protein
Sodium channel protein type 2 subunit alpha
Gene
SCN2A
Organism
Homo sapiens(9606)
Length
2005 aa
Mass
227,975 Da
SCN2A encodes a voltage-gated sodium channel subunit that mediates sodium ion permeability across excitable cell membranes, allowing sodium influx according to electrochemical gradients (UniProt: Q99250). The protein is also implicated in regulating hippocampal replay during sharp wave ripples, which are important for memory consolidation.
SCN2A is expressed in neuronal tissues and plays a critical role in neuronal excitability. Mutations in this gene are associated with multiple seizure disorders: benign familial infantile seizures 3 (BFIS3), developmental and epileptic encephalopathy 11 (DEE11), which can progress to West syndrome, and episodic ataxia 9 (EA9), characterized by episodes of ataxia and early-onset seizures with occasional developmental delay and speech problems (UniProt: Q99250).
SCN2A is classified as SFARI Category 1, indicating strong evidence for association with autism spectrum disorder (SFARI Cat 1), and is noted as syndromic. The gene's involvement in neurodevelopmental and epileptic conditions, particularly those presenting with autism-like features and developmental delays, establishes its relevance to autism and related neurodevelopmental disorders.
Generated from the curated entity record below. May contain errors — verify against source links.
Proteomics Evidence · AD
↓ Down in ADP3
not detected
P2
not detected
S2
not detected
S3
-0.450
Mean log₂FC across detected fractions: -0.4501 (1 of 4 fractions detected)
Human post-mortem AD brain vs age-matched controls, TMT-labeled, 4 subcellular fractions (P2, P3, S2, S3), DDA proteomics.
Genetic Evidence · ASD
High confidence — strong genetic evidence from multiple studies
Source: SFARI Gene database · gene.sfari.org
This protein is implicated in both ASD and Alzheimer's Disease. View all cross-disease proteins →
Related Publications
Browse all →Tau molecular diversity contributes to clinical heterogeneity in Alzheimer's disease.
Dujardin Simon et al.Nature medicine2020PMID 32572268Deep Multilayer Brain Proteomics Identifies Molecular Networks in Alzheimer's Disease Progression.
Bai Bing et al.Neuron2020PMID 31926610A Multi-network Approach Identifies Protein-Specific Co-expression in Asymptomatic and Symptomatic Alzheimer's Disease.
Seyfried Nicholas T et al.Cell systems2017PMID 27989508Large-scale deep multi-layer analysis of Alzheimer's disease brain reveals strong proteomic disease-related changes not observed at the RNA level.
Johnson Erik C B et al.Nature neuroscience2022PMID 35115731Organization and regulation of gene transcription.
Cramer PatrickNature2019PMID 31462772Inherited and De Novo Genetic Risk for Autism Impacts Shared Networks.
Ruzzo Elizabeth K et al.Cell2019PMID 31398340Inherited and multiple de novo mutations in autism/developmental delay risk genes suggest a multifactorial model.
Guo Hui et al.Molecular autism2018PMID 30564305Whole genome sequencing resource identifies 18 new candidate genes for autism spectrum disorder.
C Yuen Ryan K et al.Nature neuroscience2017PMID 28263302Identification of common genetic risk variants for autism spectrum disorder.
Grove Jakob et al.Nature genetics2019PMID 30804558Synaptic, transcriptional and chromatin genes disrupted in autism.
De Rubeis Silvia et al.Nature2014PMID 25363760
Function
Mediates the voltage-dependent sodium ion permeability of excitable membranes. Assuming opened or closed conformations in response to the voltage difference across the membrane, the protein forms a sodium-selective channel through which Na(+) ions may pass in accordance with their electrochemical gradient (PubMed:1325650, PubMed:17021166, PubMed:28256214, PubMed:29844171). Implicated in the regulation of hippocampal replay occurring within sharp wave ripples (SPW-R) important for memory (By similarity)
Disease associations
Seizures, benign familial infantile, 3BFIS3
A form of benign familial infantile epilepsy, a neurologic disorder characterized by afebrile seizures occurring in clusters during the first year of life, without neurologic sequelae. BFIS3 inheritance is autosomal dominant.
Developmental and epileptic encephalopathy 11DEE11
An autosomal dominant seizure disorder characterized by neonatal or infantile onset of refractory seizures with resultant delayed neurologic development and persistent neurologic abnormalities. Patients may progress to West syndrome, which is characterized by tonic spasms with clustering, arrest of psychomotor development, and hypsarrhythmia on EEG.
Episodic ataxia 9EA9
An autosomal dominant neurologic disorder characterized by episodic ataxia manifesting in the first years of life, early-onset seizures, difficulty walking, dizziness, slurred speech, headache, vomiting, and pain. The duration of ataxic episodes is heterogeneous. Most patients show episodes lasting minutes to maximum several hours, but periods lasting days up to weeks have been reported. Some patients have mildly delayed development with speech delay and/or autistic features or mildly impaired intellectual development.
Sources
Last updated 5/8/2026, 1:12:07 AM