Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT04YLXE)

• DOT Name: Torsin-3A (TOR3A)
• Synonyms: ATP-dependent interferon-responsive protein; Torsin family 3 member A
• Gene Name: TOR3A
• Related Disease:
  Autism spectrum disorder
  Autism
  Intellectual disability
• UniProt ID: TOR3A_HUMAN
• Pfam ID: PF21376 ; PF06309
• Sequence:
  MLRGPWRQLWLFFLLLLPGAPEPRGASRPWEGTDEPGSAWAWPGFQRLQEQLRAAGALSK
  RYWTLFSCQVWPDDCDEDEEAATGPLGWRLPLLGQRYLDLLTTWYCSFKDCCPRGDCRIS
  NNFTGLEWDLNVRLHGQHLVQQLVLRTVRGYLETPQPEKALALSFHGWSGTGKNFVARML
  VENLYRDGLMSDCVRMFIATFHFPHPKYVDLYKEQLMSQIRETQQLCHQTLFIFDEAEKL
  HPGLLEVLGPHLERRAPEGHRAESPWTIFLFLSNLRGDIINEVVLKLLKAGWSREEITME
  HLEPHLQAEIVETIDNGFGHSRLVKENLIDYFIPFLPLEYRHVRLCARDAFLSQELLYKE
  ETLDEIAQMMVYVPKEEQLFSSQGCKSISQRINYFLS
• Tissue Specificity: Ubiquitously expressed. Highest expression in stomach, salivary glands and lymph nodes. Isoform 2 is expressed in placenta.

Molecular Interaction Atlas (MIA) of This DOT

3 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Autism spectrum disorder	DISXK8NV	Strong	Biomarker	[1]
Autism	DISV4V1Z	Disputed	Biomarker	[2]
Intellectual disability	DISMBNXP	Disputed	Biomarker	[2]

2 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 Torsin-3A (TOR3A).	[3]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of Torsin-3A (TOR3A).	[14]

11 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 Torsin-3A (TOR3A).	[4]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Torsin-3A (TOR3A).	[5]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Torsin-3A (TOR3A).	[6]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Torsin-3A (TOR3A).	[7]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Torsin-3A (TOR3A).	[8]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Torsin-3A (TOR3A).	[9]
Testosterone enanthate	DMB6871	Approved	Testosterone enanthate affects the expression of Torsin-3A (TOR3A).	[10]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Torsin-3A (TOR3A).	[11]
Nabiximols	DMHKJ5I	Phase 3	Nabiximols increases the expression of Torsin-3A (TOR3A).	[12]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol increases the expression of Torsin-3A (TOR3A).	[13]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Torsin-3A (TOR3A).	[15]

References

• [1] Frequency of risk factors and coexisting abnormalities in a population of Egyptian children with autism spectrum disorder.Asian J Psychiatr. 2018 Feb;32:54-58. doi: 10.1016/j.ajp.2017.11.037. Epub 2017 Dec 1.
• [2] Some children with autism have latent social skills that can be tested.Neuropsychiatr Dis Treat. 2017 Mar 16;13:827-833. doi: 10.2147/NDT.S131661. eCollection 2017.
• [3] 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.
• [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] 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] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [7] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [8] 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.
• [9] Quantitative proteomics reveals a broad-spectrum antiviral property of ivermectin, benefiting for COVID-19 treatment. J Cell Physiol. 2021 Apr;236(4):2959-2975. doi: 10.1002/jcp.30055. Epub 2020 Sep 22.
• [10] Transcriptional profiling of testosterone-regulated genes in the skeletal muscle of human immunodeficiency virus-infected men experiencing weight loss. J Clin Endocrinol Metab. 2007 Jul;92(7):2793-802. doi: 10.1210/jc.2006-2722. Epub 2007 Apr 17.
• [11] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [12] Clinical response to Nabiximols correlates with the downregulation of immune pathways in multiple sclerosis. Eur J Neurol. 2018 Jul;25(7):934-e70. doi: 10.1111/ene.13623. Epub 2018 Apr 16.
• [13] Selenium and vitamin E: cell type- and intervention-specific tissue effects in prostate cancer. J Natl Cancer Inst. 2009 Mar 4;101(5):306-20.
• [14] 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.
• [15] Bisphenol A Exposure Changes the Transcriptomic and Proteomic Dynamics of Human Retinoblastoma Y79 Cells. Genes (Basel). 2021 Feb 11;12(2):264. doi: 10.3390/genes12020264.