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GeneE
10 sources retrieved · Most recent: April 2026 · Index updated 15 days ago
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SCN4B
sodium voltage-gated channel beta subunit 4
Chromosome 11 · 11q23.3
NCBI Gene: 6330Ensembl: ENSG00000177098.9HGNC: HGNC:10592UniProt: B0YJ93
37PubMed Papers
22Diseases
0Drugs
2Pathogenic Variants
FUNCTIONAL ROLE
Transporter
CLINICAL
OMIM Disease Gene
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
voltage-gated sodium channel activityprotein bindingsodium channel regulator activitytransmembrane transporter bindingfamilial atrial fibrillationlong QT syndrome 10Romano-Ward syndromeneurodegenerative disease
✦AI Summary

SCN4B encodes the β4 subunit of voltage-gated sodium channels (Nav), serving as a regulatory component that modulates channel activity and localization in excitable membranes 1. The protein functions as an auxiliary subunit that participates in the functional modulation of Nav channels, contributing to membrane depolarization and electrical signal propagation 1. Beyond its classical role in excitable tissues, SCN4B has emerged as a metastasis-suppressor gene in cancer biology. In breast cancer, reduced SCN4B expression correlates with high-grade tumors and promotes cell migration through RhoA pathway activation, independent of its sodium channel function 2. Similarly, SCN4B is downregulated in lung adenocarcinoma, where higher expression associates with better prognosis and inhibits tumor progression by suppressing the cGMP-PKG signaling pathway 3. Regarding cardiac disease associations, SCN4B was initially reported to cause Long QT syndrome; however, recent evidence-based reappraisal classified it as having only limited or disputed evidence for LQTS causation 4. In neurological contexts, SCN4B knockout mice demonstrate increased sensitivity to sedative effects of ethanol and other drugs, though without affecting ethanol consumption behaviors 5. These findings highlight SCN4B's dual roles in both ion channel regulation and cancer suppression.

Sources cited
1
SCN4B serves as regulatory β4 subunit of voltage-gated sodium channels
PMID: 30190309
2
SCN4B acts as metastasis-suppressor gene in breast cancer through RhoA pathway modulation
PMID: 27917859
3
SCN4B is downregulated in lung adenocarcinoma and inhibits tumor progression via cGMP-PKG pathway
PMID: 38678552
4
SCN4B has limited evidence for causing Long QT syndrome based on evidence-based reappraisal
PMID: 31983240
5
SCN4B knockout increases sensitivity to sedative effects of ethanol and other drugs
PMID: 30817077
Disease Associationsⓘ22
familial atrial fibrillationOpen Targets
0.63Moderate
long QT syndrome 10Open Targets
0.49Moderate
Romano-Ward syndromeOpen Targets
0.42Moderate
neurodegenerative diseaseOpen Targets
0.30Weak
familial long QT syndromeOpen Targets
0.20Weak
Abnormality of the cardiovascular systemOpen Targets
0.19Weak
Prolonged QT intervalOpen Targets
0.18Weak
sudden infant death syndromeOpen Targets
0.12Weak
dilated cardiomyopathyOpen Targets
0.12Weak
catecholaminergic polymorphic ventricular tachycardia 1Open Targets
0.11Weak
cancerOpen Targets
0.08Suggestive
lung adenocarcinomaOpen Targets
0.08Suggestive
papillary thyroid carcinomaOpen Targets
0.08Suggestive
Autosomal recessive spastic paraplegia type 24Open Targets
0.08Suggestive
Young adult-onset ParkinsonismOpen Targets
0.07Suggestive
essential tremorOpen Targets
0.07Suggestive
Hereditary late-onset Parkinson diseaseOpen Targets
0.07Suggestive
Spinocerebellar ataxia type 40Open Targets
0.07Suggestive
spinocerebellar ataxia type 15/16Open Targets
0.07Suggestive
Benign familial choreaOpen Targets
0.07Suggestive
Atrial fibrillation, familial, 17UniProt
Long QT syndrome 10UniProt
Pathogenic Variants2
NM_174934.4(SCN4B):c.485T>G (p.Val162Gly)Pathogenic
Atrial fibrillation, familial, 17
☆☆☆☆2013→ Residue 162
NM_174934.4(SCN4B):c.496A>C (p.Ile166Leu)Pathogenic
Atrial fibrillation, familial, 17
☆☆☆☆2013→ Residue 166
View on ClinVar ↗
Related Genes
PRKACAProtein interaction97%PRKACBProtein interaction96%PRKACGProtein interaction96%SCN8AProtein interaction94%SCN1AProtein interaction88%CAV3Protein interaction88%
Tissue Expression6 tissues
Heart
100%
Brain
37%
Lung
13%
Bone Marrow
7%
Liver
3%
Ovary
1%
Gene Interaction Network
Click a node to explore
SCN4BPRKACAPRKACBPRKACGSCN8ASCN1ACAV3
PROTEIN STRUCTURE
Preparing viewer…
PDB6VSV · 1.62 Å · X-ray
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
1.32LoF Tolerant
pLIⓘ
0.00Tolerant
Observed/Expected LoF0.87 [0.59–1.32]
RankingsWhere SCN4B stands among ~20K protein-coding genes
  • #10,688of 20,598
    Most Researched37
  • #4,479of 5,498
    Most Pathogenic Variants2
  • #13,900of 17,882
    Most Constrained (LOEUF)1.32
Genes detectedSCN4B
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
An International, Multicentered, Evidence-Based Reappraisal of Genes Reported to Cause Congenital Long QT Syndrome.
PMID: 31983240
Circulation · 2020
1.00
2
Structure of the human voltage-gated sodium channel Na
PMID: 30190309
Science · 2018
0.90
3
Results of genetic testing in 855 consecutive unrelated patients referred for long QT syndrome in a clinical laboratory.
PMID: 23631430
Genet Test Mol Biomarkers · 2013
0.80
4
SCN4B inhibits the progression of lung adenocarcinoma and is associated with better prognosis.
PMID: 37826914
Clin Respir J · 2023
0.70
5
Scn4b regulates the hypnotic effects of ethanol and other sedative drugs.
PMID: 30817077
Genes Brain Behav · 2019
0.60