Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTXL5KQW)

DOT Name BLOC-2 complex member HPS6 (HPS6)
Synonyms Hermansky-Pudlak syndrome 6 protein; Ruby-eye protein homolog; Ru
Gene Name HPS6
Related Disease
Hermansky-Pudlak syndrome 6 ( )
Coagulation defect ( )
Factor IX deficiency ( )
Hermansky-Pudlak syndrome ( )
Ocular albinism ( )
Hantavirus infection ( )
Hermansky-Pudlak syndrome without pulmonary fibrosis ( )
Oculocutaneous albinism ( )
UniProt ID
HPS6_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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Pfam ID
PF15702 ; PF20468
Sequence
MKRSGTLRLLSDLSAFGGAARLRELVAGDSAVRVRGSPDGRHLLLLRPPGAVAPQLLVAS
RGPGAELERAWPAGQPSPLDAFFLPWPARPALVLVWESGLAEVWGAGVGPGWRPLQSTEL
CPGGGARVVAVAALRGRLVWCEERQARAEGPSGSPAAAFSHCVCVRTLEPSGEASTSLGR
THVLLHHCPAFGLLASCRQLFLVPTATTWPGVAHVLLIWSPGKGKVMVAAPRLGLSYSKS
LNPGRGDTWDFRTLLRGLPGLLSPREPLAVHTWAPTPQGLLLLDFGGTVSLLQSHGGTRA
VGTLQEAPVGPWGSAALGTFQGTLACVLGSTLELLDMGSGQLLERKVLSTDRVHLLEPPA
PGMEDEEELETRGNLRLLSALGLFCVGWEAPQGVELPSAKDLVFEEACGYYQRRSLRGAQ
LTPEELRHSSTFRAPQALASILQGHLPPSALLTMLRTELRDYRGLEQLKAQLVAGDDEEA
GWTELAEQEVARLLRTELIGDQLAQLNTVFQALPTAAWGATLRALQLQLDGNGKLRSQAP
PDVWKKVLGGITAGKEPPNGILPPFELLCQCLCQLEPRWLPPFVELAQQQGGPGWGAGGP
GLPLYRRALAVLGEEGTRPEALELELLLSSGRPKAVLQAVGQLVQKEQWDRALDAGLALG
PSSPLLRSEIFKLLLAEFAQHRRLDAHLPLLCRLCPPELAPAELLLLLRTYLPDEVGPPT
PFPEPGAEPPLTVGLLKALLEQTGAQGWLSGPVLSPYEDILWDPSTPPPTPPRDL
Function
May regulate the synthesis and function of lysosomes and of highly specialized organelles, such as melanosomes and platelet dense granules. Acts as a cargo adapter for the dynein-dynactin motor complex to mediate the transport of lysosomes from the cell periphery to the perinuclear region. Facilitates retrograde lysosomal trafficking by linking the motor complex to lysosomes, and perinuclear positioning of lysosomes is crucial for the delivery of endocytic cargos to lysosomes, for lysosome maturation and functioning.
Tissue Specificity Ubiquitous.

Molecular Interaction Atlas (MIA) of This DOT

8 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Hermansky-Pudlak syndrome 6 DISIWQ1G Definitive Autosomal recessive [1]
Coagulation defect DIS9X3H6 Strong Genetic Variation [2]
Factor IX deficiency DISHN9SC Strong Genetic Variation [2]
Hermansky-Pudlak syndrome DISCY0HQ Strong CausalMutation [3]
Ocular albinism DIS5IHK1 Strong Genetic Variation [4]
Hantavirus infection DISZFTMH moderate Biomarker [5]
Hermansky-Pudlak syndrome without pulmonary fibrosis DIS0UYNY Supportive Autosomal recessive [6]
Oculocutaneous albinism DISJS7CU Disputed Genetic Variation [7]
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⏷ Show the Full List of 8 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
11 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Valproate DMCFE9I Approved Valproate decreases the expression of BLOC-2 complex member HPS6 (HPS6). [8]
Ciclosporin DMAZJFX Approved Ciclosporin decreases the expression of BLOC-2 complex member HPS6 (HPS6). [9]
Cupric Sulfate DMP0NFQ Approved Cupric Sulfate decreases the expression of BLOC-2 complex member HPS6 (HPS6). [10]
Ivermectin DMDBX5F Approved Ivermectin decreases the expression of BLOC-2 complex member HPS6 (HPS6). [11]
Marinol DM70IK5 Approved Marinol decreases the expression of BLOC-2 complex member HPS6 (HPS6). [12]
Cannabidiol DM0659E Approved Cannabidiol decreases the expression of BLOC-2 complex member HPS6 (HPS6). [13]
Urethane DM7NSI0 Phase 4 Urethane decreases the expression of BLOC-2 complex member HPS6 (HPS6). [14]
Leflunomide DMR8ONJ Phase 1 Trial Leflunomide decreases the expression of BLOC-2 complex member HPS6 (HPS6). [15]
Milchsaure DM462BT Investigative Milchsaure decreases the expression of BLOC-2 complex member HPS6 (HPS6). [16]
chloropicrin DMSGBQA Investigative chloropicrin decreases the expression of BLOC-2 complex member HPS6 (HPS6). [17]
methyl p-hydroxybenzoate DMO58UW Investigative methyl p-hydroxybenzoate increases the expression of BLOC-2 complex member HPS6 (HPS6). [18]
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⏷ Show the Full List of 11 Drug(s)

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 Identification of a novel mutation in HPS6 in a patient with hemophilia B and oculocutaneous albinism.Mol Genet Metab. 2016 Nov;119(3):284-287. doi: 10.1016/j.ymgme.2016.08.009. Epub 2016 Sep 3.
3 Diagnostic high-throughput sequencing of 2396 patients with bleeding, thrombotic, and platelet disorders.Blood. 2019 Dec 5;134(23):2082-2091. doi: 10.1182/blood.2018891192.
4 Novel HPS6 mutations identified by whole-exome sequencing in two Japanese sisters with suspected ocular albinism.J Hum Genet. 2016 Sep;61(9):839-42. doi: 10.1038/jhg.2016.56. Epub 2016 May 26.
5 The ophthalmic presentation of Hermansky-Pudlak syndrome 6.Br J Ophthalmol. 2016 Nov;100(11):1521-1524. doi: 10.1136/bjophthalmol-2015-308067. Epub 2016 Jan 28.
6 Clinical Practice Guidelines for Rare Diseases: The Orphanet Database. PLoS One. 2017 Jan 18;12(1):e0170365. doi: 10.1371/journal.pone.0170365. eCollection 2017.
7 Severe bleeding with subclinical oculocutaneous albinism in a patient with a novel HPS6 missense variant.Am J Med Genet A. 2018 Dec;176(12):2819-2823. doi: 10.1002/ajmg.a.40514. Epub 2018 Oct 4.
8 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.
9 Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
10 Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
11 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.
12 THC exposure of human iPSC neurons impacts genes associated with neuropsychiatric disorders. Transl Psychiatry. 2018 Apr 25;8(1):89. doi: 10.1038/s41398-018-0137-3.
13 Cannabidiol enhances cytotoxicity of anti-cancer drugs in human head and neck squamous cell carcinoma. Sci Rep. 2020 Nov 26;10(1):20622. doi: 10.1038/s41598-020-77674-y.
14 Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
15 Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
16 Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
17 Transcriptomic analysis of human primary bronchial epithelial cells after chloropicrin treatment. Chem Res Toxicol. 2015 Oct 19;28(10):1926-35.
18 Comparison of the global gene expression profiles produced by methylparaben, n-butylparaben and 17beta-oestradiol in MCF7 human breast cancer cells. J Appl Toxicol. 2007 Jan-Feb;27(1):67-77. doi: 10.1002/jat.1200.