CDH23

Chr 10ADARDigenic recessive

cadherin related 23

CDH23 encodes a calcium-dependent cell adhesion protein required for proper organization of stereocilia bundles in cochlear and vestibular hair cells and normal hearing. Mutations cause autosomal recessive nonsyndromic deafness (DFNB12), Usher syndrome type 1D (combining congenital deafness with progressive vision loss), and digenic forms of Usher syndrome, with some cases showing autosomal dominant inheritance. The gene is not loss-of-function intolerant (pLI near zero), suggesting recessive mutations typically cause disease through effects on protein function rather than simple protein loss.

OMIMResearchSummary from RefSeq, OMIM, UniProt
LOFmechanismAD/AR/Digenic recessiveLOEUF 0.574 OMIM phenotypes
Clinical SummaryCDH23
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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.
Some data sources returned errors (1)

ncbi: 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

Moderate LoF intolerance
LoF Constraint
0.57LOEUF
pLI 0.000
Z-score 3.93
OE 0.38 (0.260.57)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
0.71Z-score
OE missense 0.93 (0.870.99)
662 obs / 715.2 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.38 (0.260.57)
00.351.4
Missense OE0.93 (0.870.99)
00.61.4
Synonymous OE0.96
01.21.6
LoF obs/exp: 18 / 47.1Missense obs/exp: 662 / 715.2Syn Z: 0.51
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
definitiveCDH23-related deafnessOTHERAR
definitiveCDH23-related Usher syndromeLOFAR

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

DN
0.76top 25%
GOF
0.74top 25%
LOF
0.3163th %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

0 submitted variants 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.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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