Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT3N88Q1)

• DOT Name: Leucine-rich repeat and immunoglobulin-like domain-containing nogo receptor-interacting protein 2 (LINGO2)
• Synonyms: Leucine-rich repeat neuronal protein 3; Leucine-rich repeat neuronal protein 6C
• Gene Name: LINGO2
• Related Disease:
  Autism
  Colitis
  Essential tremor
  Helminth infection
  Liver cancer
  Non-insulin dependent diabetes
  Obesity
  Parkinson disease
  Acute myelogenous leukaemia
  Bladder cancer
  Breast cancer
  Breast carcinoma
  Esophageal squamous cell carcinoma
  Gastric cancer
  Lung cancer
  Lung carcinoma
  Megalencephaly
  Stomach cancer
  Urinary bladder cancer
  Urinary bladder neoplasm
• UniProt ID: LIGO2_HUMAN
• Pfam ID: PF07679 ; PF00560 ; PF13855
• Sequence:
  MLHTAISCWQPFLGLAVVLIFMGSTIGCPARCECSAQNKSVSCHRRRLIAIPEGIPIETK
  ILDLSKNRLKSVNPEEFISYPLLEEIDLSDNIIANVEPGAFNNLFNLRSLRLKGNRLKLV
  PLGVFTGLSNLTKLDISENKIVILLDYMFQDLHNLKSLEVGDNDLVYISHRAFSGLLSLE
  QLTLEKCNLTAVPTEALSHLRSLISLHLKHLNINNMPVYAFKRLFHLKHLEIDYWPLLDM
  MPANSLYGLNLTSLSVTNTNLSTVPFLAFKHLVYLTHLNLSYNPISTIEAGMFSDLIRLQ
  ELHIVGAQLRTIEPHSFQGLRFLRVLNVSQNLLETLEENVFSSPRALEVLSINNNPLACD
  CRLLWILQRQPTLQFGGQQPMCAGPDTIRERSFKDFHSTALSFYFTCKKPKIREKKLQHL
  LVDEGQTVQLECSADGDPQPVISWVTPRRRFITTKSNGRATVLGDGTLEIRFAQDQDSGM
  YVCIASNAAGNDTFTASLTVKGFASDRFLYANRTPMYMTDSNDTISNGTNANTFSLDLKT
  ILVSTAMGCFTFLGVVLFCFLLLFVWSRGKGKHKNSIDLEYVPRKNNGAVVEGEVAGPRR
  FNMKMI

Molecular Interaction Atlas (MIA) of This DOT

20 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Autism	DISV4V1Z	Strong	Genetic Variation	[1]
Colitis	DISAF7DD	Strong	Altered Expression	[2]
Essential tremor	DIS7GBKQ	Strong	Biomarker	[3]
Helminth infection	DIS7CGKY	Strong	Biomarker	[2]
Liver cancer	DISDE4BI	Strong	Biomarker	[4]
Non-insulin dependent diabetes	DISK1O5Z	Strong	Genetic Variation	[5]
Obesity	DIS47Y1K	Strong	Genetic Variation	[5]
Parkinson disease	DISQVHKL	Strong	Genetic Variation	[6]
Acute myelogenous leukaemia	DISCSPTN	moderate	Genetic Variation	[7]
Bladder cancer	DISUHNM0	Limited	Genetic Variation	[8]
Breast cancer	DIS7DPX1	Limited	Genetic Variation	[8]
Breast carcinoma	DIS2UE88	Limited	Genetic Variation	[8]
Esophageal squamous cell carcinoma	DIS5N2GV	Limited	Genetic Variation	[8]
Gastric cancer	DISXGOUK	Limited	Genetic Variation	[8]
Lung cancer	DISCM4YA	Limited	Genetic Variation	[8]
Lung carcinoma	DISTR26C	Limited	Genetic Variation	[8]
Megalencephaly	DISYW5SV	Limited	Genetic Variation	[9]
Stomach cancer	DISKIJSX	Limited	Genetic Variation	[8]
Urinary bladder cancer	DISDV4T7	Limited	Genetic Variation	[8]
Urinary bladder neoplasm	DIS7HACE	Limited	Genetic Variation	[8]

This DOT Affected the Drug Response of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Methamphetamine	DMPM4SK	Approved	Leucine-rich repeat and immunoglobulin-like domain-containing nogo receptor-interacting protein 2 (LINGO2) affects the response to substance of Methamphetamine.	[17]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the methylation of Leucine-rich repeat and immunoglobulin-like domain-containing nogo receptor-interacting protein 2 (LINGO2).	[10]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Leucine-rich repeat and immunoglobulin-like domain-containing nogo receptor-interacting protein 2 (LINGO2).	[14]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the methylation of Leucine-rich repeat and immunoglobulin-like domain-containing nogo receptor-interacting protein 2 (LINGO2).	[15]

4 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 and immunoglobulin-like domain-containing nogo receptor-interacting protein 2 (LINGO2).	[11]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Leucine-rich repeat and immunoglobulin-like domain-containing nogo receptor-interacting protein 2 (LINGO2).	[12]
Panobinostat	DM58WKG	Approved	Panobinostat increases the expression of Leucine-rich repeat and immunoglobulin-like domain-containing nogo receptor-interacting protein 2 (LINGO2).	[13]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Leucine-rich repeat and immunoglobulin-like domain-containing nogo receptor-interacting protein 2 (LINGO2).	[16]

References

• [1] Modeling prior information of common genetic variants improves gene discovery for neuroticism.Hum Mol Genet. 2017 Nov 15;26(22):4530-4539. doi: 10.1093/hmg/ddx340.
• [2] TFF3 interacts with LINGO2 to regulate EGFR activation for protection against colitis and gastrointestinal helminths.Nat Commun. 2019 Sep 27;10(1):4408. doi: 10.1038/s41467-019-12315-1.
• [3] Increased LINGO1 in the cerebellum of essential tremor patients.Mov Disord. 2014 Nov;29(13):1637-47. doi: 10.1002/mds.25819. Epub 2014 Feb 14.
• [4] Multiple genes exhibit phenobarbital-induced constitutive active/androstane receptor-mediated DNA methylation changes during liver tumorigenesis and in liver tumors.Toxicol Sci. 2009 Apr;108(2):273-89. doi: 10.1093/toxsci/kfp031. Epub 2009 Feb 20.
• [5] A genetic variant in LINGO2 contributes to the risk of gestational diabetes mellitus in a Chinese population.J Cell Physiol. 2019 May;234(5):7012-7018. doi: 10.1002/jcp.27454. Epub 2018 Nov 13.
• [6] Analysis and meta-analysis of five polymorphisms of the LINGO1 and LINGO2 genes in Parkinson's disease and multiple system atrophy in a Chinese population.J Neurol. 2015 Nov;262(11):2478-83. doi: 10.1007/s00415-015-7870-9. Epub 2015 Aug 8.
• [7] Genome-wide haplotype association study identify the FGFR2 gene as a risk gene for acute myeloid leukemia.Oncotarget. 2017 Jan 31;8(5):7891-7899. doi: 10.18632/oncotarget.13631.
• [8] Genetic polymorphisms in the 9p21 region associated with risk of multiple cancers.Carcinogenesis. 2014 Dec;35(12):2698-705. doi: 10.1093/carcin/bgu203. Epub 2014 Sep 19.
• [9] Haploinsufficiency of the miR-873/miR-876 microRNA cluster is associated with craniofacial abnormalities.Gene. 2015 Apr 25;561(1):95-100. doi: 10.1016/j.gene.2015.02.018. Epub 2015 Feb 11.
• [10] 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.
• [11] Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
• [12] Temozolomide induces activation of Wnt/-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278. doi: 10.1007/s10565-019-09502-7. Epub 2019 Nov 22.
• [13] A transcriptome-based classifier to identify developmental toxicants by stem cell testing: design, validation and optimization for histone deacetylase inhibitors. Arch Toxicol. 2015 Sep;89(9):1599-618.
• [14] 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.
• [15] 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.
• [16] 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.
• [17] Genome-wide association for methamphetamine dependence: convergent results from 2 samples. Arch Gen Psychiatry. 2008 Mar;65(3):345-55. doi: 10.1001/archpsyc.65.3.345.