Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTY3LAD9)

• DOT Name: Thyrotroph embryonic factor (TEF)
• Gene Name: TEF
• Related Disease:
  Hypothyroidism
  leukaemia
  Leukemia
  Major depressive disorder
  Multiple sclerosis
  VACTERL/vater association
  Vitiligo
  Bladder cancer
  Congenital heart disease
  Parkinson disease
  Rheumatoid arthritis
  Urinary bladder cancer
  Urinary bladder neoplasm
• UniProt ID: TEF_HUMAN
• PDB ID: 4U5T
• Pfam ID: PF07716
• Sequence:
  MSDAGGGKKPPVDPQAGPGPGPGRAAGERGLSGSFPLVLKKLMENPPREARLDKEKGKEK
  LEEDEAAAASTMAVSASLMPPIWDKTIPYDGESFHLEYMDLDEFLLENGIPASPTHLAHN
  LLLPVAELEGKESASSSTASPPSSSTAIFQPSETVSSTESSLEKERETPSPIDPNCVEVD
  VNFNPDPADLVLSSVPGGELFNPRKHKFAEEDLKPQPMIKKAKKVFVPDEQKDEKYWTRR
  KKNNVAAKRSRDARRLKENQITIRAAFLEKENTALRTEVAELRKEVGKCKTIVSKYETKY
  GPL
• Function: Transcription factor that binds to and transactivates the TSHB promoter. Binds to a minimal DNA-binding sequence 5'-[TC][AG][AG]TTA[TC][AG]-3'.

Molecular Interaction Atlas (MIA) of This DOT

13 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Hypothyroidism	DISR0H6D	Strong	Altered Expression	[1]
leukaemia	DISS7D1V	Strong	Altered Expression	[2]
Leukemia	DISNAKFL	Strong	Altered Expression	[2]
Major depressive disorder	DIS4CL3X	Strong	Biomarker	[3]
Multiple sclerosis	DISB2WZI	Strong	Genetic Variation	[4]
VACTERL/vater association	DISJNE30	Strong	Biomarker	[5]
Vitiligo	DISR05SL	Strong	Genetic Variation	[6]
Bladder cancer	DISUHNM0	Limited	Altered Expression	[7]
Congenital heart disease	DISQBA23	Limited	Biomarker	[8]
Parkinson disease	DISQVHKL	Limited	Genetic Variation	[9]
Rheumatoid arthritis	DISTSB4J	Limited	Biomarker	[10]
Urinary bladder cancer	DISDV4T7	Limited	Altered Expression	[7]
Urinary bladder neoplasm	DIS7HACE	Limited	Altered Expression	[7]

9 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 Thyrotroph embryonic factor (TEF).	[11]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Thyrotroph embryonic factor (TEF).	[12]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Thyrotroph embryonic factor (TEF).	[13]
Vorinostat	DMWMPD4	Approved	Vorinostat decreases the expression of Thyrotroph embryonic factor (TEF).	[14]
Methotrexate	DM2TEOL	Approved	Methotrexate increases the expression of Thyrotroph embryonic factor (TEF).	[15]
Amiodarone	DMUTEX3	Phase 2/3 Trial	Amiodarone increases the expression of Thyrotroph embryonic factor (TEF).	[16]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Thyrotroph embryonic factor (TEF).	[17]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Thyrotroph embryonic factor (TEF).	[18]
Milchsaure	DM462BT	Investigative	Milchsaure increases the expression of Thyrotroph embryonic factor (TEF).	[19]

References

• [1] Disruption of the Pituitary Circadian Clock Induced by Hypothyroidism and Hyperthyroidism: Consequences on Daily Pituitary Hormone Expression Profiles.Thyroid. 2019 Apr;29(4):502-512. doi: 10.1089/thy.2018.0578. Epub 2019 Mar 13.
• [2] The proto-oncogene HLF and the related basic leucine zipper protein TEF display highly similar DNA-binding and transcriptional regulatory properties.Blood. 1996 Jun 1;87(11):4607-17.
• [3] Resequencing three candidate genes discovers seven potentially deleterious variants susceptibility to major depressive disorder and suicide attempts in Chinese.Gene. 2017 Mar 1;603:34-41. doi: 10.1016/j.gene.2016.12.006. Epub 2016 Dec 10.
• [4] Analysis of immune-related loci identifies 48 new susceptibility variants for multiple sclerosis.Nat Genet. 2013 Nov;45(11):1353-60. doi: 10.1038/ng.2770. Epub 2013 Sep 29.
• [5] Second study on the recurrence risk of isolated esophageal atresia with or without trachea-esophageal fistula among first-degree relatives: no evidence for increased risk of recurrence of EA/TEF or for malformations of the VATER/VACTERL association spectrum.Birth Defects Res A Clin Mol Teratol. 2013 Dec;97(12):786-91. doi: 10.1002/bdra.23205. Epub 2013 Dec 5.
• [6] Genome-wide association studies of autoimmune vitiligo identify 23 new risk loci and highlight key pathways and regulatory variants.Nat Genet. 2016 Nov;48(11):1418-1424. doi: 10.1038/ng.3680. Epub 2016 Oct 10.
• [7] Thyrotroph embryonic factor is downregulated in bladder cancer and suppresses proliferation and tumorigenesis via the AKT/FOXOs signalling pathway.Cell Prolif. 2019 Mar;52(2):e12560. doi: 10.1111/cpr.12560. Epub 2018 Dec 4.
• [8] Characteristics and outcomes of children with ductal-dependent congenital heart disease and esophageal atresia/tracheoesophageal fistula: A multi-institutional analysis.Surgery. 2018 Apr;163(4):847-853. doi: 10.1016/j.surg.2017.09.010. Epub 2018 Jan 8.
• [9] Tef polymorphism is associated with sleep disturbances in patients with Parkinson's disease.Sleep Med. 2012 Mar;13(3):297-300. doi: 10.1016/j.sleep.2011.06.023. Epub 2012 Jan 17.
• [10] TNF- modulates expression of the circadian clock gene Per2 in rheumatoid synovial cells.Scand J Rheumatol. 2013;42(4):276-80. doi: 10.3109/03009742.2013.765031. Epub 2013 Mar 16.
• [11] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [12] 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.
• [13] Bringing in vitro analysis closer to in vivo: studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling. Toxicol Lett. 2018 Sep 15;294:184-192.
• [14] Definition of transcriptome-based indices for quantitative characterization of chemically disturbed stem cell development: introduction of the STOP-Toxukn and STOP-Toxukk tests. Arch Toxicol. 2017 Feb;91(2):839-864.
• [15] Global molecular effects of tocilizumab therapy in rheumatoid arthritis synovium. Arthritis Rheumatol. 2014 Jan;66(1):15-23.
• [16] Identification by automated screening of a small molecule that selectively eliminates neural stem cells derived from hESCs but not dopamine neurons. PLoS One. 2009 Sep 23;4(9):e7155.
• [17] 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.
• [18] 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.
• [19] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.