OTOA

Chr 16AR

otoancorin

Also known as: CT108, DFNB22

NCBI Gene: 146183ENSG00000155719UniProt: Q7RTW8

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]

Primary Disease Associations & Inheritance

Deafness, autosomal recessive 22MIM #607039
AR
510
ClinVar variants
84
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— OTOA
🧬
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
84 Pathogenic / Likely Pathogenic· 202 VUS of 510 total submissions

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.
0.69LOEUF
pLI 0.000
Z-score 3.29
OE 0.49 (0.35–0.69)
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.
0.28Z-score
OE missense 0.96 (0.89–1.04)
463 obs / 480.4 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.0.49 (0.35–0.69)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.96 (0.89–1.04)
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.0.95
0≤1.21.6
LoF obs/exp: 24 / 48.8Missense obs/exp: 463 / 480.4Syn Z: 0.51

ClinVar Variant Classifications

510 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic52
Likely Pathogenic32
VUS202
Likely Benign188
Benign19
Conflicting17
52
Pathogenic
32
Likely Pathogenic
202
VUS
188
Likely Benign
19
Benign
17
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
12
0
40
0
52
Likely Pathogenic
16
7
9
0
32
VUS
0
165
34
3
202
Likely Benign
0
9
94
85
188
Benign
0
1
13
5
19
Conflicting
—17
Total2818219093510

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

View in ClinVar →

Protein Context — Lollipop Plot

OTOA · protein map & ClinVar variants

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

Gene2Phenotype Curations

OTOA-related deafness

limited
ARLoss Of FunctionAbsent Gene Product
Ear
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
OTOANCORIN; OTOA
MIM #607038 · *

Deafness, autosomal recessive 22

MIM #607039

Molecular basis of disorder known

Autosomal recessive
📖
GeneReview available — OTOA
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Association of Genetic Diagnoses for Childhood-Onset Hearing Loss With Cochlear Implant Outcomes.
Carlson RJ et al.·JAMA Otolaryngol Head Neck Surg
2023
DNA Diagnostics of Hereditary Hearing Loss: A Targeted Resequencing Approach Combined with a Mutation Classification System.
Sommen M et al.·Hum Mutat
2016
Genetic etiology of non-syndromic hearing loss in Europe.
Del Castillo I et al.·Hum Genet
2022Review
Unveiling Secondary Mutations in Blended Phenotypes: Dual ERCC4 and OTOA Pathogenic Variants Through WES Analysis.
Failla P et al.·Int J Mol Sci
2024
Clarification of glycosylphosphatidylinositol anchorage of OTOANCORIN and human OTOA variants associated with deafness.
Kim BJ et al.·Hum Mutat
2019
Mid-Frequency Hearing Loss Is Characteristic Clinical Feature of OTOA-Associated Hearing Loss.
Sugiyama K et al.·Genes (Basel)
2019
[Phenotype-genotype analysis of the autosomal recessive hereditary hearing loss caused by OTOA variations].
Yang JY et al.·Zhonghua Er Bi Yan Hou Tou Jing Wai Ke Za Zhi
2023
Molecular characterization of pathogenic OTOA gene conversions in hearing loss patients.
Laurent S et al.·Hum Mutat
2021Case report
Targeted next-generation sequencing and parental genotyping in sporadic Chinese Han deaf patients.
He L et al.·Clin Genet
2018Cohort
Whole-exome sequencing identifies genetic variants of hearing loss in 113 Chinese families.
Pan J et al.·Clin Chim Acta
2022
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