Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTRV6LXB)

• DOT Name: Nucleolar protein 11 (NOL11)
• Gene Name: NOL11
• Related Disease:
  Hereditary North American Indian childhood cirrhosis
  Tooth agenesis
  Tooth agenesis, selective, 1
• UniProt ID: NOL11_HUMAN
• Pfam ID: PF20998 ; PF08168
• Sequence:
  MAALEEEFTLSSVVLSAGPEGLLGVEQSDKTDQFLVTDSGRTVILYKVSDQKPLGSWSVK
  QGQIITCPAVCNFQTGEYVVVHDNKVLRIWNNEDVNLDKVFKATLSAEVYRILSVQGTEP
  LVLFKEGAVRGLEALLADPQQKIETVISDEEVIKWTKFFVVFRHPVLIFITEKHGNYFAY
  VQMFNSRILTKYTLLLGQDENSVIKSFTASVDRKFISLMSLSSDGCIYETLIPIRPADPE
  KNQSLVKSLLLKAVVSGNARNGVALTALDQDHVAVLGSPLAASKECLSVWNIKFQTLQTS
  KELPQGTSGQLWYYGEHLFMLHGKSLTVIPYKCEVSSLAGALGKLKHSQDPGTHVVSHFV
  NWETPQGCGLGFQNSEQSRRILRRRKIEVSLQPEVPPSKQLLSTIMKDSEKHIEVEVRKF
  LALKQTPDFHTVIGDTVTGLLERCKAEPSFYPRNCLMQLIQTHVLSYSLCPDLMEIALKK
  KDVQLLQLCLQQFPDIPESVTCACLKIFLSIGDDSLQETDVNMESVFDYSINSVHDEKME
  EQTEILQNGFNPEEDKCNNCDQELNKKPQDETKESTSCPVVQKRAALLNAILHSAYSETF
  LLPHLKDIPAQHITLFLKYLYFLYLKCSENATMTLPGIHPPTLNQIMDWICLLLDANFTV
  VVMMPEAKRLLINLYKLVKSQISVYSELNKIEVSFRELQKLNQEKNNRGLYSIEVLELF
• Function: Ribosome biogenesis factor. May be required for both optimal rDNA transcription and small subunit (SSU) pre-rRNA processing at sites A', A0, 1 and 2b.
• Reactome Pathway:
  Major pathway of rRNA processing in the nucleolus and cytosol (R-HSA-6791226)
  rRNA modification in the nucleus and cytosol (R-HSA-6790901)

Molecular Interaction Atlas (MIA) of This DOT

3 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Hereditary North American Indian childhood cirrhosis	DISBJ6T5	Strong	Biomarker	[1]
Tooth agenesis	DIS1PWC7	Strong	Genetic Variation	[2]
Tooth agenesis, selective, 1	DIS84ERL	Strong	Genetic Variation	[2]

13 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 Nucleolar protein 11 (NOL11).	[3]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Nucleolar protein 11 (NOL11).	[4]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Nucleolar protein 11 (NOL11).	[5]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Nucleolar protein 11 (NOL11).	[6]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Nucleolar protein 11 (NOL11).	[7]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Nucleolar protein 11 (NOL11).	[8]
Marinol	DM70IK5	Approved	Marinol decreases the expression of Nucleolar protein 11 (NOL11).	[9]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Nucleolar protein 11 (NOL11).	[10]
GSK2110183	DMZHB37	Phase 2	GSK2110183 decreases the expression of Nucleolar protein 11 (NOL11).	[11]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Nucleolar protein 11 (NOL11).	[12]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Nucleolar protein 11 (NOL11).	[13]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A affects the expression of Nucleolar protein 11 (NOL11).	[14]
KOJIC ACID	DMP84CS	Investigative	KOJIC ACID decreases the expression of Nucleolar protein 11 (NOL11).	[15]

References

• [1] NOL11, implicated in the pathogenesis of North American Indian childhood cirrhosis, is required for pre-rRNA transcription and processing.PLoS Genet. 2012;8(8):e1002892. doi: 10.1371/journal.pgen.1002892. Epub 2012 Aug 16.
• [2] Rare and Common Variants Conferring Risk of Tooth Agenesis.J Dent Res. 2018 May;97(5):515-522. doi: 10.1177/0022034517750109. Epub 2018 Jan 24.
• [3] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [4] 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.
• [5] 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.
• [6] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [7] 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.
• [8] Temozolomide induces activation of Wnt/-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278. doi: 10.1007/s10565-019-09502-7. Epub 2019 Nov 22.
• [9] 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.
• [10] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [11] Novel ATP-competitive Akt inhibitor afuresertib suppresses the proliferation of malignant pleural mesothelioma cells. Cancer Med. 2017 Nov;6(11):2646-2659. doi: 10.1002/cam4.1179. Epub 2017 Sep 27.
• [12] 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.
• [13] Bisphenol A induces DSB-ATM-p53 signaling leading to cell cycle arrest, senescence, autophagy, stress response, and estrogen release in human fetal lung fibroblasts. Arch Toxicol. 2018 Apr;92(4):1453-1469.
• [14] A trichostatin A expression signature identified by TempO-Seq targeted whole transcriptome profiling. PLoS One. 2017 May 25;12(5):e0178302. doi: 10.1371/journal.pone.0178302. eCollection 2017.
• [15] Toxicogenomics of kojic acid on gene expression profiling of a375 human malignant melanoma cells. Biol Pharm Bull. 2006 Apr;29(4):655-69.