Deciphering SCN2A: A comprehensive review of rodent models of Scn2a dysfunction.

ABSTRACT: SCN2A encodes for the alpha subunit of the voltage-gated sodium channel Na_V1.2, which is involved in action potential initiation and backpropagation in excitatory neurons. Currently, it is one of the highest monogenetic risk factors for both epilepsy and autism spectrum disorder. However, SCN2A-related disorders manifest in a broad clinical neuropsychiatric spectrum, including distinct neurological and psychiatric disorders. This clinical heterogeneity presents challenges for mechanistic understanding and treatment development. SCN2A mutations are generally classified as either gain-of-function (GOF) or loss-of-function (LOF); however, many mutations do not perfectly align to this binary framework. SCN2A dysfunction alters neuronal excitability, channel kinetics, and synaptic tr

SUBMITTER: Scott KEJ 

PROVIDER: S-EPMC12779317 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature