Details of Drug Off-Target (DOT)

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

• DOT Name: INO80 complex subunit C (INO80C)
• Synonyms: IES6 homolog; hIes6
• Gene Name: INO80C
• Related Disease:
  Acute myelogenous leukaemia
  Adult respiratory distress syndrome
  Anxiety
  Anxiety disorder
  Depression
  Post-traumatic stress disorder
• UniProt ID: IN80C_HUMAN
• PDB ID: 7ZI4
• Pfam ID: PF08265
• Sequence:
  MAAQIPIVATTSTPGIVRNSKKRPASPSHNGSSGGGYGASKKKKASASSFAQGISMEAMS
  ENKMVPSEFSTGPVEKAAKPLPFKDPNFVHSGHGGAVAGKKNRTWKNLKQILASERALPW
  QLNDPNYFSIDAPPSFKPAKKYSDVSGLLANYTDPQSKLRFSTIEEFSYIRRLPSDVVTG
  YLALRKATSIVP
• Function: Proposed core component of the chromatin remodeling INO80 complex which is involved in transcriptional regulation, DNA replication and probably DNA repair.
• KEGG Pathway: ATP-dependent chromatin remodeling (hsa03082)
• Reactome Pathway:
  DNA Damage Recognition in GG-NER (R-HSA-5696394)
  UCH proteinases (R-HSA-5689603)

Molecular Interaction Atlas (MIA) of This DOT

6 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Acute myelogenous leukaemia	DISCSPTN	Strong	Biomarker	[1]
Adult respiratory distress syndrome	DISIJV47	Strong	Biomarker	[2]
Anxiety	DISIJDBA	Strong	Biomarker	[2]
Anxiety disorder	DISBI2BT	Strong	Biomarker	[2]
Depression	DIS3XJ69	Strong	Biomarker	[2]
Post-traumatic stress disorder	DISHL1EY	Strong	Genetic Variation	[2]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of INO80 complex subunit C (INO80C).	[3]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of INO80 complex subunit C (INO80C).	[4]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of INO80 complex subunit C (INO80C).	[5]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of INO80 complex subunit C (INO80C).	[6]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of INO80 complex subunit C (INO80C).	[7]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of INO80 complex subunit C (INO80C).	[8]
QUERCITRIN	DM1DH96	Investigative	QUERCITRIN decreases the expression of INO80 complex subunit C (INO80C).	[9]

References

• [1] Identifying functions and prognostic biomarkers of network motifs marked by diverse chromatin states in human cell lines.Oncogene. 2020 Jan;39(3):677-689. doi: 10.1038/s41388-019-1005-1. Epub 2019 Sep 19.
• [2] Screening for posttraumatic stress disorder in ARDS survivors: validation of the Impact of Event Scale-6 (IES-6).Crit Care. 2019 Aug 7;23(1):276. doi: 10.1186/s13054-019-2553-z.
• [3] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [4] 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.
• [5] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [6] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [7] Identification of a transcriptomic signature of food-relevant genotoxins in human HepaRG hepatocarcinoma cells. Food Chem Toxicol. 2020 Jun;140:111297. doi: 10.1016/j.fct.2020.111297. Epub 2020 Mar 28.
• [8] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [9] Molecular mechanisms of quercitrin-induced apoptosis in non-small cell lung cancer. Arch Med Res. 2014 Aug;45(6):445-54.