SCN2A

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). 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). == Function ==

The principal function of Nav1.2, similar to other members of the voltage-gated sodium channel family, is to mediate sodium influx into neurons upon membrane depolarization, thereby generating and propagating action potentials across distinct neuronal subtypes. However, the distribution of Nav1.2 changes during development. Nav1.2 channels are initially expressed at the axon initial segments (the site of action potential initiation) of excitatory pyramidal cells in both hippocampal and cortical excitatory cells. While these levels remain constant in the hippocampus, in cortical excitatory cells, Nav1.2 becomes restricted to the portion of the axon initial segment closest to the cell body and in dendrites at the age of 1–2 years in humans. Nav1.6 gradually becomes the predominant channel type at the distal axon initial segment and axonal nodes of Ranvier. In mature neurons, Nav1.2 is distributed only throughout unmyelinated axons. In contrast, its expression pattern in the cerebellum seems to persist throughout development, suggesting distinct roles for Nav1.2 in mature neurons of the neocortex and cerebellum. When Nav1.6 takes over the initiation of action potentials, Nav1.2 might play a crucial role in driving their backpropagation into dendrites. This backpropagation could impact activity-dependent processes such as synaptic maturation, plasticity, and gene transcription. The activity of Nav1.2 is influenced by several factors, such as protein-protein interactions, posttranslational modifications (e.g. phosphorylation, pamitoylation), and changes in intracellular Ca2+ concentration. == Clinical significance ==

Mutations in the SCN2A gene can cause a broad spectrum of disorders collectively referred to as SCN2A-related disorders. These include cases of ASD, Notably, SCN2A is known to be the most prominent genetic risk factor for autism-spectrum-disorders. and bipolar disorder. Furthermore, mutations in SCN2A have been demonstrated to impair enteric neuron migration during development, which may result in gastrointestinal dysmotility, consistent with gastric motility symptoms reported in ASD patients with underlying SCN2A mutations. == See also ==