Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT7H4LYA)

• DOT Name: Mesoderm posterior protein 2 (MESP2)
• Synonyms: Class C basic helix-loop-helix protein 6; bHLHc6
• Gene Name: MESP2
• Related Disease:
  Sexually transmitted infection
  Spondylocostal dysostosis 2, autosomal recessive
  Dysplasia
  Autosomal recessive spondylocostal dysostosis
  Spondylocostal dysostosis 5
  Sickle-cell anaemia
  Spondylocostal dysostosis
  Systemic primary carnitine deficiency disease
• UniProt ID: MESP2_HUMAN
• Pfam ID: PF00010
• Sequence:
  MAQSPPPQSLLGHDHWIFAQGWGWAGHWDSTSPASSSDSSGSCPCDGARGLPQPQPPSCS
  SRAAEAAATTPRRARTGPAGGQRQSASEREKLRMRTLARALHELRRFLPPSLAPAGQSLT
  KIETLRLAIRYIGHLSAVLGLSEESLQCRRRQRGDAGSPWGCPLCPDRGPAEAQTQAEGQ
  GQGQGQGQGQGQGQGQGQGQGQGQGRRPGLVSAVLAEASWGSPSACPGAQAAPERLGRGV
  HDTDPWATPPYCPKIQSPPYSSQGTTSDASLWTPPQGCPWTQSSPEPRNPPVPWTAAPAT
  LELAAVYQGLSVSPEPCLSLGAPSLLPHPSCQRLQPQTPGRCWSHSAEVVPNSEDQGPGA
  AFQLSEASPPQSSGLRFSGCPELWQEDLEGARLGIFY
• Function: Transcription factor with important role in somitogenesis. Defines the rostrocaudal patterning of the somite by participating in distinct Notch pathways. Regulates also the FGF signaling pathway. Specifies the rostral half of the somites. Generates rostro-caudal polarity of somites by down-regulating in the presumptive rostral domain DLL1, a Notch ligand. Participates in the segment border formation by activating in the anterior presomitic mesoderm LFNG, a negative regulator of DLL1-Notch signaling. Acts as a strong suppressor of Notch activity. Together with MESP1 is involved in the epithelialization of somitic mesoderm and in the development of cardiac mesoderm.
• Reactome Pathway: Somitogenesis (R-HSA-9824272)

Molecular Interaction Atlas (MIA) of This DOT

8 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Sexually transmitted infection	DISIVIAL	Definitive	Genetic Variation	[1]
Spondylocostal dysostosis 2, autosomal recessive	DISR3NXE	Definitive	Autosomal recessive	[2]
Dysplasia	DISHPNVX	Strong	Genetic Variation	[1]
Autosomal recessive spondylocostal dysostosis	DISAJI27	Supportive	Autosomal recessive	[3]
Spondylocostal dysostosis 5	DISOB4HV	Disputed	Genetic Variation	[1]
Sickle-cell anaemia	DIS5YNZB	Limited	Biomarker	[4]
Spondylocostal dysostosis	DISTPWFK	Limited	Genetic Variation	[1]
Systemic primary carnitine deficiency disease	DIS9OPZ4	Limited	Biomarker	[4]

8 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 Mesoderm posterior protein 2 (MESP2).	[5]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Mesoderm posterior protein 2 (MESP2).	[5]
Fluorouracil	DMUM7HZ	Approved	Fluorouracil increases the expression of Mesoderm posterior protein 2 (MESP2).	[5]
Isotretinoin	DM4QTBN	Approved	Isotretinoin decreases the expression of Mesoderm posterior protein 2 (MESP2).	[5]
Thalidomide	DM70BU5	Approved	Thalidomide decreases the expression of Mesoderm posterior protein 2 (MESP2).	[5]
Nilotinib	DM7HXWT	Approved	Nilotinib decreases the expression of Mesoderm posterior protein 2 (MESP2).	[5]
Abacavir	DMMN36E	Approved	Abacavir decreases the expression of Mesoderm posterior protein 2 (MESP2).	[5]
Ramelteon	DM7IW9J	Approved	Ramelteon increases the expression of Mesoderm posterior protein 2 (MESP2).	[5]

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 Mesoderm posterior protein 2 (MESP2).	[6]

References

• [1] Mutations in the MESP2 gene cause spondylothoracic dysostosis/Jarcho-Levin syndrome. Am J Hum Genet. 2008 Jun;82(6):1334-41. doi: 10.1016/j.ajhg.2008.04.014. Epub 2008 May 15.
• [2] Mutated MESP2 causes spondylocostal dysostosis in humans. Am J Hum Genet. 2004 Jun;74(6):1249-54. doi: 10.1086/421053. Epub 2004 Apr 30.
• [3] Spondylocostal Dysostosis, Autosomal Recessive. 2009 Aug 25 [updated 2023 Aug 17]. 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.
• [4] Defective somitogenesis and abnormal vertebral segmentation in man.Adv Exp Med Biol. 2008;638:164-89. doi: 10.1007/978-0-387-09606-3_9.
• [5] Exposure-based assessment of chemical teratogenicity using morphogenetic aggregates of human embryonic stem cells. Reprod Toxicol. 2020 Jan;91:74-91. doi: 10.1016/j.reprotox.2019.10.004. Epub 2019 Nov 8.
• [6] 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.