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Symbol SCN10A contributors: mct/npt/pgu - updated : 08-02-2019
HGNC name sodium channel, voltage-gated, type X, alpha subunit
HGNC id 10582
Corresponding disease
FEPS2 episodic pain syndrome, familial, 2
Location 3p22.2      Physical location : 38.738.837 - 38.835.501
Synonym name
  • sodium channel, voltage-gated, type X, alpha polypeptide
  • voltage-gated sodium channel subunit alpha Nav1.8
  • peripheral nerve sodium channel 3
  • Synonym symbol(s) Nav1.8, hPN3, SNS, PN3
    TYPE functioning gene
    STRUCTURE 96.66 kb     27 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    MAPPING cloned Y linked N status provisional
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    27 - 5874 - 1956 - 2010 19953341
    27 - 5871 - 1955 - 2010 19953341
    26 - 5580 - 1858 - 2010 19953341
    Type restricted
       expressed in (based on citations)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Cardiovascularheartconducting system    Homo sapiensAdult
    Nervousgangliasensory gangliadorsal root predominantly Homo sapiensAdult
     nervespinal nervesciatic  
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Nervousperipherous    Homo sapiens
    SystemCellPubmedSpeciesStageRna symbol
    Nervousneuron Homo sapiens
    cell lineage
    cell lines
    at STAGE
  • four transmembrane domains of homology, each with six alpha helical membrane spanning segments, and two cytoplasmic loops
  • an Iq domain
  • sodium channel family
  • CATEGORY transport channel
    SUBCELLULAR LOCALIZATION     plasma membrane
    basic FUNCTION
  • voltage-gated, type X,tetrodotoxin resistant, specific to sensory neurons
  • mediates the voltage-dependent sodium ion permeability of excitable membranes
  • contributes a substantial fraction of the current underlying the depolarizing phase of the action potential of dorsal root ganglion (DRG) neurons
  • plays a role in neuropathic pain mechanisms
  • have a central role in the propagation of action potentials in nociceptive nerve fibers
  • may play a role in different pain conditions, and its signaling might be involved in visceral pain
  • modulatory role in the development of cold, but not mechanical allodynia in neuropathic pain conditions
  • function in the transmission of pain signals induced by cold, heat, and mechanical stimuli
  • implicated in modulating the activity of CNS neurons
  • implicated in transducing pain initiated by cold and additionally implicate SCN10A in previously unknown functions in the central nervous system and heart
  • plays a critical role in pain perception
  • activation of ASIC3 and TRPV1 as well as enhanced SCN10A activity are essential for the development of long-lasting hyperalgesia in acid-induced, chronic, widespread muscle pain
  • tetrodotoxin-resistant (TTX-R) sodium channel, that contributes most of the sodium current underlying the action potential upstroke and accounts for most of the current in later spikes in a train
  • strikingly distinct properties of SCN10A, which contribute to the firing properties of human dorsal root ganglion (DRG) neurons
  • plays likely a role in modulating specific aspects of the retinal physiology
    a component
  • protein constituent of membrane
    small molecule
  • binding SCLT1
  • interacting with calmodulin (in native neurons, implicated in the regulation of SCN10A currents that can significantly affect electrogenesis of dorsal root ganglion neurons in which SCN10A is normally expressed)
  • interacting with AQP1 (Aquaporin-1 tunes pain perception by interaction with SCN10A in dorsal root ganglion neurons)
  • KIF5B is required for the forward transport and axonal function of SCN10A, suggesting a mechanism for axonal accumulation of SCN10A in inflammatory pain
  • constitutive binding of SCN10A with ANK3 could contribute to the pathological aspects of illnesses where SCN10A is ectopically expressed in CNS neurons
  • cell & other
    corresponding disease(s) FEPS2
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional     --low  
    may be one of the pathophysiological mechanisms involved in limb lengthening-induced neuropathy
    constitutional germinal mutation     loss of function
    associated with kidney stone disease
    tumoral     --over  
    functional upregulation of SCN10A channels on the membrane of DRG neurons contributes to the development of cancer-induced bone pain
  • to heart block
  • to Brugada syndrome
  • to sudden cardiac death
  • to Sudden unexplained nocturnal death syndrome (SUNDS)
  • Variant & Polymorphism other
  • rs6795970 is associated with a higher risk of heart block and a lower risk of ventricular fibrillation
  • variants at SCN5A-SCN10A associated with Brugada syndrome
  • association between genetic variation in SCN10A, the late sodium current, and alterations in cardiac conduction
  • variants involving SCN10A, which encodes a voltage-gated sodium channel, were already associated with alterations of cardiac conduction parameters and the cardiac rhythm disorder, thereby influencing the cardiac physiology and predisposing to arrhythmia, and sudden cardiac death
  • association of common and rare variants of SCN10A gene with sudden unexplained nocturnal death syndrome
  • rs6795970 in the SCN10A gene, which is reported to carry a high risk of heart block, might be associated with cardiac conduction abnormalities in hypertrophic cardiomyopathy (HCM) patients
  • Candidate gene
    Therapy target
    is a novel target in understanding cardiac electrophysiology and SCN10A-related arrhythmias
    immunologyautoimmunemultiple sclerosis
    could serve as a target for future drug-based interventions to treat cerebellar dysfunction in MS
  • PR interval is shorter in Scn10a-/-mice than in wild-type mice
  • dominant neurobehavioral phenotype termed Possum, characterized by transient whole-body tonic immobility induced by pinching the skin at the back of the neck (“scruffing”)