SCN4B

Chr 11AD

sodium voltage-gated channel beta subunit 4

Also known as: ATFB17, LQT10, Navbeta4

NCBI Gene: 6330 ENSG00000177098 UniProt: Q8IWT1 OMIM: 608256

The protein encoded by this gene is one of several sodium channel beta subunits. These subunits interact with voltage-gated alpha subunits to change sodium channel kinetics. The encoded transmembrane protein forms interchain disulfide bonds with SCN2A. Defects in this gene are a cause of long QT syndrome type 10 (LQT10). Three protein-coding and one non-coding transcript variant have been found for this gene.[provided by RefSeq, Mar 2009]

OMIM Research

OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Atrial fibrillation, familial, 17MIM #611819

Long QT syndrome 10MIM #611819

Clinical highlights

Gene–disease validity (ClinGen)

Disputed · long QT syndrome · AD · ClinGen 2018

evidence questions this relationship

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.78

LOEUF

Multiple*

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.78LOEUF

pLI 0.000

Z-score -0.27

OE 1.10 (0.66–1.78)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-0.18Z-score

OE missense 1.04 (0.91–1.21)

136 obs / 130.2 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?1.10 (0.66–1.78)

0≤0.351.4

Missense OE?1.04 (0.91–1.21)

0≤0.61.4

Synonymous OE?1.02

0≤1.21.6

LoF obs/exp: 9 / 8.2Missense obs/exp: 136 / 130.2Syn Z: -0.12

Background carrier burden — how many people carry a rare variant somewhere in SCN4B?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 210

287 rare PASS variants

Rare truncating (LoF)

1 in 5,500

36 rare PASS variants

Rare synonymous (reference)

1 in 760

137 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for SCN4B. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 260	1 in 6,900
South Asian	~43k	1 in 230	1 in 2,900
Remaining (unassigned)	~30k	1 in 210	≈ 1 in 7,500
European (Finnish)	~27k	1 in 2,400	1 in 2,900
Admixed American	~22k	1 in 230	1 in 2,000
African / African American	~21k	1 in 160	≈ 1 in 8,400
East Asian	~20k	1 in 200	≈ 1 in 5,000
Ashkenazi Jewish	~13k	1 in 470	1 in 2,200
Middle Eastern	~2,884	1 in 260	≈ 1 in 1,400

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): All 5 coding exons well covered in gnomAD exomes and genomes.? see exons ↓