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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
  • 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”)