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Protein / target

ATP-sensitive inward rectifier potassium channel 11

Encoded byKCNJ11Q14654Homo sapiensSwiss-Prot
Clinically validated
Therapeutic maturity
15
Approved medicines
Open Targets target-level
View by indication →
30
Clinical trials
Small-molecule tractable
Druggability
Approved Drug

Protein at a glance

Biological role

ATP-activated inward rectifier potassium channel

Strongest disease association

Diabetes mellitus, permanent neonatal 2

Via encoding gene KCNJ11 · Genetic evidence · score 0.96

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

Inward rectifier potassium channel that forms the pore of ATP-sensitive potassium channels (KATP), regulating potassium permeability as a function of cytoplasmic ATP and ADP concentrations in many different cells.

View complete UniProt function annotation

Inward rectifier potassium channel that forms the pore of ATP-sensitive potassium channels (KATP), regulating potassium permeability as a function of cytoplasmic ATP and ADP concentrations in many different cells (PubMed:29286281, PubMed:34815345). Inward rectifier potassium channels are characterized by a greater tendency to allow potassium to flow into the cell rather than out of it. Their voltage dependence is regulated by the concentration of extracellular potassium; as external potassium is raised, the voltage range of the channel opening shifts to more positive voltages. The inward rectification is mainly due to the blockage of outward current by internal magnesium. Can be blocked by extracellular barium (By similarity). In pancreatic cells, it forms KATP channels with ABCC8/SUR1 (PubMed:29286281, PubMed:34815345). Can form cardiac and smooth muscle-type KATP channels with ABCC9

Subcellular location

Membrane
Domains and Gene Ontology detail (22)

Gene Ontology

  • Ccytoplasm
  • Cinward rectifying potassium channel
  • Cplasma membrane
  • CT-tubule
  • Fankyrin binding
  • FATP binding
  • FATP-activated inward rectifier potassium channel activity
  • FATPase-coupled monoatomic cation transmembrane transporter activity
  • Fpotassium ion binding
  • Ftransmembrane transporter binding
  • Fvoltage-gated monoatomic ion channel activity involved in regulation of presynaptic membrane potential
  • Fvoltage-gated potassium channel activity

390 aa · 44 kDa · 2 isoforms

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

  • ·ATPase-coupled monoatomic cation transmembrane transporter activity
  • ·voltage-gated monoatomic ion channel activity involved in regulation of presynaptic memb…
  • ·potassium ion transmembrane transport

Synaptic signalling

  • ·voltage-gated monoatomic ion channel activity involved in regulation of presynaptic memb…
View underlying pathways (6)

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.

ABCC8ABCC9KCNJ8DIABLO…DIABLOGABBR1GABBR2GCKXIAPINSKCNJ11

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.

Approved medicines with mapped indications

4 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.

Diabetes Mellitus4 medicines
Diabetes Mellitus, Type 23 medicines

15 medicines meet Open Targets' target-level approved-medicine definition; the 4 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

4

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.

Glyburide
ApprovedBlocker

Sulfonylurea receptor 1, Kir6.2 blocker

Indicated for Diabetes Mellitus, Diabetes Mellitus, Type 2

Acts on a complex — shared with ABCC8 · 1 of 2 recorded protein targets — narrow recorded profile

glimepiride
ApprovedBlocker

Sulfonylurea receptor 1, Kir6.2 blocker

Indicated for Diabetes Mellitus, Diabetes Mellitus, Type 2

Acts on a complex — shared with ABCC8 · 1 of 2 recorded protein targets — narrow recorded profile

repaglinide
ApprovedBlocker

Sulfonylurea receptor 1, Kir6.2 blocker

Indicated for Diabetes Mellitus, Diabetes Mellitus, Type 2

Acts on a complex — shared with ABCC8 · 1 of 2 recorded protein targets — narrow recorded profile

gliclazide
ApprovedBlocker

Sulfonylurea receptor 1, Kir6.2 blocker

Indicated for Diabetes Mellitus

Acts on a complex — shared with ABCC8 · 1 of 2 recorded protein targets — narrow recorded profile

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 KCNJ11

Gene-level evidence surfaced through the gene KCNJ11that 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.

Diabetes Mellitus, Type 2
0.99Well supported

Genetic evidence dominant · Open Targets 0.86

Diabetes Mellitus
0.98Well supported

Genetic evidence dominant · Open Targets 0.79

Diabetes mellitus, permanent neonatal 2
0.96Well supported

Genetic evidence dominant · Open Targets 0.81

Hyperinsulinemic hypoglycemia, familial, 2
0.96Well supported

Genetic evidence dominant · Open Targets 0.84

Diabetes mellitus, transient neonatal, 3
0.91Well supported

Genetic evidence dominant · Open Targets 0.80

View evidence synthesis (5)
Diabetes Mellitus, Type 2Well supported
0.99
agreement 0.901.00
Genetic41%Clinical33%Somatic mutation20%Literature6%Genetic literaturedup

Open Targets aggregate 0.86 · 4 independent evidence families · 1 not counted as duplicate

Diabetes MellitusWell supported
0.98
agreement 0.881.00
Genetic48%Clinical39%Animal model8%Literature6%

Open Targets aggregate 0.79 · 4 independent evidence families

Diabetes mellitus, permanent neonatal 2Well supported
0.96
agreement 0.841.00
Genetic89%Animal model12%Genetic literaturedup

Open Targets aggregate 0.81 · 2 independent evidence families · 1 not counted as duplicate

Hyperinsulinemic hypoglycemia, familial, 2Well supported
0.96
agreement 0.841.00
Genetic89%Animal model11%Literature0%Genetic literaturedup

Open Targets aggregate 0.84 · 3 independent evidence families · 1 not counted as duplicate

Diabetes mellitus, transient neonatal, 3Well supported
0.91
agreement 0.791.00
Genetic85%Animal model15%Literature0%Genetic literaturedup

Open Targets aggregate 0.80 · 3 independent evidence families · 1 not counted as duplicate

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
Diabetes Mellitus, Type 20.86
Hyperinsulinemic hypoglycemia, familial, 20.84
Diabetes mellitus, permanent neonatal 20.81
Diabetes mellitus, transient neonatal, 30.80
Diabetes Mellitus0.79
Permanent neonatal diabetes mellitus0.73
Transient neonatal diabetes mellitus0.72
MODY0.70
autosomal dominant hyperinsulinism due to Kir6.2 deficiency0.69
diazoxide-resistant focal hyperinsulinism due to Kir6.2 deficiency0.69

Drug development

15 compounds recorded · 15 approved

Open Targets' development universe — every compound recorded against the target at any stage, not all approved medicines. Distinct from the 4 drugs that target this protein in Forefront's canonical graph (4 with a mapped approved indication, shown above): these count different sets and are not a subset relation.

View all recorded compounds (10)
GLIPIZIDEApproval
CHLORPROPAMIDEApproval
REPAGLINIDEApproval
MITIGLINIDE CALCIUM DIHYDRATEApproval
GLIMEPIRIDEApproval
ACETOHEXAMIDEApproval
TOLAZAMIDEApproval
MINOXIDILApproval
DIAZOXIDEApproval
NATEGLINIDEApproval

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 (go cc high conf and uniprot sigp or tmhmm) — no clinical-stage drug of this modality recorded.

Protein degradersEmerging

Feasibility evidence (database ubiquitination and half-life data) — no clinical-stage drug of this modality recorded.

Other modalitiesStrong

Advanced Clinical support this modality.

View underlying tractability evidence (10)
SM · Approved DrugSM · Structure with LigandSM · High-Quality LigandSM · Druggable FamilyAB · GO CC high confAB · UniProt SigP or TMHMMPR · Database UbiquitinationPR · Half-life DataPR · Small Molecule BinderOC · Advanced Clinical

Raw Open Targets tractability assessment buckets, by modality.

Safety-related annotations

abnormal pulseLynch et al. (2017)increased/decreased blood glucoseLynch et al. (2017)increased urinary sodium excretionLynch et al. (2017)decreased heart rateLynch et al. (2017)decreased blood glucoseLynch et al. (2017)cardiac lesionsLynch et al. (2017)decreased blood pressureLynch et al. (2017)increased heart rateLynch et al. (2017)cardiac arrhythmiaLynch et al. (2017)atrioventricular blockLynch et al. (2017)decreased blood insulinLynch et al. (2017)decreased convulsionsLynch et al. (2017)

Terms indexed against this target in Open Targets' safety data, with their datasource. These are annotations, not causal claims: the direction of effect (whether activation or inhibition is implicated), species and evidence strength are not captured here, so an entry does not mean that modulating this target is known to cause that condition.

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)

UNKNOWN · via glimepiride · NCT04287387

WITHDRAWN · via Glyburide · NCT03078725

ClinicalTrials.gov via the drug-target graph.

What's happening now

12

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. Label change2026-08-11

    Label change: GLYBURIDE AND METFORMIN HYDROCHLORIDE (ANDA077870)

    fda · regulatory · fda · via Glyburide

  2. Label change2026-08-11

    Label change: GLYBURIDE AND METFORMIN HYDROCHLORIDE (ANDA206748)

    fda · regulatory · fda · via Glyburide

  3. Label change2026-08-11

    Label change: GLYBURIDE-METFORMIN HYDROCHLORIDE (ANDA079009)

    fda · regulatory · fda · via Glyburide

  4. Supplemental approval2026-08-07

    Supplemental approval: REPAGLINIDE (ANDA207209)

    fda · regulatory · fda · via repaglinide

  5. Label change2026-06-30

    Label change: GLYBURIDE AND METFORMIN HYDROCHLORIDE (ANDA206748)

    fda · regulatory · fda · via Glyburide

  6. Label change2026-06-30

    Label change: GLYBURIDE AND METFORMIN HYDROCHLORIDE (ANDA206748)

    fda · regulatory · fda · via Glyburide

  7. Label change2025-06-20

    Label change: GLYBURIDE-METFORMIN HYDROCHLORIDE (ANDA079009)

    fda · regulatory · fda · via Glyburide

  8. Label change2025-06-20

    Label change: GLYBURIDE-METFORMIN HYDROCHLORIDE (ANDA079009)

    fda · regulatory · fda · via Glyburide

  9. New publication2019-10-25
    Pharmacological Inhibitors of the NLRP3 Inflammasome.

    Frontiers in immunology · 2019 · 518 citations · Europe PMC · via Glyburide

  10. New publication2015-08-01
    Glyburide in Women With Mild Gestational Diabetes: A Randomized Controlled Trial.

    Obstetrics and gynecology · 2015 · 26 citations · Europe PMC · via Glyburide

  11. New publication2009-02-01
    Efficacy and safety of the dipeptidyl peptidase-4 inhibitor alogliptin in patients with type 2 diabetes inadequately controlled by glyburide monotherapy.

    Diabetes, obesity & metabolism · 2009 · 124 citations · Europe PMC · via Glyburide

  12. New publication2007-06-26
    Efficacy and safety of the dipeptidyl peptidase-4 inhibitor, sitagliptin, in patients with type 2 diabetes mellitus inadequately controlled on glimepiride alone or on glimepiride and metformin.

    Diabetes, obesity & metabolism · 2007 · 352 citations · Europe PMC · via glimepiride

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.