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FLASH GENE

Symbol

SCN10A

contributors: mct/npt/pgu - updated : 08-02-2019

HGNC name	sodium channel, voltage-gated, type X, alpha subunit
HGNC id	10582

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains	four transmembrane domains of homology, each with six alpha helical membrane spanning segments, and two cytoplasmic loops
	an Iq domain

HOMOLOGY

Homologene

FAMILY

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

CELLULAR PROCESS

PHYSIOLOGICAL PROCESS

PATHWAY

metabolism

signaling

a component

protein constituent of membrane

INTERACTION

DNA

RNA

small molecule

protein	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

REGULATION

ASSOCIATED DISORDERS

corresponding disease(s)

FEPS2

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein 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

Susceptibility

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
Marker
Therapy target
	System Type Disorder Pubmed cardiovascular rythm   is a novel target in understanding cardiac electrophysiology and SCN10A-related arrhythmias immunology autoimmune multiple sclerosis could serve as a target for future drug-based interventions to treat cerebellar dysfunction in MS

ANIMAL & CELL MODELS

	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”)