Details of Drug Off-Target (DOT)

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

• DOT Name: Protein ripply2 (RIPPLY2)
• Gene Name: RIPPLY2
• Related Disease:
  Autosomal dominant spondylocostal dysostosis
  Spondylocostal dysostosis
  Spondylocostal dysostosis 2, autosomal recessive
  Spondylocostal dysostosis 3, autosomal recessive
  Spondylocostal dysostosis 4, autosomal recessive
  Spondylocostal dysostosis 5
  Spondylocostal dysostosis 6, autosomal recessive
  Klippel-Feil syndrome 2, autosomal recessive
  Autosomal recessive spondylocostal dysostosis
  Sickle-cell anaemia
  Systemic primary carnitine deficiency disease
• UniProt ID: RIPP2_HUMAN
• Pfam ID: PF14998
• Sequence:
  MENAGGAEGTESGAAACAATDGPTRRAGADSGYAGFWRPWVDAGGKKEEETPNHAAEAMP
  DGPGMTAASGKLYQFRHPVRLFWPKSKCYDYLYQEAEALLKNFPIQATISFYEDSDSEDE
  IEDLTCEN
• Function: Plays a role in somitogenesis. Required for somite segregation and establishment of rostrocaudal polarity in somites.
• Reactome Pathway: Somitogenesis (R-HSA-9824272)

Molecular Interaction Atlas (MIA) of This DOT

11 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Autosomal dominant spondylocostal dysostosis	DIS7OT0S	Strong	Biomarker	[1]
Spondylocostal dysostosis	DISTPWFK	Strong	Biomarker	[2]
Spondylocostal dysostosis 2, autosomal recessive	DISR3NXE	Strong	Biomarker	[1]
Spondylocostal dysostosis 3, autosomal recessive	DIS10LTO	Strong	Biomarker	[1]
Spondylocostal dysostosis 4, autosomal recessive	DIS3HQRC	Strong	Biomarker	[1]
Spondylocostal dysostosis 5	DISOB4HV	Strong	Biomarker	[1]
Spondylocostal dysostosis 6, autosomal recessive	DISITM5J	Strong	Autosomal recessive	[3]
Klippel-Feil syndrome 2, autosomal recessive	DISZ0FWV	moderate	Genetic Variation	[4]
Autosomal recessive spondylocostal dysostosis	DISAJI27	Supportive	Autosomal recessive	[4]
Sickle-cell anaemia	DIS5YNZB	Limited	Biomarker	[5]
Systemic primary carnitine deficiency disease	DIS9OPZ4	Limited	Biomarker	[5]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Protein ripply2 (RIPPLY2).	[6]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Protein ripply2 (RIPPLY2).	[8]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Protein ripply2 (RIPPLY2).	[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 increases the methylation of Protein ripply2 (RIPPLY2).	[7]

References

• [1] Ripply2 is essential for precise somite formation during mouse early development.FEBS Lett. 2007 Jun 12;581(14):2691-6. doi: 10.1016/j.febslet.2007.05.017. Epub 2007 May 21.
• [2] A Cryptic Cause of Cardiac Arrest.J Emerg Med. 2019 Jan;56(1):e1-e4. doi: 10.1016/j.jemermed.2018.09.044. Epub 2018 Nov 9.
• [3] Rare variants in the notch signaling pathway describe a novel type of autosomal recessive Klippel-Feil syndrome. Am J Med Genet A. 2015 Nov;167A(11):2795-9. doi: 10.1002/ajmg.a.37263. Epub 2015 Aug 4.
• [4] Compound heterozygous mutations in RIPPLY2 associated with vertebral segmentation defects. Hum Mol Genet. 2015 Mar 1;24(5):1234-42. doi: 10.1093/hmg/ddu534. Epub 2014 Oct 24.
• [5] Homozygous DMRT2 variant associates with severe rib malformations in a newborn.Am J Med Genet A. 2018 May;176(5):1216-1221. doi: 10.1002/ajmg.a.38668.
• [6] Predictive toxicology using systemic biology and liver microfluidic "on chip" approaches: application to acetaminophen injury. Toxicol Appl Pharmacol. 2012 Mar 15;259(3):270-80.
• [7] 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.
• [8] Synergistic effect of JQ1 and rapamycin for treatment of human osteosarcoma. Int J Cancer. 2015 May 1;136(9):2055-64.
• [9] Cell-based two-dimensional morphological assessment system to predict cancer drug-induced cardiotoxicity using human induced pluripotent stem cell-derived cardiomyocytes. Toxicol Appl Pharmacol. 2019 Nov 15;383:114761. doi: 10.1016/j.taap.2019.114761. Epub 2019 Sep 15.