Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTEN6QN7)

• DOT Name: Ribonuclease P protein subunit p25 (RPP25)
• Synonyms: RNase P protein subunit p25
• Gene Name: RPP25
• Related Disease:
  Autism
  Autism spectrum disorder
  Brain disease
  Pervasive developmental disorder
• UniProt ID: RPP25_HUMAN
• PDB ID: 6AHR; 6AHU; 6CWX; 6LT7
• Pfam ID: PF01918
• Sequence:
  MENFRKVRSEEAPAGCGAEGGGPGSGPFADLAPGAVHMRVKEGSKIRNLMAFATASMAQP
  ATRAIVFSGCGRATTKTVTCAEILKRRLAGLHQVTRLRYRSVREVWQSLPPGPTQGQTPG
  EPAASLSVLKNVPGLAILLSKDALDPRQPGYQPPNPHPGPSSPPAAPASKRSLGEPAAGE
  GSAKRSQPEPGVADEDQTA
• Function: Component of ribonuclease P, a ribonucleoprotein complex that generates mature tRNA molecules by cleaving their 5'-ends. Also a component of the MRP ribonuclease complex, which cleaves pre-rRNA sequences.
• KEGG Pathway: Ribosome biogenesis in eukaryotes (hsa03008)
• 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
Autism	DISV4V1Z	Strong	Altered Expression	[1]
Autism spectrum disorder	DISXK8NV	Strong	Altered Expression	[1]
Brain disease	DIS6ZC3X	Strong	Biomarker	[1]
Pervasive developmental disorder	DIS51975	Strong	Altered Expression	[1]

10 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 Ribonuclease P protein subunit p25 (RPP25).	[2]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Ribonuclease P protein subunit p25 (RPP25).	[3]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Ribonuclease P protein subunit p25 (RPP25).	[4]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Ribonuclease P protein subunit p25 (RPP25).	[5]
Arsenic	DMTL2Y1	Approved	Arsenic affects the expression of Ribonuclease P protein subunit p25 (RPP25).	[6]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Ribonuclease P protein subunit p25 (RPP25).	[7]
Triclosan	DMZUR4N	Approved	Triclosan increases the expression of Ribonuclease P protein subunit p25 (RPP25).	[8]
Panobinostat	DM58WKG	Approved	Panobinostat increases the expression of Ribonuclease P protein subunit p25 (RPP25).	[9]
Cytarabine	DMZD5QR	Approved	Cytarabine decreases the expression of Ribonuclease P protein subunit p25 (RPP25).	[10]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Ribonuclease P protein subunit p25 (RPP25).	[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 increases the methylation of Ribonuclease P protein subunit p25 (RPP25).	[11]

References

• [1] RPP25 is developmentally regulated in prefrontal cortex and expressed at decreased levels in autism spectrum disorder.Autism Res. 2010 Aug;3(4):153-61. doi: 10.1002/aur.141.
• [2] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [3] Blood transcript immune signatures distinguish a subset of people with elevated serum ALT from others given acetaminophen. Clin Pharmacol Ther. 2016 Apr;99(4):432-41.
• [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] 17-Estradiol Activates HSF1 via MAPK Signaling in ER-Positive Breast Cancer Cells. Cancers (Basel). 2019 Oct 11;11(10):1533. doi: 10.3390/cancers11101533.
• [6] Drinking-water arsenic exposure modulates gene expression in human lymphocytes from a U.S. population. Environ Health Perspect. 2008 Apr;116(4):524-31. doi: 10.1289/ehp.10861.
• [7] 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.
• [8] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [9] A transcriptome-based classifier to identify developmental toxicants by stem cell testing: design, validation and optimization for histone deacetylase inhibitors. Arch Toxicol. 2015 Sep;89(9):1599-618.
• [10] Cytosine arabinoside induces ectoderm and inhibits mesoderm expression in human embryonic stem cells during multilineage differentiation. Br J Pharmacol. 2011 Apr;162(8):1743-56.
• [11] 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.