CNTNAP2 Gene: Function, Expression, and Disease Associations | Biomedical Resource

CNTNAP2 encodes contactin-associated protein 2 (CASPR2), a member of the neurexin family of cell adhesion molecules. It is predominantly expressed in the nervous system, where it plays a critical role in neuronal-glial interactions, clustering of voltage-gated potassium channels at the juxtaparanodal regions of myelinated axons, and in the development of neural circuits. Mutations and variants in CNTNAP2 have been associated with a spectrum of neurodevelopmental disorders, including autism spectrum disorder (ASD), intellectual disability, epilepsy, and specific language impairment. The gene is also implicated in cortical development and synaptic function, making it a key candidate for understanding the molecular basis of these conditions.

Tissue Expression

Cell Line Expression

Hotspot Mutations

Mutation functional classification

• Neurexin and neuroligin signaling

• Potassium channel clustering

• Axon guidance and neuronal migration

• Synaptic vesicle cycle

CASPR2 is a single-pass type I membrane protein with a large extracellular domain containing multiple laminin G, EGF-like, and fibronectin type III domains. It interacts with contactin-2 (CNTN2) to mediate cell adhesion and is essential for the localization of voltage-gated potassium channels (Kv1.1/Kv1.2) at the juxtaparanodal region of myelinated axons. CASPR2 also plays roles in neuronal migration, dendritic arborization, and synaptic plasticity. Its cytoplasmic domain interacts with PDZ-domain proteins, linking it to intracellular signaling pathways. Mutations affecting CASPR2 function lead to altered neuronal excitability and connectivity, underpinning various neurodevelopmental disorders.