CDH2

Chr 18ARAD

cadherin 2

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

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]

Primary Disease Associations & Inheritance

?Attention deficit-hyperactivity disorder 8MIM #619957
AR
Agenesis of corpus callosum, cardiac, ocular, and genital syndromeMIM #618929
AD
Arrhythmogenic right ventricular dysplasia 14MIM #618920
AD
2
Active trials
99
Pubs (1 yr)
0
P/LP submissions
P/LP missense
0.29
LOEUF· LoF intol.
LOF
Mechanism· predicted
Clinical SummaryCDH2
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Gene-Disease Validity (ClinGen)
arrhythmogenic right ventricular cardiomyopathy · ADLimited

Limited evidence — not for standalone diagnostic reporting

2 total gene-disease associations curated

Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.99). One damaged copy is likely sufficient to cause disease.
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Clinical Trials
2 active or recruiting trials — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

LoF intolerant — likely haploinsufficient
LoF Constraint
0.29LOEUF
pLI 0.992
Z-score 5.05
OE 0.15 (0.080.29)
Highly constrained

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

Missense Constraint
2.09Z-score
OE missense 0.74 (0.680.81)
376 obs / 508.9 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios
LoF OE0.15 (0.080.29)
00.351.4
Missense OE0.74 (0.680.81)
00.61.4
Synonymous OE0.98
01.21.6
LoF obs/exp: 6 / 40.8Missense obs/exp: 376 / 508.9Syn Z: 0.17
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
limitedCDH2-related arrhythmogenic right ventricular cardiomyopathyOTHERAD
strongCDH2-related syndromic neurodevelopmental disorder with corpus callosum, axon, cardiac, ocular, and genital defectsOTHERAD
DN
0.5082th %ile
GOF
0.6346th %ile
LOF
0.63top 25%

The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).

LOF1 literature citation · LOEUF 0.29

Literature Evidence

LOFCHD2 haploinsufficiency is associated with developmental delay, intellectual disability, epilepsy and neurobehavioural problemsPMID:24834135

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

0 submitted variants 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.

Clinical Literature
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