Affinage

SCN1B

Sodium channel regulatory subunit beta-1 · UniProt Q07699

Length
218 aa
Mass
24.7 kDa
Annotated
2026-04-28
65 papers in source corpus 27 papers cited in narrative 27 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

SCN1B encodes the voltage-gated sodium channel β1 (and β1B) auxiliary subunits, which function as multifunctional regulators of neuronal and cardiac excitability by modulating Na+ channel gating kinetics, promoting α-subunit cell-surface expression, and acting as immunoglobulin-superfamily cell adhesion molecules that direct axonal pathfinding, fasciculation, and neuronal migration. The β1 subunit is required for normal Na+ channel inactivation and controls cell-surface density of multiple α-subunit isoforms (Nav1.1, Nav1.3, Nav1.5, Nav1.6) in an isoform-specific manner; loss of β1 increases persistent and late Na+ current, disrupts Ca²⁺ homeostasis in cardiomyocytes, and enhances intrinsic excitability of cortical pyramidal neurons, hippocampal neurons, and cerebellar Purkinje cells while reducing parvalbumin interneuron firing (PMID:7851891, PMID:17884088, PMID:23277545, PMID:37845033, PMID:40923316). β1 additionally participates in regulated intramembrane proteolysis (RIP)-coupled signaling at cardiac intercalated discs, linking its adhesion function to intracellular signaling (PMID:38942073). Loss-of-function and gain-of-function SCN1B mutations cause developmental and epileptic encephalopathy 52 (DEE52), generalized epilepsy with febrile seizures plus (GEFS+), Brugada syndrome, and cardiac arrhythmias including atrial fibrillation and long QT syndrome, and early postnatal AAV-mediated β1 gene replacement rescues seizure severity and lifespan in Scn1b-null mice (PMID:9697698, PMID:35603785, PMID:24662403, PMID:39847501).

Mechanistic history

Synthesis pass · year-by-year structured walk · 13 steps
  1. 1994 High

    Identifying the genomic structure of SCN1B and establishing that the β1 subunit is required for normal Na+ channel inactivation kinetics resolved why α subunits alone exhibit abnormal gating behavior.

    Evidence Genomic cloning, sequencing, and FISH mapping of the SCN1B locus on chromosome 19q13.1–q13.2

    PMID:7851891

    Open questions at the time
    • No protein structure resolved
    • Mechanism of β1–α subunit interaction unknown
  2. 1998 High

    Demonstrating that the GEFS+ C121W mutation disrupts the extracellular Ig-fold disulfide bridge and abolishes β1-mediated channel modulation established SCN1B as a disease gene and linked its adhesion-like domain to channel-gating function.

    Evidence Xenopus oocyte co-expression electrophysiology with mutant β1 and brain Na+ channel α subunit

    PMID:9697698

    Open questions at the time
    • In vivo consequences of C121W not yet characterized
    • Whether C121W is pure loss-of-function or gain-of-function unknown
  3. 2007 High

    Showing that Scn1b-null cardiomyocytes have increased peak and persistent INa, prolonged QT/RR intervals, and upregulated Nav1.5 established β1 as a negative regulator of cardiac Na+ current and a determinant of cardiac repolarization.

    Evidence Patch-clamp of ventricular myocytes, ECG, and immunostaining in Scn1b-null mice

    PMID:17884088

    Open questions at the time
    • Mechanism of Nav1.5 upregulation (transcriptional vs. post-translational) unclear
    • Whether cardiac phenotype is cell-autonomous not resolved
  4. 2008 Medium

    Zebrafish studies confirmed evolutionary conservation of β1 dual function as both a Na+ current modulator and a cell adhesion molecule required for axonal pathfinding and sensory neuron development.

    Evidence Heterologous co-expression electrophysiology of zebrafish scn1ba with scn8aa; morpholino knockdown of scn1bb with behavioral, electrophysiological, and immunohistochemical readouts

    PMID:17623064 PMID:19020043

    Open questions at the time
    • Morpholino off-target effects not fully controlled
    • Mammalian in vivo CAM function not yet demonstrated
  5. 2009 High

    Establishing that the R125C mutation causes a trafficking-null phenotype (retained intracellularly despite normal total expression) while Scn1b-null hippocampal neurons fire with higher amplitude action potentials connected disease mutations to surface-expression failure and neuronal hyperexcitability.

    Evidence Biochemical surface-expression assays in heterologous cells; hippocampal slice and dissociated neuron recordings from Scn1b-null mice

    PMID:19710327

    Open questions at the time
    • Downstream transcriptional consequences of β1 loss in hippocampus not explored
  6. 2011 High

    Discovery that β1 regulates not only Na+ currents but also K+ currents and Nav1.9 surface expression in DRG neurons, and independently modulates late INa in cardiac myocytes, broadened β1's role beyond canonical fast Na+ channel gating.

    Evidence Patch-clamp of Scn1b-null DRG neurons with Nav1.9 immunostaining; siRNA knockdown of SCN1B in canine ventricular myocytes with electrophysiology

    PMID:21555511 PMID:21705762

    Open questions at the time
    • Direct physical interaction between β1 and K+ channels not demonstrated
    • Molecular basis of isoform-specific late INa modulation unknown
  7. 2012 High

    Demonstrating disrupted parallel fiber fasciculation, aberrant neuronal migration, and defective axonal pathfinding in Scn1b-null mouse brains established β1 as a bona fide cell adhesion molecule required for postnatal brain development.

    Evidence Immunohistochemistry, c-Fos staining, and electrophysiology in hippocampal and cortical slices of Scn1b-null mice

    PMID:23277545

    Open questions at the time
    • Trans-binding partners for β1 CAM activity not identified
    • Whether CAM and channel-modulation functions are separable in vivo unclear
  8. 2014 High

    Cell-type-specific analysis showed C121W increases excitatory neuron firing (via increased input resistance) without affecting interneurons, and cardiac-specific Scn1b deletion causes Ca²⁺ dysregulation and arrhythmia susceptibility, delineating tissue- and cell-type-specific consequences of β1 loss.

    Evidence Patch-clamp in brain slices of Scn1b-C121W mice with retigabine rescue; macropatch, Ca²⁺ imaging, and arrhythmia protocols in cardiac-specific Scn1b-null mice with TTX rescue

    PMID:24747835 PMID:25772295

    Open questions at the time
    • Mechanism by which β1 loss increases input resistance not resolved
    • Upstream signaling linking increased Na+ influx to Ca²⁺ release not fully defined
  9. 2016 High

    Showing that C121W β1 reaches the neuronal surface but fails to associate with α subunits and is excluded from axon initial segments and nodes of Ranvier—and that heterozygous C121W mice are more seizure-susceptible than heterozygous nulls—established a dominant-negative/gain-of-function mechanism beyond simple haploinsufficiency.

    Evidence Co-immunoprecipitation from brain, immunofluorescence at AIS and nodes, hyperthermia seizure comparison of Scn1b+/W vs. Scn1b+/− mice

    PMID:27277800

    Open questions at the time
    • Nature of the gain-of-function mechanism not molecularly defined
    • Whether mislocalized C121W exerts CAM-related toxicity unknown
  10. 2022 High

    Scn1b loss in the heart causes sinoatrial node dysfunction, atrial fibrillation susceptibility with autonomic dysregulation, and diastolic dysfunction via increased late INa and disrupted Ca²⁺ transients—all rescued pharmacologically—establishing β1 as essential for multiple aspects of cardiac physiology beyond ventricular conduction.

    Evidence Pacing-induced AF with atropine rescue in Scn1b-null neonatal mice; inducible cardiac-specific KO with echocardiography, hemodynamics, Ca²⁺ imaging, and GS967 rescue in adult mice

    PMID:35394857 PMID:35603785

    Open questions at the time
    • Mechanism of increased cholinergic innervation in null SAN not resolved
    • Whether fibrosis is a direct consequence of altered Na+/Ca²⁺ handling unclear
  11. 2023 Medium

    Revealing that β1 loss disrupts INa density heterogeneity across cortical pyramidal neurons and impairs parvalbumin and somatostatin interneuron recruitment in hippocampal circuits explained how β1 shapes network-level spike pattern diversity and synchronization thresholds relevant to seizure generation.

    Evidence Patch-clamp from constitutive and inducible Scn1b-null cortical neurons with computational modeling; multi-cell-type recordings in hippocampal slices of Scn1b KO mice

    PMID:37264112 PMID:37845033

    Open questions at the time
    • Computational predictions of synchronization thresholds not validated in vivo
    • Molecular basis of reduced interneuron firing not identified
  12. 2024 Medium

    Demonstrating that β1 mimetic peptides disrupt intercellular adhesion at cardiac perinexii and modulate regulated intramembrane proteolysis (RIP) linked β1's CAM function to a signaling pathway, with RIP inhibition partially rescuing adhesion disruption.

    Evidence ECIS adhesion assay and patch-clamp in neonatal cardiomyocytes with DAPT (γ-secretase inhibitor) pharmacological rescue

    PMID:38942073

    Open questions at the time
    • Downstream transcriptional targets of β1-RIP signaling not identified
    • Whether RIP occurs in neurons in vivo not established
  13. 2025 High

    AAV-mediated β1 gene replacement at postnatal day 2 rescued seizures and extended lifespan in Scn1b-null mice; cell-type-specific deletion showed β1 is required for Purkinje cell resurgent Na+ current and repetitive firing, with PC-specific loss sufficient for ataxia; and a knock-in DEE52 model confirmed increased Ito as a conserved cardiac phenotype in both mouse and human iPSC-CMs.

    Evidence AAV-Navβ1 ICV injection with EEG/seizure monitoring and electrophysiology; PC-specific conditional KO with patch-clamp and behavioral testing; CRISPR knock-in R89C mice and patient iPSC-CMs

    PMID:39847501 PMID:40763036 PMID:40923316

    Open questions at the time
    • Therapeutic window for gene replacement in humans undefined
    • Whether gene therapy rescues CAM-dependent developmental phenotypes not assessed
    • Mechanism of β1-dependent Ito regulation in cardiomyocytes unknown

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key open questions include: the structural basis of β1–α subunit interaction, the identity of β1 trans-binding CAM partners, whether channel-modulation and adhesion functions are genetically separable in vivo, the downstream transcriptional targets of β1-RIP signaling, and whether early gene replacement can rescue developmental (CAM-mediated) as well as electrophysiological phenotypes.
  • No high-resolution structure of β1–α complex
  • Trans-binding partners for β1 CAM adhesion not identified
  • RIP transcriptional targets unknown
  • Separability of channel-modulation vs. CAM functions in vivo untested

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0098772 molecular function regulator activity 8 GO:0005198 structural molecule activity 3 GO:0098631 cell adhesion mediator activity 3
Localization
GO:0005886 plasma membrane 4 GO:0005856 cytoskeleton 1
Pathway
R-HSA-112316 Neuronal System 8 R-HSA-382551 Transport of small molecules 5 R-HSA-162582 Signal Transduction 1
Partners
SCN11ASCN1ASCN2ASCN3ASCN4ASCN5ASCN8A
Complex memberships
Voltage-gated sodium channel complex

Evidence

Reading pass · 27 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1998 SCN1B C121W mutation disrupts a conserved cysteine involved in a disulfide bridge maintaining the extracellular immunoglobulin-like fold; co-expression of mutant β1 with a brain Na+ channel α subunit in Xenopus oocytes demonstrated that the mutation interferes with the ability of β1 to modulate channel-gating kinetics, consistent with loss-of-function. Xenopus oocyte co-expression electrophysiology, mutational analysis Nature genetics High 9697698
1994 The SCN1B gene is located on chromosome 19q13.1-q13.2, contains five exons spanning ~9.0 kb, and encodes the β1 subunit required for normal Na+ channel inactivation kinetics; the α subunit alone exhibits voltage-gated Na+ channel function but requires β1 for normal inactivation. Genomic DNA cloning, sequencing, fluorescence in situ hybridization (FISH) Genomics High 7851891
2009 The SCN1B p.R125C mutation causes loss of cell surface expression of the β1 subunit despite normal total cellular expression, regardless of co-expression with Nav1.1 α subunits, resulting in a functional null; Scn1b−/− CA3 neurons fire action potentials with higher peak voltage and amplitude compared to wild type. Biochemical characterization in heterologous system, hippocampal slice recordings in Scn1b−/− mice, acutely dissociated neuron recordings The Journal of neuroscience High 19710327
2007 Loss of β1 (Scn1b null mice) results in ~1.6-fold increase in both peak and persistent sodium current in ventricular myocytes, increased Nav1.5 expression (~1.3-fold), slowed action potential repolarization, and prolonged QT and RR intervals; no discernible alterations in subcellular localization of Na+ channel subunits or associated proteins were observed. ECG recordings, patch-clamp of acutely dissociated ventricular myocytes, immunostaining, Scn1b null mouse model Journal of molecular and cellular cardiology High 17884088
2012 Scn1b null mice show disrupted fasciculation of cerebellar parallel fibers, reduced dentate gyrus granule cell neuron density, increased proliferation of granule cell precursors in the hilus, and defective axonal extension and misorientation of inhibitory neurons, demonstrating that β1 functions as a cell adhesion molecule (CAM) critical for neuronal proliferation, migration, and pathfinding during postnatal brain development. Immunohistochemistry, c-Fos staining, hippocampal/cortical slice recordings, Scn1b null mouse model Proceedings of the National Academy of Sciences of the United States of America High 23277545
2016 β1-C121W subunits are expressed at neuronal cell surfaces in vivo but are incompletely glycosylated and do not associate with VGSC α subunits in the brain; β1-C121W subcellular localization is restricted to neuronal cell bodies and is absent from axon initial segments (cortex, cerebellum) and optic nerve nodes of Ranvier; Scn1b+/W mice are more seizure-susceptible than Scn1b+/− mice, indicating C121W confers a deleterious gain-of-function rather than simple loss-of-function. Co-immunoprecipitation from brain, immunofluorescence, hyperthermia-induced convulsion model comparing heterozygous C121W vs. null mice The Journal of neuroscience High 27277800
2011 Scn1b null dorsal root ganglion (DRG) neurons exhibit a depolarizing shift in voltage dependence of TTX-sensitive INa inactivation, reduced persistent TTX-resistant INa, prolonged recovery of TTX-R INa from inactivation, reduced cell surface expression of Nav1.9, reduced transient outward K+ current, and are hyperexcitable; demonstrating that β1 regulates both INa and IK in nociceptive DRG neurons in vivo. Patch-clamp electrophysiology of acutely dissociated DRG neurons from Scn1b null mice, immunostaining for Nav1.9 cell surface expression The Journal of biological chemistry High 21555511
2014 Loss of Scn1b in cardiac-specific null mice increases tetrodotoxin-sensitive INa (associated with increased Scn3a/Nav1.3 expression) specifically at the cell midsection, causes delayed after-depolarizations, triggered beats, delayed Ca2+ transients, frequent spontaneous Ca2+ release events, and increased susceptibility to polymorphic ventricular arrhythmias; Ca2+ homeostasis alterations were prevented by tetrodotoxin, linking β1-regulated Na+ influx to Ca2+ dysregulation. Macropatch and scanning ion conductance microscopy, patch-clamp, confocal Ca2+ imaging, whole-heart arrhythmia recordings, Scn1b null mouse models The Journal of physiology High 25772295
2014 In a Scn1b-C121W homozygous mouse model, subicular and layer 2/3 pyramidal neurons show increased action potential firing rates due to increased input resistance; no changes in GABAergic interneuron firing; reduced dendritic arborization in subicular pyramidal neurons; retigabine (K+ channel opener reducing input resistance) reduced firing and protected against thermal seizures, implicating a non-interneuron mechanism distinct from Scn1a-based Dravet syndrome models. Patch-clamp in acute brain slices, morphological analysis, pharmacological rescue with retigabine, mouse model Brain : a journal of neurology High 24747835
2008 Zebrafish scn1ba splice variants modulate Na+ currents expressed by zebrafish scn8aa, producing shifts in channel gating mode, increased current amplitude, negative shifts in voltage dependence of activation and inactivation, and increased rate of recovery from inactivation—functions similar to mammalian β1; a C-terminal tyrosine residue critical for ankyrin association in mammalian β1 is conserved in scn1ba_tv1 but absent in the species-specific tv2 isoform. Heterologous expression with patch-clamp electrophysiology, immunohistochemistry in zebrafish BMC genomics Medium 17623064
2008 Morpholino knockdown of zebrafish scn1bb reduces Na+ current amplitudes in Rohon-Beard neurons, impairs touch sensitivity, causes defects in ventrally projecting spinal neuron axon development, olfactory nerve defasciculation, and increased hair cell numbers in the inner ear—demonstrating dual roles as a Na+ current modulator and cell adhesion molecule (CAM) in development. Morpholino knockdown, patch-clamp in Rohon-Beard neurons, behavioral touch assay, immunostaining in zebrafish The Journal of neuroscience Medium 19020043
2011 Post-transcriptional silencing of SCN1B (Nav-β1) in dog cardiac ventricular myocytes reduces late sodium current (INaL) density and accelerates its decay, while SCN2B silencing has the opposite effect; SCN1A mRNA and protein and transient INa remain unchanged, demonstrating isoform-specific modulation of INaL by β1 subunits. siRNA knockdown via viral delivery, whole-cell and perforated patch-clamp, real-time RT-PCR, Western blot in normal and failing canine ventricular myocytes American journal of physiology. Heart and circulatory physiology Medium 21705762
2013 Antisense oligonucleotide silencing of SCN1B (~50% knockdown) in GH3 and H9C2 cell lines reduces α subunit mRNA, protein expression, and Na+ current density without altering voltage-dependent or kinetic properties; β1 silencing differentially reduces Nav1.1, Nav1.3, and Nav1.6 in GH3 cells while Nav1.2 is unaffected, and reduces Nav1.5 in H9C2 cells, demonstrating isoform-specific regulation of Na+ channel expression. Antisense oligonucleotide silencing, RT-PCR, Western blot, patch-clamp in rat cell lines Biology of the cell Medium 24138709
2018 The GEFS+ mutation β1-p.D25N causes a maturation (glycosylation) defect of the β1 protein leading to reduced plasma membrane targeting; co-expression of D25N-β1 with Nav1.2, Nav1.4, or Nav1.5 in HEK293 cells results in reduced Na+ channel functional expression and negative shifts in steady-state activation and inactivation curves, suggesting D25N abolishes β1's ability to interact with α subunits. Heterologous co-expression in HEK293 cells, patch-clamp, glycosylation analysis, membrane targeting assay Human mutation Medium 29992740
2014 The SCN1B β1b-P213T mutation increases late Na+ current and subtly alters Nav1.5 function (shifts window current, accelerates recovery from inactivation, decreases slow inactivation rate) in HEK cells; overexpression of mutant β1b in HL-1 cardiomyocytes significantly increases action potential duration, implicating SCN1Bb as a susceptibility gene for long QT syndrome. Patch-clamp in HEK and HL-1 cells with β1b overexpression Heart rhythm Medium 24662403
2019 SCN1B-p.Arg85Cys expressed in heterologous cells shows normal cell surface expression but loss of β1-mediated modification of Nav1.1-generated sodium current, establishing this variant as a loss-of-function mutation that disrupts channel modulation without trafficking deficiency. Heterologous cell expression with patch-clamp electrophysiology and surface expression assay Annals of clinical and translational neurology Medium 31709768
2020 SCN1B mutation c.308A>T (β1-p.D103V) decreases Na+ current density when co-expressed with Nav1.5 or Nav1.1 in tsA201 cells; β1b-D103V does not affect Nav1.1 current density but induces a positive shift in inactivation voltage-dependence and faster recovery from inactivation for Nav1.1, and has no effect on Nav1.5 properties—demonstrating subunit- and α-subunit-specific loss-of-function effects. Whole-cell patch-clamp in tsA201 cells with co-expression of α and β subunits Frontiers in cell and developmental biology Medium 33134290
2022 Scn1b null neonatal mice have sinoatrial node dysfunction, increased atrial collagen accumulation, susceptibility to pacing-induced atrial fibrillation (AF), increased cholinergic innervation of the SAN, prolonged action potential duration in atrial myocytes with increased late INa and reduced L-type Ca2+ current; atropine reduced AF incidence, implicating autonomic dysregulation as a contributing mechanism. Electrophysiology (patch-clamp), pacing-induced AF protocol, histology, pharmacological intervention (atropine), Scn1b null mouse model JCI insight High 35603785
2022 Cardiac-specific inducible deletion of Scn1b in adult mice increases fast (+20%) and slow (+140%) inactivating components of INa, compromises diastolic function and ventricular compliance (with preserved systolic function), and delays Ca2+ transient kinetics; inhibition of late INa with GS967 normalizes LV filling pattern and Ca2+ transient defects, demonstrating that β1/β1B subunits regulate Na+ influx and Ca2+ cycling to control diastolic function. Conditional cardiac-specific Scn1b knockout, patch-clamp, echocardiography, invasive hemodynamics, Ca2+ imaging, pharmacological rescue American journal of physiology. Heart and circulatory physiology High 35394857
2025 Bilateral intracerebroventricular administration of AAV encoding β1 cDNA (AAV-Navβ1) at postnatal day 2 (but not P10) in Scn1b null mice reduces spontaneous seizure severity and duration, prolongs lifespan, prevents hyperthermia-induced seizures, and restores cortical neuron excitability; β1 expression is confirmed in both excitatory and inhibitory neurons—demonstrating that early gene replacement is sufficient to rescue key disease phenotypes. AAV gene delivery, EEG/seizure monitoring, hyperthermia challenge, patch-clamp electrophysiology in Scn1b null mouse model The Journal of clinical investigation High 39847501
2025 Scn1b null Purkinje cells (PCs) have reduced transient and resurgent Na+ current densities, increased thresholds for action potential initiation, and decreased repetitive firing frequency; PC-specific deletion of Scn1b produces ataxia, and reduced PC excitability is proposed to underlie the ataxic phenotype and potentially impair seizure termination via cerebellar output. PC-specific conditional Scn1b knockout, patch-clamp in cerebellar slices, behavioral ataxia testing, CRISPR V5-tagged β1 mouse for expression mapping JCI insight High 40923316
2023 Loss of Scn1b in hippocampal CA1 pyramidal neurons results in enhanced intrinsic excitability, smaller but more facilitating EPSCs and IPSCs, larger postsynaptic potentials, reduced intrinsic firing of parvalbumin-expressing interneurons, and disrupted recruitment of parvalbumin- and somatostatin-expressing interneurons, producing fundamentally altered hippocampal input/output functions. Slice electrophysiology (patch-clamp), interneuron-specific recording, patterned Schaffer collateral stimulation in Scn1b KO mice The Journal of neuroscience High 37845033
2024 SCN1B mimetic peptide βadp1 disrupts β1-mediated intercellular adhesion in cardiac perinexii (intercalated disc nanodomains enriched in Nav channels) and increases β1-regulated intramembrane proteolysis (RIP) continuously over 48 h; a shorter peptide LQLEED mimics inhibitory effects, while dimeric LQLEED peptides paradoxically promote adhesion and only transiently boost RIP; DAPT (RIP inhibitor) reduces βadp1's adhesion-disrupting effects, linking β1 CAM function to RIP-mediated signaling. Patch-clamp in neonatal rat cardiomyocytes, electric cell substrate impedance sensing (ECIS) in β1-expressing cells, pharmacological inhibition of RIP with DAPT Journal of molecular and cellular cardiology Medium 38942073
2025 Self-administered (but not experimenter-administered) heroin reduces NAc β1 (SCN1b) protein levels in rats; viral-mediated reduction of NAc SCN1b increases medium spiny neuron (MSN) intrinsic excitability without altering glutamatergic or GABAergic synaptic transmission; reduced NAc SCN1b significantly increases cue-reinstated heroin seeking, demonstrating that β1 normally limits MSN excitability and cue-driven opioid seeking in the nucleus accumbens. Heroin self-administration, viral knockdown, patch-clamp electrophysiology in NAc MSNs, reinstatement behavioral testing in rats eNeuro Medium 39947903
2025 Scn1b-c.265C>T (p.R89C) knock-in mouse cardiomyocytes show increased transient outward K+ current (Ito) density and ventricular fibrosis; mice are susceptible to pacing-induced cardiac arrhythmias; patient-derived iPSC-CMs with biallelic SCN1B-c.265C>T show increased INa, late INa, and Ito densities; increased Ito is a common cardiac alteration in both mouse and human DEE52 models. CRISPR knock-in mouse model, patch-clamp, pacing-induced arrhythmia, iPSC-CM differentiation from DEE52 patients, cardiac histology JCI insight High 40763036
2020 SCN1B variant A197V in Brugada syndrome patients markedly decreases Na+ current density when co-expressed with SCN5A/Nav1.5 in HEK293 cells, decelerates activation velocity, and reduces Nav1.5 plasma membrane distribution; no significant changes in recovery from inactivation. Whole-cell patch-clamp in HEK293 cells, cell surface protein analysis Archives of medical research Medium 32192759
2023 Reduced variability of INa density in Scn1b null cortical pyramidal neurons enhances spike timing correlations between neurons and impairs spike-triggered average current pattern diversity; computational modeling shows that broad INa density ranges (dependent on β1 expression) confer a broad spectrum of spike patterning and displace synchronization thresholds in network models, demonstrating that β1-regulated INa heterogeneity regulates spike pattern diversity and network synchronization. Patch-clamp recording from constitutive and inducible Scn1b null cortical neurons, computational network modeling, TTX pharmacology Scientific reports Medium 37264112

Source papers

Stage 0 corpus · 65 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1998 Febrile seizures and generalized epilepsy associated with a mutation in the Na+-channel beta1 subunit gene SCN1B. Nature genetics 816 9697698
2006 Temporal lobe epilepsy and GEFS+ phenotypes associated with SCN1B mutations. Brain : a journal of neurology 209 17020904
2009 A functional null mutation of SCN1B in a patient with Dravet syndrome. The Journal of neuroscience : the official journal of the Society for Neuroscience 194 19710327
2003 A deletion in SCN1B is associated with febrile seizures and early-onset absence epilepsy. Neurology 135 14504340
2002 Generalized epilepsy with febrile seizures plus: mutation of the sodium channel subunit SCN1B. Neurology 119 12011299
2007 Sodium channel Scn1b null mice exhibit prolonged QT and RR intervals. Journal of molecular and cellular cardiology 118 17884088
2012 A homozygous mutation of voltage-gated sodium channel β(I) gene SCN1B in a patient with Dravet syndrome. Epilepsia 71 23148524
2014 Scn1b deletion leads to increased tetrodotoxin-sensitive sodium current, altered intracellular calcium homeostasis and arrhythmias in murine hearts. The Journal of physiology 64 25772295
2012 Abnormal neuronal patterning occurs during early postnatal brain development of Scn1b-null mice and precedes hyperexcitability. Proceedings of the National Academy of Sciences of the United States of America 64 23277545
2008 SCN1A, SCN1B, and GABRG2 gene mutation analysis in Chinese families with generalized epilepsy with febrile seizures plus. Journal of human genetics 56 18566737
2005 Mutation in the Na+ channel subunit SCN1B produces paradoxical changes in peripheral nerve excitability. Brain : a journal of neurology 51 15857929
2004 Generalized epilepsy with febrile seizures plus (GEFS+): clinical spectrum in seven Italian families unrelated to SCN1A, SCN1B, and GABRG2 gene mutations. Epilepsia 49 14738422
2014 Reduced dendritic arborization and hyperexcitability of pyramidal neurons in a Scn1b-based model of Dravet syndrome. Brain : a journal of neurology 47 24747835
1994 Genomic organization and chromosomal assignment of the human voltage-gated Na+ channel beta 1 subunit gene (SCN1B). Genomics 42 7851891
2011 Na+ channel Scn1b gene regulates dorsal root ganglion nociceptor excitability in vivo. The Journal of biological chemistry 41 21555511
2019 SCN1B-linked early infantile developmental and epileptic encephalopathy. Annals of clinical and translational neurology 37 31709768
2017 Confirming the recessive inheritance of SCN1B mutations in developmental epileptic encephalopathy. Clinical genetics 37 28218389
2016 β1-C121W Is Down But Not Out: Epilepsy-Associated Scn1b-C121W Results in a Deleterious Gain-of-Function. The Journal of neuroscience : the official journal of the Society for Neuroscience 35 27277800
2014 A missense mutation in the sodium channel β1b subunit reveals SCN1B as a susceptibility gene underlying long QT syndrome. Heart rhythm 32 24662403
2013 Case-control association study of polymorphisms in the voltage-gated sodium channel genes SCN1A, SCN2A, SCN3A, SCN1B, and SCN2B and epilepsy. Human genetics 31 24337656
2019 Studying Brugada Syndrome With an SCN1B Variants in Human-Induced Pluripotent Stem Cell-Derived Cardiomyocytes. Frontiers in cell and developmental biology 26 31737628
2011 Post-transcriptional silencing of SCN1B and SCN2B genes modulates late sodium current in cardiac myocytes from normal dogs and dogs with chronic heart failure. American journal of physiology. Heart and circulatory physiology 26 21705762
2014 SCN1B gene variants in Brugada Syndrome: a study of 145 SCN5A-negative patients. Scientific reports 21 25253298
2010 New mutation c.374C>T and a putative disease-associated haplotype within SCN1B gene in Tunisian families with febrile seizures. European journal of neurology 21 21040232
2022 Neonatal Scn1b-null mice have sinoatrial node dysfunction, altered atrial structure, and atrial fibrillation. JCI insight 19 35603785
2007 Cloning and expression of a zebrafish SCN1B ortholog and identification of a species-specific splice variant. BMC genomics 18 17623064
2008 scn1bb, a zebrafish ortholog of SCN1B expressed in excitable and nonexcitable cells, affects motor neuron axon morphology and touch sensitivity. The Journal of neuroscience : the official journal of the Society for Neuroscience 17 19020043
2022 SCN1B Genetic Variants: A Review of the Spectrum of Clinical Phenotypes and a Report of Early Myoclonic Encephalopathy. Children (Basel, Switzerland) 16 36291443
2013 Antisense-mediated post-transcriptional silencing of SCN1B gene modulates sodium channel functional expression. Biology of the cell 16 24138709
2018 Lack of genotype-phenotype correlation in Brugada Syndrome and Sudden Arrhythmic Death Syndrome families with reported pathogenic SCN1B variants. Heart rhythm 15 29758173
2023 Epilepsy and sudden unexpected death in epilepsy in a mouse model of human SCN1B-linked developmental and epileptic encephalopathy. Brain communications 14 38425576
2019 SCN1B and SCN2B gene variants analysis in dravet syndrome patients: Analysis of 22 cases. Medicine 13 30921204
2020 An SCN1B Variant Affects Both Cardiac-Type (NaV1.5) and Brain-Type (NaV1.1) Sodium Currents and Contributes to Complex Concomitant Brain and Cardiac Disorders. Frontiers in cell and developmental biology 12 33134290
2019 Developmental and epileptic encephalopathy in two siblings with a novel, homozygous missense variant in SCN1B. American journal of medical genetics. Part A 12 31465153
2012 Do mutations in SCN1B cause Dravet syndrome? Epilepsy research 12 23182416
2000 Study of the voltage-gated sodium channel beta 1 subunit gene (SCN1B) in the benign familial infantile convulsions syndrome (BFIC). Human mutation 12 10923035
2020 Long non-coding RNA LINC01116 regulated miR-744-5p/SCN1B axis to exacerbate lung squamous cell carcinoma. Cancer biomarkers : section A of Disease markers 11 32538822
2007 Floxed allele for conditional inactivation of the voltage-gated sodium channel beta1 subunit Scn1b. Genesis (New York, N.Y. : 2000) 11 17868089
2022 Scn1b expression in the adult mouse heart modulates Na+ influx in myocytes and reveals a mechanistic link between Na+ entry and diastolic function. American journal of physiology. Heart and circulatory physiology 10 35394857
2023 The relationship between miRNA-210 and SCN1B in fetal rats with hypoxic-ischemic brain injury. Bioscience reports 7 36541246
2018 A mutation of SCN1B associated with GEFS+ causes functional and maturation defects of the voltage-dependent sodium channel. Human mutation 7 29992740
2025 Neonatal but not juvenile gene therapy reduces seizures and prolongs lifespan in SCN1B-Dravet syndrome mice. The Journal of clinical investigation 6 39847501
2021 Generation of SCN1B knock out induced pluripotent stem cell (iPSC) line (refractory epilepsy syndrome and Brugada syndrome related cell line). Stem cell research 6 34583279
2007 Mutation analysis of candidate genes SCN1B, KCND3 and ANK2 in patients with clinical diagnosis of long QT syndrome. Physiological research 6 18052691
2011 SCN1B is not related to benign partial epilepsy in infancy or convulsions with gastroenteritis. Neuropediatrics 5 21882141
2020 Brugada Syndrome Caused by Sodium Channel Dysfunction Associated with a SCN1B Variant A197V. Archives of medical research 4 32192759
2017 Association of a synonymous SCN1B variant affecting splicing efficiency with Benign Familial Infantile Epilepsy (BFIE). European journal of paediatric neurology : EJPN : official journal of the European Paediatric Neurology Society 4 28566192
2017 Dravet syndrome with SCN1B gene mutation: A rare entity. Neurology India 4 28681755
2010 A novel microsatellite polymorphism of sodium channel beta1-subunit gene (SCN1B) may underlie abnormal cardiac excitation manifested by coved-type ST-elevation compatible with Brugada syndrome in Japanese. International journal of clinical pharmacology and therapeutics 4 20137763
2008 GEFS+ is not related to the most common mutations of SCN1B, SCN1A and GABRG2 in two Tunisian families. Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology 4 18175077
2025 Altered cardiac excitability and arrhythmia in models of SCN1B-linked developmental and epileptic encephalopathy. JCI insight 3 40763036
2024 Development and characterization of the mode-of-action of inhibitory and agonist peptides targeting the voltage-gated sodium channel SCN1B beta-subunit. Journal of molecular and cellular cardiology 3 38942073
2023 Heterogeneity of voltage gated sodium current density between neurons decorrelates spiking and suppresses network synchronization in Scn1b null mouse models. Scientific reports 3 37264112
2015 SCN1A and SCN1B gene polymorphisms and their association with plasma concentrations of carbamazepine and carbamazepine 10, 11 epoxide in Iranian epileptic patients. Iranian journal of basic medical sciences 3 26877851
2005 Involvement of Scn1b and Kcna1 ion channels in audiogenic seizures and PTZ-induced epilepsy. Epilepsy research 3 16157473
2025 Ataxia and cerebellar hypoexcitability in a mouse model of SCN1B-linked Dravet syndrome. JCI insight 2 40923316
2023 Complex Synaptic and Intrinsic Interactions Disrupt Input/Output Functions in the Hippocampus of Scn1b Knock-Out Mice. The Journal of neuroscience : the official journal of the Society for Neuroscience 2 37845033
2012 Mutation analysis of the candidate genes SCN1B-4B, FHL1, and LMNA in patients with arrhythmogenic right ventricular cardiomyopathy. Applied & translational genomics 2 27896052
2025 Heroin Regulates the Voltage-Gated Sodium Channel Auxiliary Subunit, SCN1b, to Modulate Nucleus Accumbens Medium Spiny Neuron Intrinsic Excitability and Cue-Induced Heroin Seeking. eNeuro 1 39947903
2026 Identification of a Novel Homozygous SCN1B Splice-Site Variant in a Consanguineous Families With Early-Onset Epilepsy: A Case Series and Review of Literature. Molecular genetics & genomic medicine 0 42046183
2025 A Novel Mouse Model for Developmental and Epileptic Encephalopathy by Purkinje Cell-Specific Deletion of Scn1b. The Journal of neuroscience : the official journal of the Society for Neuroscience 0 41162148
2024 Decreased ability to manage increases in reactive oxygen species may underlie susceptibility to arrhythmias in mice lacking Scn1b. American journal of physiology. Heart and circulatory physiology 0 39120465
2024 A novel mouse model for developmental and epileptic encephalopathy by Purkinje cell-specific deletion of Scn1b. bioRxiv : the preprint server for biology 0 39605540
2023 Complex synaptic and intrinsic interactions disrupt input/output functions in the hippocampus of Scn1b knockout mice. bioRxiv : the preprint server for biology 0 37163033
2012 [Expression of Kir2.1, SCN5a and SCN1b channel genes in mouse cardiomyocytes with various electric properties: patch clamp combined with single cell RT-PCR study]. Sheng li xue bao : [Acta physiologica Sinica] 0 22348965