SCN2A

Sodium channel protein type 2 subunit alpha, also known as Nav1.2, is an ion channel protein encoded by the SCN2A gene in humans. It represents one member of the sodium channel alpha subunit gene family. The SCN2A gene is located on chromosome 2 (2q24.3) in proximity to two other voltage-gated sodium channel genes, namely SCN1A and SCN9A. Nav1.2 is distributed throughout the human central nervous system where it plays a major role in the initiation and propagation of action potentials. It is absent from peripheral tissues, with the exception of enteric neurons. Pathologic mutations in the SCN2A gene cause a broad spectrum of neurological conditions, such as epilepsy, autism spectrum disorder (ASD), intellectual disability (ID) and/or developmental delay, called SCN2A-related disorders.

== Structure == The SCN2A gene is composed of 27 exons and comprises more than 150 kilobases. There are two major splice variants known, a neonatal isoform and an adult isoform, which differ in one amino acid at position 209 (Asn versus Asp). The neonatal isoform might limit neuronal excitability during development. The voltage-gated sodium channel Nav1.2 encoded by the SCN2A gene consists of 2005 amino acids. This single polypeptide forms a pseudotetrameric channel of four similar domains (I - IV) where each domain contains 6 transmembrane segments, including a voltage sensing region, a pore forming region and an ion-selectivity filter. In the living organism, Nav1.2 is a transmembrane glycoprotein complex composed of a large alpha subunit (encoded by the SCN2A gene) and one or more regulatory beta subunits (encoded by SCNxB genes).