Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTVZUR1Z)

• DOT Name: TLC domain-containing protein 3A (TLCD3A)
• Synonyms: Protein CT120; Protein FAM57A
• Gene Name: TLCD3A
• Related Disease:
  Advanced cancer
  Lung cancer
  Lung carcinoma
  Lung neoplasm
  Neoplasm
• UniProt ID: TLC3A_HUMAN
• Pfam ID: PF03798
• Sequence:
  MLLTLAGGALFFPGLFALCTWALRRSQPGWSRTDCVMISTRLVSSVHAVLATGSGIVIIR
  SCDDVITGRHWLAREYVWFLIPYMIYDSYAMYLCEWCRTRDQNRAPSLTLRNFLSRNRLM
  ITHHAVILFVLVPVAQRLRGDLGDFFVGCIFTAELSTPFVSLGRVLIQLKQQHTLLYKVN
  GILTLATFLSCRILLFPFMYWSYGRQQGLSLLQVPFSIPFYCNVANAFLVAPQIYWFCLL
  CRKAVRLFDTPQAKKDG
• Tissue Specificity: Highly expressed in pancreas. Detected at intermediate levels in heart, placenta and kidney, and at low levels in brain, liver and skeletal muscle. Not detected in normal lung.

Molecular Interaction Atlas (MIA) of This DOT

5 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Advanced cancer	DISAT1Z9	Strong	Genetic Variation	[1]
Lung cancer	DISCM4YA	Strong	Altered Expression	[2]
Lung carcinoma	DISTR26C	Strong	Altered Expression	[2]
Lung neoplasm	DISVARNB	Strong	Altered Expression	[1]
Neoplasm	DISZKGEW	Strong	Biomarker	[1]

12 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 TLC domain-containing protein 3A (TLCD3A).	[3]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of TLC domain-containing protein 3A (TLCD3A).	[4]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of TLC domain-containing protein 3A (TLCD3A).	[5]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of TLC domain-containing protein 3A (TLCD3A).	[6]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of TLC domain-containing protein 3A (TLCD3A).	[7]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of TLC domain-containing protein 3A (TLCD3A).	[8]
Calcitriol	DM8ZVJ7	Approved	Calcitriol decreases the expression of TLC domain-containing protein 3A (TLCD3A).	[9]
Vorinostat	DMWMPD4	Approved	Vorinostat decreases the expression of TLC domain-containing protein 3A (TLCD3A).	[10]
Zoledronate	DMIXC7G	Approved	Zoledronate increases the expression of TLC domain-containing protein 3A (TLCD3A).	[11]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of TLC domain-containing protein 3A (TLCD3A).	[12]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of TLC domain-containing protein 3A (TLCD3A).	[13]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of TLC domain-containing protein 3A (TLCD3A).	[14]

References

• [1] Altered gene expression profiles of NIH3T3 cells regulated by human lung cancer associated gene CT120.Cell Res. 2004 Dec;14(6):487-96. doi: 10.1038/sj.cr.7290252.
• [2] Silencing of CT120 by antisense oligonucleotides could inhibit the lung cancer cells growth.Ir J Med Sci. 2010 Jun;179(2):217-23. doi: 10.1007/s11845-009-0418-1. Epub 2009 Dec 20.
• [3] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [4] 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.
• [5] Blood transcript immune signatures distinguish a subset of people with elevated serum ALT from others given acetaminophen. Clin Pharmacol Ther. 2016 Apr;99(4):432-41.
• [6] 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.
• [7] 17-Estradiol Activates HSF1 via MAPK Signaling in ER-Positive Breast Cancer Cells. Cancers (Basel). 2019 Oct 11;11(10):1533. doi: 10.3390/cancers11101533.
• [8] Temozolomide induces activation of Wnt/-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278. doi: 10.1007/s10565-019-09502-7. Epub 2019 Nov 22.
• [9] Large-scale in silico and microarray-based identification of direct 1,25-dihydroxyvitamin D3 target genes. Mol Endocrinol. 2005 Nov;19(11):2685-95.
• [10] 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.
• [11] The proapoptotic effect of zoledronic acid is independent of either the bone microenvironment or the intrinsic resistance to bortezomib of myeloma cells and is enhanced by the combination with arsenic trioxide. Exp Hematol. 2011 Jan;39(1):55-65.
• [12] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [13] 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.
• [14] 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.