SCN4B

sodium voltage-gated channel beta subunit 4, the group of Sodium voltage-gated channel beta subunits|V-set domain containing

Basic information

Region (hg38): 11:118133376-118152888

Links

ENSG00000177098 ∙ NCBI:6330 ∙ OMIM:608256 ∙ HGNC:10592 ∙ Uniprot:Q8IWT1 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• long QT syndrome 10 (Limited), mode of inheritance: Unknown
• familial atrial fibrillation (Supportive), mode of inheritance: AD
• long QT syndrome 10 (Limited), mode of inheritance: Unknown
• long QT syndrome 10 (Limited), mode of inheritance: AD
• long QT syndrome (Disputed Evidence), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Long QT syndrome 10; Atrial fibrilliation, familial 17	AD	Cardiovascular	In Atrial fibrillation and Long QT syndrome, surveillance and medical and/or surgical management related to arrhythmias may be helpful to help decrease morbidity	Cardiovascular	17592081; 20301308; 23604097

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the SCN4B gene.

• Long QT syndrome 10 (119 variants)
• Cardiovascular phenotype (96 variants)
• Congenital long QT syndrome (73 variants)
• not provided (65 variants)
• not specified (28 variants)
• Long QT syndrome (11 variants)
• Primary dilated cardiomyopathy (1 variants)
• SUDDEN INFANT DEATH SYNDROME (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the SCN4B 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			1	46	1	48
missense			81	3		84
nonsense			2			2
start loss			1			1
frameshift			4		1	5
inframe indel			2			2
splice donor/acceptor (+/-2bp)			6			6
splice region			2	5		7
non coding			38	43	27	108
Total	0	0	135	92	29

Variants in SCN4B

This is a list of pathogenic ClinVar variants found in the SCN4B region.

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

Position	Type	Phenotype	Significance	ClinVar
11-118133394-TA-T		Congenital long QT syndrome • Long QT syndrome	Uncertain significance (Jun 14, 2016)
11-118133415-AAATAC-A		Congenital long QT syndrome • Long QT syndrome	Likely benign (Jun 14, 2016)
11-118133478-C-T		Congenital long QT syndrome	Uncertain significance (Jun 14, 2016)
11-118133748-C-T		Congenital long QT syndrome	Likely benign (Jun 14, 2016)
11-118133973-A-G		Congenital long QT syndrome	Likely benign (Jun 14, 2016)
11-118134023-C-T		Congenital long QT syndrome	Uncertain significance (Jun 14, 2016)
11-118134050-T-C		Congenital long QT syndrome • Long QT syndrome 10	Uncertain significance (Sep 14, 2021)
11-118134075-C-T		Congenital long QT syndrome	Likely benign (Jun 14, 2016)
11-118134088-C-G		Congenital long QT syndrome	Conflicting classifications of pathogenicity (Aug 01, 2022)
11-118134109-T-C		Congenital long QT syndrome	Likely benign (Jun 14, 2016)
11-118134148-A-G		Congenital long QT syndrome	Likely benign (Jun 14, 2016)
11-118134151-A-G		Congenital long QT syndrome	Uncertain significance (Jun 14, 2016)
11-118134242-G-A		Congenital long QT syndrome	Likely benign (Jun 14, 2016)
11-118134404-T-C		Congenital long QT syndrome	Likely benign (Jun 14, 2016)
11-118134436-C-A		Congenital long QT syndrome	Uncertain significance (Jun 14, 2016)
11-118134530-C-T		Congenital long QT syndrome	Uncertain significance (Jun 14, 2016)
11-118134531-G-A		Congenital long QT syndrome	Likely benign (Jun 14, 2016)
11-118134540-C-G		Congenital long QT syndrome	Uncertain significance (Jun 14, 2016)
11-118134703-T-A		Congenital long QT syndrome	Uncertain significance (Jun 14, 2016)
11-118134759-G-A		Congenital long QT syndrome	Uncertain significance (Jun 14, 2016)
11-118134807-C-A		Congenital long QT syndrome	Uncertain significance (Jun 14, 2016)
11-118134831-C-T		Congenital long QT syndrome • Long QT syndrome 10	Uncertain significance (Sep 28, 2021)
11-118134890-G-C		Congenital long QT syndrome	Uncertain significance (Jun 14, 2016)
11-118134907-T-G		Congenital long QT syndrome	Likely benign (Jun 14, 2016)
11-118134947-C-A		Congenital long QT syndrome	Uncertain significance (Jun 14, 2016)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
SCN4B	protein_coding	protein_coding	ENST00000324727	5	19512

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
6.45e-7	0.152	125720	0	28	125748	0.000111

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.182	136	130	1.04	0.00000786	1487
Missense in Polyphen		46	46.201	0.99565		534
Synonymous	-0.116	62	60.9	1.02	0.00000418	468
Loss of Function	-0.270	9	8.17	1.10	4.50e-7	101

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000145	0.000145
Ashkenazi Jewish	0.000496	0.000496
East Asian	0.000109	0.000109
Finnish	0.00	0.00
European (Non-Finnish)	0.0000880	0.0000879
Middle Eastern	0.000109	0.000109
South Asian	0.000196	0.000196
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Modulates channel gating kinetics. Causes negative shifts in the voltage dependence of activation of certain alpha sodium channels, but does not affect the voltage dependence of inactivation. Modulates the susceptibility of the sodium channel to inhibition by toxic peptides from spider, scorpion, wasp and sea anemone venom. {ECO:0000269|PubMed:24297919}.
• Disease: DISEASE: Long QT syndrome 10 (LQT10) [MIM:611819]: A heart disorder characterized by a prolonged QT interval on the ECG and polymorphic ventricular arrhythmias. They cause syncope and sudden death in response to exercise or emotional stress, and can present with a sentinel event of sudden cardiac death in infancy. {ECO:0000269|PubMed:17592081}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Atrial fibrillation, familial, 17 (ATFB17) [MIM:611819]: 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:23604097}. 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;Sudden Infant Death Syndrome (SIDS) Susceptibility Pathways;Developmental Biology;Phase 0 - rapid depolarisation;Cardiac conduction;Muscle contraction;Interaction between L1 and Ankyrins;L1CAM interactions;Axon guidance (Consensus)

Recessive Scores

• pRec: 0.127

Intolerance Scores

• loftool: 0.363
• rvis_EVS: -0.38
• rvis_percentile_EVS: 27.42

Haploinsufficiency Scores

• pHI: 0.222
• hipred: N
• hipred_score: 0.275
• ghis: 0.580

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.436

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Scn4b
• Phenotype: behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); 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)

Gene ontology

• Biological process: sodium ion transport;positive regulation of sodium ion transport;sodium ion transmembrane transport;cardiac muscle contraction;regulation of ventricular cardiac muscle cell membrane repolarization;cardiac muscle cell action potential involved in contraction;membrane depolarization during cardiac muscle cell action potential;AV 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;intercalated disc;intrinsic component of plasma membrane
• Molecular function: voltage-gated ion channel activity;voltage-gated sodium channel activity;sodium channel regulator activity;ion channel binding;voltage-gated sodium channel activity involved in cardiac muscle cell action potential