CDH15

Chr 16AD

cadherin 15

Also known as: CDH14, CDH3, CDHM, MCAD, MRD3

This gene encodes M-cadherin, a calcium-dependent cell adhesion protein that is essential for myogenesis and provides a trigger for terminal muscle cell differentiation. Mutations cause autosomal dominant intellectual developmental disorder. The gene is highly intolerant to loss-of-function variants, indicating that proper protein function is critical for normal development.

OMIMResearchSummary from RefSeq, OMIM, UniProt
LOFmechanismADLOEUF 1.101 OMIM phenotype
Clinical SummaryCDH15
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Gene-Disease Validity (ClinGen)
intellectual disability · ADDisputed

Disputed — evidence questions this relationship

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

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.10LOEUF
pLI 0.000
Z-score 1.09
OE 0.79 (0.581.10)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
-1.01Z-score
OE missense 1.12 (1.051.20)
591 obs / 526.0 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE0.79 (0.581.10)
00.351.4
Missense OE1.12 (1.051.20)
00.61.4
Synonymous OE1.18
01.21.6
LoF obs/exp: 25 / 31.6Missense obs/exp: 591 / 526.0Syn Z: -2.20
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
limitedCDH15-related intellectual developmental disorderLOFAD
DN
0.7327th %ile
GOF
0.78top 25%
LOF
0.3454th %ile

This gene has evidence for multiple mechanisms of pathogenicity (gain-of-function and dominant-negative). Both the Badonyi & Marsh prediction and the broader genomic evidence point to gain-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

GOFprediction above median
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

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

CDH15 · 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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