SCN2B

Chr 11AD

sodium voltage-gated channel beta subunit 2

Also known as: ATFB14

The protein encodes the beta 2 subunit of type II voltage-gated sodium channels and functions in cell-cell adhesion and cell migration. Mutations cause autosomal dominant familial atrial fibrillation and have been associated with Brugada syndrome and sudden infant death syndrome. The pathogenic mechanism involves gain-of-function effects on sodium channel activity.

GeneReviewsOMIMResearchSummary from RefSeq, OMIM, UniProt, Mechanism
MultiplemechanismADLOEUF 1.401 OMIM phenotype
Clinical SummarySCN2B
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Gene-Disease Validity (ClinGen)
Brugada syndrome 1 · ADDisputed

Disputed — evidence questions this relationship

Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
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ClinVar Variants
28 unique Pathogenic / Likely Pathogenic· 129 VUS of 285 total submissions
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GeneReview available — SCN2B
Authoritative clinical overview · Recommended first read
Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.40LOEUF
pLI 0.002
Z-score 0.83
OE 0.67 (0.351.40)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
0.32Z-score
OE missense 0.92 (0.791.07)
120 obs / 130.2 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.67 (0.351.40)
00.351.4
Missense OE0.92 (0.791.07)
00.61.4
Synonymous OE1.13
01.21.6
LoF obs/exp: 5 / 7.4Missense obs/exp: 120 / 130.2Syn Z: -0.76
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
limitedSCN2B-related Brugada syndromeOTHERAD
DN
0.6743th %ile
GOF
0.73top 25%
LOF
0.2969th %ile

This gene has evidence for multiple mechanisms of pathogenicity (gain-of-function and dominant-negative). Both the Badonyi & Marsh prediction and the broader genomic evidence point to gain-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

GOFprediction above median
DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

285 submitted variants in ClinVar

Classification Summary

Pathogenic26
Likely Pathogenic2
VUS129
Likely Benign97
Benign13
Conflicting13
26
Pathogenic
2
Likely Pathogenic
129
VUS
97
Likely Benign
13
Benign
13
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
26
0
26
Likely Pathogenic
0
0
2
0
2
VUS
5
112
11
1
129
Likely Benign
0
9
22
66
97
Benign
0
0
13
0
13
Conflicting
13
Total51217467280

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

SCN2B · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 results · since 2015Search PubMed ↗