Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT96NE03)

• DOT Name: Biogenesis of lysosome-related organelles complex 1 subunit 6 (BLOC1S6)
• Synonyms: BLOC-1 subunit 6; Pallid protein homolog; Pallidin; Syntaxin 13-interacting protein
• Gene Name: BLOC1S6
• Related Disease:
  Hermansky-Pudlak syndrome 9
  Albinism
  Hantavirus infection
  Hermansky-Pudlak syndrome
  Platelet storage pool deficiency
  Schizophrenia
• UniProt ID: BL1S6_HUMAN
• Pfam ID: PF14712
• Sequence:
  MSVPGPSSPDGALTRPPYCLEAGEPTPGLSDTSPDEGLIEDLTIEDKAVEQLAEGLLSHY
  LPDLQRSKQALQELTQNQVVLLDTLEQEISKFKECHSMLDINALFAEAKHYHAKLVNIRK
  EMLMLHEKTSKLKKRALKLQQKRQKEELEREQQREKEFEREKQLTARPAKRM
• 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. May play a role in intracellular vesicle trafficking, particularly in the vesicle-docking and fusion process.
• Tissue Specificity: Widely expressed.
• Reactome Pathway: Golgi Associated Vesicle Biogenesis (R-HSA-432722)

Molecular Interaction Atlas (MIA) of This DOT

6 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Hermansky-Pudlak syndrome 9	DISVT0J8	Definitive	Autosomal recessive	[1]
Albinism	DIS5D82I	Strong	Biomarker	[2]
Hantavirus infection	DISZFTMH	Strong	Biomarker	[2]
Hermansky-Pudlak syndrome	DISCY0HQ	Strong	Genetic Variation	[2]
Platelet storage pool deficiency	DISHODOH	Strong	Biomarker	[3]
Schizophrenia	DISSRV2N	Strong	Biomarker	[4]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Biogenesis of lysosome-related organelles complex 1 subunit 6 (BLOC1S6).	[5]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Biogenesis of lysosome-related organelles complex 1 subunit 6 (BLOC1S6).	[6]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of Biogenesis of lysosome-related organelles complex 1 subunit 6 (BLOC1S6).	[7]
Phenobarbital	DMXZOCG	Approved	Phenobarbital affects the expression of Biogenesis of lysosome-related organelles complex 1 subunit 6 (BLOC1S6).	[8]
Heroin diacetylmorphine	DMDBWHY	Approved	Heroin diacetylmorphine decreases the expression of Biogenesis of lysosome-related organelles complex 1 subunit 6 (BLOC1S6).	[9]
Coumestrol	DM40TBU	Investigative	Coumestrol decreases the expression of Biogenesis of lysosome-related organelles complex 1 subunit 6 (BLOC1S6).	[11]

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 affects the methylation of Biogenesis of lysosome-related organelles complex 1 subunit 6 (BLOC1S6).	[10]

References

• [1] Technical standards for the interpretation and reporting of constitutional copy-number variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics (ACMG) and the Clinical Genome Resource (ClinGen). Genet Med. 2020 Feb;22(2):245-257. doi: 10.1038/s41436-019-0686-8. Epub 2019 Nov 6.
• [2] A BLOC-1 mutation screen reveals that PLDN is mutated in Hermansky-Pudlak Syndrome type 9. Am J Hum Genet. 2011 Jun 10;88(6):778-787. doi: 10.1016/j.ajhg.2011.05.009.
• [3] Dysregulation of PLDN (pallidin) is a mechanism for platelet dense granule deficiency in RUNX1 haplodeficiency.J Thromb Haemost. 2017 Apr;15(4):792-801. doi: 10.1111/jth.13619. Epub 2017 Feb 23.
• [4] Pallidin protein in neurodevelopment and its relation to the pathogenesis of schizophrenia.Mol Med Rep. 2017 Feb;15(2):665-672. doi: 10.3892/mmr.2016.6064. Epub 2016 Dec 21.
• [5] Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
• [6] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [7] 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.
• [8] 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.
• [9] Distinctive profiles of gene expression in the human nucleus accumbens associated with cocaine and heroin abuse. Neuropsychopharmacology. 2006 Oct;31(10):2304-12. doi: 10.1038/sj.npp.1301089. Epub 2006 May 3.
• [10] Effect of aflatoxin B(1), benzo[a]pyrene, and methapyrilene on transcriptomic and epigenetic alterations in human liver HepaRG cells. Food Chem Toxicol. 2018 Nov;121:214-223. doi: 10.1016/j.fct.2018.08.034. Epub 2018 Aug 26.
• [11] Pleiotropic combinatorial transcriptomes of human breast cancer cells exposed to mixtures of dietary phytoestrogens. Food Chem Toxicol. 2009 Apr;47(4):787-95.