Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTGP2DCY)

• DOT Name: Leucine-rich repeat neuronal protein 2 (LRRN2)
• Synonyms: Glioma amplified on chromosome 1 protein; Leucine-rich repeat neuronal protein 5
• Gene Name: LRRN2
• Related Disease:
  Anaplastic astrocytoma
  Astrocytoma
  Glioblastoma multiforme
  Malignant glioma
  Schizophrenia
  Asthma
  Neoplasm
• UniProt ID: LRRN2_HUMAN
• Pfam ID: PF07679 ; PF13855
• Sequence:
  MRLLVAPLLLAWVAGATAAVPVVPWHVPCPPQCACQIRPWYTPRSSYREATTVDCNDLFL
  TAVPPALPAGTQTLLLQSNSIVRVDQSELGYLANLTELDLSQNSFSDARDCDFHALPQLL
  SLHLEENQLTRLEDHSFAGLASLQELYLNHNQLYRIAPRAFSGLSNLLRLHLNSNLLRAI
  DSRWFEMLPNLEILMIGGNKVDAILDMNFRPLANLRSLVLAGMNLREISDYALEGLQSLE
  SLSFYDNQLARVPRRALEQVPGLKFLDLNKNPLQRVGPGDFANMLHLKELGLNNMEELVS
  IDKFALVNLPELTKLDITNNPRLSFIHPRAFHHLPQMETLMLNNNALSALHQQTVESLPN
  LQEVGLHGNPIRCDCVIRWANATGTRVRFIEPQSTLCAEPPDLQRLPVREVPFREMTDHC
  LPLISPRSFPPSLQVASGESMVLHCRALAEPEPEIYWVTPAGLRLTPAHAGRRYRVYPEG
  TLELRRVTAEEAGLYTCVAQNLVGADTKTVSVVVGRALLQPGRDEGQGLELRVQETHPYH
  ILLSWVTPPNTVSTNLTWSSASSLRGQGATALARLPRGTHSYNITRLLQATEYWACLQVA
  FADAHTQLACVWARTKEATSCHRALGDRPGLIAILALAVLLLAAGLAAHLGTGQPRKGVG
  GRRPLPPAWAFWGWSAPSVRVVSAPLVLPWNPGRKLPRSSEGETLLPPLSQNS
• Tissue Specificity: Overamplified in malignant gliomas.

Molecular Interaction Atlas (MIA) of This DOT

7 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Anaplastic astrocytoma	DISSBE0K	Strong	Altered Expression	[1]
Astrocytoma	DISL3V18	Strong	Biomarker	[2]
Glioblastoma multiforme	DISK8246	Strong	Altered Expression	[1]
Malignant glioma	DISFXKOV	Strong	Biomarker	[1]
Schizophrenia	DISSRV2N	Strong	Genetic Variation	[3]
Asthma	DISW9QNS	Limited	Biomarker	[4]
Neoplasm	DISZKGEW	Limited	Biomarker	[5]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of Leucine-rich repeat neuronal protein 2 (LRRN2).	[6]
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Leucine-rich repeat neuronal protein 2 (LRRN2).	[10]

8 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 neuronal protein 2 (LRRN2).	[7]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Leucine-rich repeat neuronal protein 2 (LRRN2).	[8]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Leucine-rich repeat neuronal protein 2 (LRRN2).	[9]
Triclosan	DMZUR4N	Approved	Triclosan increases the expression of Leucine-rich repeat neuronal protein 2 (LRRN2).	[11]
Marinol	DM70IK5	Approved	Marinol increases the expression of Leucine-rich repeat neuronal protein 2 (LRRN2).	[12]
Cytarabine	DMZD5QR	Approved	Cytarabine decreases the expression of Leucine-rich repeat neuronal protein 2 (LRRN2).	[13]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Leucine-rich repeat neuronal protein 2 (LRRN2).	[14]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Leucine-rich repeat neuronal protein 2 (LRRN2).	[15]

References

• [1] GAC1, a new member of the leucine-rich repeat superfamily on chromosome band 1q32.1, is amplified and overexpressed in malignant gliomas.Oncogene. 1998 Jun 11;16(23):2997-3002. doi: 10.1038/sj.onc.1201828.
• [2] Real-time quantitative PCR analysis of regions involved in gene amplification reveals gene overdose in low-grade astrocytic gliomas.Diagn Mol Pathol. 2005 Dec;14(4):224-9. doi: 10.1097/01.pas.0000177799.58336.1a.
• [3] Pleiotropic Meta-Analysis of Cognition, Education, and Schizophrenia Differentiates Roles of Early Neurodevelopmental and Adult Synaptic Pathways.Am J Hum Genet. 2019 Aug 1;105(2):334-350. doi: 10.1016/j.ajhg.2019.06.012.
• [4] Effect of Antiasthma Simplified Herbal Medicine Intervention on neutrophil predominant airway inflammation in a ragweed sensitized murine asthma model.Ann Allergy Asthma Immunol. 2014 Apr;112(4):339-47.e1-2. doi: 10.1016/j.anai.2014.01.021.
• [5] Marked differences in unilateral isolated retinoblastomas from young and older children studied by comparative genomic hybridization.Hum Genet. 2001 Feb;108(2):98-104. doi: 10.1007/s004390000450.
• [6] Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
• [7] 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.
• [8] Predictive toxicology using systemic biology and liver microfluidic "on chip" approaches: application to acetaminophen injury. Toxicol Appl Pharmacol. 2012 Mar 15;259(3):270-80.
• [9] 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.
• [10] Prenatal arsenic exposure and the epigenome: identifying sites of 5-methylcytosine alterations that predict functional changes in gene expression in newborn cord blood and subsequent birth outcomes. Toxicol Sci. 2015 Jan;143(1):97-106. doi: 10.1093/toxsci/kfu210. Epub 2014 Oct 10.
• [11] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [12] THC exposure of human iPSC neurons impacts genes associated with neuropsychiatric disorders. Transl Psychiatry. 2018 Apr 25;8(1):89. doi: 10.1038/s41398-018-0137-3.
• [13] Cytosine arabinoside induces ectoderm and inhibits mesoderm expression in human embryonic stem cells during multilineage differentiation. Br J Pharmacol. 2011 Apr;162(8):1743-56.
• [14] Identification of a transcriptomic signature of food-relevant genotoxins in human HepaRG hepatocarcinoma cells. Food Chem Toxicol. 2020 Jun;140:111297. doi: 10.1016/j.fct.2020.111297. Epub 2020 Mar 28.
• [15] Bisphenol A and bisphenol S induce distinct transcriptional profiles in differentiating human primary preadipocytes. PLoS One. 2016 Sep 29;11(9):e0163318.