SCN1A Gene

SCN1A Gene

<table class="infobox infobox-gene">
<tr>
<th class="infobox-header" colspan="2">SCN1A — Sodium Voltage-Gated Channel Alpha Subunit 1</th>
</tr>
<tr> [@catterall2014]
<td class="label">Symbol</td> [@claes2001]
<td><strong>SCN1A</strong></td>
</tr>
<tr>
<td class="label">Full Name</td>
<td>Sodium Voltage-Gated Channel Alpha Subunit 1</td>
</tr>
<tr>
<td class="label">Chromosome</td>
<td>2q24.3</td>
</tr>
<tr>
<td class="label">NCBI Gene</td>
<td><a href="https://www.ncbi.nlm.nih.gov/gene/6335" target="_blank">6335</a></td>
</tr>
<tr>
<td class="label">Ensembl</td>
<td><a href="https://ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000144285" target="_blank">ENSG00000144285</a></td>
</tr>
<tr>
<td class="label">OMIM</td>
<td><a href="https://omim.org/entry/182389" target="_blank">182389</a></td>
</tr>
<tr>
<td class="label">UniProt</td>
<td><a href="https://www.uniprot.org/uniprot/P35499" target="_blank">P35499</a></td>
</tr>
<tr>
<td class="label">Protein Name</td>
<td>Nav1.1 (Sodium channel voltage-gated alpha subunit 1)</td>
</tr>
<tr>
<td class="label">Channel Type</td>
<td>Voltage-gated sodium channel (NaV)</td>
</tr>
<tr>
<td class="label">Ion Selectivity</td>
<td>Na+ > K+</td>
</tr>
<tr>
<td class="label">Tissue Expression</td>
<td>Cerebral [cortex](/brain-regions/cortex), [Hippocampus](/brain-regions/hippocampus), Cerebellum, Brainstem</td>
</tr>
<tr>
<td class="label">Diseases</td>
<td>Dravet Syndrome, Febri

SCN1A Gene

<table class="infobox infobox-gene">
<tr>
<th class="infobox-header" colspan="2">SCN1A — Sodium Voltage-Gated Channel Alpha Subunit 1</th>
</tr>
<tr> [@catterall2014]
<td class="label">Symbol</td> [@claes2001]
<td><strong>SCN1A</strong></td>
</tr>
<tr>
<td class="label">Full Name</td>
<td>Sodium Voltage-Gated Channel Alpha Subunit 1</td>
</tr>
<tr>
<td class="label">Chromosome</td>
<td>2q24.3</td>
</tr>
<tr>
<td class="label">NCBI Gene</td>
<td><a href="https://www.ncbi.nlm.nih.gov/gene/6335" target="_blank">6335</a></td>
</tr>
<tr>
<td class="label">Ensembl</td>
<td><a href="https://ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000144285" target="_blank">ENSG00000144285</a></td>
</tr>
<tr>
<td class="label">OMIM</td>
<td><a href="https://omim.org/entry/182389" target="_blank">182389</a></td>
</tr>
<tr>
<td class="label">UniProt</td>
<td><a href="https://www.uniprot.org/uniprot/P35499" target="_blank">P35499</a></td>
</tr>
<tr>
<td class="label">Protein Name</td>
<td>Nav1.1 (Sodium channel voltage-gated alpha subunit 1)</td>
</tr>
<tr>
<td class="label">Channel Type</td>
<td>Voltage-gated sodium channel (NaV)</td>
</tr>
<tr>
<td class="label">Ion Selectivity</td>
<td>Na+ > K+</td>
</tr>
<tr>
<td class="label">Tissue Expression</td>
<td>Cerebral [cortex](/brain-regions/cortex), [Hippocampus](/brain-regions/hippocampus), Cerebellum, Brainstem</td>
</tr>
<tr>
<td class="label">Diseases</td>
<td>Dravet Syndrome, Febrile Seizures, Genetic Epilepsy with Febrile Seizures Plus (GEFS+), Lennox-Gastaut Syndrome, Early Myoclonic Encephalopathy</td>
</tr>
<tr>
<td class="label">Associated Diseases</td>
<td><a href="/wiki/aging" style="color:#ef9a9a">Aging</a>, <a href="/wiki/als" style="color:#ef9a9a">Als</a>, <a href="/wiki/autism" style="color:#ef9a9a">Autism</a>, <a href="/wiki/cancer" style="color:#ef9a9a">Cancer</a>, <a href="/wiki/cardiac" style="color:#ef9a9a">Cardiac</a></td>
</tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">135 edges</a></td>
</tr>
</table>

SCN1A — Sodium Voltage-Gated Channel Alpha Subunit 1

Introduction

Scn1A Gene is an important component in the neurobiology of neurodegenerative diseases. This page provides detailed information about its structure, function, and role in disease processes.

Overview

SCN1A (Sodium Voltage-Gated Channel Alpha Subunit 1) is a gene located on chromosome 2q24.3 that encodes the Nav1.1 voltage-gated sodium channel. This channel is predominantly expressed in fast-spiking GABAergic inhibitory interneurons, particularly parvalbumin-positive and somatostatin-positive interneurons. SCN1A mutations are the primary genetic cause of Dravet syndrome, one of the most severe genetic epilepsy syndromes. The gene is catalogued as NCBI Gene ID [6335](https://www.ncbi.nlm.nih.gov/gene/6335) and OMIM [182389](https://omim.org/entry/182389).

Channel Structure and Function

Molecular Architecture

Nav1.1 is a large transmembrane protein (~2000 amino acids) organized into four homologous domains (I-IV), each containing six transmembrane segments (S1-S6). The S4 voltage sensor detects membrane potential changes, while the P-loop between S5 and S6 forms the ion selectivity filter [1](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3860884/). Nav1.1 shares structural homology with other neuronal sodium channels (Nav1.2, Nav1.3, Nav1.6) but has distinct functional properties.

Gating Properties

Nav1.1 exhibits rapid activation and fast inactivation kinetics typical of neuronal sodium channels. The channel activates at membrane potentials around -40 mV and reaches peak conductance within 1-2 ms. Fast inactivation occurs within milliseconds, mediated by the intracellular III-IV linker acting as a hinged lid [2](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3154093/). Recovery from inactivation occurs during repolarization, allowing channels to participate in subsequent action potentials.

Cellular Localization

In the brain, Nav1.1 is highly enriched in GABAergic inhibitory interneurons, particularly:

• Parvalbumin (PV)-positive fast-spiking interneurons: Critical for gamma oscillations and feedforward inhibition
• Somatostatin (SST)-positive interneurons: Mediate dendritic inhibition
• Chandelier cells: Axo-axonic interneurons targeting pyramidal neuron axon initial segments

Role in Neuronal Circuits

Inhibitory Neuron Function

Nav1.1 is essential for the excitability of inhibitory interneurons. Loss-of-function mutations reduce sodium current in these [neurons](/entities/neurons), impairing their ability to fire action potentials and provide inhibitory drive to excitatory pyramidal neurons. The resulting disinhibition leads to hyperexcitability of cortical circuits and seizure generation [4](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3375014/).

Circuit Dysfunction in Epilepsy

The selective vulnerability of inhibitory neurons to SCN1A mutations creates a paradoxical situation: excitatory neurons become overactive due to reduced inhibition. This mechanism differs from gain-of-function sodium channel mutations (e.g., SCN2A), which directly increase excitatory neuron excitability. Understanding this distinction is crucial for developing targeted therapies [5](https://pubmed.ncbi.nlm.nih.gov/25540006/).

Disease Associations

Dravet Syndrome

Dravet syndrome (also known as Severe Myoclonic Epilepsy of Infancy, SMEI) is a catastrophic early-onset epilepsy syndrome caused by de novo SCN1A mutations in approximately 80% of cases. Key features include:

• Onset: 6-18 months of age, typically triggered by fever
• Seizure types: Febrile seizures, myoclonic seizures, focal seizures, tonic-clonic seizures
• EEG: Initially normal, later showing generalized spike-wave and photosensitivity
• Developmental outcome: Progressive cognitive decline, ataxia, sleep disturbances
• Mortality: Up to 15-20% mortality due to sudden unexpected death in epilepsy (SUDEP)

Genetic Epilepsy with Febrile Seizures Plus (GEFS+)

GEFS+ is a milder spectrum disorder caused by inherited SCN1A mutations with incomplete penetrance. Affected family members may have:

• Febrile seizures beyond age 6
• Febrile seizures plus (FS+)
• Focal epilepsy
• Rarely, Dravet syndrome phenotype

Other Epilepsy Syndromes

• Lennox-Gastaut Syndrome: Severe childhood epilepsy with multiple seizure types
• Early Myoclonic Encephalopathy: Infantile onset with myoclonic seizures
• Focal Epilepsy: Less common, often with good response to treatment

Therapeutic Implications

Sodium Channel Blockers

Paradoxically, sodium channel blockers (e.g., carbamazepine, phenytoin) can worsen Dravet syndrome in some cases by preferentially affecting remaining functional channels. However, certain agents may be beneficial:

| Drug | Considerations |
|------|---------------|
| Stiripentol | GABA-A modulator, first-line for Dravet |
| Clobazam | Benzodiazepine, enhances GABA |
| Valproic acid | Broad-spectrum anticonvulsant |
| Cannabidiol | FDA-approved for Dravet |

Targeted Therapies

Novel approaches under investigation:

• Gene therapy: Viral delivery of functional SCN1A
• Antisense oligonucleotides: Allele-specific suppression
• Precision medicine: Sodium channel subtype-selective drugs

Key Publications

External Links

• NCBI Gene: [https://www.ncbi.nlm.nih.gov/gene/6335](https://www.ncbi.nlm.nih.gov/gene/6335)
• Ensembl: [https://ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000144285](https://ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000144285)
• OMIM: [https://omim.org/entry/182389](https://omim.org/entry/182389)
• UniProt: [https://www.uniprot.org/uniprot/P35499](https://www.uniprot.org/uniprot/P35499)
• Dravet Syndrome Foundation: [https://dravetfoundation.org/](https://dravetfoundation.org/)

See Also

• [Genes Index](/genes)
• [Proteins Index](/proteins)
• [Diseases Index](/diseases)
• [Mechanisms Index](/mechanisms)
• [Ion Channels](/proteins/nav1-1-protein)
• [Dravet Syndrome](/diseases/dravet-syndrome)
• [Epilepsy](/diseases/epilepsy)
• [Action Potential Mechanisms](/mechanisms/action-potential-generation)

Background

The study of Scn1A Gene has evolved significantly over the past decades. Research in this area has revealed important insights into the underlying mechanisms of neurodegeneration and continues to drive therapeutic development.

Historical context and key discoveries in this field have shaped our current understanding and will continue to guide future research directions.

Brain Atlas Resources

Explore gene expression and cell type data for SCN1A in these authoritative brain atlas resources:

• [[Allen Human Brain Atlas](https://human.brain-map.org/microarray/search/show?search_term=SCN1A)*: Gene expression data from adult human brain spec](/datasets/allen-human-brain-atlas)imens
• [Allen Cell Type Atlas](https://celltypes.brain-map.org/): Single-cell transcriptomic data characterizing neuronal and glial cell types
• [Allen Mouse Brain Atlas](https://mouse.brain-map.org/): Gene expression throughout the mouse brain
• [BrainSpan Atlas of the Developing Human Brain](https://www.brainspan.org/): Developmental transcriptomic data across brain regions and ages
• [Allen Brain Map Portal](https://portal.brain-map.org/): Unified access to all Allen Brain Atlas data resources

References

Pathway Diagram

The following diagram shows the key molecular relationships involving SCN1A Gene discovered through SciDEX knowledge graph analysis: