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    GENE:

    SCN8A (Sodium Voltage-Gated Channel Alpha Subunit 8)

    i
    Other names: SCN8A, Sodium Voltage-Gated Channel Alpha Subunit 8, Sodium Channel Voltage Gated, Type VIII Alpha Subunit, Voltage-Gated Sodium Channel Subunit Alpha Nav1.6, Sodium Channel Protein Type 8 Subunit Alpha, MED, Sodium Channel Voltage Gated Type VIII Alpha Polypeptide, Sodium Channel Voltage Gated Type VIII Alpha Subunit, Voltage-Gated Sodium Channel Type VIII Alpha Protein, Sodium Channel Protein Type VIII Subunit Alpha, HNa6/Scn8a Voltage-Gated Sodium Channel, CERIII, EIEE13, MYOCL2, Nav1.6, BFIS5, NaCh6, CIAT, PN4
    25d
    EMBOLD: A Clinical Trial of PRAX-562 in Subjects With Developmental and Epileptic Encephalopathies (DEE) (clinicaltrials.gov)
    P2/3, N=77, Active, not recruiting, Praxis Precision Medicines | Recruiting --> Active, not recruiting | Trial primary completion date: Mar 2026 --> Nov 2025
    Enrollment closed • Trial primary completion date
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    SCN8A (Sodium Voltage-Gated Channel Alpha Subunit 8)
    5ms
    Identification of novel variants with predicted pathogenicity as key targets in esophageal cancer. (PubMed, Cell Mol Biol (Noisy-le-grand))
    Protein stability analysis confirmed their destabilizing effects, while functional enrichment highlighted their involvement in key pathways driving tumorigenesis. This study identified 11 key DEGs harboring potentially pathogenic novel missense variants, highlighting vulnerabilities for precision-targeted therapies in EC.
    Journal
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    ABCC2 (ATP Binding Cassette Subfamily C Member 2) • HNRNPD (Heterogeneous Nuclear Ribonucleoprotein D) • SCN8A (Sodium Voltage-Gated Channel Alpha Subunit 8) • CALM2 (Calmodulin 2) • COL5A2 (Collagen Type V Alpha 2 Chain) • PSMC1 (Proteasome 26S Subunit, ATPase 1) • RPL23 (Ribosomal Protein L23) • TBL1XR1 (TBL1X Receptor 1)
    5ms
    Voltage-Gated sodium channel Nav1.6 mediates glioblastoma proliferation and migration via Na+/H+ Exchanger-1 and inhibits apoptosis through ERK-AKT pathway. (PubMed, Mol Biol Rep)
    Nav1.6 promotes GBM progression by regulating ion homeostasis via NHE1 and activating AKT/ERK pathways. Dual targeting of Nav1.6 and NHE1 may offer a promising strategy to inhibit proliferation and induce apoptosis in GBM.
    Journal
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    CASP3 (Caspase 3) • SCN8A (Sodium Voltage-Gated Channel Alpha Subunit 8)
    5ms
    Structure and function of voltage-gated sodium channel Nav1.6: Involvement in the pathological process of neural injury. (PubMed, Neural Regen Res)
    Key findings include the following: (1) Epilepsy studies reveal more than 250 sodium voltage-gated channel alpha subunit 8 mutations with distinct genotype-phenotype correlations, where gain-of-function variants lead to severe epileptic encephalopathies, while loss-of-function variants are associated with generalized epilepsy, highlighting the potential of Nav1.6-selective blockers such as XEN901 and GS967...(4) Amyotrophic lateral sclerosis involves Nav1.6-dependent cortical hyperexcitability preceding motor neuron degeneration, with riluzole showing partial efficacy through sodium current modulation...Future directions emphasize the integration of advanced technologies-such as singlecell multiomics to map neuronal subtype-specific expression patterns, patient-derived organoids for personalized drug testing, and machine learning-assisted drug design-to accelerate translation. Large-scale collaborative efforts will be essential to validate therapeutic candidates and establish genotype-guided treatment protocols for Nav1.6-related disorders.
    Journal
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    TNFA (Tumor Necrosis Factor-Alpha) • APP (Amyloid Beta Precursor Protein) • NFATC1 (Nuclear Factor Of Activated T Cells 1) • SCN8A (Sodium Voltage-Gated Channel Alpha Subunit 8)
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    riluzole
    6ms
    Effectiveness and safety of riluzole for the treatment of seizures in individuals with SCN8A developmental and epileptic encephalopathy (SCN8A-DEE). (ACTRN12625000845437)
    P2/3, N=5, Not yet recruiting, University of Melbourne
    New P2/3 trial
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    SCN8A (Sodium Voltage-Gated Channel Alpha Subunit 8)
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    riluzole
    7ms
    Nav1.6 drives colorectal cancer proliferation and invasion through MAPK signaling pathway. (PubMed, World J Gastrointest Oncol)
    These findings suggest that Nav1.6 promotes CRC cell proliferation and invasion which is related to the MAPK signaling pathway.
    Journal
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    SCN8A (Sodium Voltage-Gated Channel Alpha Subunit 8)
    7ms
    Extension Study to Evaluate How Safe and Tolerable NBI-921352 is as an Adjunctive Therapy for Participants With SCN8A-DEE (clinicaltrials.gov)
    P2, N=8, Active, not recruiting, Neurocrine Biosciences | Enrolling by invitation --> Active, not recruiting | N=52 --> 8
    Enrollment closed • Enrollment change
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    SCN8A (Sodium Voltage-Gated Channel Alpha Subunit 8)
    7ms
    Study to Evaluate NBI-921352 as Adjunctive Therapy in Subjects With SCN8A Developmental and Epileptic Encephalopathy Syndrome (SCN8A-DEE) (clinicaltrials.gov)
    P2, N=8, Terminated, Neurocrine Biosciences | N=52 --> 8 | Active, not recruiting --> Terminated; This study was prematurely terminated due to sponsor decision.
    Enrollment change • Trial termination
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    SCN8A (Sodium Voltage-Gated Channel Alpha Subunit 8)
    10ms
    Retrospective clinical and molecular characterisation of patients with penile intraepithelial neoplasia. (PubMed, BJU Int)
    We identified seven overexpressed genes in patients with PeIN recurrence. Some of these transcripts were previously reported to be involved in invasive penile cancer. These findings provide molecular evidence, that PeIN is a precursor lesion with a correlation to invasive penile cancer, and could potentially lead to new topical treatment strategies for PeIN and low-risk penile cancer.
    Retrospective data • Journal
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    MYC (V-myc avian myelocytomatosis viral oncogene homolog) • SCN8A (Sodium Voltage-Gated Channel Alpha Subunit 8)
    12ms
    Study to Evaluate NBI-921352 as Adjunctive Therapy in Subjects With SCN8A Developmental and Epileptic Encephalopathy Syndrome (SCN8A-DEE) (clinicaltrials.gov)
    P2, N=52, Active, not recruiting, Neurocrine Biosciences | Recruiting --> Active, not recruiting
    Enrollment closed
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    SCN8A (Sodium Voltage-Gated Channel Alpha Subunit 8)
    2years
    Study to Evaluate NBI-921352 as Adjunctive Therapy in Subjects With SCN8A Developmental and Epileptic Encephalopathy Syndrome (SCN8A-DEE) (clinicaltrials.gov)
    P2, N=52, Recruiting, Neurocrine Biosciences | Trial completion date: Feb 2024 --> Dec 2025 | Trial primary completion date: Jan 2024 --> Dec 2025
    Trial completion date • Trial primary completion date
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    SCN8A (Sodium Voltage-Gated Channel Alpha Subunit 8)