Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTNWI55E)

• DOT Name: U4/U6.U5 small nuclear ribonucleoprotein 27 kDa protein (SNRNP27)
• Synonyms: U4/U6.U5 snRNP 27 kDa protein; U4/U6.U5-27K; Nucleic acid-binding protein RY-1; U4/U6.U5 tri-snRNP-associated 27 kDa protein; 27K; U4/U6.U5 tri-snRNP-associated protein 3
• Gene Name: SNRNP27
• Related Disease:
  Malignant hyperthermia of anesthesia
  Familial atrial fibrillation
  Atrial fibrillation
• UniProt ID: SNR27_HUMAN
• PDB ID: 6QW6; 6QX9
• Pfam ID: PF08648
• Sequence:
  MGRSRSRSPRRERRRSRSTSRERERRRRERSRSRERDRRRSRSRSPHRRRSRSPRRHRST
  SPSPSRLKERRDEEKKETKETKSKERQITEEDLEGKTEEEIEMMKLMGFASFDSTKGKKV
  DGSVNAYAINVSQKRKYRQYMNRKGGFNRPLDFIA
• Function: May play a role in mRNA splicing.
• KEGG Pathway: Spliceosome (hsa03040)
• Reactome Pathway: mRNA Splicing - Major Pathway (R-HSA-72163)

Molecular Interaction Atlas (MIA) of This DOT

3 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Malignant hyperthermia of anesthesia	DISYC9XI	Strong	Genetic Variation	[1]
Familial atrial fibrillation	DISL4AGF	moderate	Biomarker	[2]
Atrial fibrillation	DIS15W6U	Limited	Biomarker	[2]

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 U4/U6.U5 small nuclear ribonucleoprotein 27 kDa protein (SNRNP27).	[3]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of U4/U6.U5 small nuclear ribonucleoprotein 27 kDa protein (SNRNP27).	[4]
Selenium	DM25CGV	Approved	Selenium decreases the expression of U4/U6.U5 small nuclear ribonucleoprotein 27 kDa protein (SNRNP27).	[5]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol decreases the expression of U4/U6.U5 small nuclear ribonucleoprotein 27 kDa protein (SNRNP27).	[5]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of U4/U6.U5 small nuclear ribonucleoprotein 27 kDa protein (SNRNP27).	[7]

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 decreases the methylation of U4/U6.U5 small nuclear ribonucleoprotein 27 kDa protein (SNRNP27).	[6]

References

• [1] The differential effect of halothane and 1,2-dichlorohexafluorocyclobutane on in vitro muscle contractures of patients susceptible to malignant hyperthermia.Anesth Analg. 2002 Apr;94(4):1028-33, table of contents. doi: 10.1097/00000539-200204000-00048.
• [2] Multi-ethnic genome-wide association study for atrial fibrillation.Nat Genet. 2018 Jun 11;50(9):1225-1233. doi: 10.1038/s41588-018-0133-9.
• [3] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [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] 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.
• [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] 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.