Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTFJ2ZSG)

• DOT Name: Leucine-rich repeat LGI family member 2 (LGI2)
• Synonyms: LGI1-like protein 2; Leucine-rich glioma-inactivated protein 2
• Gene Name: LGI2
• Related Disease:
  Listeriosis
  Focal epilepsy
  Epilepsy
• UniProt ID: LGI2_HUMAN
• Pfam ID: PF03736 ; PF13855
• Sequence:
  MALRRGGCGALGLLLLLLGAACLIPRSAQVRRLARCPATCSCTKESIICVGSSWVPRIVP
  GDISSLSLVNGTFSEIKDRMFSHLPSLQLLLLNSNSFTIIRDDAFAGLFHLEYLFIEGNK
  IETISRNAFRGLRDLTHLSLANNHIKALPRDVFSDLDSLIELDLRGNKFECDCKAKWLYL
  WLKMTNSTVSDVLCIGPPEYQEKKLNDVTSFDYECTTTDFVVHQTLPYQSVSVDTFNSKN
  DVYVAIAQPSMENCMVLEWDHIEMNFRSYDNITGQSIVGCKAILIDDQVFVVVAQLFGGS
  HIYKYDESWTKFVKFQDIEVSRISKPNDIELFQIDDETFFVIADSSKAGLSTVYKWNSKG
  FYSYQSLHEWFRDTDAEFVDIDGKSHLILSSRSQVPIILQWNKSSKKFVPHGDIPNMEDV
  LAVKSFRMQNTLYLSLTRFIGDSRVMRWNSKQFVEIQALPSRGAMTLQPFSFKDNHYLAL
  GSDYTFSQIYQWDKEKQLFKKFKEIYVQAPRSFTAVSTDRRDFFFASSFKGKTKIFEHII
  VDLSL
• Function: Required for the development of soma-targeting inhibitory GABAergic synapses made by parvalbumin-positive basket cells.
• Tissue Specificity: Brain, heart and placenta.
• Reactome Pathway: LGI-ADAM interactions (R-HSA-5682910)

Molecular Interaction Atlas (MIA) of This DOT

3 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Listeriosis	DISKMQBM	Strong	Biomarker	[1]
Focal epilepsy	DIS4LY5L	Disputed	Biomarker	[2]
Epilepsy	DISBB28L	Limited	Genetic Variation	[3]

5 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 Leucine-rich repeat LGI family member 2 (LGI2).	[4]
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of Leucine-rich repeat LGI family member 2 (LGI2).	[5]
Zoledronate	DMIXC7G	Approved	Zoledronate decreases the expression of Leucine-rich repeat LGI family member 2 (LGI2).	[6]
Folic acid	DMEMBJC	Approved	Folic acid increases the expression of Leucine-rich repeat LGI family member 2 (LGI2).	[8]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Leucine-rich repeat LGI family member 2 (LGI2).	[10]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Fulvestrant	DM0YZC6	Approved	Fulvestrant decreases the methylation of Leucine-rich repeat LGI family member 2 (LGI2).	[7]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Leucine-rich repeat LGI family member 2 (LGI2).	[9]

References

• [1] The Arsenic Resistance-Associated Listeria Genomic Island LGI2 Exhibits Sequence and Integration Site Diversity and a Propensity for Three Listeria monocytogenes Clones with Enhanced Virulence.Appl Environ Microbiol. 2017 Oct 17;83(21):e01189-17. doi: 10.1128/AEM.01189-17. Print 2017 Nov 1.
• [2] LGI2 truncation causes a remitting focal epilepsy in dogs.PLoS Genet. 2011 Jul;7(7):e1002194. doi: 10.1371/journal.pgen.1002194. Epub 2011 Jul 28.
• [3] LGI Proteins and Epilepsy in Human and Animals.J Vet Intern Med. 2015 Jul-Aug;29(4):997-1005. doi: 10.1111/jvim.12610. Epub 2015 Jun 1.
• [4] 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.
• [5] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [6] Interleukin-19 as a translational indicator of renal injury. Arch Toxicol. 2015 Jan;89(1):101-6.
• [7] 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.
• [8] Folic acid supplementation dysregulates gene expression in lymphoblastoid cells--implications in nutrition. Biochem Biophys Res Commun. 2011 Sep 9;412(4):688-92. doi: 10.1016/j.bbrc.2011.08.027. Epub 2011 Aug 16.
• [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] Cell-based two-dimensional morphological assessment system to predict cancer drug-induced cardiotoxicity using human induced pluripotent stem cell-derived cardiomyocytes. Toxicol Appl Pharmacol. 2019 Nov 15;383:114761. doi: 10.1016/j.taap.2019.114761. Epub 2019 Sep 15.