Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT0CZ85H)

• DOT Name: Leucine-rich repeat LGI family member 3 (LGI3)
• Synonyms: LGI1-like protein 4; Leucine-rich glioma-inactivated protein 3
• Gene Name: LGI3
• Related Disease:
  Advanced cancer
  Glioma
  Lung cancer
  Lung carcinoma
  Non-small-cell lung cancer
  Vitiligo
  Intellectual developmental disorder with muscle tone abnormalities and distal skeletal defects
• UniProt ID: LGI3_HUMAN
• Pfam ID: PF03736 ; PF13855
• Sequence:
  MAGLRARGGPGPGLLALSALGFCLMLQVSAKRPPKTPPCPPSCSCTRDTAFCVDSKAVPR
  NLPSEVISLTLVNAAFSEIQDGAFSHLPLLQFLLLNSNKFTLIGDNAFTGLSHLQYLFIE
  NNDIWALSKFTFRGLKSLTHLSLANNNLQTLPRDIFRPLDILNDLDLRGNSLNCDCKVKW
  LVEWLAHTNTTVAPIYCASPPRFQEHKVQDLPLREFDCITTDFVLYQTLAFPAVSAEPFL
  YSSDLYLALAQPGVSACTILKWDYVERQLRDYDRIPAPSAVHCKPMVVDSQLYVVVAQLF
  GGSYIYHWDPNTTRFTRLQDIDPQRVRKPNDLEAFRIDGDWYFAVADSSKAGATSLYRWH
  QNGFYSHQALHPWHRDTDLEFVDGEGKPRLIVSSSSQAPVIYQWSRTQKQFVAQGEVTQV
  PDAQAVKHFRAGRDSYLCLSRYIGDSKILRWEGTRFSEVQALPSRGSLALQPFLVGGRRY
  LALGSDFSFTQIYQWDEGRQKFVRFQELAVQAPRAFCYMPAGDAQLLLAPSFKGQTLVYR
  HIVVDLSA
• Function: May participate in the regulation of neuronal exocytosis.
• Tissue Specificity: Widely expressed, with highest levels in brain and lung.
• Reactome Pathway: LGI-ADAM interactions (R-HSA-5682910)

Molecular Interaction Atlas (MIA) of This DOT

7 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Advanced cancer	DISAT1Z9	Strong	Altered Expression	[1]
Glioma	DIS5RPEH	Strong	Biomarker	[2]
Lung cancer	DISCM4YA	Strong	Altered Expression	[1]
Lung carcinoma	DISTR26C	Strong	Altered Expression	[1]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Genetic Variation	[3]
Vitiligo	DISR05SL	Strong	Altered Expression	[4]
Intellectual developmental disorder with muscle tone abnormalities and distal skeletal defects	DISO0SJ7	Limited	Unknown	[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 LGI family member 3 (LGI3).	[6]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Leucine-rich repeat LGI family member 3 (LGI3).	[9]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of Leucine-rich repeat LGI family member 3 (LGI3).	[7]
Methotrexate	DM2TEOL	Approved	Methotrexate increases the expression of Leucine-rich repeat LGI family member 3 (LGI3).	[8]

References

• [1] Leucine-rich glioma inactivated 3: Integrative analyses reveal its potential prognostic role in cancer.Mol Med Rep. 2018 Mar;17(3):3993-4002. doi: 10.3892/mmr.2017.8279. Epub 2017 Dec 14.
• [2] Leucine-rich glioma inactivated 3: integrative analyses support its prognostic role in glioma.Onco Targets Ther. 2017 May 24;10:2721-2728. doi: 10.2147/OTT.S138912. eCollection 2017.
• [3] Leucine rich repeat LGI family member 3: Integrative analyses reveal its prognostic association with non-small cell lung cancer.Oncol Lett. 2019 Sep;18(3):3388-3398. doi: 10.3892/ol.2019.10648. Epub 2019 Jul 22.
• [4] Leucine-rich glioma inactivated 3: a novel keratinocyte-derived melanogenic cytokine in vitiligo patients.An Bras Dermatol. 2019 Oct 17;94(4):434-441. doi: 10.1590/abd1806-4841.20198250. eCollection 2019.
• [5] Next Generation Sequencing and Genome-Wide Genotyping Identify the Genetic Causes of Intellectual Disability in Ten Consanguineous Families from Jordan. Tohoku J Exp Med. 2017 Dec;243(4):297-309. doi: 10.1620/tjem.243.297.
• [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] Essential role of cell cycle regulatory genes p21 and p27 expression in inhibition of breast cancer cells by arsenic trioxide. Med Oncol. 2011 Dec;28(4):1225-54.
• [8] Global molecular effects of tocilizumab therapy in rheumatoid arthritis synovium. Arthritis Rheumatol. 2014 Jan;66(1):15-23.
• [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.