Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTQR4I2N)

• DOT Name: Transmembrane 6 superfamily member 1 (TM6SF1)
• Gene Name: TM6SF1
• Related Disease:
  Breast cancer
  Breast carcinoma
• UniProt ID: TM6S1_HUMAN
• Pfam ID: PF05241
• Sequence:
  MSASAATGVFVLSLSAIPVTYVFNHLAAQHDSWTIVGVAALILFLVALLARVLVKRKPPR
  DPLFYVYAVFGFTSVVNLIIGLEQDGIIDGFMTHYLREGEPYLNTAYGHMICYWDGSAHY
  LMYLVMVAAIAWEETYRTIGLYWVGSIIMSVVVFVPGNIVGKYGTRICPAFFLSIPYTCL
  PVWAGFRIYNQPSENYNYPSKVIQEAQAKDLLRRPFDLMLVVCLLLATGFCLFRGLIALD
  CPSELCRLYTQFQEPYLKDPAAYPKIQMLAYMFYSVPYFVTALYGLVVPGCSWMPDITLI
  HAGGLAQAQFSHIGASLHARTAYVYRVPEEAKILFLALNIAYGVLPQLLAYRCIYKPEFF
  IKTKAEEKVE
• Function: May function as sterol isomerase.
• Tissue Specificity: Enhanced expression in spleen, testis and peripheral blood leukocytes.

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Breast cancer	DIS7DPX1	Limited	Biomarker	[1]
Breast carcinoma	DIS2UE88	Limited	Biomarker	[1]

3 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 Transmembrane 6 superfamily member 1 (TM6SF1).	[2]
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Transmembrane 6 superfamily member 1 (TM6SF1).	[5]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Transmembrane 6 superfamily member 1 (TM6SF1).	[12]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Transmembrane 6 superfamily member 1 (TM6SF1).	[3]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Transmembrane 6 superfamily member 1 (TM6SF1).	[4]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of Transmembrane 6 superfamily member 1 (TM6SF1).	[6]
Progesterone	DMUY35B	Approved	Progesterone increases the expression of Transmembrane 6 superfamily member 1 (TM6SF1).	[7]
Dasatinib	DMJV2EK	Approved	Dasatinib increases the expression of Transmembrane 6 superfamily member 1 (TM6SF1).	[8]
Cyclophosphamide	DM4O2Z7	Approved	Cyclophosphamide decreases the expression of Transmembrane 6 superfamily member 1 (TM6SF1).	[6]
Lindane	DMB8CNL	Approved	Lindane increases the expression of Transmembrane 6 superfamily member 1 (TM6SF1).	[6]
Racecadotril	DMFOTZ7	Approved	Racecadotril increases the expression of Transmembrane 6 superfamily member 1 (TM6SF1).	[9]
Resveratrol	DM3RWXL	Phase 3	Resveratrol decreases the expression of Transmembrane 6 superfamily member 1 (TM6SF1).	[10]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol decreases the expression of Transmembrane 6 superfamily member 1 (TM6SF1).	[11]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Transmembrane 6 superfamily member 1 (TM6SF1).	[13]
Coumestrol	DM40TBU	Investigative	Coumestrol decreases the expression of Transmembrane 6 superfamily member 1 (TM6SF1).	[10]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane increases the expression of Transmembrane 6 superfamily member 1 (TM6SF1).	[14]

References

• [1] Validation of DNA promoter hypermethylation biomarkers in breast cancer--a short report.Cell Oncol (Dordr). 2014 Aug;37(4):297-303. doi: 10.1007/s13402-014-0189-1. Epub 2014 Aug 16.
• [2] 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.
• [3] Cyclosporine A--induced oxidative stress in human renal mesangial cells: a role for ERK 1/2 MAPK signaling. Toxicol Sci. 2012 Mar;126(1):101-13.
• [4] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [5] Prenatal arsenic exposure and the epigenome: identifying sites of 5-methylcytosine alterations that predict functional changes in gene expression in newborn cord blood and subsequent birth outcomes. Toxicol Sci. 2015 Jan;143(1):97-106. doi: 10.1093/toxsci/kfu210. Epub 2014 Oct 10.
• [6] Transcriptome-based functional classifiers for direct immunotoxicity. Arch Toxicol. 2014 Mar;88(3):673-89.
• [7] Effects of progesterone treatment on expression of genes involved in uterine quiescence. Reprod Sci. 2011 Aug;18(8):781-97.
• [8] Dasatinib reverses cancer-associated fibroblasts (CAFs) from primary lung carcinomas to a phenotype comparable to that of normal fibroblasts. Mol Cancer. 2010 Jun 27;9:168.
• [9] Successful validation of genomic biomarkers for human immunotoxicity in Jurkat T cells in vitro. J Appl Toxicol. 2015 Jul;35(7):831-41.
• [10] Pleiotropic combinatorial transcriptomes of human breast cancer cells exposed to mixtures of dietary phytoestrogens. Food Chem Toxicol. 2009 Apr;47(4):787-95.
• [11] Selenium and vitamin E: cell type- and intervention-specific tissue effects in prostate cancer. J Natl Cancer Inst. 2009 Mar 4;101(5):306-20.
• [12] 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.
• [13] 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.
• [14] Sulforaphane-induced apoptosis in human leukemia HL-60 cells through extrinsic and intrinsic signal pathways and altering associated genes expression assayed by cDNA microarray. Environ Toxicol. 2017 Jan;32(1):311-328.