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GeneBe

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

ENSG00000177098NCBI:6330OMIM:608256HGNC:10592Uniprot:Q8IWT1AlphaFoldGenCCjaxSfariGnomADPubmedClinVar

Phenotypes

GenCC

Source: genCC

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

Clinical Genomic Database

Source: CGD

ConditionInheritanceIntervention CategoriesIntervention/Rationale Manifestation CategoriesReferences
Long QT syndrome 10; Atrial fibrilliation, familial 17ADCardiovascularIn Atrial fibrillation and Long QT syndrome, surveillance and medical and/or surgical management related to arrhythmias may be helpful to help decrease morbidityCardiovascular17592081; 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
clinvar
46
clinvar
1
clinvar
48
missense
81
clinvar
3
clinvar
84
nonsense
2
clinvar
2
start loss
1
clinvar
1
frameshift
4
clinvar
1
clinvar
5
inframe indel
2
clinvar
2
splice donor/acceptor (+/-2bp)
6
clinvar
6
splice region
2
5
7
non coding
38
clinvar
43
clinvar
27
clinvar
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)302581
11-118133415-AAATAC-A Congenital long QT syndrome • Long QT syndrome Likely benign (Jun 14, 2016)302582
11-118133478-C-T Congenital long QT syndrome Uncertain significance (Jun 14, 2016)302583
11-118133748-C-T Congenital long QT syndrome Likely benign (Jun 14, 2016)302584
11-118133973-A-G Congenital long QT syndrome Likely benign (Jun 14, 2016)302585
11-118134023-C-T Congenital long QT syndrome Uncertain significance (Jun 14, 2016)302586
11-118134050-T-C Congenital long QT syndrome • Long QT syndrome 10 Uncertain significance (Sep 14, 2021)302587
11-118134075-C-T Congenital long QT syndrome Likely benign (Jun 14, 2016)302588
11-118134088-C-G Congenital long QT syndrome Conflicting classifications of pathogenicity (Aug 01, 2022)302589
11-118134109-T-C Congenital long QT syndrome Likely benign (Jun 14, 2016)302590
11-118134148-A-G Congenital long QT syndrome Likely benign (Jun 14, 2016)302591
11-118134151-A-G Congenital long QT syndrome Uncertain significance (Jun 14, 2016)302592
11-118134242-G-A Congenital long QT syndrome Likely benign (Jun 14, 2016)302593
11-118134404-T-C Congenital long QT syndrome Likely benign (Jun 14, 2016)302594
11-118134436-C-A Congenital long QT syndrome Uncertain significance (Jun 14, 2016)302595
11-118134530-C-T Congenital long QT syndrome Uncertain significance (Jun 14, 2016)302596
11-118134531-G-A Congenital long QT syndrome Likely benign (Jun 14, 2016)302597
11-118134540-C-G Congenital long QT syndrome Uncertain significance (Jun 14, 2016)302598
11-118134703-T-A Congenital long QT syndrome Uncertain significance (Jun 14, 2016)302599
11-118134759-G-A Congenital long QT syndrome Uncertain significance (Jun 14, 2016)302600
11-118134807-C-A Congenital long QT syndrome Uncertain significance (Jun 14, 2016)302601
11-118134831-C-T Congenital long QT syndrome • Long QT syndrome 10 Uncertain significance (Sep 28, 2021)302602
11-118134890-G-C Congenital long QT syndrome Uncertain significance (Jun 14, 2016)302603
11-118134907-T-G Congenital long QT syndrome Likely benign (Jun 14, 2016)302604
11-118134947-C-A Congenital long QT syndrome Uncertain significance (Jun 14, 2016)302605

GnomAD

Source: gnomAD

GeneTypeBio TypeTranscript Coding Exons Length
SCN4Bprotein_codingprotein_codingENST00000324727 519512
pLI Probability
LOF Intolerant
pRec Probability
LOF Recessive
Individuals with
no LOFs
Individuals with
Homozygous LOFs
Individuals with
Heterozygous LOFs
Defined p
6.45e-70.1521257200281257480.000111
Z-Score Observed Expected Observed/Expected Mutation Rate Total Possible in Transcript
Missense-0.1821361301.040.000007861487
Missense in Polyphen4646.2010.99565534
Synonymous-0.1166260.91.020.00000418468
Loss of Function-0.27098.171.104.50e-7101

LoF frequencies by population

EthnicitySum of pLOFs p
African & African-American0.0001450.000145
Ashkenazi Jewish0.0004960.000496
East Asian0.0001090.000109
Finnish0.000.00
European (Non-Finnish)0.00008800.0000879
Middle Eastern0.0001090.000109
South Asian0.0001960.000196
Other0.000.00

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

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium

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