protein
Sodium channel protein type 1 subunit alpha
Gene
SCN1A
Organism
Homo sapiens(9606)
Length
2009 aa
Mass
228,972 Da
SCN1A encodes the pore-forming alpha subunit of Nav1.1, a voltage-gated sodium channel essential for neuronal excitability. This protein mediates the depolarizing phase of action potentials by selectively permitting sodium ion influx across cell membranes, thereby initiating electrical signal propagation. Nav1.1 regulates neuronal excitability to maintain the balance between excitation and inhibition in brain circuits and contributes to sensory pain perception through somatosensory neuron signaling (UniProt: P35498).
SCN1A is predominantly expressed in excitable tissues and functions within neural circuits controlling seizure susceptibility and neuronal communication. Mutations in this gene are associated with multiple epilepsy-related conditions, including Dravet syndrome, generalized epilepsy with febrile seizures plus, intractable childhood epilepsy with generalized tonic-clonic seizures, developmental and epileptic encephalopathy 6B, familial febrile seizures, and familial hemiplegic migraine. These disorders range from relatively mild febrile seizure presentations to severe, therapy-resistant epileptic encephalopathies with developmental consequences (UniProt: P35498).
SCN1A is curated as a syndromic autism-associated gene in the SFARI database (SFARI Cat 2), indicating a probable link to autism spectrum disorder within syndromic presentations. The relationship likely reflects shared neurodevelopmental mechanisms, as mutations causing severe seizure disorders often co-occur with cognitive and developmental impairments characteristic of autism spectrum conditions.
Generated from the curated entity record below. May contain errors — verify against source links.
Genetic Evidence · ASD
Strong candidate — functional studies support ASD association
Source: SFARI Gene database · gene.sfari.org
Related Publications
Browse all →Inherited 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
Pore-forming subunit of Nav1.1, a voltage-gated sodium (Nav) channel that directly mediates the depolarizing phase of action potentials in excitable membranes. Navs, also called VGSCs (voltage-gated sodium channels) or VDSCs (voltage-dependent sodium channels), operate by switching between closed and open conformations depending on the voltage difference across the membrane. In the open conformation they allow Na(+) ions to selectively pass through the pore, along their electrochemical gradient. The influx of Na(+) ions provokes membrane depolarization, initiating the propagation of electrical signals throughout cells and tissues (PubMed:14672992). By regulating the excitability of neurons, ensures that they respond appropriately to synaptic inputs, maintaining the balance between excitation and inhibition in brain neural circuits (By similarity). Nav1.1 plays a role in controlling the excitability and action potential propagation from somatosensory neurons, thereby contributing to the sensory perception of mechanically-induced pain (By similarity)
Disease associations
Generalized epilepsy with febrile seizures plus 2GEFSP2
A rare autosomal dominant, familial condition with incomplete penetrance and large intrafamilial variability. Patients display febrile seizures persisting sometimes beyond the age of 6 years and/or a variety of afebrile seizure types. This disease combines febrile seizures, generalized seizures often precipitated by fever at age 6 years or more, and partial seizures, with a variable degree of severity.
Dravet syndromeDRVT
A severe form of epileptic encephalopathy characterized by generalized tonic, clonic, and tonic-clonic seizures that are initially induced by fever and begin during the first year of life. Later, patients also manifest other seizure types, including absence, myoclonic, and simple and complex partial seizures. Psychomotor development delay is observed around the second year of life. Some patients manifest a borderline disease phenotype and do not necessarily fulfill all diagnostic criteria for core DRVT. DRVT is considered to be the most severe phenotype within the spectrum of generalized epilepsies with febrile seizures-plus.
Intractable childhood epilepsy with generalized tonic-clonic seizuresICEGTC
A disorder characterized by generalized tonic-clonic seizures beginning usually in infancy and induced by fever. Seizures are associated with subsequent mental decline, as well as ataxia or hypotonia. ICEGTC is similar to SMEI, except for the absence of myoclonic seizures.
Migraine, familial hemiplegic, 3FHM3
A subtype of migraine associated with transient blindness in some families. Migraine is a disabling symptom complex of periodic headaches, usually temporal and unilateral. Headaches are often accompanied by irritability, nausea, vomiting and photophobia, preceded by constriction of the cranial arteries. The two major subtypes are common migraine (migraine without aura) and classic migraine (migraine with aura). Classic migraine is characterized by recurrent attacks of reversible neurological symptoms (aura) that precede or accompany the headache. Aura may include a combination of sensory disturbances, such as blurred vision, hallucinations, vertigo, numbness and difficulty in concentrating and speaking.
Febrile seizures, familial, 3AFEB3A
Seizures associated with febrile episodes in childhood without any evidence of intracranial infection or defined pathologic or traumatic cause. It is a common condition, affecting 2-5% of children aged 3 months to 5 years. The majority are simple febrile seizures (generally defined as generalized onset, single seizures with a duration of less than 30 minutes). Complex febrile seizures are characterized by focal onset, duration greater than 30 minutes, and/or more than one seizure in a 24 hour period. The likelihood of developing epilepsy following simple febrile seizures is low. Complex febrile seizures are associated with a moderately increased incidence of epilepsy.
Developmental and epileptic encephalopathy 6BDEE6B
A form of epileptic encephalopathy, a heterogeneous group of severe early-onset epilepsies characterized by refractory seizures, neurodevelopmental impairment, and poor prognosis. Development is normal prior to seizure onset, after which cognitive and motor delays become apparent. DEE6B is an autosomal dominant condition characterized by onset of seizures in early infancy, profoundly impaired intellectual development, and a hyperkinetic movement disorder.
Sources
Last updated 5/6/2026, 5:23:53 AM