Protein detail

SCN9A

Sodium channel protein type 9 subunit alpha (Neuroendocrine sodium channel) (hNE-Na) (Peripheral sodium channel 1) (PN1) (Sodium channel protein type IX subunit alpha) (Voltage-gated sodium channel subunit alpha Nav1.7)

Entry name SCN9A	UniProt ID Q15858	EVMP score 0.50
Frequency 1	Transmembrane count 24	Protein classification Disease related genesFDA approved drug targetsHuman disease related genesMetabolic proteinsPredicted membrane proteinsTransportersVoltage-gated ion channels

EVMP score: annotation confidence score.

Extremely high >= 0.85High >= 0.70Medium >= 0.55Low >= 0.40

Basic Information

Protein Names

Protein Class

Disease related genesFDA approved drug targetsHuman disease related genesMetabolic proteinsPredicted membrane proteinsTransportersVoltage-gated ion channels

Protein Function

Human disease related genes:Cardiovascular diseases:Vascular diseases
Human disease related genes:Nervous system diseases:Other nervous and sensory system diseases
Voltage-gated ion channels:Voltage-Gated Sodium Channels
Transporters:Transporter channels and pores
Disease related genes
FDA approved drug targets:Small molecule drugs

Transmembrane

126..145; Helical; Name=S1 of repeat I; 151..172; Helical; Name=S2 of repeat I; 186..204; Helical; Name=S3 of repeat I; 211..227; Helical; Name=S4 of repeat I; 242..267; Helical; Name=S5 of repeat I; 377..402; Helical; Name=S6 of repeat I; 746..762; Helical; Name=S1 of repeat II; 772..796; Helical; Name=S2 of repeat II; 806..822; Helical; Name=S3 of repeat II; 832..848; Helical; Name=S4 of repeat II; 866..888; Helical; Name=S5 of repeat II; 941..967; Helical; Name=S6 of repeat II; 1188..1212; Helical; Name=S1 of repeat III; 1225..1250; Helical; Name=S2 of repeat III; 1253..1278; Helical; Name=S3 of repeat III; 1288..1304; Helical; Name=S4 of repeat III; 1318..1342; Helical; Name=S5 of repeat III; 1432..1457; Helical; Name=S6 of repeat III; 1515..1534; Helical; Name=S1 of repeat IV; 1546..1567; Helical; Name=S2 of repeat IV; 1577..1598; Helical; Name=S3 of repeat IV; 1608..1627; Helical; Name=S4 of repeat IV; 1641..1663; Helical; Name=S5 of repeat IV; 1734..1759; Helical; Name=S6 of repeat IV

Transmembrane Count

Ensembl

ENSG00000169432

Entrez Gene Symbol

SCN9A

Gene Synonym

ETHANav1.7NE-NANENAPN1

Gene Description

Sodium voltage-gated channel alpha subunit 9

Chromosome

Position

166195185-166376001

Frequency

EVMP Score

0.50

Fluorescence & Localization

Tissue Specificadrenal glandBrain Regional Specificbasal gangliaCell SpecificBrain excitatory neuronsSingle-Nuclei Brain Specificmedium spiny neuron

Function & Pathway

Protein Function

Human disease related genes:Cardiovascular diseases:Vascular diseases
Human disease related genes:Nervous system diseases:Other nervous and sensory system diseases
Voltage-gated ion channels:Voltage-Gated Sodium Channels
Transporters:Transporter channels and pores
Disease related genes
FDA approved drug targets:Small molecule drugs

Cellular Component

Molecular Function

Biological Process

KEGG

hsa04742 Taste transduction

Reactome

Mediation Categories

Clinical-translation mediationFusion and delivery mediation

Relations & Evidence

Enzyme-Mediated Modification

3 records.

Substrate Gene Symbol	Enzyme Gene Symbol	Enzyme UniProt ID	Residue Type	Residue Offset	Modification	Database
SCN9A	FYN	P06241	Y	1,482	phosphorylation	PhosphoSite
SCN9A	FYN	P06241	Y	1,481	phosphorylation	PhosphoSite
SCN9A	PRKCA	P17252	I	848	phosphorylation	PhosphoSite

Ligand-Receptor Signaling

25 records.

Category	Parent	Database	Transmitter	Receiver	Secreted	Plasma Membrane (Transmembrane)	Plasma Membrane (Peripheral)
ion_channel	ion_channel	OmniPath	No	Yes	No	No	No
transmembrane	transmembrane	UniProt_location	No	No	No	No	No
transmembrane	transmembrane	UniProt_topology	No	No	No	No	No
transmembrane	transmembrane	UniProt_keyword	No	No	No	No	No
transmembrane	transmembrane	TopDB	No	No	No	No	No
transmembrane	transmembrane	Ramilowski_location	No	No	No	No	No
transmembrane	transmembrane	OmniPath	No	No	No	No	No
peripheral	peripheral	UniProt_topology	No	No	No	No	No
peripheral	peripheral	OmniPath	No	No	No	No	No
plasma_membrane	plasma_membrane	UniProt_location	No	No	No	No	No

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Regulatory Interaction Network

6 records.

Source Protein Symbol	Source UniProt ID	Target Protein Symbol	Target UniProt ID	Is Directed	Is Stimulation	Is Inhibition	Database	References
FGF11	Q92914	SCN9A	Q15858	Yes	No	Yes	SIGNOR	SIGNOR:20679355
FYN	P06241	SCN9A	Q15858	Yes	Yes	No	PhosphoSite_norefSIGNORProtMapperPhosphoSitePhosphoSite_ProtMapper	PhosphoSite:29790812 SIGNOR:29790812
NED4L	Q96PU5	SCN9A	Q15858	Yes	No	Yes	SIGNOR	SIGNOR:23778145
FGF14	Q92915	SCN9A	Q15858	Yes	No	Yes	SIGNOR	SIGNOR:20679355
FGF12	P61328	SCN9A	Q15858	Yes	No	Yes	SIGNOR	SIGNOR:20679355
FGF13	Q92913	SCN9A	Q15858	Yes	No	Yes	SIGNOR	SIGNOR:20679355

Protein Complex Composition

1 record.

Component Name	Component Gene Symbols	Component UniProt ID	Stoichiometry	Database	Database IDs	References
	SCN1B SCN9A	Q07699 Q15858	1:1	PDB	PDB:8j4fPDB:8xmm

Isolation & Detection Technology

1 record.

EV Isolation Method	Detection Method	Number of References	References
Differential UltracentrifugationUltrafiltration / Tangential Flow FiltrationSize Exclusion ChromatographyMicrofluidics-Based Methods	Mass spectrometry	22	39290459 23376485 31508500 34071777 40545963 39443544 37702715 32795414 30382917 38731868 26801919 30071318 32927759 37686366 41201090 30760538 36982312 40311616 40091455 38136601 38612515 41315767

Sequence, Structure & Domains

Sequences

Length

1,988

Mass

226,372

Sequence

MAMLPPPGPQSFVHFTKQSLALIEQRIAERKSKEPKEEKKDDDEEAPKPSSDLEAGKQLPFIYGDIPPGMVSEPLEDLDPYYADKKTFIVLNKGKTIFRFNATPALYMLSPFSPLRRISIKILVHSLFSMLIMCTILTNCIFMTMNNPPDWTKNVEYTFTGIYTFESLVKILARGFCVGEFTFLRDPWNWLDFVVIVFAYLTEFVNLGNVSALRTFRVLRALKTISVIPGLKTIVGALIQSVKKLSDVMILTVFCLSVFALIGLQLFMGNLKHKCFRNSLENNETLESIMNTLESEEDFRKYFYYLEGSKDALLCGFSTDSGQCPEGYTCVKIGRNPDYGYTSFDTFSWAFLALFRLMTQDYWENLYQQTLRAAGKTYMIFFVVVIFLGSFYLINLILAVVAMAYEEQNQANIEEAKQKELEFQQMLDRLKKEQEEAEAIAAAAAEYTSIRRSRIMGLSESSSETSKLSSKSAKERRNRRKKKNQKKLSSGEEKGDAEKLSKSESEDSIRRKSFHLGVEGHRRAHEKRLSTPNQSPLSIRGSLFSARRSSRTSLFSFKGRGRDIGSETEFADDEHSIFGDNESRRGSLFVPHRPQERRSSNISQASRSPPMLPVNGKMHSAVDCNGVVSLVDGRSALMLPNGQLLPEVIIDKATSDDSGTTNQIHKKRRCSSYLLSEDMLNDPNLRQRAMSRASILTNTVEELEESRQKCPPWWYRFAHKFLIWNCSPYWIKFKKCIYFIVMDPFVDLAITICIVLNTLFMAMEHHPMTEEFKNVLAIGNLVFTGIFAAEMVLKLIAMDPYEYFQVGWNIFDSLIVTLSLVELFLADVEGLSVLRSFRLLRVFKLAKSWPTLNMLIKIIGNSVGALGNLTLVLAIIVFIFAVVGMQLFGKSYKECVCKINDDCTLPRWHMNDFFHSFLIVFRVLCGEWIETMWDCMEVAGQAMCLIVYMMVMVIGNLVVLNLFLALLLSSFSSDNLTAIEEDPDANNLQIAVTRIKKGINYVKQTLREFILKAFSKKPKISREIRQAEDLNTKKENYISNHTLAEMSKGHNFLKEKDKISGFGSSVDKHLMEDSDGQSFIHNPSLTVTVPIAPGESDLENMNAEELSSDSDSEYSKVRLNRSSSSECSTVDNPLPGEGEEAEAEPMNSDEPEACFTDGCVWRFSCCQVNIESGKGKIWWNIRKTCYKIVEHSWFESFIVLMILLSSGALAFEDIYIERKKTIKIILEYADKIFTYIFILEMLLKWIAYGYKTYFTNAWCWLDFLIVDVSLVTLVANTLGYSDLGPIKSLRTLRALRPLRALSRFEGMRVVVNALIGAIPSIMNVLLVCLIFWLIFSIMGVNLFAGKFYECINTTDGSRFPASQVPNRSECFALMNVSQNVRWKNLKVNFDNVGLGYLSLLQVATFKGWTIIMYAAVDSVNVDKQPKYEYSLYMYIYFVVFIIFGSFFTLNLFIGVIIDNFNQQKKKLGGQDIFMTEEQKKYYNAMKKLGSKKPQKPIPRPGNKIQGCIFDLVTNQAFDISIMVLICLNMVTMMVEKEGQSQHMTEVLYWINVVFIILFTGECVLKLISLRHYYFTVGWNIFDFVVVIISIVGMFLADLIETYFVSPTLFRVIRLARIGRILRLVKGAKGIRTLLFALMMSLPALFNIGLLLFLVMFIYAIFGMSNFAYVKKEDGINDMFNFETFGNSMICLFQITTSAGWDGLLAPILNSKPPDCDPKKVHPGSSVEGDCGNPSVGIFYFVSYIIISFLVVVNMYIAVILENFSVATEESTEPLSEDDFEMFYEVWEKFDPDATQFIEFSKLSDFAAALDPPLLIAKPNKVQLIAMDLPMVSGDRIHCLDILFAFTKRVLGESGEMDSLRSQMEERFMSANPSKVSYEPITTTLKRKQEDVSATVIQRAYRRYRLRQNVKNISSIYIKDGDRDDDLLNKKDMAFDNVNENSSPEKTDATSSTTSPPSYDSVTKPDKEKYEQDRTEKEDKGKDSKESKK

Alternative Products

Event=Alternative splicing; Named isoforms=4; Name=1; IsoId=Q15858-1; Sequence=Displayed; Name=2; IsoId=Q15858-2; Sequence=VSP_012028; Name=3; IsoId=Q15858-3; Sequence=VSP_012029; Name=4; IsoId=Q15858-4; Sequence=VSP_012028, VSP_012029

Alternative Sequence

200..229; YLTEFVNLGNVSALRTFRVLRALKTISVIP -> YVTEFVDLGNVSALRTFRVLRALKTISVIP (in isoform 2 and isoform 4); 648..658; Missing (in isoform 3 and isoform 4)

3D Structural Models

Turn

51..53; 68..70; 93..95; 106..108; 300..302; 337..341; 389..391; 743..745; 831..833; 863..866; 1344..1347; 1353..1356; 1427..1430; 1467..1469; 1600..1602; 1696..1699; 1712..1714; 1787..1789; 1806..1808; 1811..1813; 1832..1834

Helix

9..11; 17..33; 61..63; 80..84; 114..123; 126..143; 150..152; 153..174; 183..185; 189..205; 210..221; 223..227; 231..244; 246..267; 270..272; 286..291; 296..299; 347..359; 363..374; 376..378; 379..388; 392..434; 729..740; 746..761; 768..772; 800..803; 807..824; 828..830; 834..846; 852..862; 867..894; 896..899; 913..925; 929..939; 941..972; 973..976; 987..1013; 1176..1189; 1192..1209; 1216..1218; 1220..1254; 1257..1277; 1284..1290; 1291..1299; 1300..1303; 1305..1343; 1367..1376; 1392..1403; 1408..1417; 1431..1433; 1434..1444; 1446..1466; 1476..1488; 1503..1512; 1515..1534; 1541..1568; 1570..1575; 1577..1599; 1606..1612; 1613..1616; 1617..1621; 1623..1626; 1631..1639; 1641..1665; 1684..1695; 1700..1707; 1733..1767; 1776..1786; 1799..1805; 1820..1825; 1838..1850; 1855..1870; 1874..1876; 1883..1890

Beta Strand

54..58; 71..73; 85..91; 96..101; 111..113; 176..182; 186..188; 228..230; 273..278; 281..283; 317..321; 328..332; 344..346; 765..767; 825..827; 901..903; 910..912; 981..984; 1278..1280; 1348..1352; 1361..1364; 1378..1384; 1386..1388; 1389..1391; 1421..1423; 1472..1474; 1628..1630; 1666..1669; 1672..1674; 1677..1683; 1722..1724; 1795..1798; 1829..1831; 1835..1837; 1879..1882

3D Structure

Electron microscopy (39); X-ray crystallography (2)

Domain & Motif Annotations

Compositional Bias

26..39; Basic and acidic residues; 461..471; Low complexity; 474..486; Basic residues; 489..510; Basic and acidic residues; 573..585; Basic and acidic residues; 1120..1131; Polar residues; 1137..1148; Acidic residues; 1948..1961; Low complexity; 1962..1988; Basic and acidic residues

Repeat

112..410; I; 726..989; II; 1180..1488; III; 1497..1795; IV

Domain (CC)

The sequence contains 4 internal repeats, each with 5 hydrophobic segments (S1, S2, S3, S5, S6) and one positively charged segment (S4). Segments S4 are probably the voltage-sensors and are characterized by a series of positively charged amino acids at every third position.

Domain (FT)

1889..1918; IQ

Region

26..55; Disordered; 461..543; Disordered; 565..611; Disordered; 1102..1148; Disordered; 1934..1988; Disordered

Protein Families

Sodium channel (TC 1.A.1.10) family
Nav1.7/SCN9A subfamily

Sequence Similarities

Belongs to the sodium channel (TC 1.A.1.10) family. Nav1.7/SCN9A subfamily.

Clinical Relevance

Disease Involvement

Disease variantEpilepsyFDA approved drug targets

Related Diseases

Asthma Bipolar disorder Chronic pain Dissociative neurological symptom disorder Extremities vasodilatation General pain disorder Osteoarthritis Pain Radiculopathy Trigeminal nerve disorder

Biomarker

Discontinued in Phase 2; Phase 2; Phase 1

Drug Targets

FDA approved drug targets

Drugs

QUINIDINE SULFATE TETRACAINE TOCAINIDE HYDROCHLORIDE NULL MORICIZINE HYDROCHLORIDE AM-6120 PROPARACAINE HYDROCHLORIDE FUNAPIDE ABBV-318 CHLOROPROCAINE NERISPIRDINE LIDOCAINE LACOSAMIDE MEPHENYTOIN PROPOFOL DRONEDARONE HYDROCHLORIDE ETIDOCAINE HYDROCHLORIDE RUFINAMIDE PROPAFENONE HYDROCHLORIDE INDECAINIDE HYDROCHLORIDE ESLICARBAZEPINE ACETATE DSP-2230 ETHOTOIN ZONISAMIDE EVENAMIDE CENOBAMATE SAFINAMIDE PROCAINE HYDROCHLORIDE RALFINAMIDE HEXYLCAINE HYDROCHLORIDE DISOPYRAMIDE PHOSPHATE MEPIVACAINE HYDROCHLORIDE PROPOXYCAINE HYDROCHLORIDE ESLICARBAZEPINE LIDOCAINE HYDROCHLORIDE TETRODOTOXIN PRIMIDONE VIXOTRIGINE XEN907 QUINIDINE GLUCONATE CD2+SAXITOXIN COCAINE HYDROCHLORIDE PRILOCAINE RG7893 ORPHENADRINE CITRATE DICHLOROBENZYL ALCOHOL RANOLAZINE ORPHENADRINE HYDROCHLORIDE PRILOCAINE HYDROCHLORIDE RG6029 PF‐06526290 PROCAINAMIDE HYDROCHLORIDE IRAMPANEL PHENAZOPYRIDINE HYDROCHLORIDE RILUZOLE TOPIRAMATE MERETHOXYLLINE PROCAINE DYCLONINE HYDROCHLORIDE PF-05089771 QUINIDINE POLYGALACTURONATE BATRACHOTOXIN PYRROLOPYRIMIDINE 48 [PMID: 22318156]PF-05241328 AZD3161 ROPIVACAINE HYDROCHLORIDE MEXILETINE HYDROCHLORIDE DS-1971A PHENYTOIN SODIUM ARTICAINE HYDROCHLORIDE ENCAINIDE HYDROCHLORIDE XEN403 PHENACEMIDE CARBAMAZEPINE NKTR-171 OXCARBAZEPINE BENOXINATE HYDROCHLORIDE N-ME-AMINOPYRIMIDINONE 9 VERATRIDINE GNE-616 FOSPHENYTOIN LAMOTRIGINE GNE-131

Antibody

CAB013679 HPA061843