Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT7411EE)

• DOT Name: TLC domain-containing protein 4 (TLCD4)
• Synonyms: Transmembrane protein 56
• Gene Name: TLCD4
• Related Disease: Bipolar disorder
• UniProt ID: TLCD4_HUMAN
• Pfam ID: PF03798
• Sequence:
  MEINTKLLISVTCISFFTFQLLFYFVSYWFSAKVSPGFNSLSFKKKIEWNSRVVSTCHSL
  VVGIFGLYIFLFDEATKADPLWGGPSLANVNIAIASGYLISDLSIIILYWKVIGDKFFIM
  HHCASLYAYYLVLKNGVLAYIGNFRLLAELSSPFVNQRWFFEALKYPKFSKAIVINGILM
  TVVFFIVRIASMLPHYGFMYSVYGTEPYIRLGVLIQLSWVISCVVLDVMNVMWMIKISKG
  CIKVISHIRQEKAKNSLQNGKLD

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Bipolar disorder	DISAM7J2	Limited	Genetic Variation	[1]

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 TLC domain-containing protein 4 (TLCD4).	[2]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of TLC domain-containing protein 4 (TLCD4).	[3]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of TLC domain-containing protein 4 (TLCD4).	[4]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of TLC domain-containing protein 4 (TLCD4).	[5]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of TLC domain-containing protein 4 (TLCD4).	[6]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of TLC domain-containing protein 4 (TLCD4).	[7]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of TLC domain-containing protein 4 (TLCD4).	[8]
Testosterone	DM7HUNW	Approved	Testosterone increases the expression of TLC domain-containing protein 4 (TLCD4).	[7]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of TLC domain-containing protein 4 (TLCD4).	[8]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of TLC domain-containing protein 4 (TLCD4).	[9]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of TLC domain-containing protein 4 (TLCD4).	[10]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of TLC domain-containing protein 4 (TLCD4).	[11]

References

• [1] Genome-wide association study identifies 30 loci associated with bipolar disorder.Nat Genet. 2019 May;51(5):793-803. doi: 10.1038/s41588-019-0397-8. Epub 2019 May 1.
• [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] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [4] Development of a neural teratogenicity test based on human embryonic stem cells: response to retinoic acid exposure. Toxicol Sci. 2011 Dec;124(2):370-7.
• [5] 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.
• [6] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [7] Effects of 1alpha,25 dihydroxyvitamin D3 and testosterone on miRNA and mRNA expression in LNCaP cells. Mol Cancer. 2011 May 18;10:58.
• [8] 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.
• [9] 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.
• [10] 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.
• [11] From transient transcriptome responses to disturbed neurodevelopment: role of histone acetylation and methylation as epigenetic switch between reversible and irreversible drug effects. Arch Toxicol. 2014 Jul;88(7):1451-68.