| 2001 |
SCN3B (Scn3b) co-expression with the cardiac alpha-subunit SCN5a in Xenopus oocytes produced a ~3-fold increase in functional sodium channel expression, suggesting SCN3B improves efficiency of channel trafficking to the plasma membrane. SCN3B also caused a significant depolarising shift in the half-voltage of steady-state inactivation compared to SCN5a alone, and recovery from inactivation was significantly slower for SCN5a+SCN3b than for SCN5a+SCN1b. |
Xenopus oocyte co-expression, cell-attached macropatch electrophysiology, Northern blot, Western blot |
The Journal of physiology |
High |
11744748
|
| 2004 |
SCN3B is a p53-inducible gene: p53 directly binds two functional response elements (RE1 upstream of exon 1, RE2 in intron 3) as shown by chromatin immunoprecipitation and reporter assays. SCN3B protein localises to the endoplasmic reticulum, and overexpression of SCN3B induces apoptosis and suppresses colony formation, identifying it as a proapoptotic effector downstream of p53. |
Chromatin immunoprecipitation, reporter gene assay, cDNA representational difference analysis, adenovirus-mediated overexpression, immunofluorescence localisation |
Oncogene |
High |
15334053
|
| 2009 |
In Scn3b knockout mice, ventricular myocytes showed reduced peak Na+ current densities and a negatively shifted inactivation curve. Intact Langendorff-perfused Scn3b−/− hearts displayed shorter ventricular effective refractory periods and inducible ventricular tachycardias, establishing that Scn3b is required for normal ventricular sodium channel function and electrophysiology. |
Scn3b knockout mice (homologous recombination), whole-cell patch clamp on isolated myocytes, Langendorff perfusion electrophysiology, RT-PCR |
Progress in biophysics and molecular biology |
High |
19351516
|
| 2009 |
Scn3b knockout mice exhibit atrial electrophysiological abnormalities including slower heart rate, prolonged PR interval, longer sinus node recovery times, and susceptibility to atrial tachycardia/fibrillation upon burst pacing, demonstrating a role for Scn3b in sino-atrial node function and intracardiac conduction. |
Scn3b knockout mice, in vivo ECG recordings, Langendorff-perfused atrial electrograms, burst pacing protocols, immunofluorescence, RT-PCR |
Acta physiologica |
High |
19796257
|
| 2009 |
A novel SCN3B missense mutation V54G (Navbeta3-V54G), identified in an idiopathic ventricular fibrillation patient, significantly decreased peak sodium current and caused a positive shift of inactivation when co-expressed with Nav1.5. Co-immunoprecipitation demonstrated physical association of Navbeta3 with Nav1.5, and immunocytochemistry showed the V54G mutation dramatically reduced trafficking of Nav1.5 to the plasma membrane. |
Whole-cell patch clamp (HEK-293 and COS cells), co-immunoprecipitation, immunocytochemistry |
Cardiovascular research |
High |
20042427
|
| 2010 |
Three SCN3B missense mutations (R6K, L10P, M161T) identified in lone atrial fibrillation patients all caused loss-of-function reduction in cardiac sodium current when expressed electrophysiologically, supporting a mechanistic link between SCN3B loss of function and AF susceptibility. |
Direct sequencing, electrophysiological studies (heterologous expression patch clamp) |
Cardiovascular research |
Medium |
21051419
|
| 2010 |
SCN3B mutation A130V dramatically decreased cardiac sodium current density in HEK293/Nav1.5 stable cells without affecting activation/inactivation kinetics or cell surface expression of Nav1.5 or SCN3B. When co-expressed with wild-type SCN3B, A130V negated wild-type function, demonstrating a dominant-negative mechanism that does not involve impaired trafficking but likely impairs ion conduction. |
Whole-cell patch clamp, biotinylation-based surface protein isolation, Western blot, co-expression dominant-negative assay |
Biochemical and biophysical research communications |
High |
20558140
|
| 2012 |
SCN3B mutation Val110Ile, found in Brugada syndrome patients, impaired cytoplasmic trafficking of Nav1.5, decreased Nav1.5 cell surface expression in transfected cells, and significantly reduced whole-cell sodium currents, establishing a trafficking-dependent loss-of-function mechanism for this BrS-associated variant. |
Direct sequencing, transfection, whole-cell patch clamp, surface expression assay (immunofluorescence/Western blot) |
Circulation journal |
Medium |
23257389
|
| 2016 |
IL-2 upregulates SCN3B transcript and protein expression (via p53) in HL-1 cardiomyocytes and increases sodium current density. The effect of IL-2 on sodium currents was shown to be independent of SCN3B itself (IL-2 increased sodium current even when SCN3B was separately manipulated), placing IL-2-p53-SCN3B in a regulatory pathway modulating cardiac sodium channel activity. |
qRT-PCR, Western blot, whole-cell patch clamp, HEK293 and HL-1 cells |
BMC cardiovascular disorders |
Medium |
26728597
|
| 2016 |
SCN3B is highly expressed in embryonic hearts and iPSC-derived cardiomyocytes. In a heterologous expression system, SCN3B augmented INa of mutated SCN5A (E1784K). Knockdown of SCN3B in LQTS3/BrS iPSC-derived cardiomyocytes unmasked the Brugada syndrome electrophysiological phenotype, demonstrating that embryonic SCN3B expression compensates for the loss-of-function effect of this SCN5A mutation. |
iPSC-derived cardiomyocytes, heterologous expression electrophysiology, SCN3B knockdown, patch clamp |
Scientific reports |
High |
27677334
|
| 2022 |
Two rare variants in the 5′UTR of SCN3B (c.-324C>A and c.-303C>T) were identified in lone AF patients. Functional reporter assays showed that the c.-324C>A (A allele) increases SCN3B transcriptional activity, and this effect is enhanced by interaction with transcription factor GATA4, identifying GATA4 as a transcriptional regulator of SCN3B. |
Luciferase reporter assay, transcription factor binding assay (GATA4 interaction) |
Life (Basel, Switzerland) |
Medium |
36362949
|
| 2022 |
miR-190a-5p directly downregulates IL-2, and this reduces the IL-2-driven increase in SCN3B sodium current; inhibition of miR-190a-5p reversed this suppression, establishing a miR-190a-5p/IL-2/SCN3B axis in cardiac arrhythmias. |
Luciferase reporter assay, qRT-PCR, whole-cell patch clamp, ELISA, FISH |
Frontiers in cardiovascular medicine |
Medium |
35083300
|
| 2025 |
A novel SCN3B in-frame deletion (ΔT138) associated with Brugada syndrome caused highly localised structural perturbations (confirmed by circular dichroism spectroscopy) without grossly disrupting protein architecture. Biotinylation and co-immunoprecipitation showed normal surface expression and interaction with Nav1.5, yet patch clamp revealed reduced peak current, decreased channel availability, and accelerated fast inactivation (especially when WT and ΔT138 β3 were co-expressed), consistent with a loss-of-function affecting gating rather than trafficking. |
Site-directed mutagenesis, circular dichroism spectroscopy, biotinylation, co-immunoprecipitation, surface cross-linking, whole-cell patch clamp, computational modelling |
Journal of molecular and cellular cardiology |
High |
39761910
|
| 2024 |
A Scn3b P87I mutation in a Brugada syndrome patient reduced peak INa by ~60% without altering activation/inactivation half-maximal voltages or late sodium current. Confocal imaging and Western blot demonstrated decreased plasma membrane localisation of both SCN3B and Nav1.5 (SCN5A), indicating loss of function via impaired trafficking. |
Whole-cell patch clamp, confocal immunofluorescence, Western blot, computational action potential simulation |
Frontiers in cardiovascular medicine |
Medium |
38450374
|