Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTA8H3LB)

• DOT Name: Small ribosomal subunit protein uS14m (MRPS14)
• Synonyms: 28S ribosomal protein S14, mitochondrial; MRP-S14; S14mt
• Gene Name: MRPS14
• Related Disease:
  Intellectual disability
  Hypertrophic cardiomyopathy
  Lactic acidosis
  Combined oxidative phosphorylation deficiency 38
• UniProt ID: RT14_HUMAN
• PDB ID: 3J9M ; 6NU2 ; 6NU3 ; 6RW4 ; 6RW5 ; 6VLZ ; 6VMI ; 6ZM5 ; 6ZM6 ; 6ZS9 ; 6ZSA ; 6ZSB ; 6ZSC ; 6ZSD ; 6ZSE ; 6ZSG ; 7A5F ; 7A5G ; 7A5I ; 7A5K ; 7L08 ; 7OG4 ; 7P2E ; 7PNX ; 7PNY ; 7PNZ ; 7PO0 ; 7PO1 ; 7PO2 ; 7PO3 ; 7QI4 ; 7QI5 ; 7QI6 ; 8ANY ; 8CSP ; 8CSQ ; 8CSR ; 8CSS ; 8CST ; 8CSU ; 8OIR ; 8OIS
• Pfam ID: PF00253
• Sequence:
  MAAFMLGSLLRTFKQMVPSSASGQVRSHYVDWRMWRDVKRRKMAYEYADERLRINSLRKN
  TILPKILQDVADEEIAALPRDSCPVRIRNRCVMTSRPRGVKRRWRLSRIVFRHLADHGQL
  SGIQRATW
• KEGG Pathway: Ribosome (hsa03010)
• Reactome Pathway:
  Mitochondrial translation elongation (R-HSA-5389840)
  Mitochondrial translation termination (R-HSA-5419276)
  Mitochondrial translation initiation (R-HSA-5368286)

Molecular Interaction Atlas (MIA) of This DOT

4 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Intellectual disability	DISMBNXP	Strong	Biomarker	[1]
Hypertrophic cardiomyopathy	DISQG2AI	moderate	Genetic Variation	[1]
Lactic acidosis	DISZI1ZK	moderate	Genetic Variation	[1]
Combined oxidative phosphorylation deficiency 38	DISNUICA	Limited	Unknown	[1]

8 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 Small ribosomal subunit protein uS14m (MRPS14).	[2]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Small ribosomal subunit protein uS14m (MRPS14).	[3]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Small ribosomal subunit protein uS14m (MRPS14).	[4]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide increases the expression of Small ribosomal subunit protein uS14m (MRPS14).	[5]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Small ribosomal subunit protein uS14m (MRPS14).	[6]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Small ribosomal subunit protein uS14m (MRPS14).	[7]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Small ribosomal subunit protein uS14m (MRPS14).	[2]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Small ribosomal subunit protein uS14m (MRPS14).	[8]

References

• [1] A variant in MRPS14 (uS14m) causes perinatal hypertrophic cardiomyopathy with neonatal lactic acidosis, growth retardation, dysmorphic features and neurological involvement. Hum Mol Genet. 2019 Feb 15;28(4):639-649. doi: 10.1093/hmg/ddy374.
• [2] From transient transcriptome responses to disturbed neurodevelopment: role of histone acetylation and methylation as epigenetic switch between reversible and irreversible drug effects. Arch Toxicol. 2014 Jul;88(7):1451-68.
• [3] Human 3D multicellular microtissues: an upgraded model for the in vitro mechanistic investigation of inflammation-associated drug toxicity. Toxicol Lett. 2019 Sep 15;312:34-44.
• [4] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [5] Oxidative stress modulates theophylline effects on steroid responsiveness. Biochem Biophys Res Commun. 2008 Dec 19;377(3):797-802.
• [6] 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.
• [7] Epigenetic influences of low-dose bisphenol A in primary human breast epithelial cells. Toxicol Appl Pharmacol. 2010 Oct 15;248(2):111-21.
• [8] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.