Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT694B27)

• DOT Name: DNA-directed RNA polymerase III subunit RPC7-like (POLR3GL)
• Synonyms: RNA polymerase III subunit C7-like; DNA-directed RNA polymerase III subunit G-like; RNA polymerase III 32 kDa beta subunit; RPC32-beta
• Gene Name: POLR3GL
• Related Disease:
  Hyperostosis corticalis generalisata
  Wiedemann-Rautenstrauch syndrome
  Tooth agenesis
• UniProt ID: RPC7L_HUMAN
• PDB ID: 5AFQ
• Pfam ID: PF11705
• Sequence:
  MASRGGGRGRGRGQLTFNVEAVGIGKGDALPPPTLQPSPLFPPLEFRPVPLPSGEEGEYV
  LALKQELRGAMRQLPYFIRPAVPKRDVERYSDKYQMSGPIDNAIDWNPDWRRLPRELKIR
  VRKLQKERITILLPKRPPKTTEDKEETIQKLETLEKKEEEVTSEEDEEKEEEEEKEEEEE
  EEYDEEEHEEETDYIMSYFDNGEDFGGDSDDNMDEAIY
• Function: DNA-dependent RNA polymerase catalyzes the transcription of DNA into RNA using the four ribonucleoside triphosphates as substrates. Specific peripheric component of RNA polymerase III which synthesizes small RNAs, such as 5S rRNA and tRNAs.
• Tissue Specificity: Widely expressed. Expressed in CD4-positive T cells.
• KEGG Pathway:
  R. polymerase (hsa03020)
  Cytosolic D.-sensing pathway (hsa04623)
• Reactome Pathway:
  RNA Polymerase III Chain Elongation (R-HSA-73780)
  RNA Polymerase III Transcription Termination (R-HSA-73980)
  RNA Polymerase III Abortive And Retractive Initiation (R-HSA-749476)
  RNA Polymerase III Transcription Initiation From Type 1 Promoter (R-HSA-76061)
  RNA Polymerase III Transcription Initiation From Type 2 Promoter (R-HSA-76066)
  RNA Polymerase III Transcription Initiation From Type 3 Promoter (R-HSA-76071)
  Cytosolic sensors of pathogen-associated DNA (R-HSA-1834949)

Molecular Interaction Atlas (MIA) of This DOT

3 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Hyperostosis corticalis generalisata	DISR4BHB	Strong	Genetic Variation	[1]
Wiedemann-Rautenstrauch syndrome	DIS11Z1N	Strong	Biomarker	[2]
Tooth agenesis	DIS1PWC7	Limited	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 decreases the expression of DNA-directed RNA polymerase III subunit RPC7-like (POLR3GL).	[3]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of DNA-directed RNA polymerase III subunit RPC7-like (POLR3GL).	[4]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of DNA-directed RNA polymerase III subunit RPC7-like (POLR3GL).	[5]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of DNA-directed RNA polymerase III subunit RPC7-like (POLR3GL).	[6]
Decitabine	DMQL8XJ	Approved	Decitabine affects the expression of DNA-directed RNA polymerase III subunit RPC7-like (POLR3GL).	[7]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A affects the expression of DNA-directed RNA polymerase III subunit RPC7-like (POLR3GL).	[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 DNA-directed RNA polymerase III subunit RPC7-like (POLR3GL).	[8]

References

• [1] Biallelic variants in POLR3GL cause endosteal hyperostosis and oligodontia.Eur J Hum Genet. 2020 Jan;28(1):31-39. doi: 10.1038/s41431-019-0427-0. Epub 2019 May 14.
• [2] A variant of neonatal progeroid syndrome, or Wiedemann-Rautenstrauch syndrome, is associated with a nonsense variant in POLR3GL.Eur J Hum Genet. 2020 Apr;28(4):461-468. doi: 10.1038/s41431-019-0539-6. Epub 2019 Nov 6.
• [3] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [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] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [7] Acute hypersensitivity of pluripotent testicular cancer-derived embryonal carcinoma to low-dose 5-aza deoxycytidine is associated with global DNA Damage-associated p53 activation, anti-pluripotency and DNA demethylation. PLoS One. 2012;7(12):e53003. doi: 10.1371/journal.pone.0053003. Epub 2012 Dec 27.
• [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] A trichostatin A expression signature identified by TempO-Seq targeted whole transcriptome profiling. PLoS One. 2017 May 25;12(5):e0178302. doi: 10.1371/journal.pone.0178302. eCollection 2017.