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Protein / target

Potassium channel subfamily K member 3

Encoded byKCNK3O14649Homo sapiensSwiss-Prot
Clinically validated
Therapeutic maturity
7
Approved medicines
Open Targets target-level
30
Clinical trials
Small-molecule tractable
Druggability
Approved Drug

Protein at a glance

Biological role

Outward rectifier potassium channel

Strongest disease association

Pulmonary hypertension, primary, 4

Via encoding gene KCNK3 · Genetic evidence · score 0.90

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

K(+) channel that conducts voltage-dependent outward rectifying currents upon membrane depolarization.

View complete UniProt function annotation

K(+) channel that conducts voltage-dependent outward rectifying currents upon membrane depolarization. Voltage sensing is coupled to K(+) electrochemical gradient in an 'ion flux gating' mode where outward but not inward ion flow opens the gate (PubMed:23169818, PubMed:26919430, PubMed:32499642, PubMed:36195757, PubMed:9312005). Changes ion selectivity and becomes permeable to Na(+) ions in response to extracellular acidification. Protonation of the pH sensor His-98 stabilizes C-type inactivation conformation likely converting the channel from outward K(+)-conducting, to inward Na(+)-conducting to nonconductive state (PubMed:22948150). Homo- and heterodimerizes to form functional channels with distinct regulatory and gating properties (PubMed:23169818, PubMed:32499642). Allows K(+) currents with fast-gating kinetics important for the repolarization and hyperpolarization phases of action potentials (By similarity). In cerebellar granule cells, heteromeric KCNK3:KCNK9 channel may hyperpolarize the resting membrane potential to limit intrinsic neuronal excitability, but once the action potential threshold is reached, it may support high-frequency action potential firing and increased neuronal excitability (By similarity). Dispensable for central chemosensory respiration i.e. breathing controlled by brainstem CO2/pH, it rather conducts pH-sensitive currents and controls the firing rate of serotonergic raphe neurons involved in potentiation of the respiratory chemoreflex. Additionally, imparts chemosensitivity to type 1 cells in carotid bodies which respond to a decrease in arterial oxygen pressure or an increase in carbon dioxide pressure or pH to initiate adaptive changes in pulmonary ventilation (By similarity). In adrenal gland, contributes to the maintenance of a hyperpolarized resting membrane potential of aldosterone-producing cells at zona glomerulosa and limits aldosterone release as part of a regulatory mechanism that controls arterial blood pressure and electrolyte homeostasis (By similarity). In brown adipocytes, mediates K(+) efflux that counteracts norepinephrine-induced membrane depolarization, limits Ca(2+) efflux and downstream cAMP and PKA signaling, ultimately attenuating lipid oxidation and adaptive thermogenesis (By similarity)

Subcellular location

Cell membrane
Domains and Gene Ontology detail (24)

Gene Ontology

  • Cplasma membrane
  • Csynapse
  • Fmetal ion binding
  • Fmonoatomic ion channel activity
  • Fopen rectifier potassium channel activity
  • Foutward rectifier potassium channel activity
  • Fpotassium channel activity
  • Fpotassium ion leak channel activity
  • Fprotein heterodimerization activity
  • FS100 protein binding
  • Fsodium channel activity
  • Pcellular response to acidic pH

394 aa · 44 kDa

Biological roles

Reactome v97

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

Ion channel gatingGOSynaptic signallingGO
View supporting evidence

Ion channel gating

  • ·monoatomic ion channel activity
  • ·monoatomic ion transmembrane transport
  • ·potassium ion transmembrane transport

Synaptic signalling

  • ·synapse
  • ·chemical synaptic transmission
View underlying pathways (2)

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

Interaction neighbourhood

STRING v12.0

Proteins with the strongest functional or physical association. Node size and line weight reflect STRING confidence; hover or select a partner to inspect one association.

KCNK9S100A10KRT76KCNK5KCNK18KCNK1KCNK10YWHABSCN10AANXA2KCNK3

10 strongest partners — larger node and heavier line mean higher confidence

Functional and physical associations from STRING v12.0. Only associations with this protein are drawn — partner-to-partner links are not part of this evidence.

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.

Isoflurane
ApprovedOpener

Potassium channel subfamily K member 3 opener

Direct interaction with this protein · 1 of 23 recorded protein targets — broad pharmacology

Halothane
ApprovedOpener

Potassium channel subfamily K member 3 opener

Direct interaction with this protein · 1 of 23 recorded protein targets — broad pharmacology

sevoflurane
ApprovedOpener

Potassium channel subfamily K member 3 opener

Direct interaction with this protein · 1 of 23 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 KCNK3

Gene-level evidence surfaced through the gene KCNK3that 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.

Pulmonary hypertension, primary, 4
0.90Well supported

Genetic evidence dominant · Open Targets 0.75

Hypertension
0.84Well supported

Genetic evidence dominant · Open Targets 0.51

Essential Hypertension
0.76Well supported

Genetic evidence dominant · Open Targets 0.46

Alcohol drinking
0.72Moderately supported

Genetic evidence dominant · Open Targets 0.44

Stroke
0.69Moderately supported

Genetic evidence dominant · Open Targets 0.42

View evidence synthesis (5)
Pulmonary hypertension, primary, 4Well supported
0.90
agreement 0.781.00
Genetic100%Genetic literaturedup

Open Targets aggregate 0.75 · 1 independent evidence family · 1 not counted as duplicate

HypertensionWell supported
0.84
agreement 0.700.98
Genetic96%Literature4%

Open Targets aggregate 0.51 · 2 independent evidence families

Essential HypertensionWell supported
0.76
agreement 0.620.90
Genetic99%Literature1%

Open Targets aggregate 0.46 · 2 independent evidence families

Alcohol drinkingModerately supported
0.72
agreement 0.600.84
Genetic100%

Open Targets aggregate 0.44 · 1 independent evidence family

StrokeModerately supported
0.69
agreement 0.550.83
Genetic98%Literature2%

Open Targets aggregate 0.42 · 2 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
Pulmonary hypertension, primary, 40.75
Hypertension0.51
Pulmonary arterial hypertension0.50
Essential Hypertension0.46
Alcohol drinking0.44
Neurodevelopmental Disorders0.43
Stroke0.42
Cardiovascular Diseases0.41
Cerebrovascular Disorders0.41

Drug development

7 compounds recorded · 7 approved

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: these count different sets and are not a subset relation.

View all recorded compounds (7)
ENFLURANEApproval
SEVOFLURANEApproval
DESFLURANEApproval
HALOTHANEApproval
DOXAPRAMApproval
DOXAPRAM HYDROCHLORIDEApproval
ISOFLURANEApproval

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

View underlying tractability evidence (8)
SM · Approved DrugSM · Structure with LigandSM · High-Quality LigandSM · Druggable FamilyAB · UniProt loc high confAB · GO CC high 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)

NOT_YET_RECRUITING · via sevoflurane · NCT07035782

ClinicalTrials.gov via the drug-target graph.

What's happening now

3

Recent therapeutic activity around this target — regulatory actions, clinical trials and safety signals for 3 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. New publication2025-02-08
    Neonatal sevoflurane exposures inhibits DHHC5-mediated palmitoylation of TfR1 in oligodendrocytes, leading to hypomyelination and neurological impairments.

    Journal of advanced research · 2025 · 9 citations · Europe PMC · via sevoflurane

  2. New publication2003-02-01
    Early exposure to common anesthetic agents causes widespread neurodegeneration in the developing rat brain and persistent learning deficits.

    The Journal of neuroscience : the official journal of the Society for Neuroscience · 2003 · 1,387 citations · Europe PMC · via Isoflurane

  3. New publication1995-01-01
    Sharp wave-associated high-frequency oscillation (200 Hz) in the intact hippocampus: network and intracellular mechanisms.

    The Journal of neuroscience : the official journal of the Society for Neuroscience · 1995 · 798 citations · Europe PMC · via Halothane

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.