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Kir6.1

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Target id: 441

Nomenclature: Kir6.1

Family: Inwardly rectifying potassium channels (KIR)

Contents:

Gene and Protein Information Click here for help
Species TM P Loops AA Chromosomal Location Gene Symbol Gene Name Reference
Human 2 0 424 12p12.1 KCNJ8 potassium inwardly rectifying channel subfamily J member 8 4
Mouse 2 0 424 6 74.31 cM Kcnj8 potassium inwardly-rectifying channel, subfamily J, member 8 9
Rat 2 0 424 4q44 Kcnj8 potassium inwardly-rectifying channel, subfamily J, member 8 5
Previous and Unofficial Names Click here for help
potassium inwardly rectifying channel subfamily J member 8 | ATP-sensitive inward rectifier potassium channel 8 | gnite | inwardly rectifier K(+) channel Kir6.1 | inward rectifier K(+) channel Kir6.1 | potassium channel, inwardly rectifying subfamily J, member 8 | potassium inwardly-rectifying channel | potassium voltage-gated channel subfamily J member 8 | slmbr | sltr | uKATP-1
Database Links Click here for help
Alphafold Q15842 (Hs), P97794 (Mm), Q63664 (Rn)
CATH/Gene3D 2.60.40.1400
ChEMBL Target CHEMBL4770 (Hs), CHEMBL4524131 (Rn)
DrugBank Target Q15842 (Hs)
Ensembl Gene ENSG00000121361 (Hs), ENSMUSG00000030247 (Mm), ENSRNOG00000013463 (Rn)
Entrez Gene 3764 (Hs), 16523 (Mm), 25472 (Rn)
Human Protein Atlas ENSG00000121361 (Hs)
KEGG Gene hsa:3764 (Hs), mmu:16523 (Mm), rno:25472 (Rn)
OMIM 600935 (Hs)
Orphanet ORPHA297206 (Hs)
Pharos Q15842 (Hs)
RefSeq Nucleotide NM_004982 (Hs), NM_008428 (Mm), NM_017099 (Rn)
RefSeq Protein NP_004973 (Hs), NP_032454 (Mm), NP_058795 (Rn)
UniProtKB Q15842 (Hs), P97794 (Mm), Q63664 (Rn)
Wikipedia KCNJ8 (Hs)
Associated Proteins Click here for help
Heteromeric Pore-forming Subunits
Name References
Not determined
Auxiliary Subunits
Name References
SUR2B 9
Other Associated Proteins
Name References
Not determined
Functional Characteristics Click here for help
ATP-sensitive, inward-rectifier current
Ion Selectivity and Conductance Click here for help
Species:  Mouse
Rank order:  K+ [33.0 pS]
References:  9
Ion Selectivity and Conductance Comments
This current was recorded in the Kir6.1/SUR2B channel.
Associated subunits (Human)
SUR1, SUR2A, SUR2B

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Activators
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Concentration range (M) Holding voltage (mV) Reference
ATP Small molecule or natural product Click here for species-specific activity table Ligand is endogenous in the given species Ligand has a PDB structure Mm Agonist - - 1x10-3 -60.0 9
⤷ Conc range: 1x10-3 M [9]
Holding voltage: -60.0 mV
UDP Small molecule or natural product Ligand has a PDB structure Mm Agonist - - 1x10-3 -60.0 – 60.0 9
⤷ Conc range: 1x10-3 M [9]
Holding voltage: -60.0 – 60.0 mV
nicorandil Small molecule or natural product Approved drug Mm Agonist - - 3x10-4 -60.0 – 60.0 9
⤷ Conc range: 3x10-4 M [9]
Holding voltage: -60.0 – 60.0 mV
diazoxide Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Mm Agonist - - 2x10-4 -60.0 9
⤷ Conc range: 2x10-4 M [9]
Holding voltage: -60.0 mV
guanosine 5'-diphosphate Small molecule or natural product Ligand is endogenous in the given species Ligand has a PDB structure Mm Agonist - - 1x10-4 -60.0 – 60.0 9
⤷ Conc range: 1x10-4 M [9]
Holding voltage: -60.0 – 60.0 mV
pinacidil Small molecule or natural product Approved drug Click here for species-specific activity table Mm Agonist - - 1x10-4 -100.0 – 60.0 9
⤷ Conc range: 1x10-4 M [9]
Holding voltage: -100.0 – 60.0 mV
guanosine-5'-triphosphate Small molecule or natural product Ligand is endogenous in the given species Ligand has a PDB structure Mm Agonist - - 1x10-7 - 1x10-4 -60.0 9
⤷ Conc range: 1x10-7 - 1x10-4 M [9]
Holding voltage: -60.0 mV
cromakalim Small molecule or natural product Hs - - - - -
⤷
minoxidil Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Hs - - - - -
⤷
View species-specific activator tables
Activator Comments
Nucleoside diphosphates activate Kir6.1 channels coexpressed with SUR2B [9]. ATP activates and inhibits these channels at low (<10-5M) and high (>10-4M) concentrations, respectively [9]. GTP activates and inhibits Kir6.1 channels at low (<10-5M) and high (>10-4M) concentrations respectively, when coexpressed with SUR2B [9].
Inhibitors
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Concentration range (M) Holding voltage (mV) Reference
glibenclamide Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Immunopharmacology Ligand Hs - - - - -
⤷
tolbutamide Small molecule or natural product Approved drug Click here for species-specific activity table Hs - - - - -
⤷
Gating inhibitors Click here for help
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Concentration range (M) Holding voltage (mV) Reference
ATP Small molecule or natural product Click here for species-specific activity table Ligand is endogenous in the given species Ligand has a PDB structure Mm Antagonist - - 1x10-3 - 3x10-3 -60.0 9
⤷ Conc range: 1x10-3 - 3x10-3 M [9]
Holding voltage: -60.0 mV
guanosine-5'-triphosphate Small molecule or natural product Ligand has a PDB structure Mm Antagonist - - 3x10-6 -60.0 9
⤷ Conc range: 3x10-6 M [9]
Holding voltage: -60.0 mV
Gating Inhibitor Comments
ATP at high concentrations (>10-4M inhibits Kir6.1 channels when coexpressed with SUB2B [9]. GTP at high concentrations (>10-4) when coexpressed with SUR2B [9]
Tissue Distribution Click here for help
Heart, ovary, adrenal grand > skeletal muscle, lung, brain, stomach, colon, testis, thyroid, pancreatic islet cells > kidney, liver, small intestine, pituitary gland.
Species:  Rat
Technique:  Northern Blot
References:  5
Functional Assays Click here for help
Patch clamp recording of Kir6.1 expressed in conjunction with SUR2B.
Species:  Mouse
Tissue:  HEK293T cells
Response measured:  Current.
References:  9
Physiological Consequences of Altering Gene Expression Click here for help
Absence of Kir6.1 expression causes increased susceptibility to endotoxemia through decreased cardiac adaptation.
Species:  Mouse
Tissue:  Heart
Technique:  Knockout
References:  6
Absence of Kir6.1 expression leads to abnormal coronary vasodilation modelling human vasospastic (Printzmetal) angina.
Species:  Mouse
Tissue:  Heart
Technique:  Knockout
References:  8
Gain of Kir6.1 mutations expressed in smooth muscle cause lowering of blood pressure, modeling one of the features of Cantu syndrome
Species:  Mouse
Tissue:  Smooth muscle
Technique:  Transgenic overexpression
References:  7
Phenotypes, Alleles and Disease Models Click here for help Mouse data from MGI

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Allele Composition & genetic background Accession Phenotype Id Phenotype Reference
Kcnj8tm1Sse Kcnj8tm1Sse/Kcnj8tm1Sse
involves: 129S1/Sv * 129X1/SvJ * C57BL/6		 MGI:1100508  MP:0004215 abnormal myocardial fiber physiology PMID: 11984590 
Kcnj8mydy Kcnj8mydy/Kcnj8mydy
involves: C57BL/6J		 MGI:1100508  MP:0001658 increased mortality induced by gamma-irradiation PMID: 18026101 
Kcnj8mydy Kcnj8mydy/Kcnj8mydy
involves: C57BL/6J		 MGI:1100508  MP:0009763 increased sensitivity to induced morbidity/mortality PMID: 18026101 
Kcnj8sltr Kcnj8sltr/Kcnj8sltr
involves: C57BL/6		 MGI:1100508  MP:0009763 increased sensitivity to induced morbidity/mortality PMID: 18026101 
Kcnj8gnite Kcnj8gnite/Kcnj8gnite
involves: C57BL/6		 MGI:1100508  MP:0009763 increased sensitivity to induced morbidity/mortality PMID: 18026101 
Kcnj8slmbr Kcnj8slmbr/Kcnj8slmbr
involves: C57BL/6		 MGI:1100508  MP:0009763 increased sensitivity to induced morbidity/mortality PMID: 18026101 
Kcnj8mydy Kcnj8mydy/Kcnj8mydy
involves: C57BL/6J		 MGI:1100508  MP:0008735 increased susceptibility to endotoxin shock PMID: 18026101 
Kcnj8sos Kcnj8sos/Kcnj8sos
C57BL/6J-Kcnj8		 MGI:1100508  MP:0008735 increased susceptibility to endotoxin shock
Kcnj8gnite Kcnj8gnite/Kcnj8gnite
C57BL/6		 MGI:1100508  MP:0002418 increased susceptibility to viral infection PMID: 16688530 
Kcnj8sltr Kcnj8sltr/Kcnj8sltr
C57BL/6		 MGI:1100508  MP:0002418 increased susceptibility to viral infection PMID: 16688530 
Kcnj8slmbr Kcnj8slmbr/Kcnj8slmbr
C57BL/6		 MGI:1100508  MP:0002418 increased susceptibility to viral infection PMID: 16688530 
Kcnj8mydy Kcnj8mydy/Kcnj8mydy
involves: C57BL/6J		 MGI:1100508  MP:0002418 increased susceptibility to viral infection PMID: 18026101 
Kcnj8tm1Sse Kcnj8tm1Sse/Kcnj8tm1Sse
involves: 129S1/Sv * 129X1/SvJ * C57BL/6		 MGI:1100508  MP:0001636 irregular heartbeat PMID: 11984590 
Kcnj8tm1Sse Kcnj8tm1Sse/Kcnj8tm1Sse
involves: 129S1/Sv * 129X1/SvJ * C57BL/6		 MGI:1100508  MP:0002083 premature death PMID: 11984590 
Clinically-Relevant Mutations and Pathophysiology Click here for help
Disease:  Brugada syndrome 1; BRGDA1
Synonyms: Brugada syndrome [Orphanet: ORPHA130] [Disease Ontology: DOID:0050451]
Disease Ontology: DOID:0050451
OMIM: 601144
Orphanet: ORPHA130
References:  1
Disease:  Cantu Syndrome
Synonyms: Hypertrichotic osteochondrodysplasia, Cantu type [Orphanet: ORPHA1517]
OMIM: 239850
Orphanet: ORPHA1517
References:  2-3

References

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1. Barajas-Martínez H, Hu D, Ferrer T, Onetti CG, Wu Y, Burashnikov E, Boyle M, Surman T, Urrutia J, Veltmann C et al.. (2012) Molecular genetic and functional association of Brugada and early repolarization syndromes with S422L missense mutation in KCNJ8. Heart Rhythm, 9 (4): 548-55. [PMID:22056721]

2. Brownstein CA, Towne MC, Luquette LJ, Harris DJ, Marinakis NS, Meinecke P, Kutsche K, Campeau PM, Yu TW, Margulies DM et al.. (2013) Mutation of KCNJ8 in a patient with Cantú syndrome with unique vascular abnormalities - support for the role of K(ATP) channels in this condition. Eur J Med Genet, 56 (12): 678-82. [PMID:24176758]

3. Cooper PE, Reutter H, Woelfle J, Engels H, Grange DK, van Haaften G, van Bon BW, Hoischen A, Nichols CG. (2014) Cantú syndrome resulting from activating mutation in the KCNJ8 gene. Hum Mutat, 35 (7): 809-13. [PMID:24700710]

4. Inagaki N, Inazawa J, Seino S. (1995) cDNA sequence, gene structure, and chromosomal localization of the human ATP-sensitive potassium channel, uKATP-1, gene (KCNJ8). Genomics, 30 (1): 102-4. [PMID:8595887]

5. Inagaki N, Tsuura Y, Namba N, Masuda K, Gonoi T, Horie M, Seino Y, Mizuta M, Seino S. (1995) Cloning and functional characterization of a novel ATP-sensitive potassium channel ubiquitously expressed in rat tissues, including pancreatic islets, pituitary, skeletal muscle, and heart. J Biol Chem, 270 (11): 5691-4. [PMID:7890693]

6. Kane GC, Lam CF, O'Cochlain F, Hodgson DM, Reyes S, Liu XK, Miki T, Seino S, Katusic ZS, Terzic A. (2006) Gene knockout of the KCNJ8-encoded Kir6.1 K(ATP) channel imparts fatal susceptibility to endotoxemia. FASEB J, 20 (13): 2271-80. [PMID:17077304]

7. Li A, Knutsen RH, Zhang H, Osei-Owusu P, Moreno-Dominguez A, Harter TM, Uchida K, Remedi MS, Dietrich HH, Bernal-Mizrachi C et al.. (2013) Hypotension due to Kir6.1 gain-of-function in vascular smooth muscle. J Am Heart Assoc, 2 (4): e000365. [PMID:23974906]

8. Miki T, Suzuki M, Shibasaki T, Uemura H, Sato T, Yamaguchi K, Koseki H, Iwanaga T, Nakaya H, Seino S. (2002) Mouse model of Prinzmetal angina by disruption of the inward rectifier Kir6.1. Nat Med, 8 (5): 466-72. [PMID:11984590]

9. Yamada M, Isomoto S, Matsumoto S, Kondo C, Shindo T, Horio Y, Kurachi Y. (1997) Sulphonylurea receptor 2B and Kir6.1 form a sulphonylurea-sensitive but ATP-insensitive K+ channel. J Physiol (Lond.), 499 ( Pt 3): 715-20. [PMID:9130167]

Contributors

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