CDH2

Chr 18ARAD

cadherin 2

Also known as: ACOGS, ADHD8, ARVD14, CD325, CDHN, CDw325, NCAD

NCBI Gene: 1000 ENSG00000170558 UniProt: P19022 OMIM: 114020

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.

OMIM ResearchSummary from RefSeq, UniProt

This gene encodes a classical cadherin and member of the cadherin superfamily. Alternative splicing results in multiple transcript variants, at least one of which encodes a preproprotein is proteolytically processed to generate a calcium-dependent cell adhesion molecule and glycoprotein. This protein plays a role in the establishment of left-right asymmetry, development of the nervous system and the formation of cartilage and bone. [provided by RefSeq, Nov 2015]

OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

?Attention deficit-hyperactivity disorder 8MIM #619957

Agenesis of corpus callosum, cardiac, ocular, and genital syndromeMIM #618929

Arrhythmogenic right ventricular dysplasia 14MIM #618920

Clinical highlights

Gene–disease validity (ClinGen)

Interpreting a novel variant

This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

147

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.29

LOEUF· LoF intol.

LOF

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

LoF intolerant — likely haploinsufficient

LoF Constraint?

0.29LOEUF

pLI 0.992

Z-score 5.05

OE 0.15 (0.08–0.29)

Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint?

2.09Z-score

OE missense 0.74 (0.68–0.81)

376 obs / 508.9 exp

Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?

LoF OE?0.15 (0.08–0.29)

0≤0.351.4

Missense OE?0.74 (0.68–0.81)

0≤0.61.4

Synonymous OE?0.98

0≤1.21.6

LoF obs/exp: 6 / 40.8Missense obs/exp: 376 / 508.9Syn Z: 0.17

Background carrier burden — how many people carry a rare variant somewhere in CDH2?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 62

969 rare PASS variants

Rare truncating (LoF)

1 in 3,700

51 rare PASS variants

Rare synonymous (reference)

1 in 100

466 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for CDH2. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 73	1 in 3,500
South Asian	~43k	1 in 65	1 in 6,200
Remaining (unassigned)	~30k	1 in 63	1 in 4,300
European (Finnish)	~27k	1 in 210	≈ 1 in 27,000
Admixed American	~22k	1 in 67	≈ 1 in 11,000
African / African American	~21k	1 in 57	1 in 4,000
East Asian	~20k	1 in 77	none seen
Ashkenazi Jewish	~13k	1 in 280	1 in 1,200
Middle Eastern	~2,884	1 in 52	none seen

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): 13 of 16 coding exons well covered in gnomAD exomes; exons 1, 2, 11 marginal. Genomes: all 16.? see exons ↓

ClinVar Variant Classifications

0 submitted variants in ClinVar

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.

External Resources

Links to major genomics databases and tools

Franklin by Genoox

AI-powered variant curation and clinical analysis

DECIPHER

Genomic variants and phenotypes in rare disease patients

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

Arrhythmogenic Cardiomyopathies

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

RECRUITING

NCT05450783Nantes University HospitalStarted 2022-09-01

Biocollection

Clinical Literature

Open Research Assistant →

Landmark / reviewRecent case evidence

Full-Text Mentions

NLP-detected gene mentions in article bodies · via PubTator3

PubTator3

Chimeric Virus-Like Particles of Prawn Nodavirus Displaying Hepatitis B Virus Immunodominant Region: Biophysical Properties and Cytokine Response

Ninyio NN et al.·Int J Mol Sci

2021