Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTZ9ZRG8)

• DOT Name: Potassium voltage-gated channel subfamily G member 1 (KCNG1)
• Synonyms: Voltage-gated potassium channel subunit Kv6.1; kH2
• Gene Name: KCNG1
• Related Disease:
  Malaria
  Plasmodium falciparum malaria
• UniProt ID: KCNG1_HUMAN
• Pfam ID: PF02214 ; PF00520
• Sequence:
  MTLLPGDNSDYDYSALSCTSDASFHPAFLPQRQAIKGAFYRRAQRLRPQDEPRQGCQPED
  RRRRIIINVGGIKYSLPWTTLDEFPLTRLGQLKACTNFDDILNVCDDYDVTCNEFFFDRN
  PGAFGTILTFLRAGKLRLLREMCALSFQEELLYWGIAEDHLDGCCKRRYLQKIEEFAEMV
  EREEEDDALDSEGRDSEGPAEGEGRLGRCMRRLRDMVERPHSGLPGKVFACLSVLFVTVT
  AVNLSVSTLPSLREEEEQGHCSQMCHNVFIVESVCVGWFSLEFLLRLIQAPSKFAFLRSP
  LTLIDLVAILPYYITLLVDGAAAGRRKPGAGNSYLDKVGLVLRVLRALRILYVMRLARHS
  LGLQTLGLTARRCTREFGLLLLFLCVAIALFAPLLYVIENEMADSPEFTSIPACYWWAVI
  TMTTVGYGDMVPRSTPGQVVALSSILSGILLMAFPVTSIFHTFSRSYLELKQEQERVMFR
  RAQFLIKTKSQLSVSQDSDILFGSASSDTRDNN
• Function: Potassium channel subunit that does not form functional channels by itself. Can form functional heterotetrameric channels with KCNB1; modulates the delayed rectifier voltage-gated potassium channel activation and deactivation rates of KCNB1.
• Tissue Specificity: Expressed in brain and placenta, and at much lower levels in kidney and pancreas .
• Reactome Pathway: Voltage gated Potassium channels (R-HSA-1296072)

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Malaria	DISQ9Y50	Strong	Genetic Variation	[1]
Plasmodium falciparum malaria	DIS3Q9KF	moderate	Genetic Variation	[2]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of Potassium voltage-gated channel subfamily G member 1 (KCNG1).	[3]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Potassium voltage-gated channel subfamily G member 1 (KCNG1).	[12]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Potassium voltage-gated channel subfamily G member 1 (KCNG1).	[4]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Potassium voltage-gated channel subfamily G member 1 (KCNG1).	[5]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Potassium voltage-gated channel subfamily G member 1 (KCNG1).	[6]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of Potassium voltage-gated channel subfamily G member 1 (KCNG1).	[7]
Progesterone	DMUY35B	Approved	Progesterone increases the expression of Potassium voltage-gated channel subfamily G member 1 (KCNG1).	[8]
Panobinostat	DM58WKG	Approved	Panobinostat increases the expression of Potassium voltage-gated channel subfamily G member 1 (KCNG1).	[9]
Dexamethasone	DMMWZET	Approved	Dexamethasone decreases the expression of Potassium voltage-gated channel subfamily G member 1 (KCNG1).	[10]
Ethanol	DMDRQZU	Approved	Ethanol increases the expression of Potassium voltage-gated channel subfamily G member 1 (KCNG1).	[11]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Potassium voltage-gated channel subfamily G member 1 (KCNG1).	[13]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Potassium voltage-gated channel subfamily G member 1 (KCNG1).	[14]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Potassium voltage-gated channel subfamily G member 1 (KCNG1).	[15]

References

• [1] Rubber plantations and drug resistant malaria: a cross-sectional survey in Cambodia.Malar J. 2019 Nov 27;18(1):379. doi: 10.1186/s12936-019-3000-y.
• [2] Genetic association between the Pfk13 gene mutation and artemisinin resistance phenotype in Plasmodium falciparum isolates from Yunnan Province, China.Malar J. 2018 Dec 18;17(1):478. doi: 10.1186/s12936-018-2619-4.
• [3] Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
• [4] Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
• [5] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [6] Gene expression profiling of human peri-implantation endometria between natural and stimulated cycles. Fertil Steril. 2008 Dec;90(6):2152-64.
• [7] Essential role of cell cycle regulatory genes p21 and p27 expression in inhibition of breast cancer cells by arsenic trioxide. Med Oncol. 2011 Dec;28(4):1225-54.
• [8] Progesterone regulation of implantation-related genes: new insights into the role of oestrogen. Cell Mol Life Sci. 2007 Apr;64(7-8):1009-32.
• [9] A transcriptome-based classifier to identify developmental toxicants by stem cell testing: design, validation and optimization for histone deacetylase inhibitors. Arch Toxicol. 2015 Sep;89(9):1599-618.
• [10] Identification of mechanisms of action of bisphenol a-induced human preadipocyte differentiation by transcriptional profiling. Obesity (Silver Spring). 2014 Nov;22(11):2333-43.
• [11] Cardiac toxicity from ethanol exposure in human-induced pluripotent stem cell-derived cardiomyocytes. Toxicol Sci. 2019 May 1;169(1):280-292.
• [12] Air pollution and DNA methylation alterations in lung cancer: A systematic and comparative study. Oncotarget. 2017 Jan 3;8(1):1369-1391. doi: 10.18632/oncotarget.13622.
• [13] Cell-based two-dimensional morphological assessment system to predict cancer drug-induced cardiotoxicity using human induced pluripotent stem cell-derived cardiomyocytes. Toxicol Appl Pharmacol. 2019 Nov 15;383:114761. doi: 10.1016/j.taap.2019.114761. Epub 2019 Sep 15.
• [14] From transient transcriptome responses to disturbed neurodevelopment: role of histone acetylation and methylation as epigenetic switch between reversible and irreversible drug effects. Arch Toxicol. 2014 Jul;88(7):1451-68.
• [15] Cystathionine metabolic enzymes play a role in the inflammation resolution of human keratinocytes in response to sub-cytotoxic formaldehyde exposure. Toxicol Appl Pharmacol. 2016 Nov 1;310:185-194.