Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT0AH12O)

• DOT Name: T-cell leukemia translocation-altered gene protein (TCTA)
• Synonyms: T-cell leukemia translocation-associated gene protein
• Gene Name: TCTA
• Related Disease:
  Schizophrenia
  T-cell leukaemia
  Crohn disease
• UniProt ID: TCTA_HUMAN
• Pfam ID: PF15128
• Sequence:
  MAESWSGQALQALPATVLGALGSEFLREWEAQDMRVTLFKLLLLWLVLSLLGIQLAWGFY
  GNTVTGLYHRPGLGGQNGSTPDGSTHFPSWEMAANEPLKTHRE
• Function: May be required for cellular fusion during osteoclastogenesis.
• Tissue Specificity: Ubiquitous. Highest level of expression in kidney. Present in monocytes, osteoclasts, macrophages, synoviocytes and synovial lining cells (at protein level).

Molecular Interaction Atlas (MIA) of This DOT

3 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Schizophrenia	DISSRV2N	Strong	Genetic Variation	[1]
T-cell leukaemia	DISJ6YIF	Strong	Genetic Variation	[2]
Crohn disease	DIS2C5Q8	moderate	Genetic Variation	[3]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the methylation of T-cell leukemia translocation-altered gene protein (TCTA).	[4]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of T-cell leukemia translocation-altered gene protein (TCTA).	[5]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of T-cell leukemia translocation-altered gene protein (TCTA).	[6]
Isotretinoin	DM4QTBN	Approved	Isotretinoin decreases the expression of T-cell leukemia translocation-altered gene protein (TCTA).	[7]
Deguelin	DMXT7WG	Investigative	Deguelin decreases the expression of T-cell leukemia translocation-altered gene protein (TCTA).	[8]

References

• [1] A new risk locus in the ZEB2 gene for schizophrenia in the Han Chinese population.Prog Neuropsychopharmacol Biol Psychiatry. 2016 Apr 3;66:97-103. doi: 10.1016/j.pnpbp.2015.12.001. Epub 2015 Dec 3.
• [2] T-cell leukemia translocation-associated gene (TCTA) protein is required for human osteoclastogenesis.Bone. 2009 Oct;45(4):627-39. doi: 10.1016/j.bone.2009.06.019. Epub 2009 Jun 25.
• [3] Genome-wide association defines more than 30 distinct susceptibility loci for Crohn's disease.Nat Genet. 2008 Aug;40(8):955-62. doi: 10.1038/ng.175. Epub 2008 Jun 29.
• [4] 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.
• [5] 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.
• [6] 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.
• [7] Temporal changes in gene expression in the skin of patients treated with isotretinoin provide insight into its mechanism of action. Dermatoendocrinol. 2009 May;1(3):177-87.
• [8] Neurotoxicity and underlying cellular changes of 21 mitochondrial respiratory chain inhibitors. Arch Toxicol. 2021 Feb;95(2):591-615. doi: 10.1007/s00204-020-02970-5. Epub 2021 Jan 29.