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Protein / target

Voltage-gated delayed rectifier potassium channel KCNH1

Encoded byKCNH1O95259Homo sapiensSwiss-Prot
Clinically validated
Therapeutic maturity
5
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

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 a voltage-gated delayed rectifier potassium channel that mediates outward-rectifying potassium currents which, on depolarization, reaches a steady-state level and do not inactivate.

View complete UniProt function annotation

Pore-forming (alpha) subunit of a voltage-gated delayed rectifier potassium channel that mediates outward-rectifying potassium currents which, on depolarization, reaches a steady-state level and do not inactivate (PubMed:10880439, PubMed:11943152, PubMed:22732247, PubMed:25420144, PubMed:25556795, PubMed:25915598, PubMed:27005320, PubMed:27325704, PubMed:27618660, PubMed:30149017, PubMed:9738473). The activation kinetics depend on the prepulse potential and external divalent cation concentration (PubMed:11943152). With negative prepulses, the current activation is delayed and slowed down several fold, whereas more positive prepulses speed up activation (PubMed:11943152). The time course of activation is biphasic with a fast and a slowly activating current component (PubMed:11943152). Activates at more positive membrane potentials and exhibit a steeper activation curve (PubMed:11943152). Channel properties are modulated by subunit assembly (PubMed:11943152). Mediates IK(NI) current in myoblasts (PubMed:9738473). Involved in the regulation of cell proliferation and differentiation, in particular adipogenic and osteogenic differentiation in bone marrow-derived mesenchymal stem cells (MSCs) (PubMed:23881642)

Subcellular location

Cell membraneNucleus inner membraneCell projection, dendriteCell projection, axonPresynaptic cell membranePerikaryonPostsynaptic density membraneEarly endosome membrane
Domains and Gene Ontology detail (21)

Domains & features

PASPAC

Gene Ontology

  • Caxon
  • Cdendrite
  • Cearly endosome membrane
  • Cnuclear inner membrane
  • Cperikaryon
  • Cplasma membrane
  • Cpostsynaptic density membrane
  • Cpresynaptic membrane
  • Cvoltage-gated potassium channel complex
  • Fcalmodulin binding
  • Fdelayed rectifier potassium channel activity
  • Fphosphatidylinositol bisphosphate binding

989 aa · 111 kDa · 2 isoforms

Biological roles

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

Synaptic signallingUniProt · GOCell proliferation & survivalUniProt · GOIon channel gatingGO
View supporting evidence

Synaptic signalling

  • ·Presynaptic cell membrane
  • ·Postsynaptic density membrane
  • ·postsynaptic density membrane
  • ·presynaptic membrane

Cell proliferation & survival

  • ·Pore-forming (alpha) subunit of a voltage-gated delayed rectifier potassium channel that…
  • ·regulation of cell population proliferation

Ion channel gating

  • ·potassium ion transmembrane transport

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
Multiple Sclerosis1 medicine

5 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.

Drug development

6 compounds recorded · 5 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 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 (6)
AMIFAMPRIDINE PHOSPHATEApproval
GUANIDINE HYDROCHLORIDEApproval
NERISPIRDINEPhase 2
AMIFAMPRIDINEApproval
TEDISAMILApproval
DALFAMPRIDINEApproval

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 High-Quality 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 (small molecule binder) — no clinical-stage drug of this modality recorded.

View underlying tractability evidence (8)
SM · Approved DrugSM · High-Quality LigandSM · Druggable FamilyAB · UniProt loc high confAB · GO CC high confAB · UniProt loc med confAB · UniProt SigP or TMHMMPR · Small Molecule Binder

Raw Open Targets tractability assessment buckets, by modality.

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)

RECRUITING · via dalfampridine · NCT06333171

RECRUITING · via dalfampridine · NCT06853015

TERMINATED · via dalfampridine · NCT04026568

COMPLETED · via dalfampridine · NCT02006160

COMPLETED · via dalfampridine · NCT01444300

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.