Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTZ8G8FE)

• DOT Name: ATP-sensitive inward rectifier potassium channel 8 (KCNJ8)
• Synonyms: Inward rectifier K(+) channel Kir6.1; Potassium channel, inwardly rectifying subfamily J member 8; uKATP-1
• Gene Name: KCNJ8
• Related Disease:
  Amelogenesis imperfecta type 1G
  Angina pectoris
  Coronary atherosclerosis
  Dilated cardiomyopathy 1A
  Hypertrichosis lanuginosa congenita
  Hypertrichotic osteochondrodysplasia Cantu type
  Myocardial ischemia
  Neoplasm
  Parkinsonian disorder
  Sciatic neuropathy
  Arrhythmia
  Ventricular fibrillation
  Brugada syndrome 1
  Conduction system disorder
  High blood pressure
  Sinoatrial node disorder
  Amyotrophic lateral sclerosis
  Atrial fibrillation
  Brugada syndrome
  Hypertrophic cardiomyopathy
  Ventricular tachycardia
• UniProt ID: KCNJ8_HUMAN
• Pfam ID: PF01007 ; PF17655
• Sequence:
  MLARKSIIPEEYVLARIAAENLRKPRIRDRLPKARFIAKSGACNLAHKNIREQGRFLQDI
  FTTLVDLKWRHTLVIFTMSFLCSWLLFAIMWWLVAFAHGDIYAYMEKSGMEKSGLESTVC
  VTNVRSFTSAFLFSIEVQVTIGFGGRMMTEECPLAITVLILQNIVGLIINAVMLGCIFMK
  TAQAHRRAETLIFSRHAVIAVRNGKLCFMFRVGDLRKSMIISASVRIQVVKKTTTPEGEV
  VPIHQLDIPVDNPIESNNIFLVAPLIICHVIDKRSPLYDISATDLANQDLEVIVILEGVV
  ETTGITTQARTSYIAEEIQWGHRFVSIVTEEEGVYSVDYSKFGNTVKVAAPRCSARELDE
  KPSILIQTLQKSELSHQNSLRKRNSMRRNNSMRRNNSIRRNNSSLMVPKVQFMTPEGNQN
  TSES
• Function: This potassium channel is controlled by G proteins. 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 external barium.
• Tissue Specificity: Predominantly detected in fetal and adult heart.
• KEGG Pathway: cGMP-PKG sig.ling pathway (hsa04022)
• Reactome Pathway: ATP sensitive Potassium channels (R-HSA-1296025)

Molecular Interaction Atlas (MIA) of This DOT

21 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Amelogenesis imperfecta type 1G	DISS8U5Q	Strong	Biomarker	[1]
Angina pectoris	DISCLMC4	Strong	Biomarker	[2]
Coronary atherosclerosis	DISKNDYU	Strong	Biomarker	[3]
Dilated cardiomyopathy 1A	DIS0RK9Z	Strong	Altered Expression	[4]
Hypertrichosis lanuginosa congenita	DISX1C1I	Strong	Biomarker	[5]
Hypertrichotic osteochondrodysplasia Cantu type	DISI9W4I	Strong	Autosomal dominant	[6]
Myocardial ischemia	DISFTVXF	Strong	Biomarker	[7]
Neoplasm	DISZKGEW	Strong	Biomarker	[8]
Parkinsonian disorder	DISHGY45	Strong	Biomarker	[9]
Sciatic neuropathy	DISMGDKX	Strong	Biomarker	[10]
Arrhythmia	DISFF2NI	moderate	Biomarker	[11]
Ventricular fibrillation	DIS7IN76	moderate	Genetic Variation	[6]
Brugada syndrome 1	DISKBA7V	Disputed	Autosomal dominant	[12]
Conduction system disorder	DISED5HG	Disputed	Biomarker	[13]
High blood pressure	DISY2OHH	Disputed	Biomarker	[14]
Sinoatrial node disorder	DISYJI6J	Disputed	Biomarker	[13]
Amyotrophic lateral sclerosis	DISF7HVM	Limited	Altered Expression	[15]
Atrial fibrillation	DIS15W6U	Limited	Biomarker	[16]
Brugada syndrome	DISSGN0E	Limited	Unknown	[17]
Hypertrophic cardiomyopathy	DISQG2AI	Limited	Biomarker	[18]
Ventricular tachycardia	DISIBXJ3	Limited	Biomarker	[16]

2 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the methylation of ATP-sensitive inward rectifier potassium channel 8 (KCNJ8).	[19]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of ATP-sensitive inward rectifier potassium channel 8 (KCNJ8).	[35]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of ATP-sensitive inward rectifier potassium channel 8 (KCNJ8).	[20]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of ATP-sensitive inward rectifier potassium channel 8 (KCNJ8).	[21]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of ATP-sensitive inward rectifier potassium channel 8 (KCNJ8).	[22]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of ATP-sensitive inward rectifier potassium channel 8 (KCNJ8).	[23]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of ATP-sensitive inward rectifier potassium channel 8 (KCNJ8).	[24]
Cisplatin	DMRHGI9	Approved	Cisplatin affects the expression of ATP-sensitive inward rectifier potassium channel 8 (KCNJ8).	[25]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of ATP-sensitive inward rectifier potassium channel 8 (KCNJ8).	[26]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of ATP-sensitive inward rectifier potassium channel 8 (KCNJ8).	[27]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of ATP-sensitive inward rectifier potassium channel 8 (KCNJ8).	[28]
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of ATP-sensitive inward rectifier potassium channel 8 (KCNJ8).	[29]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of ATP-sensitive inward rectifier potassium channel 8 (KCNJ8).	[30]
Decitabine	DMQL8XJ	Approved	Decitabine increases the expression of ATP-sensitive inward rectifier potassium channel 8 (KCNJ8).	[31]
Progesterone	DMUY35B	Approved	Progesterone increases the expression of ATP-sensitive inward rectifier potassium channel 8 (KCNJ8).	[32]
Glibenclamide	DM8JXPZ	Approved	Glibenclamide decreases the activity of ATP-sensitive inward rectifier potassium channel 8 (KCNJ8).	[33]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol increases the expression of ATP-sensitive inward rectifier potassium channel 8 (KCNJ8).	[34]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of ATP-sensitive inward rectifier potassium channel 8 (KCNJ8).	[36]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of ATP-sensitive inward rectifier potassium channel 8 (KCNJ8).	[37]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of ATP-sensitive inward rectifier potassium channel 8 (KCNJ8).	[38]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane decreases the expression of ATP-sensitive inward rectifier potassium channel 8 (KCNJ8).	[39]
Deguelin	DMXT7WG	Investigative	Deguelin increases the expression of ATP-sensitive inward rectifier potassium channel 8 (KCNJ8).	[40]

References

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