SCN1A
Chr 2ADsodium voltage-gated channel alpha subunit 1
Also known as: DEE6, DEE6A, DEE6B, DRVT, EIEE6, FEB3, FEB3A, FHM3
This gene encodes a voltage-gated sodium channel alpha subunit that controls sodium influx and is essential for action potential generation and propagation in neurons. Mutations cause a spectrum of epileptic disorders including Dravet syndrome, developmental and epileptic encephalopathy, generalized epilepsy with febrile seizures plus, familial febrile seizures, and familial hemiplegic migraine through autosomal dominant inheritance. Disease mechanisms are variant-dependent, with truncating mutations typically causing haploinsufficiency while specific missense variants can produce gain-of-function or dominant-negative effects.
Definitive — sufficient evidence for diagnostic panels
4 total gene-disease associations curated
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Among the most LoF-intolerant genes (~top 3%)
Extremely missense-constrained (top ~0.01%)
Nav1.1 is the most commonly mutated gene in epilepsy. LOF (truncation, severe missense with loss of current) causes Dravet syndrome via reduced inhibitory interneuron firing. GOF missense variants (increased persistent current) cause GEFS+. Mechanism is variant- and phenotype-dependent.
This gene has evidence for multiple mechanisms of pathogenicity (loss-of-function and gain-of-function). The Badonyi & Marsh model scores gain-of-function highest among its predictions, but genomic evidence (constraint, ClinVar variant spectrum, and literature) most strongly supports loss-of-function (haploinsufficiency). Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.
Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.
Literature Evidence
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.
ClinVar Variant Classifications
0 submitted variants in ClinVar
Protein Context — Lollipop Plot
SCN1A · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
3D Protein StructureAlphaFold
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
Longitudinal Study of Phenotypic and Developmental Severity in Patients With Dravet Syndrome With SCN1A Gene Mutation
RECRUITINGOnline Study of People Who Have Genetic Changes and Features of Autism: Simons Searchlight
RECRUITINGA Clinical Study to Evaluate the Safety and Efficacy of ETX101 in Infants and Children With SCN1A-Positive Dravet Syndrome
RECRUITINGNeurodevelopmental Impact of Epilepsy on Autonomic Function in Dravet Syndrome
ACTIVE NOT RECRUITINGA Clinical Study to Evaluate the Safety and Efficacy of ETX101, an AAV9-Delivered Gene Therapy in Children With SCN1A-positive Dravet Syndrome (Australia Only)
ACTIVE NOT RECRUITINGA Clinical Study to Evaluate the Safety and Efficacy of ETX101, an AAV9-Delivered Gene Therapy in Children With SCN1A-positive Dravet Syndrome
ACTIVE NOT RECRUITINGA PET-MRI Study of Serotoninergic Brainstem Pathway in Patients With Dravet Syndrome
RECRUITINGEXploring novEl Molecular Determinants of DRAvet Syndrome Phenotype Heterogeneity
ENROLLING BY INVITATIONExternal Resources
Links to major genomics databases and tools