Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTV7F59X)

• DOT Name: Lymphocyte antigen 6 complex locus protein G6c (LY6G6C)
• Gene Name: LY6G6C
• Related Disease:
  Classic Hodgkin lymphoma
  Congestive heart failure
  Gastrointestinal mucositis
  Rheumatoid arthritis
  Type-1 diabetes
  Neoplasm
  Systemic lupus erythematosus
• UniProt ID: LY66C_HUMAN
• Sequence:
  MKALMLLTLSVLLCWVSADIRCHSCYKVPVLGCVDRQSCRLEPGQQCLTTHAYLGKMWVF
  SNLRCGTPEEPCQEAFNQTNRKLGLTYNTTCCNKDNCNSAGPRPTPALGLVFLTSLAGLG
  LWLLH
• Tissue Specificity: Highly expressed at the leading edges of cells, on filopodia.
• 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]
Congestive heart failure	DIS32MEA	Strong	Biomarker	[2]
Gastrointestinal mucositis	DIS140OB	Strong	Biomarker	[3]
Rheumatoid arthritis	DISTSB4J	Strong	Genetic Variation	[4]
Type-1 diabetes	DIS7HLUB	Strong	Genetic Variation	[5]
Neoplasm	DISZKGEW	Limited	Genetic Variation	[6]
Systemic lupus erythematosus	DISI1SZ7	Limited	Genetic Variation	[7]

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 G6c (LY6G6C) affects the response to substance of Fluorouracil.	[12]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Lymphocyte antigen 6 complex locus protein G6c (LY6G6C).	[8]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Lymphocyte antigen 6 complex locus protein G6c (LY6G6C).	[9]
Acetaldehyde	DMJFKG4	Investigative	Acetaldehyde increases the expression of Lymphocyte antigen 6 complex locus protein G6c (LY6G6C).	[11]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Lymphocyte antigen 6 complex locus protein G6c (LY6G6C).	[10]

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] Exercise training upregulates Nrf2 protein in the rostral ventrolateral medulla of mice with heart failure.J Appl Physiol (1985). 2019 Nov 1;127(5):1349-1359. doi: 10.1152/japplphysiol.00469.2019. Epub 2019 Sep 26.
• [3] Oral mucosa tissue gene expression profiling before, during, and after radiation therapy for tonsil squamous cell carcinoma.PLoS One. 2018 Jan 16;13(1):e0190709. doi: 10.1371/journal.pone.0190709. eCollection 2018.
• [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] Expression of the pituitary transcription factor Ptx-1, but not that of the trans-activating factor prop-1, is reduced in human corticotroph adenomas and is associated with decreased alpha-subunit secretion.J Clin Endocrinol Metab. 2000 Jul;85(7):2537-42. doi: 10.1210/jcem.85.7.6683.
• [7] GWAS identifies novel SLE susceptibility genes and explains the association of the HLA region.Genes Immun. 2014 Sep;15(6):347-54. doi: 10.1038/gene.2014.23. Epub 2014 May 29.
• [8] Predictive toxicology using systemic biology and liver microfluidic "on chip" approaches: application to acetaminophen injury. Toxicol Appl Pharmacol. 2012 Mar 15;259(3):270-80.
• [9] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [10] 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.
• [11] Transcriptome profile analysis of saturated aliphatic aldehydes reveals carbon number-specific molecules involved in pulmonary toxicity. Chem Res Toxicol. 2014 Aug 18;27(8):1362-70.
• [12] 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.