SCN2A

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Protein-coding gene in the species Homo sapiens

title: "SCN2A" type: doc version: 1 created: 2026-02-28 author: "Wikipedia contributors" status: active scope: public tags: ["sodium-channels"] description: "Protein-coding gene in the species Homo sapiens" topic_path: "general/sodium-channels" source: "https://en.wikipedia.org/wiki/SCN2A" license: "CC BY-SA 4.0" wikipedia_page_id: 0 wikipedia_revision_id: 0

::summary Protein-coding gene in the species Homo sapiens ::

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. 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. 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.

Nav1.2 functions mainly in excitatory neurons in cortical structures similar to Nav1.6, whereas expression of Nav1.1 (encoded by the SCN1A gene) is found in mutual distinct, inhibitory neuronal classes. 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, self-limited epilepsy, early infantile developmental and epileptic encephalopathy, later onset developmental and epileptic encephalopathy, infantile spasms, SCN2A-related disorders without epilepsy, episodic ataxia, and further movement disorders. Notably, SCN2A is known to be the most prominent genetic risk factor for autism-spectrum-disorders.

SCN2A gene mutations have also been identified in bitemporal glucose hypometabolism, and bipolar disorder.

References

References

  1. "Entrez Gene: SCN2A sodium channel, voltage-gated, type II, alpha subunit".
  2. (April 2012). "De novo mutations revealed by whole-exome sequencing are strongly associated with autism". Nature.
  3. (2024). "SCN2A-related disorders". Cambridge University Press.
  4. (September 2015). "Voltage-Gated Sodium Channels: Structure, Function, Pharmacology, and Clinical Indications". Journal of Medicinal Chemistry.
  5. (December 2010). "Voltage-gated sodium channel organization in neurons: protein interactions and trafficking pathways". Neuroscience Letters.
  6. (June 2010). "NaV1.1 channels and epilepsy". The Journal of Physiology.
  7. (July 2013). "SCN2A mutation is associated with infantile spasms and bitemporal glucose hypometabolism". Pediatric Neurology.
  8. (May 2019). "Genome-wide association study identifies 30 loci associated with bipolar disorder". Nature Genetics.
  9. "ICD-10-CM/PCS MS-DRG v43.0 Definitions Manual".

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