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Protein / target

Potassium channel subfamily K member 18

Encoded byKCNK18Q7Z418Homo sapiensSwiss-Prot
Clinically validated
Therapeutic maturity
5
Approved medicines
Open Targets target-level
30
Clinical trials
Small-molecule tractable
Druggability
Approved Drug

Protein at a glance

Biological role

Calcium-activated potassium channel

Strongest disease association

Migraine Disorders

Via encoding gene KCNK18 · Genetic literature evidence · score 0.55

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 outward and inward rectifying currents at depolarized and hyperpolarized membrane potentials, respectively.

View complete UniProt function annotation

K(+) channel that conducts outward and inward rectifying currents at depolarized and hyperpolarized membrane potentials, respectively. The outward rectifying currents are voltage-dependent, coupled to K(+) electrochemical gradient across the membrane, whereas the inward currents can be induced in response to activation of Ca(2+)-mobilizing receptors (PubMed:12754259, PubMed:15562060, PubMed:20871611, PubMed:22355750, PubMed:26919430, PubMed:30573346). Homo- and heterodimerizes to form functional channels with distinct regulatory and gating properties. In trigeminal ganglia sensory neurons, the heterodimers of KCNK18/TRESK and KCNK2/TREK-1 or KCNK10/TREK-2 inhibit neuronal firing and neurogenic inflammation by stabilizing the resting membrane potential at K(+) equilibrium potential as well as by regulating the threshold of action potentials and the spike frequency (By similarity). In thymocytes, conducts K(+) currents upon T cell receptor (TCR) signaling leading to sustained Ca(2+) influx and NF-kappa-B activation, FOXP3 transcription and positive selection of regulatory T cell (Treg) progenitor subsets (PubMed:34702947). Appears to mediate the analgesics effects of hydroxy-alpha-sanshool, a metabolite naturally present in Schezuan pepper and other Xanthoxylum plants (By similarity)

Subcellular location

Cell membrane
Domains and Gene Ontology detail (10)

Gene Ontology

  • Cplasma membrane
  • Fcalcium-activated potassium channel activity
  • Fmetal ion binding
  • Foutward rectifier potassium channel activity
  • Fpotassium ion leak channel activity
  • Pcellular response to pH
  • Ppotassium ion export across plasma membrane
  • Ppotassium ion transmembrane transport
  • Ppotassium ion transport
  • Pregulation of CD4-positive, CD25-positive, alpha-beta regulatory T cell differentiation

384 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 gatingGOImmune signallingUniProt · GO
View supporting evidence

Ion channel gating

  • ·potassium ion transmembrane transport

Immune signalling

  • ·K(+) channel that conducts outward and inward rectifying currents at depolarized and hyp…
  • ·regulation of CD4-positive, CD25-positive, alpha-beta regulatory T cell differentiation
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.

KRT76KCNK13KCNK12KCNK7KCNK17ATP1A2KCNK3KCNK10SCN1AKCNK1KCNK18

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 18 opener

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

Halothane
ApprovedOpener

Potassium channel subfamily K member 18 opener

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

sevoflurane
ApprovedOpener

Potassium channel subfamily K member 18 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 KCNK18

Gene-level evidence surfaced through the gene KCNK18 that 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.

Migraine Disorders
0.61Moderately supported

Genetic literature evidence dominant · Open Targets 0.43

Neurodevelopmental Disorders
0.33Limited support

Clinical evidence dominant · Open Targets 0.26

View evidence synthesis (2)
Migraine DisordersModerately supported
0.61
agreement 0.490.74
Genetic literature57%Animal model30%Literature14%

Open Targets aggregate 0.43 · 3 independent evidence families

Neurodevelopmental DisordersLimited support
0.33
agreement 0.170.48
Clinical97%Literature3%

Open Targets aggregate 0.26 · 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
Migraine Disorders0.43
Neurodevelopmental Disorders0.26

Drug development

5 compounds recorded · 5 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 (5)
ISOFLURANEApproval
SEVOFLURANEApproval
HALOTHANEApproval
DESFLURANEApproval
ENFLURANEApproval

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 Druggable Family 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 (6)
SM · Approved DrugSM · 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

4

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. Trial status changed2026-08-25

    The Effect of Low-Flow Sevoflurane and Low-Flow Desflurane Anesthesia on Postoperative Sore Throat in Laparoscopic Cholecystectomy Surgery

    Status changed to Completed · ClinicalTrials.gov · via sevoflurane

  2. 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

  3. 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

  4. 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.