CNTN2
Chr 1ARcontactin 2
Also known as: AXT, EPEO5, FAME5, TAG-1, TAX, TAX1
This protein is a GPI-anchored neuronal membrane glycoprotein that organizes axonal domains at nodes of Ranvier by maintaining voltage-gated potassium channels at the juxtaparanodal region and functions in neuronal proliferation, migration, and axon guidance during cerebellar development. Autosomal recessive mutations cause early-onset epilepsy with or without developmental delay. The gene is highly constrained against loss-of-function variants (LOEUF 0.437), indicating that complete loss of protein function is likely pathogenic.
Definitive — sufficient evidence for diagnostic panels
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
More LoF-intolerant than ~75% of genes
Moderately missense-constrained (top ~2.5%)
This gene has evidence for multiple mechanisms of pathogenicity (dominant-negative and gain-of-function). Both the Badonyi & Marsh prediction and the broader genomic evidence point to dominant-negative as the predominant mechanism. 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.
ClinVar Variant Classifications
0 submitted variants in ClinVar
Protein Context — Lollipop Plot
CNTN2 · 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