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GeneE
10 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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SCN1B
sodium voltage-gated channel beta subunit 1
Chromosome 19 · 19q13.11
NCBI Gene: 6324Ensembl: ENSG00000105711.14HGNC: HGNC:10586UniProt: A0A1W2PR05
86PubMed Papers
24Diseases
0Drugs
37Pathogenic Variants
FUNCTIONAL ROLE
Transporter
CLINICAL
OMIM Disease Gene
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
protein bindingsodium channel regulator activitypositive regulation of sodium ion transportsodium ion transmembrane transportGeneralized epilepsy with febrile seizures-plusdevelopmental and epileptic encephalopathy, 52atrial fibrillation, familial, 13Brugada syndrome 5
✦AI Summary

SCN1B encodes the voltage-gated sodium channel β1 subunit, a multifunctional protein essential for neuronal and cardiac excitability 1. Beyond its canonical role as a sodium channel regulator, SCN1B functions as a cell adhesion molecule stimulating neurite outgrowth and regulating gene transcription through regulated intramembrane proteolysis 1. The protein modulates both sodium and potassium currents with subtype-specific effects on different sodium channel α subunits 1. SCN1B is expressed in both brain and heart, where it interacts with other regulatory proteins like FGF13A and LRRC37B to fine-tune neuronal excitability 2. Biallelic SCN1B pathogenic variants cause developmental and epileptic encephalopathy 52 (DEE52), clinically overlapping Dravet syndrome 1. SCN1B-linked disease mechanisms involve variable loss-of-function effects; the recessive variant SCN1B-c.265C>T produces incomplete loss-of-function with altered sodium channel regulation, distinct from complete null effects 1. Beyond seizures, DEE52 patients exhibit high sudden unexpected death in epilepsy (SUDEP) risk, potentially involving cardiac arrhythmias: patient-derived cardiomyocytes show increased sodium and potassium currents with altered electrophysiology 3. SCN1B variants are also associated with Brugada syndrome, atrial fibrillation, and generalized epilepsy with febrile seizures plus 1 1. Phenotypic severity varies substantially even within families carrying identical variants, influenced by polygenic background 4.

Sources cited
1
SCN1B encodes β1 subunits that regulate excitability by modulating sodium and potassium currents, function as cell adhesion molecules, and regulate gene transcription; biallelic pathogenic variants cause DEE52 with Dravet syndrome features
PMID: 38425576
2
SCN1B interacts with regulatory proteins LRRC37B and FGF13A to modulate voltage-gated sodium channel function and neuronal excitability at the axon initial segment
PMID: 38134874
3
SCN1B-c.265C>T variant causes cardiac electrical and structural abnormalities including increased potassium and sodium currents in patient-derived cardiomyocytes, contributing to SUDEP risk
PMID: 40763036
4
Phenotypic variability in SCN1B-linked epilepsy is influenced by polygenic background, with higher epilepsy polygenic risk scores associated with more severe phenotypes in affected relatives
PMID: 39476534
⚠Limited data available — This gene has 4 indexed publications. Summary and analysis may be incomplete.
Disease Associationsⓘ24
Generalized epilepsy with febrile seizures-plusOpen Targets
0.76Strong
developmental and epileptic encephalopathy, 52Open Targets
0.75Strong
atrial fibrillation, familial, 13Open Targets
0.72Strong
Brugada syndrome 5Open Targets
0.72Strong
genetic developmental and epileptic encephalopathyOpen Targets
0.65Moderate
Familial progressive cardiac conduction defectOpen Targets
0.62Moderate
conduction system disorderOpen Targets
0.54Moderate
Abnormality of the cardiovascular systemOpen Targets
0.47Moderate
generalized epilepsy with febrile seizures plusOpen Targets
0.47Moderate
developmental and epileptic encephalopathyOpen Targets
0.47Moderate
Dravet syndromeOpen Targets
0.46Moderate
early-infantile DEEOpen Targets
0.37Weak
Rolandic epilepsyOpen Targets
0.35Weak
self-limited epilepsy with centrotemporal spikesOpen Targets
0.34Weak
cardiomyopathyOpen Targets
0.33Weak
neurodegenerative diseaseOpen Targets
0.33Weak
Brugada syndromeOpen Targets
0.30Weak
Prolonged QT intervalOpen Targets
0.30Weak
undetermined early-onset epileptic encephalopathyOpen Targets
0.28Weak
Epileptic encephalopathyOpen Targets
0.27Weak
Atrial fibrillation, familial, 13UniProt
Brugada syndrome 5UniProt
Developmental and epileptic encephalopathy 52UniProt
Generalized epilepsy with febrile seizures plus 1UniProt
Pathogenic Variants37
NM_001037.5(SCN1B):c.449-2A>GPathogenic
Developmental and epileptic encephalopathy, 52|Generalized epilepsy with febrile seizures plus, type 1|Brugada syndrome 5|not provided|Genetic developmental and epileptic encephalopathy
★★★☆2025
NM_001037.5(SCN1B):c.363C>G (p.Cys121Trp)Pathogenic
Generalized epilepsy with febrile seizures plus, type 1|not provided|Atrial fibrillation, familial, 13|Brugada syndrome 5|Developmental and epileptic encephalopathy, 52;Generalized epilepsy with febrile seizures plus, type 1;Brugada syndrome 5;Atrial fibrillation, familial, 13|Cardiovascular phenotype|SCN1B-related disorder
★★☆☆2026→ Residue 121
NM_001037.5(SCN1B):c.253C>T (p.Arg85Cys)Pathogenic
Generalized epilepsy with febrile seizures plus, type 1|Cardiovascular phenotype|Brugada syndrome 5|not provided|Developmental and epileptic encephalopathy, 52
★★☆☆2025→ Residue 85
NM_001037.5(SCN1B):c.347del (p.Ser116fs)Pathogenic
not provided|Brugada syndrome 5|Cardiovascular phenotype
★★☆☆2025→ Residue 116
NM_001037.5(SCN1B):c.472G>A (p.Val158Met)Pathogenic
not provided|Brugada syndrome 5
★★☆☆2025→ Residue 158
NM_001037.5(SCN1B):c.254G>A (p.Arg85His)Pathogenic
Atrial fibrillation, familial, 13|not provided|Generalized epilepsy with febrile seizures plus, type 1;Atrial fibrillation, familial, 13;Brugada syndrome 5;Developmental and epileptic encephalopathy, 52|Brugada syndrome 5|Cardiovascular phenotype|SCN1B-related disorder
★★☆☆2025→ Residue 85
NM_001037.5(SCN1B):c.357C>A (p.Tyr119Ter)Pathogenic
Brugada syndrome 5
★☆☆☆2025→ Residue 119
NM_001037.5(SCN1B):c.178del (p.Arg60fs)Pathogenic
Brugada syndrome 5
★☆☆☆2025→ Residue 60
NM_001037.5(SCN1B):c.40+1G>TPathogenic
not provided
★☆☆☆2025
NM_001037.5(SCN1B):c.24_25insT (p.Val9fs)Pathogenic
Brugada syndrome 5
★☆☆☆2025→ Residue 9
NM_001037.5(SCN1B):c.77C>A (p.Ser26Ter)Pathogenic
Brugada syndrome 5
★☆☆☆2025→ Residue 26
NM_001037.5(SCN1B):c.449-1G>TLikely pathogenic
Brugada syndrome 5
★☆☆☆2025
NM_001037.5(SCN1B):c.510G>C (p.Leu170Phe)Likely pathogenic
Long QT syndrome
★☆☆☆2025→ Residue 170
NM_001037.5(SCN1B):c.59dup (p.Cys21fs)Pathogenic
Brugada syndrome 5
★☆☆☆2025→ Residue 21
NM_001037.5(SCN1B):c.207+1G>APathogenic
Brugada syndrome 5
★☆☆☆2025
NM_001037.5(SCN1B):c.312_315del (p.Ile106fs)Pathogenic
Brugada syndrome 5
★☆☆☆2024→ Residue 106
NM_001037.5(SCN1B):c.449-1G>APathogenic
not provided
★☆☆☆2024
NM_001037.5(SCN1B):c.105del (p.Phe36fs)Pathogenic
Brugada syndrome 5
★☆☆☆2024→ Residue 36
NM_001037.5(SCN1B):c.166G>T (p.Glu56Ter)Pathogenic
Brugada syndrome 5
★☆☆☆2024→ Residue 56
NM_001037.5(SCN1B):c.40+1G>APathogenic
not provided
★☆☆☆2024
View on ClinVar ↗
Related Genes
KCNQ2Protein interaction100%CAMK2AProtein interaction100%CAMK2BProtein interaction100%PRKACBProtein interaction97%PRKACAProtein interaction97%PRKACGProtein interaction96%
Tissue Expression6 tissues
Brain
100%
Heart
72%
Lung
21%
Liver
14%
Ovary
13%
Bone Marrow
5%
Gene Interaction Network
Click a node to explore
SCN1BKCNQ2CAMK2ACAMK2BPRKACBPRKACAPRKACG
PROTEIN STRUCTURE
Preparing viewer…
PDB7W9K · 2.20 Å · EM
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
0.71LoF Tolerant
pLIⓘ
0.20Tolerant
Observed/Expected LoF0.43 [0.27–0.71]
RankingsWhere SCN1B stands among ~20K protein-coding genes
  • #5,570of 20,598
    Most Researched86
  • #1,621of 5,498
    Most Pathogenic Variants37
  • #5,447of 17,882
    Most Constrained (LOEUF)0.71
Genes detectedSCN1B
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
Epilepsy and sudden unexpected death in epilepsy in a mouse model of human
PMID: 38425576
Brain Commun · 2023
1.00
2
Clinical exome sequencing: results from 2819 samples reflecting 1000 families.
PMID: 27848944
Eur J Hum Genet · 2017
0.90
3
LRRC37B is a human modifier of voltage-gated sodium channels and axon excitability in cortical neurons.
PMID: 38134874
Cell · 2023
0.80
4
PMID: 39637100
0.70
5
SCN1B and SCN2B gene variants analysis in dravet syndrome patients: Analysis of 22 cases.
PMID: 30921204
Medicine (Baltimore) · 2019
0.60