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GeneBe

SCN1B

sodium voltage-gated channel beta subunit 1, the group of Sodium voltage-gated channel beta subunits|V-set domain containing

Basic information

Region (hg38): 19:35030469-35040449

Links

ENSG00000105711NCBI:6324OMIM:600235HGNC:10586Uniprot:Q07699AlphaFoldGenCCjaxSfariGnomADPubmedClinVar

Phenotypes

GenCC

Source: genCC

  • generalized epilepsy with febrile seizures plus, type 1 (Definitive), mode of inheritance: AD
  • Brugada syndrome 5 (Definitive), mode of inheritance: AD
  • Brugada syndrome 5 (Limited), mode of inheritance: AR
  • Brugada syndrome 5 (Moderate), mode of inheritance: AD
  • developmental and epileptic encephalopathy (Supportive), mode of inheritance: AD
  • progressive familial heart block (Supportive), mode of inheritance: AD
  • Dravet syndrome (Supportive), mode of inheritance: AD
  • generalized epilepsy with febrile seizures plus (Supportive), mode of inheritance: AD
  • generalized epilepsy with febrile seizures plus, type 1 (Moderate), mode of inheritance: AD
  • Brugada syndrome 1 (Disputed Evidence), mode of inheritance: AD
  • generalized epilepsy with febrile seizures plus (Definitive), mode of inheritance: AD
  • developmental and epileptic encephalopathy (Definitive), mode of inheritance: AR
  • atrial fibrillation, familial, 13 (Limited), mode of inheritance: Unknown
  • developmental and epileptic encephalopathy, 52 (Strong), mode of inheritance: AR
  • Brugada syndrome 5 (Limited), mode of inheritance: AD
  • generalized epilepsy with febrile seizures plus, type 1 (Strong), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

ConditionInheritanceIntervention CategoriesIntervention/Rationale Manifestation CategoriesReferences
Atrial fibrillation, familial 13; Brugada syndrome 5ADCardiovascular; PharmacogenomicIn Atrial fibrillation, surveillance (eg, with echocardiogram and electrocardiogram) may allow early medical and/or surgical management (eg, atrioventricular nodal ablation followed by dual-chamber pacemaker implantation has been described), which may be beneficial; In Brugada syndrome, surveillance with approximately yearly EKG and medical interventions, including daily quinidine for prevention (though treatment of asymptomatic individuals is controversial), ICD placement in individuals with previous cardiac arrest/syncope, and isoproterenol for electrical storms, may be beneficial; Certain agents should be avoided, including medications such as certain anesthetics, antidepressants, and antipsychotics, and care should be taken in the instance of high feverCardiovascular; Neurologic9697698; 12011299; 14504340; 18464934; 19808477; 20301690; 23148524; 28218389

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the SCN1B gene.

  • Brugada syndrome 5 (401 variants)
  • not provided (189 variants)
  • Cardiovascular phenotype (111 variants)
  • not specified (83 variants)
  • Generalized epilepsy with febrile seizures plus, type 1 (52 variants)
  • Seizure (8 variants)
  • Inborn genetic diseases (7 variants)
  • Developmental and epileptic encephalopathy, 52 (7 variants)
  • Generalized epilepsy with febrile seizures plus, type 1;Developmental and epileptic encephalopathy, 52;Atrial fibrillation, familial, 13;Brugada syndrome 5 (5 variants)
  • Atrial fibrillation, familial, 13 (5 variants)
  • SCN1B-related condition (3 variants)
  • Brugada syndrome 5;Developmental and epileptic encephalopathy, 52;Generalized epilepsy with febrile seizures plus, type 1;Atrial fibrillation, familial, 13 (3 variants)
  • Developmental and epileptic encephalopathy, 52;Brugada syndrome 5;Generalized epilepsy with febrile seizures plus, type 1;Atrial fibrillation, familial, 13 (2 variants)
  • Cardiac arrhythmia (2 variants)
  • Generalized epilepsy with febrile seizures plus, type 1;Atrial fibrillation, familial, 13;Developmental and epileptic encephalopathy, 52;Brugada syndrome 5 (2 variants)
  • Long QT syndrome (2 variants)
  • Generalized epilepsy with febrile seizures plus, type 1;Developmental and epileptic encephalopathy, 52;Brugada syndrome 5;Atrial fibrillation, familial, 13 (2 variants)
  • Atrial fibrillation, familial, 13;Generalized epilepsy with febrile seizures plus, type 1;Brugada syndrome 5;Developmental and epileptic encephalopathy, 52 (2 variants)
  • Developmental and epileptic encephalopathy, 52;Generalized epilepsy with febrile seizures plus, type 1;Atrial fibrillation, familial, 13;Brugada syndrome 5 (2 variants)
  • Generalized epilepsy with febrile seizures plus, type 1;Brugada syndrome 5;Developmental and epileptic encephalopathy, 52;Atrial fibrillation, familial, 13 (2 variants)
  • Conduction system disorder (1 variants)
  • Atrial fibrillation, familial, 13;Developmental and epileptic encephalopathy, 52;Brugada syndrome 5;Generalized epilepsy with febrile seizures plus, type 1 (1 variants)
  • Severe myoclonic epilepsy in infancy (1 variants)
  • Brugada syndrome 5;Atrial fibrillation, familial, 13 (1 variants)
  • See cases (1 variants)
  • Ventricular fibrillation (1 variants)
  • Generalized epilepsy with febrile seizures plus (1 variants)
  • Childhood absence epilepsy (1 variants)
  • Childhood epilepsy with centrotemporal spikes (1 variants)
  • Death in early adulthood (1 variants)
  • Brugada syndrome 5;Generalized epilepsy with febrile seizures plus, type 1;Atrial fibrillation, familial, 1;Developmental and epileptic encephalopathy, 1 (1 variants)
  • Atrial fibrillation, familial, 13;Generalized epilepsy with febrile seizures plus, type 1;Developmental and epileptic encephalopathy, 52;Brugada syndrome 5 (1 variants)
  • Developmental and epileptic encephalopathy, 52;Generalized epilepsy with febrile seizures plus, type 1;Brugada syndrome 5;Atrial fibrillation, familial, 13 (1 variants)
  • Epileptic encephalopathy (1 variants)
  • Brugada syndrome (1 variants)
  • Developmental and epileptic encephalopathy, 52;Brugada syndrome 5;Atrial fibrillation, familial, 13;Generalized epilepsy with febrile seizures plus, type 1 (1 variants)
  • Brugada syndrome 5;Generalized epilepsy with febrile seizures plus, type 1;Developmental and epileptic encephalopathy, 52;Atrial fibrillation, familial, 13 (1 variants)
  • Generalized epilepsy with febrile seizures plus, type 1;Atrial fibrillation, familial, 13;Brugada syndrome 5;Developmental and epileptic encephalopathy, 52 (1 variants)
  • Developmental and epileptic encephalopathy, 52;Atrial fibrillation, familial, 13;Generalized epilepsy with febrile seizures plus, type 1;Brugada syndrome 5 (1 variants)
  • SCN1B-Related Disorder (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the SCN1B gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type Pathogenic Likely pathogenic VUS Likely benign Benign Sum
synonymous
4
clinvar
87
clinvar
2
clinvar
93
missense
2
clinvar
206
clinvar
7
clinvar
5
clinvar
220
nonsense
1
clinvar
13
clinvar
14
start loss
1
clinvar
1
frameshift
4
clinvar
12
clinvar
16
inframe indel
5
clinvar
5
splice donor/acceptor (+/-2bp)
1
clinvar
3
clinvar
6
clinvar
10
splice region
9
9
3
21
non coding
15
clinvar
47
clinvar
25
clinvar
87
Total 6 5 262 141 32

Variants in SCN1B

This is a list of pathogenic ClinVar variants found in the SCN1B region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position Type Phenotype Significance ClinVar
19-35030556-G-A Likely benign (Jun 26, 2018)1190623
19-35030595-C-T Likely benign (Jun 14, 2018)675777
19-35030689-C-G Generalized epilepsy with febrile seizures plus, type 1 • Brugada syndrome 5 Uncertain significance (Jan 13, 2018)328829
19-35030698-A-T Brugada syndrome 5 • Generalized epilepsy with febrile seizures plus, type 1 Uncertain significance (Jan 13, 2018)889254
19-35030726-C-T Generalized epilepsy with febrile seizures plus, type 1 • Brugada syndrome 5 Benign/Likely benign (Jan 12, 2018)328830
19-35030728-G-C Brugada syndrome 5 • Generalized epilepsy with febrile seizures plus, type 1 Uncertain significance (Jan 13, 2018)328831
19-35030733-A-C Generalized epilepsy with febrile seizures plus, type 1 • Brugada syndrome 5 • Generalized epilepsy with febrile seizures plus, type 1;Atrial fibrillation, familial, 13;Developmental and epileptic encephalopathy, 52;Brugada syndrome 5 Uncertain significance (Dec 28, 2021)328832
19-35030749-G-A Brugada syndrome 5 • Generalized epilepsy with febrile seizures plus, type 1 Uncertain significance (Jan 13, 2018)889934
19-35030780-C-G not specified Likely benign (Nov 20, 2017)513312
19-35030781-C-G not specified Benign (Mar 14, 2014)139001
19-35030790-G-A not specified • Brugada syndrome 5 • Generalized epilepsy with febrile seizures plus, type 1 Conflicting classifications of pathogenicity (Mar 02, 2018)516623
19-35030794-G-C Generalized epilepsy with febrile seizures plus, type 1 • Brugada syndrome 5 Benign (Jan 13, 2018)328833
19-35030794-G-T not specified Likely benign (Aug 09, 2012)190851
19-35030795-G-C not specified Likely benign (Oct 21, 2015)379366
19-35030812-C-A not specified • Generalized epilepsy with febrile seizures plus, type 1 • Brugada syndrome 5 Benign/Likely benign (Jan 13, 2018)139002
19-35030820-C-T not specified • Cardiovascular phenotype Uncertain significance (Mar 17, 2020)373645
19-35030821-A-C Brugada syndrome 5 • Cardiovascular phenotype • not specified Conflicting classifications of pathogenicity (Jan 03, 2024)489074
19-35030822-T-C Brugada syndrome 5 Conflicting classifications of pathogenicity (Dec 17, 2022)1191122
19-35030823-G-A Brugada syndrome 5 Pathogenic (Jan 02, 2023)2891167
19-35030823-G-C Brugada syndrome 5 Conflicting classifications of pathogenicity (Apr 06, 2023)1040220
19-35030825-G-T Brugada syndrome 5 Uncertain significance (Jun 18, 2023)2727503
19-35030828-G-T Cardiovascular phenotype • Brugada syndrome 5 Uncertain significance (Jan 31, 2024)1302666
19-35030832-G-A Cardiovascular phenotype Likely benign (Aug 30, 2019)1769364
19-35030833-C-A Brugada syndrome 5 • Cardiovascular phenotype Uncertain significance (Sep 22, 2021)424188
19-35030836-G-C Brugada syndrome 5 Uncertain significance (Aug 23, 2022)941917

GnomAD

Source: gnomAD

GeneTypeBio TypeTranscript Coding Exons Length
SCN1Bprotein_codingprotein_codingENST00000415950 39765
pLI Probability
LOF Intolerant
pRec Probability
LOF Recessive
Individuals with
no LOFs
Individuals with
Homozygous LOFs
Individuals with
Heterozygous LOFs
Defined p
0.1020.784125743031257460.0000119
Z-Score Observed Expected Observed/Expected Mutation Rate Total Possible in Transcript
Missense1.221181620.7290.00001111728
Missense in Polyphen2641.1310.63213402
Synonymous-0.06276867.31.010.00000493555
Loss of Function1.2224.910.4072.15e-766

LoF frequencies by population

EthnicitySum of pLOFs p
African & African-American0.000.00
Ashkenazi Jewish0.000.00
East Asian0.000.00
Finnish0.000.00
European (Non-Finnish)0.000008830.00000879
Middle Eastern0.000.00
South Asian0.00003270.0000327
Other0.0001630.000163

dbNSFP

Source: dbNSFP

Function
FUNCTION: Crucial in the assembly, expression, and functional modulation of the heterotrimeric complex of the sodium channel. The subunit beta-1 can modulate multiple alpha subunit isoforms from brain, skeletal muscle, and heart. Its association with NFASC may target the sodium channels to the nodes of Ranvier of developing axons and retain these channels at the nodes in mature myelinated axons. {ECO:0000269|PubMed:14622265}.;
Disease
DISEASE: Brugada syndrome 5 (BRGDA5) [MIM:612838]: A tachyarrhythmia characterized by right bundle branch block and ST segment elevation on an electrocardiogram (ECG). It can cause the ventricles to beat so fast that the blood is prevented from circulating efficiently in the body. When this situation occurs, the individual will faint and may die in a few minutes if the heart is not reset. {ECO:0000269|PubMed:18464934}. Note=The gene represented in this entry may be involved in disease pathogenesis.; DISEASE: Atrial fibrillation, familial, 13 (ATFB13) [MIM:615377]: A familial form of atrial fibrillation, a common sustained cardiac rhythm disturbance. Atrial fibrillation is characterized by disorganized atrial electrical activity and ineffective atrial contraction promoting blood stasis in the atria and reduces ventricular filling. It can result in palpitations, syncope, thromboembolic stroke, and congestive heart failure. {ECO:0000269|PubMed:19808477}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Epileptic encephalopathy, early infantile, 52 (EIEE52) [MIM:617350]: A form of epileptic encephalopathy, a heterogeneous group of severe childhood 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. EIEE52 inheritance is autosomal recessive. {ECO:0000269|PubMed:19710327, ECO:0000269|PubMed:23148524}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
Pathway
Adrenergic signaling in cardiomyocytes - Homo sapiens (human);Antiarrhythmic Pathway, Pharmacodynamics;Levomethadyl Acetate Action Action Pathway;Fluoxetine Action Pathway;Citalopram Action Pathway;Escitalopram Action Pathway;Imipramine Action Pathway;Desipramine Action Pathway;Levallorphan Action Pathway;Dimethylthiambutene Action Pathway;Ethylmorphine Action Pathway;Pentazocine Action Pathway;Naltrexone Action Pathway;Buprenorphine Action Pathway;Alvimopan Action Pathway;Naloxone Action Pathway;Dihydromorphine Action Pathway;Lidocaine (Local Anaesthetic) Metabolism Pathway;Nicotine Action Pathway;Nalbuphine Action Pathway;Ketobemidone Action Pathway;Lidocaine (Local Anaesthetic) Action Pathway;Mepivacaine Action Pathway;Chloroprocaine Action Pathway;Cocaine Action Pathway;Dibucaine Action Pathway;Levobupivacaine Action Pathway;Benzocaine Action Pathway;Bupivacaine Action Pathway;Levorphanol Action Pathway;Propoxyphene Action Pathway;Tramadol Action Action Pathway;Diphenoxylate Action Pathway;Anileridine Action Pathway;Methadone Action Pathway;Oxycodone Action Pathway;Oxybuprocaine Action Pathway;Prilocaine Action Pathway;Procaine Action Pathway;Proparacaine Action Pathway;Ropivacaine Action Pathway;Codeine Action Pathway;Morphine Action Pathway;Heroin Action Pathway;Alfentanil Action Pathway;Oxymorphone Action Pathway;Hydrocodone Action Pathway;Hydromorphone Action Pathway;Sufentanil Action Pathway;Remifentanil Action Pathway;Fentanyl Action Pathway;Carfentanil Action Pathway;3-Methylthiofentanyl Action Pathway;Methadyl Acetate Action Pathway;Dezocine Action Pathway;Developmental Biology;Phase 0 - rapid depolarisation;Cardiac conduction;Muscle contraction;Interaction between L1 and Ankyrins;L1CAM interactions;Axon guidance (Consensus)

Recessive Scores

pRec
0.158

Intolerance Scores

loftool
0.0653
rvis_EVS
0.62
rvis_percentile_EVS
83.25

Haploinsufficiency Scores

pHI
0.174
hipred
N
hipred_score
0.277
ghis
0.608

Essentials

essential_gene_CRISPR
N
essential_gene_CRISPR2
N
essential_gene_gene_trap
N
gene_indispensability_pred
E
gene_indispensability_score
0.683

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium

Mouse Genome Informatics

Gene name
Scn1b
Phenotype
behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); normal phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); vision/eye phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); growth/size/body region phenotype;

Zebrafish Information Network

Gene name
scn1bb
Affected structure
motor neuron
Phenotype tag
abnormal
Phenotype quality
branchiness

Gene ontology

Biological process
cell adhesion;chemical synaptic transmission;axon guidance;positive regulation of sodium ion transport;positive regulation of neuron projection development;neuronal action potential propagation;corticospinal neuron axon guidance;sodium ion transmembrane transport;locomotion;response to pyrethroid;membrane depolarization;cardiac muscle contraction;regulation of ventricular cardiac muscle cell membrane repolarization;regulation of atrial cardiac muscle cell membrane depolarization;cardiac conduction;cardiac muscle cell action potential involved in contraction;membrane depolarization during cardiac muscle cell action potential;membrane depolarization during Purkinje myocyte cell action potential;regulation of heart rate by cardiac conduction;regulation of sodium ion transmembrane transporter activity
Cellular component
voltage-gated sodium channel complex;extracellular region;plasma membrane;intercalated disc;T-tubule;node of Ranvier
Molecular function
voltage-gated ion channel activity;voltage-gated sodium channel activity;protein binding;sodium channel regulator activity;sodium channel inhibitor activity;ion channel binding;voltage-gated sodium channel activity involved in cardiac muscle cell action potential;voltage-gated sodium channel activity involved in Purkinje myocyte action potential