Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTQUOZC2)

• DOT Name: BLOC-1-related complex subunit 7 (BORCS7)
• Synonyms: Diaskedin
• Gene Name: BORCS7
• Related Disease:
  High blood pressure
  Parkinson disease
• UniProt ID: BORC7_HUMAN
• Pfam ID: PF16088
• Sequence:
  MMATGTPESQARFGQSVKGLLTEKVTTCGTDVIALTKQVLKGSRSSELLGQAARNMVLQE
  DAILHSEDSLRKMAIITTHLQYQQEAIQKNVEQSSDLQDQLNHLLK
• Function: As part of the BORC complex may play a role in lysosomes movement and localization at the cell periphery. Associated with the cytosolic face of lysosomes, the BORC complex may recruit ARL8B and couple lysosomes to microtubule plus-end-directed kinesin motor.

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
High blood pressure	DISY2OHH	Strong	Genetic Variation	[1]
Parkinson disease	DISQVHKL	Strong	Genetic Variation	[2]

This DOT Affected the Regulation of Drug Effects of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	BLOC-1-related complex subunit 7 (BORCS7) decreases the metabolism of Arsenic.	[15]

11 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 BLOC-1-related complex subunit 7 (BORCS7).	[3]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of BLOC-1-related complex subunit 7 (BORCS7).	[4]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of BLOC-1-related complex subunit 7 (BORCS7).	[5]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of BLOC-1-related complex subunit 7 (BORCS7).	[6]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of BLOC-1-related complex subunit 7 (BORCS7).	[7]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of BLOC-1-related complex subunit 7 (BORCS7).	[8]
Demecolcine	DMCZQGK	Approved	Demecolcine increases the expression of BLOC-1-related complex subunit 7 (BORCS7).	[9]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of BLOC-1-related complex subunit 7 (BORCS7).	[10]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of BLOC-1-related complex subunit 7 (BORCS7).	[12]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A affects the expression of BLOC-1-related complex subunit 7 (BORCS7).	[14]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of BLOC-1-related complex subunit 7 (BORCS7).	[9]

2 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 increases the methylation of BLOC-1-related complex subunit 7 (BORCS7).	[11]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of BLOC-1-related complex subunit 7 (BORCS7).	[13]

References

• [1] Interethnic analyses of blood pressure loci in populations of East Asian and European descent.Nat Commun. 2018 Nov 28;9(1):5052. doi: 10.1038/s41467-018-07345-0.
• [2] Genome-wide association study reveals genetic risk underlying Parkinson's disease.Nat Genet. 2009 Dec;41(12):1308-12. doi: 10.1038/ng.487. Epub 2009 Nov 15.
• [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] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [5] Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
• [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] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [8] 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.
• [9] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [10] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [11] 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.
• [12] 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.
• [13] Quantitative phosphoproteomics reveal cellular responses from caffeine, coumarin and quercetin in treated HepG2 cells. Toxicol Appl Pharmacol. 2022 Aug 15;449:116110. doi: 10.1016/j.taap.2022.116110. Epub 2022 Jun 7.
• [14] A trichostatin A expression signature identified by TempO-Seq targeted whole transcriptome profiling. PLoS One. 2017 May 25;12(5):e0178302. doi: 10.1371/journal.pone.0178302. eCollection 2017.
• [15] Genetic Determinants of Reduced Arsenic Metabolism Efficiency in the 10q24.32 Region Are Associated With Reduced AS3MT Expression in Multiple Human Tissue Types. Toxicol Sci. 2020 Aug 1;176(2):382-395. doi: 10.1093/toxsci/kfaa075.