ArticleThe Journal of clinical investigation2014
A common genetic variant within SCN10A modulates cardiac SCN5A expression.
Article in The Journal of clinical investigation, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 113 papers, 1 of them a synthesis that pooled it.
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Who cites it
113 citing papers in PubMed, 1 synthesis or guideline pooled it, 188 citations in OpenAlex.
- Genome-wide association analyses identify new Brugada syndrome risk loci and highlight a new mechanism of sodium channel regulation in disease susceptibility.Nature genetics · 2022Pooled it
- Long-term predictors of outcome in Brugada syndrome patients after implantable cardioverter-defibrillator implant.Europace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology · 2026Article
- Whole-genome sequencing implicates rare, low-frequency and structural non-coding variation at themedRxiv : the preprint server for health sciences · 2026Article
- Gene-gene interactions between a LMNA variant and common polymorphisms drive early-onset atrial fibrillation.Nature communications · 2026Article
- The cardiac conduction system: development, function and therapeutic targets.Nature reviews. Cardiology · 2026Review
- Genotype-Phenotype Discordance in Cardiomyopathies: Pathophysiology, Clinical Expression, and Therapeutic Considerations.Health science reports · 2026Article
- Enhancer-mediated Etv4 activation stimulates osteogenic differentiation.Nature communications · 2026Article
- The prevalence of Brugada syndrome in patients presenting to an emergency room in Riyadh, Saudi Arabia.Frontiers in cardiovascular medicine · 2026Article
- Genetic loci responsible for atrioventricular block in children.Frontiers in cell and developmental biology · 2026Review
- SCN10A-short gene therapy to restore conduction and protect against malignant cardiac arrhythmias.European heart journal · 2025Article
- Genomic analysis reveals population structure and selection signatures in plateau dairy cattle.BMC genomics · 2025Article
- The impact of common and rare genetic variants on bradyarrhythmia development.Nature genetics · 2025Article
- Characterization of novel arrhythmogenic patterns arising secondary to heterogeneous expression and activation of Nav1.8.Frontiers in cardiovascular medicine · 2025Article
- Integrated Genomic Approaches to Elucidate the Genetic Basis of Brugada Syndrome in Taiwanese Patients.Bioinformatics and biology insights · 2025Article
- Genetics and Pharmacogenetics of Atrial Fibrillation: A Mechanistic Perspective.JACC. Basic to translational science · 2024Review
- A Genomic Link From Heart Failure to Atrial Fibrillation Risk: FOG2 Modulates a TBX5/GATA4-Dependent Atrial Gene Regulatory Network.Circulation · 2024Article
- Stem cell models of inherited arrhythmias.Nature cardiovascular research · 2024Review
- Review
- Review
- Brugada Syndrome: More than a Monogenic Channelopathy.Biomedicines · 2023Review
53 more citing papers are in PubMed but not listed here.
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21 authors at 6 institutions in 2 countries.
Funding
Abstract
Variants in SCN10A, which encodes a voltage-gated sodium channel, are associated with alterations of cardiac conduction parameters and the cardiac rhythm disorder Brugada syndrome; however, it is unclear how SCN10A variants promote dysfunctional cardiac conduction. Here we showed by high-resolution 4C-seq analysis of the Scn10a-Scn5a locus in murine heart tissue that a cardiac enhancer located in Scn10a, encompassing SCN10A functional variant rs6801957, interacts with the promoter of Scn5a, a sodium channel-encoding gene that is critical for cardiac conduction. We observed that SCN5A transcript levels were several orders of magnitude higher than SCN10A transcript levels in both adult human and mouse heart tissue. Analysis of BAC transgenic mouse strains harboring an engineered deletion of the enhancer within Scn10a revealed that the enhancer was essential for Scn5a expression in cardiac tissue. Furthermore, the common SCN10A variant rs6801957 modulated Scn5a expression in the heart. In humans, the SCN10A variant rs6801957, which correlated with slowed conduction, was associated with reduced SCN5A expression. These observations establish a genomic mechanism for how a common genetic variation at SCN10A influences cardiac physiology and predisposes to arrhythmia.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.