CDH2
Chr 18ARADcadherin 2
Also known as: ACOGS, ADHD8, ARVD14, CD325, CDHN, CDw325, NCAD
CDH2 encodes N-cadherin, a calcium-dependent cell adhesion protein that mediates cell-cell adhesion and is essential for proper neurite branching, synaptic organization, and dendritic spine density in neurons. Mutations cause autosomal dominant neurodevelopmental disorders with intellectual disability, developmental delay, and brain malformations. This gene is highly constrained against loss-of-function variants (pLI = 0.99, LOEUF = 0.29), indicating that haploinsufficiency is likely not tolerated in the general population.
Limited evidence — not for standalone diagnostic reporting
2 total gene-disease associations curated
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Highly LoF-intolerant (top ~10% of genes)
Moderately missense-constrained (top ~2.5%)
The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).
Literature Evidence
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.
ClinVar Variant Classifications
100 submitted variants in ClinVar
Classification Summary
Curated Variants Distribution
Classified variants from ClinVar · 5 ACMG categories
| Classification | LoF | Missense + Inframe | Non-coding | Synonymous | Total |
|---|---|---|---|---|---|
Pathogenic | 0 | 0 | 0 | 0 | 0 |
Likely Pathogenic | 0 | 0 | 0 | 0 | 0 |
VUS | 2 | 48 | 1 | 1 | 52 |
Likely Benign | 0 | 1 | 5 | 17 | 23 |
Benign | 0 | 0 | 0 | 0 | 0 |
Conflicting | — | 1 | |||
| Total | 2 | 49 | 6 | 18 | 76 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
CDH2 · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
3D Protein StructureAlphaFold
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
Tissue and Metabolic Characterization of Arrhythmogenic Cardiomyopathies by Hybrid PET-MRI Imaging, Impact of the Observed Profiles on the Phenotype and on the Evolution of Cardiomyopathy
RECRUITINGDifferences in N-CAD Concentration and Brain Function Between Children With ASD and TD
RECRUITINGExternal Resources
Links to major genomics databases and tools