Protein / target
Potassium channel subfamily K member 9
Protein at a glance
Biological role
Outward rectifier potassium channel
Strongest disease association
Birk-Barel syndrome
Therapeutic position
Established drug target
Derived from structured UniProt, Open Targets and literature data on this page.
Protein profile
Canonical identity and biological annotation from UniProt.
Function overview
K(+) channel that conducts voltage-dependent outward rectifying currents upon membrane depolarization.
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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:11042359, PubMed:11431495, PubMed:26919430, PubMed:38630723). 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, PubMed:38630723). Homo- and heterodimerizes to form functional channels with distinct regulatory and gating properties (By similarity) (PubMed:23169818, PubMed:38630723). Allows K(+) currents with fast-gating kinetics important for the repolarization and hyperpolarization phases of action potentials (By similarity). In granule neurons, hyperpolarizes the resting membrane potential to limit intrinsic neuronal excitability, but once the action potential threshold is reached, supports high-frequency action potential firing and increased neuronal excitability. Homomeric and/or heteromeric KCNK3:KCNK9 channels operate in cerebellar granule cells, whereas heteromeric KCNK1:KCNK9 enables currents in hippocampal dentate gyrus granule neurons (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 (By similarity). In retinal ganglion cells, mediates outward currents that regulate action potentials in response to acidification of the synaptic cleft. Involved in transmission of image-forming and nonimage-forming visual information in the retina (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)
Subcellular location
Domains and Gene Ontology detail (18)Hide
Gene Ontology
- Cdendrite
- Cmitochondrial inner membrane
- Cplasma membrane
- Csynaptic vesicle
- Fidentical protein binding
- Fmetal ion binding
- Foutward rectifier potassium channel activity
- Fpotassium channel activity
- Fpotassium ion leak channel activity
- Fprotein heterodimerization activity
- Fsodium channel activity
- Pcellular response to acidic pH
Biological roles
What this protein does, drawn together from its UniProt function, Gene Ontology terms and Reactome pathways.
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
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.
Potassium channel subfamily K member 9 opener
Potassium channel subfamily K member 9 opener
Potassium channel subfamily K member 9 opener
ChEMBL mechanism, action type, target identity and approved indications. Open Targets clinical status.
Translational evidence
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 KCNK9
Gene-level evidence surfaced through the gene KCNK9that 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.
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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.
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Drug development
7 compounds recorded · 7 approved
View all recorded compounds (7)Hide
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
Antibodies — Emerging
Protein degraders — Emerging
View underlying tractability evidence (9)Hide
Raw Open Targets tractability assessment buckets, by modality.
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. Ranked by active status, then clinical phase and recency, and spread across the targeting drugs.
View all trials (26)Hide
ClinicalTrials.gov via the drug-target graph.
What's happening now
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.
- 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.