SCN3B

sodium voltage-gated channel beta subunit 3, the group of V-set domain containing|Sodium voltage-gated channel beta subunits

Basic information

Region (hg38): 11:123629186-123655244

Links

ENSG00000166257 ∙ NCBI:55800 ∙ OMIM:608214 ∙ HGNC:20665 ∙ Uniprot:Q9NY72 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• Brugada syndrome 7 (Limited), mode of inheritance: AD
• familial atrial fibrillation (Supportive), mode of inheritance: AD
• Brugada syndrome 7 (Limited), mode of inheritance: Unknown
• Brugada syndrome 7 (Limited), mode of inheritance: AD
• Brugada syndrome 1 (Disputed Evidence), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Brugada syndrome 7; Atrial fibrillation, familial 16	AD	Cardiovascular; Pharmacogenomic	In Atrial fibrilliation, medical/preventive management may decrease morbidity; 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	20031595; 20301690; 20558140; 21051419

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the SCN3B gene.

• Brugada syndrome 7 (97 variants)
• Cardiovascular phenotype (95 variants)
• not provided (71 variants)
• not specified (23 variants)
• Brugada syndrome (10 variants)
• Inborn genetic diseases (4 variants)
• Cardiac arrhythmia (2 variants)
• Atrial fibrillation, familial, 16 (2 variants)
• Death in infancy (1 variants)
• Cardiomyopathy (1 variants)
• Long QT syndrome (1 variants)
• Sudden cardiac death (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the SCN3B 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				42	3	45
missense			78	1		79
nonsense			2			2
start loss						0
frameshift			4			4
inframe indel			2			2
splice donor/acceptor (+/-2bp)			5			5
splice region			1	7		8
non coding			9	24	25	58
Total	0	0	100	67	28

Variants in SCN3B

This is a list of pathogenic ClinVar variants found in the SCN3B region.

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

Position	Type	Phenotype	Significance	ClinVar
11-123629211-A-G		Brugada syndrome	Uncertain significance (Jun 14, 2016)
11-123630998-TTTC-T		Brugada syndrome	Uncertain significance (Jun 14, 2016)
11-123631433-C-T		Brugada syndrome	Uncertain significance (Jun 14, 2016)
11-123631839-TAATA-T		Brugada syndrome	Uncertain significance (Jun 14, 2016)
11-123632791-C-CA		Brugada syndrome	Uncertain significance (Jun 14, 2016)
11-123633290-C-T			Benign (Mar 03, 2015)
11-123633352-G-T		Brugada syndrome	Uncertain significance (Jun 14, 2016)
11-123633646-G-A			Benign (Mar 03, 2015)
11-123633773-C-T			Benign (Mar 03, 2015)
11-123633791-A-T		not specified	Likely benign (Dec 27, 2016)
11-123633965-C-G			Benign (Jun 19, 2018)
11-123634105-T-G		not specified	Benign (May 15, 2014)
11-123634159-A-C		Brugada syndrome 7	Uncertain significance (Mar 15, 2018)
11-123634160-C-T		Cardiovascular phenotype	Uncertain significance (May 26, 2023)
11-123634161-C-T		Brugada syndrome 7 • Cardiovascular phenotype	Likely benign (Oct 15, 2020)
11-123634162-G-A		not specified • Brugada syndrome 7 • Cardiovascular phenotype	Benign/Likely benign (Mar 03, 2023)
11-123634163-C-T		Cardiovascular phenotype	Uncertain significance (Apr 21, 2022)
11-123634167-G-A		Brugada syndrome 7	Likely benign (Dec 26, 2023)
11-123634170-C-T		Cardiovascular phenotype	Likely benign (Feb 18, 2024)
11-123634173-C-G		Brugada syndrome 7	Uncertain significance (Feb 04, 2022)
11-123634177-T-C		Cardiovascular phenotype • Brugada syndrome 7	Uncertain significance (Aug 24, 2021)
11-123634183-G-A		Cardiovascular phenotype	Uncertain significance (Jan 08, 2023)
11-123634190-T-C		Brugada syndrome 7	Uncertain significance (Dec 11, 2023)
11-123634194-A-G		Cardiovascular phenotype	Likely benign (Feb 16, 2024)
11-123634199-A-AG		Cardiovascular phenotype	Uncertain significance (Mar 20, 2017)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
SCN3B	protein_coding	protein_coding	ENST00000392770	5	26058

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.0510	0.930	125742	0	5	125747	0.0000199

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.794	100	125	0.800	0.00000822	1400
Missense in Polyphen		33	43.125	0.76522		480
Synonymous	0.0743	52	52.7	0.987	0.00000376	418
Loss of Function	2.04	4	11.4	0.350	5.97e-7	131

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000289	0.0000289
Ashkenazi Jewish	0.00	0.00
East Asian	0.0000544	0.0000544
Finnish	0.00	0.00
European (Non-Finnish)	0.00000881	0.00000879
Middle Eastern	0.0000544	0.0000544
South Asian	0.0000654	0.0000653
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Modulates channel gating kinetics. Causes unique persistent sodium currents. Inactivates the sodium channel opening more slowly than the subunit beta-1. 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 (By similarity). {ECO:0000250}.
• Disease: DISEASE: Atrial fibrillation, familial, 16 (ATFB16) [MIM:613120]: 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:20558140, ECO:0000269|PubMed:21051419}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Antiarrhythmic Pathway, Pharmacodynamics;Sudden Infant Death Syndrome (SIDS) Susceptibility Pathways;Developmental Biology;Phase 0 - rapid depolarisation;Cardiac conduction;Muscle contraction;Interaction between L1 and Ankyrins;L1CAM interactions;Direct p53 effectors;Axon guidance (Consensus)

Recessive Scores

• pRec: 0.149

Intolerance Scores

• loftool: 0.182
• rvis_EVS: -0.27
• rvis_percentile_EVS: 33.97

Haploinsufficiency Scores

• pHI: 0.145
• hipred: Y
• hipred_score: 0.542
• ghis: 0.631

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.512

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Scn3b
• Phenotype: skeleton phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan)

Gene ontology

• Biological process: sodium ion transport;nervous system development;positive regulation of heart rate;positive regulation of sodium ion transport;sensory perception of pain;sodium ion transmembrane transport;membrane depolarization;cardiac muscle contraction;regulation of atrial cardiac muscle cell membrane depolarization;regulation of ventricular cardiac muscle cell membrane depolarization;protein localization to plasma membrane;cardiac muscle cell action potential involved in contraction;ventricular cardiac muscle cell action potential;membrane depolarization during action potential;membrane depolarization during cardiac muscle cell action potential;atrial cardiac muscle cell action potential;SA node cell action potential;regulation of heart rate by cardiac conduction;regulation of sodium ion transmembrane transporter activity
• Cellular component: voltage-gated sodium channel complex;plasma membrane;integral component of membrane;Z disc
• Molecular function: voltage-gated ion channel activity;voltage-gated sodium channel activity;sodium channel regulator activity;sodium channel inhibitor activity;ion channel binding;voltage-gated sodium channel activity involved in cardiac muscle cell action potential