Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTAT6H8Q)

• DOT Name: BLOC-1-related complex subunit 5 (BORCS5)
• Synonyms: Loss of heterozygosity 12 chromosomal region 1; Myristoylated lysosomal protein; Myrlysin
• Gene Name: BORCS5
• Related Disease:
  Colorectal carcinoma
  Ewing sarcoma
  Neoplasm
  Complex neurodevelopmental disorder
• UniProt ID: BORC5_HUMAN
• Pfam ID: PF10158
• Sequence:
  MGSEQSSEAESRPNDLNSSVTPSPAKHRAKMDDIVVVAQGSQASRNVSNDPDVIKLQEIP
  TFQPLLKGLLSGQTSPTNAKLEKLDSQQVLQLCLRYQDHLHQCAEAVAFDQNALVKRIKE
  MDLSVETLFSFMQERQKRYAKYAEQIQKVNEMSAILRRIQMGIDQTVPLLDRLNSMLPEG
  ERLEPFSMKPDRELRL
• 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. Thereby, it may indirectly play a role in cell spreading and motility.
• Tissue Specificity: Ubiquitously expressed (at protein level).

Molecular Interaction Atlas (MIA) of This DOT

4 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Colorectal carcinoma	DIS5PYL0	Strong	Altered Expression	[1]
Ewing sarcoma	DISQYLV3	Strong	Biomarker	[2]
Neoplasm	DISZKGEW	Strong	Biomarker	[2]
Complex neurodevelopmental disorder	DISB9AFI	Limited	Autosomal recessive	[3]

7 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 BLOC-1-related complex subunit 5 (BORCS5).	[4]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of BLOC-1-related complex subunit 5 (BORCS5).	[5]
Doxorubicin	DMVP5YE	Approved	Doxorubicin affects the expression of BLOC-1-related complex subunit 5 (BORCS5).	[6]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate affects the expression of BLOC-1-related complex subunit 5 (BORCS5).	[7]
Testosterone	DM7HUNW	Approved	Testosterone increases the expression of BLOC-1-related complex subunit 5 (BORCS5).	[8]
Phenobarbital	DMXZOCG	Approved	Phenobarbital affects the expression of BLOC-1-related complex subunit 5 (BORCS5).	[9]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of BLOC-1-related complex subunit 5 (BORCS5).	[11]

1 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of BLOC-1-related complex subunit 5 (BORCS5).	[10]

References

• [1] LOH12CR1 is a Novel Tumor Suppressor Inhibiting Tumor Growth Through Deregulation of G1/S Checkpoint in Human Colorectal Carcinoma.Curr Mol Med. 2018;18(1):25-35. doi: 10.2174/1566524018666180608084005.
• [2] Newly identified LMO3-BORCS5 fusion oncogene in Ewing sarcoma at relapse is a driver of tumor progression.Oncogene. 2019 Nov;38(47):7200-7215. doi: 10.1038/s41388-019-0914-3. Epub 2019 Sep 5.
• [3] Classification of Genes: Standardized Clinical Validity Assessment of Gene-Disease Associations Aids Diagnostic Exome Analysis and Reclassifications. Hum Mutat. 2017 May;38(5):600-608. doi: 10.1002/humu.23183. Epub 2017 Feb 13.
• [4] 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.
• [5] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [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] The exosome-like vesicles derived from androgen exposed-prostate stromal cells promote epithelial cells proliferation and epithelial-mesenchymal transition. Toxicol Appl Pharmacol. 2021 Jan 15;411:115384. doi: 10.1016/j.taap.2020.115384. Epub 2020 Dec 25.
• [9] Reproducible chemical-induced changes in gene expression profiles in human hepatoma HepaRG cells under various experimental conditions. Toxicol In Vitro. 2009 Apr;23(3):466-75. doi: 10.1016/j.tiv.2008.12.018. Epub 2008 Dec 30.
• [10] 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.
• [11] Comparison of transcriptome expression alterations by chronic exposure to low-dose bisphenol A in different subtypes of breast cancer cells. Toxicol Appl Pharmacol. 2019 Dec 15;385:114814. doi: 10.1016/j.taap.2019.114814. Epub 2019 Nov 9.