Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTOXZQ4K)

• DOT Name: Leucine-rich repeat-containing protein 57 (LRRC57)
• Gene Name: LRRC57
• Related Disease:
  Bipolar disorder
  Schizophrenia
• UniProt ID: LRC57_HUMAN
• Pfam ID: PF00560 ; PF13855
• Sequence:
  MGNSALRAHVETAQKTGVFQLKDRGLTEFPADLQKLTSNLRTIDLSNNKIESLPPLLIGK
  FTLLKSLSLNNNKLTVLPDEICNLKKLETLSLNNNHLRELPSTFGQLSALKTLSLSGNQL
  GALPPQLCSLRHLDVMDLSKNQIRSIPDSVGELQVIELNLNQNQISQISVKISCCPRLKI
  LRLEENCLELSMLPQSILSDSQICLLAVEGNLFEIKKLRELEGYDKYMERFTATKKKFA

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Bipolar disorder	DISAM7J2	Strong	Altered Expression	[1]
Schizophrenia	DISSRV2N	Strong	Altered Expression	[1]

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 Leucine-rich repeat-containing protein 57 (LRRC57).	[2]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Leucine-rich repeat-containing protein 57 (LRRC57).	[3]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Leucine-rich repeat-containing protein 57 (LRRC57).	[4]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Leucine-rich repeat-containing protein 57 (LRRC57).	[5]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Leucine-rich repeat-containing protein 57 (LRRC57).	[6]
Testosterone	DM7HUNW	Approved	Testosterone increases the expression of Leucine-rich repeat-containing protein 57 (LRRC57).	[7]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Leucine-rich repeat-containing protein 57 (LRRC57).	[8]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Leucine-rich repeat-containing protein 57 (LRRC57).	[10]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of Leucine-rich repeat-containing protein 57 (LRRC57).	[9]

References

• [1] Expression quantitative trait loci in the developing human brain and their enrichment in neuropsychiatric disorders.Genome Biol. 2018 Nov 12;19(1):194. doi: 10.1186/s13059-018-1567-1.
• [2] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [3] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [4] Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
• [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] Low doses of cisplatin induce gene alterations, cell cycle arrest, and apoptosis in human promyelocytic leukemia cells. Biomark Insights. 2016 Aug 24;11:113-21.
• [7] The exosome-like vesicles derived from androgen exposed-prostate stromal cells promote epithelial cells proliferation and epithelial-mesenchymal transition. Toxicol Appl Pharmacol. 2021 Jan 15;411:115384. doi: 10.1016/j.taap.2020.115384. Epub 2020 Dec 25.
• [8] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [9] Effect of aflatoxin B(1), benzo[a]pyrene, and methapyrilene on transcriptomic and epigenetic alterations in human liver HepaRG cells. Food Chem Toxicol. 2018 Nov;121:214-223. doi: 10.1016/j.fct.2018.08.034. Epub 2018 Aug 26.
• [10] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.