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Protein / target

Potassium voltage-gated channel subfamily KQT member 1

Encoded byKCNQ1P51787Homo sapiensSwiss-Prot
Clinically validated
Therapeutic maturity
6
Approved medicines
Open Targets target-level
View by indication →
30
Clinical trials
Small-molecule tractable
Druggability
Approved Drug

Protein at a glance

Biological role

Phosphatidylinositol-4,5-bisphosphate binding

Strongest disease association

Arrhythmias, Cardiac

Via encoding gene KCNQ1 · Genetic evidence · score 0.85

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 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.

View complete UniProt function annotation

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)

Subcellular location

Cell membraneCytoplasmic vesicle membraneEarly endosomeMembrane raftEndoplasmic reticulumBasolateral cell membraneApical cell membrane
Domains and Gene Ontology detail (84)

Gene Ontology

  • Capical plasma membrane
  • Cbasolateral part of cell
  • Cbasolateral plasma membrane
  • Cciliary base
  • Ccytoplasm
  • Ccytoplasmic vesicle membrane
  • Cearly endosome
  • Cendoplasmic reticulum
  • Clate endosome
  • Clumenal side of membrane
  • Clysosome
  • Cmembrane

676 aa · 75 kDa · 2 isoforms

Biological roles

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

Chloride transportUniProt · GOIon channel gatingGOMuscle contractionGO
View supporting evidence

Chloride transport

  • ·Pore-forming subunit of the voltage-gated potassium (Kv) channel involved in the regulat…
  • ·intracellular chloride ion homeostasis

Ion channel gating

  • ·monoatomic ion channel complex
  • ·positive regulation of potassium ion transmembrane transport
  • ·potassium ion transmembrane transport

Muscle contraction

  • ·cardiac muscle contraction
  • ·positive regulation of cardiac muscle contraction

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

Approved medicines with mapped indications

3 medicines · 4 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.

Epilepsy1 medicine
Lambert-Eaton Myasthenic Syndrome1 medicine
Multiple Sclerosis1 medicine
Seizures1 medicine

6 medicines meet Open Targets' target-level approved-medicine definition; the 3 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

3

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.

dalfampridine
ApprovedBlocker

Voltage-gated potassium channel blocker

Indicated for Multiple Sclerosis

Acts on a complex — shared with KCNC4, KCNC3, KCNB1 +36 more · 1 of 40 recorded protein targets — broad pharmacology

ezogabine
ApprovedOpener

KCNQ (Kv7) potassium channel opener

Indicated for Epilepsy, Seizures

Acts on a complex — shared with KCNQ2, KCNQ3, KCNQ5 +1 more · 1 of 5 recorded protein targets

amifampridine
ApprovedBlocker

Voltage-gated potassium channel blocker

Indicated for Lambert-Eaton Myasthenic Syndrome

Acts on a complex — shared with KCNC4, KCNC3, KCNB1 +36 more · 1 of 40 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 KCNQ1

Gene-level evidence surfaced through the gene KCNQ1that 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.

Arrhythmias, Cardiac
0.93Well supported

Genetic evidence dominant · Open Targets 0.70

View evidence synthesis (1)
Arrhythmias, CardiacWell supported
0.93
agreement 0.821.00
Genetic62%Clinical33%Literature5%

Open Targets aggregate 0.70 · 3 independent evidence families

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
Arrhythmias, Cardiac0.70

Drug development

7 compounds recorded · 6 approved · 1 in clinical development

Open Targets' development universe — every compound recorded against the target at any stage, not all approved medicines. Distinct from the 3 drugs that target this protein in Forefront's canonical graph (3 with a mapped approved indication, shown above): these count different sets and are not a subset relation.

View all recorded compounds (7)
AMIFAMPRIDINEApproval
AMIFAMPRIDINE PHOSPHATEApproval
DALFAMPRIDINEApproval
EZOGABINEApproval
GUANIDINE HYDROCHLORIDEApproval
TEDISAMILApproval
NERISPIRDINEPhase 2

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 (12)
SM · Approved DrugSM · Structure with LigandSM · High-Quality LigandSM · Druggable FamilyAB · UniProt loc high confAB · GO CC high confAB · UniProt loc med confAB · UniProt SigP or TMHMMAB · Human Protein Atlas locPR · UniProt UbiquitinationPR · Database UbiquitinationPR · Small Molecule Binder

Raw Open Targets tractability assessment buckets, by modality.

Safety-related annotations

deafnessUrban et al. (2012)atrial fibrillationUrban et al. (2012)deafnessBowes et al. (2012)gastrointestinal symptomsUrban et al. (2012)hearing impairmentUrban et al. (2012)long QT syndromeBowes et al. (2012)new-onset diabetes after transplantationClinPGxatrial fibrillationBowes et al. (2012)long QT syndromeUrban et al. (2012)gastrointestinal symptomsBowes et al. (2012)potential hearing impairmentBowes et al. (2012)

Terms indexed against this target in Open Targets' safety data, with their datasource. These are annotations, not causal claims: the direction of effect (whether activation or inhibition is implicated), species and evidence strength are not captured here, so an entry does not mean that modulating this target is known to cause that condition.

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)

NOT_YET_RECRUITING · via dalfampridine · NCT06294821

RECRUITING · via dalfampridine · NCT06333171

RECRUITING · via dalfampridine · NCT06853015

TERMINATED · via dalfampridine · NCT04026568

COMPLETED · via dalfampridine · NCT02006160

COMPLETED · via ezogabine · NCT03043560

ClinicalTrials.gov via the drug-target graph.

What's happening now

6

Recent therapeutic activity around this target — regulatory actions, clinical trials and safety signals for 2 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. Supplemental approval2026-08-10

    Supplemental approval: DALFAMPRIDINE (ANDA210158)

    fda · regulatory · fda · via dalfampridine

  2. Label change2023-04-11

    Label change: DALFAMPRIDINE (ANDA210158)

    fda · regulatory · fda · via dalfampridine

  3. Label change2021-09-15

    Label change: DALFAMPRIDINE (ANDA210158)

    fda · regulatory · fda · via dalfampridine

  4. Label change2020-08-14

    Label change: DALFAMPRIDINE (ANDA210158)

    fda · regulatory · fda · via dalfampridine

  5. Regulatory approval2019-03-11

    Approval: DALFAMPRIDINE (ANDA210158)

    fda · regulatory · fda · via dalfampridine

  6. Regulatory approval2009-12-23

    Approval: Firdapse (previously Zenas) (EMA)

    ema · regulatory · ema · via amifampridine

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.