Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTG75QOC)

• DOT Name: Lymphocyte antigen 6 complex locus protein G6d (LY6G6D)
• Synonyms: Protein Ly6-D; Megakaryocyte-enhanced gene transcript 1 protein
• Gene Name: LY6G6D
• Related Disease:
  Classic Hodgkin lymphoma
  B-cell neoplasm
  Clear cell renal carcinoma
  Renal cell carcinoma
  Rheumatoid arthritis
  Type-1 diabetes
  Colorectal carcinoma
• UniProt ID: LY66D_HUMAN
• PDB ID: 7S4G
• Sequence:
  MKPQFVGILLSSLLGAALGNRMRCYNCGGSPSSSCKEAVTTCGEGRPQPGLEQIKLPGNP
  PVTLIHQHPACVAAHHCNQVETESVGDVTYPAHRDCYLGDLCNSAVASHVAPAGILAAAA
  TALTCLLPGLWSG
• Tissue Specificity: Expressed in the adult lung, and in fetal liver, lung, kidney, brain and spleen.
• Reactome Pathway: Post-translational modification (R-HSA-163125)

Molecular Interaction Atlas (MIA) of This DOT

7 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Classic Hodgkin lymphoma	DISV1LU6	Definitive	Genetic Variation	[1]
B-cell neoplasm	DISVY326	Strong	Biomarker	[2]
Clear cell renal carcinoma	DISBXRFJ	Strong	Biomarker	[3]
Renal cell carcinoma	DISQZ2X8	Strong	Biomarker	[3]
Rheumatoid arthritis	DISTSB4J	Strong	Genetic Variation	[4]
Type-1 diabetes	DIS7HLUB	Strong	Genetic Variation	[5]
Colorectal carcinoma	DIS5PYL0	Limited	Altered Expression	[6]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Fluorouracil	DMUM7HZ	Approved	Lymphocyte antigen 6 complex locus protein G6d (LY6G6D) affects the response to substance of Fluorouracil.	[11]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Triclosan	DMZUR4N	Approved	Triclosan increases the expression of Lymphocyte antigen 6 complex locus protein G6d (LY6G6D).	[7]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN decreases the expression of Lymphocyte antigen 6 complex locus protein G6d (LY6G6D).	[9]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Lymphocyte antigen 6 complex locus protein G6d (LY6G6D).	[10]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Lymphocyte antigen 6 complex locus protein G6d (LY6G6D).	[8]

References

• [1] Variation at 3p24.1 and 6q23.3 influences the risk of Hodgkin's lymphoma.Nat Commun. 2013;4:2549. doi: 10.1038/ncomms3549.
• [2] NG25, a novel inhibitor of TAK1, suppresses KRAS-mutant colorectal cancer growth in vitro and in vivo.Apoptosis. 2019 Feb;24(1-2):83-94. doi: 10.1007/s10495-018-1498-z.
• [3] Identification of TGF--activated kinase 1 as a possible novel target for renal cell carcinoma intervention.Biochem Biophys Res Commun. 2014 Oct 10;453(1):106-11. doi: 10.1016/j.bbrc.2014.09.070. Epub 2014 Sep 26.
• [4] A genome-wide association study suggests contrasting associations in ACPA-positive versus ACPA-negative rheumatoid arthritis.Ann Rheum Dis. 2011 Feb;70(2):259-65. doi: 10.1136/ard.2009.126821. Epub 2010 Dec 14.
• [5] A genome-wide association study identifies KIAA0350 as a type 1 diabetes gene.Nature. 2007 Aug 2;448(7153):591-4. doi: 10.1038/nature06010. Epub 2007 Jul 15.
• [6] JAK/Stat5-mediated subtype-specific lymphocyte antigen 6 complex, locus G6D (LY6G6D) expression drives mismatch repair proficient colorectal cancer.J Exp Clin Cancer Res. 2019 Jan 22;38(1):28. doi: 10.1186/s13046-018-1019-5.
• [7] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [8] 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.
• [9] Chemical stresses fail to mimic the unfolded protein response resulting from luminal load with unfolded polypeptides. J Biol Chem. 2018 Apr 13;293(15):5600-5612.
• [10] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [11] Gene expression profiling of 30 cancer cell lines predicts resistance towards 11 anticancer drugs at clinically achieved concentrations. Int J Cancer. 2006 Apr 1;118(7):1699-712. doi: 10.1002/ijc.21570.