Na<sub>v</sub>1.7 | Voltage-gated sodium channels | IUPHAR/BPS Guide to PHARMACOLOGY

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Nav1.7

Target id: 584

Nomenclature: Nav1.7

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 Nav1.7 in GtoImmuPdb

Gene and Protein Information
Species TM P Loops AA Chromosomal Location Gene Symbol Gene Name Reference
Human 24 1 1977 2q24 SCN9A sodium voltage-gated channel alpha subunit 9 45
Mouse 24 1 1975 2 C1.3 Scn9a sodium channel, voltage-gated, type IX, alpha 3,46
Rat 24 1 1984 3q21 Scn9a sodium voltage-gated channel alpha subunit 9 56,63
Previous and Unofficial Names
hNE-Na | Nas | PN1 | ETHA | NENA | NE-NA | peripheral sodium channel 1 | sodium channel protein type 9 subunit alpha | sodium channel, voltage-gated, type IX, alpha subunit | sodium channel, voltage gated, type IX 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
β2 27,42
β1 29,41,50
Other Associated Proteins
Name References
Not determined
Functional Characteristics
Activation V0.5 = -27 mV. Fast inactivation (0.5 ms)
Ion Selectivity and Conductance
Species:  Rat
Rank order:  Na+ [- pS]
References:  55
Species:  Rat
Single channel conductance (pS):  19.5
References:  55
Voltage Dependence
  V0.5 (mV)  τ (msec)  Reference  Cell type  Species 
Activation  -25.6 – -27.9 (median: -26.0) - 10,64 Xenopus laevis oocyte Rat
Inactivation  -61.9 – -68.4 (median: -67.0) 1.0 – 429.0 10,64
  V0.5 (mV)  τ (msec)  Reference  Cell type  Species 
Activation  -24.6 - 18 HEK 293 cells. Human
Inactivation  -73.6 1.0 18
Comments  This is a human channel with a TTX resistant mutation (Y362S).
  V0.5 (mV)  τ (msec)  Reference  Cell type  Species 
Activation  -27.3 0.1 10 Nav1.8 null mouse DRG neurons. Human
Inactivation  -71.3 1.0 10
Comments  Human channel with a TTX resistant mutation (Y362S), kinetics measured at 10mV.

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 - - - - -
veratridine Hs - - - - -
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 8.5 pIC50 - - 33
pIC50 8.5 (IC50 3x10-9 M) [33]
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.
GNE-131 Hs Binding 8.0 pIC50 - - 33
pIC50 8.0 (IC50 1x10-8 M) [33]
Description: Value from radioligand binding assay; IC50 for displacement of [3H]GX-545.
Gating 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
PF‐06526290 Hs Inhibition 9.6 pEC50 - - 66
pEC50 9.6 (EC50 2.7x10-10 M) [66]
N-Me-aminopyrimidinone 9 Hs Inhibition 7.1 pIC50 - - 53
pIC50 7.1 (IC50 8x10-8 M) [53]
Description: Electrophysiology
Gating Inhibitor Comments
Scorpion toxins are known inhibitors of Nav1.7 for example the α-scorpion toxins (Odonthobuthus doriae) [49] and other scopion toxins (Lqh-2 and Lqh-3) [6].
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
XEN907 Hs Inhibition 8.5 pIC50 - - 15
pIC50 8.5 (IC50 3x10-9 M) [15]
Description: [14C]guanidinium influx
tetrodotoxin Rn Pore blocker 8.4 pIC50 - -100.0 56
pIC50 8.4 [56]
Holding voltage: -100.0 mV
tetrodotoxin Hs Pore blocker 7.6 pIC50 - -100.0 45
pIC50 7.6 (IC50 2.45x10-8 M) [45]
Holding voltage: -100.0 mV
pyrrolopyrimidine 48 [PMID: 22318156] Hs Inhibition 7.0 pIC50 - - 5
pIC50 7.0 (IC50 1.1x10-7 M) [5]
Description: Electrophysiology
saxitoxin Hs Pore blocker 6.2 pIC50 - - 65
pIC50 6.2 (IC50 7.02x10-7 M) [65]
lacosamide Hs Antagonist 3.7 pIC50 - - 57
pIC50 3.7 (IC50 1.82x10-4 M) [57]
lidocaine Rn Pore blocker 3.3 pIC50 - -100.0 10
pIC50 3.3 [10]
Holding voltage: -100.0 mV
Cd2+ Hs Pore blocker 3.0 pIC50 - -100.0 45
pIC50 3.0 [45]
Holding voltage: -100.0 mV
View species-specific channel blocker tables
Tissue Distribution
All types of DRG neurons, sympathetic neurons, Schwann cells and neuroendocrine cells.
Species:  Rat
Technique:  In situ hybridisation
References:  30
All types of DRG neurons, sympathetic neurons, Schwann cells and neuroendorcrine cells.
Species:  Rat
Technique:  Northern Blot
References:  45
All types of DRG neurons, sympathetic neurons, Schwann cells and neuroendocrine cells.
Species:  Rat
Technique:  RT-PCR
References:  56
Physiological Consequences of Altering Gene Expression
Epilepsy
Species:  Mouse
Tissue: 
Technique:  Knock-in of N641Y
References:  59
Minett et al. suggest that NaV1.7 in sympathetic ganglion neurons is essential for neuropathic pain
Species:  Mouse
Tissue:  DRG-neuron, sympathetic ganglion neurons
Technique:  Cell type-specific knockout
References:  52
NaV1.7 is essential for heat pain after burning injuries
Species:  Mouse
Tissue:  DRG neurons
Technique:  Knockout
References:  58
Phenotypes, Alleles and Disease Models Mouse data from MGI

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Allele Composition & genetic background Accession Phenotype Id Phenotype Reference
Scn9atm1.1Naas Scn9atm1.1Naas/Scn9atm1.1Naas
B6.129-Scn9a
MGI:107636  MP:0001499 abnormal kindling response PMID: 19763161 
Scn10a+|Scn10atm2(cre)Jnw|Scn9atm1Jnw Scn10atm2(cre)Jnw/Scn10a+,Scn9atm1Jnw/Scn9atm1Jnw
involves: 129
MGI:107636  MGI:108029  MP:0002736 abnormal nociception after inflammation PMID: 15314237 
Scn10a+|Scn10atm2(cre)Jnw|Scn9atm1Jnw Scn10atm2(cre)Jnw/Scn10a+,Scn9atm1Jnw/Scn9atm1Jnw
involves: 129
MGI:107636  MGI:108029  MP:0001970 abnormal pain threshold PMID: 15314237 
Scn9atm1.1Naas Scn9atm1.1Naas/Scn9atm1.1Naas
involves: 129S1/Sv * 129X1/SvJ * C57BL/6J
MGI:107636  MP:0001650 abnormal seizure response to electrical stimulation PMID: 19763161 
Scn9a+|Scn9atm1Dgen Scn9atm1Dgen/Scn9a+
involves: 129P2/OlaHsd * C57BL/6
MGI:107636  MP:0009141 increased prepulse inhibition
Scn10a+|Scn10atm2(cre)Jnw|Scn9atm1Jnw Scn10atm2(cre)Jnw/Scn10a+,Scn9atm1Jnw/Scn9atm1Jnw
involves: 129
MGI:107636  MGI:108029  MP:0001973 increased thermal nociceptive threshold PMID: 15314237 
Scn9atm1.1Naas Scn9atm1.1Naas/Scn9atm1.1Naas
involves: 129S1/Sv * 129X1/SvJ * C57BL/6J
MGI:107636  MP:0002193 minimal clonic seizures PMID: 19763161 
Scn9atm1.1Jnw Scn9atm1.1Jnw/Scn9atm1.1Jnw
involves: 129
MGI:107636  MP:0002058 neonatal lethality PMID: 15314237 
Scn9atm1Dgen Scn9atm1Dgen/Scn9atm1Dgen
involves: 129P2/OlaHsd * C57BL/6
MGI:107636  MP:0002081 perinatal lethality
Clinically-Relevant Mutations and Pathophysiology
Disease:  Acromesomelia and painful neuropathy
Synonyms: acromesomelic dysplasia [Disease Ontology: DOID:0080049]
neuropathy [Disease Ontology: DOID:870]
Disease Ontology: DOID:870, DOID:0080049
Click column headers to sort
Type Species Amino acid change Nucleotide change Description Reference
Missense Human G856D 40
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
Disease:  Erythermalgia
Synonyms: Primary erythermalgia [Orphanet: ORPHA90026]
Sodium channelopathy-related small fiber neuropathy [Orphanet: ORPHA306577]
OMIM: 133020
Orphanet: ORPHA1956, ORPHA90026, ORPHA306577
Role: 
References:  13,16,19,21,51,67-68
Click column headers to sort
Type Species Amino acid change Nucleotide change Description Reference
In-frame deletion Human L955del A TTA deletion from exon 16 results in the deletion of a leucine residue. 7
Missense Human Q10R 35
Missense Human R185H Associated with Small-Fiber Peripheral Neuropathy 37
Missense Human F216S 13,22
Missense Human I228M Associated with Small-Fiber Peripheral Neuropathy 25
Missense Human I234T 1
Missense Human S241T 48,51
Missense Human S241P 23
Missense Human N395K 22
Missense Human V400M 32
Missense Human P610T 22
Missense Human G616R 12
Missense Human D623N Associated with Small-Fiber Peripheral Neuropathy 28
Missense Human I720K Associated with Small-Fiber Peripheral Neuropathy 28
Missense Human I739V Associated with Small-Fiber Peripheral Neuropathy 36
Missense Human G823R 47
Missense Human I848T 18,22
Missense Human L858H 18
Missense Human L858F 22,38
Missense Human A863P 39
Missense Human V872G 14
Missense Human M932L c.2794A>C Associated with Small-Fiber Peripheral Neuropathy 28
Missense Human V991L c.2971G>T Associated with Small-Fiber Peripheral Neuropathy 28
Missense Human M1136V 8
Missense Human P1308L 9
Missense Human F1449V 21
Missense Human M1532I Associated with Small-Fiber Peripheral Neuropathy 28
Missense Human A1632E 24
Disease:  Generalized epilepsy with febrile seizures plus, type 7; GEFSP7
Synonyms: Generalized epilepsy with febrile seizures-plus [Orphanet: ORPHA36387] [Disease Ontology: DOID:0060170]
Disease Ontology: DOID:0060170
OMIM: 613863
Orphanet: ORPHA36387
Click column headers to sort
Type Species Amino acid change Nucleotide change Description Reference
Missense Human N461Y 59
Disease:  Hereditary sensory and autonomic neuropathy type 2
Synonyms: Hereditary sensory and autonomic neuropathy [Disease Ontology: DOID:11533]
Disease Ontology: DOID:11533
Orphanet: ORPHA970
References:  69
Disease:  Hyperalgesia
Click column headers to sort
Type Species Amino acid change Nucleotide change Description Reference
Missense Human R1150W 26,54
Disease:  Indifference to pain, congenital, autosomal recessive; CIP
Synonyms: Channelopathy-associated congenital insensitivity to pain [Orphanet: ORPHA88642]
OMIM: 243000
Orphanet: ORPHA88642
Role: 
References:  17,34
Click column headers to sort
Type Species Amino acid change Nucleotide change Description Reference
Deletion Human IVS17+3delA This mutation causes exon 17 to be skipped. Found in compound heteozygousity with missense mutation C1719R. 60
Missense Human C1719R c.5155T>C Found in compound heterozygousity with IVS17+3delA. 60
Nonsense Human R277X 34
Nonsense Human Y328X 34
Nonsense Human S459X 17
Nonsense Human K767X 17
Nonsense Human W897X 17
Disease:  Paroxysmal Extreme Pain Disorder
OMIM: 167400
Orphanet: ORPHA46348
Role: 
References:  4,11,31
Click column headers to sort
Type Species Amino acid change Nucleotide change Description Reference
Missense Human R996C 31
Missense Human V1298D 31
Missense Human V1298F 9,31
Missense Human V1299F 31,62
Missense Human I1461T 31,43-44
Missense Human F1462V 31
Missense Human T1464I 31
Missense Human G1607R 11
Missense Human M1627K 20,31
General Comments
Strong genetic evidence (either gain-of-function or loss-of-function) supports the crucial role of NaV1.7 (SCN9A) in pain sensation [17,34,68]. As a result, there is pharmaceutical industry interest in developing small molecule NaV1.7 inhibitors as analgesics [2,61].

References

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1. Ahn HS, Dib-Hajj SD, Cox JJ, Tyrrell L, Elmslie FV, Clarke AA, Drenth JP, Woods CG, Waxman SG. (2010) A new Nav1.7 sodium channel mutation I234T in a child with severe pain. Eur J Pain, 14 (9): 944-50. [PMID:20385509]

2. Bagal SK, Chapman ML, Marron BE, Prime R, Storer RI, Swain NA. (2014) Recent progress in sodium channel modulators for pain. Bioorg. Med. Chem. Lett., 24 (16): 3690-9. [PMID:25060923]

3. Beckers MC, Ernst E, Belcher S, Howe J, Levenson R, Gros P. (1996) A new sodium channel alpha-subunit gene (Scn9a) from Schwann cells maps to the Scn1a, Scn2a, Scn3a cluster of mouse chromosome 2. Genomics, 36 (1): 202-5. [PMID:8812438]

4. Catterall WA, Yu FH. (2006) Painful channels. Neuron, 52 (5): 743-4. [PMID:17145494]

5. Chakka N, Bregman H, Du B, Nguyen HN, Buchanan JL, Feric E, Ligutti J, Liu D, McDermott JS, Zou A et al.. (2012) Discovery and hit-to-lead optimization of pyrrolopyrimidines as potent, state-dependent Na(v)1.7 antagonists. Bioorg. Med. Chem. Lett., 22 (5): 2052-62. [PMID:22318156]

6. Chen H, Lu S, Leipold E, Gordon D, Hansel A, Heinemann SH. (2002) Differential sensitivity of sodium channels from the central and peripheral nervous system to the scorpion toxins Lqh-2 and Lqh-3. Eur. J. Neurosci., 16 (4): 767-70. [PMID:12270053]

7. Cheng X, Dib-Hajj SD, Tyrrell L, Te Morsche RH, Drenth JP, Waxman SG. (2011) Deletion mutation of sodium channel Na(V)1.7 in inherited erythromelalgia: enhanced slow inactivation modulates dorsal root ganglion neuron hyperexcitability. Brain, 134 (Pt 7): 1972-86. [PMID:21705421]

8. Cheng X, Dib-Hajj SD, Tyrrell L, Waxman SG. (2008) Mutation I136V alters electrophysiological properties of the Na(v)1.7 channel in a family with onset of erythromelalgia in the second decade. Mol Pain, 4: 1. [PMID:18171466]

9. Cheng X, Dib-Hajj SD, Tyrrell L, Wright DA, Fischer TZ, Waxman SG. (2010) Mutations at opposite ends of the DIII/S4-S5 linker of sodium channel Na V 1.7 produce distinct pain disorders. Mol Pain, 6: 24. [PMID:20429905]

10. Chevrier P, Vijayaragavan K, Chahine M. (2004) Differential modulation of Nav1.7 and Nav1.8 peripheral nerve sodium channels by the local anesthetic lidocaine. Br. J. Pharmacol., 142 (3): 576-84. [PMID:15148257]

11. Choi JS, Boralevi F, Brissaud O, Sánchez-Martín J, Te Morsche RH, Dib-Hajj SD, Drenth JP, Waxman SG. (2011) Paroxysmal extreme pain disorder: a molecular lesion of peripheral neurons. Nat Rev Neurol, 7 (1): 51-5. [PMID:21079636]

12. Choi JS, Cheng X, Foster E, Leffler A, Tyrrell L, Te Morsche RH, Eastman EM, Jansen HJ, Huehne K, Nau C et al.. (2010) Alternative splicing may contribute to time-dependent manifestation of inherited erythromelalgia. Brain, 133 (Pt 6): 1823-35. [PMID:20478850]

13. Choi JS, Dib-Hajj SD, Waxman SG. (2006) Inherited erythermalgia: limb pain from an S4 charge-neutral Na channelopathy. Neurology, 67 (9): 1563-7. [PMID:16988069]

14. Choi JS, Zhang L, Dib-Hajj SD, Han C, Tyrrell L, Lin Z, Wang X, Yang Y, Waxman SG. (2009) Mexiletine-responsive erythromelalgia due to a new Na(v)1.7 mutation showing use-dependent current fall-off. Exp. Neurol., 216 (2): 383-9. [PMID:19162012]

15. Chowdhury S, Chafeev M, Liu S, Sun J, Raina V, Chui R, Young W, Kwan R, Fu J, Cadieux JA. (2011) Discovery of XEN907, a spirooxindole blocker of NaV1.7 for the treatment of pain. Bioorg. Med. Chem. Lett., 21 (12): 3676-81. [PMID:21570288]

16. Coulter DA, Rafiq A, Shumate M, Gong QZ, DeLorenzo RJ, Lyeth BG. (1996) Brain injury-induced enhanced limbic epileptogenesis: anatomical and physiological parallels to an animal model of temporal lobe epilepsy. Epilepsy Res., 26 (1): 81-91. [PMID:8985690]

17. Cox JJ, Reimann F, Nicholas AK, Thornton G, Roberts E, Springell K, Karbani G, Jafri H, Mannan J, Raashid Y, Al-Gazali L, Hamamy H, Valente EM, Gorman S, Williams R, McHale DP, Wood JN, Gribble FM, Woods CG. (2006) An SCN9A channelopathy causes congenital inability to experience pain. Nature, 444 (7121): 894-8. [PMID:17167479]

18. Cummins TR, Dib-Hajj SD, Waxman SG. (2004) Electrophysiological properties of mutant Nav1.7 sodium channels in a painful inherited neuropathy. J. Neurosci., 24 (38): 8232-6. [PMID:15385606]

19. Dib-Hajj SD, Cummins TR, Black JA, Waxman SG. (2010) Sodium channels in normal and pathological pain. Annu. Rev. Neurosci., 33: 325-47. [PMID:20367448]

20. Dib-Hajj SD, Estacion M, Jarecki BW, Tyrrell L, Fischer TZ, Lawden M, Cummins TR, Waxman SG. (2008) Paroxysmal extreme pain disorder M1627K mutation in human Nav1.7 renders DRG neurons hyperexcitable. Mol Pain, 4: 37. [PMID:18803825]

21. Dib-Hajj SD, Rush AM, Cummins TR, Hisama FM, Novella S, Tyrrell L, Marshall L, Waxman SG. (2005) Gain-of-function mutation in Nav1.7 in familial erythromelalgia induces bursting of sensory neurons. Brain, 128 (Pt 8): 1847-54. [PMID:15958509]

22. Drenth JP, te Morsche RH, Guillet G, Taieb A, Kirby RL, Jansen JB. (2005) SCN9A mutations define primary erythermalgia as a neuropathic disorder of voltage gated sodium channels. J. Invest. Dermatol., 124 (6): 1333-8. [PMID:15955112]

23. Estacion M, Choi JS, Eastman EM, Lin Z, Li Y, Tyrrell L, Yang Y, Dib-Hajj SD, Waxman SG. (2010) Can robots patch-clamp as well as humans? Characterization of a novel sodium channel mutation. J. Physiol. (Lond.), 588 (Pt 11): 1915-27. [PMID:20123784]

24. Estacion M, Dib-Hajj SD, Benke PJ, Te Morsche RH, Eastman EM, Macala LJ, Drenth JP, Waxman SG. (2008) NaV1.7 gain-of-function mutations as a continuum: A1632E displays physiological changes associated with erythromelalgia and paroxysmal extreme pain disorder mutations and produces symptoms of both disorders. J. Neurosci., 28 (43): 11079-88. [PMID:18945915]

25. Estacion M, Han C, Choi JS, Hoeijmakers JG, Lauria G, Drenth JP, Gerrits MM, Dib-Hajj SD, Faber CG, Merkies IS et al.. (2011) Intra- and interfamily phenotypic diversity in pain syndromes associated with a gain-of-function variant of NaV1.7. Mol Pain, 7: 92. [PMID:22136189]

26. Estacion M, Harty TP, Choi JS, Tyrrell L, Dib-Hajj SD, Waxman SG. (2009) A sodium channel gene SCN9A polymorphism that increases nociceptor excitability. Ann. Neurol., 66 (6): 862-6. [PMID:20033988]

27. Eubanks J, Srinivasan J, Dinulos MB, Disteche CM, Catterall WA. (1997) Structure and chromosomal localization of the beta2 subunit of the human brain sodium channel. Neuroreport, 8 (12): 2775-9. [PMID:9295116]

28. Faber CG, Hoeijmakers JG, Ahn HS, Cheng X, Han C, Choi JS, Estacion M, Lauria G, Vanhoutte EK, Gerrits MM et al.. (2012) Gain of function Naν1.7 mutations in idiopathic small fiber neuropathy. Ann. Neurol., 71 (1): 26-39. [PMID:21698661]

29. Farmer C, Cox JJ, Fletcher EV, Woods CG, Wood JN, Schorge S. (2012) Splice variants of Na(V)1.7 sodium channels have distinct β subunit-dependent biophysical properties. PLoS ONE, 7 (7): e41750. [PMID:22911851]

30. Felts PA, Yokoyama S, Dib-Hajj S, Black JA, Waxman SG. (1997) Sodium channel alpha-subunit mRNAs I, II, III, NaG, Na6 and hNE (PN1): different expression patterns in developing rat nervous system. Brain Res. Mol. Brain Res., 45 (1): 71-82. [PMID:9105672]

31. Fertleman CR, Baker MD, Parker KA, Moffatt S, Elmslie FV, Abrahamsen B, Ostman J, Klugbauer N, Wood JN, Gardiner RM, Rees M. (2006) SCN9A mutations in paroxysmal extreme pain disorder: allelic variants underlie distinct channel defects and phenotypes. Neuron, 52 (5): 767-74. [PMID:17145499]

32. Fischer TZ, Gilmore ES, Estacion M, Eastman E, Taylor S, Melanson M, Dib-Hajj SD, Waxman SG. (2009) A novel Nav1.7 mutation producing carbamazepine-responsive erythromelalgia. Ann. Neurol., 65 (6): 733-41. [PMID:19557861]

33. Focken T, Chowdhury S, Zenova A, Grimwood ME, Chabot C, Sheng T, Hemeon I, Decker SM, Wilson M, Bichler P et al.. (2018) Design of Conformationally Constrained Acyl Sulfonamide Isosteres: Identification of N-([1,2,4]Triazolo[4,3- a]pyridin-3-yl)methane-sulfonamides as Potent and Selective hNaV1.7 Inhibitors for the Treatment of Pain. J. Med. Chem., 61 (11): 4810-4831. [PMID:29737846]

34. Goldberg YP, MacFarlane J, MacDonald ML, Thompson J, Dube MP, Mattice M, Fraser R, Young C, Hossain S, Pape T, Payne B, Radomski C, Donaldson G, Ives E, Cox J, Younghusband HB, Green R, Duff A, Boltshauser E, Grinspan GA, Dimon JH, Sibley BG, Andria G, Toscano E, Kerdraon J, Bowsher D, Pimstone SN, Samuels ME, Sherrington R, Hayden MR. (2007) Loss-of-function mutations in the Nav1.7 gene underlie congenital indifference to pain in multiple human populations. Clin. Genet., 71 (4): 311-9. [PMID:17470132]

35. Han C, Dib-Hajj SD, Lin Z, Li Y, Eastman EM, Tyrrell L, Cao X, Yang Y, Waxman SG. (2009) Early- and late-onset inherited erythromelalgia: genotype-phenotype correlation. Brain, 132 (Pt 7): 1711-22. [PMID:19369487]

36. Han C, Hoeijmakers JG, Ahn HS, Zhao P, Shah P, Lauria G, Gerrits MM, te Morsche RH, Dib-Hajj SD, Drenth JP et al.. (2012) Nav1.7-related small fiber neuropathy: impaired slow-inactivation and DRG neuron hyperexcitability. Neurology, 78 (21): 1635-43. [PMID:22539570]

37. Han C, Hoeijmakers JG, Liu S, Gerrits MM, te Morsche RH, Lauria G, Dib-Hajj SD, Drenth JP, Faber CG, Merkies IS et al.. (2012) Functional profiles of SCN9A variants in dorsal root ganglion neurons and superior cervical ganglion neurons correlate with autonomic symptoms in small fibre neuropathy. Brain, 135 (Pt 9): 2613-28. [PMID:22826602]

38. Han C, Rush AM, Dib-Hajj SD, Li S, Xu Z, Wang Y, Tyrrell L, Wang X, Yang Y, Waxman SG. (2006) Sporadic onset of erythermalgia: a gain-of-function mutation in Nav1.7. Ann. Neurol., 59 (3): 553-8. [PMID:16392115]

39. Harty TP, Dib-Hajj SD, Tyrrell L, Blackman R, Hisama FM, Rose JB, Waxman SG. (2006) Na(V)1.7 mutant A863P in erythromelalgia: effects of altered activation and steady-state inactivation on excitability of nociceptive dorsal root ganglion neurons. J. Neurosci., 26 (48): 12566-75. [PMID:17135418]

40. Hoeijmakers JG, Han C, Merkies IS, Macala LJ, Lauria G, Gerrits MM, Dib-Hajj SD, Faber CG, Waxman SG. (2012) Small nerve fibres, small hands and small feet: a new syndrome of pain, dysautonomia and acromesomelia in a kindred with a novel NaV1.7 mutation. Brain, 135 (Pt 2): 345-58. [PMID:22286749]

41. Isom LL, De Jongh KS, Patton DE, Reber BF, Offord J, Charbonneau H, Walsh K, Goldin AL, Catterall WA. (1992) Primary structure and functional expression of the beta 1 subunit of the rat brain sodium channel. Science, 256 (5058): 839-42. [PMID:1375395]

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William A. Catterall, Alan L. Goldin, Stephen G. Waxman.
Voltage-gated sodium channels: Nav1.7. Last modified on 26/06/2018. Accessed on 21/11/2018. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=584.