SCN2B

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

Basic information

Region (hg38): 11:118162806-118176639

Links

ENSG00000149575

∙ NCBI:6327 ∙ OMIM:601327 ∙ HGNC:10589 ∙ Uniprot:O60939 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

Brugada syndrome (Limited), mode of inheritance: AD
Brugada syndrome (Supportive), mode of inheritance: AD
familial atrial fibrillation (Supportive), mode of inheritance: AD
atrial fibrillation, familial, 14 (Moderate), mode of inheritance: AD
atrial fibrillation, familial, 14 (Limited), mode of inheritance: Unknown
atrial fibrillation, familial, 14 (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
Atrial fibrillation, familial 14	AD	Cardiovascular	In Atrial fibrillation, surveillance (eg, with echocardiogram and electrocardiogram) may allow early management, which may be beneficial	Cardiovascular	19808477

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the SCN2B gene.

Atrial_fibrillation,_familial,_14 (142 variants)
Cardiovascular_phenotype (137 variants)
not_provided (23 variants)
not_specified (10 variants)
SCN2B-related_disorder (3 variants)
Primary_dilated_cardiomyopathy (1 variants)
Variant_of_unknown_significance (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the SCN2B gene is commonly pathogenic or not. These statistics are base on transcript: NM_000004588.5. Only rare variants are included in the table.

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.

Effect	PathogenicP	Likely pathogenicLP	VUSVUS	Likely benignLB	BenignB	Sum
synonymous			1 clinvar	62 clinvar		63
missense			107 clinvar	20 clinvar		127
nonsense						0
start loss						0
frameshift			3 clinvar			3
splice donor/acceptor (+/-2bp)			2 clinvar			2
Total	0	0	113	82	0

Loading clinvar variants...

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
SCN2B	protein_coding	protein_coding	ENST00000278947	4	14723

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00171	0.723	125730	1	17	125748	0.0000716

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.317	120	130	0.922	0.00000875	1419
Missense in Polyphen		40	51.537	0.77615		545
Synonymous	-0.765	63	55.7	1.13	0.00000400	425
Loss of Function	0.827	5	7.43	0.673	3.25e-7	93

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000870	0.0000870
Ashkenazi Jewish	0.00	0.00
East Asian	0.000598	0.000598
Finnish	0.0000462	0.0000462
European (Non-Finnish)	0.0000353	0.0000264
Middle Eastern	0.000598	0.000598
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

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}.;
Pathway: Antiarrhythmic Pathway, Pharmacodynamics;Developmental Biology;Phase 0 - rapid depolarisation;Cardiac conduction;Muscle contraction;Interaction between L1 and Ankyrins;L1CAM interactions;Axon guidance (Consensus)

Recessive Scores

pRec: 0.133

Intolerance Scores

loftool: 0.268
rvis_EVS: -0.45
rvis_percentile_EVS: 24

Haploinsufficiency Scores

pHI: 0.214
hipred: N
hipred_score: 0.345
ghis: 0.707

Essentials

essential_gene_CRISPR: N
essential_gene_CRISPR2: N
essential_gene_gene_trap: N
gene_indispensability_pred: N
gene_indispensability_score: 0.248

Gene Damage Prediction

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

Mouse Genome Informatics

Gene name: Scn2b
Phenotype: homeostasis/metabolism 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: chemical synaptic transmission;nervous system development;sodium ion transmembrane transport;response to pyrethroid;cardiac muscle contraction;regulation of atrial cardiac muscle cell membrane depolarization;cardiac muscle cell action potential involved in contraction;membrane depolarization during cardiac muscle cell action potential;regulation of heart rate by cardiac conduction;regulation of sodium ion transmembrane transporter activity
Cellular component: voltage-gated sodium channel complex
Molecular function: voltage-gated ion channel activity;sodium channel regulator activity;voltage-gated sodium channel activity involved in cardiac muscle cell action potential