Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT7VCU13)

• DOT Name: Leucine-rich repeat-containing protein 31 (LRRC31)
• Gene Name: LRRC31
• Related Disease:
  Rheumatoid arthritis
  Central nervous system neoplasm
  Glioma
  Plasma cell myeloma
  Eosinophilic esophagitis
• UniProt ID: LRC31_HUMAN
• Pfam ID: PF13516
• Sequence:
  MSQTRKKTSSEGETKPQTSTVNKFLRGSNAESRKEDNDLKTSDSQPSDWIQKTATSETAK
  PLSSEMEWRSSMEKNEHFLQKLGKKAVNKCLDLNNCGLTTADMKEMVALLPFLPDLEELD
  ISWNGFVGGTLLSITQQMHLVSKLKILRLGSCRLTTDDVQALGEAFEMIPELEELNLSWN
  SKVGGNLPLILQKFQKGSKIQMIELVDCSLTSEDGTFLGQLLPMLQSLEVLDLSINRDIV
  GSLNSIAQGLKSTSNLKVLKLHSCGLSQKSVKILDAAFRYLGELRKLDLSCNKDLGGGFE
  DSPAQLVMLKHLQVLDLHQCSLTADDVMSLTQVIPLLSNLQELDLSANKKMGSSSENLLS
  RLRFLPALKSLVINNCALESETFTALAEASVHLSALEVFNLSWNKCVGGNLKLLLETLKL
  SMSLQVLRLSSCSLVTEDVALLASVIQTGHLAKLQKLDLSYNDSICDAGWTMFCQNVRFL
  KELIELDISLRPSNFRDCGQWFRHLLYAVTKLPQITEIGMKRWILPASQEEELECFDQDK
  KRSIHFDHGGFQ

Molecular Interaction Atlas (MIA) of This DOT

5 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Rheumatoid arthritis	DISTSB4J	Definitive	Biomarker	[1]
Central nervous system neoplasm	DISFC18W	Strong	Genetic Variation	[2]
Glioma	DIS5RPEH	Strong	Genetic Variation	[2]
Plasma cell myeloma	DIS0DFZ0	Strong	Genetic Variation	[3]
Eosinophilic esophagitis	DISR8WSB	Limited	Altered Expression	[4]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Leucine-rich repeat-containing protein 31 (LRRC31).	[5]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Leucine-rich repeat-containing protein 31 (LRRC31).	[6]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Leucine-rich repeat-containing protein 31 (LRRC31).	[7]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Leucine-rich repeat-containing protein 31 (LRRC31).	[5]
Fenofibrate	DMFKXDY	Approved	Fenofibrate increases the expression of Leucine-rich repeat-containing protein 31 (LRRC31).	[8]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Leucine-rich repeat-containing protein 31 (LRRC31).	[10]

2 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 increases the methylation of Leucine-rich repeat-containing protein 31 (LRRC31).	[9]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Leucine-rich repeat-containing protein 31 (LRRC31).	[11]

References

• [1] Circulating Biomarkers for Predicting Infliximab Response in Rheumatoid Arthritis: A Systematic Bioinformatics Analysis.Med Sci Monit. 2017 Apr 17;23:1849-1855. doi: 10.12659/msm.900897.
• [2] Variants near TERT and TERC influencing telomere length are associated with high-grade glioma risk.Nat Genet. 2014 Jul;46(7):731-5. doi: 10.1038/ng.3004. Epub 2014 Jun 8.
• [3] Common variation at 3q26.2, 6p21.33, 17p11.2 and 22q13.1 influences multiple myeloma risk.Nat Genet. 2013 Oct;45(10):1221-1225. doi: 10.1038/ng.2733. Epub 2013 Aug 18.
• [4] LRRC31 is induced by IL-13 and regulates kallikrein expression and barrier function in the esophageal epithelium.Mucosal Immunol. 2016 May;9(3):744-56. doi: 10.1038/mi.2015.98. Epub 2015 Oct 14.
• [5] 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.
• [6] 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.
• [7] Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
• [8] Transcriptomic analysis of untreated and drug-treated differentiated HepaRG cells over a 2-week period. Toxicol In Vitro. 2015 Dec 25;30(1 Pt A):27-35.
• [9] 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.
• [10] CCAT1 is an enhancer-templated RNA that predicts BET sensitivity in colorectal cancer. J Clin Invest. 2016 Feb;126(2):639-52.
• [11] DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.