Details of Drug Off-Target (DOT)

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

• DOT Name: Small ribosomal subunit protein mS22 (MRPS22)
• Synonyms: 28S ribosomal protein S22, mitochondrial; MRP-S22; S22mt
• Gene Name: MRPS22
• Related Disease:
  Mitochondrial disease
  Breast cancer
  Breast carcinoma
  Breast neoplasm
  Hypotonia with lactic acidemia and hyperammonemia
  Lactic acidosis
  Obesity
  Ovarian dysfunction
  Ovarian dysgenesis 1
  Movement disorder
  46 XX gonadal dysgenesis
  Alopecia
  Androgenetic alopecia
  Baldness, male pattern
  Hypertrophic cardiomyopathy
  Ovarian dysgenesis 7
• UniProt ID: RT22_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: PF10245
• Sequence:
  MAPLGTTVLLWSLLRSSPGVERVCFRARIQPWHGGLLQPLPCSFEMGLPRRRFSSEAAES
  GSPETKKPTFMDEEVQSILTKMTGLNLQKTFKPAIQELKPPTYKLMTQAQLEEATRQAVE
  AAKVRLKMPPVLEERVPINDVLAEDKILEGTETTKYVFTDISYSIPHRERFIVVREPSGT
  LRKASWEERDRMIQVYFPKEGRKILTPIIFKEENLRTMYSQDRHVDVLNLCFAQFEPDST
  EYIKVHHKTYEDIDKRGKYDLLRSTRYFGGMVWYFVNNKKIDGLLIDQIQRDLIDDATNL
  VQLYHVLHPDGQSAQGAKDQAAEGINLIKVFAKTEAQKGAYIELTLQTYQEALSRHSAAS
• 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

16 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Mitochondrial disease	DISKAHA3	Definitive	Autosomal recessive	[1]
Breast cancer	DIS7DPX1	Strong	Biomarker	[2]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[2]
Breast neoplasm	DISNGJLM	Strong	Biomarker	[2]
Hypotonia with lactic acidemia and hyperammonemia	DISEO02G	Strong	Autosomal recessive	[3]
Lactic acidosis	DISZI1ZK	Strong	Genetic Variation	[4]
Obesity	DIS47Y1K	Strong	Genetic Variation	[5]
Ovarian dysfunction	DIST09IB	Strong	Biomarker	[6]
Ovarian dysgenesis 1	DISXIXHW	Strong	GermlineCausalMutation	[6]
Movement disorder	DISOJJ2D	moderate	CausalMutation	[7]
46 XX gonadal dysgenesis	DISBB9HA	Supportive	Autosomal dominant	[6]
Alopecia	DIS37HU4	Limited	Genetic Variation	[8]
Androgenetic alopecia	DISSJR1P	Limited	Genetic Variation	[9]
Baldness, male pattern	DIS9C9RO	Limited	Genetic Variation	[9]
Hypertrophic cardiomyopathy	DISQG2AI	Limited	Biomarker	[10]
Ovarian dysgenesis 7	DISNRVHK	Limited	Autosomal recessive	[6]

8 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate affects the expression of Small ribosomal subunit protein mS22 (MRPS22).	[11]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Small ribosomal subunit protein mS22 (MRPS22).	[12]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Small ribosomal subunit protein mS22 (MRPS22).	[13]
Quercetin	DM3NC4M	Approved	Quercetin affects the expression of Small ribosomal subunit protein mS22 (MRPS22).	[14]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Small ribosomal subunit protein mS22 (MRPS22).	[11]
Sodium phenylbutyrate	DMXLBCQ	Approved	Sodium phenylbutyrate decreases the expression of Small ribosomal subunit protein mS22 (MRPS22).	[15]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Small ribosomal subunit protein mS22 (MRPS22).	[16]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A affects the expression of Small ribosomal subunit protein mS22 (MRPS22).	[17]

References

• [1] Technical standards for the interpretation and reporting of constitutional copy-number variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics (ACMG) and the Clinical Genome Resource (ClinGen). Genet Med. 2020 Feb;22(2):245-257. doi: 10.1038/s41436-019-0686-8. Epub 2019 Nov 6.
• [2] An integrative approach to identify YB-1-interacting proteins required for cisplatin resistance in MCF7 and MDA-MB-231 breast cancer cells. Cancer Sci. 2011 Jul;102(7):1410-7. doi: 10.1111/j.1349-7006.2011.01948.x. Epub 2011 May 5.
• [3] Antenatal mitochondrial disease caused by mitochondrial ribosomal protein (MRPS22) mutation. J Med Genet. 2007 Dec;44(12):784-6. doi: 10.1136/jmg.2007.053116. Epub 2007 Sep 14.
• [4] MRPS22 mutation causes fatal neonatal lactic acidosis with brain and heart abnormalities.Neurogenetics. 2015 Jul;16(3):237-40. doi: 10.1007/s10048-015-0440-6. Epub 2015 Feb 10.
• [5] Genome-wide scan for loci of adolescent obesity and their relationship with blood pressure.J Clin Endocrinol Metab. 2012 Jan;97(1):E145-50. doi: 10.1210/jc.2011-1801. Epub 2011 Oct 19.
• [6] Mutations in the mitochondrial ribosomal protein MRPS22 lead to primary ovarian insufficiency. Hum Mol Genet. 2018 Jun 1;27(11):1913-1926. doi: 10.1093/hmg/ddy098.
• [7] A patient with mitochondrial disorder due to a novel mutation in MRPS22.Metab Brain Dis. 2017 Oct;32(5):1389-1393. doi: 10.1007/s11011-017-0074-5. Epub 2017 Jul 27.
• [8] Genetic prediction of male pattern baldness.PLoS Genet. 2017 Feb 14;13(2):e1006594. doi: 10.1371/journal.pgen.1006594. eCollection 2017 Feb.
• [9] GWAS for male-pattern baldness identifies 71 susceptibility loci explaining 38% of the risk.Nat Commun. 2017 Nov 17;8(1):1584. doi: 10.1038/s41467-017-01490-8.
• [10] Mutation in mitochondrial ribosomal protein MRPS22 leads to Cornelia de Lange-like phenotype, brain abnormalities and hypertrophic cardiomyopathy.Eur J Hum Genet. 2011 Apr;19(4):394-9. doi: 10.1038/ejhg.2010.214. Epub 2010 Dec 29.
• [11] 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.
• [12] 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.
• [13] 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.
• [14] Protein expression profiling identifies molecular targets of quercetin as a major dietary flavonoid in human colon cancer cells. Proteomics. 2004 Jul;4(7):2160-74.
• [15] Gene expression profile analysis of 4-phenylbutyrate treatment of IB3-1 bronchial epithelial cell line demonstrates a major influence on heat-shock proteins. Physiol Genomics. 2004 Jan 15;16(2):204-11.
• [16] Alternatives for the worse: Molecular insights into adverse effects of bisphenol a and substitutes during human adipocyte differentiation. Environ Int. 2021 Nov;156:106730. doi: 10.1016/j.envint.2021.106730. Epub 2021 Jun 27.
• [17] 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.