Details of Drug Off-Target (DOT)

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

• DOT Name: Immunoglobulin superfamily containing leucine-rich repeat protein (ISLR)
• Gene Name: ISLR
• Related Disease: Gaucher disease
• UniProt ID: ISLR_HUMAN
• Pfam ID: PF13855
• Sequence:
  MQELHLLWWALLLGLAQACPEPCDCGEKYGFQIADCAYRDLESVPPGFPANVTTLSLSAN
  RLPGLPEGAFREVPLLQSLWLAHNEIRTVAAGALASLSHLKSLDLSHNLISDFAWSDLHN
  LSALQLLKMDSNELTFIPRDAFRSLRALRSLQLNHNRLHTLAEGTFTPLTALSHLQINEN
  PFDCTCGIVWLKTWALTTAVSIPEQDNIACTSPHVLKGTPLSRLPPLPCSAPSVQLSYQP
  SQDGAELRPGFVLALHCDVDGQPAPQLHWHIQIPSGIVEITSPNVGTDGRALPGTPVASS
  QPRFQAFANGSLLIPDFGKLEEGTYSCLATNELGSAESSVDVALATPGEGGEDTLGRRFH
  GKAVEGKGCYTVDNEVQPSGPEDNVVIIYLSRAGNPEAAVAEGVPGQLPPGLLLLGQSLL
  LFFFLTSF
• Tissue Specificity: Expressed in various tissues including retina, heart, skeletal muscle, prostate, ovary, small intestine, thyroid, adrenal cortex, testis, stomach and spinal cord.
• Reactome Pathway: Platelet degranulation (R-HSA-114608)

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Gaucher disease	DISTW5JG	Strong	Altered Expression	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the methylation of Immunoglobulin superfamily containing leucine-rich repeat protein (ISLR).	[2]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Immunoglobulin superfamily containing leucine-rich repeat protein (ISLR).	[11]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Immunoglobulin superfamily containing leucine-rich repeat protein (ISLR).	[3]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Immunoglobulin superfamily containing leucine-rich repeat protein (ISLR).	[4]
Triclosan	DMZUR4N	Approved	Triclosan increases the expression of Immunoglobulin superfamily containing leucine-rich repeat protein (ISLR).	[5]
Demecolcine	DMCZQGK	Approved	Demecolcine increases the expression of Immunoglobulin superfamily containing leucine-rich repeat protein (ISLR).	[6]
Isotretinoin	DM4QTBN	Approved	Isotretinoin increases the expression of Immunoglobulin superfamily containing leucine-rich repeat protein (ISLR).	[7]
DTI-015	DMXZRW0	Approved	DTI-015 decreases the expression of Immunoglobulin superfamily containing leucine-rich repeat protein (ISLR).	[8]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Immunoglobulin superfamily containing leucine-rich repeat protein (ISLR).	[9]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol increases the expression of Immunoglobulin superfamily containing leucine-rich repeat protein (ISLR).	[10]

References

• [1] Gene expression profile in patients with Gaucher disease indicates activation of inflammatory processes.Sci Rep. 2019 Apr 15;9(1):6060. doi: 10.1038/s41598-019-42584-1.
• [2] Integrative "-Omics" analysis in primary human hepatocytes unravels persistent mechanisms of cyclosporine A-induced cholestasis. Chem Res Toxicol. 2016 Dec 19;29(12):2164-2174.
• [3] 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.
• [4] 17-Estradiol Activates HSF1 via MAPK Signaling in ER-Positive Breast Cancer Cells. Cancers (Basel). 2019 Oct 11;11(10):1533. doi: 10.3390/cancers11101533.
• [5] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [6] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [7] Temporal changes in gene expression in the skin of patients treated with isotretinoin provide insight into its mechanism of action. Dermatoendocrinol. 2009 May;1(3):177-87.
• [8] Gene expression profile induced by BCNU in human glioma cell lines with differential MGMT expression. J Neurooncol. 2005 Jul;73(3):189-98.
• [9] 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.
• [10] Selenium and vitamin E: cell type- and intervention-specific tissue effects in prostate cancer. J Natl Cancer Inst. 2009 Mar 4;101(5):306-20.
• [11] 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.