Protein / target
Potassium channel subfamily K member 18
Protein at a glance
Biological role
Calcium-activated potassium channel activity
Primary system
Nervous system
Strongest disease association
migraine disorder
Therapeutic maturity
Clinically validated target
Druggability
Small molecule
Clinical development
5 approved
Derived from structured UniProt, Open Targets and literature data on this page.
Protein profile
Canonical identity and biological annotation from UniProt.
Function
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
Domains and Gene Ontology detail (10)Hide
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
Biological roles
What this protein does, drawn together from its UniProt function, Gene Ontology terms and Reactome pathways.
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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
Ion channel gating
- ·potassium ion transmembrane transport
Transcriptional regulation
- ·K(+) channel that conducts outward and inward rectifying currents at depolarized and hyp…
View underlying pathways (2)Hide underlying pathways
Concepts derived from UniProt GO Reactome — each badge above shows which sources supported that role.
Interaction neighbourhood
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.
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
Whether each drug engages this protein directly or through a complex, and how many other targets are recorded for it. Direct binders with few recorded targets are listed first.
Potassium channel subfamily K member 18 opener
Appears in clinical studies involving kidney injury, Hydrocephalus, delirium, sedation
Potassium channel subfamily K member 18 opener
Appears in clinical studies involving septic shock, Sepsis
Potassium channel subfamily K member 18 opener
Appears in clinical studies involving endometrial cancer, myocardial infarction, sedation, delirium
ChEMBL mechanism, action type and target identity. Open Targets clinical status and indications.
Translational evidence
Why this target matters therapeutically — disease associations, drugs in development, tractability and safety, from Open Targets.
Strongest genetic associations
Human genetic evidence — the most direct causal link between this target and a disease.
Highest-confidence therapeutic associations
Diseases where a drug acting on this target has already reached clinical development.
Highest overall evidence
Remaining associations by Open Targets' aggregated evidence score.
Show all associationsHide all associations
Open Targets ranks 242 associations for this target and we store the top 10 by aggregated score. The long tail is largely literature co-mention and RNA-expression evidence, not evidence that this target drives those diseases.
Known drugs · 5 total
kidney injury · Hydrocephalus · delirium
endometrial cancer · myocardial infarction · sedation
septic shock · Sepsis
Intellectual disability · cognitive disorder · delirium
septic shock · Sepsis
Tractability
Clinical trials
Trials of drugs that target this protein — reached indirectly through those drugs, so a trial listed here studies the drug, not the protein.
Show remaining trials (24)Hide
ClinicalTrials.gov via the drug-target graph.
Forefront confidence
Our own weighting of the evidence behind each disease association. Human genetics and clinical evidence count for most; literature co-mention counts for little, because two entities sharing an abstract is not evidence that one drives the other.
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 underlying per-type scores are shown above so the calculation can be checked.
What's happening now
Recent activity around this target, drawn from one canonical event stream. Every item is reached through 3 drugs that target this protein, so each event is news about that drug rather than about the protein directly.
- New publicationNeonatal sevoflurane exposures inhibits DHHC5-mediated palmitoylation of TfR1 in oligodendrocytes, leading to hypomyelination and neurological impairments.
- New publicationEarly exposure to common anesthetic agents causes widespread neurodegeneration in the developing rat brain and persistent learning deficits.
- New publicationSharp wave-associated high-frequency oscillation (200 Hz) in the intact hippocampus: network and intracellular mechanisms.
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.