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): 19:35030470-35040449

Links

ENSG00000105711 ∙ NCBI:6324 ∙ OMIM:600235 ∙ HGNC:10586 ∙ Uniprot:Q07699 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

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
• 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
• 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

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Atrial fibrillation, familial 13; Brugada syndrome 5	AD	Cardiovascular; Pharmacogenomic	In 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 fever	Cardiovascular; Neurologic	9697698; 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 (9 variants)
• not provided (2 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			5	102	2	109
missense		2	229	8	3	242
nonsense	1		13			14
start loss	1					1
frameshift	6	1	11			18
inframe indel			5			5
splice donor/acceptor (+/-2bp)	2	4	3			9
splice region			11	9	3	23
non coding			16	50	25	91
Total	10	7	282	160	30

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)
19-35030595-C-T			Likely benign (Jun 14, 2018)
19-35030689-C-G		Generalized epilepsy with febrile seizures plus, type 1 • Brugada syndrome 5	Uncertain significance (Jan 13, 2018)
19-35030698-A-T		Brugada syndrome 5 • Generalized epilepsy with febrile seizures plus, type 1	Uncertain significance (Jan 13, 2018)
19-35030726-C-T		Generalized epilepsy with febrile seizures plus, type 1 • Brugada syndrome 5	Benign/Likely benign (Jan 12, 2018)
19-35030728-G-C		Brugada syndrome 5 • Generalized epilepsy with febrile seizures plus, type 1	Uncertain significance (Jan 13, 2018)
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)
19-35030749-G-A		Brugada syndrome 5 • Generalized epilepsy with febrile seizures plus, type 1	Uncertain significance (Jan 13, 2018)
19-35030780-C-G		not specified	Likely benign (Nov 20, 2017)
19-35030781-C-G		not specified	Benign (Mar 14, 2014)
19-35030790-G-A		not specified • Brugada syndrome 5 • Generalized epilepsy with febrile seizures plus, type 1	Conflicting classifications of pathogenicity (Mar 02, 2018)
19-35030794-G-C		Generalized epilepsy with febrile seizures plus, type 1 • Brugada syndrome 5	Benign (Jan 13, 2018)
19-35030794-G-T		not specified	Likely benign (Aug 09, 2012)
19-35030795-G-C		not specified	Likely benign (Oct 21, 2015)
19-35030812-C-A		not specified • Generalized epilepsy with febrile seizures plus, type 1 • Brugada syndrome 5	Benign/Likely benign (Jan 13, 2018)
19-35030820-C-A		Cardiovascular phenotype	Uncertain significance (Oct 16, 2023)
19-35030820-C-T		not specified • Cardiovascular phenotype	Uncertain significance (Jan 09, 2024)
19-35030821-A-C		Brugada syndrome 5 • Cardiovascular phenotype • not specified	Conflicting classifications of pathogenicity (Jan 03, 2024)
19-35030822-T-C		Brugada syndrome 5	Conflicting classifications of pathogenicity (Dec 17, 2022)
19-35030823-G-A		Brugada syndrome 5	Pathogenic (Jan 02, 2023)
19-35030823-G-C		Brugada syndrome 5	Conflicting classifications of pathogenicity (Apr 06, 2023)
19-35030825-G-T		Brugada syndrome 5	Uncertain significance (Jun 18, 2023)
19-35030828-G-T		Cardiovascular phenotype • Brugada syndrome 5	Uncertain significance (Jan 31, 2024)
19-35030832-G-A		Cardiovascular phenotype	Likely benign (Aug 30, 2019)
19-35030833-C-A		Brugada syndrome 5 • Cardiovascular phenotype	Uncertain significance (Feb 22, 2024)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
SCN1B	protein_coding	protein_coding	ENST00000415950	3	9765

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.102	0.784	125743	0	3	125746	0.0000119

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.22	118	162	0.729	0.0000111	1728
Missense in Polyphen		26	41.131	0.63213		402
Synonymous	-0.0627	68	67.3	1.01	0.00000493	555
Loss of Function	1.22	2	4.91	0.407	2.15e-7	66

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.00000883	0.00000879
Middle Eastern	0.00	0.00
South Asian	0.0000327	0.0000327
Other	0.000163	0.000163

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

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

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