Details of Drug Off-Target (DOT)

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

• DOT Name: Guanine nucleotide-binding protein-like 1 (GNL1)
• Synonyms: GTP-binding protein HSR1
• Gene Name: GNL1
• Related Disease:
  Gastric cancer
  Graves disease
  Major depressive disorder
  Rheumatoid arthritis
  Severe acute respiratory syndrome (SARS)
• UniProt ID: GNL1_HUMAN
• Pfam ID: PF01926
• Sequence:
  MPRKKPFSVKQKKKQLQDKRERKRGLQDGLRSSSNSRSGSRERREEQTDTSDGESVTHHI
  RRLNQQPSQGLGPRGYDPNRYRLHFERDSREEVERRKRAAREQVLQPVSAELLELDIREV
  YQPGSVLDFPRRPPWSYEMSKEQLMSQEERSFQDYLGKIHGAYSSEKLSYFEHNLETWRQ
  LWRVLEMSDIVLLITDIRHPVVNFPPALYEYVTGELGLALVLVLNKVDLAPPALVVAWKH
  YFHQHYPQLHVVLFTSFPRDPRTPQDPSSVLKKSRRRGRGWTRALGPEQLLRACEAITVG
  KVDLSSWREKIARDVAGATWGNGSGEEEEEEDGPAVLVEQQTDSAMEPTGPTQERYKDGV
  VTIGCVGFPNVGKSSLINGLVGRKVVSVSRTPGHTRYFQTYFLTPSVKLCDCPGLIFPSL
  LPRQLQVLAGIYPIAQIQEPYTAVGYLASRIPVQALLHLRHPEAEDPSAEHPWCAWDICE
  AWAEKRGYKTAKAARNDVYRAANSLLRLAVDGRLSLCFHPPGYSEQKGTWESHPETTELV
  VLQGRVGPAGDEEEEEEEELSSSCEEEGEEDRDADEEGEGDEETPTSAPGSSLAGRNPYA
  LLGEDEC
• Function: Possible regulatory or functional link with the histocompatibility cluster.

Molecular Interaction Atlas (MIA) of This DOT

5 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Gastric cancer	DISXGOUK	Strong	Altered Expression	[1]
Graves disease	DISU4KOQ	Strong	Biomarker	[2]
Major depressive disorder	DIS4CL3X	Strong	Genetic Variation	[3]
Rheumatoid arthritis	DISTSB4J	Strong	Genetic Variation	[4]
Severe acute respiratory syndrome (SARS)	DISYW14W	Limited	Biomarker	[5]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of Guanine nucleotide-binding protein-like 1 (GNL1).	[6]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Guanine nucleotide-binding protein-like 1 (GNL1).	[7]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Guanine nucleotide-binding protein-like 1 (GNL1).	[8]
Selenium	DM25CGV	Approved	Selenium increases the expression of Guanine nucleotide-binding protein-like 1 (GNL1).	[11]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Guanine nucleotide-binding protein-like 1 (GNL1).	[12]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Guanine nucleotide-binding protein-like 1 (GNL1).	[13]

5 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 Guanine nucleotide-binding protein-like 1 (GNL1).	[9]
Quercetin	DM3NC4M	Approved	Quercetin increases the phosphorylation of Guanine nucleotide-binding protein-like 1 (GNL1).	[10]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of Guanine nucleotide-binding protein-like 1 (GNL1).	[10]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Guanine nucleotide-binding protein-like 1 (GNL1).	[14]
Coumarin	DM0N8ZM	Investigative	Coumarin decreases the phosphorylation of Guanine nucleotide-binding protein-like 1 (GNL1).	[10]

References

• [1] Interplay between human nucleolar GNL1 and RPS20 is critical to modulate cell proliferation.Sci Rep. 2018 Jul 30;8(1):11421. doi: 10.1038/s41598-018-29802-y.
• [2] Single nucleotide polymorphisms at the PRR3, ABCF1, and GNL1 genes in the HLA class I region are associated with Graves' ophthalmopathy in a gender-dependent manner.Ophthalmology. 2014 Oct;121(10):2033-9. doi: 10.1016/j.ophtha.2014.04.027. Epub 2014 Jun 5.
• [3] Identification of 15 genetic loci associated with risk of major depression in individuals of European descent.Nat Genet. 2016 Sep;48(9):1031-6. doi: 10.1038/ng.3623. Epub 2016 Aug 1.
• [4] REL, encoding a member of the NF-kappaB family of transcription factors, is a newly defined risk locus for rheumatoid arthritis.Nat Genet. 2009 Jul;41(7):820-3. doi: 10.1038/ng.395. Epub 2009 Jun 7.
• [5] Coronaviridae and SARS-associated coronavirus strain HSR1.Emerg Infect Dis. 2004 Mar;10(3):413-8. doi: 10.3201/eid1003.030683.
• [6] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [7] Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
• [8] 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.
• [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] Quantitative phosphoproteomics reveal cellular responses from caffeine, coumarin and quercetin in treated HepG2 cells. Toxicol Appl Pharmacol. 2022 Aug 15;449:116110. doi: 10.1016/j.taap.2022.116110. Epub 2022 Jun 7.
• [11] Selenium and vitamin E: cell type- and intervention-specific tissue effects in prostate cancer. J Natl Cancer Inst. 2009 Mar 4;101(5):306-20.
• [12] New insights into BaP-induced toxicity: role of major metabolites in transcriptomics and contribution to hepatocarcinogenesis. Arch Toxicol. 2016 Jun;90(6):1449-58.
• [13] 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.
• [14] 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.