Details of Drug Off-Target (DOT)

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

• DOT Name: Leucine-rich repeat-containing protein 40 (LRRC40)
• Gene Name: LRRC40
• UniProt ID: LRC40_HUMAN
• Pfam ID: PF13855
• Sequence:
  MSRLKRIAGQDLRAGFKAGGRDCGTSVPQGLLKAARKSGQLNLSGRNLSEVPQCVWRINV
  DIPEEANQNLSFGATERWWEQTDLTKLIISNNKLQSLTDDLRLLPALTVLDIHDNQLTSL
  PSAIRELENLQKLNVSHNKLKILPEEITNLRNLKCLYLQHNELTCISEGFEQLSNLEDLD
  LSNNHLTTVPASFSSLSSLVRLNLSSNELKSLPAEINRMKRLKHLDCNSNLLETIPPELA
  GMESLELLYLRRNKLRFLPEFPSCSLLKELHVGENQIEMLEAEHLKHLNSILVLDLRDNK
  LKSVPDEIILLRSLERLDLSNNDISSLPYSLGNLHLKFLALEGNPLRTIRREIISKGTQE
  VLKYLRSKIKDDGPSQSESATETAMTLPSESRVNIHAIITLKILDYSDKQATLIPDEVFD
  AVKSNIVTSINFSKNQLCEIPKRMVELKEMVSDVDLSFNKLSFISLELCVLQKLTFLDLR
  NNFLNSLPEEMESLVRLQTINLSFNRFKMLPEVLYRIFTLETILISNNQVGSVDPQKMKM
  MENLTTLDLQNNDLLQIPPELGNCVNLRTLLLDGNPFRVPRAAILMKGTAAILEYLRDRI
  PT

Molecular Interaction Atlas (MIA) of This DOT

12 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 Leucine-rich repeat-containing protein 40 (LRRC40).	[1]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Leucine-rich repeat-containing protein 40 (LRRC40).	[2]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Leucine-rich repeat-containing protein 40 (LRRC40).	[3]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Leucine-rich repeat-containing protein 40 (LRRC40).	[4]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Leucine-rich repeat-containing protein 40 (LRRC40).	[5]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Leucine-rich repeat-containing protein 40 (LRRC40).	[6]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Leucine-rich repeat-containing protein 40 (LRRC40).	[7]
Folic acid	DMEMBJC	Approved	Folic acid decreases the expression of Leucine-rich repeat-containing protein 40 (LRRC40).	[9]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Leucine-rich repeat-containing protein 40 (LRRC40).	[10]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Leucine-rich repeat-containing protein 40 (LRRC40).	[11]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Leucine-rich repeat-containing protein 40 (LRRC40).	[12]
methyl p-hydroxybenzoate	DMO58UW	Investigative	methyl p-hydroxybenzoate decreases the expression of Leucine-rich repeat-containing protein 40 (LRRC40).	[13]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic increases the methylation of Leucine-rich repeat-containing protein 40 (LRRC40).	[8]

References

• [1] Antiepileptic drugs are endocrine disruptors for the human fetal testis ex vivo. Toxicol Sci. 2023 Sep 28;195(2):169-183. doi: 10.1093/toxsci/kfad076.
• [2] 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.
• [3] Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
• [4] Gene expression analysis of precision-cut human liver slices indicates stable expression of ADME-Tox related genes. Toxicol Appl Pharmacol. 2011 May 15;253(1):57-69.
• [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] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [7] Quantitative proteomics reveals a broad-spectrum antiviral property of ivermectin, benefiting for COVID-19 treatment. J Cell Physiol. 2021 Apr;236(4):2959-2975. doi: 10.1002/jcp.30055. Epub 2020 Sep 22.
• [8] Identification of novel gene targets and putative regulators of arsenic-associated DNA methylation in human urothelial cells and bladder cancer. Chem Res Toxicol. 2015 Jun 15;28(6):1144-55. doi: 10.1021/tx500393y. Epub 2015 Jun 3.
• [9] Folic acid supplementation dysregulates gene expression in lymphoblastoid cells--implications in nutrition. Biochem Biophys Res Commun. 2011 Sep 9;412(4):688-92. doi: 10.1016/j.bbrc.2011.08.027. Epub 2011 Aug 16.
• [10] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [11] Environmental pollutant induced cellular injury is reflected in exosomes from placental explants. Placenta. 2020 Jan 1;89:42-49. doi: 10.1016/j.placenta.2019.10.008. Epub 2019 Oct 17.
• [12] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [13] Transcriptome dynamics of alternative splicing events revealed early phase of apoptosis induced by methylparaben in H1299 human lung carcinoma cells. Arch Toxicol. 2020 Jan;94(1):127-140. doi: 10.1007/s00204-019-02629-w. Epub 2019 Nov 20.