KCNQ1 potassium voltage-gated channel subfamily Q member 1
ENSG00000053918 · protein coding · Open Targets profile
Pore-forming subunit of the voltage-gated potassium (Kv) channel involved in the regulation of cardiomyocyte excitability and important in normal development and functions of myocardium, inner ear, stomach and colon (PubMed:10646604, PubMed:25441029). Associates with KCNE beta subunits that modulates current kinetics (PubMed:10646604, PubMed:11101505, PubMed:19687231, PubMed:8900283, PubMed:9108097, PubMed:9312006). Induces a voltage-dependent current by rapidly activating and slowly deactivating potassium-selective outward current (PubMed:10646604, PubMed:11101505, PubMed:25441029, PubMed:8900283, PubMed:9108097, PubMed:9312006). Also promotes a delayed voltage activated potassium current showing outward rectification characteristic (By similarity). During beta-adrenergic receptor stimulation, participates in cardiac repolarization by associating with KCNE1 to form the I(Ks) cardiac potassium current that increases the amplitude and slows down the activation kinetics of outward potassium current I(Ks) (By similarity) (PubMed:10646604, PubMed:11101505, PubMed:8900283, PubMed:9108097, PubMed:9312006). Muscarinic agonist oxotremorine-M strongly suppresses KCNQ1/KCNE1 current (PubMed:10713961). When associated with KCNE3, forms the potassium channel that is important for cyclic AMP-stimulated intestinal secretion of chloride ions (PubMed:10646604). This interaction with KCNE3 is reduced by 17beta-estradiol, resulting in the reduction of currents (By similarity). During conditions of increased substrate load, maintains the driving force for proximal tubular and intestinal sodium ions absorption, gastric acid secretion, and cAMP-induced jejunal chloride ions secretion (By similarity). Allows the provision of potassium ions to the luminal membrane of the secretory canaliculus in the resting state as well as during stimulated acid secretion (By similarity). When associated with KCNE2, forms a heterooligomer complex leading to currents with an apparently instantaneous activation, a rapid deactivation process and a linear current-voltage relationship and decreases the amplitude of the outward current (PubMed:11101505). When associated with KCNE4, inhibits voltage-gated potassium channel activity (PubMed:19687231). When associated with KCNE5, this complex only conducts current upon strong and continued depolarization (PubMed:12324418). Also forms a heterotetramer with KCNQ5; has a voltage-gated potassium channel activity (PubMed:24855057). Binds with phosphatidylinositol 4,5-bisphosphate (PubMed:25037568). KCNQ1-KCNE2 channel associates with Na(+)-coupled myo-inositol symporter in the apical membrane of choroid plexus epithelium and regulates the myo- inositol gradient between blood and cerebrospinal fluid with an impact on neuron excitability (By similarity). {ECO:0000250|UniProtKB:P97414, ECO:0000250|UniProtKB:Q9Z0N7, ECO:0000269|PubMed:10646604, ECO:0000269|PubMed:10713961, ECO:0000269|PubMed:11101505, ECO:0000269|PubMed:12324418, ECO:0000269|PubMed:19687231, ECO:0000269|PubMed:24595108, ECO:0000269|PubMed:24855057, ECO:0000269|PubMed:25037568, ECO:0000269|PubMed:8900283, ECO:0000269|PubMed:9108097, ECO:0000269|PubMed:9312006}.
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 loc med conf, UniProt SigP or TMHMM, Human Protein Atlas loc
- PROTAC
- UniProt Ubiquitination, Database Ubiquitination, Small Molecule Binder
gnomAD loss of function constraint: o/e 0.6772500276565552 (upper bound 0.8592900037765503). 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 400 registry trials, updated in the last three years, of the most advanced drugs against KCNQ1 (amifampridine, guanidine, tedisamil, dalfampridine, nerispirdine), ranked by Phase 2+ trials. Live from ClinicalTrials.gov.
- Howard FineWeill Medical College of Cornell University · 2 of 2 trials Phase 2+
- Jennifer JohnsonThomas Jefferson University · 2 of 2 trials Phase 2+
- Scott M LippmanUniversity of California, San Diego Moores Cancer Center · 2 of 2 trials Phase 2+
- Sherry McKeeYale University · 2 of 2 trials Phase 2+
- Gregory YanikUniversity of Michigan Rogel Cancer Center · 1 of 2 trials Phase 2+
- Jianren MaoMassachusetts General Hospital · 1 of 2 trials Phase 2+
- John M. MarisChildren's Hospital of Philadelphia · 1 of 2 trials Phase 2+
- Katherine K. MatthayUniversity of California, San Francisco · 1 of 2 trials Phase 2+
- Abhay MuthaDiabetes Care & Research Centre · 1 of 1 trials Phase 2+
- Abigail GoshenSheba Medical Center · 1 of 1 trials Phase 2+
- Adam KonopkaUniversity of Wisconsin, Madison · 1 of 1 trials Phase 2+
- Adriana ColettaHuntsman Cancer Institute · 1 of 1 trials Phase 2+
- Agnieszka AdamskaMedical University of Bialystok · 1 of 1 trials Phase 2+
- Aileen ChangGeorge Washington University · 1 of 1 trials Phase 2+
- Akiko OkifujiUniversity of Utah · 1 of 1 trials Phase 2+
Registry trials of amifampridine, guanidine, tedisamil, dalfampridine, nerispirdine 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; 361 of 383 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. 17 trials list no sites and are left out. Source: ClinicalTrials.gov, fetched live.
263 trials of drugs against KCNQ1 were stopped early; 11 of the 200 most recent give no reason
Terminated, withdrawn and suspended interventional trials of amifampridine, guanidine, tedisamil, dalfampridine, nerispirdine, 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 263.
- withdrawn · 2026-11-03 · Hellenic Institute for the Study of Sepsis · matched by the registry's drug synonyms“It was not conducted due to the emergency restrictive measures implemented during the COVID-19 pandemic, which made it impossible to carry out the patient visits required by the study protocol.”
- terminated · 2026-10-28 · King's College London · matched by the registry's drug synonyms“CTIMP randomised part of the study was halted early due to difficulty to recruit sufficient participants.”
- terminated · 2026-10-20 · University of Hawaii · matched by the registry's drug synonyms“During the COVID pandemic, our IRB halted enrollment into the study among other changes. Post COVID it was decided that too long an interval between patient enrollment was problematic for the study and a discussion was made to terminate.”
- terminated · 2026-09-18 · Gilead Sciences · matched by the registry's drug synonyms“MBX-102 did not meet the target efficacy profile of HbA1c change.”
- withdrawn · 2026-09-08 · Eli Lilly and Company · matched by the registry's drug synonyms“The sponsor made a business decision to withdraw the trial.”
- terminated · 2026-08-31 · Emory University · matched by the registry's drug synonyms“The study was suspended and during this time recruitment and study activities were halted. The study was ultimately terminated in April 2026 without having re-opened for recruitment additional participants.”
- terminated · 2026-08-27 · James Wang · matched by the registry's drug synonyms“The study funding has ended.”
- terminated · 2026-07-31 · Massachusetts General Hospital · matched by the registry's drug synonyms“End of NIH funding”
- terminated · 2026-07-29 · Canadian Urologic Oncology Group · matched by the registry's drug synonyms“Manufacturer discontinued the production of study drugs.”
- withdrawn · 2026-07-16 · ARKAY Therapeutics · matched by the registry's drug synonyms“Clinical stage asset and the sponsorship have been acquired by Myopharm Limited.”
- withdrawn · 2026-07-10 · McMaster University · matched by the registry's drug synonyms“Study halted prematurely, prior to enrollment of first participant”
- withdrawn · 2026-07-10 · University of Minnesota · matched by the registry's drug synonyms“Study was not initiated because funding was not received.”
- terminated · 2026-07-06 · Massachusetts General Hospital · matched by the registry's drug synonyms“End of NIH funding”
- terminated · 2026-06-17 · University of Illinois Chicago · matched by the registry's drug synonyms“Low recruitment rate and an inability to meet power.”
- withdrawn · 2026-06-12 · McMaster University · matched by the registry's drug synonyms“Withdrawn”
- terminated · 2026-05-06 · Amsterdam UMC, location VUmc · matched by the registry's drug synonyms“In line with the study protocol, due to slow recruitment, a futility analysis has been performed in the first quarter of 2025 by an independent statistician. The result of the analysis was restricted to a "no-go".”
- terminated · 2026-04-22 · Sidney Kimmel Comprehensive Cancer Center at Thomas Jefferson University · matched by the registry's drug synonyms“study closed early due to slow accrual”
- terminated · 2026-04-17 · Rachel G. Greenberg, MD, MB, MHS · matched by the registry's drug synonyms“Study was stopped after careful review of product manufacturing needs and available resources. Decision reflects consideration of feasibility, enrollment challenges, and overall program goals.”
- terminated · 2026-03-12 · University of Iowa · matched by the registry's drug synonyms“Lack of funding”
- terminated · 2026-03-05 · Medical University of South Carolina · matched by the registry's drug synonyms“Investigator retired from clinical practice prior to enrollment goal being met.”
- suspended · 2026-03-04 · NYU Langone Health · matched by the registry's drug synonyms“Project is on indefinite hold due to a lack of funding”
- withdrawn · 2026-02-23 · University of Virginia · matched by the registry's drug synonyms“No funding, time, or personnel to complete this study.”
- terminated · 2026-01-29 · Sidney Kimmel Comprehensive Cancer Center at Thomas Jefferson University · matched by the registry's drug synonyms“Insufficient staff to conduct the trial”
- withdrawn · 2025-12-24 · Diana Jalal · matched by the registry's drug synonyms“No funding”
- withdrawn · 2025-12-18 · Eurofarma Laboratorios S.A. · matched by the registry's drug synonyms“Strategic change in development priorities”
Paediatric incentives and obligations for KCNQ1's drugs
For amifampridine, guanidine, tedisamil, dalfampridine, nerispirdine: 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 · KCNQ1 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: no · No EMA paediatric investigation plan decision names amifampridine, guanidine, tedisamil, dalfampridine, nerispirdineRule: An EMA PIP decision (agreement, modification or waiver) lists the drug as its active substance, exact name. Source: EMA data download (dated snapshot), 2026-11-11
- EU orphan designation: yes · EU/3/02/124 withdrawn 19 Dec 2002: Treatment of Lambert-Eaton myasthenic syndromeRule: 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 EU/3/02/124, 2026-11-11
- Authorised in the EU: yes · Firdapse (previously Zenas): authorised since 23 Dec 2009, exceptional circumstances; Amifampridine SERB: authorised since 19 May 2022Rule: 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 data download (dated snapshot), 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 amifampridine, guanidine, tedisamil, dalfampridine, nerispirdineRule: FDA's Pediatric Oncology Drug Approvals table names the drug. Source: FDA Pediatric Oncology Drug Approvals (content current as of 2026-03-03), 2026-11-12
- Registered studies open to children: yes · 319 interventional studies of amifampridine, guanidine, tedisamil, dalfampridine, nerispirdine include patients under 18; 36 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, 2026-11-12
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 7 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.