Details of Drug Off-Target (DOT)

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

• DOT Name: Leucine-rich repeats and immunoglobulin-like domains protein 2 (LRIG2)
• Synonyms: LIG-2
• Gene Name: LRIG2
• Related Disease:
  Bladder disease
  Brain neoplasm
  Glioma
  Hepatocellular carcinoma
  Neoplasm
  Non-small-cell lung cancer
  Peripheral neuropathy
  Urofacial syndrome 2
  Urofacial syndrome type 1
  Advanced cancer
  Ochoa syndrome
  Adult glioblastoma
  Endometrium adenocarcinoma
  Endometrium neoplasm
  Glioblastoma multiforme
  Skin carcinoma
  Squamous cell carcinoma
• UniProt ID: LRIG2_HUMAN
• Pfam ID: PF07679 ; PF13927 ; PF13855 ; PF01463
• Sequence:
  MAPAPLGVPEEQLLGCRSRVLSRLLFIAQTALLLLPAAGAGLCPAPCSCRIPLLDCSRRK
  LPAPSWRALSGLLPPDTAILDFSHNRLSNWNISLESQTLQEVKMNYNELTEIPYFGEPTS
  NITLLSLVHNIIPEINAQALQFYPALESLDLSSNIISEIKTSSFPRMQLKYLNLSNNRIT
  TLEAGCFDNLSSSLLVVKLNRNRMSMIPPKIFKLPHLQFLELKRNRIKIVEGLTFQGLDS
  LRSLKMQRNGISKLKDGAFFGLNNMEELELEHNNLTRVNKGWLYGLRMLQQLYVSQNAIE
  RISPDAWEFCQRLSELDLSYNQLTRLDESAFVGLSLLERLNLGDNRVTHIADGVFRFLSN
  LQTLDLRNNEISWAIEDASEAFAGLTSLTKLILQGNQIKSITKKAFIGLESLEHLDLNNN
  AIMSIQENAFSQTHLKELILNTSSLLCDCHLKWLLQWLVDNNFQHSVNVSCAHPEWLAGQ
  SILNVDLKDFVCDDFLKPQIRTHPETIIALRGMNVTLTCTAVSSSDSPMSTVWRKDSEIL
  YDVDTENFVRYWQQAGEALEYTSILHLFNVNFTDEGKYQCIVTNHFGSNYSQKAKLTVNE
  MPSFLKTPMDLTIRTGAMARLECAAEGHPAPQISWQKDGGTDFPAARERRMHVMPEDDVF
  FIANVKIEDMGIYSCMAQNTAGGLSANASLTVLETPSFIRPLEDKTVTRGETAVLQCIAG
  GSPAPRLNWTKDDGPLLVTERHFFAAANQLLIIVDAGLEDAGKYTCIMSNTLGTERGHIY
  LNVISSPNCDSSQSSIGHEDDGWTTVGIVIIVVVCCVVGTSLIWVIVIYHMRRKNEDYSI
  TNTEELNLPADIPSYLSSQGTLSEPQEGYSNSEAGSHQQLMPPANGYIHKGTDGGTGTRV
  ICSDCYDNANIYSRTREYCPYTYIAEEDVLDQTLSSLMVQMPKETYLVHPPQDTTALESL
  IPSANREPSAFPTNHERISEKKLPSTQMSGETLQRPVWNINRELGLPHPPFSQQPVHESP
  QLHQNEGLAGREPDCSASSMSCHRLQDHAFDFSRTRNIQDGSEGT
• Tissue Specificity: Detected in all tissues analyzed.
• KEGG Pathway: Axon guidance (hsa04360)

Molecular Interaction Atlas (MIA) of This DOT

17 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Bladder disease	DISTVIQI	Strong	Genetic Variation	[1]
Brain neoplasm	DISY3EKS	Strong	Biomarker	[2]
Glioma	DIS5RPEH	Strong	Altered Expression	[3]
Hepatocellular carcinoma	DIS0J828	Strong	Biomarker	[4]
Neoplasm	DISZKGEW	Strong	Altered Expression	[5]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Biomarker	[6]
Peripheral neuropathy	DIS7KN5G	Strong	Biomarker	[7]
Urofacial syndrome 2	DISQPHGF	Strong	Autosomal recessive	[1]
Urofacial syndrome type 1	DISDUYJH	Strong	Autosomal recessive	[8]
Advanced cancer	DISAT1Z9	moderate	Biomarker	[5]
Ochoa syndrome	DIS1MDEZ	Supportive	Autosomal recessive	[1]
Adult glioblastoma	DISVP4LU	Disputed	Biomarker	[9]
Endometrium adenocarcinoma	DISY6744	Disputed	Biomarker	[5]
Endometrium neoplasm	DIS6OS2L	Disputed	Biomarker	[5]
Glioblastoma multiforme	DISK8246	Disputed	Biomarker	[9]
Skin carcinoma	DISUZREN	Limited	Biomarker	[10]
Squamous cell carcinoma	DISQVIFL	Limited	Biomarker	[10]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of Leucine-rich repeats and immunoglobulin-like domains protein 2 (LRIG2).	[11]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Leucine-rich repeats and immunoglobulin-like domains protein 2 (LRIG2).	[12]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide increases the expression of Leucine-rich repeats and immunoglobulin-like domains protein 2 (LRIG2).	[13]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Leucine-rich repeats and immunoglobulin-like domains protein 2 (LRIG2).	[14]

References

• [1] LRIG2 mutations cause urofacial syndrome. Am J Hum Genet. 2013 Feb 7;92(2):259-64. doi: 10.1016/j.ajhg.2012.12.002. Epub 2013 Jan 11.
• [2] Lrig2-deficient mice are protected against PDGFB-induced glioma.PLoS One. 2013 Sep 4;8(9):e73635. doi: 10.1371/journal.pone.0073635. eCollection 2013.
• [3] Downregulation of LRIG2 expression inhibits angiogenesis of glioma via EGFR/VEGF-A pathway.Oncol Lett. 2017 Oct;14(4):4021-4028. doi: 10.3892/ol.2017.6671. Epub 2017 Jul 26.
• [4] Long non-coding RNA LINC00461/miR-149-5p/LRIG2 axis regulates hepatocellular carcinoma progression.Biochem Biophys Res Commun. 2019 Apr 30;512(2):176-181. doi: 10.1016/j.bbrc.2019.03.049. Epub 2019 Mar 14.
• [5] LRIG2 is a growth suppressor of Hec-1A and Ishikawa endometrial adenocarcinoma cells by regulating PI3K/AKT- and EGFR-mediated apoptosis and cell-cycle.Oncogenesis. 2018 Jan 23;7(1):3. doi: 10.1038/s41389-017-0019-1.
• [6] LncRNA-PCAT-1 promotes non-small cell lung cancer progression by regulating miR-149-5p/LRIG2 axis.J Cell Biochem. 2019 May;120(5):7725-7733. doi: 10.1002/jcb.28046. Epub 2018 Dec 19.
• [7] Lrig2 and Hpse2, mutated in urofacial syndrome, pattern nerves in the urinary bladder.Kidney Int. 2019 May;95(5):1138-1152. doi: 10.1016/j.kint.2018.11.040. Epub 2019 Mar 8.
• [8] Flexible and scalable diagnostic filtering of genomic variants using G2P with Ensembl VEP. Nat Commun. 2019 May 30;10(1):2373. doi: 10.1038/s41467-019-10016-3.
• [9] [Corrigendum] LRIG2 promotes the proliferation and cell cycle progression of glioblastoma cells in vitro and in vivo through enhancing PDGFR signaling.Int J Oncol. 2019 Jun;54(6):2257. doi: 10.3892/ijo.2019.4769. Epub 2019 Apr 2.
• [10] The transmembrane protein LRIG2 increases tumor progression in skin carcinogenesis.Mol Oncol. 2019 Nov;13(11):2476-2492. doi: 10.1002/1878-0261.12579. Epub 2019 Oct 21.
• [11] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [12] Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
• [13] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [14] Gene expression changes in primary human nasal epithelial cells exposed to formaldehyde in vitro. Toxicol Lett. 2010 Oct 5;198(2):289-95.