KCNJ11

Summary

KCNJ11 (potassium inwardly rectifying channel subfamily J member 11, HGNC:6257) is a protein-coding gene on chromosome 11p15.1, encoding ATP-sensitive inward rectifier potassium channel 11 (Q14654). 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.

Potassium channels are present in most mammalian cells, where they participate in a wide range of physiologic responses. The protein encoded by this gene is an integral membrane protein and inward-rectifier type potassium channel. The encoded protein, which has a greater tendency to allow potassium to flow into a cell rather than out of a cell, is controlled by G-proteins and is found associated with the sulfonylurea receptor SUR. Mutations in this gene are a cause of familial persistent hyperinsulinemic hypoglycemia of infancy (PHHI), an autosomal recessive disorder characterized by unregulated insulin secretion. Defects in this gene may also contribute to autosomal dominant non-insulin-dependent diabetes mellitus type II (NIDDM), transient neonatal diabetes mellitus type 3 (TNDM3), and permanent neonatal diabetes mellitus (PNDM). Multiple alternatively spliced transcript variants that encode different protein isoforms have been described for this gene.

Source: NCBI Gene 3767 — RefSeq curated summary.

At a glance

• Gene–disease (curated): hyperinsulinemic hypoglycemia, familial, 2 (Definitive, ClinGen) — +13 more curated relationships
• GWAS associations: 36
• Clinical variants (ClinVar): 562 total — 21 pathogenic, 36 likely-pathogenic
• Phenotypes (HPO): 132
• Druggable target: yes — 7 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_000525

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:6257
Approved symbol	KCNJ11
Name	potassium inwardly rectifying channel subfamily J member 11
Location	11p15.1
Locus type	gene with protein product
Status	Approved
Aliases	Kir6.2, BIR
Ensembl gene	ENSG00000187486
Ensembl biotype	protein_coding
OMIM	600937
Entrez	3767

Gene structure

Transcript identifiers

Ensembl transcripts: 8 — 7 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000339994, ENST00000526747, ENST00000526912, ENST00000528731, ENST00000528992, ENST00000682350, ENST00000682764, ENST00000948565

RefSeq mRNA: 4 — MANE Select: NM_000525 NM_000525, NM_001166290, NM_001377296, NM_001377297

CCDS: CCDS31436, CCDS53606

Canonical transcript exons

ENST00000339994 — 1 exons

Exon	Start	End
ENSE00001366321	17385248	17388659

Expression profiles

Bgee: expression breadth ubiquitous, 161 present calls, max score 96.62.

FANTOM5 (CAGE): breadth broad, TPM avg 1.2207 / max 43.6572, expressed in 439 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
118859	0.7379	358
118858	0.2779	160
118857	0.1148	54
118856	0.0901	44

Top tissues by expression

251 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
gastrocnemius	UBERON:0001388	96.62	gold quality
hindlimb stylopod muscle	UBERON:0004252	96.47	gold quality
muscle of leg	UBERON:0001383	94.45	gold quality
tibialis anterior	UBERON:0001385	87.36	silver quality
apex of heart	UBERON:0002098	86.45	gold quality
right hemisphere of cerebellum	UBERON:0014890	86.45	gold quality
cerebellar hemisphere	UBERON:0002245	85.98	gold quality
cerebellar cortex	UBERON:0002129	85.91	gold quality
cerebellum	UBERON:0002037	84.33	gold quality
islet of Langerhans	UBERON:0000006	81.80	gold quality
right frontal lobe	UBERON:0002810	81.75	gold quality
prefrontal cortex	UBERON:0000451	81.41	gold quality
heart left ventricle	UBERON:0002084	81.22	gold quality
skeletal muscle tissue	UBERON:0001134	80.89	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	80.50	gold quality
cardiac ventricle	UBERON:0002082	79.86	gold quality
right atrium auricular region	UBERON:0006631	79.36	gold quality
Brodmann (1909) area 9	UBERON:0013540	79.35	gold quality
anterior cingulate cortex	UBERON:0009835	78.75	gold quality
cortical plate	UBERON:0005343	78.52	gold quality
body of pancreas	UBERON:0001150	78.13	gold quality
cardiac atrium	UBERON:0002081	78.07	gold quality
body of stomach	UBERON:0001161	77.82	gold quality
pancreas	UBERON:0001264	77.82	gold quality
muscle tissue	UBERON:0002385	77.76	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	77.37	gold quality
frontal cortex	UBERON:0001870	76.61	gold quality
neocortex	UBERON:0001950	76.39	gold quality
caudate nucleus	UBERON:0001873	75.61	gold quality
heart	UBERON:0000948	75.33	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	2.05

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): E2F1, EPAS1, FOXA2, HNF4A, ISL1, PDX1, ZGLP1

miRNA regulators (miRDB)

57 targeting KCNJ11, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-4673	100.00	66.64	1490
HSA-MIR-4500	99.99	72.72	2367
HSA-LET-7A-5P	99.98	72.29	1790
HSA-LET-7B-5P	99.98	72.31	1790
HSA-LET-7C-5P	99.98	72.29	1790
HSA-LET-7E-5P	99.98	72.29	1790
HSA-LET-7F-5P	99.98	72.56	1784
HSA-LET-7G-5P	99.98	72.37	1784
HSA-LET-7I-5P	99.98	72.37	1788
HSA-MIR-98-5P	99.98	72.33	1787
HSA-MIR-4645-5P	99.98	65.81	1284
HSA-LET-7D-5P	99.96	71.76	1632
HSA-MIR-4458	99.96	71.64	1650
HSA-MIR-6778-3P	99.96	67.29	2693
HSA-MIR-335-3P	99.93	73.36	4958
HSA-MIR-3143	99.93	71.96	3104
HSA-MIR-497-5P	99.92	71.83	2674
HSA-MIR-15A-5P	99.90	72.80	2787
HSA-MIR-15B-5P	99.90	72.78	2798
HSA-MIR-16-5P	99.90	72.80	2780
HSA-MIR-195-5P	99.90	72.81	2805
HSA-MIR-6838-5P	99.89	71.94	2690
HSA-MIR-424-5P	99.89	71.90	2641
HSA-MIR-4524A-3P	99.72	66.85	2406
HSA-MIR-6752-3P	99.72	66.71	1587
HSA-MIR-4729	99.69	72.18	4233
HSA-MIR-4530	99.69	66.47	1509
HSA-MIR-7157-5P	99.66	69.33	1829
HSA-MIR-6715B-5P	99.64	69.63	1420
HSA-MIR-4310	99.59	68.84	2527

Literature-anchored findings (GeneRIF, showing 40)

• Assembly limits the pharmacological complexity of ATP-sensitive potassium channels (PMID:11825905)
• The prevalent Glu23Lys polymorphism in the potassium inward rectifier 6.2 (KIR6.2) gene is associated with impaired glucagon suppression in response to hyperglycemia. (PMID:12196481)
• ABCC8 (SUR1) and KCNJ11 (KIR6.2) mutations in persistent hyperinsulinemic hypoglycemia of infancy and evaluation of different therapeutic measures. May account for the different therapeutic responses. (PMID:12199344)
• the MDR-like core of SUR is linked with the K(IR) pore in KATP channels (PMID:12213829)
• the E23K mutation in the KIR6.2 gene is not associated with detectable alterations in glucose-stimulated insulin secretion (PMID:12351459)
• down-regulation of this channel may facilitate myometrial function during late pregnancy (PMID:12356945)
• Localization of ATP-sensitive K+ (KATP) channels in human skeletal muscle and the functional importance of these channels for human muscle K+ distribution at rest and during muscle activity (PMID:12388475)
• E23K variant is associated with type 2 diabetes. (PMID:12540637)
• The E23K variant associates with impaired post-OGTT serum insulin response and increased risk of type 2 diabetes. (PMID:12540638)
• No association for NIDDM susceptibility polymorphism in Kir6.2. (PMID:12819904)
• Binding of the alpha phosphate group of ATP to R201 then stabilizes the closed state. R50 on the N-terminus controls ATP binding by facilitating the interaction of the beta phosphate group of ATP with K185 to destabilize the open state. (PMID:12860923)
• In corporal smooth muscle is composed of Kir6.1-Kir6.2 construct expressed with SUR2B.K(ATP) channel in corporal smooth muscle cells is composed of heteromultimers of Kir6.1 and Kir6.2 with the ratio of 3 : 1 or 4 : 0 and SUR2B. (PMID:12934053)
• E23K/I337V polymorphism may have a diabetogenic effect via increased KATP channel activity in response to endogenous levels of LC-CoAs in tissues involved in the maintenance of glucose homeostasis. (PMID:14514649)
• a compensatory increase in I(Ca) counteracts a mild activation of ATP-insensitive K(ATP) channels to maintain the action potential duration and elevate the inotropic state of transgenic hearts (PMID:14656703)
• binding of ATP to Kir6.2 alters the interaction between the N- and C-terminal domains (PMID:14681552)
• In this study of acute myocardial infarct patients, sudden cardiac death was not related to polymorphisms in the KCNJ11 gene (PMID:14871556)
• Association of this gene’s single nucleotide polymorphism with type 2 diabetes. (PMID:14988278)
• SUR1/Kir6.2 gene region contributes to risk of type 2 diabetes and encodes targets for hypoglycemic medications. Link between mechanism of disease and targets for pharmacological treatment. (PMID:15111507)
• Heterozygous activating mutations in the gene encoding Kir6.2 cause permanent neonatal diabetes and may also be associated with developmental delay, muscle weakness, and epilepsy. (PMID:15115830)
• Insulin-dependent patients with mutations in Kir6.2 may be managed on an oral sulfonylurea with sustained metabolic control rather than insulin injections. (PMID:15448106)
• Kir6.2 mutations are a common cause (53%) of permanent neonatal diabetes in Caucasians. (PMID:15448107)
• KCNJ11 mutations are rare in patients diagnosed with type 1 diabetes, the identification of a KCNJ11 mutation may have important treatment implications. (PMID:15504982)
• Mutations can yield partially functioning channels, including cases of hyperinsulinism that are fully responsive to diazoxide. (PMID:15562009)
• Polymorphisms of SUR1 gene predicted conversion from impaired glucose tolerance to type 2 diabetes, and the effect of these polymorphisms on diabetes risk was additive with E23K polymorphism of Kir6.2 gene. (PMID:15579791)
• KCNJ11 mutations are a common cause of permanent neonatal diabetes mellitus either in isolation or associated with developmental delay (PMID:15580558)
• mutations in the slide helix of Kir6.2 (V59G) influence the channel kinetics, providing evidence that this domain is involved in Kir channel gating (PMID:15583126)
• mutations in KCNJ11 are the first genetic cause for remitting as well as permanent diabetes (PMID:15718250)
• Heterozygote mutation in a patient with severe diabetic ketoacidosis, was nevertheless able to tolerate glibenclamide despite transitory diarrhea. (PMID:15735229)
• the epoxyeicosatrienoic acid-Kir6.2 interaction may allosterically change the ATP binding site on Kir6.2, reducing the channel sensitivity to ATP (PMID:15760904)
• Amino acid substituion polymorphism increases the risk of type 2 diabetes. (PMID:15797964)
• an R201H missense mutation, and sulfonylurea-treatable diabetes in a newborn (PMID:15838686)
• E23K variant in muscular K(ATP) channels affects systemic glucose homeostasis and poses an important risk factor for type 2 diabetes and obesity. (PMID:15855351)
• Kir6.2 and INS VNTR variants may have roles in glucose homeostasis in young obese (PMID:15956217)
• Mutations in Kir6.2 altered Kir6.2/SUR1 interactions. (PMID:15962003)
• Effects of side-chain length and the degree of saturation of various acyl CoAs on channel activity. (PMID:15983208)
• KCNJ11 mutations cause neonatal diabetes, and increase the current magnitude of heterozygous K(ATP) channels in two ways: by increasing MgATP activation and by decreasing ATP inhibition. (PMID:16087682)
• The E23K polymorphism of KCNJ11 seems to predispose to gestational diabetes mellitus (GDM) in Scandinavian women. (PMID:16320083)
• identification of a novel KCNJ11 mutation associated with congenital hyperinsulinism that renders a missense mutation, F55L, in the Kir6.2 protein. (PMID:16332676)
• The greater ATP inhibition of mutant Kir6.2/SUR2A than of Kir6.2/SUR1 can explain why gain-of-function Kir6.2 mutations manifest effects in brain and beta-cells but not in the heart. (PMID:16339180)
• analysis of mutations in Kir6.2 (KCNJ11) and SUR1 (ABCC8), the spectrum of phenotypes, and the implications for treatment when patients are diagnosed with mutations in these genes [review] (PMID:16416420)

Cross-species orthologs

9 orthologs

Organism	Symbol	Gene ID
danio_rerio	kcnj11	ENSDARG00000051880
mus_musculus	Kcnj11	ENSMUSG00000096146
rattus_norvegicus	Kcnj11	ENSRNOG00000021128
drosophila_melanogaster	Irk3	FBGN0032706
drosophila_melanogaster	Irk2	FBGN0039081
drosophila_melanogaster	Irk1	FBGN0265042
caenorhabditis_elegans		WBGENE00002149
caenorhabditis_elegans		WBGENE00002150
caenorhabditis_elegans		WBGENE00002151

Paralogs (15): KCNJ13 (ENSG00000115474), KCNJ5 (ENSG00000120457), KCNJ8 (ENSG00000121361), KCNJ2 (ENSG00000123700), KCNJ1 (ENSG00000151704), KCNJ16 (ENSG00000153822), KCNJ6 (ENSG00000157542), KCNJ15 (ENSG00000157551), KCNJ9 (ENSG00000162728), KCNJ3 (ENSG00000162989), KCNJ4 (ENSG00000168135), KCNJ10 (ENSG00000177807), KCNJ14 (ENSG00000182324), KCNJ12 (ENSG00000184185), KCNJ18 (ENSG00000260458)

Protein

Protein identifiers

ATP-sensitive inward rectifier potassium channel 11 — Q14654 (reviewed: Q14654)

Alternative names: IKATP, Inward rectifier K(+) channel Kir6.2, Potassium channel, inwardly rectifying subfamily J member 11

All UniProt accessions (5): A0A804HHV7, B2RC52, E9PPF1, Q14654, H0YES9

UniProt curated annotations — full annotation on UniProt →

Function. 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. 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. In pancreatic cells, it forms KATP channels with ABCC8/SUR1. Can form cardiac and smooth muscle-type KATP channels with ABCC9.

Subunit / interactions. Homotetramer; the homotetramer binds four ATP molecules (one ATP per subunit). Forms an heterooctamer with ABCC8/SUR1; one KCNJ11 homotetramer interacts with four ABCC8/SUR1 molecules. Interacts with ABCC9/SUR2.

Subcellular location. Membrane.

Post-translational modifications. Phosphorylation by MAPK1 results in changes in channel gating that destabilize the closed states and reduce the ATP sensitivity.

Disease relevance. Hyperinsulinemic hypoglycemia, familial, 2 (HHF2) [MIM:601820] A form of hyperinsulinemic hypoglycemia, a clinically and genetically heterogeneous disorder characterized by inappropriate insulin secretion from the pancreatic beta-cells in the presence of low blood glucose levels. HHF2 is a common cause of persistent hypoglycemia in infancy. Unless early and aggressive intervention is undertaken, brain damage from recurrent episodes of hypoglycemia may occur. HHF2 inheritance can be autosomal dominant or autosomal recessive. The disease is caused by variants affecting the gene represented in this entry. Diabetes mellitus, permanent neonatal, 2 (PNDM2) [MIM:618856] A form of permanent neonatal diabetes mellitus, a type of diabetes characterized by onset of persistent hyperglycemia within the first six months of life. Initial clinical manifestations include intrauterine growth retardation, hyperglycemia, glycosuria, osmotic polyuria, severe dehydration, and failure to thrive. Some PNDM2 patients may also have developmental delay, muscle weakness, epilepsy and dysmorphic features. PNDM2 transmission pattern is consistent with autosomal dominant inheritance. The disease is caused by variants affecting the gene represented in this entry. Diabetes mellitus, transient neonatal, 3 (TNDM3) [MIM:610582] An autosomal dominant form of diabetes mellitus defined by the onset of insulin-requiring hyperglycemia within the first month of life. In about half of the neonates, diabetes is transient and resolves at a median age of 3 months, whereas the rest have a permanent form of diabetes. TNDM3 onset is variable and onset in the third decade of life has been described in some patients. The disease is caused by variants affecting the gene represented in this entry. Defects in KCNJ11 may contribute to non-insulin-dependent diabetes mellitus (NIDDM), also known as diabetes mellitus type 2. Maturity-onset diabetes of the young 13 (MODY13) [MIM:616329] A form of diabetes that is characterized by an autosomal dominant mode of inheritance, onset in childhood or early adulthood (usually before 25 years of age), a primary defect in insulin secretion and frequent insulin-independence at the beginning of the disease. The disease is caused by variants affecting the gene represented in this entry.

Activity regulation. KATP channels are regulated by cytoplasmic ATP/ADP ratios; ATP inhibits the channel by closing the pore, while ADP activates the channel. Activated by phosphatidylinositol 4,5-biphosphate (PtdIns(4,5)P2).

Domain organisation. There are two PtdIns(4,5)P2 binding sites: A canonical site where the phosphate groups of one PtdIns(4,5)P2 molecule are coordinated at least by residues Lys-67, Trp-68 and Arg-176; a non-canonical site where the second PtdIns(4,5)P2 molecule is coordinated by both KCNJ11 and ABCC8/SUR1 residues.

Similarity. Belongs to the inward rectifier-type potassium channel (TC 1.A.2.1) family. KCNJ11 subfamily.

Isoforms (2)

UniProt ID	Names	Canonical?
Q14654-1	1	yes
Q14654-2	2

RefSeq proteins (4): NP_000516, NP_001159762, NP_001364225, NP_001364226 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR003279	K_chnl_inward-rec_Kir6.2	Family
IPR013518	K_chnl_inward-rec_Kir_cyto	Homologous_superfamily
IPR014756	Ig_E-set	Homologous_superfamily
IPR016449	K_chnl_inward-rec_Kir	Family
IPR040445	Kir_TM	Domain
IPR041647	IRK_C	Domain

Pfam: PF01007, PF17655

Catalyzed reactions (Rhea), 1 shown:

• K(+)(in) = K(+)(out) (RHEA:29463)

UniProt features (110 total): sequence variant 58, strand 17, helix 9, binding site 6, topological domain 4, mutagenesis site 3, turn 2, modified residue 2, transmembrane region 2, chain 1, site 1, disulfide bond 1, splice variant 1, intramembrane region 1, short sequence motif 1, sequence conflict 1

Structure

Experimental structures (PDB)

9 structures.

PDB	Method	Resolution (Å)
9KGL	ELECTRON MICROSCOPY	2.88
7S5T	ELECTRON MICROSCOPY	3.1
7S5X	ELECTRON MICROSCOPY	3.7
7S60	ELECTRON MICROSCOPY	3.7
6C3O	ELECTRON MICROSCOPY	3.9
7S5Y	ELECTRON MICROSCOPY	3.9
7S5Z	ELECTRON MICROSCOPY	3.9
7S61	ELECTRON MICROSCOPY	4
6C3P	ELECTRON MICROSCOPY	5.6

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q14654-F1	83.79	0.64

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Catalytic / active sites (1): 160 (role in the control of polyamine-mediated channel gating and in the blocking by intracellular magnesium)

Ligand- & substrate-binding residues (6): 50; 130; 133; 176; 330; 48

Post-translational modifications (2): 341, 385

Disulfide bonds (1): 110–142

Mutagenesis-validated functional residues (3):

Position	Phenotype
64	displays gain of function; increased open state stability, reduced atp sensitivity and increased channel activity; almos
166	the mutant channel is locked in an open conformation; when associated in cis with d-334.
334	the mutant channel is locked in an open conformation; when associated in cis with s-166.

Function

Pathways and Gene Ontology

Reactome pathways

17 pathways

ID	Pathway
R-HSA-1296025	ATP sensitive Potassium channels
R-HSA-382556	ABC-family protein mediated transport
R-HSA-422356	Regulation of insulin secretion
R-HSA-5578775	Ion homeostasis
R-HSA-5678420	Defective ABCC9 causes CMD10, ATFB12 and Cantu syndrome
R-HSA-5683177	Defective ABCC8 can cause hypo- and hyper-glycemias
R-HSA-112316	Neuronal System
R-HSA-1296065	Inwardly rectifying K+ channels
R-HSA-1296071	Potassium Channels
R-HSA-1430728	Metabolism
R-HSA-163685	Integration of energy metabolism
R-HSA-1643685	Disease
R-HSA-382551	Transport of small molecules
R-HSA-397014	Muscle contraction
R-HSA-5576891	Cardiac conduction
R-HSA-5619084	ABC transporter disorders
R-HSA-5619115	Disorders of transmembrane transporters

MSigDB gene sets: 428 (showing top): GSE45365_NK_CELL_VS_BCELL_DN, GOBP_POTASSIUM_ION_TRANSPORT, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, GOBP_MUSCLE_TISSUE_DEVELOPMENT, PID_HNF3B_PATHWAY, REACTOME_POTASSIUM_CHANNELS, REACTOME_INWARDLY_RECTIFYING_K_CHANNELS, SP3_Q3, GOBP_INSULIN_SECRETION, AREB6_03, GOBP_REGULATION_OF_HORMONE_LEVELS, GOBP_NEGATIVE_REGULATION_OF_PEPTIDE_SECRETION, GOBP_HORMONE_TRANSPORT, GOBP_NEGATIVE_REGULATION_OF_PROTEIN_LOCALIZATION, GOBP_MONOATOMIC_CATION_TRANSPORT

GO Biological Process (26): action potential (GO:0001508), response to hypoxia (GO:0001666), response to ischemia (GO:0002931), ventricular cardiac muscle tissue development (GO:0003229), glucose metabolic process (GO:0006006), apoptotic process (GO:0006915), determination of adult lifespan (GO:0008340), response to xenobiotic stimulus (GO:0009410), cellular response to nutrient levels (GO:0031669), response to ATP (GO:0033198), regulation of monoatomic ion transmembrane transport (GO:0034765), regulation of membrane potential (GO:0042391), negative regulation of insulin secretion (GO:0046676), regulation of insulin secretion (GO:0050796), nervous system process (GO:0050877), CAMKK-AMPK signaling cascade (GO:0061762), potassium ion transmembrane transport (GO:0071805), obsolete inorganic cation transmembrane transport (GO:0098662), response to resveratrol (GO:1904638), potassium ion import across plasma membrane (GO:1990573), monoatomic ion transport (GO:0006811), potassium ion transport (GO:0006813), response to stress (GO:0006950), monoatomic ion transmembrane transport (GO:0034220), monoatomic cation transmembrane transport (GO:0098655), regulation of presynaptic membrane potential (GO:0099505)

GO Molecular Function (12): voltage-gated potassium channel activity (GO:0005249), ATP binding (GO:0005524), ATP-activated inward rectifier potassium channel activity (GO:0015272), ATPase-coupled monoatomic cation transmembrane transporter activity (GO:0019829), ankyrin binding (GO:0030506), potassium ion binding (GO:0030955), transmembrane transporter binding (GO:0044325), voltage-gated monoatomic ion channel activity involved in regulation of presynaptic membrane potential (GO:0099508), nucleotide binding (GO:0000166), inward rectifier potassium channel activity (GO:0005242), protein binding (GO:0005515), metal ion binding (GO:0046872)

GO Cellular Component (7): cytoplasm (GO:0005737), plasma membrane (GO:0005886), inward rectifying potassium channel (GO:0008282), T-tubule (GO:0030315), membrane (GO:0016020), protein-containing complex (GO:0032991), monoatomic ion channel complex (GO:0034702)

Reactome top-level categories

Rollup of top-11 pathways:

Category	Pathways
ABC transporter disorders	2
Inwardly rectifying K+ channels	1
Transport of small molecules	1
Integration of energy metabolism	1
Cardiac conduction	1
Potassium Channels	1
Neuronal System	1
Metabolism	1
Muscle contraction	1
Disorders of transmembrane transporters	1
Disease	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
response to stress	2
response to oxygen-containing compound	2
monoatomic ion transmembrane transport	2
insulin secretion	2
regulation of membrane potential	1
response to decreased oxygen levels	1
cardiac muscle tissue development	1
hexose metabolic process	1
programmed cell death	1
apoptotic signaling pathway	1
execution phase of apoptosis	1
multicellular organismal process	1
response to chemical	1
response to nutrient levels	1
cellular response to stimulus	1
response to purine-containing compound	1
response to organophosphorus	1
regulation of transmembrane transport	1
regulation of monoatomic ion transport	1
regulation of biological quality	1
negative regulation of protein secretion	1
regulation of insulin secretion	1
negative regulation of peptide hormone secretion	1
regulation of protein secretion	1
regulation of peptide hormone secretion	1
system process	1
AMP-activated protein kinase activity	1
calcium/calmodulin-dependent protein kinase activity	1
calcium ion binding	1
calmodulin binding	1
calcium-mediated signaling	1
potassium ion transport	1
monoatomic cation transmembrane transport	1
response to stilbenoid	1
potassium ion transmembrane transport	1
inorganic cation import across plasma membrane	1
potassium channel activity	1
voltage-gated monoatomic cation channel activity	1
adenyl ribonucleotide binding	1

Protein interactions and networks

STRING

1638 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
KCNJ11	ABCC8	Q09428	999
KCNJ11	KCNJ8	Q15842	982
KCNJ11	ABCC9	O60706	978
KCNJ11	DIABLO	Q9NR28	924
KCNJ11	GCK	P35557	899
KCNJ11	XIAP	P98170	878
KCNJ11	INS	P01308	874
KCNJ11	CDKAL1	Q5VV42	857
KCNJ11	SLC30A8	Q8IWU4	840
KCNJ11	TCF7L2	Q9NQB0	839
KCNJ11	ABCB5	Q2M3G0	831
KCNJ11	HNF1A	P20823	829
KCNJ11	SLC2A2	P11168	814
KCNJ11	HHEX	Q03014	798
KCNJ11	GCG	P01275	783

IntAct

34 interactions, top by confidence:

A	B	Type	Score
KCNJ11	ANK2	psi-mi:“MI:0407”(direct interaction)	0.590
KCNJ11	ANK2	psi-mi:“MI:0915”(physical association)	0.590
KCNJ11	ANK2	psi-mi:“MI:0914”(association)	0.590
KCNJ11	EXOSC8	psi-mi:“MI:0915”(physical association)	0.560
GDPD5	GOLIM4	psi-mi:“MI:0914”(association)	0.530
PCDHB16	UPK3BL1	psi-mi:“MI:0914”(association)	0.530
PCDHAC2	TMEM223	psi-mi:“MI:0914”(association)	0.530
ABCC8	KCNJ11	psi-mi:“MI:0915”(physical association)	0.500
Kcnj11		psi-mi:“MI:0915”(physical association)	0.400
KCNJ11	MINDY2	psi-mi:“MI:0915”(physical association)	0.400
KCNJ11	ABCC8	psi-mi:“MI:0407”(direct interaction)	0.360
ANK2	ABCC8	psi-mi:“MI:0914”(association)	0.350
PCDHAC2	TMEM223	psi-mi:“MI:0914”(association)	0.350
CDH5	ARVCF	psi-mi:“MI:0914”(association)	0.350
SLC17A2	PSMD11	psi-mi:“MI:0914”(association)	0.350
IL17RC	C2CD2L	psi-mi:“MI:0914”(association)	0.350
TRPM8	TMBIM6	psi-mi:“MI:0914”(association)	0.350
TTMP	TMEM223	psi-mi:“MI:0914”(association)	0.350
TTYH1	TMEM223	psi-mi:“MI:0914”(association)	0.350
SIDT2	KLRG2	psi-mi:“MI:0914”(association)	0.350
SLC17A2	ABCD4	psi-mi:“MI:0914”(association)	0.350
TRPM8	STX5	psi-mi:“MI:0914”(association)	0.350
KCNJ10	KCNJ12	psi-mi:“MI:0914”(association)	0.350
MFSD2A	CAND2	psi-mi:“MI:0914”(association)	0.350
SLC2A14	ADCY3	psi-mi:“MI:0914”(association)	0.350
ABCC9	KCNJ11	psi-mi:“MI:2364”(proximity)	0.270

BioGRID (43): FAM63B (Affinity Capture-MS), KCNJ11 (Affinity Capture-MS), KCNJ11 (Affinity Capture-MS), KCNJ11 (Affinity Capture-MS), KCNJ11 (Affinity Capture-MS), KCNJ11 (Affinity Capture-MS), KCNJ11 (Affinity Capture-MS), KCNJ11 (Affinity Capture-MS), FAM63B (Affinity Capture-MS), KCNJ11 (Affinity Capture-Western), KCNJ11 (Two-hybrid), KCNJ11 (Proximity Label-MS), KCNJ8 (Affinity Capture-Western), KCNJ11 (Proximity Label-MS), KCNJ11 (Proximity Label-MS)

ESM2 similar proteins: B7U540, E1BNE9, F1MYR9, F1NHE9, O02670, O02822, O18839, O19182, O70617, P35561, P48050, P48051, P48542, P48543, P48544, P48545, P48548, P48549, P48550, P49656, P49658, P52185, P52186, P52187, P52188, P52189, P52190, P52191, P52192, P63250, P63251, P63252, P63253, P70673, P97794, Q14500, Q14654, Q15842, Q4TZY1, Q5NVJ6

Diamond homologs: B7U540, E1BN00, E1BNE9, F1MYR9, F1NHE9, O02670, O02822, O18839, O19182, O60928, O70339, O70596, O70617, O88335, O88932, P35560, P35561, P48048, P48050, P48051, P48542, P48543, P48544, P48545, P48548, P48549, P48550, P49655, P49656, P49658, P52185, P52186, P52187, P52188, P52189, P52190, P52191, P52192, P63250, P63251

SIGNOR signaling

3 interactions.

A	Effect	B	Mechanism
CAMK2D	down-regulates	KCNJ11	phosphorylation
phenformin	“down-regulates activity”	KCNJ11	“chemical inhibition”
KCNJ11	“form complex”	“KATP channel”	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 32 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Neuronal System	5	11.1×	2e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

562 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	21
Likely pathogenic	36
Uncertain significance	251
Likely benign	98
Benign	10

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1338558	NM_000525.4(KCNJ11):c.331_332del (p.Val111fs)	Pathogenic
158677	NM_000525.4(KCNJ11):c.521C>G (p.Ala174Gly)	Pathogenic
158687	NM_000525.4(KCNJ11):c.8C>G (p.Ser3Cys)	Pathogenic
2034644	NM_000525.4(KCNJ11):c.813_814insT (p.Pro272fs)	Pathogenic
21203	NM_000525.4(KCNJ11):c.964G>A (p.Glu322Lys)	Pathogenic
2137003	NM_000525.4(KCNJ11):c.148C>G (p.Arg50Gly)	Pathogenic
2704823	NM_000525.4(KCNJ11):c.31G>T (p.Glu11Ter)	Pathogenic
2735541	NM_000525.4(KCNJ11):c.491T>C (p.Leu164Pro)	Pathogenic
2735543	NM_000525.4(KCNJ11):c.151G>T (p.Glu51Ter)	Pathogenic
2768880	NM_000525.4(KCNJ11):c.279dup (p.Ala94fs)	Pathogenic
2834748	NM_000525.4(KCNJ11):c.317del (p.Thr106fs)	Pathogenic
2841775	NM_000525.4(KCNJ11):c.62del (p.Pro21fs)	Pathogenic
2846265	NM_000525.4(KCNJ11):c.393del (p.Ile131fs)	Pathogenic
3639451	NM_000525.4(KCNJ11):c.554_557dup (p.His186fs)	Pathogenic
3721001	NM_000525.4(KCNJ11):c.136C>T (p.His46Tyr)	Pathogenic
4709807	NM_000525.4(KCNJ11):c.998T>C (p.Phe333Ser)	Pathogenic
8666	NM_000525.4(KCNJ11):c.602G>A (p.Arg201His)	Pathogenic
8667	NM_000525.4(KCNJ11):c.175G>A (p.Val59Met)	Pathogenic
8668	NM_000525.4(KCNJ11):c.601C>T (p.Arg201Cys)	Pathogenic
8670	NM_000525.4(KCNJ11):c.149G>C (p.Arg50Pro)	Pathogenic
8682	NM_000525.4(KCNJ11):c.157G>C (p.Gly53Arg)	Pathogenic
1338354	NM_000525.4(KCNJ11):c.944T>C (p.Phe315Ser)	Likely pathogenic
1525998	NM_000525.4(KCNJ11):c.190G>A (p.Val64Met)	Likely pathogenic
1525999	NM_000525.4(KCNJ11):c.754G>T (p.Val252Leu)	Likely pathogenic
1526000	NM_000525.4(KCNJ11):c.1001G>T (p.Gly334Val)	Likely pathogenic
158676	NM_000525.4(KCNJ11):c.498C>G (p.Cys166Trp)	Likely pathogenic
211229	NM_000525.4(KCNJ11):c.866G>T (p.Gly289Val)	Likely pathogenic
2137001	NM_000525.4(KCNJ11):c.271T>C (p.Trp91Arg)	Likely pathogenic
2676203	NM_000525.4(KCNJ11):c.993dup (p.Lys332fs)	Likely pathogenic
2676204	NM_000525.4(KCNJ11):c.639del (p.Thr214fs)	Likely pathogenic

SpliceAI

511 predictions. Top by Δscore:

Variant	Effect	Δscore
11:17372169:G:GT	donor_gain	1.0000
11:17367004:GACA:G	acceptor_loss	0.9900
11:17367006:CA:C	acceptor_loss	0.9900
11:17367007:A:AG	acceptor_gain	0.9900
11:17367007:A:C	acceptor_loss	0.9900
11:17367008:G:C	acceptor_loss	0.9900
11:17367008:G:GG	acceptor_gain	0.9900
11:17367245:G:GT	donor_gain	0.9900
11:17367344:TCTGG:T	donor_loss	0.9900
11:17367345:CTGGT:C	donor_loss	0.9900
11:17367346:TGG:T	donor_loss	0.9900
11:17367347:GGTAA:G	donor_loss	0.9900
11:17367348:GTA:G	donor_loss	0.9900
11:17367349:T:TC	donor_loss	0.9900
11:17368865:A:AG	acceptor_gain	0.9900
11:17368866:G:GG	acceptor_gain	0.9900
11:17372144:G:GT	donor_gain	0.9900
11:17372169:G:T	donor_gain	0.9900
11:17367008:GC:G	acceptor_gain	0.9800
11:17367008:GCTT:G	acceptor_gain	0.9800
11:17368861:CTGCA:C	acceptor_loss	0.9800
11:17368862:TGCA:T	acceptor_loss	0.9800
11:17368863:GCAGA:G	acceptor_loss	0.9800
11:17368864:CAGAA:C	acceptor_loss	0.9800
11:17368865:A:AC	acceptor_loss	0.9800
11:17368866:G:T	acceptor_loss	0.9800
11:17367003:T:A	acceptor_gain	0.9700
11:17367008:GCTTC:G	acceptor_gain	0.9700
11:17367348:G:GG	donor_gain	0.9700
11:17368960:AAAAG:A	donor_loss	0.9700

AlphaMissense

2573 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
11:17387148:A:G	F315S	0.999
11:17387161:A:G	W311R	0.999
11:17387161:A:T	W311R	0.999
11:17387182:A:C	Y304D	0.999
11:17387184:G:A	S303F	0.999
11:17387184:G:T	S303Y	0.999
11:17387227:C:G	G289R	0.999
11:17387232:A:G	L287P	0.999
11:17387297:G:C	S265R	0.999
11:17387297:G:T	S265R	0.999
11:17387299:T:G	S265R	0.999
11:17387331:G:T	P254Q	0.999
11:17387484:C:T	G203D	0.999
11:17387532:G:T	A187E	0.999
11:17387540:G:C	S184R	0.999
11:17387540:G:T	S184R	0.999
11:17387541:C:A	S184I	0.999
11:17387542:T:G	S184R	0.999
11:17387543:G:C	F183L	0.999
11:17387543:G:T	F183L	0.999
11:17387545:A:G	F183L	0.999
11:17387693:A:C	F133L	0.999
11:17387693:A:T	F133L	0.999
11:17387695:A:G	F133L	0.999
11:17387093:A:C	F333L	0.998
11:17387093:A:T	F333L	0.998
11:17387094:A:G	F333S	0.998
11:17387095:A:G	F333L	0.998
11:17387169:T:A	E308V	0.998
11:17387185:A:G	S303P	0.998

dbSNP variants (sampled 300 via entrez): RS1000139070 (11:17388942 G>A), RS1000713736 (11:17389155 C>T), RS1001402819 (11:17388303 C>A,G,T), RS1001604718 (11:17389537 TG>T,TGG), RS1001873841 (11:17387973 C>T), RS1002097934 (11:17389236 G>A), RS1002463440 (11:17386421 C>T), RS1002716098 (11:17386502 G>C,T), RS1003348413 (11:17385423 G>A), RS1003662920 (11:17390927 C>A), RS1004469535 (11:17386945 T>C), RS1004540916 (11:17388819 A>C), RS1004606705 (11:17385603 G>A,C), RS1004641233 (11:17385797 C>T), RS1005169892 (11:17391223 ACTCCTTGCT>A)

Disease associations

OMIM: gene MIM:600937 | disease phenotypes: MIM:610582, MIM:618856, MIM:125850, MIM:606391, MIM:125853, MIM:601820, MIM:616329, MIM:606176, MIM:256450, MIM:222100, MIM:600496, MIM:612520, MIM:603165

GenCC curated gene-disease

Disease	Classification	Inheritance
hyperinsulinemic hypoglycemia, familial, 2	Definitive	Autosomal recessive
diabetes mellitus, transient neonatal, 3	Definitive	Autosomal dominant
diabetes mellitus, noninsulin-dependent	Strong	Autosomal dominant
maturity-onset diabetes of the young type 13	Strong	Autosomal dominant
diabetes mellitus, permanent neonatal 2	Strong	Autosomal dominant
autosomal dominant hyperinsulinism due to Kir6.2 deficiency	Supportive	Autosomal dominant
diazoxide-resistant focal hyperinsulinism due to Kir6.2 deficiency	Supportive	Autosomal recessive
maturity-onset diabetes of the young	Supportive	Autosomal dominant
DEND syndrome	Supportive	Autosomal dominant
autosomal recessive hyperinsulinism due to Kir6.2 deficiency	Supportive	Autosomal recessive
permanent neonatal diabetes mellitus	Supportive	Autosomal dominant
transient neonatal diabetes mellitus	Supportive	Autosomal dominant
intermediate DEND syndrome	Supportive	Autosomal dominant

ClinGen Gene-Disease Validity (3)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
hyperinsulinemic hypoglycemia, familial, 2	Definitive	AR
monogenic diabetes	Definitive	AD
hyperinsulinemic hypoglycemia, familial, 2	Limited	AD

Mondo (28): diabetes mellitus, transient neonatal, 3 (MONDO:0012522), diabetes mellitus, permanent neonatal 2 (MONDO:0030087), maturity-onset diabetes of the young (MONDO:0018911), type 2 diabetes mellitus (MONDO:0005148), hyperinsulinemic hypoglycemia, familial, 2 (MONDO:0011153), maturity-onset diabetes of the young type 13 (MONDO:0014589), permanent neonatal diabetes mellitus 1 (MONDO:0100165), permanent neonatal diabetes mellitus (MONDO:0100164), familial hyperinsulinism (MONDO:0017182), neonatal diabetes mellitus (MONDO:0016391), hyperinsulinism (MONDO:0002177), hyperinsulinemic hypoglycemia (MONDO:0005803), diabetes mellitus (MONDO:0005015), monogenic diabetes (MONDO:0015967), transient neonatal diabetes mellitus (MONDO:0020525)

Orphanet (13): Transient neonatal diabetes mellitus (Orphanet:99886), MODY (Orphanet:552), Autosomal dominant hyperinsulinism due to Kir6.2 deficiency (Orphanet:276580), Diazoxide-resistant focal hyperinsulinism due to Kir6.2 deficiency (Orphanet:276603), Isolated permanent neonatal diabetes mellitus (Orphanet:99885), Familial hyperinsulinism (Orphanet:276525), Neonatal diabetes mellitus (Orphanet:224), Hyperinsulinemic hypoglycaemia (Orphanet:443095), Rare genetic diabetes mellitus (Orphanet:183625), Hereditary ataxia (Orphanet:183518), Rare disorder with hypertrichosis (Orphanet:79365), DEND syndrome (Orphanet:79134), NON RARE IN EUROPE: Diabetes mellitus type 1 (Orphanet:243377)

HPO phenotypes

132 total (30 of 132 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000007	Autosomal recessive inheritance
HP:0000077	Abnormality of the kidney
HP:0000079	Abnormality of the urinary system
HP:0000107	Renal cyst
HP:0000112	Nephropathy
HP:0000119	Abnormality of the genitourinary system
HP:0000124	Renal tubular dysfunction
HP:0000158	Macroglossia
HP:0000343	Long philtrum
HP:0000365	Hearing impairment
HP:0000463	Anteverted nares
HP:0000488	Retinopathy
HP:0000707	Abnormality of the nervous system
HP:0000713	Agitation
HP:0000819	Diabetes mellitus
HP:0000821	Hypothyroidism
HP:0000825	Hyperinsulinemic hypoglycemia
HP:0000831	Insulin-resistant diabetes mellitus
HP:0000842	Hyperinsulinemia
HP:0000845	Elevated circulating growth hormone concentration
HP:0000855	Insulin resistance
HP:0000857	Neonatal insulin-dependent diabetes mellitus
HP:0000956	Acanthosis nigricans
HP:0000980	Pallor
HP:0001069	Episodic hyperhidrosis
HP:0001249	Intellectual disability
HP:0001250	Seizure
HP:0001251	Ataxia
HP:0001252	Hypotonia

GWAS associations

36 associations (top):

Study	Trait	p-value
GCST000024_1	Type 2 diabetes	7.000000e-11
GCST000025_6	Type 2 diabetes	5.000000e-11
GCST000028_3	Type 2 diabetes	7.000000e-11
GCST000167_14	Type 2 diabetes	4.000000e-07
GCST000277_1	Type 2 diabetes	1.000000e-09
GCST000277_4	Type 2 diabetes	5.000000e-07
GCST002352_12	Type 2 diabetes	3.000000e-11
GCST002367_9	Social communication problems	7.000000e-06
GCST002783_288	Body mass index	6.000000e-07
GCST002783_544	Body mass index	2.000000e-06
GCST004894_109	Type 2 diabetes	1.000000e-20
GCST004894_5	Type 2 diabetes	8.000000e-14
GCST004904_235	Body mass index	3.000000e-11
GCST005047_17	Type 2 diabetes	9.000000e-10
GCST005047_69	Type 2 diabetes	3.000000e-06
GCST005414_23	Type 2 diabetes	7.000000e-08
GCST005951_67	Body mass index	6.000000e-09
GCST006228_10	Systolic blood pressure	5.000000e-12
GCST006230_11	Pulse pressure	3.000000e-07
GCST006231_47	Mean arterial pressure	4.000000e-09
GCST006434_30	Systolic blood pressure x alcohol consumption interaction (2df test)	5.000000e-15
GCST006867_97	Type 2 diabetes	2.000000e-20
GCST007267_66	Systolic blood pressure	4.000000e-17
GCST007269_195	Pulse pressure	2.000000e-17
GCST007515_14	Type 2 diabetes	6.000000e-22
GCST007516_13	Type 2 diabetes (adjusted for BMI)	2.000000e-22
GCST007517_16	Type 2 diabetes	4.000000e-17
GCST007518_20	Type 2 diabetes (adjusted for BMI)	5.000000e-22
GCST007847_73	Type 2 diabetes	4.000000e-06
GCST007923_21	Medication use (drugs used in diabetes)	8.000000e-09

EFO canonical traits (8, from GWAS)

EFO ID	Trait name
EFO:0005427	social communication impairment
EFO:0004340	body mass index
EFO:0006335	systolic blood pressure
EFO:0005763	pulse pressure measurement
EFO:0006340	mean arterial pressure
EFO:0004329	alcohol drinking
EFO:0009924	Drugs used in diabetes use measurement
EFO:0005000	leptin measurement

MeSH disease descriptors (13)

Descriptor	Name	Tree numbers
D003876	Dermatitis, Atopic	C16.320.850.210; C17.800.174.193; C17.800.815.193; C17.800.827.210; C20.543.480.343
D003920	Diabetes Mellitus	C18.452.394.750; C19.246
D003922	Diabetes Mellitus, Type 1	C18.452.394.750.124; C19.246.267; C20.111.327
D003924	Diabetes Mellitus, Type 2	C18.452.394.750.149; C19.246.300
D006946	Hyperinsulinism	C18.452.394.968
D006983	Hypertrichosis	C17.800.329.875
D007003	Hypoglycemia	C18.452.394.984
C567286	Diabetes Mellitus, Insulin-Dependent, 20 (supp.)
C563425	Diabetes Mellitus, Permanent Neonatal (supp.)
C566432	Diabetes Mellitus, Transient Neonatal, 3 (supp.)
C531684	Hereditary spinal ataxia (supp.)
C562772	Mason-Type Diabetes (supp.)
C563933	Maturity-Onset Diabetes of the Young, Type 3 (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (4): CHEMBL1886 (SINGLE PROTEIN), CHEMBL2095152 (PROTEIN COMPLEX GROUP), CHEMBL2095198 (PROTEIN COMPLEX), CHEMBL2096972 (PROTEIN COMPLEX)

Molecules with ChEMBL bioactivity

7 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 100,543 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL1159	PINACIDIL ANHYDROUS	4	6,303
CHEMBL472	GLYBURIDE	4	53,236
CHEMBL631	PROPAFENONE	4	12,711
CHEMBL181	DIAZOXIDE	4	27,974
CHEMBL49035	CROMAKALIM	2	135
CHEMBL12531	CLAMIKALANT	2	80
CHEMBL135191	TIFENAZOXIDE	2	104

PharmGKB: 1 entry (VIP=true, CPIC=false)

PharmGKB clinical annotations

8 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs2285676	Efficacy	3	sitagliptin	Diabetes Mellitus;Type 2
rs5219	Efficacy	3	sulfonamides;urea derivatives	Diabetes Mellitus;Type 2
rs5219	Efficacy	3	repaglinide	Diabetes Mellitus;Type 2
rs5219	Efficacy	3	metformin;sulfonamides;urea derivatives	Diabetes Mellitus;Type 2
rs5219	Toxicity	3	tacrolimus	Diabetes Mellitus;Type 2
rs5219	Efficacy	3	gliclazide	Diabetes Mellitus
rs5219	Efficacy	3	sulfonamides;urea derivatives	Diabetes Mellitus
rs757110	Efficacy	3	sulfonamides;urea derivatives	Diabetes Mellitus

PharmGKB variants

7 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs5215	KCNJ11		0.00	0
rs5219	ABCC8, KCNJ11	3	3.75	6	repaglinide;metformin;sulfonamides;urea derivatives;tacrolimus;gliclazide;sulfonamides
rs757110	ABCC8, KCNJ11	3	0.75	1	sulfonamides;urea derivatives
rs587783672	KCNJ11		0.00	0
rs2285676	KCNJ11	3	2.25	1	sitagliptin
rs5218	KCNJ11		0.00	0
rs5210	KCNJ11		0.00	0

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: vgic — Inwardly rectifying potassium channels (K_IR)

Most potent curated ligand interactions (1 total), top 1:

Ligand	Action	Affinity	Parameter
diazoxide	Agonist	4.2	pEC50

ChEMBL bioactivities

661 potent at pChembl≥5 of 711 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
9.27	EC50	0.537	nM	CHEMBL321455
9.17	EC50	0.6761	nM	CHEMBL217511
9.04	EC50	0.912	nM	CHEMBL426334
9.00	EC50	1	nM	CHEMBL218564
8.93	EC50	1.175	nM	CHEMBL214561
8.74	EC50	1.82	nM	CHEMBL413532
8.56	EC50	2.754	nM	CHEMBL217810
8.52	IC50	3	nM	CHEMBL134168
8.43	EC50	3.715	nM	CHEMBL218564
8.41	EC50	3.89	nM	CHEMBL384564
8.37	IC50	4.3	nM	GLYBURIDE
8.30	EC50	5.012	nM	CHEMBL3138573
8.30	EC50	5.012	nM	CHEMBL2111694
8.29	EC50	5.129	nM	CHEMBL218564
8.26	EC50	5.495	nM	CHEMBL426334
8.22	EC50	6.026	nM	CHEMBL217847
8.20	EC50	6.31	nM	CHEMBL323159
8.06	EC50	8.71	nM	CHEMBL3392139
8.05	EC50	9	nM	CHEMBL48848
8.05	EC50	8.913	nM	CHEMBL50760
8.01	EC50	9.772	nM	CHEMBL386363
7.95	EC50	11.22	nM	CHEMBL2111694
7.92	EC50	12	nM	CHEMBL50374
7.92	EC50	12	nM	CHEMBL49806
7.90	EC50	12.59	nM	CHEMBL3138553
7.89	EC50	12.88	nM	CHEMBL108723
7.85	EC50	14.13	nM	CHEMBL386119
7.85	EC50	14.13	nM	CHEMBL108251
7.84	EC50	14.45	nM	CHEMBL265269
7.82	EC50	15	nM	CHEMBL50760
7.77	EC50	16.98	nM	CHEMBL216766
7.75	EC50	18	nM	CHEMBL299167
7.74	EC50	18.2	nM	CHEMBL216284
7.72	EC50	19.05	nM	CHEMBL215375
7.70	EC50	19.95	nM	CHEMBL386119
7.70	IC50	20	nM	CROMAKALIM
7.66	EC50	21.88	nM	CHEMBL11458
7.66	EC50	21.88	nM	CHEMBL3138587
7.65	EC50	22.39	nM	CHEMBL107888
7.64	EC50	22.91	nM	CHEMBL216546
7.64	EC50	22.91	nM	CHEMBL3138607
7.64	EC50	23	nM	CHEMBL300958
7.63	EC50	23.44	nM	CHEMBL110399
7.62	EC50	23.99	nM	CHEMBL386582
7.62	EC50	24	nM	CHEMBL48797
7.59	EC50	25.7	nM	CHEMBL3138549
7.59	EC50	25.7	nM	CHEMBL2112487
7.57	EC50	26.92	nM	CHEMBL386582
7.57	EC50	26.92	nM	CHEMBL261996
7.57	EC50	26.92	nM	CHEMBL426160

PubChem BioAssay actives

672 with measured affinity, of 1429 total; 50 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
9-(3-bromo-4-fluorophenyl)-5,13-dithia-2-azatricyclo[8.4.0.03,8]tetradeca-1(10),3(8)-diene-7,11-dione	93975: Evaluated for K-ATP activity in terms of membrane potential change, through guinea pig bladder assay	ec50	0.0005	uM
8-(3-bromo-4-fluorophenyl)-5,12-dioxa-2-azatricyclo[7.4.0.03,7]trideca-1(9),3(7)-diene-6,10-dione	272331: Activity against pig bladder KATP channel opening assessed as ability to relax spontaneous bladder contraction	ec50	0.0007	uM
(4S,8R)-8-(3-bromo-4-fluorophenyl)-4-methyl-5,12-dioxa-2-azatricyclo[7.4.0.03,7]trideca-1(9),3(7)-diene-6,10-dione	272328: Ability to open human urinary bladder Kir6.2 channel containing SUR2B in Ltk cells by FLIPR assay	ec50	0.0009	uM
(4S,8R)-8-(3-bromo-4-fluorophenyl)-4-propyl-5,12-dioxa-2-azatricyclo[7.4.0.03,7]trideca-1(9),3(7)-diene-6,10-dione	272328: Ability to open human urinary bladder Kir6.2 channel containing SUR2B in Ltk cells by FLIPR assay	ec50	0.0010	uM
(4R,8S)-8-(3-bromo-4-fluorophenyl)-4-ethyl-12-oxa-2-azatricyclo[7.4.0.03,7]trideca-1(9),3(7)-diene-6,10-dione	272328: Ability to open human urinary bladder Kir6.2 channel containing SUR2B in Ltk cells by FLIPR assay	ec50	0.0012	uM
(8R,13R)-8-(3-bromo-4-fluorophenyl)-13-methyl-5,12-dioxa-2-azatricyclo[7.4.0.03,7]trideca-1(9),3(7)-diene-6,10-dione	272328: Ability to open human urinary bladder Kir6.2 channel containing SUR2B in Ltk cells by FLIPR assay	ec50	0.0018	uM
(4S,8S)-8-(3-bromo-4-fluorophenyl)-4,5-dimethyl-12-oxa-2,5-diazatricyclo[7.4.0.03,7]tridec-3(7)-ene-6,10-dione	272328: Ability to open human urinary bladder Kir6.2 channel containing SUR2B in Ltk cells by FLIPR assay	ec50	0.0028	uM
6-chloro-N-(1-methylcyclobutyl)-1,1-dioxo-4H-thieno[3,2-e][1,2,4]thiadiazin-3-imine	208994: Inhibition of [3H]glibenclamide binding to HEK293 cells co-expressing human Sulfonylurea receptor SUR1 and Inward rectifier K+ channel Kir6.2 at high affinity state with 2 mM MgATP	ic50	0.0030	uM
(4S,8R)-8-(3-bromo-4-fluorophenyl)-4-ethyl-5,12-dioxa-2-azatricyclo[7.4.0.03,7]trideca-1(9),3(7)-diene-6,10-dione	272328: Ability to open human urinary bladder Kir6.2 channel containing SUR2B in Ltk cells by FLIPR assay	ec50	0.0039	uM
glyburide	201322: Inhibition of human SUR1/Kir6.2 expressed in CHO cells	ic50	0.0043	uM
(8R)-8-(3-bromo-4-fluorophenyl)-6,6-dioxo-12-oxa-6lambda6-thia-2-azatricyclo[7.4.0.03,7]trideca-1(9),3(7)-dien-10-one	93975: Evaluated for K-ATP activity in terms of membrane potential change, through guinea pig bladder assay	ec50	0.0050	uM
(8S)-8-(3-bromo-4-fluorophenyl)-5,12-dioxa-2-azatricyclo[7.4.0.03,7]trideca-1(9),3(7)-diene-6,10-dione	93985: Evaluated for K-ATP activity as in vitro bladder relaxation in spontaneous Landrace pig detrusor strips (SLPD)	ec50	0.0050	uM
(4S,8R)-8-(3-bromo-4-fluorophenyl)-4-ethyl-5,11-dioxa-2-azatricyclo[7.3.0.03,7]dodeca-1(9),3(7)-diene-6,10-dione	272328: Ability to open human urinary bladder Kir6.2 channel containing SUR2B in Ltk cells by FLIPR assay	ec50	0.0060	uM
(9S)-9-(3-bromo-4-fluorophenyl)-3,4,5,6,7,9-hexahydrofuro[3,4-b]quinoline-1,8-dione	93975: Evaluated for K-ATP activity in terms of membrane potential change, through guinea pig bladder assay	ec50	0.0063	uM
8-(3-bromo-4-fluorophenyl)-10,10-dioxo-5-oxa-10lambda6-thia-2-azatricyclo[7.4.0.03,7]trideca-1(9),3(7)-dien-6-one	93975: Evaluated for K-ATP activity in terms of membrane potential change, through guinea pig bladder assay	ec50	0.0087	uM
N-[2-(1,1,1,3,3,3-hexafluoro-2-hydroxypropan-2-yl)naphthalen-1-yl]propanamide	159672: Potent effective concentration was evaluated for KATP channel opening activity in pig bladder strips	ec50	0.0089	uM
N-[2-(1,1,1,3,3,3-hexafluoro-2-hydroxypropan-2-yl)naphthalen-1-yl]furan-2-carboxamide	95530: Potassium channel opening activity in vitro using LtK cells transfected with Kir6.2/SUR2B exon 17	ec50	0.0090	uM
(4R,8R)-8-(3-bromo-4-fluorophenyl)-4-(methoxymethyl)-5,12-dioxa-2-azatricyclo[7.4.0.03,7]trideca-1(9),3(7)-diene-6,10-dione	272328: Ability to open human urinary bladder Kir6.2 channel containing SUR2B in Ltk cells by FLIPR assay	ec50	0.0098	uM
N-[2-(1,1,1,3,3,3-hexafluoro-2-hydroxypropan-2-yl)naphthalen-1-yl]thiophene-2-carboxamide	95530: Potassium channel opening activity in vitro using LtK cells transfected with Kir6.2/SUR2B exon 17	ec50	0.0120	uM
3-cyano-N-[2-(1,1,1,3,3,3-hexafluoro-2-hydroxypropan-2-yl)naphthalen-1-yl]benzamide	95530: Potassium channel opening activity in vitro using LtK cells transfected with Kir6.2/SUR2B exon 17	ec50	0.0120	uM
(9R)-9-(3-bromo-4-fluorophenyl)-1,1-dioxo-3,4,5,6,7,9-hexahydro-2H-thieno[3,2-b]quinolin-8-one	93984: Evaluated for K-ATP activity as in vitro bladder relaxation in spontaneous Landrace pig detrusor strips (SLPD)	ec50	0.0126	uM
8-(3-bromo-4-fluorophenyl)-5-methyl-12-oxa-2,5-diazatricyclo[7.4.0.03,7]trideca-1(9),3(7)-diene-6,10-dione	93975: Evaluated for K-ATP activity in terms of membrane potential change, through guinea pig bladder assay	ec50	0.0129	uM
8-(3-bromo-4-fluorophenyl)-5,11-dioxa-2-azatricyclo[7.4.0.03,7]trideca-1(9),3(7)-diene-6,10-dione	93975: Evaluated for K-ATP activity in terms of membrane potential change, through guinea pig bladder assay	ec50	0.0141	uM
(4S,9R)-9-(3-bromo-4-fluorophenyl)-4-ethyl-5,13-dioxa-2-azatricyclo[8.4.0.03,8]tetradeca-1(10),3(8)-diene-7,11-dione	272328: Ability to open human urinary bladder Kir6.2 channel containing SUR2B in Ltk cells by FLIPR assay	ec50	0.0141	uM
(4S,8R)-8-(3-bromo-4-fluorophenyl)-4-ethyl-11,11-dimethyl-5,12-dioxa-2-azatricyclo[7.4.0.03,7]trideca-1(9),3(7)-diene-6,10-dione	272328: Ability to open human urinary bladder Kir6.2 channel containing SUR2B in Ltk cells by FLIPR assay	ec50	0.0144	uM
9-(3-bromo-4-fluorophenyl)-6,6-dimethyl-5,13-dioxa-2-azatricyclo[8.4.0.03,8]tetradeca-1(10),3(8)-diene-7,11-dione	272328: Ability to open human urinary bladder Kir6.2 channel containing SUR2B in Ltk cells by FLIPR assay	ec50	0.0170	uM
N-[2-(1,1,1,3,3,3-hexafluoro-2-hydroxypropan-2-yl)naphthalen-1-yl]acetamide	95530: Potassium channel opening activity in vitro using LtK cells transfected with Kir6.2/SUR2B exon 17	ec50	0.0180	uM
(8R,13R)-8-(3-bromo-4-fluorophenyl)-13-ethyl-5,12-dioxa-2-azatricyclo[7.4.0.03,7]trideca-1(9),3(7)-diene-6,10-dione	272328: Ability to open human urinary bladder Kir6.2 channel containing SUR2B in Ltk cells by FLIPR assay	ec50	0.0182	uM
(4R,8R)-8-(3-bromo-4-fluorophenyl)-4-ethyl-5,12-dioxa-2-azatricyclo[7.4.0.03,7]trideca-1(9),3(7)-diene-6,10-dione	272331: Activity against pig bladder KATP channel opening assessed as ability to relax spontaneous bladder contraction	ec50	0.0191	uM
3-hydroxy-2,2-dimethyl-4-(2-oxopyrrolidin-1-yl)-3,4-dihydrochromene-6-carbonitrile	78296: Contraction and relaxation of guinea pig portal vein with KCl and glibenclamide respectively	ic50	0.0200	uM
(9S)-9-(3-iodo-4-methylphenyl)-1,1-dioxo-3,4,5,6,7,9-hexahydro-2H-thieno[3,2-b]quinolin-8-one	93974: Evaluated for K-ATP activity in terms of change in membrane potential through guinea pig bladder assay	ec50	0.0219	uM
1-cyano-2-(2-methylbutan-2-yl)-3-pyridin-3-ylguanidine	272331: Activity against pig bladder KATP channel opening assessed as ability to relax spontaneous bladder contraction	ec50	0.0219	uM
(8S)-8-(3-bromo-4-fluorophenyl)-5-oxa-2-azatricyclo[7.3.0.03,7]dodeca-1(9),3(7)-diene-6,10-dione	93975: Evaluated for K-ATP activity in terms of membrane potential change, through guinea pig bladder assay	ec50	0.0224	uM
(4S,8R)-8-(3-bromo-4-fluorophenyl)-4-(methoxymethyl)-5,12-dioxa-2-azatricyclo[7.4.0.03,7]trideca-1(9),3(7)-diene-6,10-dione	272328: Ability to open human urinary bladder Kir6.2 channel containing SUR2B in Ltk cells by FLIPR assay	ec50	0.0229	uM
(9S)-9-(3-bromo-4-fluorophenyl)-1,1-dioxo-3,4,5,6,7,9-hexahydro-2H-thieno[3,2-b]quinolin-8-one	93984: Evaluated for K-ATP activity as in vitro bladder relaxation in spontaneous Landrace pig detrusor strips (SLPD)	ec50	0.0229	uM
N-[2-(1,1,1,3,3,3-hexafluoro-2-hydroxypropan-2-yl)naphthalen-1-yl]-3-methylbenzamide	95530: Potassium channel opening activity in vitro using LtK cells transfected with Kir6.2/SUR2B exon 17	ec50	0.0230	uM
8-(3-bromo-4-fluorophenyl)-5,11-dioxa-2-azatricyclo[7.3.0.03,7]dodeca-1(9),3(7)-diene-6,10-dione	93985: Evaluated for K-ATP activity as in vitro bladder relaxation in spontaneous Landrace pig detrusor strips (SLPD)	ec50	0.0234	uM
8-(3-bromo-4-fluorophenyl)-11,11-dimethyl-5,12-dioxa-2-azatricyclo[7.4.0.03,7]trideca-1(9),3(7)-diene-6,10-dione	272328: Ability to open human urinary bladder Kir6.2 channel containing SUR2B in Ltk cells by FLIPR assay	ec50	0.0240	uM
N-[2-(1,1,1,3,3,3-hexafluoro-2-hydroxypropan-2-yl)naphthalen-1-yl]-1,3-oxazole-5-carboxamide	95530: Potassium channel opening activity in vitro using LtK cells transfected with Kir6.2/SUR2B exon 17	ec50	0.0240	uM
(8R)-8-(3-bromo-4-fluorophenyl)-5,12-dioxa-2-azatricyclo[7.4.0.03,7]trideca-1(9),3(7)-diene-6,10-dione	93975: Evaluated for K-ATP activity in terms of membrane potential change, through guinea pig bladder assay	ec50	0.0257	uM
(9S)-9-(3-bromo-4-chlorophenyl)-1,1-dioxo-3,4,5,6,7,9-hexahydro-2H-thieno[3,2-b]quinolin-8-one	93974: Evaluated for K-ATP activity in terms of change in membrane potential through guinea pig bladder assay	ec50	0.0257	uM
8-(3-bromo-4-fluorophenyl)-4,4-dimethyl-5,12-dioxa-2-azatricyclo[7.4.0.03,7]trideca-1(9),3(7)-diene-6,10-dione	272328: Ability to open human urinary bladder Kir6.2 channel containing SUR2B in Ltk cells by FLIPR assay	ec50	0.0269	uM
9-(3-bromo-4-fluorophenyl)-5,13-dioxa-2-azatricyclo[8.4.0.03,8]tetradeca-1(10),3(8)-diene-7,11-dione	93975: Evaluated for K-ATP activity in terms of membrane potential change, through guinea pig bladder assay	ec50	0.0269	uM
(4R,8R)-8-(4-fluoro-3-iodophenyl)-4-propyl-5,12-dioxa-2-azatricyclo[7.4.0.03,7]trideca-1(9),3(7)-diene-6,10-dione	272328: Ability to open human urinary bladder Kir6.2 channel containing SUR2B in Ltk cells by FLIPR assay	ec50	0.0269	uM
7-(3-bromo-4-fluorophenyl)-5-methyl-1,1-dioxo-2,3,4,7-tetrahydrothieno[3,2-b]pyridine-6-carbonitrile	93974: Evaluated for K-ATP activity in terms of change in membrane potential through guinea pig bladder assay	ec50	0.0275	uM
(4R,8R)-8-(3-bromo-4-fluorophenyl)-4-propyl-5,12-dioxa-2-azatricyclo[7.4.0.03,7]trideca-1(9),3(7)-diene-6,10-dione	272328: Ability to open human urinary bladder Kir6.2 channel containing SUR2B in Ltk cells by FLIPR assay	ec50	0.0275	uM
(4S,8R)-8-(3-bromo-4-fluorophenyl)-4-(2-methylpropyl)-5,12-dioxa-2-azatricyclo[7.4.0.03,7]trideca-1(9),3(7)-diene-6,10-dione	272328: Ability to open human urinary bladder Kir6.2 channel containing SUR2B in Ltk cells by FLIPR assay	ec50	0.0275	uM
(9S)-9-(4-fluoro-3-iodophenyl)-1,1-dioxo-3,4,5,6,7,9-hexahydro-2H-thieno[3,2-b]quinolin-8-one	93974: Evaluated for K-ATP activity in terms of change in membrane potential through guinea pig bladder assay	ec50	0.0282	uM
(4S,8R)-8-(3-bromo-4-fluorophenyl)-4-butyl-5,12-dioxa-2-azatricyclo[7.4.0.03,7]trideca-1(9),3(7)-diene-6,10-dione	272328: Ability to open human urinary bladder Kir6.2 channel containing SUR2B in Ltk cells by FLIPR assay	ec50	0.0295	uM
9-(3-bromo-4-fluorophenyl)-5,6,7,9-tetrahydro-4H-pyrazolo[5,1-b]quinazolin-8-one	73908: Potassium channel opening activity determined in cultured guinea pig urinary bladder cells	ec50	0.0300	uM

CTD chemical–gene interactions

29 total (human), top 29 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Tolbutamide	increases activity, decreases activity, affects cotreatment, decreases response to substance, decreases reaction	2
bisphenol A	decreases expression	1
ethyl-p-hydroxybenzoate	decreases expression	1
manganese chloride	decreases expression, increases abundance	1
glimepiride	affects cotreatment, decreases response to substance	1
mitiglinide	affects cotreatment, increases response to substance	1
abrine	decreases expression	1
bisphenol S	decreases expression	1
jinfukang	affects cotreatment, increases expression	1
(+)-JQ1 compound	decreases expression	1
imeglimin	increases expression	1
Sunitinib	increases expression	1
Acetaminophen	decreases expression	1
Allergens	increases expression	1
Benzo(a)pyrene	affects methylation, increases methylation	1
Cadmium	decreases expression	1
Chlorpropamide	affects cotreatment, decreases response to substance	1
Cisplatin	affects cotreatment, increases expression	1
Diazoxide	decreases expression	1
Folic Acid	decreases expression	1
Gliclazide	affects cotreatment, increases response to substance	1
Lovastatin	increases expression	1
Manganese	decreases expression, increases abundance	1
Rotenone	increases expression	1
Silicon Dioxide	decreases expression	1
Triclosan	decreases expression	1
Valproic Acid	increases methylation	1
1-Methyl-4-phenylpyridinium	increases expression	1
Acrylamide	decreases expression	1

ChEMBL screening assays

102 unique, capped per target: 59 functional, 43 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL2160412	Binding	Inhibition of Kir6.2 by patch clamp assay	Lead optimization of antimalarial propafenone analogues. — J Med Chem
CHEMBL678531	Functional	Potassium channel opening activity determined in cultured guinea pig urinary bladder cells	Structure-Activity studies for a novel series of tricyclic dihydropyrimidines as K(ATP) channel openers (KCOs). — Bioorg Med Chem Lett

Cellosaurus cell lines

7 cell lines: 3 cancer cell line, 1 transformed cell line, 1 spontaneously immortalized cell line, 1 embryonic stem cell, 1 induced pluripotent stem cell

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_B1V1	Abcam HeLa KCNJ11 KO	Cancer cell line	Female
CVCL_D1JT	PrecisION hKir6.2/SUR2A (KATP)-HEK	Transformed cell line	Female
CVCL_LB87	NISK9	Spontaneously immortalized cell line
CVCL_LI07	WAe001-A-12	Embryonic stem cell	Male
CVCL_QX69	UPSFRi012-A	Induced pluripotent stem cell	Male
CVCL_SU01	HAP1 KCNJ11 (-) 1	Cancer cell line	Male
CVCL_SU02	HAP1 KCNJ11 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

304 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT02624817	PHASE4	COMPLETED	Long-Term Sulfonylurea Response in KCNJ11 Neonatal Diabetes
NCT02624830	PHASE4	UNKNOWN	Long-Term Sulfonylurea Response in ABCC8 Neonatal Diabetes (SuResponsSUR)
NCT00006163	PHASE4	COMPLETED	Computer-assisted Diabetes Self-management Interventions
NCT00036504	PHASE4	COMPLETED	Efficacy and Safety of Twice-Daily Insulin Lispro Low Mixture Compared to a Once-Daily Long Acting Insulin Comparator in Patients Who Have Been Using One or More Oral Antihyperglycemic Agents Without Insulin
NCT00044460	PHASE4	COMPLETED	Efficacy and Safety In Poorly Controlled Type 2 Diabetics
NCT00095446	PHASE4	COMPLETED	NovoLog Observation Trial in Subjects With Type 1 and Type 2 Diabetes
NCT00101751	PHASE4	COMPLETED	INITIATE Plus (INITiation of Insulin to Reach A1c TargEt) Study
NCT00110370	PHASE4	COMPLETED	Comparing Pre-Mixed Insulin With Insulin Glargine Combined With Rapid-Acting Insulin in Patients With Type 2 Diabetes
NCT00110448	PHASE4	COMPLETED	Japanese Primary Prevention of Atherosclerosis With Aspirin for Diabetes (JPAD) Trial
NCT00118950	PHASE4	COMPLETED	Effect of Metformin Versus Repaglinide Treatment in Non-Obese Type 2 Diabetic Patients Uncontrolled by Diet
NCT00118963	PHASE4	COMPLETED	Effect of Repaglinide Versus Metformin Treatment in Non-Obese Patients With Type-2-Diabetes
NCT00121966	PHASE4	COMPLETED	South Danish Diabetes Study: Evaluation of the Antidiabetic Treatment of Type 2 Diabetes Mellitus
NCT00123604	PHASE4	COMPLETED	Vascular Effects of Carvedilol Versus Metoprolol in Hypertensive Patients With Type 2 Diabetes
NCT00123643	PHASE4	COMPLETED	Vascular Effects of Rosiglitazone Versus Glyburide in Type 2 Diabetic Patients
NCT00124397	PHASE4	COMPLETED	Atorvastatin and Endothelial Function in Type 2 Diabetes Mellitus (ATTEND-Study)
NCT00129233	PHASE4	COMPLETED	Comparison of Valsartan With Amlodipine in Hypertensive Patients With Glucose Intolerance
NCT00133718	PHASE4	COMPLETED	A 2 Year Trial of Patients With Type 2 Diabetes Focusing on Cardiovascular Diagnostics and Metabolic Control
NCT00135070	PHASE4	TERMINATED	Hospital In-Patient Insulin Study
NCT00141232	PHASE4	COMPLETED	Evaluating Atorvastatin With Omega-3 Fatty Acids in Cardiovascular Risk Reduction in Patients With Type 2 Diabetes
NCT00144144	PHASE4	UNKNOWN	A Study on Ca Blocker Versus AII Antagonists in Hypertension With Type 2 Diabetes
NCT00149331	PHASE4	COMPLETED	The Effects of Two Education Strategies About Insulin on Patient Preferences and Perceptions About Insulin Therapy
NCT00162357	PHASE4	COMPLETED	Post-PCI:Cardiac Imaging in Patients With Diabetes to Detect Coronary Artery Blockages Previously Opened by Angioplasty
NCT00174681	PHASE4	COMPLETED	Tulip Study: Testing the Usefulness of Lantus When Initiated Prematurely In Patients With Type 2 Diabetes
NCT00174824	PHASE4	COMPLETED	Comparison of Insulin Glargine and NPH Human Insulin in Progression of Diabetic Retinopathy in Type 2 Diabetic Patients
NCT00177398	PHASE4	COMPLETED	Effect of Glargine Insulin on Glucose Control in Hospitalized Patients Who Receive Tube Feedings
NCT00179400	PHASE4	COMPLETED	The Role of Acute Combined PPAR Alpha and Gamma Stimulation on Insulin Action in Humans
NCT00184561	PHASE4	COMPLETED	Effectiveness and Safety of Biphasic Insulin Aspart 70/30 in Subjects With Type 2 Diabetes
NCT00184626	PHASE4	COMPLETED	Comparison of Insulin Glargine Versus Biphasic Insulin Aspart 30/70 or Biphasic Insulin Aspart 30/70 in Combination With Metformin in Subjects With Type 2 Diabetes.
NCT00191178	PHASE4	COMPLETED	Effects of Insulin in Perceived Mood Symptoms in Patients With Type 2 Diabetes
NCT00191282	PHASE4	COMPLETED	Hyperglycemia and Cardiovascular Outcomes With Type 2 Diabetes
NCT00191464	PHASE4	COMPLETED	Long-Term Effects of Insulin Plus Metformin Regimens on the Overall and Postprandial Glycemic Control of Patients With Type 2 Diabetes
NCT00192803	PHASE4	UNKNOWN	Non-Insulin Dependent Diabetes Mellitus (NIDDM) and Angiotensin Converting Enzyme 2 (ACE2): Diabetic Patients Treated With Antihypertensive Drugs
NCT00202033	PHASE4	COMPLETED	Impact of Self-Monitoring Blood Glucose Frequency on Glycemic Control in Patients With Type 2 Diabetes
NCT00205660	PHASE4	COMPLETED	Changes in Adiposity, Metabolic Measures From Atypicals to Aripiprazole
NCT00212290	PHASE4	COMPLETED	Insulin Resistance and Central Nervous System (CNS) Function in Type 2 Diabetes
NCT00212303	PHASE4	COMPLETED	Exercise Training in Type 2 Diabetes and Hypertension
NCT00225342	PHASE4	WITHDRAWN	Study Protocol for Rosiglitazone Versus Gliclazide in Diabetics With Angina
NCT00238472	PHASE4	COMPLETED	A Pilot Study to Evaluate the Effects of Nateglinide vs. Glibenclamide on Renal Hemodynamics and Albumin Excretion
NCT00239538	PHASE4	COMPLETED	SMOOTH - Blood Pressure Control in Diabetic/Obese Patients
NCT00240253	PHASE4	COMPLETED	A Study Evaluating the Efficacy and Safety of Adding Symlin® to Lantus® (Insulin Glargine) in Subjects With Type 2 Diabetes