Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTE3LL6Q)

• DOT Name: Biogenesis of lysosome-related organelles complex 1 subunit 5 (BLOC1S5)
• Synonyms: BLOC-1 subunit 5; Protein Muted homolog
• Gene Name: BLOC1S5
• Related Disease:
  Hermansky-Pudlak syndrome 11
  Platelet storage pool deficiency
  Hermansky-Pudlak syndrome
• UniProt ID: BL1S5_HUMAN
• Pfam ID: PF14942
• Sequence:
  MSGGGTETPVGCEAAPGGGSKKRDSLGTAGSAHLIIKDLGEIHSRLLDHRPVIQGETRYF
  VKEFEEKRGLREMRVLENLKNMIHETNEHTLPKCRDTMRDSLSQVLQRLQAANDSVCRLQ
  QREQERKKIHSDHLVASEKQHMLQWDNFMKEQPNKRAEVDEEHRKAMERLKEQYAEMEKD
  LAKFSTF
• 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. Plays a role in intracellular vesicle trafficking.

Molecular Interaction Atlas (MIA) of This DOT

3 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Hermansky-Pudlak syndrome 11	DIS30IDN	Strong	Autosomal recessive	[1]
Platelet storage pool deficiency	DISHODOH	Strong	Biomarker	[2]
Hermansky-Pudlak syndrome	DISCY0HQ	Moderate	Autosomal recessive	[3]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Biogenesis of lysosome-related organelles complex 1 subunit 5 (BLOC1S5).	[4]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Biogenesis of lysosome-related organelles complex 1 subunit 5 (BLOC1S5).	[5]
Zoledronate	DMIXC7G	Approved	Zoledronate increases the expression of Biogenesis of lysosome-related organelles complex 1 subunit 5 (BLOC1S5).	[6]
Permethrin	DMZ0Q1G	Approved	Permethrin increases the expression of Biogenesis of lysosome-related organelles complex 1 subunit 5 (BLOC1S5).	[7]

References

• [1] BLOC1S5 pathogenic variants cause a new type of Hermansky-Pudlak syndrome. Genet Med. 2020 Oct;22(10):1613-1622. doi: 10.1038/s41436-020-0867-5. Epub 2020 Jun 22.
• [2] Characterization of melanosomes in murine Hermansky-Pudlak syndrome: mechanisms of hypopigmentation.J Invest Dermatol. 2004 Feb;122(2):452-60. doi: 10.1046/j.0022-202X.2004.22117.x.
• [3] 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.
• [4] Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
• [5] Gene expression analysis of precision-cut human liver slices indicates stable expression of ADME-Tox related genes. Toxicol Appl Pharmacol. 2011 May 15;253(1):57-69.
• [6] The proapoptotic effect of zoledronic acid is independent of either the bone microenvironment or the intrinsic resistance to bortezomib of myeloma cells and is enhanced by the combination with arsenic trioxide. Exp Hematol. 2011 Jan;39(1):55-65.
• [7] Exposure to Insecticides Modifies Gene Expression and DNA Methylation in Hematopoietic Tissues In Vitro. Int J Mol Sci. 2023 Mar 26;24(7):6259. doi: 10.3390/ijms24076259.