Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT53MDNE)

• DOT Name: Ribonuclease P protein subunit p21 (RPP21)
• Synonyms: RNaseP protein p21; Ribonuclease P/MRP 21 kDa subunit; Ribonucleoprotein V
• Gene Name: RPP21
• Related Disease:
  Barrett esophagus
  Leukoencephalopathy with vanishing white matter
  Rheumatoid arthritis
  Cutaneous lupus erythematosus
• UniProt ID: RPP21_HUMAN
• PDB ID: 6AHR; 6AHU
• Pfam ID: PF04032
• Sequence:
  MAGPVKDREAFQRLNFLYQAAHCVLAQDPENQALARFYCYTERTIAKRLVLRRDPSVKRT
  LCRGCSSLLVPGLTCTQRQRRCRGQRWTVQTCLTCQRSQRFLNDPGHLLWGDRPEAQLGS
  QADSKPLQPLPNTAHSISDRLPEEKMQTQGSSNQ
• Function: Component of ribonuclease P, a ribonucleoprotein complex that generates mature tRNA molecules by cleaving their 5'-ends.
• Reactome Pathway:
  Major pathway of rRNA processing in the nucleolus and cytosol (R-HSA-6791226)
  tRNA processing in the nucleus (R-HSA-6784531)

Molecular Interaction Atlas (MIA) of This DOT

4 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Barrett esophagus	DIS416Y7	Strong	Biomarker	[1]
Leukoencephalopathy with vanishing white matter	DIS3J8NN	Strong	Biomarker	[1]
Rheumatoid arthritis	DISTSB4J	Strong	Genetic Variation	[2]
Cutaneous lupus erythematosus	DISOIX6L	moderate	Genetic Variation	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate affects the expression of Ribonuclease P protein subunit p21 (RPP21).	[3]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Ribonuclease P protein subunit p21 (RPP21).	[4]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Ribonuclease P protein subunit p21 (RPP21).	[5]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Ribonuclease P protein subunit p21 (RPP21).	[6]
Azacitidine	DMTA5OE	Approved	Azacitidine increases the expression of Ribonuclease P protein subunit p21 (RPP21).	[7]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A affects the expression of Ribonuclease P protein subunit p21 (RPP21).	[9]

1 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 affects the methylation of Ribonuclease P protein subunit p21 (RPP21).	[8]

References

• [1] Genome-wide association study identifies new susceptibility loci for cutaneous lupus erythematosus.Exp Dermatol. 2015 Jul;24(7):510-5. doi: 10.1111/exd.12708. Epub 2015 May 4.
• [2] 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.
• [3] Gene Expression Regulation and Pathway Analysis After Valproic Acid and Carbamazepine Exposure in a Human Embryonic Stem Cell-Based Neurodevelopmental Toxicity Assay. Toxicol Sci. 2015 Aug;146(2):311-20. doi: 10.1093/toxsci/kfv094. Epub 2015 May 15.
• [4] Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
• [5] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [6] 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.
• [7] The effect of DNA methylation inhibitor 5-Aza-2'-deoxycytidine on human endometrial stromal cells. Hum Reprod. 2010 Nov;25(11):2859-69.
• [8] 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.
• [9] Comprehensive analysis of transcriptomic changes induced by low and high doses of bisphenol A in HepG2 spheroids in vitro and rat liver in vivo. Environ Res. 2019 Jun;173:124-134. doi: 10.1016/j.envres.2019.03.035. Epub 2019 Mar 18.