GeneBe

SCN2B

protein-coding

sodium voltage-gated channel beta subunit 2, the group of Sodium voltage-gated channel beta subunits|V-set domain containing

Gene summary

The protein encoded by this gene is the beta 2 subunit of the type II voltage-gated sodium channel. The encoded protein is involved in cell-cell adhesion and cell migration. Defects in this gene can be a cause of Brugada Syndrome, atrial fibrillation, or sudden infant death syndrome. [provided by RefSeq, Jul 2015]

MANE transcript

NM_004588.5

Inheritance

AD

ClinVar variants

U:120B:91

Top phenotype

Atrial fibrillation, familial 14

gnomAD constraint

pLI —, LoF o/e 0.67

Max pathogenic AF

—

Genomic locus

chr11:118,162,806-118,176,639

External References & Databases

Ensembl (ENSG00000149575)NCBI Gene (6327)OMIM (601327)HGNC:10589GenCCUniProt (O60939)AlphaFoldClinVar (SCN2B)gnomADPubMedJAXSFARI

Transcript & Mutation Effects

hg38 • Region Span ~13.8 kb
Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

familial atrial fibrillationSUPPORTIVE

Inheritance Pattern: AD

Disease ID:MONDO:0018054

Submitter: Orphanet

atrial fibrillation, familial, 14LIMITED

Inheritance Pattern: AD

Disease ID:MONDO:0014156

Submitter: Labcorp Genetics (formerly Invitae)

Brugada syndrome 1NO_KNOWN

Inheritance Pattern: AD

Disease ID:MONDO:0011001

Submitter: ClinGen

atrial fibrillation, familial, 14LIMITED

Inheritance Pattern: Unknown

Disease ID:MONDO:0014156

Submitter: Labcorp Genetics (formerly Invitae)

Brugada syndromeSUPPORTIVE

Inheritance Pattern: AD

Disease ID:MONDO:0015263

Submitter: Orphanet

Brugada syndromeNO_KNOWN

Inheritance Pattern: AD

Disease ID:MONDO:0015263

Submitter: G2P

atrial fibrillation, familial, 14MODERATE

Inheritance Pattern: AD

Disease ID:MONDO:0014156

Submitter: Ambry Genetics

Brugada syndromeLIMITED

Inheritance Pattern: AD

Disease ID:MONDO:0015263

Submitter: Genomics England PanelApp

Clinical Genomic Database (CGD)

Atrial fibrillation, familial 14AD

Manifestation: Cardiovascular

Intervention: Cardiovascular

Rationale: In Atrial fibrillation, surveillance (eg, with echocardiogram and electrocardiogram) may allow early management, which may be beneficial

Refs: 19808477Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to SCN2B variants in ClinVar

7 Conditions Cataloged
Atrial fibrillation, familial, 14Total: 157
Cardiovascular phenotypeTotal: 147
not providedTotal: 24
not specifiedTotal: 12
SCN2B-related disorderTotal: 7
Primary dilated cardiomyopathyTotal: 1
Variant of unknown significanceTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_004588.5. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

EffectPLPVUSLBBSum
synonymous
1
clinvar
68
clinvar
 69
missense
114
clinvar
23
clinvar
 137
nonsense
0
start loss
0
frameshift
3
clinvar
 3
splice donor/acceptor (+/-2bp)
2
clinvar
 2
Total00120910211
Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 4 transcripts
Transcript IDSourceProtein IDCoding ExonsMANE Status
NM_004588.5RefSeqNP_004579.14MANE Select
ENST00000278947.6EnsemblENSP00000278947.54MANE Select
ENST00000658882.1EnsemblENSP00000499572.13Standard
ENST00001028710.1EnsemblENSP00000698527.14Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

  • Antiarrhythmic Pathway, Pharmacodynamics
  • Developmental Biology
  • Phase 0 - rapid depolarisation
  • Cardiac conduction
  • Muscle contraction

Biological Process

  • chemical synaptic transmission
  • nervous system development
  • sodium ion transmembrane transport
  • response to pyrethroid
  • cardiac muscle contraction

Molecular Function

  • voltage-gated ion channel activity
  • sodium channel regulator activity
  • voltage-gated sodium channel activity involved in cardiac muscle cell action potential

Cellular Component

  • voltage-gated sodium channel complex

gnomAD Constraint

Source: gnomAD

Gene type
protein_coding
Transcript type
protein_coding
Transcript
ENST00000278947
Coding exons
4
Length
14723
Individuals with no LoFs
125730
Homozygous LoFs
1
Heterozygous LoFs
17
Defined
125748
p
0.0000716
Z-ScoreObservedExpectedObserved/ExpectedMutation RateTotal Possible
Missense0.3171201300.9220.000008751419
Missense (PolyPhen)4051.5370.77615545
Synonymous-0.7656355.71.130.00000400425
Loss of Function0.82757.430.6733.25e-793

Population LoF Frequency

PopulationCAFp-valueStatus
African00.0absent
Latino/Admixed American0.0000870.000087rare
Ashkenazi Jewish00.0absent
East Asian0.000600.00060rare
Finnish0.0000460.000046rare
European (Non-Finnish)0.0000350.000026rare
South Asian00.0absent
Other00.0absent

dbNSFP Gene Annotations

Source: dbNSFP

Function
FUNCTION: Crucial in the assembly, expression, and functional modulation of the heterotrimeric complex of the sodium channel. The subunit beta-2 causes an increase in the plasma membrane surface area and in its folding into microvilli. Interacts with TNR may play a crucial role in clustering and regulation of activity of sodium channels at nodes of Ranvier (By similarity). {ECO:0000250}.;
Disease
DISEASE: Note=Genetic variations in SCN2B may be involved in Brugada syndrome (PubMed:23559163). This tachyarrhythmia is 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:23559163}.;

Recessive Scores

pRec
0.133

Intolerance Scores

LoFtool
0.268
RVIS EVS
-0.45
RVIS percentile EVS
24

Essentials

Essential (CRISPR)
N
Essential (CRISPR2)
N
Essential (gene trap)
N
Indispensability pred.
N
Indispensability score
0.248

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium
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