CDH23

Chr 10ADARDigenic recessive

cadherin related 23

Also known as: CDHR23, PITA5, USH1D

NCBI Gene: 64072ENSG00000107736UniProt: Q9H251

This gene is a member of the cadherin superfamily, whose genes encode calcium dependent cell-cell adhesion glycoproteins. The encoded protein is thought to be involved in stereocilia organization and hair bundle formation. The gene is located in a region containing the human deafness loci DFNB12 and USH1D. Usher syndrome 1D and nonsyndromic autosomal recessive deafness DFNB12 are caused by allelic mutations of this cadherin-like gene. Upregulation of this gene may also be associated with breast cancer. Alternative splice variants encoding different isoforms have been described. [provided by RefSeq, May 2013]

Primary Disease Associations & Inheritance

{Pituitary adenoma 5, multiple types}MIM #617540
AD
Deafness, autosomal recessive 12MIM #601386
AR
Usher syndrome, type 1DMIM #601067
ARDigenic recessive
Usher syndrome, type 1D/F digenicMIM #601067
ARDigenic recessive
UniProtUsher syndrome 1D
UniProtUsher syndrome 1D/F
300
ClinVar variants
30
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— CDH23
🧬
Gene-Disease Validity (ClinGen)
nonsyndromic genetic hearing loss · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

2 total gene-disease associations curated

⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
30 Pathogenic / Likely Pathogenic· 198 VUS of 300 total submissions
Some data sources returned errors (1)

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

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Moderate LoF intolerance
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.
0.57LOEUF
pLI 0.000
Z-score 3.93
OE 0.38 (0.26–0.57)
Moderately constrained

More LoF-intolerant than ~75% of genes

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.
0.71Z-score
OE missense 0.93 (0.87–0.99)
662 obs / 715.2 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.0.38 (0.26–0.57)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.93 (0.87–0.99)
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.0.96
0≤1.21.6
LoF obs/exp: 18 / 47.1Missense obs/exp: 662 / 715.2Syn Z: 0.51

ClinVar Variant Classifications

300 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic16
Likely Pathogenic14
VUS198
Likely Benign72
16
Pathogenic
14
Likely Pathogenic
198
VUS
72
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
10
0
6
0
16
Likely Pathogenic
11
2
1
0
14
VUS
1
163
16
18
198
Likely Benign
0
1
38
33
72
Benign
0
0
0
0
0
Total221666151300

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

View in ClinVar →

Protein Context — Lollipop Plot

CDH23 · protein map & ClinVar variants

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

Gene2Phenotype Curations

CDH23-related deafness

definitive
ARUndeterminedAltered Gene Product Structure
Dev. DisordersEar
G2P ↗
missense variantinframe deletioninframe insertion

CDH23-related Usher syndrome

definitive
ARLoss Of FunctionAbsent Gene Product
Dev. DisordersEye
G2P ↗

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

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
CADHERIN 23; CDH23
MIM #605516 · *

{Pituitary adenoma 5, multiple types}

MIM #617540

Molecular basis of disorder known

Autosomal dominant

Deafness, autosomal recessive 12

MIM #601386

Molecular basis of disorder known

Autosomal recessive

Usher syndrome, type 1D

MIM #601067

Molecular basis of disorder known

Autosomal recessiveDigenic recessive

Usher syndrome, type 1D/F digenic

MIM #601067

Molecular basis of disorder known

Autosomal recessiveDigenic recessive
📖
GeneReview available — CDH23
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Genetic screening of a Chinese cohort of children with hearing loss using a next-generation sequencing panel.
Ma J et al.·Hum Genomics
2023Cohort
Comprehensive Molecular Screening in Chinese Usher Syndrome Patients.
Sun T et al.·Invest Ophthalmol Vis Sci
2018Cohort
Comprehensive sequence analysis of nine Usher syndrome genes in the UK National Collaborative Usher Study.
Le Quesne Stabej P et al.·J Med Genet
2012
The genetic and phenotypic landscapes of Usher syndrome: from disease mechanisms to a new classification.
Delmaghani S et al.·Hum Genet
2022Review
Variants in CDH23 cause a broad spectrum of hearing loss: from non-syndromic to syndromic hearing loss as well as from congenital to age-related hearing loss.
Usami SI et al.·Hum Genet
2022
Trends and mechanisms of Alzheimer's disease and hearing impairment: A 20-year perspective.
Li FF et al.·Ageing Res Rev
2025Functional
The p.P240L variant of CDH23 and the risk of nonsyndromic hearing loss: a meta-analysis.
Xu T et al.·Eur Arch Otorhinolaryngol
2019Review
A Novel Biallelic Variant in CDH23 Gene in a Family with Atypical USH1D Manifestation: A Literature Review and Investigation of Genotype-Phenotype Correlation.
Khorram E et al.·Audiol Neurootol
2023Review
Phenotypic and Genetic Spectrum in 309 Consecutive Pediatric Patients with Inherited Retinal Disease.
Priglinger CS et al.·Int J Mol Sci
2024Cohort
Mutation spectrum of hearing loss patients in Northwest China: Identification of 20 novel variants.
Ma P et al.·Mol Genet Genomic Med
2024Cohort
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
CDH23-associated Usher syndrome: genotype-phenotype correlations.
de Guimaraes TAC et al.·Ophthalmic Genet
2026
A Novel Pathogenic Haplotype in CDH23 Causing DFNB12: The Combined Effect of Two Individually Benign Variants
Tian ZX et al.·Balkan Med J
2026
Do variants in the CDH23 gene cause non-syndromic retinitis pigmentosa? Dual validation using whole exome sequencing and a zebrafish model.
Fan X et al.·BMJ Open Ophthalmol
2025🔓 Open AccessFunctional
[Analysis of pathogenic variant carriage for MYO7A, PCDH15, and CDH23 genes among newborns based on high-throughput sequencing technique].
Li Y et al.·Zhonghua Yi Xue Yi Chuan Xue Za Zhi
2025
Zebrafish cdh23 Affects Rod Cell Phototransduction Through Regulating Ca2+ Transport and MAPK Signaling Pathway.
Zheng X et al.·Int J Mol Sci
2025🔓 Open AccessFunctional
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