Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTXEMR2U)

• DOT Name: T-box transcription factor TBX19 (TBX19)
• Synonyms: T-box protein 19; T-box factor, pituitary
• Gene Name: TBX19
• Related Disease:
  Congenital isolated adrenocorticotropic hormone deficiency
  Adenoma
  Alcohol dependence
  Alcohol use disorder
  Cardiac arrest
  Common variable immunodeficiency
  Cushing disease
  Depression
  Adrenocortical insufficiency
• UniProt ID: TBX19_HUMAN
• Pfam ID: PF00907
• Sequence:
  MAMSELGTRKPSDGTVSHLLNVVESELQAGREKGDPTEKQLQIILEDAPLWQRFKEVTNE
  MIVTKNGRRMFPVLKISVTGLDPNAMYSLLLDFVPTDSHRWKYVNGEWVPAGKPEVSSHS
  CVYIHPDSPNFGAHWMKAPISFSKVKLTNKLNGGGQIMLNSLHKYEPQVHIVRVGSAHRM
  VTNCSFPETQFIAVTAYQNEEITALKIKYNPFAKAFLDAKERNHLRDVPEAISESQHVTY
  SHLGGWIFSNPDGVCTAGNSNYQYAAPLPLPAPHTHHGCEHYSGLRGHRQAPYPSAYMHR
  NHSPSVNLIESSSNNLQVFSGPDSWTSLSSTPHASILSVPHTNGPINPGPSPYPCLWTIS
  NGAGGPSGPGPEVHASTPGAFLLGNPAVTSPPSVLSTQAPTSAGVEVLGEPSLTSIAVST
  WTAVASHPFAGWGGPGAGGHHSPSSLDG
• Function: Transcriptional regulator involved in developmental processes. Can activate POMC gene expression and repress the alpha glycoprotein subunit and thyroid-stimulating hormone beta promoters.

Molecular Interaction Atlas (MIA) of This DOT

9 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Congenital isolated adrenocorticotropic hormone deficiency	DISYMJJV	Definitive	Autosomal recessive	[1]
Adenoma	DIS78ZEV	Strong	Biomarker	[2]
Alcohol dependence	DIS4ZSCO	Strong	Biomarker	[3]
Alcohol use disorder	DISMB65Y	Strong	Biomarker	[3]
Cardiac arrest	DIS9DIA4	Strong	Altered Expression	[4]
Common variable immunodeficiency	DISHE7JQ	Strong	Genetic Variation	[5]
Cushing disease	DISOG6P2	Strong	Altered Expression	[4]
Depression	DIS3XJ69	Strong	Biomarker	[6]
Adrenocortical insufficiency	DISZ0CPT	moderate	Biomarker	[7]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ethanol	DMDRQZU	Approved	T-box transcription factor TBX19 (TBX19) affects the response to substance of Ethanol.	[3]

This DOT Affected the Regulation of Drug Effects of 2 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Hydrocortisone	DMGEMB7	Approved	T-box transcription factor TBX19 (TBX19) decreases the abundance of Hydrocortisone.	[12]
Estriol	DMOEM2I	Approved	T-box transcription factor TBX19 (TBX19) decreases the abundance of Estriol.	[12]

2 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 T-box transcription factor TBX19 (TBX19).	[8]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 increases the expression of T-box transcription factor TBX19 (TBX19).	[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 T-box transcription factor TBX19 (TBX19).	[9]

References

• [1] Classification of Genes: Standardized Clinical Validity Assessment of Gene-Disease Associations Aids Diagnostic Exome Analysis and Reclassifications. Hum Mutat. 2017 May;38(5):600-608. doi: 10.1002/humu.23183. Epub 2017 Feb 13.
• [2] PROP1 overexpression in corticotrophinomas: evidence for the role of PROP1 in the maintenance of cells committed to corticotrophic differentiation.Clinics (Sao Paulo). 2013 Jun;68(6):887-91. doi: 10.6061/clinics/2013(06)26.
• [3] Substance dependence low-density whole genome association study in two distinct American populations. Hum Genet. 2008 Jun;123(5):495-506. doi: 10.1007/s00439-008-0501-0. Epub 2008 Apr 26.
• [4] Differential gene expression in ACTH -secreting and non-functioning pituitary tumors.Eur J Endocrinol. 2007 Dec;157(6):717-24. doi: 10.1530/EJE-07-0428.
• [5] Deficit in anterior pituitary function and variable immune deficiency (DAVID) in children presenting with adrenocorticotropin deficiency and severe infections.J Clin Endocrinol Metab. 2012 Jan;97(1):E121-8. doi: 10.1210/jc.2011-0407. Epub 2011 Oct 19.
• [6] Nature and nurture in suicidal behavior, the role of genetics: some novel findings concerning personality traits and neural conduction.Physiol Behav. 2007 Sep 10;92(1-2):245-9. doi: 10.1016/j.physbeh.2007.05.061. Epub 2007 May 25.
• [7] A rare cause of neonatal hypoglycemia in two siblings: TBX19 gene mutation.Hormones (Athens). 2018 Jun;17(2):269-273. doi: 10.1007/s42000-018-0028-2. Epub 2018 May 3.
• [8] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [9] 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.
• [10] Loss of TRIM33 causes resistance to BET bromodomain inhibitors through MYC- and TGF-beta-dependent mechanisms. Proc Natl Acad Sci U S A. 2016 Aug 2;113(31):E4558-66.
• [11] Substance dependence low-density whole genome association study in two distinct American populations. Hum Genet. 2008 Jun;123(5):495-506. doi: 10.1007/s00439-008-0501-0. Epub 2008 Apr 26.
• [12] Low estriol levels in the maternal triple-marker screen as a predictor of isolated adrenocorticotropic hormone deficiency caused by a new mutation in the TPIT gene. Pediatrics. 2006 Feb;117(2):e322-7. doi: 10.1542/peds.2005-1973. Epub 2006 Jan 3.