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Protein / target

Voltage-gated inwardly rectifying potassium channel KCNH2

Encoded byKCNH2Q12809Homo sapiensSwiss-Prot
UniProt: Q12809Ensembl: ENSG00000055118HGNC: HGNC:6251NCBI Gene: 3757
Clinically validated
Therapeutic maturity
14
Approved medicines
Open Targets target-level
View by indication →
30
Clinical trials
Small-molecule tractable
Druggability
Approved Drug

Protein at a glance

Biological role

Delayed rectifier potassium channel

Strongest disease association

Arrhythmias, Cardiac

Via encoding gene KCNH2 · Genetic evidence · score 0.83

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 (alpha) subunit of voltage-gated inwardly rectifying potassium channel.

View complete UniProt function annotation

Pore-forming (alpha) subunit of voltage-gated inwardly rectifying potassium channel (PubMed:10219239, PubMed:10753933, PubMed:10790218, PubMed:10837251, PubMed:11997281, PubMed:12063277, PubMed:18559421, PubMed:22314138, PubMed:22359612, PubMed:26363003, PubMed:27916661, PubMed:9230439, PubMed:9351446, PubMed:9765245). Channel properties are modulated by cAMP and subunit assembly (PubMed:10837251). Characterized by unusual gating kinetics by producing relatively small outward currents during membrane depolarization and large inward currents during subsequent repolarization which reflect a rapid inactivation during depolarization and quick recovery from inactivation but slow deactivation (closing) during repolarization (PubMed:10219239, PubMed:10753933, PubMed:10790218, PubMed:10837251, PubMed:11997281, PubMed:12063277, PubMed:18559421, PubMed:22314138, PubMed:22359612, PubMed:26363003, PubMed:27916661, PubMed:9230439, PubMed:9351446, PubMed:9765245). Forms a stable complex with KCNE1 or KCNE2, and that this heteromultimerization regulates inward rectifier potassium channel activity (PubMed:10219239, PubMed:9230439)

Subcellular location

Cell membrane
Domains and Gene Ontology detail (39)

Domains & features

PASPAC

Gene Ontology

  • Ccell surface
  • Cinward rectifier potassium channel complex
  • Cperinuclear region of cytoplasm
  • Cplasma membrane
  • Cvoltage-gated potassium channel complex
  • Fdelayed rectifier potassium channel activity
  • Fidentical protein binding
  • Finward rectifier potassium channel activity
  • Fprotein homodimerization activity
  • Fscaffold protein binding
  • Ftranscription cis-regulatory region binding
  • Fubiquitin protein ligase binding

1159 aa · 127 kDa · 6 isoforms

Biological roles

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

Ion channel gatingGOTranscriptional regulationGO
View supporting evidence

Ion channel gating

  • ·negative regulation of potassium ion transmembrane transport
  • ·positive regulation of potassium ion transmembrane transport
  • ·potassium ion transmembrane transport
  • ·regulation of potassium ion transmembrane transport

Transcriptional regulation

  • ·transcription cis-regulatory region binding
  • ·positive regulation of DNA-templated transcription

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

Approved medicines with mapped indications

2 medicines · 2 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.

Lambert-Eaton Myasthenic Syndrome1 medicine
amifampridine
Multiple Sclerosis1 medicine
dalfampridine

14 medicines meet Open Targets' target-level approved-medicine definition; the 2 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

2

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

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 KCNH2

Gene-level evidence surfaced through the gene KCNH2that 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
0.94Well supported

Genetic evidence dominant · Open Targets 0.73

Atrial Fibrillation
0.89Well supported

Clinical evidence dominant · Open Targets 0.73

Ventricular Fibrillation
0.86Well supported

Clinical evidence dominant · Open Targets 0.68

Atrial Flutter
0.85Well supported

Clinical evidence dominant · Open Targets 0.60

Tachycardia, Ventricular
0.79Well supported

Clinical evidence dominant · Open Targets 0.62

View evidence synthesis (5)
Arrhythmias, CardiacWell supported
0.94
agreement 0.84–1.00
Genetic53%Clinical43%Literature4%

Open Targets aggregate 0.73 · 3 independent evidence families

Atrial FibrillationWell supported
0.89
agreement 0.78–1.00
Clinical52%Genetic44%Literature4%Genetic literaturedup

Open Targets aggregate 0.73 · 3 independent evidence families · 1 not counted as duplicate

Ventricular FibrillationWell supported
0.86
agreement 0.75–0.97
Clinical59%Genetic literature40%Literature1%

Open Targets aggregate 0.68 · 3 independent evidence families

Atrial FlutterWell supported
0.85
agreement 0.74–0.96
Clinical51%Genetic48%Literature1%

Open Targets aggregate 0.60 · 3 independent evidence families

Tachycardia, VentricularWell supported
0.79
agreement 0.68–0.90
Clinical73%Genetic25%Literature2%

Open Targets aggregate 0.62 · 3 independent evidence families

This ranking differs from Open Targets' own: re-weighting moves genetically-evidenced diseases above more heavily co-mentioned ones. 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
Atrial Fibrillation0.73
Arrhythmias, Cardiac0.73
Ventricular Fibrillation0.68
Tachycardia, Ventricular0.62
Atrial Flutter0.60
Multiple Sclerosis0.59

Drug development

17 compounds recorded · 14 approved · 3 in clinical development

Open Targets' development universe — every compound recorded against the target at any stage, not all approved medicines. Distinct from the 2 drugs that target this protein in Forefront's canonical graph (2 with a mapped approved indication, shown above): these count different sets and are not a subset relation.

View all recorded compounds (10)
DOFETILIDEApproval
SOTALOL HYDROCHLORIDEApproval
NERISPIRDINEPhase 2
AZD1305Phase 2
IBUTILIDEApproval
DALFAMPRIDINEApproval
IBUTILIDE FUMARATEApproval
SOTALOLApproval
AMIFAMPRIDINEApproval
GUANIDINE HYDROCHLORIDEApproval

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 molecules — Strong

Approved Drug and Structure with Ligand support this modality.

Antibodies — Emerging

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

Protein degraders — Emerging

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

View underlying tractability evidence (10)
SM · Approved DrugSM · Structure with LigandSM · High-Quality LigandSM · Med-Quality PocketSM · Druggable FamilyAB · UniProt loc high confAB · GO CC high confAB · UniProt SigP or TMHMMPR · Database UbiquitinationPR · Small Molecule Binder

Raw Open Targets tractability assessment buckets, by modality.

Safety-related annotations

Torsades de PointClinPGxIncreased MortalityAOP-WikiReduced, survivalAOP-Wikireceptor bindingToxCastprolongation of QT interval of ECGBowes 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.

Dalfampridine Combined With Physical Therapy for Mobility Impairment in People With Multiple SclerosisPHASE4

RECRUITING · via dalfampridine · NCT06136728

Pilot Study on the Usefulness of 3,4-diaminopyridine in the Treatment of BotulismPHASE2/PHASE3

COMPLETED · via amifampridine · NCT01441557

4-aminopyridine Treatment for Nerve Injury Resulting From Radical Retro-Pubic ProstatectomyPHASE2/PHASE3

RECRUITING · via dalfampridine · NCT03701581

4-Aminopyridine to Delay Carpal Tunnel Release or Resolve Carpal Tunnel SyndromePHASE2

NOT_YET_RECRUITING · via dalfampridine · NCT06294821

View all trials (26)
4-aminopyridine for Skin Wound HealingPHASE2

RECRUITING · via dalfampridine · NCT06333171

Pharmaco-Diagnostic Crossover Trial for Peripheral Nerve Continuity After TraumaPHASE2

RECRUITING · via dalfampridine · NCT06003166

Effects of Twice-daily Dosing 4-AP on Functional Recovery After Spinal Cord InjuryPHASE1/PHASE2

RECRUITING · via dalfampridine · NCT06853015

Phase I Study of Preoperative Therapy Imatinib Mesylate and Fampridine in KIT Mutant Gastrointestinal Stromal Tumor (GIST)PHASE1

RECRUITING · via dalfampridine · NCT07171203

A Multicenter, 18-week Open Label Safety and Efficacy Trial of Dalfampridine in Primary Lateral SclerosisPHASE1

ACTIVE_NOT_RECRUITING · via dalfampridine · NCT02868567

Randomised, Double-Blind, Placebo-Controlled, Crossover Study Investigating the Role of Potassium Channels in Working Memory Impairments of Chronic Cocaine UsersNA

NOT_YET_RECRUITING · via dalfampridine · NCT07532460

A Phase IV Double Blind, Randomized, Placebo Controlled, Crossover Study of the Effectiveness of Oral Fampridine in Improving Upper Limb Function in Progressive Multiple SclerosisPHASE4

COMPLETED · via dalfampridine · NCT02208050

Short and Long Term Fampridine Treatment in Persons With Multiple Sclerosis: Cognitive and Motor PerformancesPHASE4

COMPLETED · via dalfampridine · NCT02849782

Dalfampridine Treatment for Nonarteritic Anterior Ischemic Optic Neuropathy (NAION)PHASE4

COMPLETED · via dalfampridine · NCT01975324

An Open-Label, Multicenter, Multinational Study to Assess the Effect of Long-Term Prolonged-Release Fampridine (BIIB041) 10 mg Twice Daily on Quality of Life as Reported by Subjects With Multiple SclerosisPHASE4

COMPLETED · via dalfampridine · NCT01480076

A Single Dose Pharmaco-Diagnostic for Peripheral Nerve Continuity After TraumaPHASE2/PHASE3

TERMINATED · via dalfampridine · NCT04026568

Quality of Life, Efficacy and Safety of High Doses of 4-aminopyridine in Patients With Clinically Complete Chronic Spinal Cord Injury: Multicenter, Randomized, Double Blind, Placebo Controlled Clinical TrialPHASE3

UNKNOWN · via dalfampridine · NCT03899584

A Multicenter, Randomized, Double Blind, Placebo Controlled Study to Assess the Long-Term Efficacy and Safety of Prolonged Release Fampridine (BIIB041) 10 mg, Administered Twice Daily in Subjects With Multiple Sclerosis (ENHANCE)PHASE3

COMPLETED · via dalfampridine · NCT02219932

Columbia SMA Project: 4-AP as a Potential SMA Therapeutic Agent and Biological Mechanisms of ActionPHASE2/PHASE3

COMPLETED · via dalfampridine · NCT01645787

Effects of Dalfampridine on Cognition in Multiple SclerosisPHASE2/PHASE3

COMPLETED · via dalfampridine · NCT02006160

Multicentric Study, Comparative, Randomized, in Double Knowledge of the Effectiveness (Versus Placebo) of a Salt Of 3,4 - Diaminopyridine in the Treatment of Tiredness During the Multiple SclerosisPHASE3

COMPLETED · via amifampridine · NCT00190268

Amifampridine for the Treatment of Transient Vocal Weakness After OnabotulinumtoxinA Injection for Spasmodic DysphoniaPHASE2

COMPLETED · via amifampridine · NCT05123053

Prospective, Randomized, Placebo-controlled, Phase 2 Study of 4-aminopyridine, Atenolol, or Placebo in the Treatment of Patients With Vestibular MigrainePHASE2

WITHDRAWN · via dalfampridine · NCT03578354

4-aminopyridine Treatment for Nerve Injury From Radical Retro-Pubic ProstatectomyPHASE2

WITHDRAWN · via dalfampridine · NCT03658408

The Effect of Dalfampridine (4-aminopyridine) on Genioglossus Muscle Activity During Wakefulness and Sleep in Healthy Control SubjectsPHASE2

COMPLETED · via dalfampridine · NCT02656160

Study and Treatment of Visual Dysfunction and Motor Fatigue in Multiple SclerosisPHASE2

COMPLETED · via dalfampridine · NCT02391961

Efficacy and Safety of 4-aminopyridine on Cognitive Performance and Motor Function of Patients With Multiple Sclerosis. Randomized, Blinded, Placebo-controlled Clinical Trial.PHASE2

COMPLETED · via dalfampridine · NCT02280096

Double-Blind, Placebo-Controlled Crossover Trial on the Safety and Efficacy of Sustained-Release Dalfampridine in Transverse Myelitis (Re-Launch)PHASE2

COMPLETED · via dalfampridine · NCT02166346

Restoring Lost Functions After Spinal Cord Injury: Combination Therapy With Dalfampridine and Locomotor Training for Persons With Chronic, Motor Incomplete Spinal Cord InjuryPHASE2

COMPLETED · via dalfampridine · NCT01621113

Dalfampridine to Improve Imbalance in Multiple Sclerosis: A Pilot StudyPHASE2

COMPLETED · via dalfampridine · NCT01444300

Fatigue in Multiple Sclerosis: Evaluated With 3 Tesla MRI and Transcranial Magnetic StimulationPHASE2

COMPLETED · via amifampridine · NCT00342381

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.