Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTLHCJ6C)

• DOT Name: Protein dpy-30 homolog (DPY30)
• Synonyms: Dpy-30-like protein; Dpy-30L
• Gene Name: DPY30
• Related Disease:
  Cholangiocarcinoma
  Congenital contractural arachnodactyly
  Epithelial ovarian cancer
  Hereditary spastic paraplegia
  Hereditary spastic paraplegia 4
  Neoplasm
  Vascular purpura
  leukaemia
  Leukemia
  Alopecia
  Androgenetic alopecia
  Baldness, male pattern
  Hepatocellular carcinoma
• UniProt ID: DPY30_HUMAN
• PDB ID: 3G36; 4RIQ; 4RT4; 4RTA; 6E2H; 6PWV; 7UD5
• Pfam ID: PF05186
• Sequence:
  MEPEQMLEGQTQVAENPHSEYGLTDNVERIVENEKINAEKSSKQKVDLQSLPTRAYLDQT
  VVPILLQGLAVLAKERPPNPIEFLASYLLKNKAQFEDRN
• Function: As part of the MLL1/MLL complex, involved in the methylation of histone H3 at 'Lys-4', particularly trimethylation. Histone H3 'Lys-4' methylation represents a specific tag for epigenetic transcriptional activation. May play some role in histone H3 acetylation. In a teratocarcinoma cell, plays a crucial role in retinoic acid-induced differentiation along the neural lineage, regulating gene induction and H3 'Lys-4' methylation at key developmental loci. May also play an indirect or direct role in endosomal transport.
• Reactome Pathway:
  Activation of anterior HOX genes in hindbrain development during early embryogenesis (R-HSA-5617472)
  RUNX1 regulates genes involved in megakaryocyte differentiation and platelet function (R-HSA-8936459)
  Formation of WDR5-containing histone-modifying complexes (R-HSA-9772755)
  PKMTs methylate histone lysines (R-HSA-3214841)

Molecular Interaction Atlas (MIA) of This DOT

13 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Cholangiocarcinoma	DIS71F6X	Strong	Biomarker	[1]
Congenital contractural arachnodactyly	DISOM1K7	Strong	Altered Expression	[1]
Epithelial ovarian cancer	DIS56MH2	Strong	Biomarker	[2]
Hereditary spastic paraplegia	DISGZQV1	Strong	Genetic Variation	[3]
Hereditary spastic paraplegia 4	DISFUYL2	Strong	Genetic Variation	[4]
Neoplasm	DISZKGEW	Strong	Altered Expression	[1]
Vascular purpura	DIS6ZZMF	Strong	Altered Expression	[5]
leukaemia	DISS7D1V	moderate	Biomarker	[6]
Leukemia	DISNAKFL	moderate	Biomarker	[6]
Alopecia	DIS37HU4	Limited	Genetic Variation	[7]
Androgenetic alopecia	DISSJR1P	Limited	Genetic Variation	[8]
Baldness, male pattern	DIS9C9RO	Limited	Genetic Variation	[8]
Hepatocellular carcinoma	DIS0J828	Limited	Altered Expression	[9]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Protein dpy-30 homolog (DPY30).	[10]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Protein dpy-30 homolog (DPY30).	[11]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Protein dpy-30 homolog (DPY30).	[12]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Protein dpy-30 homolog (DPY30).	[13]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Protein dpy-30 homolog (DPY30).	[14]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Protein dpy-30 homolog (DPY30).	[15]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Protein dpy-30 homolog (DPY30).	[16]

References

• [1] Upregulation of DPY30 promotes cell proliferation and predicts a poor prognosis in cholangiocarcinoma.Biomed Pharmacother. 2020 Mar;123:109766. doi: 10.1016/j.biopha.2019.109766. Epub 2019 Dec 14.
• [2] DPY30 is required for the enhanced proliferation, motility and epithelial-mesenchymal transition of epithelial ovarian cancer cells.Int J Mol Med. 2018 Dec;42(6):3065-3072. doi: 10.3892/ijmm.2018.3869. Epub 2018 Sep 11.
• [3] Mechanistic basis of an epistatic interaction reducing age at onset in hereditary spastic paraplegia.Brain. 2018 May 1;141(5):1286-1299. doi: 10.1093/brain/awy034.
• [4] Partial SPAST and DPY30 deletions in a Japanese spastic paraplegia type 4 family.Neurogenetics. 2011 Feb;12(1):25-31. doi: 10.1007/s10048-010-0260-7. Epub 2010 Sep 22.
• [5] Novel SPAST deletion and reduced DPY30 expression in a Spastic Paraplegia type 4 kindred.BMC Med Genet. 2014 Apr 1;15:39. doi: 10.1186/1471-2350-15-39.
• [6] Specific inhibition of DPY30 activity by ASH2L-derived peptides suppresses blood cancer cell growth.Exp Cell Res. 2019 Sep 15;382(2):111485. doi: 10.1016/j.yexcr.2019.06.030. Epub 2019 Jun 26.
• [7] Genetic prediction of male pattern baldness.PLoS Genet. 2017 Feb 14;13(2):e1006594. doi: 10.1371/journal.pgen.1006594. eCollection 2017 Feb.
• [8] GWAS for male-pattern baldness identifies 71 susceptibility loci explaining 38% of the risk.Nat Commun. 2017 Nov 17;8(1):1584. doi: 10.1038/s41467-017-01490-8.
• [9] DPY30 functions in glucose homeostasis via integrating activated histone epigenetic modifications.Biochem Biophys Res Commun. 2018 Dec 9;507(1-4):286-290. doi: 10.1016/j.bbrc.2018.11.023. Epub 2018 Nov 15.
• [10] Bringing in vitro analysis closer to in vivo: studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling. Toxicol Lett. 2018 Sep 15;294:184-192.
• [11] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [12] Genistein and bisphenol A exposure cause estrogen receptor 1 to bind thousands of sites in a cell type-specific manner. Genome Res. 2012 Nov;22(11):2153-62.
• [13] 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.
• [14] 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.
• [15] 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.
• [16] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.