Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT1EGCDU)

• DOT Name: Torsin-2A (TOR2A)
• Synonyms: Torsin family 2 member A; Torsin-related protein 1
• Gene Name: TOR2A
• Related Disease:
  Arteriosclerosis
  Atherosclerosis
  Parkinson disease
  Dilated cardiomyopathy 1A
  Epithelial ovarian cancer
  Essential hypertension
  Multiple sclerosis
  Ovarian cancer
  Ovarian neoplasm
  Polycystic ovarian syndrome
  Relapsing-remitting multiple sclerosis
  Cardiac failure
  Cardiovascular disease
  Congestive heart failure
  High blood pressure
  Neuroblastoma
  Type-1/2 diabetes
• UniProt ID: TOR2A_HUMAN
• Pfam ID: PF21376 ; PF06309
• Sequence:
  MAAATRGCRPWGSLLGLLGLVSAAAAAWDLASLRCTLGAFCECDFRPDLPGLECDLAQHL
  AGQHLAKALVVKALKAFVRDPAPTKPLVLSLHGWTGTGKSYVSSLLAHYLFQGGLRSPRV
  HHFSPVLHFPHPSHIERYKKDLKSWVQGNLTACGRSLFLFDEMDKMPPGLMEVLRPFLGS
  SWVVYGTNYRKAIFIFISNTGGKQINQVALEAWRSRRDREEILLQELEPVISRAVLDNPH
  HGFSNSGIMEERLLDAVVPFLPLQRHHVRHCVLNELAQLGLEPRDEVVQAVLDSTTFFPE
  DEQLFSSNGCKTVASRIAFFL
• Tissue Specificity: Isoform 1 is expressed ubiquitously, except in cardiac and endothelial tissues.

Molecular Interaction Atlas (MIA) of This DOT

17 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Arteriosclerosis	DISK5QGC	Definitive	Altered Expression	[1]
Atherosclerosis	DISMN9J3	Definitive	Altered Expression	[1]
Parkinson disease	DISQVHKL	Definitive	Biomarker	[2]
Dilated cardiomyopathy 1A	DIS0RK9Z	Strong	Biomarker	[3]
Epithelial ovarian cancer	DIS56MH2	Strong	Biomarker	[4]
Essential hypertension	DIS7WI98	Strong	Altered Expression	[5]
Multiple sclerosis	DISB2WZI	Strong	Altered Expression	[6]
Ovarian cancer	DISZJHAP	Strong	Biomarker	[4]
Ovarian neoplasm	DISEAFTY	Strong	Biomarker	[4]
Polycystic ovarian syndrome	DISZ2BNG	Strong	Altered Expression	[4]
Relapsing-remitting multiple sclerosis	DISSXFCF	Strong	Altered Expression	[6]
Cardiac failure	DISDC067	moderate	Altered Expression	[7]
Cardiovascular disease	DIS2IQDX	moderate	Biomarker	[7]
Congestive heart failure	DIS32MEA	moderate	Altered Expression	[7]
High blood pressure	DISY2OHH	moderate	Biomarker	[7]
Neuroblastoma	DISVZBI4	moderate	Altered Expression	[8]
Type-1/2 diabetes	DISIUHAP	Limited	Biomarker	[9]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate affects the expression of Torsin-2A (TOR2A).	[10]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Torsin-2A (TOR2A).	[11]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Torsin-2A (TOR2A).	[12]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of Torsin-2A (TOR2A).	[13]
Methotrexate	DM2TEOL	Approved	Methotrexate decreases the expression of Torsin-2A (TOR2A).	[14]
Zoledronate	DMIXC7G	Approved	Zoledronate decreases the expression of Torsin-2A (TOR2A).	[15]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Torsin-2A (TOR2A).	[16]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Torsin-2A (TOR2A).	[18]

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 decreases the methylation of Torsin-2A (TOR2A).	[17]

References

• [1] Relationship of salusin-alpha and salusin-beta levels with atherosclerosis in patients undergoing haemodialysis.Singapore Med J. 2019 Apr;60(4):210-215. doi: 10.11622/smedj.2018123. Epub 2018 Oct 10.
• [2] Salusin- mediate neuroprotective effects for Parkinson's disease.Biochem Biophys Res Commun. 2018 Sep 10;503(3):1428-1433. doi: 10.1016/j.bbrc.2018.07.059. Epub 2018 Jul 13.
• [3] Salusin- contributes to oxidative stress and inflammation in diabetic cardiomyopathy.Cell Death Dis. 2017 Mar 23;8(3):e2690. doi: 10.1038/cddis.2017.106.
• [4] Overexpression of salusin- is associated with poor prognosis in ovarian cancer.Oncol Rep. 2017 Mar;37(3):1826-1832. doi: 10.3892/or.2017.5429. Epub 2017 Feb 7.
• [5] Correlation of Salusin Beta with hs-CRP and ADMA in Hypertensive Children and Adolescents.Curr Pharm Des. 2018;24(30):3551-3557. doi: 10.2174/1381612824666180607124531.
• [6] Increased level of plasma salusin- and salusin- in patients with multiple sclerosis.Mult Scler Relat Disord. 2019 May;30:76-80. doi: 10.1016/j.msard.2019.02.003. Epub 2019 Feb 5.
• [7] Silencing salusin ameliorates heart failure in aged spontaneously hypertensive rats by ROS-relative MAPK/NF-B pathways in the paraventricular nucleus.Int J Cardiol. 2019 Apr 1;280:142-151. doi: 10.1016/j.ijcard.2018.12.020. Epub 2018 Dec 7.
• [8] Expression of prosalusin in human neuroblastoma cells.Peptides. 2009 Jul;30(7):1362-7. doi: 10.1016/j.peptides.2009.03.021. Epub 2009 Apr 9.
• [9] Salusin- mediates high glucose-induced endothelial injury via disruption of AMPK signaling pathway.Biochem Biophys Res Commun. 2017 Sep 16;491(2):515-521. doi: 10.1016/j.bbrc.2017.06.126. Epub 2017 Jun 21.
• [10] Gene Expression Regulation and Pathway Analysis After Valproic Acid and Carbamazepine Exposure in a Human Embryonic Stem Cell-Based Neurodevelopmental Toxicity Assay. Toxicol Sci. 2015 Aug;146(2):311-20. doi: 10.1093/toxsci/kfv094. Epub 2015 May 15.
• [11] Integrative "-Omics" analysis in primary human hepatocytes unravels persistent mechanisms of cyclosporine A-induced cholestasis. Chem Res Toxicol. 2016 Dec 19;29(12):2164-2174.
• [12] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [13] 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.
• [14] The contribution of methotrexate exposure and host factors on transcriptional variance in human liver. Toxicol Sci. 2007 Jun;97(2):582-94.
• [15] Interleukin-19 as a translational indicator of renal injury. Arch Toxicol. 2015 Jan;89(1):101-6.
• [16] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [17] 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.
• [18] 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.