Details of Drug Off-Target (DOT)

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

• DOT Name: Glutamine-rich protein 2 (QRICH2)
• Gene Name: QRICH2
• Related Disease:
  Gout
  Male infertility
  Spermatogenic failure 35
  Epithelial ovarian cancer
• UniProt ID: QRIC2_HUMAN
• Pfam ID: PF16043
• Sequence:
  MKDAAEELSFARVLLQRVDELEKLFKDREQFLELVSRKLSLVPGAEEVTMVTWEELEQAI
  TDGWRASQAGSETLMGFSKHGGFTSLTSPEGTLSGDSTKQPSIEQALDSASGLGPDRTAS
  GSGGTAHPSDGVSSREQSKVPSGTGRQQQPRARDEAGVPRLHQSSTFQFKSDSDRHRSRE
  KLTSTQPRRNARPGPVQQDLPLARDQPSSVPASQSQVHLRPDRRGLEPTGMNQPGLVPAS
  TYPHGVVPLSMGQLGVPPPEMDDRELIPFVVDEQRMLPPSVPGRDQQGLELPSTDQHGLV
  SVSAYQHGMTFPGTDQRSMEPLGMDQRGCVISGMGQQGLVPPGIDQQGLTLPVVDQHGLV
  LPFTDQHGLVSPGLMPISADQQGFVQPSLEATGFIQPGTEQHDLIQSGRFQRALVQRGAY
  QPGLVQPGADQRGLVRPGMDQSGLAQPGADQRGLVWPGMDQSGLAQPGRDQHGLIQPGTG
  QHDLVQSGTGQGVLVQPGVDQPGMVQPGRFQRALVQPGAYQPGLVQPGADQIDVVQPGAD
  QHGLVQSGADQSDLAQPGAVQHGLVQPGVDQRGLAQPRADHQRGLVPPGADQRGLVQPGA
  DQHGLVQPGVDQHGLAQPGEVQRSLVQPGIVQRGLVQPGAVQRGLVQPGAVQRGLVQPGV
  DQRGLVQPGAVQRGLVQPGAVQHGLVQPGADQRGLVQPGVDQRGLVQPGVDQRGLVQPGM
  DQRGLIQPGADQPGLVQPGAGQLGMVQPGIGQQGMVQPQADPHGLVQPGAYPLGLVQPGA
  YLHDLSQSGTYPRGLVQPGMDQYGLRQPGAYQPGLIAPGTKLRGSSTFQADSTGFISVRP
  YQHGMVPPGREQYGQVSPLLASQGLASPGIDRRSLVPPETYQQGLMHPGTDQHSPIPLST
  GLGSTHPDQQHVASPGPGEHDQVYPDAAQHGHAFSLFDSHDSMYPGYRGPGYLSADQHGQ
  EGLDPNRTRASDRHGIPAQKAPGQDVTLFRSPDSVDRVLSEGSEVSSEVLSERRNSLRRM
  SSSFPTAVETFHLMGELSSLYVGLKESMKDLDEEQAGQTDLEKIQFLLAQMVKRTIPPEL
  QEQLKTVKTLAKEVWQEKAKVERLQRILEGEGNQEAGKELKAGELRLQLGVLRVTVADIE
  KELAELRESQDRGKAAMENSVSEASLYLQDQLDKLRMIIESMLTSSSTLLSMSMAPHKAH
  TLAPGQIDPEATCPACSLDVSHQVSTLVRRYEQLQDMVNSLAVSRPSKKAKLQRQDEELL
  GRVQSAILQVQGDCEKLNITTSNLIEDHRQKQKDIAMLYQGLEKLEKEKANREHLEMEID
  VKADKSALATKVSRVQFDATTEQLNHMMQELVAKMSGQEQDWQKMLDRLLTEMDNKLDRL
  ELDPVKQLLEDRWKSLRQQLRERPPLYQADEAAAMRRQLLAHFHCLSCDRPLETPVTGHA
  IPVTPAGPGLPGHHSIRPYTVFELEQVRQHSRNLKLGSAFPRGDLAQMEQSVGRLRSMHS
  KMLMNIEKVQIHFGGSTKASSQIIRELLHAQCLGSPCYKRVTDMADYTYSTVPRRCGGSH
  TLTYPYHRSRPQHLPRGLYPTEEIQIAMKHDEVDILGLDGHIYKGRMDTRLPGILRKDSS
  GTSKRKSQQPRPHVHRPPSLSSNGQLPSRPQSAQISAGNTSER
• Function: Has an essential role in the formation of sperm flagella and flagellar structure maintainance. It acts as a suppressor of ubiquitination and degradation of proteins involved in flagellar development and motility.
• Tissue Specificity: Expressed in the sperm.

Molecular Interaction Atlas (MIA) of This DOT

4 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Gout	DISHC0U7	Strong	Genetic Variation	[1]
Male infertility	DISY3YZZ	Strong	Biomarker	[2]
Spermatogenic failure 35	DIS8RY95	Strong	Autosomal recessive	[2]
Epithelial ovarian cancer	DIS56MH2	moderate	Biomarker	[3]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of Glutamine-rich protein 2 (QRICH2).	[4]
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Glutamine-rich protein 2 (QRICH2).	[6]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of Glutamine-rich protein 2 (QRICH2).	[9]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Glutamine-rich protein 2 (QRICH2).	[5]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of Glutamine-rich protein 2 (QRICH2).	[7]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Glutamine-rich protein 2 (QRICH2).	[8]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane increases the expression of Glutamine-rich protein 2 (QRICH2).	[10]

References

• [1] Genome-wide association analyses identify 18 new loci associated with serum urate concentrations. Nat Genet. 2013 Feb;45(2):145-54. doi: 10.1038/ng.2500. Epub 2012 Dec 23.
• [2] Loss-of-function mutations in QRICH2 cause male infertility with multiple morphological abnormalities of the sperm flagella. Nat Commun. 2019 Jan 25;10(1):433. doi: 10.1038/s41467-018-08182-x.
• [3] Loss of heterozygosity and transcriptome analyses of a 1.2 Mb candidate ovarian cancer tumor suppressor locus region at 17q25.1-q25.2.Mol Carcinog. 2005 Jul;43(3):141-54. doi: 10.1002/mc.20096.
• [4] 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.
• [5] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [6] 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.
• [7] 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.
• [8] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [9] Air pollution and DNA methylation alterations in lung cancer: A systematic and comparative study. Oncotarget. 2017 Jan 3;8(1):1369-1391. doi: 10.18632/oncotarget.13622.
• [10] Transcriptome and DNA methylation changes modulated by sulforaphane induce cell cycle arrest, apoptosis, DNA damage, and suppression of proliferation in human liver cancer cells. Food Chem Toxicol. 2020 Feb;136:111047. doi: 10.1016/j.fct.2019.111047. Epub 2019 Dec 12.