Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTDYB66V)

• DOT Name: Putative pre-mRNA-splicing factor ATP-dependent RNA helicase DHX32 (DHX32)
• Synonyms: EC 3.6.4.13; DEAD/H box 32; DEAD/H helicase-like protein 1; DHLP1; DEAH box protein 32; HuDDX32
• Gene Name: DHX32
• Related Disease:
  Breast cancer
  Breast carcinoma
  Colorectal carcinoma
  Leukemia
  Acute lymphocytic leukaemia
  Adult lymphoma
  Advanced cancer
  Lymphoma
  Pediatric lymphoma
  Retinopathy
  Rheumatoid arthritis
• UniProt ID: DHX32_HUMAN
• EC Number: 3.6.4.13
• Pfam ID: PF21010 ; PF04408 ; PF07717
• Sequence:
  MEEEGLECPNSSSEKRYFPESLDSSDGDEEEVLACEDLELNPFDGLPYSSRYYKLLKERE
  DLPIWKEKYSFMENLLQNQIVIVSGDAKCGKSAQVPQWCAEYCLSIHYQHGGVICTQVHK
  QTVVQLALRVADEMDVNIGHEVGYVIPFENCCTNETILRYCTDDMLQREMMSNPFLGSYG
  VIILDDIHERSIATDVLLGLLKDVLLARPELKLIINSSPHLISKLNSYYGNVPVIEVKNK
  HPVEVVYLSEAQKDSFESILRLIFEIHHSGEKGDIVVFLACEQDIEKVCETVYQGSNLNP
  DLGELVVVPLYPKEKCSLFKPLDETEKRCQVYQRRVVLTTSSGEFLIWSNSVRFVIDVGV
  ERRKVYNPRIRANSLVMQPISQSQAEIRKQILGSSSSGKFFCLYTEEFASKDMTPLKPAE
  MQEANLTSMVLFMKRIDIAGLGHCDFMNRPAPESLMQALEDLDYLAALDNDGNLSEFGII
  MSEFPLDPQLSKSILASCEFDCVDEVLTIAAMVTAPNCFSHVPHGAEEAALTCWKTFLHP
  EGDHFTLISIYKAYQDTTLNSSSEYCVEKWCRDYFLNCSALRMADVIRAELLEIIKRIEL
  PYAEPAFGSKENTLNIKKALLSGYFMQIARDVDGSGNYLMLTHKQVAQLHPLSGYSITKK
  MPEWVLFHKFSISENNYIRITSEISPELFMQLVPQYYFSNLPPSESKDILQQVVDHLSPV
  STMNKEQQMCETCPETEQRCTLQ
• Tissue Specificity: Expressed in lymphoid tissues (at protein level). Expressed in brain, heart, skeletal muscle, colon, thymus, spleen, kidney, liver, small intestine, placenta, lung, lymphoid tissues and blood leukocytes.

Molecular Interaction Atlas (MIA) of This DOT

11 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Breast cancer	DIS7DPX1	Strong	Altered Expression	[1]
Breast carcinoma	DIS2UE88	Strong	Altered Expression	[1]
Colorectal carcinoma	DIS5PYL0	Strong	Biomarker	[2]
Leukemia	DISNAKFL	Strong	Altered Expression	[3]
Acute lymphocytic leukaemia	DISPX75S	Limited	Biomarker	[4]
Adult lymphoma	DISK8IZR	Limited	Altered Expression	[4]
Advanced cancer	DISAT1Z9	Limited	Biomarker	[1]
Lymphoma	DISN6V4S	Limited	Altered Expression	[4]
Pediatric lymphoma	DIS51BK2	Limited	Altered Expression	[4]
Retinopathy	DISB4B0F	Limited	Autosomal recessive	[5]
Rheumatoid arthritis	DISTSB4J	Limited	Altered Expression	[6]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Putative pre-mRNA-splicing factor ATP-dependent RNA helicase DHX32 (DHX32).	[7]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Putative pre-mRNA-splicing factor ATP-dependent RNA helicase DHX32 (DHX32).	[8]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Putative pre-mRNA-splicing factor ATP-dependent RNA helicase DHX32 (DHX32).	[10]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Putative pre-mRNA-splicing factor ATP-dependent RNA helicase DHX32 (DHX32).	[11]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Putative pre-mRNA-splicing factor ATP-dependent RNA helicase DHX32 (DHX32).	[13]

2 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Putative pre-mRNA-splicing factor ATP-dependent RNA helicase DHX32 (DHX32).	[9]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Putative pre-mRNA-splicing factor ATP-dependent RNA helicase DHX32 (DHX32).	[12]

References

• [1] DHX32 expression is an indicator of poor breast cancer prognosis.Oncol Lett. 2017 Feb;13(2):942-948. doi: 10.3892/ol.2016.5503. Epub 2016 Dec 14.
• [2] DHX32 Promotes Angiogenesis in Colorectal Cancer Through Augmenting -catenin Signaling to Induce Expression of VEGFA.EBioMedicine. 2017 Apr;18:62-72. doi: 10.1016/j.ebiom.2017.03.012. Epub 2017 Mar 9.
• [3] The novel helicase homologue DDX32 is down-regulated in acute lymphoblastic leukemia.Leuk Res. 2002 Oct;26(10):945-54. doi: 10.1016/s0145-2126(02)00040-1.
• [4] Expression of DHX32 in lymphoid tissues.Exp Mol Pathol. 2005 Dec;79(3):219-23. doi: 10.1016/j.yexmp.2005.07.002. Epub 2005 Sep 21.
• [5] Classification of Genes: Standardized Clinical Validity Assessment of Gene-Disease Associations Aids Diagnostic Exome Analysis and Reclassifications. Hum Mutat. 2017 May;38(5):600-608. doi: 10.1002/humu.23183. Epub 2017 Feb 13.
• [6] Variation at FCGR2A and functionally related genes is associated with the response to anti-TNF therapy in rheumatoid arthritis.PLoS One. 2015 Apr 7;10(4):e0122088. doi: 10.1371/journal.pone.0122088. eCollection 2015.
• [7] Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
• [8] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [9] Prenatal arsenic exposure and the epigenome: identifying sites of 5-methylcytosine alterations that predict functional changes in gene expression in newborn cord blood and subsequent birth outcomes. Toxicol Sci. 2015 Jan;143(1):97-106. doi: 10.1093/toxsci/kfu210. Epub 2014 Oct 10.
• [10] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [11] Cell-based two-dimensional morphological assessment system to predict cancer drug-induced cardiotoxicity using human induced pluripotent stem cell-derived cardiomyocytes. Toxicol Appl Pharmacol. 2019 Nov 15;383:114761. doi: 10.1016/j.taap.2019.114761. Epub 2019 Sep 15.
• [12] DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.
• [13] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.