Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTNEL2PZ)

• DOT Name: Torsin-1B (TOR1B)
• Synonyms: Torsin ATPase-1B; EC 3.6.4.-; Torsin family 1 member B
• Gene Name: TOR1B
• Related Disease:
  Influenza
  Leprosy
  Segmental dystonia
  Dystonia
  Tuberculosis
• UniProt ID: TOR1B_HUMAN
• EC Number: 3.6.4.-
• Pfam ID: PF21376 ; PF06309
• Sequence:
  MLRAGWLRGAAALALLLAARVVAAFEPITVGLAIGAASAITGYLSYNDIYCRFAECCREE
  RPLNASALKLDLEEKLFGQHLATEVIFKALTGFRNNKNPKKPLTLSLHGWAGTGKNFVSQ
  IVAENLHPKGLKSNFVHLFVSTLHFPHEQKIKLYQDQLQKWIRGNVSACANSVFIFDEMD
  KLHPGIIDAIKPFLDYYEQVDGVSYRKAIFIFLSNAGGDLITKTALDFWRAGRKREDIQL
  KDLEPVLSVGVFNNKHSGLWHSGLIDKNLIDYFIPFLPLEYRHVKMCVRAEMRARGSAID
  EDIVTRVAEEMTFFPRDEKIYSDKGCKTVQSRLDFH
• Function: May serve as a molecular chaperone assisting in the proper folding of secreted and/or membrane proteins. Plays a role in non-neural cells nuclear envelope and endoplasmic reticulum integrity. May have a redundant function with TOR1A in non-neural tissues.
• Tissue Specificity: Widely expressed with low levels in brain.
• Reactome Pathway: Cargo recognition for clathrin-mediated endocytosis (R-HSA-8856825)

Molecular Interaction Atlas (MIA) of This DOT

5 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Influenza	DIS3PNU3	Strong	Biomarker	[1]
Leprosy	DISAA4UI	Strong	Biomarker	[2]
Segmental dystonia	DISOACMU	Strong	Genetic Variation	[3]
Dystonia	DISJLFGW	moderate	Biomarker	[4]
Tuberculosis	DIS2YIMD	Limited	Genetic Variation	[5]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of Torsin-1B (TOR1B).	[6]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Torsin-1B (TOR1B).	[7]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Torsin-1B (TOR1B).	[8]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Torsin-1B (TOR1B).	[9]
Marinol	DM70IK5	Approved	Marinol decreases the expression of Torsin-1B (TOR1B).	[10]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Torsin-1B (TOR1B).	[11]
Tamibarotene	DM3G74J	Phase 3	Tamibarotene increases the expression of Torsin-1B (TOR1B).	[7]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 increases the expression of Torsin-1B (TOR1B).	[12]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Torsin-1B (TOR1B).	[13]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Torsin-1B (TOR1B).	[14]

References

• [1] A host transcriptional signature for presymptomatic detection of infection in humans exposed to influenza H1N1 or H3N2.PLoS One. 2013;8(1):e52198. doi: 10.1371/journal.pone.0052198. Epub 2013 Jan 9.
• [2] Leprosy in a high-prevalence Egyptian village: epidemiology and risk factors.Int J Dermatol. 2002 Oct;41(10):681-6. doi: 10.1046/j.1365-4362.2002.01602.x.
• [3] Genetic evidence for an association of the TOR1A locus with segmental/focal dystonia.Mov Disord. 2010 Oct 15;25(13):2183-7. doi: 10.1002/mds.23225.
• [4] Strong genetic evidence for association of TOR1A/TOR1B with idiopathic dystonia.Neurology. 2006 Nov 28;67(10):1857-9. doi: 10.1212/01.wnl.0000244423.63406.17.
• [5] HLA antigen profile in pulmonary tuberculosis patients & their spouses.Indian J Med Res. 1998 Apr;107:155-8.
• [6] Stem cell transcriptome responses and corresponding biomarkers that indicate the transition from adaptive responses to cytotoxicity. Chem Res Toxicol. 2017 Apr 17;30(4):905-922.
• [7] Differential modulation of PI3-kinase/Akt pathway during all-trans retinoic acid- and Am80-induced HL-60 cell differentiation revealed by DNA microarray analysis. Biochem Pharmacol. 2004 Dec 1;68(11):2177-86.
• [8] 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.
• [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] THC exposure of human iPSC neurons impacts genes associated with neuropsychiatric disorders. Transl Psychiatry. 2018 Apr 25;8(1):89. doi: 10.1038/s41398-018-0137-3.
• [11] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [12] Inhibition of BRD4 attenuates tumor cell self-renewal and suppresses stem cell signaling in MYC driven medulloblastoma. Oncotarget. 2014 May 15;5(9):2355-71.
• [13] Environmental pollutant induced cellular injury is reflected in exosomes from placental explants. Placenta. 2020 Jan 1;89:42-49. doi: 10.1016/j.placenta.2019.10.008. Epub 2019 Oct 17.
• [14] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.