Protein / target

Sodium channel protein type 4 subunit alpha

SCN4AP35499Homo sapiensSwiss-Prot
UniProt: P35499Ensembl: ENSG00000007314HGNC: HGNC:10591NCBI Gene: 6329
Clinically validated
Therapeutic maturity
63
Approved medicines
30
Clinical trials
Small-molecule tractable
Druggability
Approved Drug

Protein at a glance

Biological role

Voltage-gated sodium channel activity

Primary system

Musculoskeletal system

Strongest disease association

potassium-aggravated myotonia

Genetic evidence · score 0.96

Therapeutic maturity

Clinically validated target

63 approved medicines against this target

Druggability

Small molecule

Open Targets tractability · Approved Drug

Clinical development

63 approved · 10 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 Nav1.4, a voltage-gated sodium (Nav) channel that directly mediates the depolarizing phase of action potentials in excitable membranes. 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. The influx of Na+ ions provokes membrane depolarization, initiating the propagation of electrical signals throughout cells and tissues (PubMed:12766226, PubMed:15318338, PubMed:16890191, PubMed:17898326, PubMed:18690054, PubMed:19347921, PubMed:25707578, PubMed:26659129, PubMed:26700687, PubMed:29992740, PubMed:30190309). Highly expressed in skeletal muscles, Nav1.4 generates the action potential crucial for muscle contraction (PubMed:16890191, PubMed:19347921, PubMed:25707578, PubMed:26659129, PubMed:26700687)

Subcellular location

Cell membrane
Domains and Gene Ontology detail (9)

Domains & features

IQ

Gene Ontology

  • Cplasma membrane
  • Cvoltage-gated sodium channel complex
  • Fvoltage-gated sodium channel activity
  • Pcardiac muscle cell action potential involved in contraction
  • Pmuscle contraction
  • Pregulation of skeletal muscle contraction by action potential
  • Psodium ion transmembrane transport
  • Psodium ion transport

1836 aa · 208 kDa

Biological roles

Reactome v97

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

Muscle contractionUniProt · GOIon channel gatingGOImmune signallingUniProt
View supporting evidence

Muscle contraction

  • ·Pore-forming subunit of Nav1.4, a voltage-gated sodium (Nav) channel that directly media…
  • ·muscle contraction
  • ·regulation of skeletal muscle contraction by action potential

Ion channel gating

  • ·sodium ion transmembrane transport

Immune signalling

  • ·Pore-forming subunit of Nav1.4, a voltage-gated sodium (Nav) channel that directly media…
View underlying pathways (2)
Interaction between L1 and Ankyrins
Phase 0 - rapid depolarisation

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.

SCN1BCALM3SCN4BCLCN1SCN3BSCN2ACALM2SCN2BSCNN1BSCNN1ASCN4A

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

3

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.

Bupivacaine
Narrow target profileApprovedBlocker

Sodium channel protein type IV alpha subunit blocker

Appears in clinical studies involving Hernia, Pain, osteoarthritis, ileus

Direct interaction with this protein · Only this protein recorded as a target

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, SCN7A, SCN2A +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, SCN7A, SCN2A +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.

potassium-aggravated myotonia0.96

Genetic · overall 0.81

hypokalemic periodic paralysis, type 20.93

Genetic · overall 0.74

paramyotonia congenita of Von Eulenburg0.93

Genetic · overall 0.84

hyperkalemic periodic paralysis0.92

Genetic · overall 0.83

congenital myasthenic syndrome 160.91

Genetic · overall 0.69

Highest-confidence therapeutic associations

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

Pain1.00

Clinical · overall 0.67

Seizure0.99

Clinical · overall 0.69

Highest overall evidence

Remaining associations by Open Targets' aggregated evidence score.

congenital myopathy 22B, severe fetal0.74

Genetic

Congenital myasthenic syndromes0.70

Genetic

hypokalemic periodic paralysis0.70

Genetic literature

Show all associations
paramyotonia congenita of Von Eulenburg0.84
hyperkalemic periodic paralysis0.83
potassium-aggravated myotonia0.81
hypokalemic periodic paralysis, type 20.74
congenital myopathy 22B, severe fetal0.74
Congenital myasthenic syndromes0.70
hypokalemic periodic paralysis0.70
congenital myasthenic syndrome 160.69
Seizure0.69
Pain0.67

Open Targets ranks 2,020 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 · 77 total

RILUZOLEApproval

amyotrophic lateral sclerosis · progressive supranuclear palsy · multiple system atrophy

TOCAINIDEApproval

cardiac arrhythmia · Ventricular arrhythmia

PHENYTOINApproval

Seizure · epilepsy · Seizure

MEXILETINEApproval

cardiac arrhythmia · ventricular tachycardia · ventricular fibrillation

HEXYLCAINEApproval
BENOXINATE HYDROCHLORIDEPhase 3
LIDOCAINEApproval

premature ejaculation · Pruritus · burn

ZONISAMIDEApproval

epilepsy · Seizure · Parkinsonism

INDECAINIDEApproval
LEVOBUPIVACAINE HYDROCHLORIDEPhase 3

neuropathic pain · lung cancer · arthropathy

Tractability

SM · Approved DrugSM · Structure with LigandSM · High-Quality LigandSM · Druggable FamilyAB · UniProt loc high confAB · GO CC high confAB · UniProt SigP or TMHMMPR · 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

Determination of the Minimum Local Anesthetic Volume of 0.125% Bupivacaine in Labour EpiduralsNA

COMPLETED · via Bupivacaine · NCT00450099

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

COMPLETED · via lamotrigine · NCT00183469

Comparison Between Dexametidomedine\Bupivacaine and Plain Bupivacaine in Superior Trunk Block for Arthroscopic Shoulder SurgeriesNA

COMPLETED · via Bupivacaine · NCT07046325

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

COMPLETED · via lamotrigine · NCT01864551

Show remaining trials (24)
The Effect of Different Volumes of Ilioinguinal-Iliohypogastric Nerve Block on Postoperative Analgesia in Inguinal Hernia SurgeryNA

NOT_YET_RECRUITING · via Bupivacaine · NCT07579975

A Phase 3, Randomized, Double-Blind, Multicenter, Active-Controlled Study to Evaluate the Efficacy, Safety, and Pharmacokinetics of EXPAREL Admixed With Bupivacaine Hydrochloric Acid (HCl) vs. Bupivacaine HCl Administered Via Adductor Canal Block for Postsurgical Analgesia in Subjects Undergoing Primary Unilateral Total Knee ArthroplastyPHASE3

COMPLETED · via Bupivacaine · NCT05139030

The Effect of Liposomal Bupivacaine on Post Operative Pain and Narcotic Use After Bariatric SurgeryPHASE4

COMPLETED · via Bupivacaine · NCT03196505

Prospective Study of Liposomal Bupivacaine for Pain Control of Split Thickness Skin Graft Donor SitesPHASE4

COMPLETED · via Bupivacaine · NCT03854344

Randomized Trial to Determine the Effect of Dorsal Penile Block on Post-Robotic Prostatectomy Foley DiscomfortPHASE1/PHASE2

WITHDRAWN · via Bupivacaine · NCT01565512

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

Effectiveness of Transversus Abdominis Plane Block Versus Quadratus Lumborum Technique in Patients After Cesarean SectionPHASE4

COMPLETED · via Bupivacaine · NCT02804126

Comparison of Clonidine and Morphine Plus Bupivacaine in Caudal Peridural Anesthesia for Postoperative Analgesia After Pediatric Urogenital SurgeryPHASE1/PHASE2

COMPLETED · via Bupivacaine · NCT00672347

Evaluation of Postoperative Analgesic Effects of Bilateral Suprazygomatic Maxillary Nerve Block Using Bupivacaine and Dexmedetomidine in Children Undergoing Cleft Palate Repair Under General Anesthesia:Randomized Controlled TrialPHASE2

COMPLETED · via Bupivacaine · NCT03412474

Comparison of Transcutaneous Pulsed Radiofrequency Therapy and Greater Occipital Nerve Block Efficiency in Migraine HeadacheNA

UNKNOWN · via Bupivacaine · NCT05499689

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

The Effects of Different Anesthetic Techniques on QT, Corrected QT (QTc), and P Wave Dispersions in Cesarean SectionPHASE4

COMPLETED · via Bupivacaine · NCT03134677

Spinal Analgesia for Laparoscopic Abdominoperineal Rectal Amputation Using an Enhanced Recovery After Surgery Program: a Randomized Double-blind Placebo-controlled TrialPHASE4

COMPLETED · via Bupivacaine · NCT05406765

Comparative Study Between Dexmedetomedine and Ketamine in Erector Spinae Plane Block for Postoperative Analgesia Following Modified Radical Mastectomy. A Prospective Randomized Controlled Study.PHASE2/PHASE3

COMPLETED · via Bupivacaine · NCT05727098

Efficacy of Multimodal Peri- and Intraarticular Drug Injections in Total Knee ArthroplastyPHASE4

COMPLETED · via Bupivacaine · NCT00562627

Efficacy and Tolerability of Riluzole in Treatment Resistant DepressionPHASE2

COMPLETED · via Riluzole · NCT01204918

The Effect of Adding Dexamethasone Versus Magnesium Sulphate Versus Dexmedetomidine to Bupivacaine in Ultrasound Guided Adductor Canal Block for Post-operative Analgesia Following Anterior Cruciate Ligament RepairPHASE2

COMPLETED · via Bupivacaine · NCT04892420

A Prospective Randomized-controlled Study on Effectiveness of Extended-release Liposomal Bupivacaine in Postoperative Pain ControlPHASE4

COMPLETED · via Bupivacaine · NCT02111746

Comparing Low-dose Bupivacaine With Epidural Volume Extension to Standard Bupivacaine Dosing for Short Obstetric Procedures: A Prospective, Randomized StudyPHASE3

COMPLETED · via Bupivacaine · NCT03110003

Effect of Adding Dexmedetomidine Versus Magnesium Sulphate to Intrathecal Bupivacaine on Spinal Block and Neonatal Outcome in Uncomplicated Caesarean DeliveryPHASE3

UNKNOWN · via Bupivacaine · NCT03067896

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

Protective Analgesia Using Bupivacaine and Conventional Release Ibuprofen Versus Bupivacaine and Sustained Release Ibuprofen for Postoperative Pain Relief in Patients Undergoing Third Molar Surgery: a Randomised Controlled TrialNA

COMPLETED · via Bupivacaine · NCT00895843

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.

paramyotonia congenita of Von EulenburgWell supported
0.97
agreement 0.87–1.00
Genetic59%Clinical21%Animal model18%Literature2%Genetic literaturedup

Open Targets aggregate 0.84 · 4 independent evidence families · 1 not counted as duplicate

potassium-aggravated myotoniaWell supported
0.97
agreement 0.85–1.00
Genetic78%Animal model21%Literature1%Genetic literaturedup

Open Targets aggregate 0.81 · 3 independent evidence families · 1 not counted as duplicate

hypokalemic periodic paralysis, type 2Well supported
0.95
agreement 0.83–1.00
Genetic79%Animal model20%Literature1%Genetic literaturedup

Open Targets aggregate 0.74 · 3 independent evidence families · 1 not counted as duplicate

hyperkalemic periodic paralysisWell supported
0.94
agreement 0.82–1.00
Genetic77%Animal model20%Literature3%Genetic literaturedup

Open Targets aggregate 0.83 · 3 independent evidence families · 1 not counted as duplicate

congenital myasthenic syndrome 16Well supported
0.93
agreement 0.81–1.00
Genetic81%Animal model19%Literature0%Genetic literaturedup

Open Targets aggregate 0.69 · 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 3 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.