Details of Drug Off-Target (DOT)

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

• DOT Name: Biogenesis of lysosome-related organelles complex 1 subunit 4 (BLOC1S4)
• Synonyms: BLOC-1 subunit 4; Protein cappuccino homolog
• Gene Name: BLOC1S4
• Related Disease:
  Anxiety
  Anxiety disorder
  Hermansky-Pudlak syndrome
  Chronic recurrent multifocal osteomyelitis
  Inflammation
• UniProt ID: BL1S4_HUMAN
• Sequence:
  MEGSFSDGGALPEGLAEEAEPQGAAWSGDSGTVSQSHSSASGPWEDEGAEDGAPGRDLPL
  LRRAAAGYAACLLPGAGARPEVEALDASLEDLLTRVDEFVGMLDMLRGDSSHVVSEGVPR
  IHAKAAEMRRIYSRIDRLEAFVRMVGGRVARMEEQVTKAEAELGTFPRAFKKLLHTMNVP
  SLFSKSAPSRPQQAGYEAPVLFRTEDYFPCCSERPQL
• 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.
• Reactome Pathway: Golgi Associated Vesicle Biogenesis (R-HSA-432722)

Molecular Interaction Atlas (MIA) of This DOT

5 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Anxiety	DISIJDBA	Definitive	Biomarker	[1]
Anxiety disorder	DISBI2BT	Definitive	Biomarker	[1]
Hermansky-Pudlak syndrome	DISCY0HQ	Strong	Genetic Variation	[2]
Chronic recurrent multifocal osteomyelitis	DIST1OU2	Limited	Biomarker	[3]
Inflammation	DISJUQ5T	Limited	Biomarker	[3]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Biogenesis of lysosome-related organelles complex 1 subunit 4 (BLOC1S4).	[4]
Diethylstilbestrol	DMN3UXQ	Approved	Diethylstilbestrol decreases the expression of Biogenesis of lysosome-related organelles complex 1 subunit 4 (BLOC1S4).	[5]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Biogenesis of lysosome-related organelles complex 1 subunit 4 (BLOC1S4).	[6]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Biogenesis of lysosome-related organelles complex 1 subunit 4 (BLOC1S4).	[7]

References

• [1] The impact of silencing feed-forward parvalbumin-expressing inhibitory interneurons in the cortico-thalamocortical network on seizure generation and behaviour.Neurobiol Dis. 2019 Dec;132:104610. doi: 10.1016/j.nbd.2019.104610. Epub 2019 Sep 5.
• [2] Defects in the cappuccino (cno) gene on mouse chromosome 5 and human 4p cause Hermansky-Pudlak syndrome by an AP-3-independent mechanism.Blood. 2000 Dec 15;96(13):4227-35.
• [3] Mutation screening of the IL-1 receptor antagonist gene in chronic non-bacterial osteomyelitis of childhood and adolescence.Clin Exp Rheumatol. 2011 Nov-Dec;29(6):1040-3. Epub 2011 Dec 22.
• [4] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [5] Identification of biomarkers and outcomes of endocrine disruption in human ovarian cortex using In Vitro Models. Toxicology. 2023 Feb;485:153425. doi: 10.1016/j.tox.2023.153425. Epub 2023 Jan 5.
• [6] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [7] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.