Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT6MMO6L)

• DOT Name: Leucine-rich repeat neuronal protein 1 (LRRN1)
• Synonyms: Neuronal leucine-rich repeat protein 1; NLRR-1
• Gene Name: LRRN1
• Related Disease:
  Narcolepsy
  Neuroblastoma
  Obesity
  Gastric cancer
  Neoplasm
  Stomach cancer
• UniProt ID: LRRN1_HUMAN
• Pfam ID: PF07679 ; PF13855
• Sequence:
  MARMSFVIAACQLVLGLLMTSLTESSIQNSECPQLCVCEIRPWFTPQSTYREATTVDCND
  LRLTRIPSNLSSDTQVLLLQSNNIAKTVDELQQLFNLTELDFSQNNFTNIKEVGLANLTQ
  LTTLHLEENQITEMTDYCLQDLSNLQELYINHNQISTISAHAFAGLKNLLRLHLNSNKLK
  VIDSRWFDSTPNLEILMIGENPVIGILDMNFKPLANLRSLVLAGMYLTDIPGNALVGLDS
  LESLSFYDNKLVKVPQLALQKVPNLKFLDLNKNPIHKIQEGDFKNMLRLKELGINNMGEL
  VSVDRYALDNLPELTKLEATNNPKLSYIHRLAFRSVPALESLMLNNNALNAIYQKTVESL
  PNLREISIHSNPLRCDCVIHWINSNKTNIRFMEPLSMFCAMPPEYKGHQVKEVLIQDSSE
  QCLPMISHDSFPNRLNVDIGTTVFLDCRAMAEPEPEIYWVTPIGNKITVETLSDKYKLSS
  EGTLEISNIQIEDSGRYTCVAQNVQGADTRVATIKVNGTLLDGTQVLKIYVKQTESHSIL
  VSWKVNSNVMTSNLKWSSATMKIDNPHITYTARVPVDVHEYNLTHLQPSTDYEVCLTVSN
  IHQQTQKSCVNVTTKNAAFAVDISDQETSTALAAVMGSMFAVISLASIAVYFAKRFKRKN
  YHHSLKKYMQKTSSIPLNELYPPLINLWEGDSEKDKDGSADTKPTQVDTSRSYYMW

Molecular Interaction Atlas (MIA) of This DOT

6 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Narcolepsy	DISLCNLI	Definitive	Genetic Variation	[1]
Neuroblastoma	DISVZBI4	Definitive	Biomarker	[2]
Obesity	DIS47Y1K	Strong	Biomarker	[3]
Gastric cancer	DISXGOUK	Disputed	Biomarker	[4]
Neoplasm	DISZKGEW	Disputed	Altered Expression	[5]
Stomach cancer	DISKIJSX	Disputed	Biomarker	[4]

4 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 1 (LRRN1).	[6]
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Leucine-rich repeat neuronal protein 1 (LRRN1).	[8]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of Leucine-rich repeat neuronal protein 1 (LRRN1).	[11]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Leucine-rich repeat neuronal protein 1 (LRRN1).	[12]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Leucine-rich repeat neuronal protein 1 (LRRN1).	[7]
Calcitriol	DM8ZVJ7	Approved	Calcitriol decreases the expression of Leucine-rich repeat neuronal protein 1 (LRRN1).	[9]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of Leucine-rich repeat neuronal protein 1 (LRRN1).	[9]
Triclosan	DMZUR4N	Approved	Triclosan increases the expression of Leucine-rich repeat neuronal protein 1 (LRRN1).	[10]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Leucine-rich repeat neuronal protein 1 (LRRN1).	[13]

References

• [1] Genome-wide association database developed in the Japanese Integrated Database Project.J Hum Genet. 2009 Sep;54(9):543-6. doi: 10.1038/jhg.2009.68. Epub 2009 Jul 24.
• [2] NLRR1 enhances EGF-mediated MYCN induction in neuroblastoma and accelerates tumor growth in vivo.Cancer Res. 2012 Sep 1;72(17):4587-96. doi: 10.1158/0008-5472.CAN-12-0943. Epub 2012 Jul 19.
• [3] Obesity-insulin targeted genes in the 3p26-25 region in human studies and LG/J and SM/J mice.Metabolism. 2012 Aug;61(8):1129-41. doi: 10.1016/j.metabol.2012.01.008. Epub 2012 Mar 3.
• [4] Leucine-rich repeat neuronal protein-1 suppresses apoptosis of gastric cancer cells through regulation of Fas/FasL.Cancer Sci. 2019 Jul;110(7):2145-2155. doi: 10.1111/cas.14042. Epub 2019 Jun 10.
• [5] N-MYC promotes cell proliferation through a direct transactivation of neuronal leucine-rich repeat protein-1 (NLRR1) gene in neuroblastoma.Oncogene. 2008 Oct 9;27(46):6075-82. doi: 10.1038/onc.2008.200. Epub 2008 Jun 30.
• [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] Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
• [8] 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.
• [9] Effects of 1alpha,25 dihydroxyvitamin D3 and testosterone on miRNA and mRNA expression in LNCaP cells. Mol Cancer. 2011 May 18;10:58.
• [10] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [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.
• [12] 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.
• [13] From transient transcriptome responses to disturbed neurodevelopment: role of histone acetylation and methylation as epigenetic switch between reversible and irreversible drug effects. Arch Toxicol. 2014 Jul;88(7):1451-68.