Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT7NKLF9)

• DOT Name: Transcription factor 19 (TCF19)
• Synonyms: TCF-19; Transcription factor SC1
• Gene Name: TCF19
• Related Disease:
  Hepatitis B virus infection
  Chronic hepatitis B virus infection
  Colon cancer
  Colonic neoplasm
  Graves disease
  Hepatocellular carcinoma
  Insulinoma
  Lung adenocarcinoma
  Membranous glomerulonephritis
  Multiple sclerosis
  Myasthenia gravis
  Psoriasis
  Retinoblastoma
  Rheumatoid arthritis
  Squamous cell carcinoma
  Stevens-Johnson syndrome
  Toxic epidermal necrolysis
  Type-1 diabetes
  Type-1/2 diabetes
  Plasma cell myeloma
  Systemic lupus erythematosus
  Lung cancer
  Non-insulin dependent diabetes
  Non-small-cell lung cancer
• UniProt ID: TCF19_HUMAN
• Pfam ID: PF00498 ; PF00628
• Sequence:
  MLPCFQLLRIGGGRGGDLYTFHPPAGAGCTYRLGHRADLCDVALRPQQEPGLISGIHAEL
  HAEPRGDDWRVSLEDHSSQGTLVNNVRLPRGHRLELSDGDLLTFGPEGPPGTSPSEFYFM
  FQQVRVKPQDFAAITIPRSRGEARVGAGFRPMLPSQGAPQRPLSTFSPAPKATLILNSIG
  SLSKLRPQPLTFSPSWGGPKSLPVPAPPGEMGTTPSAPPQRNRRKSVHRVLAELDDESEP
  PENPPPVLMEPRKKLRVDKAPLTPTGNRRGRPRKYPVSAPMAPPAVGGGEPCAAPCCCLP
  QEETVAWVQCDGCDVWFHVACVGCSIQAAREADFRCPGCRAGIQT
• Function: Potential trans-activating factor that could play an important role in the transcription of genes required for the later stages of cell cycle progression.

Molecular Interaction Atlas (MIA) of This DOT

24 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Hepatitis B virus infection	DISLQ2XY	Definitive	Biomarker	[1]
Chronic hepatitis B virus infection	DISHL4NT	Strong	Genetic Variation	[2]
Colon cancer	DISVC52G	Strong	Biomarker	[3]
Colonic neoplasm	DISSZ04P	Strong	Biomarker	[3]
Graves disease	DISU4KOQ	Strong	Genetic Variation	[4]
Hepatocellular carcinoma	DIS0J828	Strong	Biomarker	[5]
Insulinoma	DISIU1JS	Strong	Biomarker	[6]
Lung adenocarcinoma	DISD51WR	Strong	Altered Expression	[7]
Membranous glomerulonephritis	DISFSUKQ	Strong	Genetic Variation	[8]
Multiple sclerosis	DISB2WZI	Strong	Genetic Variation	[9]
Myasthenia gravis	DISELRCI	Strong	Genetic Variation	[10]
Psoriasis	DIS59VMN	Strong	Biomarker	[11]
Retinoblastoma	DISVPNPB	Strong	Altered Expression	[1]
Rheumatoid arthritis	DISTSB4J	Strong	Genetic Variation	[12]
Squamous cell carcinoma	DISQVIFL	Strong	Biomarker	[7]
Stevens-Johnson syndrome	DISZG4YX	Strong	Genetic Variation	[13]
Toxic epidermal necrolysis	DISIWPFR	Strong	Genetic Variation	[13]
Type-1 diabetes	DIS7HLUB	Strong	Biomarker	[5]
Type-1/2 diabetes	DISIUHAP	Strong	Biomarker	[6]
Plasma cell myeloma	DIS0DFZ0	moderate	Genetic Variation	[14]
Systemic lupus erythematosus	DISI1SZ7	moderate	Genetic Variation	[15]
Lung cancer	DISCM4YA	Limited	Genetic Variation	[16]
Non-insulin dependent diabetes	DISK1O5Z	Limited	Genetic Variation	[17]
Non-small-cell lung cancer	DIS5Y6R9	Limited	Biomarker	[5]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of Transcription factor 19 (TCF19).	[18]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Transcription factor 19 (TCF19).	[19]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Transcription factor 19 (TCF19).	[20]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Transcription factor 19 (TCF19).	[21]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Transcription factor 19 (TCF19).	[22]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Transcription factor 19 (TCF19).	[23]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of Transcription factor 19 (TCF19).	[24]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of Transcription factor 19 (TCF19).	[25]
Calcitriol	DM8ZVJ7	Approved	Calcitriol decreases the expression of Transcription factor 19 (TCF19).	[26]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of Transcription factor 19 (TCF19).	[26]
Fluorouracil	DMUM7HZ	Approved	Fluorouracil increases the expression of Transcription factor 19 (TCF19).	[27]
Fulvestrant	DM0YZC6	Approved	Fulvestrant decreases the expression of Transcription factor 19 (TCF19).	[28]
Demecolcine	DMCZQGK	Approved	Demecolcine decreases the expression of Transcription factor 19 (TCF19).	[29]
Bortezomib	DMNO38U	Approved	Bortezomib decreases the expression of Transcription factor 19 (TCF19).	[30]
Azathioprine	DMMZSXQ	Approved	Azathioprine decreases the expression of Transcription factor 19 (TCF19).	[31]
Dasatinib	DMJV2EK	Approved	Dasatinib decreases the expression of Transcription factor 19 (TCF19).	[32]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Transcription factor 19 (TCF19).	[33]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Transcription factor 19 (TCF19).	[34]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide decreases the expression of Transcription factor 19 (TCF19).	[35]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Transcription factor 19 (TCF19).	[36]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN decreases the expression of Transcription factor 19 (TCF19).	[37]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Transcription factor 19 (TCF19).	[38]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Transcription factor 19 (TCF19).	[29]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Transcription factor 19 (TCF19).	[39]
Coumestrol	DM40TBU	Investigative	Coumestrol increases the expression of Transcription factor 19 (TCF19).	[40]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane decreases the expression of Transcription factor 19 (TCF19).	[41]
D-glucose	DMMG2TO	Investigative	D-glucose affects the activity of Transcription factor 19 (TCF19).	[42]

References

• [1] TCF19 enhances cell proliferation in hepatocellular carcinoma by activating the ATK/FOXO1 signaling pathway.Neoplasma. 2019 Jan 15;66(1):46-53. doi: 10.4149/neo_2018_171227N845. Epub 2018 Aug 9.
• [2] Genetic variants in five novel loci including CFB and CD40 predispose to chronic hepatitis B.Hepatology. 2015 Jul;62(1):118-28. doi: 10.1002/hep.27794. Epub 2015 Apr 28.
• [3] Global gene expression analysis of rat colon cancers induced by a food-borne carcinogen, 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine.Carcinogenesis. 2004 Aug;25(8):1495-505. doi: 10.1093/carcin/bgh155. Epub 2004 Apr 1.
• [4] Identification of independent risk loci for Graves' disease within the MHC in the Japanese population.J Hum Genet. 2011 Nov;56(11):772-8. doi: 10.1038/jhg.2011.99. Epub 2011 Sep 8.
• [5] TCF19 Promotes Cell Proliferation through Binding to the Histone H3K4me3 Mark.Biochemistry. 2020 Feb 4;59(4):389-399. doi: 10.1021/acs.biochem.9b00771. Epub 2019 Dec 2.
• [6] Tcf19 is a novel islet factor necessary for proliferation and survival in the INS-1 -cell line.Am J Physiol Endocrinol Metab. 2013 Sep 1;305(5):E600-10. doi: 10.1152/ajpendo.00147.2013. Epub 2013 Jul 16.
• [7] TCF19 contributes to cell proliferation of non-small cell lung cancer by inhibiting FOXO1.Cell Biol Int. 2019 Dec;43(12):1416-1424. doi: 10.1002/cbin.11189. Epub 2019 Jul 11.
• [8] Risk HLA-DQA1 and PLA(2)R1 alleles in idiopathic membranous nephropathy.N Engl J Med. 2011 Feb 17;364(7):616-26. doi: 10.1056/NEJMoa1009742.
• [9] Evidence for VAV2 and ZNF433 as susceptibility genes for multiple sclerosis.J Neuroimmunol. 2010 Oct 8;227(1-2):162-6. doi: 10.1016/j.jneuroim.2010.06.003. Epub 2010 Jul 2.
• [10] Risk for myasthenia gravis maps to a (151) ProAla change in TNIP1 and to human leukocyte antigen-B*08.Ann Neurol. 2012 Dec;72(6):927-35. doi: 10.1002/ana.23691. Epub 2012 Oct 10.
• [11] Inflammatory peeling skin syndrome caused by homozygous genomic deletion in the PSORS1 region encompassing the CDSN gene.Exp Dermatol. 2014 Jan;23(1):60-3. doi: 10.1111/exd.12292.
• [12] REL, encoding a member of the NF-kappaB family of transcription factors, is a newly defined risk locus for rheumatoid arthritis.Nat Genet. 2009 Jul;41(7):820-3. doi: 10.1038/ng.395. Epub 2009 Jun 7.
• [13] Genome-wide association study of Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis in Europe.Orphanet J Rare Dis. 2011 Jul 29;6:52. doi: 10.1186/1750-1172-6-52.
• [14] Identification of miRSNPs associated with the risk of multiple myeloma.Int J Cancer. 2017 Feb 1;140(3):526-534. doi: 10.1002/ijc.30465. Epub 2016 Nov 9.
• [15] 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.
• [16] Influence of common genetic variation on lung cancer risk: meta-analysis of 14 900 cases and 29 485 controls.Hum Mol Genet. 2012 Nov 15;21(22):4980-95. doi: 10.1093/hmg/dds334. Epub 2012 Aug 16.
• [17] Refining the accuracy of validated target identification through coding variant fine-mapping in type 2 diabetes.Nat Genet. 2018 Apr;50(4):559-571. doi: 10.1038/s41588-018-0084-1. Epub 2018 Apr 9.
• [18] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [19] 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.
• [20] 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.
• [21] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [22] Low doses of cisplatin induce gene alterations, cell cycle arrest, and apoptosis in human promyelocytic leukemia cells. Biomark Insights. 2016 Aug 24;11:113-21.
• [23] Global gene expression profiles induced by phytoestrogens in human breast cancer cells. Endocr Relat Cancer. 2008 Mar;15(1):161-73.
• [24] Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
• [25] Identification of transcriptome signatures and biomarkers specific for potential developmental toxicants inhibiting human neural crest cell migration. Arch Toxicol. 2016 Jan;90(1):159-80.
• [26] Effects of 1alpha,25 dihydroxyvitamin D3 and testosterone on miRNA and mRNA expression in LNCaP cells. Mol Cancer. 2011 May 18;10:58.
• [27] Identification of novel genes associated with the response to 5-FU treatment in gastric cancer cell lines using a cDNA microarray. Cancer Lett. 2004 Oct 8;214(1):19-33.
• [28] mTOR inhibition reverses acquired endocrine therapy resistance of breast cancer cells at the cell proliferation and gene-expression levels. Cancer Sci. 2008 Oct;99(10):1992-2003. doi: 10.1111/j.1349-7006.2008.00955.x.
• [29] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [30] Bortezomib induces caspase-dependent apoptosis in Hodgkin lymphoma cell lines and is associated with reduced c-FLIP expression: a gene expression profiling study with implications for potential combination therapies. Leuk Res. 2008 Feb;32(2):275-85. doi: 10.1016/j.leukres.2007.05.024. Epub 2007 Jul 19.
• [31] A transcriptomics-based in vitro assay for predicting chemical genotoxicity in vivo. Carcinogenesis. 2012 Jul;33(7):1421-9.
• [32] 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.
• [33] Identification of a transcriptomic signature of food-relevant genotoxins in human HepaRG hepatocarcinoma cells. Food Chem Toxicol. 2020 Jun;140:111297. doi: 10.1016/j.fct.2020.111297. Epub 2020 Mar 28.
• [34] Inhibition of BRD4 attenuates tumor cell self-renewal and suppresses stem cell signaling in MYC driven medulloblastoma. Oncotarget. 2014 May 15;5(9):2355-71.
• [35] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [36] 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.
• [37] Endoplasmic reticulum stress impairs insulin signaling through mitochondrial damage in SH-SY5Y cells. Neurosignals. 2012;20(4):265-80.
• [38] Bisphenol A induces DSB-ATM-p53 signaling leading to cell cycle arrest, senescence, autophagy, stress response, and estrogen release in human fetal lung fibroblasts. Arch Toxicol. 2018 Apr;92(4):1453-1469.
• [39] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [40] Pleiotropic combinatorial transcriptomes of human breast cancer cells exposed to mixtures of dietary phytoestrogens. Food Chem Toxicol. 2009 Apr;47(4):787-95.
• [41] Transcriptome and DNA methylation changes modulated by sulforaphane induce cell cycle arrest, apoptosis, DNA damage, and suppression of proliferation in human liver cancer cells. Food Chem Toxicol. 2020 Feb;136:111047. doi: 10.1016/j.fct.2019.111047. Epub 2019 Dec 12.
• [42] Transcription factor 19 interacts with histone 3 lysine 4 trimethylation and controls gluconeogenesis via the nucleosome-remodeling-deacetylase complex. J Biol Chem. 2017 Dec 15;292(50):20362-20378. doi: 10.1074/jbc.M117.786863. Epub 2017 Oct 17.