Affinage

Showing SCN5A — NAV1.5 is a alias.

SCN5A

Sodium channel protein type 5 subunit alpha · UniProt Q14524

Length
2016 aa
Mass
226.9 kDa
Annotated
2026-06-10
100 papers in source corpus 38 papers cited in narrative 36 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

SCN5A encodes Nav1.5, the pore-forming α-subunit of the cardiac voltage-gated Na+ channel that initiates and propagates the action potential, with gain-of-function mutations producing persistent (late) Na+ current to cause LQT3 and loss-of-function mutations causing Brugada syndrome and conduction disease (PMID:10973849, PMID:19027780, PMID:29798782). The channel's biophysical phenotype is gated by discrete structural determinants: the domain I-II linker and domain IVS6 govern inactivation gating and recovery (PMID:12673799, PMID:12650885), a depolarizing shift in steady-state inactivation can predispose to atrial fibrillation independent of late current (PMID:18929244), and an in vivo transgenic LQT3 model confirms that persistent Na+ current is directly arrhythmogenic and reversible by late-current blockade (PMID:14736542). A recurring theme is that disease severity tracks with how much functional channel reaches the surface: trafficking-defective mutants are retained in the ER or fail to mature, with surface expression and dominant-negative interference determining penetrance (PMID:11786529, PMID:16301357, PMID:15890323, PMID:35305865). Nav1.5 abundance and surface density are set by a multi-layered regulatory network — transcriptional activators (TBX5, GATA4/5, MEF2C) and repressors (Foxo1, β-catenin/TCF4, Zfhx3), a cardiac super-enhancer cluster, mRNA stabilization by HuR, and post-translational control by ubiquitination (Nedd4-2, UBE1/UBA6), acetylation, glycosylation, and stabilizing partners (αB-crystallin, FAT10) (PMID:22728936, PMID:26961874, PMID:22400069, PMID:27894866, PMID:27068063, PMID:29454929, PMID:31666509, PMID:32315024, PMID:33414395, PMID:27638876). A feed-forward loop in which late INa activates CaMKII, which in turn phosphorylates Nav1.5 to enhance late current, couples channel activity to its own regulation (PMID:21677263). Nav1.5 occupies distinct cardiomyocyte microdomains — the SIV PDZ-binding motif targets it to the lateral membrane and controls proteasomal turnover there — and it functionally interacts with Kir2.1/2.2 to co-regulate IK1 (PMID:24895455, PMID:29184507, PMID:30232268). Beyond the heart, Nav1.5 has documented roles in breast cancer invasiveness, macrophage endosomal localization and innate immune signaling, and it is the target of pathogenic autoantibodies in Brugada syndrome (PMID:26452220, PMID:39078224, PMID:22951351, PMID:25368329).

Mechanistic history

Synthesis pass · year-by-year structured walk · 28 steps
  1. 2000 High

    Established the core disease paradigm that opposite biophysical defects in a single channel gene produce distinct arrhythmia syndromes, defining the field's mechanistic framework.

    Evidence Mutational analysis and patch-clamp in heterologous expression systems

    PMID:10973849 PMID:19027780 PMID:29798782

    Open questions at the time
    • Does not resolve which structural elements control late current vs. peak current loss
    • In vitro biophysics not yet linked to in vivo arrhythmia
  2. 2003 Medium

    Mapped specific channel domains to specific gating defects, showing the I-II linker and domain IVS6 control inactivation gating and recovery kinetics.

    Evidence Whole-cell patch-clamp in HEK293 and two-electrode voltage clamp in Xenopus oocytes for LQT3 mutants L619F and I1768V

    PMID:12650885 PMID:12673799

    Open questions at the time
    • Single-lab, single-method biophysics
    • No structural model of how these residues couple to the inactivation gate
  3. 2008 Medium

    Distinguished an AF-causing gain-of-function mechanism (depolarizing shift in inactivation) from the LQT3 late-current mechanism, broadening the genotype-phenotype map.

    Evidence Whole-cell patch-clamp of M1875T mutant in heterologous cells

    PMID:18929244

    Open questions at the time
    • Single in vitro study
    • Atrial-specific consequences not tested in vivo
  4. 2004 High

    Demonstrated in vivo that LQT3 persistent Na+ current is causally arrhythmogenic and pharmacologically reversible, validating the in vitro mechanism in a whole animal.

    Evidence Cardiac-specific N1325S transgenic mouse with ECG, action potential recording, voltage-clamp, and mexiletine rescue

    PMID:14736542

    Open questions at the time
    • Mouse repolarization differs from human
    • Does not address mutation-specific differences in surface expression
  5. 2005 High

    Showed that channel surface trafficking, not just gating, determines disease expressivity, with misfolded mutants rescuable pharmacologically and capable of dominant-negative effects.

    Evidence Patch-clamp, surface quantification, temperature manipulation, and pharmacological rescue (cisapride, mexiletine, curcumin) of trafficking-defective mutants in CHO/HEK293

    PMID:11786529 PMID:15890323 PMID:16301357

    Open questions at the time
    • Identity of the trafficking machinery and chaperones not defined
    • Fever-modulation mechanism at the molecular level not resolved
  6. 2008 Medium

    Identified telethonin as a Nav1.5-interacting partner that alters channel window current, extending Nav1.5 regulation to cytoskeletal/sarcomeric proteins.

    Evidence Reciprocal Co-IP, immunofluorescence co-localization, and patch-clamp in HEK293 and GI smooth muscle

    PMID:18408010

    Open questions at the time
    • Single lab
    • Binding interface on Nav1.5 not mapped
  7. 2010 High

    Revealed Nav1.5 mechanosensitivity, showing that mechanical force shifts voltage dependence by accelerating voltage-sensor movement, a property relevant to mechano-electric feedback.

    Evidence Cell-attached patch-clamp with controlled pressure in HEK293

    PMID:21041530

    Open questions at the time
    • Physiological relevance in intact myocardium not established
    • Structural basis of force-sensing unknown
  8. 2010 Medium

    Showed that a common polymorphism (H558R) modifies mutant channel phenotype in a mutation-specific manner, providing a mechanism for variable penetrance.

    Evidence Patch-clamp and surface biotinylation across 13 SSS mutants on H558 vs R558 backgrounds in HEK293

    PMID:20384651

    Open questions at the time
    • Mechanism of allele-specific rescue/aggravation not resolved structurally
    • Single lab heterologous data
  9. 2011 High

    Defined a feed-forward loop linking Nav1.5 late current to CaMKII activation and subsequent CaMKII phosphorylation of the channel, explaining self-amplifying late INa.

    Evidence siRNA knockdown, CaMKII autophosphorylation assays, Co-IP, patch-clamp, and N1325S mouse with pharmacology in cardiomyocytes

    PMID:21677263

    Open questions at the time
    • Phosphorylation sites mediating the loop not fully mapped here
    • In vivo contribution to arrhythmia quantification incomplete
  10. 2012 High

    Established transcriptional control of SCN5A by both activators and repressors, identifying TBX5 as an enhancer-driven activator in the conduction system and Foxo1 as a redox-responsive repressor.

    Evidence Conditional KO, in vivo enhancer reporter with T-box mutagenesis, optical mapping (TBX5); ChIP, nuclear-Foxo1 mutant, RNAi, voltage-clamp (Foxo1)

    PMID:22400069 PMID:22728936

    Open questions at the time
    • Combinatorial logic among transcription factors not resolved
    • Link between Foxo1 redox sensing and physiological INa modulation incomplete
  11. 2012 High

    Showed microdomain-specific regulation: the C-terminal SIV PDZ-binding motif targets Nav1.5 to the lateral membrane and controls its proteasomal degradation, distinct from intercalated-disk pools.

    Evidence ΔSIV knock-in mouse, optical mapping, patch-clamp, MG132 rescue, HEK293 internalization assay

    PMID:24895455

    Open questions at the time
    • Identity of all PDZ partners at the lateral membrane not fully defined
    • Disk-specific scaffolding mechanism not addressed here
  12. 2012 High

    Identified αB-crystallin as a chaperone-like partner that stabilizes surface Nav1.5 by limiting Nedd4-2-dependent ubiquitination and internalization.

    Evidence Yeast two-hybrid, GST pulldown, Co-IP, immunostaining, patch-clamp, and Nedd4-2 site mutagenesis in HEK293

    PMID:26961874

    Open questions at the time
    • In vivo cardiac contribution not tested
    • Stoichiometry and binding interface not defined
  13. 2016 High

    Expanded the transcriptional network with GATA4/5 as direct co-occupying activators and β-catenin/TCF4 as a redox-driven repressor of SCN5A.

    Evidence ChIP/Re-ChIP in human ventricle and luciferase assays (GATA); IF, Co-IP, ChIP, reporter, and recording in HL-1 (β-catenin/TCF4)

    PMID:27068063 PMID:27894866

    Open questions at the time
    • Hierarchy among activators/repressors at the locus unresolved
    • Physiological triggers in vivo not defined
  14. 2015 Medium

    Linked N-glycosylation state to channel functionality, showing only fully-glycosylated Nav1.5 conducts and that Brugada mutants act dominant-negatively by trapping this form.

    Evidence Patch-clamp, surface biotinylation, deglycosylation, and brefeldin A treatment in HEK293T

    PMID:25721215

    Open questions at the time
    • Glycosyltransferases responsible not identified
    • Unconventional Golgi-independent route mechanism incompletely defined
  15. 2016 Medium

    Demonstrated acetylation as a post-translational regulator of Nav1.5 abundance, with HDAC inhibition reducing channel protein and current without affecting mRNA.

    Evidence Patch-clamp, Western blot, and anti-acetyl-lysine Co-IP in cardiomyocytes and hiPSC-CMs

    PMID:27638876

    Open questions at the time
    • Specific acetylated residues not mapped
    • Responsible acetyltransferase/deacetylase not identified
  16. 2017 Medium

    Showed physical and functional coupling of Nav1.5 with Kir2.1 in cardiomyocyte membranes, with shared trafficking and degradation machinery (dynein/dynactin, Nedd4-2).

    Evidence Proximity ligation assay, patch-clamp with antibody dialysis, and pathway inhibitors in heterologous and cardiomyocyte systems

    PMID:29184507

    Open questions at the time
    • Stoichiometry of the channelosome unresolved
    • Single-lab functional inference
  17. 2018 High

    Established post-transcriptional and additional transcriptional control via HuR, which stabilizes SCN5A mRNA directly and indirectly through MEF2C, with therapeutic rescue of conduction post-MI.

    Evidence RNP-IP, AAV9 overexpression with optical mapping (HuR); RNP-IP, ChIP-qPCR, EMSA, siRNA epistasis (HuR→MEF2C)

    PMID:29454929 PMID:29678826

    Open questions at the time
    • Signals controlling HuR downregulation in failing hearts not defined
    • Relative contribution of direct vs. MEF2C-mediated pathway not quantified
  18. 2018 High

    Revealed an autoimmune mechanism in Brugada syndrome, with anti-Nav1.5 autoantibodies reducing current and transferring the ECG phenotype to mice.

    Evidence Antibody screening, patch-clamp, and BrS plasma injection in wild-type mice

    PMID:39078224

    Open questions at the time
    • Epitopes on Nav1.5 not mapped
    • Trigger for autoantibody generation unknown
  19. 2018 High

    Refined the trafficking-defect model by showing Brugada mutants disrupt Kir2.1/2.2 modulation (reducing IK1) and that ER-trapped Nav1.5 can be partially rescued via a GRASP-dependent unconventional secretory route.

    Evidence SCN5A haploinsufficiency mouse, rat cardiomyocytes, hiPSC-CMs, and heterologous patch-clamp

    PMID:30232268

    Open questions at the time
    • Mechanistic detail of GRASP-mediated rescue incomplete
    • Clinical relevance of dual INa/IK1 loss not quantified
  20. 2018 Medium

    Identified a coding synonymous SNP that modulates miR-24-mediated suppression of SCN5A, linking microRNA regulation to channel expression and myocardial ROS.

    Evidence miRNA binding site mapping, luciferase reporters, human tissue correlation, and mouse Scn5a-reduction ROS model

    PMID:29457789

    Open questions at the time
    • Causal arrhythmia link not directly tested
    • Mechanism connecting reduced Nav1.5 to ROS accumulation undefined
  21. 2019 High

    Defined epigenetic and enhancer-architecture control of SCN5A, with LMNA mutation recruiting PRC2/H3K27me3 to repress the locus and a downstream super-enhancer cluster organizing chromatin to drive cardiac expression.

    Evidence Patient iPSC-CMs with ChIP and CRISPR correction (LMNA); enhancer deletion series in mice with conduction phenotype and 3C/Hi-C

    PMID:31118417 PMID:31666509

    Open questions at the time
    • How LMNA mutation recruits PRC2 mechanistically not resolved
    • Individual enhancer element functions within the cluster not fully dissected
  22. 2020 High

    Pinpointed ubiquitination as a direct degradation signal, identifying K590/K591 as E1-dependent (UBE1/UBA6, UBC9) ubiquitination sites controlling channel abundance and current.

    Evidence Ubiquitination assay, patch-clamp, knockdown/overexpression, and K590A/K591A mutagenesis in HEK293 and neonatal cardiomyocytes

    PMID:32315024

    Open questions at the time
    • Relationship to Nedd4-2-mediated ubiquitination not fully integrated
    • In vivo significance not established
  23. 2021 High

    Identified FAT10 as a stabilizing modifier that competes with Nedd4-2 to protect Nav1.5 from degradation, with cardiac deletion reducing peak INa and increasing arrhythmia.

    Evidence Cardiac-specific Fat10 knockout mouse, patch-clamp, Co-IP, and immunoblot

    PMID:33414395

    Open questions at the time
    • FAT10 lysine binding sites on Nav1.5 not precisely mapped
    • Regulation of FAT10 expression in disease not defined
  24. 2021 Medium

    Added Zfhx3 as a transcriptional repressor acting both directly on the SCN5A promoter and indirectly by suppressing TBX5 and inducing Nedd4-2, integrating transcriptional and proteasomal control.

    Evidence Reporter assay, siRNA, overexpression, and patch-clamp in HL-1 cardiomyocytes

    PMID:34884836

    Open questions at the time
    • In vivo validation lacking
    • Direct vs. indirect contributions not separately quantified
  25. 2022 High

    Showed TBX5 simultaneously controls peak INa and late INa by regulating SCN5A, CAMK2D, and SPTBN4, with variant-specific failures producing distinct conduction vs. repolarization phenotypes.

    Evidence hiPSC-CM and HL-1 electrophysiology, transgenic mouse ECG, ranolazine rescue, and transcriptional assays for TBX5 variants

    PMID:33576403

    Open questions at the time
    • Full TBX5 target network in human cardiomyocytes not mapped
    • Mechanism distinguishing activation vs. repression by the same factor unresolved
  26. 2022 High

    Systematically established that most SCN5A loss-of-function missense variants act dominant-negatively, with dominant-negative variants conferring markedly higher Brugada burden than haploinsufficient ones.

    Evidence Automated heterozygous co-expression patch-clamp of 50 variants in HEK293T with clinical cohort comparison

    PMID:35305865

    Open questions at the time
    • Molecular basis of dominant-negative interference per variant not resolved
    • Modifier effects on penetrance not addressed
  27. 2016 Medium

    Documented non-cardiac Nav1.5 localization to late endosomes/phagolysosomes in macrophages, consistent with a role in endosomal acidification for myelin degradation.

    Evidence Triple immunolabeling of Nav1.5 and endosomal markers in human MS lesion tissue

    PMID:22951351

    Open questions at the time
    • No functional manipulation
    • Endosomal Na+ flux contribution to acidification not directly measured
  28. 2014 Medium

    Extended Nav1.5 function to innate immunity and cancer, linking an intracellular channel variant to ADCY8/ATF2 interferon signaling in macrophages and channel activity to breast cancer invasiveness.

    Evidence Patch-clamp with poly(I:C) and pathway pharmacology in macrophages; shRNA knockdown with orthotopic xenograft and invasion assays for breast cancer

    PMID:25368329 PMID:26452220

    Open questions at the time
    • Mechanistic detail of intracellular variant activation limited
    • CD44-src-cortactin axis link inferential, not directly demonstrated

Open questions

Synthesis pass · forward-looking unresolved questions
  • How the multilayered regulatory network (transcription factors, enhancers, miRNAs, ubiquitin/acetyl/glyco modifications, scaffolding partners, and microdomain targeting) is integrated to set Nav1.5 surface density and microdomain distribution in vivo remains unresolved.
  • No unified model coupling transcriptional and post-translational control
  • Crosstalk between lateral-membrane and intercalated-disk channel pools mechanistically undefined
  • Translation of variant-specific biophysics to individual clinical phenotype incomplete

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0005215 transporter activity 5 GO:0060089 molecular transducer activity 3
Localization
GO:0005886 plasma membrane 4 GO:0005783 endoplasmic reticulum 3 GO:0005768 endosome 1
Pathway
R-HSA-74160 Gene expression (Transcription) 6 R-HSA-1643685 Disease 4 R-HSA-392499 Metabolism of proteins 4 R-HSA-397014 Muscle contraction 2
Partners
CAMK2DCRYABFAT10HURKCNJ2NEDD4LTBX5TCAP
Complex memberships
Kir2.1-Nav1.5 channel complex

Evidence

Reading pass · 36 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2000 SCN5A encodes the pore-forming α-subunit of the cardiac sodium channel responsible for action potential initiation and propagation; gain-of-function mutations cause persistent (late) sodium current leading to LQT3, while distinct mutations cause loss-of-function associated with Brugada syndrome. Mutational analysis and patch-clamp electrophysiology in heterologous expression systems Circulation High 10973849 19027780 29798782
2002 The Brugada syndrome double mutant R1232W/T1620M abolishes Nav1.5 functional expression because the channel is retained in the endoplasmic reticulum rather than trafficking to the cell surface; a positively charged residue at position 1232 (R or K) is required for proper channel transport. Whole-cell patch-clamp, immunofluorescence, confocal microscopy with FLAG-tagged constructs, calnexin co-localization in tsA201 cells Circulation research High 11786529
2003 The LQT3 mutation L619F in the domain I-II linker of Nav1.5 increases maintained (persistent) Na+ current and causes a +5.8 mV shift in steady-state inactivation, implicating the I-II linker in inactivation gating. Whole-cell patch-clamp in transiently expressed HEK293 cells Human mutation Medium 12673799
2003 The LQT3 mutation I1768V in domain IVS6 causes faster recovery from inactivation and less slow inactivation without increasing persistent Na+ current, implicating domain IVS6 in inactivation kinetics. Two-electrode voltage clamp in Xenopus oocytes Cardiovascular research Medium 12650885
2004 Transgenic mice with cardiac-specific expression of the LQT3 mutation N1325S in SCN5A display QT prolongation, spontaneous polymorphic VT/VF, and slow recovery from inactivation of INa; mexiletine (a late Na+ current blocker) suppresses arrhythmias and restores inactivation recovery, establishing that the N1325S-induced persistent Na+ current causes arrhythmogenesis in vivo. Transgenic mouse model, ECG, action potential recording, voltage-clamp in isolated myocytes, mexiletine pharmacology Cardiovascular research High 14736542
2005 The LQT3 mutant L1825P fails to traffic to the cell surface (only ~9% of wild-type surface expression) and therefore does not prolong QT interval; cisapride rescues misprocessing to ~30% of wild-type surface expression and simultaneously increases late Na+ current, revealing that cell surface trafficking determines LQT3 phenotype expressivity. Patch-clamp, confocal imaging and cell-counting with epitope-tagged constructs in CHO cells Circulation High 16301357
2005 Two Brugada syndrome mutations (L325R and R535X) cause severe Nav1.5 loss-of-function; the L325R mutant is likely misfolded (rescued partially by mexiletine or curcumin) and exerts a dominant-negative effect on wild-type channels when co-expressed. Fever accelerates Nav1.5 activation and fast inactivation kinetics, providing the mechanism by which reduced INa patients are vulnerable to fever-exacerbated Brugada syndrome. Whole-cell patch-clamp at various temperatures, Western blot protein expression, co-expression dominant-negative experiments, action potential modelling in HEK293 cells Cardiovascular research High 15890323
2008 Telethonin (encoded by TCAP) is a Nav1.5-interacting protein: it co-localizes with Nav1.5 in gastrointestinal smooth muscle, co-immunoprecipitates with sodium channels, and a disease-associated telethonin mutation doubles the window current of Nav1.5 when co-expressed in HEK293 cells by altering steady-state activation kinetics. Co-immunoprecipitation, immunofluorescence co-localization, whole-cell patch-clamp in HEK293 cells The Journal of biological chemistry Medium 18408010
2010 Nav1.5 is mechanosensitive: applying negative patch pressure produces dose-dependent hyperpolarizing shifts in voltage dependence of activation and inactivation (~0.7 mV/mmHg), accelerates voltage-sensor movement but not gate-opening or fast inactivation rate constants, and increases peak current by recruiting more active channels, without changing unitary conductance or maximum open probability. Cell-attached patch-clamp with controlled pressure in HEK293 cells expressing Nav1.5 The Journal of physiology High 21041530
2011 Nav1.5-dependent persistent Na+ influx (late INa) activates CaMKII in cardiomyocytes; Nav1.5 knockdown (but not Nav1.1 or Nav1.2) prevents ATX-II-induced CaMKII phosphorylation, and CaMKII co-immunoprecipitates with Nav1.5 after late INa activation, establishing a feed-forward loop where Nav1.5 late current → CaMKII activation → CaMKII phosphorylation of Nav1.5 → further late current. siRNA knockdown, CaMKII autophosphorylation assays, co-immunoprecipitation, patch-clamp, transgenic N1325S mouse model, pharmacological inhibition (ranolazine, KN93) in neonatal rat ventricular myocytes American journal of physiology. Cell physiology High 21677263
2012 TBX5 directly drives Scn5a expression in the ventricular conduction system through a TBX5-responsive enhancer downstream of Scn5a that requires canonical T-box binding sites; conditional deletion of Tbx5 from the ventricular conduction system reduces Nav1.5 protein expression and causes severe conduction dysfunction. Conditional mouse knockout, in vivo enhancer assay, T-box site mutagenesis, immunostaining, optical mapping, ECG The Journal of clinical investigation High 22728936
2012 αB-crystallin physically interacts with Nav1.5 (validated by yeast two-hybrid, GST pulldown, Co-IP, and immunostaining); overexpression increases peak INa by reducing Nav1.5 internalization and ubiquitination via interaction with Nedd4-2; knockout of αB-crystallin decreases Nav1.5 cell surface expression. Yeast two-hybrid, GST pulldown, co-immunoprecipitation, immunostaining, whole-cell patch-clamp, mutagenesis of Nav1.5 Nedd4-2 binding site in HEK293 cells The Journal of biological chemistry High 26961874
2012 The PDZ domain-binding SIV motif (last 3 residues of Nav1.5) is required for Nav1.5 expression and INa specifically at the lateral cardiomyocyte membrane but not at intercalated disks; deletion of the SIV motif in knock-in mice reduces lateral-membrane INa and decreases transverse conduction velocity, increasing anisotropy. The SIV motif regulates Nav1.5 degradation via the proteasome. Knock-in mouse (ΔSIV), optical mapping, whole-cell patch-clamp, proteasome inhibitor rescue (MG132), HEK293 internalization assay, patient mutation screening Circulation High 24895455
2012 Foxo1 transcription factor negatively regulates Nav1.5 expression by directly binding to insulin-responsive elements (IRE) in the SCN5A promoter; reactive oxygen species (H2O2) promote Foxo1 nuclear localization and thereby suppress Nav1.5 expression and Na+ current. Chromatin immunoprecipitation, constitutively nuclear Foxo1 mutant expression, RNAi knockdown, whole-cell voltage-clamp in HL-1 cardiomyocytes PloS one High 22400069
2014 Nav1.5 promotes breast cancer cell invasiveness through activity-dependent mechanisms; shRNA-mediated stable knockdown of Nav1.5 reduces tumor growth, local invasion, and metastasis to liver, lungs and spleen in an orthotopic model, and in vitro Nav1.5 down-regulation reduces CD44 expression, suggesting regulation of invasion via the CD44-src-cortactin axis. Stable shRNA knockdown, orthotopic mouse xenograft model, in vitro invasion assay, immunohistochemistry, flow cytometry Oncotarget Medium 26452220
2015 Nav1.5 channels reach the plasma membrane through two distinct N-glycosylation states; only the fully-glycosylated form generates sodium current, while core-glycosylated channels can reach the membrane via an unconventional Golgi-independent route but are non-functional. Brugada syndrome mutants exert dominant-negative effects by trapping the fully-glycosylated form. Patch-clamp, surface biotinylation assays, enzymatic deglycosylation, brefeldin A treatment, HEK293T cells Biochimica et biophysica acta Medium 25721215
2016 GATA4 and GATA5 transcription factors directly co-occupy SCN5A promoter and intron 1 regions in human cardiac tissue and synergistically activate SCN5A transcription through predicted GATA binding sites; GATA4 mRNA levels are strongly correlated with SCN5A transcript levels in human heart. Chromatin immunoprecipitation (ChIP) and Re-ChIP in human left ventricle, luciferase reporter with site mutagenesis, ddPCR quantification Journal of molecular and cellular cardiology High 27894866
2016 Wnt/β-catenin signaling transcriptionally suppresses Nav1.5 expression: H2O2 activates β-catenin nuclear localization, β-catenin interacts with TCF4, and the β-catenin/TCF4 complex is recruited to the SCN5A promoter to repress its activity in a dose-dependent manner. Immunofluorescence, immunoprecipitation, ChIP, luciferase reporter, siRNA knockdown, whole-cell recording in HL-1 cardiomyocytes Free radical biology & medicine High 27068063
2017 Kir2.1 and Nav1.5 channels form complexes in ventricular cardiomyocyte membranes (within <40 nm by proximity ligation assay); CaMKII inhibition decreases INa and IK1 only when channels are co-expressed but not Kir2.1 alone, and Nedd4-2 ubiquitin-ligase promotes Nav1.5 (and Kir2.1-Nav1.5 complex) degradation via the proteasome. The dynein/dynactin motor governs forward trafficking of Nav1.5 and of Kir2.1-Nav1.5 complexes. Proximity ligation assay, patch-clamp with intracellular antibody dialysis, pharmacological inhibition of CaMKII/14-3-3/dynamin/dynein in heterologous and cardiomyocyte systems Frontiers in physiology Medium 29184507
2018 Brugada syndrome-associated endoplasmic reticulum (ER) trafficking-defective Nav1.5 mutants fail to positively modulate Kir2.1/2.2 channels, thereby reducing IK1 in addition to INa. Golgi trafficking-defective Nav1.5 mutants additionally exert a dominant-negative effect, further reducing IK1. ER-trapped Nav1.5 can be partially rescued by Kir2.1/2.2 through an unconventional secretory route involving GRASPs. SCN5A haploinsufficiency mouse model, heterologous expression, rat ventricular cardiomyocytes, hiPSC-CMs, patch-clamp JCI insight High 30232268
2018 The RNA-binding protein HuR stabilizes SCN5A mRNA in cardiomyocytes; HuR expression is downregulated in failing hearts. AAV9-mediated overexpression of HuR in a mouse MI model increases SCN5A expression, improves action potential upstroke and conduction velocity in the infarct border zone, and reduces reentrant arrhythmia risk. Ribonucleoprotein immunoprecipitation, AAV9 overexpression in mice, optical mapping of intact heart, quantitative RT-PCR Heart rhythm High 29454929
2018 HuR protects MEF2C mRNA from degradation, thereby maintaining MEF2C protein levels, which in turn binds the SCN5A promoter to enhance its transcription; HuR overexpression increases SCN5A mRNA and this effect is abolished by MEF2C siRNA, placing HuR upstream of MEF2C in an SCN5A regulatory network. Ribonucleoprotein immunoprecipitation, ChIP-qPCR, EMSA, siRNA knockdown, RT-PCR in cardiomyocytes Journal of the American Heart Association Medium 29678826
2018 Anti-Nav1.5 autoantibodies are detectable in 90% of Brugada syndrome patients vs. 6% of controls; these autoantibodies reduce sodium current density in cellular models and injection of BrS patient plasma into wild-type mice induces Brugada-like ECG abnormalities, demonstrating a pathogenic immunological mechanism. Western blot, immunoprecipitation, immunofluorescence screening with HEK293A cells expressing Nav1.5; patch-clamp for current density; plasma injection in vivo mouse ECG European heart journal High 39078224
2019 K219T mutation in LMNA causes increased binding of Lamin A/C to the SCN5A promoter and enhanced recruitment of PRC2 protein SUZ12 and deposition of repressive histone mark H3K27me3 at SCN5A, resulting in downregulated Nav1.5 expression, reduced peak sodium current density, and slower conduction velocity in iPSC-derived cardiomyocytes. CRISPR/Cas9 correction of the mutation restores sodium current density and SCN5A expression. iPSC-derived cardiomyocytes from patient cells, ChIP for Lamin A/C and H3K27me3 at SCN5A promoter, patch-clamp, conduction velocity measurement, CRISPR/Cas9 correction Nature communications High 31118417
2019 An evolutionarily conserved enhancer cluster downstream of SCN5A with super-enhancer characteristics drives cardiac-specific Scn5a expression; genome editing to delete individual enhancer elements or the entire cluster in mice reduces Scn5a expression, impairs cardiac conduction, and affects embryonic development. This cluster also controls chromatin conformation across a >0.5 Mb genomic region. Genome editing (deletion series) in mice, gene expression analysis, cardiac conduction measurements, chromatin conformation capture (3C/Hi-C) Nature communications High 31666509
2020 UBE1 and UBA6 are E1 ubiquitin-activating enzymes that ubiquitinate Nav1.5 at lysine residues K590 and K591; overexpression reduces Nav1.5 expression and sodium current density, knockdown increases them, and the effects require the UBC9 E2 enzyme. Mutation of K590A/K591A abolishes the effects. Western blot ubiquitination assay, patch-clamp, siRNA knockdown, overexpression, site-directed mutagenesis in HEK293/Nav1.5 cells and neonatal cardiomyocytes The Biochemical journal High 32315024
2021 FAT10 stabilizes Nav1.5 by binding to lysine residues in the C-terminal fragments of Nav1.5 and competing with Nedd4-2 ubiquitin E3 ligase binding, thereby preventing ubiquitination and proteasomal degradation of Nav1.5. Cardiac-specific Fat10 deletion reduces peak Na+ current and membrane Nav1.5 expression, increases late Na+ current, and increases arrhythmia after MI. Cardiac-specific conditional knockout mouse (Myh6-Cre × Fat10F/F), patch-clamp, co-immunoprecipitation, immunoblot/immunofluorescence Cell death & disease High 33414395
2021 Zfhx3 transcription factor directly represses the SCN5A promoter and also suppresses TBX5 expression and increases Nedd4-2 expression, thereby reducing peak INa density in cardiomyocytes through transcriptional and post-translational (proteasomal) mechanisms. Transcriptional reporter assay, siRNA knockdown, overexpression, patch-clamp in HL-1 cardiomyocytes International journal of molecular sciences Medium 34884836
2022 TBX5 variant p.F206L fails to transactivate the SCN5A promoter, markedly decreasing peak INa and causing QRS widening in mice; variant p.D111Y increases SCN5A expression but fails to repress CAMK2D and SPTBN4, resulting in increased late INa (INaL) and QT prolongation. This establishes that TBX5 controls both peak INa and INaL in human cardiomyocytes by regulating SCN5A, CaMKIIδ, and βIV-spectrin expression. hiPSC-CM electrophysiology, HL-1 cell patch-clamp, in vivo ECG of transgenic mice, molecular transcriptional assays Cardiovascular research High 33576403
2022 Most SCN5A missense loss-of-function variants exert dominant-negative effects on wild-type Nav1.5 when co-expressed in heterozygous conditions; 32 of 35 complete LoF variants reduced peak current to <75% of wild-type alone. Individuals with dominant-negative variants have 2.7-fold higher Brugada syndrome burden than those with haploinsufficient variants. Automated patch-clamp in HEK293T cells with heterozygous WT + mutant co-expression for 50 variants; clinical cohort comparison with gnomAD Genetics in medicine High 35305865
2008 SCN5A gain-of-function mutation M1875T causes a +16.4 mV depolarized shift in the voltage-dependence of steady-state inactivation without generating persistent Na+ current, increasing atrial excitability and predisposing to familial atrial fibrillation through a mechanism distinct from LQT3. Whole-cell patch-clamp in heterologous expression system with M1875T mutant Journal of the American College of Cardiology Medium 18929244
2016 Nav1.5 protein is localized to late endosomes and phagolysosomes (Rab7+, LAMP-1+) rather than early endosomes in macrophages within active MS lesions, consistent with a role in endosomal acidification for myelin degradation. Immunohistochemistry with triple immunolabeling for Nav1.5, endosomal markers, and myelin protein in human MS lesion tissue Multiple sclerosis Medium 22951351
2014 In macrophages, an intracellular SCN5A variant initiates innate immune signaling through ADCY8 and ATF2 transcription factor; cytoplasmic poly(I:C) (viral dsRNA mimic) activates this pathway and markedly augments an inward voltage-sensitive sodium current mediated by the channel, linking pathogen recognition to Nav1.5 channel activation and downstream transcriptional regulation of interferon β. Electrophysiology (patch-clamp), pharmacological channel stimulation, poly(I:C) treatment, signaling pathway pharmacology in macrophages The Journal of biological chemistry Medium 25368329
2010 The common H558R polymorphism has mutation-specific effects on SCN5A-related sick sinus syndrome: it rescues the loss-of-function D1275N mutant by enhancing cell surface targeting and improving steady-state activation, but aggravates defects of E161K, P1298L, and R1632H mutants by reducing steady-state availability. Whole-cell patch-clamp, cell surface biotinylation in HEK293 cells with all 13 known SSS-related hNav1.5 mutants on H558 vs R558 backgrounds Journal of cardiovascular electrophysiology Medium 20384651
2016 Pan-HDAC inhibitors (TSA, vorinostat, romidepsin) reduce peak INa density and increase Nav1.5 acetylation in cardiomyocytes; Nav1.5 protein levels are significantly reduced after HDAC inhibition without changes in Scn5a mRNA, and co-immunoprecipitation with anti-acetyl-lysine antibody confirms Nav1.5 acetylation is increased in vivo after HDAC inhibition. Whole-cell patch-clamp, Western blot, immunoprecipitation with anti-acetyl-lysine antibody in neonatal mouse ventricular cardiomyocytes and hiPSC-CMs American journal of physiology. Heart and circulatory physiology Medium 27638876
2018 A synonymous SNP (rs1805126) in the SCN5A coding sequence adjacent to a miR-24 binding site modulates miR-24-mediated suppression of SCN5A expression; miR-24 potently suppresses SCN5A expression and the minor allele of rs1805126 is associated with decreased cardiac SCN5A expression. In mice, decreased Scn5a expression leads to accumulation of myocardial reactive oxygen species. miRNA binding site mapping, luciferase reporter assays, human heart tissue expression correlation, mouse Scn5a reduction model with ROS measurement The Journal of clinical investigation Medium 29457789

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2000 Spectrum of mutations in long-QT syndrome genes. KVLQT1, HERG, SCN5A, KCNE1, and KCNE2. Circulation 962 10973849
2004 SCN5A mutation associated with dilated cardiomyopathy, conduction disorder, and arrhythmia. Circulation 346 15466643
2018 Clinical Spectrum of SCN5A Mutations: Long QT Syndrome, Brugada Syndrome, and Cardiomyopathy. JACC. Clinical electrophysiology 270 29798782
2009 SCN5A mutations and the role of genetic background in the pathophysiology of Brugada syndrome. Circulation. Cardiovascular genetics 246 20031634
2000 The elusive link between LQT3 and Brugada syndrome: the role of flecainide challenge. Circulation 185 10961955
2008 Cardiac sodium channel overlap syndromes: different faces of SCN5A mutations. Trends in cardiovascular medicine 163 18436145
2005 Brugada syndrome and fever: genetic and molecular characterization of patients carrying SCN5A mutations. Cardiovascular research 158 15890323
2011 Biology of cardiac sodium channel Nav1.5 expression. Cardiovascular research 157 21937582
2008 A novel SCN5A gain-of-function mutation M1875T associated with familial atrial fibrillation. Journal of the American College of Cardiology 150 18929244
2010 Mechanosensitivity of Nav1.5, a voltage-sensitive sodium channel. The Journal of physiology 145 21041530
2015 The cardiac sodium channel gene SCN5A and its gene product NaV1.5: Role in physiology and pathophysiology. Gene 137 26361848
2008 SCN5A channelopathies--an update on mutations and mechanisms. Progress in biophysics and molecular biology 131 19027780
2010 Environmental regulation of lateral root emergence in Medicago truncatula requires the HD-Zip I transcription factor HB1. The Plant cell 129 20675575
2012 R222Q SCN5A mutation is associated with reversible ventricular ectopy and dilated cardiomyopathy. Journal of the American College of Cardiology 127 22999724
2012 TBX5 drives Scn5a expression to regulate cardiac conduction system function. The Journal of clinical investigation 124 22728936
2014 Ranolazine inhibits NaV1.5-mediated breast cancer cell invasiveness and lung colonization. Molecular cancer 121 25496128
2018 SCN5A Variants: Association With Cardiac Disorders. Frontiers in physiology 114 30364184
2019 The K219T-Lamin mutation induces conduction defects through epigenetic inhibition of SCN5A in human cardiac laminopathy. Nature communications 101 31118417
2002 Expression and intracellular localization of an SCN5A double mutant R1232W/T1620M implicated in Brugada syndrome. Circulation research 89 11786529
2011 Nav1.5-dependent persistent Na+ influx activates CaMKII in rat ventricular myocytes and N1325S mice. American journal of physiology. Cell physiology 86 21677263
2015 Nav1.5 regulates breast tumor growth and metastatic dissemination in vivo. Oncotarget 85 26452220
2014 PDZ domain-binding motif regulates cardiomyocyte compartment-specific NaV1.5 channel expression and function. Circulation 85 24895455
2015 Regulation of the cardiac Na+ channel NaV1.5 by post-translational modifications. Journal of molecular and cellular cardiology 83 25748040
2004 Mechanisms by which SCN5A mutation N1325S causes cardiac arrhythmias and sudden death in vivo. Cardiovascular research 74 14736542
2016 The role of mutations in the SCN5A gene in cardiomyopathies. Biochimica et biophysica acta 71 26916278
2006 SCN5A mutation associated with cardiac conduction defect and atrial arrhythmias. Journal of cardiovascular electrophysiology 67 16684018
2009 Inherited cardiac diseases caused by mutations in the Nav1.5 sodium channel. Journal of cardiovascular electrophysiology 66 19845816
2012 Novel SCN3B mutation associated with brugada syndrome affects intracellular trafficking and function of Nav1.5. Circulation journal : official journal of the Japanese Circulation Society 60 23257389
2007 SCN5A and sinoatrial node pacemaker function. Cardiovascular research 59 17368591
2007 Novel mutation in the SCN5A gene associated with arrhythmic storm development during acute myocardial infarction. Heart rhythm 59 17675083
2020 SCN5A Mutation Type and a Genetic Risk Score Associate Variably With Brugada Syndrome Phenotype in SCN5A Families. Circulation. Genomic and precision medicine 58 33164571
2008 A mutation in telethonin alters Nav1.5 function. The Journal of biological chemistry 56 18408010
2018 Dysfunctional Nav1.5 channels due to SCN5A mutations. Experimental biology and medicine (Maywood, N.J.) 51 29806494
2016 Physiological and Pathophysiological Insights of Nav1.4 and Nav1.5 Comparison. Frontiers in pharmacology 51 26834636
2012 Cardiac sodium channel Nav1.5 mutations and cardiac arrhythmia. Pediatric cardiology 48 22460359
2018 Systematic re-evaluation of SCN5A variants associated with Brugada syndrome. Journal of cardiovascular electrophysiology 47 30203441
2023 SCN5A channelopathy: arrhythmia, cardiomyopathy, epilepsy and beyond. Philosophical transactions of the Royal Society of London. Series B, Biological sciences 46 37122208
2018 Colorectal cancer invasiveness in vitro: Predominant contribution of neonatal Nav1.5 under normoxia and hypoxia. Journal of cellular physiology 46 30341901
2016 αB-Crystallin Interacts with Nav1.5 and Regulates Ubiquitination and Internalization of Cell Surface Nav1.5. The Journal of biological chemistry 44 26961874
2018 Brugada syndrome trafficking-defective Nav1.5 channels can trap cardiac Kir2.1/2.2 channels. JCI insight 43 30232268
2005 New mechanism contributing to drug-induced arrhythmia: rescue of a misprocessed LQT3 mutant. Circulation 42 16301357
2021 Arrhythmic Phenotypes Are a Defining Feature of Dilated Cardiomyopathy-Associated SCN5A Variants: A Systematic Review. Circulation. Genomic and precision medicine 41 34949099
2018 A common variant alters SCN5A-miR-24 interaction and associates with heart failure mortality. The Journal of clinical investigation 41 29457789
2015 Nav1.5 channels can reach the plasma membrane through distinct N-glycosylation states. Biochimica et biophysica acta 40 25721215
2002 Localization of Nav1.5 sodium channel protein in the mouse brain. Neuroreport 40 12499865
2012 Reactive oxygen species suppress cardiac NaV1.5 expression through Foxo1. PloS one 37 22400069
2012 Nav1.5 sodium channels in macrophages in multiple sclerosis lesions. Multiple sclerosis (Houndmills, Basingstoke, England) 37 22951351
2010 Epidemiologic, molecular, and functional evidence suggest A572D-SCN5A should not be considered an independent LQT3-susceptibility mutation. Heart rhythm 37 20403459
2017 Kir2.1-Nav1.5 Channel Complexes Are Differently Regulated than Kir2.1 and Nav1.5 Channels Alone. Frontiers in physiology 36 29184507
2012 p.D1690N Nav1.5 rescues p.G1748D mutation gating defects in a compound heterozygous Brugada syndrome patient. Heart rhythm 36 23085483
2003 A novel mutation L619F in the cardiac Na+ channel SCN5A associated with long-QT syndrome (LQT3): a role for the I-II linker in inactivation gating. Human mutation 36 12673799
2016 Activation of Wnt/β-catenin signaling by hydrogen peroxide transcriptionally inhibits NaV1.5 expression. Free radical biology & medicine 34 27068063
2018 Disease Modifiers of Inherited SCN5A Channelopathy. Frontiers in cardiovascular medicine 32 30327767
2013 Silencing of desmoplakin decreases connexin43/Nav1.5 expression and sodium current in HL‑1 cardiomyocytes. Molecular medicine reports 32 23877755
2010 Mutation-specific effects of polymorphism H558R in SCN5A-related sick sinus syndrome. Journal of cardiovascular electrophysiology 32 20384651
2008 Mouse models of SCN5A-related cardiac arrhythmias. Progress in biophysics and molecular biology 32 19041666
2006 Functional expression of "cardiac-type" Nav1.5 sodium channel in canine intracardiac ganglia. Heart rhythm 32 16818219
1979 DNA fragments of the Mus musculus beta globin haplotypes Hbbs and Hbbd. Proceedings of the National Academy of Sciences of the United States of America 32 286321
2018 Copy number variations of SCN5A in Brugada syndrome. Heart rhythm 30 29574140
2015 The multi-faceted aspects of the complex cardiac Nav1.5 protein in membrane function and pathophysiology. Biochimica et biophysica acta 30 26209461
2014 Changes in Cx43 and NaV1.5 expression precede the occurrence of substantial fibrosis in calcineurin-induced murine cardiac hypertrophy. PloS one 30 24498049
2016 Transcriptional regulation of the sodium channel gene (SCN5A) by GATA4 in human heart. Journal of molecular and cellular cardiology 28 27894866
2015 The RyR2-P2328S mutation downregulates Nav1.5 producing arrhythmic substrate in murine ventricles. Pflugers Archiv : European journal of physiology 28 26545784
2018 HuR-mediated SCN5A messenger RNA stability reduces arrhythmic risk in heart failure. Heart rhythm 27 29454929
2022 Tbx5 variants disrupt Nav1.5 function differently in patients diagnosed with Brugada or Long QT Syndrome. Cardiovascular research 26 33576403
2019 An enhancer cluster controls gene activity and topology of the SCN5A-SCN10A locus in vivo. Nature communications 26 31666509
2014 NaV1.5 sodium channel window currents contribute to spontaneous firing in olfactory sensory neurons. Journal of neurophysiology 26 24872539
2016 Variants in the SCN5A Promoter Associated With Various Arrhythmia Phenotypes. Journal of the American Heart Association 25 27625342
2006 Involvement of Kv1.1 and Nav1.5 in proliferation of gastric epithelial cells. Journal of cellular physiology 25 16331678
2018 Predicting changes to INa from missense mutations in human SCN5A. Scientific reports 24 30143662
2016 Sodium channel diversity in the vestibular ganglion: NaV1.5, NaV1.8, and tetrodotoxin-sensitive currents. Journal of neurophysiology 24 26936982
2016 Changes in cardiac Nav1.5 expression, function, and acetylation by pan-histone deacetylase inhibitors. American journal of physiology. Heart and circulatory physiology 24 27638876
2022 Subcellular diversity of Nav1.5 in cardiomyocytes: distinct functions, mechanisms and targets. The Journal of physiology 23 36469003
2018 RNA Binding Protein, HuR, Regulates SCN5A Expression Through Stabilizing MEF2C transcription factor mRNA. Journal of the American Heart Association 22 29678826
2018 SCN5A mutation type and topology are associated with the risk of ventricular arrhythmia by sodium channel blockers. International journal of cardiology 22 29709244
2014 Suppression of PPARβ, and DHA treatment, inhibit NaV1.5 and NHE-1 pro-invasive activities. Pflugers Archiv : European journal of physiology 22 25017107
2022 Dominant negative effects of SCN5A missense variants. Genetics in medicine : official journal of the American College of Medical Genetics 21 35305865
2018 A homozygous SCN5A mutation associated with atrial standstill and sudden death. Pacing and clinical electrophysiology : PACE 21 29781517
2016 A novel NaV1.5 voltage sensor mutation associated with severe atrial and ventricular arrhythmias. Journal of molecular and cellular cardiology 21 26801742
2014 Human macrophage SCN5A activates an innate immune signaling pathway for antiviral host defense. The Journal of biological chemistry 21 25368329
2014 Atrial Fibrillation and SCN5A Variants. Cardiac electrophysiology clinics 21 25484998
2021 FAT10 protects against ischemia-induced ventricular arrhythmia by decreasing Nedd4-2/Nav1.5 complex formation. Cell death & disease 19 33414395
2008 New variants of Nav1.5/SCN5A encode Na+ channels in the brain. Journal of neurogenetics 19 18386309
2003 A novel LQT3 mutation implicates the human cardiac sodium channel domain IVS6 in inactivation kinetics. Cardiovascular research 19 12650885
2018 Blocking the Nav1.5 channel using eicosapentaenoic acid reduces migration and proliferation of ovarian cancer cells. International journal of oncology 18 29901108
2018 Potent Inactivation-Dependent Inhibition of Adult and Neonatal NaV1.5 Channels by Lidocaine and Levobupivacaine. Anesthesia and analgesia 18 29958221
2009 Atrial arrhythmogenesis in wild-type and Scn5a+/delta murine hearts modelling LQT3 syndrome. Pflugers Archiv : European journal of physiology 18 19184093
2023 Familial atrial fibrillation mutation M1875T-SCN5A increases early sodium current and dampens the effect of flecainide. 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 17 36504385
2017 Infant sudden death: Mutations responsible for impaired Nav1.5 channel trafficking and function. Pacing and clinical electrophysiology : PACE 17 28370132
2009 Stable expression of neurogenin 1 induces LGR5, a novel stem cell marker, in an immortalized human neural stem cell line HB1.F3. Cellular and molecular neurobiology 17 19813087
2024 NaV1.5 autoantibodies in Brugada syndrome: pathogenetic implications. European heart journal 16 39078224
2023 Beneficial effects of chronic mexiletine treatment in a human model of SCN5A overlap syndrome. 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 16 37369559
2016 Negative-dominance phenomenon with genetic variants of the cardiac sodium channel Nav1.5. Biochimica et biophysica acta 16 26907222
2015 Arrhythmogenic Biophysical Phenotype for SCN5A Mutation S1787N Depends upon Splice Variant Background and Intracellular Acidosis. PloS one 16 25923670
2008 In calcineurin-induced cardiac hypertrophy expression of Nav1.5, Cx40 and Cx43 is reduced by different mechanisms. Journal of molecular and cellular cardiology 16 18662696
2007 Cardiac sodium channel Nav1.5 and its associated proteins. Archives des maladies du coeur et des vaisseaux 16 18033008
2021 Zfhx3 Transcription Factor Represses the Expression of SCN5A Gene and Decreases Sodium Current Density (INa). International journal of molecular sciences 15 34884836
2020 Ubiquitination-activating enzymes UBE1 and UBA6 regulate ubiquitination and expression of cardiac sodium channel Nav1.5. The Biochemical journal 15 32315024
2019 Protein structure aids predicting functional perturbation of missense variants in SCN5A and KCNQ1. Computational and structural biotechnology journal 15 30828412
2022 SCN5A overlap syndromes: An open-minded approach. Heart rhythm 14 35351625

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