Na<sub>v</sub>1.1 | Voltage-gated sodium channels | IUPHAR/BPS Guide to PHARMACOLOGY

Nav1.1

Target id: 578

Nomenclature: Nav1.1

Family: Voltage-gated sodium channels

Annotation status:  image of a green circle Annotated and expert reviewed. Please contact us if you can help with updates.  » Email us

   GtoImmuPdb view: OFF :     Currently no data for Nav1.1 in GtoImmuPdb

Gene and Protein Information
Species TM P Loops AA Chromosomal Location Gene Symbol Gene Name Reference
Human 24 4 1998 2q24.3 SCN1A sodium voltage-gated channel alpha subunit 1
Mouse 24 4 1998 2 C1.3 Scn1a sodium channel, voltage-gated, type I, alpha
Rat 24 4 2009 3q21 Scn1a sodium voltage-gated channel alpha subunit 1 24-25
Previous and Unofficial Names
RI | Brain type-1 | Rat-I | sodium channel, voltage-gated, type I, alpha subunit | sodium channel, voltage gated, type I alpha subunit | sodium channel
Database Links
ChEMBL Target
DrugBank Target
Ensembl Gene
Entrez Gene
Human Protein Atlas
KEGG Gene
OMIM
Orphanet
RefSeq Nucleotide
RefSeq Protein
UniProtKB
Wikipedia
Associated Proteins
Heteromeric Pore-forming Subunits
Name References
Not determined
Auxiliary Subunits
Name References
β1 1,32,34
β2 32,48
Other Associated Proteins
Name References
Not determined
Associated Protein Comments
β3 and β4 subunits are also likely to associate singly or in pairs with Nav1.1 but there are limited data on co-expression in heterologous cells and no biochemical data that show association in native tissues.
Functional Characteristics
Activation V0.5 = -20 mV. Fast inactivation (τ = 0.7 ms for peak sodium current).
Voltage Dependence
  V0.5 (mV)  τ (msec)  Reference  Cell type  Species 
Activation  -19.0 – -17.0 (median: -18.0) - 32 Xenopus laevis oocyte Rat
Inactivation  -43.0 – -35.0 (median: -37.0) - 32
Comments  This study included Nav1.1 expressed alone or with β1 or β2.
  V0.5 (mV)  τ (msec)  Reference  Cell type  Species 
Activation  -33.0 - 8 HEK 293 cells. Human
Inactivation  -72.0 - 8
Comments  Cs fluoride as the major intracellular solute.
  V0.5 (mV)  τ (msec)  Reference  Cell type  Species 
Activation  -7.5 - 23 HEK 293 cells. Human
Inactivation  -37.6 - 23
Comments  Cs aspartate as the major intracellular solute.
  V0.5 (mV)  τ (msec)  Reference  Cell type  Species 
Activation  -19.6 – -13.7 - 1 Xenopus laevis oocyte Human
Inactivation  -41.9 – -37.9 - 1
Comments  This study included Nav1.1 expressed with and without β1.
  V0.5 (mV)  τ (msec)  Reference  Cell type  Species 
Activation  -20.5 0.35 3 Human embryonic kidney cells: cell line tsA-201, a derivative of HEK293 Rat
Inactivation  -56.0 - 3
Comments  N-methyl-D-glucamine as major intracellular solute.

Download all structure-activity data for this target as a CSV file

Activators
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Affinity Units Concentration range (M) Holding voltage (mV) Reference
batrachotoxin Hs Activation - - - -
veratridine Hs Activation - - - -
Activator Comments
As Nav1.1 shows close similarity to Nav1.2 in amino acid sequence and in functional properties, it is expected that the activators of Nav1.1 will resemble those of Nav1.2, however there is no published work directly on Nav1.1.
Inhibitors
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Affinity Units Concentration range (M) Holding voltage (mV) Reference
GNE-131 Hs Inhibition 7.3 pIC50 - - 13
pIC50 7.3 (IC50 4.5x10-8 M) [13]
Description: IC50s were generated on a PatchXpress automated voltage-clamp platform, with the membrane potential maintained at a voltage yielding full inactivation of the channel.
Gating inhibitors
Key to terms and symbols Click column headers to sort
Ligand Sp. Action Affinity Units Concentration range (M) Holding voltage (mV) Reference
ATX-II Hs Slows inactivation 8.2 pEC50 - -80.0 28
pEC50 8.2 Inhibitor of fast activation [28]
Holding voltage: -80.0 mV
cangitoxin II Hs Slows inactivation 6.8 pEC50 - -90.0 50
pEC50 6.8 (EC50 1.65x10-7 M) Inhibits inactivation [50]
Holding voltage: -90.0 mV
Description: hole-cell voltage clamp of human Nav1.1 expressed in human embryonic kidney cell line HEK293.
Bc-III Hs Slows inactivation 6.5 pEC50 - -80.0 28
pEC50 6.5 Inhibitor of fast activation [28]
Holding voltage: -80.0 mV
AFT-II Hs Slows inactivation 6.4 pEC50 - -80.0 28
pEC50 6.4 Inhibitor of fast activation [28]
Holding voltage: -80.0 mV
Gating Inhibitor Comments
As Nav1.1 shows close similarity to Nav1.2 in amino acid sequence and in functional properties, it is expected that gating inhibitors of Nav1.1 will resemble those of Nav1.2, however there is little published work directly on Nav1.1. Other sea anemone toxins have lower affinity for Nav1.1 channels [50].
Channel Blockers
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Affinity Units Concentration range (M) Holding voltage (mV) Reference
tetrodotoxin Hs Pore blocker - - 1x10-8 -
Conc range: 1x10-8 M
tetrodotoxin Rn Pore blocker 8.0 pKd - -100.0 32
pKd 8.0 [32]
Holding voltage: -100.0 mV
μ-conotoxin SmIIIA Rn Pore blocker 8.4 pKi - -80.0 47
pKi 8.4 [47]
Holding voltage: -80.0 mV
Description: Two-microelectrode voltage clamp on rat Nav1.1 in Xenopus oocytes
saxitoxin Hs Pore blocker - - - -
Hm1a Rn - - - - - 30
[30]
View species-specific channel blocker tables
Channel Blocker Comments
As Nav1.1 shows close similarity to Nav1.2 in amino acid sequence and in functional properties, it is expected that pore blockers of Nav1.1 will resemble those of Nav1.2, however there is little published work directly on Nav1.1. Many other μ-conotoxins block Nav1.1 channels with lower affinity [47].
Tissue Distribution
Spinal neurons, primarily cell bodies.
Species:  Human
Technique:  Immunohistochemistry
References:  46
Brain neurons.
Species:  Human
Technique:  In situ hybridisation
References:  45
Cardiac myocytes (sino-atrial node, atrial myocytes and transverse tubules of ventricular myocytes).
Species:  Mouse
Technique:  Immunohistochemistry
References:  21-22
Brain neurons, primarily cell bodies and axon initial segments.
Species:  Rat
Technique:  Immunohistochemistry
References:  26,44,49
Physiological Functions
Action potential conduction in transverse tubule of ventricular myocytes. Coupling of cell surface depolarisation to contraction is impaired by tetrodotoxin at concentrations that are selective for Nav1.1 channels versus Nav1.5 channels in ventricular myocytes.
Species:  Mouse
Tissue:  Heart
References:  21-22
Action potential initiation and repetitive firing in central neurons. Sodium currents and action potential firing in GABAergic neurons are impaired in mice lacking Nav1.1 channels.
Species:  Mouse
Tissue:  Brain
References:  18,26,44,49
Physiological Consequences of Altering Gene Expression
Impaired sodium currents and action potential firing in GABAergic neurons.
Species:  Mouse
Tissue:  GABAergic neurons.
Technique:  Electrophysiology
References:  6,18,26,49
Phenotypes, Alleles and Disease Models Mouse data from MGI

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Allele Composition & genetic background Accession Phenotype Id Phenotype Reference
Scn1atm1Wac Scn1atm1Wac/Scn1atm1Wac
B6.129-Scn1a
MGI:98246  MP:0005402 abnormal action potential PMID: 16921370 
Scn1a+|Scn1atm1Wac Scn1atm1Wac/Scn1a+
B6.129-Scn1a
MGI:98246  MP:0005402 abnormal action potential PMID: 16921370 
Scn1a+|Scn1atm1Wac Scn1atm1Wac/Scn1a+
B6.129-Scn1a
MGI:98246  MP:0004994 abnormal brain wave pattern PMID: 16921370 
Scn1atm1.1Aesc Scn1atm1.1Aesc/Scn1atm1.1Aesc
involves: 129X1/SvJ * C57BL/6J * SJL
MGI:98246  MP:0004008 abnormal GABA-mediated receptor currents PMID: 20100831 
Scn1a+|Scn1atm1.1Aesc Scn1atm1.1Aesc/Scn1a+
involves: 129X1/SvJ * C57BL/6J * SJL
MGI:98246  MP:0004008 abnormal GABA-mediated receptor currents PMID: 20100831 
Scn1atm1Kzy Scn1atm1Kzy/Scn1atm1Kzy
involves: 129 * C57BL/6 * SJL
MGI:98246  MP:0001406 abnormal gait PMID: 17537961 
Scn1atm1Kzy Scn1atm1Kzy/Scn1atm1Kzy
involves: 129 * C57BL/6 * SJL
MGI:98246  MP:0003492 abnormal involuntary movement PMID: 17537961 
Scn1atm1Wac Scn1atm1Wac/Scn1atm1Wac
B6.129-Scn1a
MGI:98246  MP:0002272 abnormal nervous system electrophysiology PMID: 16921370 
Scn1a+|Scn1atm1Wac Scn1atm1Wac/Scn1a+
B6.129-Scn1a
MGI:98246  MP:0002272 abnormal nervous system electrophysiology PMID: 16921370 
Scn1atm1Wac Scn1atm1Wac/Scn1atm1Wac
B6.129-Scn1a
MGI:98246  MP:0002980 abnormal postural reflex PMID: 16921370 
Scn1atm1Wac Scn1atm1Wac/Scn1atm1Wac
B6.129-Scn1a
MGI:98246  MP:0001504 abnormal posture PMID: 16921370 
Scn1a+|Scn1atm1Wac Scn1atm1Wac/Scn1a+
involves: 129S1/Sv * 129X1/SvJ * FVB/NJ
MGI:98246  MP:0008840 abnormal spike wave discharge PMID: 17881658 
Scn1a+|Scn1atm1Wac|Scn8a+|Scn8amed-jo Scn1atm1Wac/Scn1a+,Scn8amed-jo/Scn8a+
involves: 129 * C57BL/6J * DBA/2WyDi * FVB/NJ
MGI:103169  MGI:98246  MP:0008840 abnormal spike wave discharge PMID: 17881658 
Scn1a+|Scn1atm1.1Aesc Scn1atm1.1Aesc/Scn1a+
involves: 129X1/SvJ * C57BL/6J * SJL
MGI:98246  MP:0008840 abnormal spike wave discharge PMID: 20100831 
Scn1atm1Wac Scn1atm1Wac/Scn1atm1Wac
B6.129-Scn1a
MGI:98246  MP:0002690 akinesia PMID: 16921370 
Scn1atm1Wac Scn1atm1Wac/Scn1atm1Wac
B6.129-Scn1a
MGI:98246  MP:0001393 ataxia PMID: 16921370 
Scn1atm1Wac Scn1atm1Wac/Scn1atm1Wac
B6.129-Scn1a
MGI:98246  MP:0003996 clonic seizures PMID: 16921370 
Scn1atm1.1Aesc Scn1atm1.1Aesc/Scn1atm1.1Aesc
involves: 129X1/SvJ * C57BL/6J * SJL
MGI:98246  MP:0003996 clonic seizures PMID: 20100831 
Scn1atm1Wac Scn1atm1Wac/Scn1atm1Wac
B6.129-Scn1a
MGI:98246  MP:0000947 convulsive seizures PMID: 16921370 
Scn1atm1Kzy Scn1atm1Kzy/Scn1atm1Kzy
involves: 129 * C57BL/6 * SJL
MGI:98246  MP:0001262 decreased body weight PMID: 17537961 
Scn1atm1.1Aesc Scn1atm1.1Aesc/Scn1atm1.1Aesc
involves: 129X1/SvJ * C57BL/6J * SJL
MGI:98246  MP:0001262 decreased body weight PMID: 20100831 
Scn1atm1Kzy Scn1atm1Kzy/Scn1atm1Kzy
involves: 129 * C57BL/6 * SJL
MGI:98246  MP:0000774 decreased brain size PMID: 17537961 
Scn1atm1Kzy Scn1atm1Kzy/Scn1atm1Kzy
involves: 129 * C57BL/6 * SJL
MGI:98246  MP:0002175 decreased brain weight PMID: 17537961 
Scn1atm1.1Aesc Scn1atm1.1Aesc/Scn1atm1.1Aesc
involves: 129X1/SvJ * C57BL/6J * SJL
MGI:98246  MP:0009358 environmentally induced seizures PMID: 20100831 
Scn1a+|Scn1atm1.1Aesc Scn1atm1.1Aesc/Scn1a+
involves: 129X1/SvJ * C57BL/6J * SJL
MGI:98246  MP:0009358 environmentally induced seizures PMID: 20100831 
Scn1a+|Scn1atm1Wac Scn1atm1Wac/Scn1a+
B6.129-Scn1a
MGI:98246  MP:0001410 head bobbing PMID: 16921370 
Scn1atm1.1Aesc Scn1atm1.1Aesc/Scn1atm1.1Aesc
involves: 129X1/SvJ * C57BL/6J * SJL
MGI:98246  MP:0002578 impaired ability to fire action potentials PMID: 20100831 
Scn1atm1Wac Scn1atm1Wac/Scn1atm1Wac
B6.129-Scn1a
MGI:98246  MP:0001523 impaired righting response PMID: 16921370 
Scn1a+|Scn1atm1Wac Scn1atm1Wac/Scn1a+
involves: 129S1/Sv * 129X1/SvJ * FVB/NJ
MGI:98246  MP:0002906 increased susceptibility to pharmacologically induced seizures PMID: 17881658 
Scn1a+|Scn1atm1.1Aesc Scn1atm1.1Aesc/Scn1a+
involves: 129X1/SvJ * C57BL/6J * SJL
MGI:98246  MP:0002906 increased susceptibility to pharmacologically induced seizures PMID: 20100831 
Scn1atm1Kzy Scn1atm1Kzy/Scn1atm1Kzy
involves: 129 * C57BL/6 * SJL
MGI:98246  MP:0005424 jerky movement PMID: 17537961 
Scn1atm1.1Aesc Scn1atm1.1Aesc/Scn1atm1.1Aesc
involves: 129X1/SvJ * C57BL/6J * SJL
MGI:98246  MP:0002194 maximal tonic hindlimb extension seizures PMID: 20100831 
Scn1atm1Wac Scn1atm1Wac/Scn1atm1Wac
B6.129-Scn1a
MGI:98246  MP:0002082 postnatal lethality PMID: 16921370 
Scn1atm1Kzy Scn1atm1Kzy/Scn1atm1Kzy
involves: 129 * C57BL/6 * SJL
MGI:98246  MP:0002082 postnatal lethality PMID: 17537961 
Scn1atm1Wac Scn1atm1Wac/Scn1atm1Wac
involves: 129S1/Sv * 129X1/SvJ * FVB/NJ
MGI:98246  MP:0002082 postnatal lethality PMID: 17881658 
Scn1atm1Wac|Scn8a+|Scn8amed-jo Scn1atm1Wac/Scn1atm1Wac,Scn8amed-jo/Scn8a+
involves: 129 * C57BL/6J * DBA/2WyDi * FVB/NJ
MGI:103169  MGI:98246  MP:0002082 postnatal lethality PMID: 17881658 
Scn1atm1Wac|Tg(Scn1a*)RH9Aesc Scn1atm1Wac/Scn1atm1Wac,Tg(Scn1a*)RH9Aesc/0
involves: 129S1/Sv * 129X1/SvJ * FVB/NJ
MGI:3851209  MGI:98246  MP:0002082 postnatal lethality PMID: 19409490 
Scn1atm1.1Aesc Scn1atm1.1Aesc/Scn1atm1.1Aesc
involves: 129X1/SvJ * C57BL/6J * SJL
MGI:98246  MP:0002082 postnatal lethality PMID: 20100831 
Scn1a+|Scn1atm1Wac Scn1atm1Wac/Scn1a+
B6.129-Scn1a
MGI:98246  MP:0002083 premature death PMID: 16921370 
Scn1a+|Scn1atm1Wac Scn1atm1Wac/Scn1a+
129-Scn1a
MGI:98246  MP:0002083 premature death PMID: 16921370 
Scn1a+|Scn1atm1Wac Scn1atm1Wac/Scn1a+
involves: 129S1/Sv * 129X1/SvJ * C57BL/6
MGI:98246  MP:0002083 premature death PMID: 16921370 
Scn1a+|Scn1atm1Kzy Scn1atm1Kzy/Scn1a+
involves: 129 * C57BL/6 * SJL
MGI:98246  MP:0002083 premature death PMID: 17537961 
Scn1a+|Scn1atm1Wac Scn1atm1Wac/Scn1a+
involves: 129S1/Sv * 129X1/SvJ * FVB/NJ
MGI:98246  MP:0002083 premature death PMID: 17881658 
Scn1atm1Wac|Tg(Scn1a*)RH9Aesc Scn1atm1Wac/Scn1atm1Wac,Tg(Scn1a*)RH9Aesc/0
involves: 129S1/Sv * 129X1/SvJ * FVB/NJ
MGI:3851209  MGI:98246  MP:0002083 premature death PMID: 19409490 
Scn1a+|Scn1atm1Wac|Tg(Scn1a*)RH9Aesc Scn1atm1Wac/Scn1a+,Tg(Scn1a*)RH9Aesc/0
involves: 129S1/Sv * 129X1/SvJ * FVB/NJ
MGI:3851209  MGI:98246  MP:0002083 premature death PMID: 19409490 
Scn1a+|Scn1atm1Wac Scn1atm1Wac/Scn1a+
involves: 129S1/Sv * 129X1/SvJ * C57BL/6
MGI:98246  MP:0001921 reduced fertility PMID: 16921370 
Scn1atm1Wac Scn1atm1Wac/Scn1atm1Wac
B6.129-Scn1a
MGI:98246  MP:0002064 seizures PMID: 16921370 
Scn1a+|Scn1atm1Wac Scn1atm1Wac/Scn1a+
B6.129-Scn1a
MGI:98246  MP:0002064 seizures PMID: 16921370 
Scn1a+|Scn1atm1Kzy Scn1atm1Kzy/Scn1a+
involves: 129 * C57BL/6 * SJL
MGI:98246  MP:0002064 seizures PMID: 17537961 
Scn1atm1Kzy Scn1atm1Kzy/Scn1atm1Kzy
involves: 129 * C57BL/6 * SJL
MGI:98246  MP:0002064 seizures PMID: 17537961 
Scn1atm1.1Aesc Scn1atm1.1Aesc/Scn1atm1.1Aesc
involves: 129X1/SvJ * C57BL/6J * SJL
MGI:98246  MP:0002064 seizures PMID: 20100831 
Scn1a+|Scn1atm1.1Aesc Scn1atm1.1Aesc/Scn1a+
involves: 129X1/SvJ * C57BL/6J * SJL
MGI:98246  MP:0002064 seizures PMID: 20100831 
Scn1atm1Kzy Scn1atm1Kzy/Scn1atm1Kzy
involves: 129 * C57BL/6 * SJL
MGI:98246  MP:0003997 tonic-clonic seizures PMID: 17537961 
Scn1a+|Scn1atm1Wac Scn1atm1Wac/Scn1a+
involves: 129S1/Sv * 129X1/SvJ * FVB/NJ
MGI:98246  MP:0003997 tonic-clonic seizures PMID: 17881658 
Scn1a+|Scn1atm1.1Aesc Scn1atm1.1Aesc/Scn1a+
involves: 129X1/SvJ * C57BL/6J * SJL
MGI:98246  MP:0003997 tonic-clonic seizures PMID: 20100831 
Scn1atm1Kzy Scn1atm1Kzy/Scn1atm1Kzy
involves: 129 * C57BL/6 * SJL
MGI:98246  MP:0002826 tonic seizures PMID: 17537961 
Scn1atm1.1Aesc Scn1atm1.1Aesc/Scn1atm1.1Aesc
involves: 129X1/SvJ * C57BL/6J * SJL
MGI:98246  MP:0002826 tonic seizures PMID: 20100831 
Scn1a+|Scn1atm1.1Aesc Scn1atm1.1Aesc/Scn1a+
involves: 129X1/SvJ * C57BL/6J * SJL
MGI:98246  MP:0002826 tonic seizures PMID: 20100831 
Scn1atm1Wac Scn1atm1Wac/Scn1atm1Wac
B6.129-Scn1a
MGI:98246  MP:0000745 tremors PMID: 16921370 
Scn1atm1Kzy Scn1atm1Kzy/Scn1atm1Kzy
involves: 129 * C57BL/6 * SJL
MGI:98246  MP:0001263 weight loss PMID: 17537961 
Scn1atm1.1Aesc Scn1atm1.1Aesc/Scn1atm1.1Aesc
involves: 129X1/SvJ * C57BL/6J * SJL
MGI:98246  MP:0001263 weight loss PMID: 20100831 
Clinically-Relevant Mutations and Pathophysiology
Disease:  Dravet syndrome
Synonyms: Epileptic encephalopathy, early infantile, 6; EIEE6 [OMIM: 607208]
Severe myoclonic epilepsy of infancy; SMEI [OMIM: 607208]
Disease Ontology: DOID:0060171
OMIM: 607208
Orphanet: ORPHA33069
References:  4,41
Click column headers to sort
Type Species Amino acid change Nucleotide change Description Reference
Frameshift Human S607 27
Frameshift Human P707 27
Frameshift Human R946 14
Frameshift Human D958 33
Frameshift Human A1002 27
Frameshift Human T1082 27
Frameshift Human A1429 27
Frameshift Human N1788 41
Frameshift Human G1880 27
Frameshift Human Q1904 33
Frameshift Human P37fsX91 41
Frameshift Human L1670fsX1678 33,40
Frameshift Human K1846fsX1856 41
Frameshift: Deletion Human G177fsX180 c.530delG 14
Frameshift: Deletion Human S219fsX275 c.657-658delAG Exon 5 7
Frameshift: Deletion Human R501fsX543 G1502del Exon 10 27
Frameshift: Insertion Human K547fsX570 1641insA Exon 10 27
Frameshift: Insertion Human Q732fsX749 c.2196insCACCCTGT 14
Frameshift: Insertion Human K1100fsX1107 c.3299-3300insAA Exon 16 7
Frameshift: Insertion Human F1765fsX1794 c.5292insT 14
In-frame deletion Human F1289del 38
In-frame deletion Human 1807delMFYE c.5419delATGTTCTATGAG 14
Missense Human S103G 14
Missense Human T112I 14
Missense Human G265W 14
Missense Human G343E 14
Missense Human F902C 27
Missense Human R931C 27
Missense Human M960V 14
Missense Human N985I 14
Missense Human L986F 40
Missense Human S1231R 14
Missense Human F1263L 14
Missense Human L1265P 27
Missense Human A1326P 41
Missense Human V1390M 27
Missense Human W1434R 27
Missense Human Q1450R 27
Missense Human R1648C 27
Missense Human G1674R 27
Missense Human A1685D 14
Missense Human W1812G 14
Missense Human F1831S 14
Missense Human E1881D 41
Missense Human T1909I 27
Nonsense Human R222X 40
Nonsense Human I448X 41
Nonsense Human R568X 27
Nonsense Human R712X 27,33
Nonsense Human R865X 27
Nonsense Human W952X 14
Nonsense Human K1027X 27
Nonsense Human W1204X 33
Nonsense Human R1213X 14
Nonsense Human W1271X 27
Nonsense Human W1284X 14
Nonsense Human R1407X 33
Nonsense Human W1408X 14
Nonsense Human S1516X 33
Nonsense Human R1892X 33
Splice site Human IVS4+1G>A 14
Splice site Human IVS18+1G>A 41
Splice site Human IVS22+1G>A Intron 22; DIII S5-S6 pore 7
Splice site Human IVS22-14T>G 41
Disease:  Generalized epilepsy with febrile seizures plus, type 2; GEFSP2
Synonyms: Generalized epilepsy with febrile seizures-plus [Orphanet: ORPHA36387] [Disease Ontology: DOID:0060170]
Disease Ontology: DOID:0060170
OMIM: 604403
Orphanet: ORPHA36387
Drugs: 
References:  4,11,42
Click column headers to sort
Type Species Amino acid change Nucleotide change Description Reference
Missense Human D188V 42
Missense Human R542Q 29
Missense Human T875M 11
Missense Human I899T 29
Missense Human M967I 29
Missense Human W1204R 10
Missense Human K1249M 29
Missense Human V1353L 42
Missense Human R1648H 11
Missense Human I1656M 42
Disease:  Lennox-Gastaut syndrome
Disease Ontology: DOID:0050561
Orphanet: ORPHA2382
Disease:  Malignant migrating partial seizures of infancy
Orphanet: ORPHA293181
Disease:  Migraine, familial hemiplegic, 3; FHM3
Synonyms: Familial hemiplegic migraine [Disease Ontology: DOID:0060178]
Familial or sporadic hemiplegic migraine [Orphanet: ORPHA569]
Disease Ontology: DOID:0060178
OMIM: 609634
Orphanet: ORPHA569
References:  9
Click column headers to sort
Type Species Amino acid change Nucleotide change Description Reference
Missense Human L263V 2
Missense Human T1174S 5,15
Missense Human Q1489H 19
Missense Human Q1489K 9
Missense Human I1498M 43
Missense Human F1499L 39
Missense Human L1649Q 9
Missense Human F1661L 43
Disease:  Myoclonic-astastic epilepsy
Orphanet: ORPHA1942
Biologically Significant Variants
Type:  Splice variant
Species:  Human
Description:  Longer splice variant.
Amino acids:  2009
Protein accession: 
References:  11,20
Type:  Splice variant
Species:  Human
Description:  Shorter splice variant
Amino acids:  1998
Nucleotide accession: 
Protein accession: 
References:  11,20
Type:  Splice variant
Species:  Human
Description:  Alternative splicing of Exon 5. Developmentally regulated in mouse, rat, and human. Physiological effect: Small change in fast inactivation. Correlated with changes in susceptibility to develop febrile seizures in infancy. Pharmacological effect: Changes in effective concentration of antiepileptic drugs for sodium channel block in vitro and in effective dose for treatment of epilepsy in patients.
Nucleotide accession: 
References:  12,16-17,31,35-37
Biologically Significant Variant Comments
Probable in-frame deletion in exon 11 by alternative splicing is responsible for the difference in sequence length [11,20]. Alternative splicing of Exon 5 is developmentally regulated and is correlated with changes in sensitivity of patients to anti-epileptic drugs, with changes in block of Nav1.1 channels by anti-epileptic drugs, and with susceptibility to develop febrile seizures [12,16,31,35-37].

References

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How to cite this page

William A. Catterall, Alan L. Goldin, Stephen G. Waxman.
Voltage-gated sodium channels: Nav1.1. Last modified on 26/06/2018. Accessed on 13/11/2018. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=578.