Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT36YA7Q)

DOT Name	EKC/KEOPS complex subunit GON7 (GON7)
Gene Name	GON7
Related Disease	Galloway-Mowat syndrome ( )
UniProt ID	GON7_HUMAN
3D Structure	Download 2D Sequence (FASTA) Download 3D Structure (PDB) Download
PDB ID	6GWJ
Pfam ID	PF15387
Sequence	MELLGEYVGQEGKPQKLRVSCEAPGDGDPFQGLLSGVAQMKDMVTELFDPLVQGEVQHRV AAAPDEDLDGDDEDDAEDENNIDNRTNFDGPSAKRPKTPS
Function	Component of the EKC/KEOPS complex that is required for the formation of a threonylcarbamoyl group on adenosine at position 37 (t(6)A37) in tRNAs that read codons beginning with adenine. The complex is probably involved in the transfer of the threonylcarbamoyl moiety of threonylcarbamoyl-AMP (TC-AMP) to the N6 group of A37. GON7 plays a supporting role to the catalytic subunit OSGEP in the complex.

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance		REF
Galloway-Mowat syndrome	DISVB7IM	Strong	Genetic Variation	[1]
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Molecular Interaction Atlas (MIA)

MIA Detail

Jump to Detail Molecular Interaction Atlas of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of EKC/KEOPS complex subunit GON7 (GON7).	[2]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of EKC/KEOPS complex subunit GON7 (GON7).	[3]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of EKC/KEOPS complex subunit GON7 (GON7).	[4]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of EKC/KEOPS complex subunit GON7 (GON7).	[5]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of EKC/KEOPS complex subunit GON7 (GON7).	[6]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of EKC/KEOPS complex subunit GON7 (GON7).	[7]
Cannabidiol	DM0659E	Approved	Cannabidiol increases the expression of EKC/KEOPS complex subunit GON7 (GON7).	[8]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of EKC/KEOPS complex subunit GON7 (GON7).	[9]
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⏷ Show the Full List of 8 Drug(s)

References

1	Defects in t(6)A tRNA modification due to GON7 and YRDC mutations lead to Galloway-Mowat syndrome. Nat Commun. 2019 Sep 3;10(1):3967. doi: 10.1038/s41467-019-11951-x.
2	Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
3	Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
4	Development of a neural teratogenicity test based on human embryonic stem cells: response to retinoic acid exposure. Toxicol Sci. 2011 Dec;124(2):370-7.
5	Bringing in vitro analysis closer to in vivo: studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling. Toxicol Lett. 2018 Sep 15;294:184-192.
6	Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
7	Definition of transcriptome-based indices for quantitative characterization of chemically disturbed stem cell development: introduction of the STOP-Toxukn and STOP-Toxukk tests. Arch Toxicol. 2017 Feb;91(2):839-864.
8	Cannabidiol Activates Neuronal Precursor Genes in Human Gingival Mesenchymal Stromal Cells. J Cell Biochem. 2017 Jun;118(6):1531-1546. doi: 10.1002/jcb.25815. Epub 2016 Dec 29.
9	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.