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Protein / target

Sodium channel protein type 9 subunit alpha

Encoded bySCN9AQ15858Homo sapiensSwiss-Prot
Clinically validated
Therapeutic maturity
59
Approved medicines
Open Targets target-level
View by indication →
30
Clinical trials
Small-molecule tractable
Druggability
Approved Drug

Protein at a glance

Biological role

Voltage-gated sodium channel

Strongest disease association

Channelopathy-associated congenital insensitivity to pain, autosomal recessive

Via encoding gene SCN9A · Genetic evidence · score 0.92

Therapeutic position

Established drug target

Small molecules

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 overview

Pore-forming subunit of Nav1.7, a voltage-gated sodium (Nav) channel that directly mediates the depolarizing phase of action potentials in excitable membranes.

View complete UniProt function annotation

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 gatingGO
View supporting evidence

Ion channel gating

  • ·sodium ion transmembrane transport
View underlying pathways (3)

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.

Approved medicines with mapped indications

10 medicines · 16 areas

Approved therapies targeting this protein, grouped by what they are approved to treat — the disease-first view of the medicines below. Relationships come from the canonical approved-indication graph (ChEMBL phase-4), the same source as the drug cards.

Epilepsies, Partial3 medicines
Amyotrophic Lateral Sclerosis1 medicine
Arrhythmias, Cardiac1 medicine
Arthritis1 medicine
Back Pain1 medicine
Bipolar Disorder1 medicine
Depressive Disorder1 medicine
Inflammation1 medicine
Migraine Disorders1 medicine
Neuralgia1 medicine
Neuralgia, Postherpetic1 medicine
Osteoarthritis1 medicine
Pain1 medicine
Pruritus1 medicine

59 medicines meet Open Targets' target-level approved-medicine definition; the 10 shown here are those on this page with a canonical approved disease indication in the graph. Approved indications from ChEMBL (phase-4), via the canonical drug→disease graph.

Drugs targeting this protein

10

How approved and investigational drugs engage this protein — mechanism and action type, direct vs complex targeting, and how broadly each acts across other targets. A drug-first view (the section above groups the approved ones disease-first); direct binders with few recorded targets are listed first.

Riluzole
ApprovedBlocker

Sodium channel alpha subunit blocker

Indicated for Amyotrophic Lateral Sclerosis

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

Indicated for Bipolar Disorder, Depressive Disorder, Epilepsies, Partial, Epilepsy

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

lidocaine
ApprovedBlocker

Sodium channel alpha subunit blocker

Indicated for Arrhythmias, Cardiac, Arthritis, Back Pain, Inflammation

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

lacosamide
ApprovedBlocker

Sodium channel alpha subunit blocker

Indicated for Epilepsies, Partial, Epilepsy, Seizures

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

phenytoin
ApprovedBlocker

Sodium channel alpha subunit blocker

Indicated for Epilepsy, Seizures

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

topiramate
ApprovedBlocker

Sodium channel alpha subunit blocker

Indicated for Epilepsy, Migraine Disorders, Seizures

Acts on a complex — shared with SCN5A, SCN4A, SCN7A +6 more · 1 of 37 recorded protein targets — broad pharmacology

View all 10 targeting drugs
cenobamate
ApprovedInhibitor

Sodium channel alpha subunit inhibitor

Indicated for Epilepsy, Seizures

Acts on a complex — shared with SCN5A, SCN4A, SCN7A +6 more · 1 of 26 recorded protein targets — broad pharmacology

Sodium channel alpha subunit blocker

Indicated for Epilepsy, Seizures

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

rufinamide
ApprovedBlocker

Sodium channel alpha subunit blocker

Indicated for Epilepsy, Seizures

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

zonisamide
ApprovedBlocker

Sodium channel alpha subunit blocker

Indicated for Epilepsies, Partial, Epilepsy, Seizures

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

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

Translational evidence

Open Targets 26

Why this target matters therapeutically, strongest evidence first. Disease associations are gene-level (via the gene that encodes this protein) and open into the full confidence synthesis; the development universe, tractability and safety annotations are target-level, from Open Targets.

Strongest disease associations · via encoding gene SCN9A

Gene-level evidence surfaced through the gene SCN9Athat encodes this protein — not a direct protein–disease relationship. Ranked by Forefront's causal-directness weighting, so genetically- and clinically-evidenced diseases lead over ones that merely share the literature.

Primary erythermalgia
0.94Well supported

Genetic evidence dominant · Open Targets 0.82

Channelopathy-associated congenital insensitivity to pain, autosomal recessive
0.93Well supported

Genetic evidence dominant · Open Targets 0.70

Paroxysmal extreme pain disorder
0.92Well supported

Genetic evidence dominant · Open Targets 0.79

Hereditary sensory and autonomic neuropathy type 2
0.88Well supported

Genetic evidence dominant · Open Targets 0.66

Epilepsy
0.82Well supported

Clinical evidence dominant · Open Targets 0.65

View evidence synthesis (5)
Primary erythermalgiaWell supported
0.94
agreement 0.831.00
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 0.811.00
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 0.801.00
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 0.751.00
Genetic85%Animal model15%

Open Targets aggregate 0.66 · 2 independent evidence families

EpilepsyWell supported
0.82
agreement 0.710.93
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 per-type scores above show the calculation.

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
Channelopathy-associated congenital insensitivity to pain0.62
Bipolar Disorder0.61
Hereditary sensory and autonomic neuropathy0.60

Drug development

79 compounds recorded · 59 approved · 16 in clinical development · 4 earlier-stage

Open Targets' development universe — every compound recorded against the target at any stage, not all approved medicines. Distinct from the 10 drugs that target this protein in Forefront's canonical graph (10 with a mapped approved indication, shown above): these count different sets and are not a subset relation.

View all recorded compounds (10)
PROPAFENONE HYDROCHLORIDEApproval
ENCAINIDE HYDROCHLORIDEUnknown
MORICIZINEApproval
MEPIVACAINE HYDROCHLORIDEPhase 3
FOSPHENYTOINApproval
ROPIVACAINE HYDROCHLORIDEApproval
DISOPYRAMIDE PHOSPHATEApproval
BENOXINATEApproval
AZD3161Phase 1
DYCLONINE HYDROCHLORIDEUnknown

Open Targets known-drugs universe. Drug name and highest clinical stage only — the disease relationship is NOT read from this slice (it carries trial-context noise); approved indications come from the canonical graph above.

Tractability

Small moleculesStrong

Approved Drug and Structure with Ligand support this modality.

AntibodiesEmerging

Feasibility evidence (uniprot loc high conf and go cc high conf) — no clinical-stage drug of this modality recorded.

Protein degradersEmerging

Feasibility evidence (uniprot ubiquitination and database ubiquitination) — no clinical-stage drug of this modality recorded.

View underlying tractability evidence (11)
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

Raw Open Targets tractability assessment buckets, by modality.

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. Ranked by active status, then clinical phase and recency, and spread across the targeting drugs.

View all trials (26)

COMPLETED · via lidocaine · NCT05670236

UNKNOWN · via topiramate · NCT06089356

ClinicalTrials.gov via the drug-target graph.

What's happening now

12

Recent therapeutic activity around this target — regulatory actions, clinical trials and safety signals for 5 drugs that target this protein, plus publications where such a drug is a genuine subject. Every item is reached indirectly through the drug, not the protein itself; incidental mentions (a paper that merely measures a drug) and press items are excluded.

  1. Regulatory approval2026-08-05

    Approval: ESLICARBAZEPINE ACETATE (ANDA216481)

    fda · regulatory · fda · via eslicarbazepine acetate

  2. Supplemental approval2026-07-29

    Supplemental approval: LACOSAMIDE (ANDA204921)

    fda · regulatory · fda · via lacosamide

  3. Regulatory approval2026-07-22

    Approval: TOPIRAMATE (ANDA220943)

    fda · regulatory · fda · via topiramate

  4. Product recall2026-07-06

    Recall (Class III): TOPIRAMATE

    fda · safety · fda · via topiramate

  5. Regulatory approval2026-06-15

    Approval: LACOSAMIDE (ANDA217596)

    fda · regulatory · fda · via lacosamide

  6. Product recall2026-06-04

    Recall (Class II): LACOSAMIDE

    fda · safety · fda · via lacosamide

  7. Safety communication2024-06-20

    Drug Safety Update: Topiramate (Topamax): introduction of new safety measures, including a Pregnancy Prevention Programme

    mhra · safety · mhra · via topiramate

  8. New publication2023-01-18
    Safety and tolerability of short-term infusions of intravenous lacosamide in pediatric patients with epilepsy: An open-label, phase 2/3 trial.

    Epilepsia open · 2023 · 3 citations · Europe PMC · via lacosamide

  9. Safety communication2022-07-21

    Drug Safety Update: Topiramate (Topamax): start of safety review triggered by a study reporting an increased risk of neurodevelopmental disabilities in children with prenatal exposure

    mhra · safety · mhra · via topiramate

  10. New publication2021-12-01
    Riluzole, a glutamate modulator, slows cerebral glucose metabolism decline in patients with Alzheimer's disease.

    Brain : a journal of neurology · 2021 · 71 citations · Europe PMC · via Riluzole

  11. New publication2021-06-29
    Safety and efficacy of adjunctive lacosamide in Chinese and Japanese adults with epilepsy and focal seizures: A long-term, open-label extension of a randomized, controlled trial.

    Epilepsy research · 2021 · 14 citations · Europe PMC · via lacosamide

  12. New publication2018-03-14
    Canadian Network for Mood and Anxiety Treatments (CANMAT) and International Society for Bipolar Disorders (ISBD) 2018 guidelines for the management of patients with bipolar disorder.

    Bipolar disorders · 2018 · 1,126 citations · Europe PMC · 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.