CDH8
Chr 16cadherin 8
Also known as: Nbla04261
This protein is a type II cadherin that mediates calcium-dependent cell-cell adhesion in the brain and is involved in synaptic adhesion, axon outgrowth and guidance. Mutations cause autosomal dominant neurodevelopmental disorders including developmental and epileptic encephalopathy and autism spectrum disorder. The gene is highly constrained against loss-of-function variants (pLI 0.99, LOEUF 0.30), indicating that even single functional copies may be insufficient for normal brain development.
Some data sources returned errors (1)
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Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Highly LoF-intolerant (top ~10% of genes)
Moderately missense-constrained (top ~2.5%)
This gene has evidence for multiple mechanisms of pathogenicity (loss-of-function and gain-of-function). The Badonyi & Marsh model scores gain-of-function highest among its predictions, but genomic evidence (constraint, ClinVar variant spectrum, and literature) most strongly supports loss-of-function (haploinsufficiency). Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.
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. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.
ClinVar Variant Classifications
125 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 | 15 | 0 | 15 |
Likely Pathogenic | 0 | 0 | 2 | 0 | 2 |
VUS | 2 | 74 | 11 | 0 | 87 |
Likely Benign | 0 | 2 | 2 | 6 | 10 |
Benign | 0 | 0 | 0 | 2 | 2 |
| Total | 2 | 76 | 30 | 8 | 116 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
CDH8 · 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
No active trials found for this gene.
Search ClinicalTrials.gov →External Resources
Links to major genomics databases and tools