Affinage

SCN1B

Sodium channel regulatory subunit beta-1 · UniProt Q07699

Length
218 aa
Mass
24.7 kDa
Annotated
2026-06-10
65 papers in source corpus 30 papers cited in narrative 30 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 4/4 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

SCN1B encodes the voltage-gated sodium channel β1 subunit (and the splice variant β1B), a multifunctional protein that modulates the gating kinetics and surface expression of multiple Nav α subunit isoforms and acts as a cell-adhesion molecule governing neuronal pathfinding (PMID:9697698, PMID:23277545, PMID:19020043). β1 modulation of channel gating depends on a conserved extracellular immunoglobulin-like disulfide bridge; the C121W mutation that disrupts this bridge abolishes β1-mediated gating modulation of co-expressed brain Nav α subunits (PMID:9697698). β1 regulates Nav α subunits in an isoform-specific manner, controlling surface density of Nav1.1, Nav1.3, Nav1.5, Nav1.6 and Nav1.9 across brain, cardiac and sensory tissues (PMID:21555511, PMID:24138709, PMID:33134290). Loss of β1 increases sodium current — including persistent/late INa — and raises Nav protein levels, producing cardiac phenotypes spanning prolonged repolarization and QTc, atrial fibrillation with sinoatrial node dysfunction, impaired diastolic function, and arrhythmia susceptibility rescued pharmacologically by late-INa or muscarinic blockade (PMID:17884088, PMID:35394857, PMID:35603785, PMID:25772295). In the brain, β1 deletion disrupts early postnatal axonal fasciculation and neuronal pathfinding before driving network hyperexcitability, with region- and cell-type-specific effects on pyramidal neuron and cerebellar Purkinje cell firing that underlie epilepsy and ataxia (PMID:23277545, PMID:24747835, PMID:40923316, PMID:41162148). β1 additionally undergoes regulated intramembrane proteolysis that is mechanistically coupled to its trans-adhesion function (PMID:38942073). Human loss-of-function and splicing variants cause epilepsy phenotypes including benign familial infantile epilepsy and the developmental and epileptic encephalopathy DEE52, and AAV-mediated restoration of β1 in neonatal Scn1b-null brain rescues seizures and excitability, establishing β1 deficiency as the disease driver (PMID:31709768, PMID:28566192, PMID:39847501).

Mechanistic history

Synthesis pass · year-by-year structured walk · 14 steps
  1. 1994 High

    Establishing the genomic structure and chromosomal location of SCN1B provided the molecular foundation for linking the gene to inherited disease.

    Evidence Genomic DNA cloning, intron-exon boundary sequencing and FISH mapping to 19q13.1-q13.2

    PMID:7851891

    Open questions at the time
    • Does not address protein function
    • No isoform/splice-variant catalog
  2. 1998 High

    The first functional study showed β1 modulates Nav α subunit gating and that the epilepsy-associated C121W mutation disrupts an extracellular disulfide bridge to abolish this modulation, defining a loss-of-function disease mechanism.

    Evidence Co-expression of mutant β1 with brain Nav α subunit in Xenopus oocytes with electrophysiology

    PMID:9697698

    Open questions at the time
    • Heterologous oocyte system, not native neurons
    • Single mutation; in vivo consequences untested
  3. 2007 High

    Cardiac null mice revealed β1 is required for normal cardiac excitability, restraining peak and persistent sodium current and Nav1.5 levels.

    Evidence Scn1b null mouse with ventricular myocyte patch-clamp, ECG and immunostaining

    PMID:17884088

    Open questions at the time
    • Mechanism of increased Nav1.5 expression unresolved
    • Constitutive KO confounds developmental vs acute roles
  4. 2009 High

    A recessive human mutation (R125C) was shown to act as a functional null via abolished surface trafficking, while native CA3 recordings dissociated β1's gating effects from sodium current density.

    Evidence Heterologous surface biotinylation plus hippocampal slice recordings in Scn1b-null mice

    PMID:19710327

    Open questions at the time
    • Trafficking machinery for β1 not identified
    • Unchanged current density vs altered AP not fully reconciled
  5. 2011 Medium

    Studies in sensory and cardiac systems established β1 as an isoform-selective regulator of sodium and potassium currents, with opposite-direction modulation of late INa relative to β2.

    Evidence DRG patch-clamp/biotinylation in Scn1b null mice and siRNA knockdown in dog ventricular cardiomyocytes

    PMID:21555511 PMID:21705762

    Open questions at the time
    • Molecular basis of β1 vs β2 opposite effects unknown
    • K+ current modulation mechanism unclear
  6. 2012 High

    β1 was shown to control early postnatal neuronal pathfinding and fasciculation, a developmental role preceding network hyperexcitability and distinguishing its adhesion function from channel modulation.

    Evidence Histology, immunofluorescence and slice electrophysiology of Scn1b null mouse brain at P5 and P16

    PMID:23277545

    Open questions at the time
    • Adhesion partners mediating pathfinding not identified here
    • Causal link between pathfinding defects and later seizures untested
  7. 2013 Medium

    Knockdown across cell lines demonstrated β1 sets α subunit mRNA, protein and current density in an isoform-specific way without changing gating, separating its trafficking/expression role from its gating role.

    Evidence Antisense knockdown with RT-PCR, Western blot and patch-clamp in GH3 and H9C2 cells

    PMID:24138709

    Open questions at the time
    • Mechanism of isoform selectivity unknown
    • Cell-line context may not reflect native neurons
  8. 2014 High

    Multiple in vivo and heterologous models showed the C121W mutation is a deleterious gain-of-function with mislocalized, under-glycosylated β1, and defined circuit-level (pyramidal vs interneuron) drivers of seizure susceptibility distinct from Scn1a-based Dravet models.

    Evidence Scn1b-C121W knock-in and homozygous mice with Co-IP, immunofluorescence, slice patch-clamp, thermal seizure assays and retigabine rescue; cardiac-specific KO with Ca2+ imaging and arrhythmia induction

    PMID:24747835 PMID:25772295 PMID:27277800

    Open questions at the time
    • Molecular nature of the C121W gain-of-function unresolved
    • Link between glycosylation defect and mislocalization mechanistically incomplete
  9. 2018 Medium

    Disease variants were resolved into distinct mechanistic classes — glycosylation/trafficking defects versus pure gating-modulation defects with normal surface expression.

    Evidence Heterologous co-expression of D25N and R85C variants with multiple Nav α subunits, patch-clamp, glycosylation Westerns and surface biotinylation

    PMID:29992740 PMID:31709768

    Open questions at the time
    • Structural basis distinguishing trafficking vs gating effects not defined
    • Patient genotype-phenotype correlation limited
  10. 2020 Medium

    β1 and β1B were shown to produce divergent, isoform-specific effects on cardiac (Nav1.5) versus brain (Nav1.1) sodium currents, explaining how single variants can produce mixed cardiac and neurological phenotypes.

    Evidence Whole-cell patch-clamp in tsA201 cells co-expressing mutant β1/β1B with Nav1.5 or Nav1.1

    PMID:33134290

    Open questions at the time
    • Single mutation tested
    • In vivo relevance of β1 vs β1B divergence untested
  11. 2022 High

    Conditional and developmental cardiac KO models linked β1 loss to late-INa-driven diastolic dysfunction and to atrial fibrillation with sinoatrial node dysfunction and increased cholinergic tone, with pharmacological rescue confirming the late-INa and muscarinic mechanisms.

    Evidence Inducible and neonatal cardiac Scn1b KO with patch-clamp, echocardiography, hemodynamics, histology and GS967/atropine rescue

    PMID:35394857 PMID:35603785

    Open questions at the time
    • Source of increased cholinergic innervation unclear
    • Fibrosis trigger downstream of β1 loss undefined
  12. 2023 Medium

    Brain network and cerebellar studies established that β1 tunes intrinsic excitability and inter-neuronal sodium current heterogeneity, with loss decorrelating spiking, amplifying hippocampal input/output, and causing cerebellar hypoexcitability and ataxia.

    Evidence Constitutive/inducible Scn1b null mice with cortical, CA1 and cerebellar slice patch-clamp, computational modeling, TTX experiments and CRISPR-V5 localization

    PMID:37264112 PMID:37845033 PMID:40923316

    Open questions at the time
    • Causal chain from cellular excitability to behavior incomplete
    • Cell-type-specific contributions not fully separated in constitutive KO
  13. 2024 Medium

    β1 trans-adhesion was mechanistically coupled to regulated intramembrane proteolysis, and β1 loss was linked to compromised mitochondrial energetics and ROS handling in cardiomyocytes, broadening its roles beyond channel modulation.

    Evidence Mimetic/agonist peptide pharmacology with ECIS adhesion and RIP assays plus DAPT inhibition in cardiomyocytes; oxidative challenge, ROS imaging and enzyme assays in Scn1b null hearts

    PMID:38942073 PMID:39120465

    Open questions at the time
    • Transcriptional targets of β1 RIP not identified
    • Mechanism linking β1 to mitochondrial/ROS function unknown
  14. 2025 Medium

    Gene-replacement, knock-in and patient-derived models established that early restoration of β1 rescues the DEE52 phenotype and that variant β1 produces additive α-subunit dysregulation plus a cardiac contribution to SUDEP.

    Evidence Neonatal AAV-β1 delivery with EEG/survival/patch-clamp; R89C knock-in mice and DEE52 iPSC-cardiomyocytes; Purkinje-specific KO with behavior; NAc viral knockdown in heroin self-administration rats

    PMID:38425576 PMID:39847501 PMID:39947903 PMID:40763036 PMID:41162148

    Open questions at the time
    • Therapeutic window narrow (P2 vs P10) and human translation untested
    • Additive transcriptional dysregulation mechanism not fully defined

Open questions

Synthesis pass · forward-looking unresolved questions
  • How β1's adhesion-coupled regulated intramembrane proteolysis controls specific downstream gene programs, and which trans-homophilic and α-subunit binding interfaces mediate isoform-selective trafficking versus gating, remain unresolved.
  • No RIP transcriptional target identified in the corpus
  • No structural model of β1–α subunit or β1–β1 adhesion interfaces
  • Mechanism of isoform-selective α subunit regulation unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0098772 molecular function regulator activity 3 GO:0060089 molecular transducer activity 2 GO:0098631 cell adhesion mediator activity 2
Localization
GO:0005886 plasma membrane 3
Pathway
R-HSA-112316 Neuronal System 3 R-HSA-397014 Muscle contraction 3 R-HSA-1266738 Developmental Biology 2
Partners
SCN1ASCN2ASCN2BSCN3ASCN5ASCN8A
Complex memberships
voltage-gated sodium channel complex

Evidence

Reading pass · 30 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1998 SCN1B encodes a β1 subunit that modulates Na+ channel-gating kinetics; the C121W mutation disrupts a conserved cysteine that maintains an extracellular immunoglobulin-like disulfide bridge, abolishing β1-mediated modulation of channel gating when co-expressed with a brain Na+ channel α subunit in Xenopus oocytes, consistent with a loss-of-function allele. Co-expression of mutant β1 with brain Na+ channel α subunit in Xenopus laevis oocytes; electrophysiology Nature genetics High 9697698
1994 The human SCN1B gene consists of five exons spanning ~9 kb of genomic DNA and maps to chromosome 19q13.1-q13.2 by fluorescence in situ hybridization. Genomic DNA cloning, intron-exon boundary sequencing, FISH Genomics High 7851891
2007 Loss of β1 (Scn1b null mice) increases both peak and persistent ventricular sodium current (~1.6-fold) and Nav1.5 protein expression (~1.3-fold), prolongs action potential repolarization, and results in extended QTc and RR intervals, demonstrating that β1 is required for normal cardiac excitability. Scn1b null mouse model; patch-clamp electrophysiology in acutely dissociated ventricular myocytes; ECG recording; immunostaining Journal of molecular and cellular cardiology High 17884088
2009 The SCN1B p.R125C recessive mutation causes near-absent cell surface expression of β1 despite normal total cellular protein levels, regardless of co-expression with Nav1.1 α subunits. In Scn1b null CA3 neurons, action potentials have higher peak voltage and greater amplitude than wild type, but sodium current density is unchanged. Heterologous expression with cell surface biotinylation; hippocampal slice recordings in Scn1b−/− vs +/+ mice The Journal of neuroscience High 19710327
2011 Scn1b regulates nociceptive DRG neuron excitability in vivo: Scn1b null neurons show a depolarizing shift in TTX-S INa inactivation, reduced persistent TTX-R INa and reduced cell-surface Nav1.9 expression, reduced transient outward K+ current, and resulting neuronal hyperexcitability. Patch-clamp electrophysiology and cell surface biotinylation in acutely dissociated DRG neurons from Scn1b null mice vs. WT The Journal of biological chemistry High 21555511
2012 Scn1b deletion disrupts neuronal pathfinding during early postnatal brain development (P5): null cerebella show disrupted parallel fiber fasciculation, reduced dentate gyrus neuron density, increased granule cell precursor proliferation in the hilus, and defective axonal extension and misorientation of inhibitory neurons, preceding hyperexcitability (onset ~P16). Histological and immunofluorescence analysis of Scn1b null mouse brain at P5 and P16; c-Fos immunostaining; hippocampal/cortical slice electrophysiology Proceedings of the National Academy of Sciences High 23277545
2014 Scn1b deletion in cardiac-specific null mice increases tetrodotoxin-sensitive INa (attributable to increased Nav1.3 protein at the cell midsection), causes delayed after-depolarizations, triggered beats, delayed Ca2+ transients, spontaneous Ca2+ release events, and increased susceptibility to polymorphic ventricular arrhythmias; most Ca2+ homeostasis alterations were prevented by 100 nM TTX. Cardiac-specific Scn1b null mouse; macropatch and scanning ion conductance microscopy; action potential and Ca2+ transient recordings; whole-heart arrhythmia induction The Journal of physiology High 25772295
2014 In an Scn1b-C121W knock-in mouse model, β1-C121W subunits are expressed at neuronal cell bodies but are incompletely glycosylated, do not associate with VGSC α subunits in brain, and are absent from axon initial segments and nodes of Ranvier. Heterozygous Scn1b+/W mice are more susceptible to hyperthermia-induced seizures than heterozygous null (Scn1b+/−) mice, demonstrating the C121W mutation confers a deleterious gain-of-function rather than simple loss-of-function. Scn1b-C121W knock-in mouse; co-immunoprecipitation; immunofluorescence; hyperthermia seizure threshold assay The Journal of neuroscience High 27277800
2014 In a mouse model bearing the human Scn1b-C121W mutation (homozygous), subicular and layer 2/3 pyramidal neurons have increased action potential firing rates due to increased input resistance, with increased spontaneous synaptic activity in the subiculum but not CA1; no changes were seen in GABAergic interneuron firing, contrasting with Scn1a-based Dravet models. Retigabine (a K+ channel opener reducing input resistance) dampened firing and protected against thermal seizures. Scn1b-C121W homozygous mouse model; patch-clamp electrophysiology in brain slices; thermal seizure threshold; pharmacological intervention Brain High 24747835
2011 Post-transcriptional silencing of SCN1B (>80% reduction) in cardiac myocytes reduces late sodium current (INaL) density and accelerates its decay, while siRNA against SCN2B has the opposite effect, demonstrating β1 and β2 subunits exert oppositely directed modulation of INaL in both normal and failing heart myocytes. siRNA-mediated knockdown via viral delivery; whole-cell and perforated patch-clamp; Western blot and RT-PCR in isolated dog ventricular cardiomyocytes American journal of physiology. Heart and circulatory physiology Medium 21705762
2013 Antisense-mediated silencing of SCN1B reduces α subunit mRNA, protein expression and sodium current density in GH3 and H9C2 cells in an isoform-specific manner: Nav1.1, Nav1.3, and Nav1.6 are reduced in GH3 cells, Nav1.5 is reduced in H9C2 cells, while Nav1.2 is unaffected, without altering channel gating kinetics. Antisense oligonucleotide knockdown; RT-PCR; Western blot; whole-cell patch-clamp in rat GH3 and H9C2 cell lines Biology of the cell Medium 24138709
2007 Zebrafish scn1ba splice variants modulate Na+ currents expressed by scn8aa: both produce negative shifts in voltage dependence of activation and inactivation, increased current amplitude, and faster recovery from inactivation, consistent with mammalian β1 subunit function. The C-terminus tyrosine critical for ankyrin association in mammalian β1 is conserved in scn1ba_tv1 but absent in tv2. Heterologous co-expression in Xenopus oocytes or cell lines; electrophysiology; immunohistochemistry in zebrafish tissue BMC genomics Medium 17623064
2008 Morpholino knockdown of zebrafish scn1bb reduces Na+ current amplitudes in Rohon-Beard neurons, impairs touch sensitivity, causes defective development of ventrally projecting spinal neuron axons, defasciculation of the olfactory nerve, and increased inner ear hair cell numbers, demonstrating dual roles as a Na+ current modulator and cell adhesion molecule in vivo. Morpholino knockdown in zebrafish; patch-clamp in Rohon-Beard neurons; behavioral touch assay; morphological analysis The Journal of neuroscience Medium 19020043
2014 The SCN1B β1b-P213T mutation increases late sodium current and subtly alters Nav1.5 gating (shifts window current, accelerates recovery from inactivation, decreases slow inactivation) and significantly prolongs action potential duration in HL-1 cells, identifying SCN1Bb as a susceptibility gene for Long QT syndrome. Whole-cell patch-clamp in HEK cells and HL-1 cardiomyocytes co-expressing β1b-P213T with Nav1.5 Heart rhythm Medium 24662403
2018 The SCN1B-D25N mutation causes a glycosylation (maturation) defect that reduces targeting of β1 to the plasma membrane, abolishes β1-dependent modulation of gating kinetics when co-expressed with Nav1.2, Nav1.4, or Nav1.5 in HEK293 cells, and impairs interaction with the α subunit. Heterologous co-expression in HEK293 cells; whole-cell patch-clamp; Western blot for glycosylation state; cell surface biotinylation Human mutation Medium 29992740
2019 The SCN1B-p.Arg85Cys variant shows normal cell surface expression but loss of β1-mediated modification of Nav1.1-generated sodium current in heterologous cells, establishing it as a loss-of-function variant through a gating modulation defect rather than a trafficking defect. Heterologous expression in HEK cells; whole-cell patch-clamp; surface expression assay Annals of clinical and translational neurology Medium 31709768
2020 The SCN1B mutation β1-D103V (c.308A>T) decreases sodium current density when co-expressed with Nav1.5 or Nav1.1, while β1b-D103V does not affect Nav1.1 current density but causes a positive shift in voltage dependence of inactivation and faster recovery from inactivation, demonstrating isoform-specific effects on cardiac (Nav1.5) and brain (Nav1.1) sodium currents. Whole-cell patch-clamp in tsA201 cells co-expressing mutant β1 or β1b with Nav1.5 or Nav1.1 Frontiers in cell and developmental biology Medium 33134290
2022 Scn1b deletion increases fast (+20%) and slow (+140%) inactivating components of INa in adult mouse cardiomyocytes, compromises diastolic function and ventricular compliance without affecting systolic function; pharmacological inhibition of late INa with GS967 normalized left ventricular filling and isovolumic relaxation time, linking β1/β1B subunits to diastolic function through control of Na+ influx and Ca2+ cycling. Adult cardiac-specific inducible Scn1b knockout mouse; patch-clamp; echocardiography; invasive hemodynamics; Ca2+ imaging; pharmacological rescue with GS967 American journal of physiology. Heart and circulatory physiology High 35394857
2022 Scn1b null neonatal mice develop sinoatrial node dysfunction, atrial fibrillation (AF), atrial collagen accumulation, and increased cholinergic innervation of the SAN. Null atrial myocytes have prolonged action potential duration, increased late sodium current, and reduced L-type calcium current. Atropine reduced AF incidence, indicating that increased cholinergic tone contributes to AF. Scn1b null neonatal mouse model; ECG; pacing-induced AF protocol; histology; patch-clamp; gene expression analysis; atropine pharmacological intervention JCI insight High 35603785
2023 In Scn1b null mice, reduced sodium current (INa) density heterogeneity between cortical layer 6 and subicular pyramidal neurons enhances spike timing correlations and impairs spike-pattern diversity. Low-concentration TTX phenocopies this effect, demonstrating that INa variability between neurons, regulated by β1, decorrelates spiking and suppresses network synchronization. Constitutive and inducible Scn1b null mice; patch-clamp in cortical pyramidal neurons; computational modeling; TTX pharmacological experiments Scientific reports Medium 37264112
2023 Scn1b null mice display ataxia; Purkinje cells (PCs) and cerebellar interneurons in null cerebellar slices have increased thresholds for AP initiation and decreased repetitive firing frequency, associated with reduced transient and resurgent sodium current densities in PCs. Cerebellar output hypoexcitability is proposed to underlie ataxia and to exacerbate seizure severity. Scn1b null mouse behavioral (rotarod, gait); cerebellar slice patch-clamp; sodium current recordings; CRISPR-V5 tagged β1 mouse for localization JCI insight Medium 40923316
2023 In Scn1b null hippocampal CA1, pyramidal neurons have enhanced intrinsic excitability, smaller facilitating EPSCs and IPSCs but larger postsynaptic potentials, and parvalbumin and somatostatin interneuron recruitment is disrupted; together these result in greatly amplified input/output functions upon patterned Schaffer collateral stimulation. Scn1b null mouse; CA1 slice patch-clamp electrophysiology; patterned stimulation protocols; interneuron-specific recordings The Journal of neuroscience Medium 37845033
2025 AAV-mediated delivery of 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 protein was expressed in both excitatory and inhibitory neurons, confirming that early restoration of β1 in brain is sufficient to rescue the DEE52 phenotype. AAV gene therapy in Scn1b null mice; intracerebroventricular injection at P2 vs P10; EEG; seizure scoring; cortical neuron patch-clamp; Western blot The Journal of clinical investigation High 39847501
2025 Self-administered heroin reduces NAc β1 (SCN1b) protein levels in rats. Viral-mediated reduction of NAc SCN1b increases MSN intrinsic excitability without altering synaptic transmission, and increases cue-reinstated heroin seeking, demonstrating that NAc β1 limits cue-induced drug seeking by modulating MSN excitability. Heroin self-administration in rats; Western blot for SCN1b protein; viral-mediated knockdown; patch-clamp electrophysiology in NAc MSNs; cue-reinstatement behavioral assay eNeuro Medium 39947903
2025 Purkinje cell-specific deletion of Scn1b in mice causes marked decrements in Purkinje cell physiology (increased AP threshold, reduced repetitive firing) and motor, social, and cognitive dysfunction without early mortality, establishing cerebellar Purkinje cells as a critical node for SCN1B-related DEE neurological disabilities. Conditional Purkinje cell-specific Scn1b knockout mouse; cerebellar slice patch-clamp; behavioral tests (motor, social, cognitive) The Journal of neuroscience Medium 41162148
2025 Scn1b-C89/C89 (DEE52 variant p.R89C knock-in) mouse cardiomyocytes show increased transient outward K+ current (Ito) and ventricular fibrosis; patient-derived iPSC-CMs with biallelic SCN1B-c.265C>T show increased peak INa, late INa, and Ito. Both models show susceptibility to cardiac arrhythmias, supporting a cardiac contribution to SUDEP in DEE52. Scn1b-p.R89C knock-in mouse; iPSC-CMs from DEE52 patients; patch-clamp; histology; pacing-induced arrhythmia protocol JCI insight Medium 40763036
2024 Loss of Scn1b compromises mitochondrial energetics and ROS-scavenging capacity: cardiomyocytes from Scn1b null mice die faster, accumulate more ROS under oxidative challenge (diamide), and have increased glutathione peroxidase protein expression and activity; intact Scn1b null hearts show higher arrhythmia scores under oxidative stress. Scn1b null mouse; isolated cardiomyocytes and hearts; oxidative challenge with diamide; ROS imaging; enzyme activity assays; gene expression American journal of physiology. Heart and circulatory physiology Medium 39120465
2024 A SCN1B mimetic peptide (βadp1) disrupts β1-mediated intercellular adhesion in cardiac perinexii and increases β1-regulated intramembrane proteolysis (RIP) over 48 h; inhibition of RIP with DAPT reduces βadp1's effect on adhesion. Dimeric agonist peptides (containing LQLEED repeats) acutely promote adhesion and transiently boost RIP, establishing a mechanistic link between β1 adhesion function and RIP-mediated transcriptional signaling. Patch-clamp in neonatal rat cardiomyocytes; electric cell substrate impedance sensing (ECIS); RIP assay; DAPT pharmacological inhibition Journal of molecular and cellular cardiology Medium 38942073
2017 A synonymous SCN1B variant (c.492T>C, p.Tyr164Tyr) disrupts a splicing silencer sequence and causes splicing imbalance between wild-type and mutant exons, confirmed by in vitro splicing assay, contributing to Benign Familial Infantile Epilepsy. Genome-wide linkage analysis; whole exome sequencing; in vitro splicing assay; in silico splicing analysis European journal of paediatric neurology Medium 28566192
2031 In Scn1b-p.R89C knock-in mice, β1-p.R89C polypeptides are expressed at normal brain levels and localize to the plasma membrane with intact regulated intramembrane proteolysis, but produce α subunit subtype-specific effects on sodium current in heterologous cells. Scn1b somatosensory cortex shows increased Scn2a, Scn3a, Scn5a, and Scn1b mRNA; Scn1b null cortex is haploinsufficient for Scn1a, indicating an additive disease mechanism. CRISPR knock-in mouse; heterologous electrophysiology; RT-qPCR; surface biotinylation; RIP assay; hyperthermia seizure threshold; EEG Brain communications Medium 38425576

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 210 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 73 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 38 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
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 22 21040232
2014 SCN1B gene variants in Brugada Syndrome: a study of 145 SCN5A-negative patients. Scientific reports 21 25253298
2022 Neonatal Scn1b-null mice have sinoatrial node dysfunction, altered atrial structure, and atrial fibrillation. JCI insight 20 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
2019 Developmental and epileptic encephalopathy in two siblings with a novel, homozygous missense variant in SCN1B. American journal of medical genetics. Part A 13 31465153
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
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
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 11 35394857
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
2025 Neonatal but not juvenile gene therapy reduces seizures and prolongs lifespan in SCN1B-Dravet syndrome mice. The Journal of clinical investigation 7 39847501
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
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
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 4 38942073
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
2025 Ataxia and cerebellar hypoexcitability in a mouse model of SCN1B-linked Dravet syndrome. JCI insight 3 40923316
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
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

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