ArticleInternational journal of cardiology2014
ABCC9 is a novel Brugada and early repolarization syndrome susceptibility gene.
Article in International journal of cardiology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 69 papers, 2 of them syntheses that pooled it.
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Who cites it
69 citing papers in PubMed, 2 syntheses or guidelines pooled it, 130 citations in OpenAlex.
- Variability in reported midpoints of (in)activation of cardiac INa.The Journal of general physiology · 2025Pooled it
- ABCC9 gene polymorphism is associated with hippocampal sclerosis of aging pathology.Acta neuropathologica · 2014Pooled it
- Ranolazine for Congenital Long-QT Syndrome Type III: Experimental and Long-Term Clinical Data.Circulation. Arrhythmia and electrophysiology · 2016Trial
- Genetic Basis of Brugada Syndrome.Biomedicines · 2025Review
- Bayliss-Starling Prize Lecture: KThe Journal of physiology · 2025Article
- Brugada syndrome.Nature reviews. Disease primers · 2025Review
- The Role of Human-Induced Pluripotent Stem Cells in Studying Cardiac Channelopathies.International journal of molecular sciences · 2024Review
- Review
- Identifying the Pathogenic Variants in Heart Genes in Vietnamese Sudden Unexplained Death Victims by Next-Generation Sequencing.Diagnostics (Basel, Switzerland) · 2024Article
- Primary Electrical Heart Disease-Principles of Pathophysiology and Genetics.International journal of molecular sciences · 2024Review
- Brugada syndrome update.Frontiers in physiology · 2024Review
- KArhiv za farmaciju · 2024Article
- Molecular Pathways and Animal Models of Arrhythmias.Advances in experimental medicine and biology · 2024Article
- Brugada Syndrome: More than a Monogenic Channelopathy.Biomedicines · 2023Review
- Review
- AnGenes · 2023Article
- Personalized Therapeutics for KAnnual review of pharmacology and toxicology · 2023Review
- Concealed Substrates in Brugada Syndrome: Isolated Channelopathy or Associated Cardiomyopathy?Genes · 2022Review
- Brugada Syndrome: Different Experimental Models and the Role of Human Cardiomyocytes From Induced Pluripotent Stem Cells.Journal of the American Heart Association · 2022Review
- The Genetics and Epigenetics of Ventricular Arrhythmias in Patients Without Structural Heart Disease.Frontiers in cardiovascular medicine · 2022Review
9 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
22 authors at 9 institutions in 4 countries.
Funding
Abstract
backgroundGenetic defects in KCNJ8, encoding the Kir6.1 subunit of the ATP-sensitive K(+) channel (I(K-ATP)), have previously been associated with early repolarization (ERS) and Brugada (BrS) syndromes. Here we test the hypothesis that genetic variants in ABCC9, encoding the ATP-binding cassette transporter of IK-ATP (SUR2A), are also associated with both BrS and ERS. METHODS AND
resultsDirect sequencing of all ERS/BrS susceptibility genes was performed on 150 probands and family members. Whole-cell and inside-out patch-clamp methods were used to characterize mutant channels expressed in TSA201-cells. Eight ABCC9 mutations were uncovered in 11 male BrS probands. Four probands, diagnosed with ERS, carried a highly-conserved mutation, V734I-ABCC9. Functional expression of the V734I variant yielded a Mg-ATP IC₅₀ that was 5-fold that of wild-type (WT). An 18-y/o male with global ERS inherited an SCN5A-E1784K mutation from his mother, who displayed long QT intervals, and S1402C-ABCC9 mutation from his father, who displayed an ER pattern. ABCC9-S1402C likewise caused a gain of function of IK-ATP with a shift of ATP IC₅₀ from 8.5 ± 2 mM to 13.4 ± 5 μM (p<0.05). The SCN5A mutation reduced peak INa to 39% of WT (p<0.01), shifted steady-state inactivation by -18.0 mV (p<0.01) and increased late I(Na) from 0.14% to 2.01% of peak I(Na) (p<0.01).
conclusionOur study is the first to identify ABCC9 as a susceptibility gene for ERS and BrS. Our findings also suggest that a gain-of-function in I(K-ATP) when coupled with a loss-of-function in SCN5A may underlie type 3 ERS, which is associated with a severe arrhythmic phenotype.
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