CTNND2
Chr 5catenin delta 2
Also known as: GT24, NPRAP
The protein regulates dendritic spine and synapse formation in neurons, controls Wnt signaling through beta-catenin regulation, and functions in neuronal cell adhesion. Mutations cause autosomal recessive intellectual disability with severe speech delay, often accompanied by autism spectrum disorder and behavioral abnormalities. This gene is extremely intolerant to loss-of-function variants, indicating its critical role in neurodevelopment.
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Among the most LoF-intolerant genes (~top 3%)
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
500 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 | 3 | 0 | 93 | 0 | 96 |
Likely Pathogenic | 8 | 2 | 7 | 0 | 17 |
VUS | 6 | 152 | 35 | 0 | 193 |
Likely Benign | 0 | 26 | 40 | 23 | 89 |
Benign | 1 | 5 | 71 | 10 | 87 |
Conflicting | — | 8 | |||
| Total | 18 | 185 | 246 | 33 | 490 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
CTNND2 · 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