Contactin1

Contactin-1 is a neuronal cell adhesion molecule encoded by the CNTN1 gene. It belongs to the contactin family of immunoglobulin superfamily proteins and is anchored to the cell surface by a glycosylphosphatidylinositol (GPI) moiety. The extracellular region typically contains immunoglobulin-like domains and fibronectin type III–like repeats, enabling a range of adhesive interactions.

The protein is expressed in both the central and peripheral nervous systems, where it localizes to the surface of neurons and to sites of contact with glial cells. Contactin-1 participates in cell–cell adhesion that supports axon outgrowth and fasciculation during development and contributes to the organization of neural networks. In myelinated fibers, it is involved in the formation and maintenance of specialized axonal–glial interfaces that contribute to efficient nerve conduction.

Functionally, contactin-1 can engage in trans interactions with other membrane proteins, promoting adhesive signaling at neuronal surfaces. Through these interactions, it influences neurite growth, synapse formation, and the maturation of neural circuits.

Clinical significance of CNTN1 variations has been described in rare cases. Pathogenic variants in CNTN1 have been associated with congenital hypomyelinating neuropathy presenting with hypotonia and respiratory insufficiency in infancy. Some reports also describe broader neurodevelopmental phenotypes linked to CNTN1 disruption, though these associations require further validation.

Genetic and expression data indicate that CNTN1 is widely expressed in neurons, with higher levels in regions rich in myelinated axons. Aberrant CNTN1 function can disrupt neural connectivity and myelination processes, highlighting its role in nervous system development and maintenance.