Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTIXCRI6)

• DOT Name: ATP-sensitive inward rectifier potassium channel 1 (KCNJ1)
• Synonyms: ATP-regulated potassium channel ROM-K; Inward rectifier K(+) channel Kir1.1; Potassium channel, inwardly rectifying subfamily J member 1
• Gene Name: KCNJ1
• Related Disease:
  Bartter disease type 2
  Obsolete antenatal Bartter syndrome
• UniProt ID: KCNJ1_HUMAN
• Pfam ID: PF01007 ; PF17655
• Sequence:
  MNASSRNVFDTLIRVLTESMFKHLRKWVVTRFFGHSRQRARLVSKDGRCNIEFGNVEAQS
  RFIFFVDIWTTVLDLKWRYKMTIFITAFLGSWFFFGLLWYAVAYIHKDLPEFHPSANHTP
  CVENINGLTSAFLFSLETQVTIGYGFRCVTEQCATAIFLLIFQSILGVIINSFMCGAILA
  KISRPKKRAKTITFSKNAVISKRGGKLCLLIRVANLRKSLLIGSHIYGKLLKTTVTPEGE
  TIILDQININFVVDAGNENLFFISPLTIYHVIDHNSPFFHMAAETLLQQDFELVVFLDGT
  VESTSATCQVRTSYVPEEVLWGYRFAPIVSKTKEGKYRVDFHNFSKTVEVETPHCAMCLY
  NEKDVRARMKRGYDNPNFILSEVNETDDTKM
• Function: In the kidney, probably plays a major role in potassium homeostasis. 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. This channel is activated by internal ATP and can be blocked by external barium.
• Tissue Specificity: In the kidney and pancreatic islets. Lower levels in skeletal muscle, pancreas, spleen, brain, heart and liver.
• KEGG Pathway:
  Aldosterone-regulated sodium reabsorption (hsa04960)
  Gastric acid secretion (hsa04971)
• Reactome Pathway: Potassium transport channels (R-HSA-1296067)

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Bartter disease type 2	DISCV46V	Strong	Autosomal recessive	[1]
Obsolete antenatal Bartter syndrome	DIS5WI27	Supportive	Autosomal recessive	[2]

7 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of ATP-sensitive inward rectifier potassium channel 1 (KCNJ1).	[3]
Testosterone	DM7HUNW	Approved	Testosterone increases the expression of ATP-sensitive inward rectifier potassium channel 1 (KCNJ1).	[3]
Zoledronate	DMIXC7G	Approved	Zoledronate decreases the expression of ATP-sensitive inward rectifier potassium channel 1 (KCNJ1).	[4]
Gentamicin	DMKINJO	Approved	Gentamicin increases the expression of ATP-sensitive inward rectifier potassium channel 1 (KCNJ1).	[5]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of ATP-sensitive inward rectifier potassium channel 1 (KCNJ1).	[6]
3R14S-OCHRATOXIN A	DM2KEW6	Investigative	3R14S-OCHRATOXIN A decreases the expression of ATP-sensitive inward rectifier potassium channel 1 (KCNJ1).	[7]
G418	DMKTJBU	Investigative	G418 increases the expression of ATP-sensitive inward rectifier potassium channel 1 (KCNJ1).	[5]

References

• [1] Clinical presentation of genetically defined patients with hypokalemic salt-losing tubulopathies. Am J Med. 2002 Feb 15;112(3):183-90. doi: 10.1016/s0002-9343(01)01086-5.
• [2] Mutations in the gene encoding the inwardly-rectifying renal potassium channel, ROMK, cause the antenatal variant of Bartter syndrome: evidence for genetic heterogeneity. International Collaborative Study Group for Bartter-like Syndromes. Hum Mol Genet. 1997 Jan;6(1):17-26. doi: 10.1093/hmg/6.1.17.
• [3] Effects of 1alpha,25 dihydroxyvitamin D3 and testosterone on miRNA and mRNA expression in LNCaP cells. Mol Cancer. 2011 May 18;10:58.
• [4] Interleukin-19 as a translational indicator of renal injury. Arch Toxicol. 2015 Jan;89(1):101-6.
• [5] Classification and rescue of ROMK mutations underlying hyperprostaglandin E syndrome/antenatal Bartter syndrome. Kidney Int. 2003 Sep;64(3):923-32. doi: 10.1046/j.1523-1755.2003.00153.x.
• [6] Transcriptional signature of human macrophages exposed to the environmental contaminant benzo(a)pyrene. Toxicol Sci. 2010 Apr;114(2):247-59.
• [7] Transcriptomic alterations induced by Ochratoxin A in rat and human renal proximal tubular in vitro models and comparison to a rat in vivo model. Arch Toxicol. 2012 Apr;86(4):571-89.