Details of Drug Off-Target (DOT)

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

• DOT Name: Immunoglobulin superfamily containing leucine-rich repeat protein 2 (ISLR2)
• Synonyms: Leucine-rich repeat domain and immunoglobulin domain-containing axon extension protein
• Gene Name: ISLR2
• Related Disease:
  Achalasia
  Congenital hydrocephalus
  Hydrocephalus
• UniProt ID: ISLR2_HUMAN
• Pfam ID: PF13855
• Sequence:
  MFPLRALWLVWALLGVAGSCPEPCACVDKYAHQFADCAYKELREVPEGLPANVTTLSLSA
  NKITVLRRGAFADVTQVTSLWLAHNEVRTVEPGALAVLSQLKNLDLSHNFISSFPWSDLR
  NLSALQLLKMNHNRLGSLPRDALGALPDLRSLRINNNRLRTLAPGTFDALSALSHLQLYH
  NPFHCGCGLVWLQAWAASTRVSLPEPDSIACASPPALQGVPVYRLPALPCAPPSVHLSAE
  PPLEAPGTPLRAGLAFVLHCIADGHPTPRLQWQLQIPGGTVVLEPPVLSGEDDGVGAEEG
  EGEGDGDLLTQTQAQTPTPAPAWPAPPATPRFLALANGSLLVPLLSAKEAGVYTCRAHNE
  LGANSTSIRVAVAATGPPKHAPGAGGEPDGQAPTSERKSTAKGRGNSVLPSKPEGKIKGQ
  GLAKVSILGETETEPEEDTSEGEEAEDQILADPAEEQRCGNGDPSRYVSNHAFNQSAELK
  PHVFELGVIALDVAEREARVQLTPLAARWGPGPGGAGGAPRPGRRPLRLLYLCPAGGGAA
  VQWSRVEEGVNAYWFRGLRPGTNYSVCLALAGEACHVQVVFSTKKELPSLLVIVAVSVFL
  LVLATVPLLGAACCHLLAKHPGKPYRLILRPQAPDPMEKRIAADFDPRASYLESEKSYPA
  GGEAGGEEPEDVQGEGLDEDAEQGDPSGDLQREESLAACSLVESQSKANQEEFEAGSEYS
  DRLPLGAEAVNIAQEINGNYRQTAG
• Function: Required for axon extension during neural development.

Molecular Interaction Atlas (MIA) of This DOT

3 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Achalasia	DISK845N	Strong	Genetic Variation	[1]
Congenital hydrocephalus	DIS7O6UL	Strong	Genetic Variation	[2]
Hydrocephalus	DISIZUF7	Strong	Biomarker	[3]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Immunoglobulin superfamily containing leucine-rich repeat protein 2 (ISLR2).	[4]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Immunoglobulin superfamily containing leucine-rich repeat protein 2 (ISLR2).	[5]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of Immunoglobulin superfamily containing leucine-rich repeat protein 2 (ISLR2).	[6]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Immunoglobulin superfamily containing leucine-rich repeat protein 2 (ISLR2).	[7]
Triclosan	DMZUR4N	Approved	Triclosan increases the expression of Immunoglobulin superfamily containing leucine-rich repeat protein 2 (ISLR2).	[8]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN decreases the expression of Immunoglobulin superfamily containing leucine-rich repeat protein 2 (ISLR2).	[10]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Immunoglobulin superfamily containing leucine-rich repeat protein 2 (ISLR2).	[11]

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 decreases the methylation of Immunoglobulin superfamily containing leucine-rich repeat protein 2 (ISLR2).	[9]
1,6-hexamethylene diisocyanate	DMLB3RT	Investigative	1,6-hexamethylene diisocyanate increases the methylation of Immunoglobulin superfamily containing leucine-rich repeat protein 2 (ISLR2).	[12]

References

• [1] Innovative and Contemporary Interventional Therapies for Esophageal Diseases.J Thorac Imaging. 2019 Jul;34(4):217-235. doi: 10.1097/RTI.0000000000000423.
• [2] A novel ISLR2-linked autosomal recessive syndrome of congenital hydrocephalus, arthrogryposis and abdominal distension.Hum Genet. 2019 Jan;138(1):105-107. doi: 10.1007/s00439-018-1963-3. Epub 2018 Nov 27.
• [3] Essential Role of Linx/Islr2 in the Development of the Forebrain Anterior Commissure.Sci Rep. 2018 May 8;8(1):7292. doi: 10.1038/s41598-018-24064-0.
• [4] Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
• [5] Blood transcript immune signatures distinguish a subset of people with elevated serum ALT from others given acetaminophen. Clin Pharmacol Ther. 2016 Apr;99(4):432-41.
• [6] 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.
• [7] Minimal peroxide exposure of neuronal cells induces multifaceted adaptive responses. PLoS One. 2010 Dec 17;5(12):e14352. doi: 10.1371/journal.pone.0014352.
• [8] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [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] Endoplasmic reticulum stress impairs insulin signaling through mitochondrial damage in SH-SY5Y cells. Neurosignals. 2012;20(4):265-80.
• [11] Transcriptomic?pathway?and?benchmark dose analysis of Bisphenol A, Bisphenol S, Bisphenol F, and 3,3',5,5'-Tetrabromobisphenol A in H9 human embryonic stem cells. Toxicol In Vitro. 2021 Apr;72:105097. doi: 10.1016/j.tiv.2021.105097. Epub 2021 Jan 18.
• [12] DNA methylation modifies urine biomarker levels in 1,6-hexamethylene diisocyanate exposed workers: a pilot study. Toxicol Lett. 2014 Dec 1;231(2):217-26. doi: 10.1016/j.toxlet.2014.10.024. Epub 2014 Oct 22.