CNTNAP2
Chr 7ARcontactin associated protein 2
Also known as: AUTS15, CASPR2, CDFE, NRXN4, PTHSL1
This protein functions as a cell adhesion molecule localized at the juxtaparanodes of myelinated axons, where it mediates neuron-glia interactions during nervous system development and localizes potassium channels within differentiating axons. Biallelic mutations cause autosomal recessive Pitt-Hopkins-like syndrome 1, characterized by intellectual disability, epilepsy, and other neurodevelopmental features. The gene is also associated with autism susceptibility through a dominant-negative mechanism.
Definitive — sufficient evidence for diagnostic panels
2 total gene-disease associations curated
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
More LoF-intolerant than ~75% of genes
Tolerant to missense variation
Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.
The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.
ClinVar Variant Classifications
300 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 | 10 | 0 | 9 | 0 | 19 |
Likely Pathogenic | 7 | 0 | 0 | 0 | 7 |
VUS | 1 | 91 | 10 | 0 | 102 |
Likely Benign | 0 | 0 | 59 | 96 | 155 |
Benign | 0 | 0 | 1 | 0 | 1 |
| Total | 18 | 91 | 79 | 96 | 284 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
CNTNAP2 · 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
External Resources
Links to major genomics databases and tools