SCN1B

Chr 19ADAR

sodium voltage-gated channel beta subunit 1

Also known as: ATFB13, BRGDA5, DEE52, EIEE52, GEFSP1

NCBI Gene: 6324 ENSG00000105711 UniProt: Q07699 OMIM: 600235

The protein encodes the beta-1 subunit of voltage-gated sodium channels, which modulates the kinetics of channel inactivation during action potential generation and propagation in muscle and neuronal cells. Mutations cause generalized epilepsy with febrile seizures plus, developmental and epileptic encephalopathy, Brugada syndrome, and cardiac conduction defects through both autosomal dominant and autosomal recessive inheritance patterns. The pathogenic mechanism involves gain-of-function effects on sodium channel activity.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt, Mechanism

Voltage-gated sodium channels are heteromeric proteins that function in the generation and propagation of action potentials in muscle and neuronal cells. They are composed of one alpha and two beta subunits, where the alpha subunit provides channel activity and the beta-1 subunit modulates the kinetics of channel inactivation. This gene encodes a sodium channel beta-1 subunit. Mutations in this gene result in generalized epilepsy with febrile seizures plus, Brugada syndrome 5, and defects in cardiac conduction. Multiple transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Oct 2009]

GeneReviews OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Atrial fibrillation, familial, 13MIM #615377

Brugada syndrome 5MIM #612838

Cardiac conduction defect, nonspecificMIM #612838

Developmental and epileptic encephalopathy 52MIM #617350

Generalized epilepsy with febrile seizures plus, type 1MIM #604233

Clinical highlights

Gene–disease validity (ClinGen · GenCC)

Definitive · generalized epilepsy with febrile seizures plus · AD · ClinGen 2022
Definitive · genetic developmental and epileptic encephalopathy · AR · ClinGen 2022
Definitive · generalized epilepsy with febrile seizures plus, type 1 · AD · G2P
Definitive · developmental and epileptic encephalopathy, 52 · AR · G2P
Limited · atrial fibrillation, familial, 13 · Unknown · Labcorp Genetics (formerly Invitae) — not for standalone diagnostic reporting
Disputed · Brugada syndrome 1 · AD · ClinGen 2017 — evidence questions this relationship
Disputed · Brugada syndrome · AD · G2P — evidence questions this relationship

+3 more curated pairs

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.26

LOEUF

Multiple*

Mechanism· predicted

📖

GeneReview available — SCN1B

Authoritative clinical overview · Recommended first read

Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.26LOEUF

pLI 0.102

Z-score 1.22

OE 0.41 (0.17–1.26)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

1.22Z-score

OE missense 0.73 (0.63–0.85)

118 obs / 161.8 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.41 (0.17–1.26)

0≤0.351.4

Missense OE?0.73 (0.63–0.85)

0≤0.61.4

Synonymous OE?1.01

0≤1.21.6

LoF obs/exp: 2 / 4.9Missense obs/exp: 118 / 161.8Syn Z: -0.06

Background carrier burden — how many people carry a rare variant somewhere in SCN1B?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 120

415 rare PASS variants

Rare truncating (LoF)

1 in 1,700

65 rare PASS variants

Rare synonymous (reference)

1 in 150

191 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for SCN1B. 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 170	1 in 2,000
South Asian	~43k	1 in 87	1 in 8,400
Remaining (unassigned)	~30k	1 in 110	1 in 2,700
European (Finnish)	~27k	1 in 260	≈ 1 in 8,800
Admixed American	~22k	1 in 78	1 in 1,100
African / African American	~21k	1 in 74	1 in 1,200
East Asian	~20k	1 in 120	≈ 1 in 20,000
Ashkenazi Jewish	~13k	1 in 270	≈ 1 in 13,000
Middle Eastern	~2,884	1 in 93	none seen

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): 4 of 5 coding exons well covered in gnomAD exomes; exon 1 poorly covered. Genomes: all 5.? see exons ↓