Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTUR3E76)

• DOT Name: Biogenesis of lysosome-related organelles complex 1 subunit 2 (BLOC1S2)
• Synonyms: BLOC-1 subunit 2; Centrosome-associated protein
• Gene Name: BLOC1S2
• Related Disease:
  Plasma cell myeloma
  Sciatica/lumbar radicular pain
  Thrombophilia
  Varicose veins
  Vein disorder
  Myeloproliferative neoplasm
  Psoriasis
  Venous thromboembolism
• UniProt ID: BL1S2_HUMAN
• Pfam ID: PF10046
• Sequence:
  MAAAAEGVLATRSDEPARDDAAVETAEEAKEPAEADITELCRDMFSKMATYLTGELTATS
  EDYKLLENMNKLTSLKYLEMKDIAINISRNLKDLNQKYAGLQPYLDQINVIEEQVAALEQ
  AAYKLDAYSKKLEAKYKKLEKR
• Function: Component of the BLOC-1 complex, a complex that is required for normal biogenesis of lysosome-related organelles (LRO), such as platelet dense granules and melanosomes. In concert with the AP-3 complex, the BLOC-1 complex is required to target membrane protein cargos into vesicles assembled at cell bodies for delivery into neurites and nerve terminals. The BLOC-1 complex, in association with SNARE proteins, is also proposed to be involved in neurite extension. 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. May play a role in cell proliferation.
• Tissue Specificity: Isoform 1 and isoform 2 are widely expressed. Expressed in various malignant tumor tissues (at protein level).

Molecular Interaction Atlas (MIA) of This DOT

8 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Plasma cell myeloma	DIS0DFZ0	Strong	Biomarker	[1]
Sciatica/lumbar radicular pain	DIS01KTQ	Strong	Biomarker	[2]
Thrombophilia	DISQR7U7	Strong	Biomarker	[3]
Varicose veins	DISIMBN2	Strong	Biomarker	[4]
Vein disorder	DISJQJNZ	Disputed	Genetic Variation	[5]
Myeloproliferative neoplasm	DIS5KAPA	Limited	Genetic Variation	[6]
Psoriasis	DIS59VMN	Limited	Genetic Variation	[7]
Venous thromboembolism	DISUR7CR	Limited	Genetic Variation	[8]

16 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 Biogenesis of lysosome-related organelles complex 1 subunit 2 (BLOC1S2).	[9]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Biogenesis of lysosome-related organelles complex 1 subunit 2 (BLOC1S2).	[10]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Biogenesis of lysosome-related organelles complex 1 subunit 2 (BLOC1S2).	[11]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Biogenesis of lysosome-related organelles complex 1 subunit 2 (BLOC1S2).	[12]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Biogenesis of lysosome-related organelles complex 1 subunit 2 (BLOC1S2).	[13]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Biogenesis of lysosome-related organelles complex 1 subunit 2 (BLOC1S2).	[14]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of Biogenesis of lysosome-related organelles complex 1 subunit 2 (BLOC1S2).	[16]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of Biogenesis of lysosome-related organelles complex 1 subunit 2 (BLOC1S2).	[17]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Biogenesis of lysosome-related organelles complex 1 subunit 2 (BLOC1S2).	[18]
Demecolcine	DMCZQGK	Approved	Demecolcine increases the expression of Biogenesis of lysosome-related organelles complex 1 subunit 2 (BLOC1S2).	[19]
Cannabidiol	DM0659E	Approved	Cannabidiol increases the expression of Biogenesis of lysosome-related organelles complex 1 subunit 2 (BLOC1S2).	[20]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Biogenesis of lysosome-related organelles complex 1 subunit 2 (BLOC1S2).	[9]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN increases the expression of Biogenesis of lysosome-related organelles complex 1 subunit 2 (BLOC1S2).	[21]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Biogenesis of lysosome-related organelles complex 1 subunit 2 (BLOC1S2).	[19]
Milchsaure	DM462BT	Investigative	Milchsaure increases the expression of Biogenesis of lysosome-related organelles complex 1 subunit 2 (BLOC1S2).	[22]
Deguelin	DMXT7WG	Investigative	Deguelin increases the expression of Biogenesis of lysosome-related organelles complex 1 subunit 2 (BLOC1S2).	[23]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Biogenesis of lysosome-related organelles complex 1 subunit 2 (BLOC1S2).	[15]

References

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• [3] Higher prevalence of thrombophilia in patients with varicose veins and venous ulcers than controls.J Vasc Surg. 2009 May;49(5):1235-41. doi: 10.1016/j.jvs.2008.12.017.
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• [5] A variant of the castor zinc finger 1 (CASZ1) gene is differentially associated with the clinical classification of chronic venous disease.Sci Rep. 2019 Sep 30;9(1):14011. doi: 10.1038/s41598-019-50586-2.
• [6] FGFR1 is fused to the centrosome-associated protein CEP110 in the 8p12 stem cell myeloproliferative disorder with t(8;9)(p12;q33).Blood. 2000 Mar 1;95(5):1788-96.
• [7] Large scale meta-analysis characterizes genetic architecture for common psoriasis associated variants.Nat Commun. 2017 May 24;8:15382. doi: 10.1038/ncomms15382.
• [8] Radiofrequency ablation with concomitant stab phlebectomy increases risk of endovenous heat-induced thrombosis.J Vasc Surg Venous Lymphat Disord. 2017 Mar;5(2):200-209. doi: 10.1016/j.jvsv.2016.10.081.
• [9] 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.
• [10] Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
• [11] 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.
• [12] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [13] The thioxotriazole copper(II) complex A0 induces endoplasmic reticulum stress and paraptotic death in human cancer cells. J Biol Chem. 2009 Sep 4;284(36):24306-19.
• [14] 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.
• [15] Prenatal arsenic exposure and the epigenome: identifying sites of 5-methylcytosine alterations that predict functional changes in gene expression in newborn cord blood and subsequent birth outcomes. Toxicol Sci. 2015 Jan;143(1):97-106. doi: 10.1093/toxsci/kfu210. Epub 2014 Oct 10.
• [16] 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.
• [17] 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.
• [18] 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.
• [19] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [20] Cannabidiol Activates Neuronal Precursor Genes in Human Gingival Mesenchymal Stromal Cells. J Cell Biochem. 2017 Jun;118(6):1531-1546. doi: 10.1002/jcb.25815. Epub 2016 Dec 29.
• [21] Endoplasmic reticulum stress impairs insulin signaling through mitochondrial damage in SH-SY5Y cells. Neurosignals. 2012;20(4):265-80.
• [22] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [23] Neurotoxicity and underlying cellular changes of 21 mitochondrial respiratory chain inhibitors. Arch Toxicol. 2021 Feb;95(2):591-615. doi: 10.1007/s00204-020-02970-5. Epub 2021 Jan 29.