Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTE5H49L)

• DOT Name: Nucleolus and neural progenitor protein (NEPRO)
• Gene Name: NEPRO
• Related Disease: Anauxetic dysplasia
• UniProt ID: NEPRO_HUMAN
• Pfam ID: PF14780
• Sequence:
  MMAAVPPGLEPWNRVRIPKAGNRSAVTVQNPGAALDLCIAAVIKECHLVILSLKSQTLDA
  ETDVLCAVLYSNHNRMGRHKPHLALKQVEQCLKRLKNMNLEGSIQDLFELFSSNENQPLT
  TKVCVVPSQPVVELVLMKVLGACKLLLRLLDCCCKTFLLTVKHLGLQEFIILNLVMVGLV
  SRLWVLYKGVLKRLILLYEPLFGLLQEVARIQPMPYFKDFTFPSDITEFLGQPYFEAFKK
  KMPIAFAAKGINKLLNKLFLINEQSPRASEETLLGISKKAKQMKINVQNNVDLGQPVKNK
  RVFKEESSEFDVRAFCNQLKHKATQETSFDFKCSQSRLKTTKYSSQKVIGTPHAKSFVQR
  FREAESFTQLSEEIQMAVVWCRSKKLKAQAIFLGNKLLKSNRLKHLEAQGTSLPKKLECI
  KTSICNHLLRGSGIKTSKHHLRQRRSQNKFLRRQRKPQRKLQSTLLREIQQFSQGTRKSA
  TDTSAKWRLSHCTVHRTDLYPNSKQLLNSGVSMPVIQTKEKMIHENLRGIHENETDSWTV
  MQINKNSTSGTIKETDDIDDIFALMGV
• Function: May play a role in cortex development as part of the Notch signaling pathway. Downstream of Notch may repress the expression of proneural genes and inhibit neuronal differentiation thereby maintaining neural progenitors. May also play a role in preimplentation embryo development.

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Anauxetic dysplasia	DISFIUUO	Supportive	Autosomal recessive	[1]

5 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 Nucleolus and neural progenitor protein (NEPRO).	[2]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Nucleolus and neural progenitor protein (NEPRO).	[3]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Nucleolus and neural progenitor protein (NEPRO).	[4]
Methotrexate	DM2TEOL	Approved	Methotrexate increases the expression of Nucleolus and neural progenitor protein (NEPRO).	[5]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Nucleolus and neural progenitor protein (NEPRO).	[8]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Nucleolus and neural progenitor protein (NEPRO).	[6]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of Nucleolus and neural progenitor protein (NEPRO).	[7]

References

• [1] An emerging ribosomopathy affecting the skeleton due to biallelic variations in NEPRO. Am J Med Genet A. 2019 Sep;179(9):1709-1717. doi: 10.1002/ajmg.a.61267. Epub 2019 Jun 27.
• [2] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [3] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [4] 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.
• [5] The contribution of methotrexate exposure and host factors on transcriptional variance in human liver. Toxicol Sci. 2007 Jun;97(2):582-94.
• [6] 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.
• [7] 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.
• [8] From transient transcriptome responses to disturbed neurodevelopment: role of histone acetylation and methylation as epigenetic switch between reversible and irreversible drug effects. Arch Toxicol. 2014 Jul;88(7):1451-68.