Protein / target

Sodium channel protein type 9 subunit alpha

SCN9AQ15858Homo sapiensSwiss-Prot
UniProt: Q15858Ensembl: ENSG00000169432HGNC: HGNC:10597NCBI Gene: 6335
Clinically validated
Therapeutic maturity
59
Approved medicines
30
Clinical trials
Small-molecule tractable
Druggability
Approved Drug

Protein at a glance

Biological role

Voltage-gated sodium channel activity

Primary system

Nervous system

Strongest disease association

channelopathy-associated congenital insensitivity to pain, autosomal recessive

Genetic evidence · score 0.92

Therapeutic maturity

Clinically validated target

59 approved medicines against this target

Druggability

Small molecule

Open Targets tractability · Approved Drug

Clinical development

59 approved · 16 in clinical development

30 linked trials

Derived from structured UniProt, Open Targets and literature data on this page.

Protein profile

UniProt 2026_02

Canonical identity and biological annotation from UniProt.

Function

Pore-forming subunit of Nav1.7, a voltage-gated sodium (Nav) channel that directly mediates the depolarizing phase of action potentials in excitable membranes (PubMed:38381792, PubMed:40768348). Navs, also called VGSCs (voltage-gated sodium channels) or VDSCs (voltage-dependent sodium channels), operate by switching between closed and open conformations depending on the voltage difference across the membrane. In the open conformation they allow Na(+) ions to selectively pass through the pore, along their electrochemical gradient (PubMed:38381792, PubMed:40768348). The influx of Na(+) ions provokes membrane depolarization, initiating the propagation of electrical signals throughout cells and tissues (PubMed:15385606, PubMed:16988069, PubMed:17145499, PubMed:17167479, PubMed:19369487, PubMed:24311784, PubMed:25240195, PubMed:26680203, PubMed:7720699). Nav1.7 plays a crucial role in controlling the excitability and action potential propagation from nociceptor neurons, thereby contributing to the sensory perception of pain (PubMed:17145499, PubMed:17167479, PubMed:19369487, PubMed:24311784)

Subcellular location

Cell membraneCell projection, neuron projectionCell projection, axon
Domains and Gene Ontology detail (16)

Domains & features

IQ

Gene Ontology

  • Caxon
  • Caxon terminus
  • Cnode of Ranvier
  • Cplasma membrane
  • Cvoltage-gated sodium channel complex
  • Fvoltage-gated sodium channel activity
  • Paction potential propagation
  • Pcardiac muscle cell action potential involved in contraction
  • Pcircadian rhythm
  • Pdetection of mechanical stimulus involved in sensory perception
  • Pdetection of temperature stimulus involved in sensory perception of pain
  • Pmembrane depolarization during action potential

1988 aa · 226 kDa · 4 isoforms

Biological roles

Reactome v97

What this protein does, drawn together from its UniProt function, Gene Ontology terms and Reactome pathways.

Ion channel gatingGOImmune signallingUniProt
View supporting evidence

Ion channel gating

  • ·sodium ion transmembrane transport

Immune signalling

  • ·Pore-forming subunit of Nav1.7, a voltage-gated sodium (Nav) channel that directly media…
View underlying pathways (3)
Interaction between L1 and Ankyrins
Phase 0 - rapid depolarisation
Sensory perception of sweet, bitter, and umami (glutamate) taste

Concepts derived from UniProt GO Reactome — each badge above shows which sources supported that role.

Interaction neighbourhood

STRING v12.0

Proteins with the strongest functional or physical association. Node size and line weight reflect STRING confidence; hover or select a partner to inspect one association.

SCN1BSCN2BSCN2ASCN3ACALHM1SCN4BGABRG2NAV1MPV17AGLSCN9A

10 strongest partners — larger node and heavier line mean higher confidence

Functional and physical associations from STRING v12.0. Only associations with this protein are drawn — partner-to-partner links are not part of this evidence.

Drugs targeting this protein

2

Whether each drug engages this protein directly or through a complex, and how many other targets are recorded for it. Direct binders with few recorded targets are listed first.

Riluzole
ApprovedBlocker

Sodium channel alpha subunit blocker

Appears in clinical studies involving amyotrophic lateral sclerosis, progressive supranuclear palsy, multiple system atrophy, Huntington disease

Acts on a complex — shared with SCN5A, SCN4A, SCN7A +6 more · 1 of 10 recorded protein targets — broad pharmacology

lamotrigine
ApprovedBlocker

Sodium channel alpha subunit blocker

Appears in clinical studies involving epilepsy, bipolar disorder, major depressive disorder, Seizure

Acts on a complex — shared with SCN5A, SCN4A, SCN7A +6 more · 1 of 10 recorded protein targets — broad pharmacology

ChEMBL mechanism, action type and target identity. Open Targets clinical status and indications.

Translational evidence

Open Targets 26

Why this target matters therapeutically — disease associations, drugs in development, tractability and safety, from Open Targets.

Strongest genetic associations

Human genetic evidence — the most direct causal link between this target and a disease.

channelopathy-associated congenital insensitivity to pain, autosomal recessive0.92

Genetic · overall 0.70

primary erythermalgia0.91

Genetic · overall 0.82

paroxysmal extreme pain disorder0.90

Genetic · overall 0.79

Channelopathy-associated congenital insensitivity to pain0.87

Genetic literature · overall 0.62

hereditary sensory and autonomic neuropathy type 20.86

Genetic · overall 0.66

Highest-confidence therapeutic associations

Diseases where a drug acting on this target has already reached clinical development.

epilepsy1.00

Clinical · overall 0.65

Pain1.00

Clinical · overall 0.61

bipolar disorder0.99

Clinical · overall 0.61

Seizure0.99

Clinical · overall 0.64

Highest overall evidence

Remaining associations by Open Targets' aggregated evidence score.

hereditary sensory and autonomic neuropathy0.60

Literature

Show all associations
primary erythermalgia0.82
paroxysmal extreme pain disorder0.79
channelopathy-associated congenital insensitivity to pain, autosomal recessive0.70
hereditary sensory and autonomic neuropathy type 20.66
epilepsy0.65
Seizure0.64
Channelopathy-associated congenital insensitivity to pain0.62
Pain0.61
bipolar disorder0.61
hereditary sensory and autonomic neuropathy0.60

Open Targets ranks 785 associations for this target and we store the top 10 by aggregated score. The long tail is largely literature co-mention and RNA-expression evidence, not evidence that this target drives those diseases.

Known drugs · 79 total

PROPAFENONE HYDROCHLORIDEApproval

atrial fibrillation · Ventricular arrhythmia

ENCAINIDE HYDROCHLORIDEUnknown
MORICIZINEApproval

cardiac arrhythmia · Arrhythmia · atrial fibrillation

MEPIVACAINE HYDROCHLORIDEPhase 3

Pain · diabetes mellitus

FOSPHENYTOINApproval

epilepsy · IgA glomerulonephritis · status epilepticus

ROPIVACAINE HYDROCHLORIDEApproval

Pain

DISOPYRAMIDE PHOSPHATEApproval

cardiac arrhythmia · Ventricular arrhythmia

BENOXINATEApproval

Pruritus · myopia

AZD3161Phase 1

peripheral neuropathy

DYCLONINE HYDROCHLORIDEUnknown

Tractability

SM · Approved DrugSM · Structure with LigandSM · High-Quality LigandSM · Druggable FamilyAB · UniProt loc high confAB · GO CC high confAB · UniProt SigP or TMHMMAB · Human Protein Atlas locPR · UniProt UbiquitinationPR · Database UbiquitinationPR · Small Molecule Binder

Clinical trials

30

Trials of drugs that target this protein — reached indirectly through those drugs, so a trial listed here studies the drug, not the protein.

Glutamatergic Dysfunction in Cognitive Aging: Riluzole in Mild Alzheimer's DiseasePHASE2

COMPLETED · via Riluzole · NCT01703117

A Phase II Trial of Riluzole in Patients With Advanced MelanomaPHASE2

COMPLETED · via Riluzole · NCT00866840

Eight-Month Maintenance Treatment of Bipolar Depression With Lamotrigine or Lamotrigine Plus Divalproex CombinationPHASE4

COMPLETED · via lamotrigine · NCT00183469

Comparison of Olanzapine and Lamotrigine in the Prevention of Recurrence of Depressive Episode in the Patients With Bipolar DisordersPHASE4

COMPLETED · via lamotrigine · NCT01864551

A Multi-Center, Double-Blind, Randomized, Placebo-Controlled, Parallel-Group Evaluation of Lamotrigine Adjunctive Therapy in Subjects Wtih Primary Generalized Tonic-Clonic SeizuresPHASE4

COMPLETED · via lamotrigine · NCT00043901

The Efficacy and Safety of First-Line Anti-Epileptic Drugs (AEDs) as Substitution Therapy in Children Who Are Resistant to Second-Line AEDsPHASE4

UNKNOWN · via lamotrigine · NCT05697614

Show remaining trials (24)
A Single-center, Randomized, Double-blind, Placebo-controlled, 6-month Trial Followed by an Open-label Extension to Evaluate the Safety, Tolerability and Clinical Endpoint Responsiveness of Ibudilast (MN-166) in Subjects With (ALS)PHASE2

COMPLETED · via Riluzole · NCT02238626

Efficacy and Tolerability of Riluzole in Treatment Resistant DepressionPHASE2

COMPLETED · via Riluzole · NCT01204918

A Randomized, Open Label, Single Dose, Crossover, Bioequivalence Study of Lamotrigine 2 x 25 mg IR Tablets of Torrent Pharmaceuticals Pvt., Ltd., India and Lamictal ® (Lamotrigine) 2 x 25 mg Tablets of Glaxo-SmithKline, USA, in Healthy Human Adult Subjects,Under Fed ConditionsPHASE1

COMPLETED · via lamotrigine · NCT00939458

Lamotrigine for Ménière's Disease: a Double-blind, Placebo-controlled Pilot StudyPHASE2

COMPLETED · via lamotrigine · NCT02158585

Single-Dose Fasting In Vivo Bioequivalence Study of Lamotrigine Tablets (25 mg; Mylan) to Lamictal® Tablets (25 mg; GSK) in Healthy VolunteersPHASE1

COMPLETED · via lamotrigine · NCT00650208

Decision-Making in Bipolar DisorderNA

COMPLETED · via lamotrigine · NCT01463111

Cognitive AED Outcomes in Pediatric Localization Related Epilepsy (COPE)PHASE3

TERMINATED · via lamotrigine · NCT01891890

Efficacy of Riluzole in Hereditary Cerebellar Ataxia: a Randomized Double-blind Placebo-controlled Trial.PHASE2/PHASE3

COMPLETED · via Riluzole · NCT01104649

Single-Dose Food In Vivo Bioequivalence Study of Lamotrigine Tablets (25 mg; Mylan) to Lamictal® Tablets (25 mg; GSK) in Healthy VolunteersPHASE1

COMPLETED · via lamotrigine · NCT00647751

A Double-Blind Placebo Controlled Add-on Study to Determine the Efficacy and Safety of Lamictal (Lamotrigine) in Patients With Trigeminal Neuralgia (Tic Doloureux)NA

COMPLETED · via lamotrigine · NCT00203229

A Phase I Trial of Riluzole and Sorafenib in Patients With Advanced Solid Tumors and MelanomaPHASE1

ACTIVE_NOT_RECRUITING · via Riluzole · NCT01303341

A Phase 1, Open-label Drug Interaction Study Between Eslicarbazepine Acetate 1200mg and Lamotrigine 150mg Following Multiple Doses Administrations in Healthy Male VolunteersPHASE1

COMPLETED · via lamotrigine · NCT02283801

Equivalence Among Antiepileptic Drug Generic and Brand Products in People With Epilepsy: Single-Dose 6-Period Replicate Design (EQUIGEN Single-Dose Study)PHASE4

COMPLETED · via lamotrigine · NCT01733394

An Open-label, Single-dose, Three-period Phase Ⅰ Study to Compare the Pharmacokinetics of Y-4 Tablets With Pregabalin Capsules and Riluzole Tablets in U.S. Healthy ParticipantsPHASE1

NOT_YET_RECRUITING · via Riluzole · NCT07618715

A Double-Blind Placebo Controlled Trial of Riluzole in Bipolar DepressionPHASE2

COMPLETED · via Riluzole · NCT00376220

Childhood Absence Epilepsy Rx PK-PD-Pharmacogenetics StudyPHASE3

COMPLETED · via lamotrigine · NCT00088452

A Double-Blind Study of Lamictal in Neurotic ExcoriationPHASE2

COMPLETED · via lamotrigine · NCT00513019

A Phase IIB Randomized, Double-Blind, Placebo-Controlled, Multi-Dose Study to Evaluate the Effects of PHENOGENE-1A (Cromolyn) as an Adjuvant Treatment in Subjects With Mild to Moderate Amyotrophic Lateral Sclerosis (ALS)PHASE2

RECRUITING · via Riluzole · NCT07142291

Olanzapine/Fluoxetine Combination Versus Lamotrigine in the Treatment of Bipolar I DepressionPHASE4

COMPLETED · via lamotrigine · NCT00485771

Multicentric, Randomized, Double-blind Study Versus Placebo, With Two Parallel Groups Treated to Evaluate the Efficacy and the Tolerance of Riluzole in Children and Young Adults (6 to 20 Years of Age) With SMA. (Type II and Type III)PHASE2/PHASE3

COMPLETED · via Riluzole · NCT00774423

Riluzole Augmentation Pilot in Depression (RAPID) TrialPHASE2

TERMINATED · via Riluzole · NCT01703039

Lamotrigine Extended-Release in Elderly Patients With EpilepsyPHASE3

COMPLETED · via lamotrigine · NCT00516139

The Efficacy and Safety of Lamotrigine Versus Carbamazepine in Focal Epilepsy: A Randomized, Open Label Clinical Trial in Dhaka Medical College HospitalPHASE4

UNKNOWN · via lamotrigine · NCT05748236

Phase II/III, Multicenter, Randomized, Parallel Group, Double-blind, Placebo Controlled Study to Assess Safety and Efficacy of TRO19622 in Amyotrophic Lateral Sclerosis (ALS) Patients Treated With RiluzolePHASE3

COMPLETED · via Riluzole · NCT00868166

ClinicalTrials.gov via the drug-target graph.

Forefront confidence

Synthesis

Our own weighting of the evidence behind each disease association. Human genetics and clinical evidence count for most; literature co-mention counts for little, because two entities sharing an abstract is not evidence that one drives the other.

primary erythermalgiaWell supported
0.94
agreement 0.83–1.00
Genetic72%Clinical25%Literature3%Genetic literaturedup

Open Targets aggregate 0.82 · 3 independent evidence families · 1 not counted as duplicate

channelopathy-associated congenital insensitivity to pain, autosomal recessiveWell supported
0.93
agreement 0.81–1.00
Genetic86%Animal model14%Genetic literaturedup

Open Targets aggregate 0.70 · 2 independent evidence families · 1 not counted as duplicate

paroxysmal extreme pain disorderWell supported
0.92
agreement 0.80–1.00
Genetic83%Animal model11%Literature6%Genetic literaturedup

Open Targets aggregate 0.79 · 3 independent evidence families · 1 not counted as duplicate

hereditary sensory and autonomic neuropathy type 2Well supported
0.88
agreement 0.75–1.00
Genetic85%Animal model15%

Open Targets aggregate 0.66 · 2 independent evidence families

epilepsyWell supported
0.82
agreement 0.71–0.93
Clinical72%Genetic19%Literature10%Genetic literaturedup

Open Targets aggregate 0.65 · 3 independent evidence families · 1 not counted as duplicate

The evidence agreement range shows how closely the independent evidence families agree — it is not a statistical confidence interval, and nothing here is fitted to outcome data. Derived from Open Targets evidence types under Forefront weighting; the underlying per-type scores are shown above so the calculation can be checked.

What's happening now

60

Recent activity around this target, drawn from one canonical event stream. Every item is reached through 2 drugs that target this protein, so each event is news about that drug rather than about the protein directly.

  1. Label change2026-07-27

    Label change: LAMOTRIGINE (ANDA206382)

    fda · regulatory · fda · via lamotrigine

  2. Label change2026-07-17

    Label change: LAMOTRIGINE (NDA218879)

    fda · regulatory · fda · via lamotrigine

  3. Label change2026-07-17

    Label change: LAMOTRIGINE (NDA218879)

    fda · regulatory · fda · via lamotrigine

  4. Label change2026-07-13

    Label change: LAMOTRIGINE (ANDA219677)

    fda · regulatory · fda · via lamotrigine

  5. Label change2026-06-26

    Label change: LAMOTRIGINE (ANDA204158)

    fda · regulatory · fda · via lamotrigine

  6. Label change2026-06-26

    Label change: LAMOTRIGINE (ANDA204158)

    fda · regulatory · fda · via lamotrigine

  7. Label change2026-06-26

    Label change: LAMOTRIGINE (ANDA204158)

    fda · regulatory · fda · via lamotrigine

  8. Label change2026-06-26

    Label change: LAMOTRIGINE (ANDA204158)

    fda · regulatory · fda · via lamotrigine

  9. Label change2025-12-31

    Label change: LAMOTRIGINE (ANDA090401)

    fda · regulatory · fda · via lamotrigine

  10. Label change2025-10-10

    Label change: LAMOTRIGINE (NDA022251)

    fda · regulatory · fda · via lamotrigine

  11. Label change2025-10-10

    Label change: LAMOTRIGINE (NDA022251)

    fda · regulatory · fda · via lamotrigine

  12. Regulatory approval2025-10-07

    Approval: LAMOTRIGINE (ANDA219677)

    fda · regulatory · fda · via lamotrigine

Objective event titles are shown unmodified; the event kind and significance line are derived from structured fields. Forefront AttentionEvent stream aggregating Europe PMC Regulatory filings ClinicalTrials.gov.