SCN4A sodium voltage-gated channel alpha subunit 4
ENSG00000007314 · protein coding · Open Targets profile
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). {ECO:0000269|PubMed:12766226, ECO:0000269|PubMed:15318338, ECO:0000269|PubMed:16890191, ECO:0000269|PubMed:17898326, ECO:0000269|PubMed:18690054, ECO:0000269|PubMed:19347921, ECO:0000269|PubMed:25707578, ECO:0000269|PubMed:26659129, ECO:0000269|PubMed:26700687, ECO:0000269|PubMed:29992740, ECO:0000269|PubMed:30190309}.
Each band is a group of drugs. It runs from the kind of drug on the left to the furthest stage that drug has reached in any disease on the right. Thicker bands mean more drugs.
Approved bands are highlighted. Withdrawn means the drug was pulled from the market or from development. A combined phase counts as the later one (Phase 1/2 is shown as Phase 2). Hover a band for the drug names. Source: Open Targets Platform, fetched live.
Each row is a cancer, strongest overall evidence first. The two dots show how strong the inherited (germline) and tumour-mutation (somatic) evidence is; the line between them is the gap.
Scores run from 0 (no evidence) to 1 (strongest). A missing dot at 0 means Open Targets holds no evidence of that kind. Source: Open Targets Platform, fetched live.
Tractability
- Small molecule
- Approved Drug, Structure with Ligand, High-Quality Ligand, Druggable Family
- Antibody
- UniProt loc high conf, GO CC high conf, UniProt SigP or TMHMM
- PROTAC
- Small Molecule Binder
gnomAD loss of function constraint: o/e 0.5123100280761719 (upper bound 0.6148999929428101). Low values mean loss of function is poorly tolerated, a safety flag for inhibition.
Who runs trials of these drugs
Principal investigators and study chairs on 280 registry trials, updated in the last three years, of the most advanced drugs against SCN4A (tocainide, hexylcaine, indecainide, etidocaine, quinidine gluconate, cocaine, propafenone, ethotoin, mephenytoin, dyclonine, mexiletine, phenytoin), ranked by Phase 2+ trials. Live from ClinicalTrials.gov.
- Heather WebberThe University of Texas Health Science Center, Houston · 1 of 3 trials Phase 2+
- Abhishek DattaSoterix Medical · 1 of 2 trials Phase 2+
- Christine BarnériasHopital universitaire Necker-Enfants Malades · 1 of 2 trials Phase 2+
- Joy M SchmitzUT Houston · 1 of 2 trials Phase 2+
- Madhukar TrivediUniversity of Texas Southwestern Medical Center · 1 of 2 trials Phase 2+
- Albert AriasVirginia Commonwealth University · 1 of 1 trials Phase 2+
- All Validations Passed BadranMedical University of SC · 1 of 1 trials Phase 2+
- Andre MalbergierDepartment of Psychiatry - University of São Paulo · 1 of 1 trials Phase 2+
- Andre TappVA Puget Sound Health Care System, Tacoma and Seattle, WA and University of Washington, Department of Psychiatry and Behavioral Sciences, Seattle, WA · 1 of 1 trials Phase 2+
- Andrea NataleTexas Cardiac Arrhythmia Research Foundation · 1 of 1 trials Phase 2+
- Andrew VickersMemorial Sloan Kettering Cancer Center · 1 of 1 trials Phase 2+
- Apinderpreet Singh Additional ProfessorPost Graduate Institute of Medical Education and Research, Chandigarh · 1 of 1 trials Phase 2+
- Ayesha AppaUniversity of California, San Francisco · 1 of 1 trials Phase 2+
- Bruce McCarthyEmbera NeuroTherapeutics, Inc. · 1 of 1 trials Phase 2+
- Cathy J. RebackFriends Research Institute, Inc. · 1 of 1 trials Phase 2+
Registry trials of tocainide, hexylcaine, indecainide, etidocaine, quinidine gluconate, cocaine, propafenone, ethotoin, mephenytoin, dyclonine, mexiletine, phenytoin updated in the last three years, counted by the country group of their listed sites. A trial with sites in several groups counts in each; 258 of 270 have all sites in one country.
Site counts are not patients per country, and trials registered only outside ClinicalTrials.gov are not covered. Where sites are is a fact about the record, not a judgement of its quality. Europe is the EU and EEA, the UK and Switzerland. 10 trials list no sites and are left out. Source: ClinicalTrials.gov, fetched live.
116 trials of drugs against SCN4A were stopped early; 17 give no reason
Terminated, withdrawn and suspended interventional trials of tocainide, hexylcaine, indecainide, etidocaine, quinidine gluconate, cocaine, propafenone, ethotoin, mephenytoin, dyclonine, mexiletine, phenytoin, newest update first, live from ClinicalTrials.gov. Each reason is quoted exactly as the registry gives it; we do not sort reasons into safety, efficacy or business. Dates are the last registry update. Showing the 25 most recent of 116.
- terminated · 2026-09-29 · Otsuka Pharmaceutical Development & Commercialization, Inc. · matched by the registry's drug synonyms“Based on the Interim Analysis outcome and recommendation by the DMC, Otsuka approved termination of the study based on futility.”
- terminated · 2026-09-14 · Milton S. Hershey Medical Center · matched by the registry's drug synonyms“technical difficulties in sample analysis”
- terminated · 2026-06-26 · Tsai-Wei Huang · matched by the registry's drug synonyms“The study was terminated prior to reaching the planned sample size due to slow participant accrual. Recruitment was substantially hindered by the COVID-19 pandemic, which restricted access to hospice inpatient units, and by the inherent difficulty of”
- terminated · 2026-05-13 · Otsuka Pharmaceutical Development & Commercialization, Inc. · matched by the registry's drug synonyms“The study was terminated prematurely because of difficulty with recruiting.”
- terminated · 2026-05-04 · Ottawa Heart Institute Research Corporation · matched by the registry's drug synonyms“Low recruitment. Pilot trial.”
- suspended · 2026-04-07 · University of California, Los Angeles · matched by the registry's drug synonyms“Departmental support”
- withdrawn · 2026-03-13 · Christopher D. Verrico · matched by the registry's drug synonyms“The study was closed due to the inability to acquire the study drug.”
- terminated · 2026-02-06 · Q2i, LLC · matched by the registry's drug synonyms“Enrollment was impacted by a massive epidemiological shift that led to reduced rates of presentation to the ED for opioid overdose. Despite more than a year of adjusting protocols and site expansion, we were not able to meet study enrollment goals.”
- terminated · 2025-11-14 · University of North Carolina, Chapel Hill · Fosphenytoin“Low recruitment”
- withdrawn · 2025-10-20 · University of Wisconsin, Madison · matched by the registry's drug synonyms“Lab schedule, Resources”
- withdrawn · 2025-10-20 · Mclean Hospital · matched by the registry's drug synonyms“Study was never funded because lorcaserin was pulled from FDA approval”
- terminated · 2025-10-15 · Otsuka Pharmaceutical Development & Commercialization, Inc. · matched by the registry's drug synonyms“The AVP-786 program was discontinued, the recruitment was stopped and all participants are no longer being examined or receiving intervention.”
- terminated · 2025-06-24 · Tonix Pharmaceuticals, Inc. · matched by the registry's drug synonyms“Tonix has discontinued enrollment and terminated the Phase 2 CATALYST study (TNX-CE-CI202) because enrollment in this emergency department-based study was slower than projected. The study was not discontinued for safety or efficacy reasons.”
- withdrawn · 2025-06-03 · University of North Carolina, Chapel Hill · matched by the registry's drug synonyms“Suspended due to COVID-19. Protocol did not resume post COVID due to funding.”
- terminated · 2025-05-30 · Otsuka Pharmaceutical Development & Commercialization, Inc. · matched by the registry's drug synonyms“The AVP-786 program was discontinued, the recruitment was stopped and all participants are no longer being examined or receiving intervention.”
- terminated · 2025-05-30 · Otsuka Pharmaceutical Development & Commercialization, Inc. · matched by the registry's drug synonyms“The AVP-786 program was discontinued, the recruitment was stopped and all participants are no longer being examined or receiving intervention.”
- terminated · 2025-02-25 · National Institute on Drug Abuse (NIDA) · matched by the registry's drug synonyms“inadequate resources to complete study”
- terminated · 2025-02-07 · Salvatore Campanella · matched by the registry's drug synonyms“Difficulties in recruitment (single addictions become rare)”
- terminated · 2024-11-06 · Tyme, Inc · SM-88 used with MPS (methoxsalen, phenytoin, sirolimus)“Sponsor's decision”
- suspended · 2024-07-16 · New York State Psychiatric Institute · matched by the registry's drug synonyms“Funding”
- terminated · 2024-05-29 · Columbia University · matched by the registry's drug synonyms“PI left the institution”
- terminated · 2024-05-23 · William Stoops · Cocaine“COVID-19”
- withdrawn · 2024-05-06 · Lupin Ltd. · Mexiletine 167 mg“Assessing novel alternative study designs and regulatory pathways”
- withdrawn · 2024-04-23 · Yong Seog Oh · PropafenoneNo reason given
- terminated · 2024-04-08 · UCB Biopharma SRL · matched by the registry's drug synonyms“Terminated (The study stopped prematurely due to enrolment challenges, the termination was not linked to any safety issues.)”
Paediatric incentives and obligations for SCN4A's drugs
For tocainide, hexylcaine, indecainide, etidocaine, quinidine gluconate, cocaine, propafenone, ethotoin, mephenytoin, dyclonine, mexiletine, phenytoin: what EMA and FDA publish about paediatric plans, orphan status and pediatric approvals, and how many registered studies take children. Each line is a yes, no or not published fact from the record linked under it; none of it is a forecast.
- FDA pediatric target list: no · SCN4A is not on the listRule: Target is on FDA's Pediatric Molecular Target List (relevant targets). Source: FDA Pediatric Molecular Target List (Listed as February 2026 on the FDA Pediatric Oncology page; the file served is 9.7.22_the_relevant_molecular_target_list.xlsx, whose Summary of Changes sheet is headed 'SEPTEMBER 2022 UPDATE' (footnote date 2022-09-01)), 2026-11-11
- EU paediatric investigation plan: yes · EMEA-002012-PIP01-16-M05 (Mexiletine hydrochloride, Treatment of myotonic disorders): PM: decision on the application for modification of an agreed PIP, 19 Jul 2024Rule: An EMA PIP decision (agreement, modification or waiver) lists the drug as its active substance, exact name. Source: EMA EMEA-002012-PIP01-16-M05, 2026-11-11
- EU orphan designation: yes · EU/3/13/1126 positive 7 Jun 2013: Treatment of non-dystrophic myotonia; EU/3/14/1353 positive 19 Nov 2014: Treatment of myotonic disorders; EU/3/13/1189 positive 7 Oct 2013: Treatment of myotonic disordersRule: An EU orphan designation lists the drug as its active substance (exact name) or belongs to a medicine that does; withdrawn and expired designations are listed with their status. Source: EMA data download (dated snapshot), 2026-11-11
- Authorised in the EU: yes · Namuscla: authorised since 18 Dec 2018, orphan medicineRule: An EMA medicine record lists the drug as its active substance or INN, exact name; national-only authorisations are not in this file. Source: EMA EPAR Namuscla, 2026-11-11
- FDA orphan designation: not published · FDA's orphan designation database turns away automated requests, so this app does not read it; search it by hand at the linkRule: Would be: an FDA orphan designation names the drug. Source: FDA orphan designations search
- FDA pediatric oncology approval: no · FDA's table lists no pediatric approval of tocainide, hexylcaine, indecainide, etidocaine, quinidine gluconate, cocaine, propafenone, ethotoin, mephenytoin, dyclonine, mexiletine, phenytoinRule: FDA's Pediatric Oncology Drug Approvals table names the drug. Source: FDA Pediatric Oncology Drug Approvals (content current as of 2026-03-03), 2026-11-11
- Registered studies open to children: yes · 117 interventional studies of tocainide, hexylcaine, indecainide, etidocaine, quinidine gluconate, cocaine, propafenone, ethotoin, mephenytoin, dyclonine, mexiletine, phenytoin include patients under 18; 19 are recruiting, not yet recruiting or activeRule: The registry's age group includes Child (birth to 17 years), which also counts studies that set no minimum age. Source: ClinicalTrials.gov search, 2026-11-11
Rare pediatric disease voucher. FDA, content current as of 29 Apr 2026: “As of February 3, 2026, enactment of the Consolidated Appropriations Act, 2026, the rare pediatric disease PRV program will sunset after September 30, 2029. FDA may not award any PRVs under this program after September 30, 2029.” Voucher sale prices are not shown here; they appear only as company-reported news. FDA: Rare Pediatric Disease Designation and Priority Review Voucher Programs
All 77 drugs and clinical candidates as a table
Each drug, stage and indication links to its Open Targets record, where the trials and approvals behind it are listed. Salt forms (for example a mesylate) are listed as Open Targets records them, as separate entries.