Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT1MVO2F)

• DOT Name: H/ACA ribonucleoprotein complex subunit 3 (NOP10)
• Synonyms: Nucleolar protein 10; Nucleolar protein family A member 3; snoRNP protein NOP10
• Gene Name: NOP10
• Related Disease:
  Dyskeratosis congenita, autosomal recessive 1
  Hoyeraal-Hreidarsson syndrome
  Dyskeratosis congenita
  Pulmonary fibrosis and/or bone marrow failure syndrome, telomere-related, 9
  Small lymphocytic lymphoma
• UniProt ID: NOP10_HUMAN
• PDB ID: 7BGB; 7TRC; 7V9A
• Pfam ID: PF04135
• Sequence:
  MFLQYYLNEQGDRVYTLKKFDPMGQQTCSAHPARFSPDDKYSRHRITIKKRFKVLMTQQP
  RPVL
• Function: Required for ribosome biogenesis and telomere maintenance. Part of the H/ACA small nucleolar ribonucleoprotein (H/ACA snoRNP) complex, which catalyzes pseudouridylation of rRNA. This involves the isomerization of uridine such that the ribose is subsequently attached to C5, instead of the normal N1. Each rRNA can contain up to 100 pseudouridine ('psi') residues, which may serve to stabilize the conformation of rRNAs. May also be required for correct processing or intranuclear trafficking of TERC, the RNA component of the telomerase reverse transcriptase (TERT) holoenzyme.
• KEGG Pathway: Ribosome biogenesis in eukaryotes (hsa03008)
• Reactome Pathway:
  rRNA modification in the nucleus and cytosol (R-HSA-6790901)
  Telomere Extension By Telomerase (R-HSA-171319)

Molecular Interaction Atlas (MIA) of This DOT

5 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Dyskeratosis congenita, autosomal recessive 1	DISO63ZJ	Strong	Autosomal recessive	[1]
Hoyeraal-Hreidarsson syndrome	DISAUR8F	moderate	Biomarker	[1]
Dyskeratosis congenita	DISSXV0K	Supportive	Autosomal dominant	[2]
Pulmonary fibrosis and/or bone marrow failure syndrome, telomere-related, 9	DISVPEI5	Limited	Unknown	[3]
Small lymphocytic lymphoma	DIS30POX	Limited	Biomarker	[4]

6 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 H/ACA ribonucleoprotein complex subunit 3 (NOP10).	[5]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of H/ACA ribonucleoprotein complex subunit 3 (NOP10).	[6]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of H/ACA ribonucleoprotein complex subunit 3 (NOP10).	[7]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of H/ACA ribonucleoprotein complex subunit 3 (NOP10).	[8]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A affects the expression of H/ACA ribonucleoprotein complex subunit 3 (NOP10).	[9]
chloropicrin	DMSGBQA	Investigative	chloropicrin increases the expression of H/ACA ribonucleoprotein complex subunit 3 (NOP10).	[10]

References

• [1] Genetic heterogeneity in autosomal recessive dyskeratosis congenita with one subtype due to mutations in the telomerase-associated protein NOP10. Hum Mol Genet. 2007 Jul 1;16(13):1619-29. doi: 10.1093/hmg/ddm111. Epub 2007 May 16.
• [2] Dyskeratosis Congenita and Related Telomere Biology Disorders. 2009 Nov 12 [updated 2023 Jan 19]. In: Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE, Bean LJH, Gripp KW, Amemiya A, editors. GeneReviews(?) [Internet]. Seattle (WA): University of Washington, Seattle; 1993C2024.
• [3] Heat shock response of the archaebacterium Methanococcus voltae. J Bacteriol. 1991 May;173(10):3224-7. doi: 10.1128/jb.173.10.3224-3227.1991.
• [4] Dysregulation of H/ACA ribonucleoprotein components in chronic lymphocytic leukemia.PLoS One. 2017 Jun 30;12(6):e0179883. doi: 10.1371/journal.pone.0179883. eCollection 2017.
• [5] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [6] Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
• [7] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [8] Quantitative proteomics reveals a broad-spectrum antiviral property of ivermectin, benefiting for COVID-19 treatment. J Cell Physiol. 2021 Apr;236(4):2959-2975. doi: 10.1002/jcp.30055. Epub 2020 Sep 22.
• [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.
• [10] Transcriptomic analysis of human primary bronchial epithelial cells after chloropicrin treatment. Chem Res Toxicol. 2015 Oct 19;28(10):1926-35.