Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT4J2VAL)

• DOT Name: Nuclear pore complex protein Nup93 (NUP93)
• Synonyms: 93 kDa nucleoporin; Nucleoporin Nup93
• Gene Name: NUP93
• Related Disease:
  Cerebellar ataxia
  Cervical cancer
  Cervical carcinoma
  Megalencephalic leukoencephalopathy with subcortical cysts
  Neoplasm
  Nephrotic syndrome, type 12
  Nephrotic syndrome, type 2
  Steroid-resistant nephrotic syndrome
  Thyroid gland papillary carcinoma
  Visceral leishmaniasis
  Influenza
  Familial idiopathic steroid-resistant nephrotic syndrome
• UniProt ID: NUP93_HUMAN
• PDB ID: 5IJN; 5IJO; 7MW0; 7MW1; 7PER; 7R5J; 7R5K
• Pfam ID: PF04097
• Sequence:
  MDTEGFGELLQQAEQLAAETEGISELPHVERNLQEIQQAGERLRSRTLTRTSQETADVKA
  SVLLGSRGLDISHISQRLESLSAATTFEPLEPVKDTDIQGFLKNEKDNALLSAIEESRKR
  TFGMAEEYHRESMLVEWEQVKQRILHTLLASGEDALDFTQESEPSYISDVGPPGRSSLDN
  IEMAYARQIYIYNEKIVNGHLQPNLVDLCASVAELDDKSISDMWTMVKQMTDVLLTPATD
  ALKNRSSVEVRMEFVRQALAYLEQSYKNYTLVTVFGNLHQAQLGGVPGTYQLVRSFLNIK
  LPAPLPGLQDGEVEGHPVWALIYYCMRCGDLLAASQVVNRAQHQLGEFKTWFQEYMNSKD
  RRLSPATENKLRLHYRRALRNNTDPYKRAVYCIIGRCDVTDNQSEVADKTEDYLWLKLNQ
  VCFDDDGTSSPQDRLTLSQFQKQLLEDYGESHFTVNQQPFLYFQVLFLTAQFEAAVAFLF
  RMERLRCHAVHVALVLFELKLLLKSSGQSAQLLSHEPGDPPCLRRLNFVRLLMLYTRKFE
  STDPREALQYFYFLRDEKDSQGENMFLRCVSELVIESREFDMILGKLENDGSRKPGVIDK
  FTSDTKPIINKVASVAENKGLFEEAAKLYDLAKNADKVLELMNKLLSPVVPQISAPQSNK
  ERLKNMALSIAERYRAQGISANKFVDSTFYLLLDLITFFDEYHSGHIDRAFDIIERLKLV
  PLNQESVEERVAAFRNFSDEIRHNLSEVLLATMNILFTQFKRLKGTSPSSSSRPQRVIED
  RDSQLRSQARTLITFAGMIPYRTSGDTNARLVQMEVLMN
• Function: Plays a role in the nuclear pore complex (NPC) assembly and/or maintenance. May anchor nucleoporins, but not NUP153 and TPR, to the NPC. During renal development, regulates podocyte migration and proliferation through SMAD4 signaling.
• KEGG Pathway:
  Nucleocytoplasmic transport (hsa03013)
  Amyotrophic lateral sclerosis (hsa05014)
• Reactome Pathway:
  Transport of the SLBP independent Mature mRNA (R-HSA-159227)
  Transport of the SLBP Dependant Mature mRNA (R-HSA-159230)
  Transport of Mature mRNA Derived from an Intronless Transcript (R-HSA-159231)
  Transport of Mature mRNA derived from an Intron-Containing Transcript (R-HSA-159236)
  Rev-mediated nuclear export of HIV RNA (R-HSA-165054)
  Transport of Ribonucleoproteins into the Host Nucleus (R-HSA-168271)
  NS1 Mediated Effects on Host Pathways (R-HSA-168276)
  Viral Messenger RNA Synthesis (R-HSA-168325)
  NEP/NS2 Interacts with the Cellular Export Machinery (R-HSA-168333)
  Regulation of Glucokinase by Glucokinase Regulatory Protein (R-HSA-170822)
  Nuclear import of Rev protein (R-HSA-180746)
  Vpr-mediated nuclear import of PICs (R-HSA-180910)
  snRNP Assembly (R-HSA-191859)
  SUMOylation of DNA damage response and repair proteins (R-HSA-3108214)
  SUMOylation of ubiquitinylation proteins (R-HSA-3232142)
  Nuclear Pore Complex (NPC) Disassembly (R-HSA-3301854)
  Regulation of HSF1-mediated heat shock response (R-HSA-3371453)
  SUMOylation of SUMOylation proteins (R-HSA-4085377)
  SUMOylation of chromatin organization proteins (R-HSA-4551638)
  SUMOylation of RNA binding proteins (R-HSA-4570464)
  SUMOylation of DNA replication proteins (R-HSA-4615885)
  Transcriptional regulation by small RNAs (R-HSA-5578749)
  Defective TPR may confer susceptibility towards thyroid papillary carcinoma (TPC) (R-HSA-5619107)
  tRNA processing in the nucleus (R-HSA-6784531)
  HCMV Early Events (R-HSA-9609690)
  HCMV Late Events (R-HSA-9610379)
  Postmitotic nuclear pore complex (NPC) reformation (R-HSA-9615933)
  SARS-CoV-2 activates/modulates innate and adaptive immune responses (R-HSA-9705671)
  ISG15 antiviral mechanism (R-HSA-1169408)

Molecular Interaction Atlas (MIA) of This DOT

12 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Cerebellar ataxia	DIS9IRAV	Strong	Genetic Variation	[1]
Cervical cancer	DISFSHPF	Strong	Biomarker	[2]
Cervical carcinoma	DIST4S00	Strong	Biomarker	[2]
Megalencephalic leukoencephalopathy with subcortical cysts	DISK9A1M	Strong	Biomarker	[3]
Neoplasm	DISZKGEW	Strong	Altered Expression	[2]
Nephrotic syndrome, type 12	DISVAN3T	Strong	Autosomal recessive	[4]
Nephrotic syndrome, type 2	DISIRFO1	Strong	Biomarker	[5]
Steroid-resistant nephrotic syndrome	DISVEBC9	Strong	Genetic Variation	[6]
Thyroid gland papillary carcinoma	DIS48YMM	Strong	Genetic Variation	[7]
Visceral leishmaniasis	DISTKEYK	Strong	Genetic Variation	[3]
Influenza	DIS3PNU3	moderate	Biomarker	[8]
Familial idiopathic steroid-resistant nephrotic syndrome	DISQ53RS	Supportive	Autosomal dominant	[5]

8 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 Nuclear pore complex protein Nup93 (NUP93).	[9]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Nuclear pore complex protein Nup93 (NUP93).	[10]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Nuclear pore complex protein Nup93 (NUP93).	[11]
Zoledronate	DMIXC7G	Approved	Zoledronate increases the expression of Nuclear pore complex protein Nup93 (NUP93).	[13]
Selenium	DM25CGV	Approved	Selenium increases the expression of Nuclear pore complex protein Nup93 (NUP93).	[14]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol increases the expression of Nuclear pore complex protein Nup93 (NUP93).	[14]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Nuclear pore complex protein Nup93 (NUP93).	[15]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Nuclear pore complex protein Nup93 (NUP93).	[17]

3 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 Nuclear pore complex protein Nup93 (NUP93).	[12]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of Nuclear pore complex protein Nup93 (NUP93).	[16]
Coumarin	DM0N8ZM	Investigative	Coumarin affects the phosphorylation of Nuclear pore complex protein Nup93 (NUP93).	[16]

References

• [1] Correction to: Biallelic Variants in the Nuclear Pore Complex Protein NUP93 Are Associated with Non-progressive Congenital Ataxia.Cerebellum. 2019 Jun;18(3):433-434. doi: 10.1007/s12311-019-01021-9.
• [2] Expression of Nup93 is associated with the proliferation, migration and invasion capacity of cervical cancer cells.Acta Biochim Biophys Sin (Shanghai). 2019 Dec 13;51(12):1276-1285. doi: 10.1093/abbs/gmz131.
• [3] Visceral leishmaniasis: A novel nuclear envelope protein 'nucleoporins-93 (NUP-93)' from Leishmania donovani prompts macrophage signaling for T-cell activation towards host protective immune response.Cytokine. 2019 Jan;113:200-215. doi: 10.1016/j.cyto.2018.07.005. Epub 2018 Jul 9.
• [4] The Gene Curation Coalition: A global effort to harmonize gene-disease evidence resources. Genet Med. 2022 Aug;24(8):1732-1742. doi: 10.1016/j.gim.2022.04.017. Epub 2022 May 4.
• [5] Mutations in nuclear pore genes NUP93, NUP205 and XPO5 cause steroid-resistant nephrotic syndrome. Nat Genet. 2016 Apr;48(4):457-65. doi: 10.1038/ng.3512. Epub 2016 Feb 15.
• [6] Molecular assay for an intronic variant in NUP93 that causes steroid resistant nephrotic syndrome.J Hum Genet. 2019 Jul;64(7):673-679. doi: 10.1038/s10038-019-0606-4. Epub 2019 Apr 23.
• [7] Targeted next-generation sequencing in papillary thyroid carcinoma patients looking for germline variants predisposing to the disease.Endocrine. 2019 Jun;64(3):622-631. doi: 10.1007/s12020-019-01878-0. Epub 2019 Mar 2.
• [8] Host Factor Nucleoporin 93 Is Involved in the Nuclear Export of Influenza Virus RNA.Front Microbiol. 2018 Jul 24;9:1675. doi: 10.3389/fmicb.2018.01675. eCollection 2018.
• [9] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [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] 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.
• [12] 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.
• [13] Interleukin-19 as a translational indicator of renal injury. Arch Toxicol. 2015 Jan;89(1):101-6.
• [14] 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.
• [15] Transcriptional signature of human macrophages exposed to the environmental contaminant benzo(a)pyrene. Toxicol Sci. 2010 Apr;114(2):247-59.
• [16] 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.
• [17] Low-dose Bisphenol A exposure alters the functionality and cellular environment in a human cardiomyocyte model. Environ Pollut. 2023 Oct 15;335:122359. doi: 10.1016/j.envpol.2023.122359. Epub 2023 Aug 9.