign377

Benign59

Conflicting28

Pathogenic

Likely Pathogenic

223

VUS

377

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	44	0	12	0	56
Likely Pathogenic	31	7	4	0	42
VUS	1	207	12	3	223
Likely Benign	0	10	201	166	377
Benign	0	1	53	5	59
Conflicting	—				28
Total	76	225	282	174	785

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

View in ClinVar →

87 pathogenic / likely-pathogenic (of 130) ClinVar copy-number / structural variants overlap OTOA — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →