Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT3B2H8F)

• DOT Name: LRP chaperone MESD (MESD)
• Synonyms: LDLR chaperone MESD; Mesoderm development LRP chaperone MESD; Mesoderm development candidate 2; Mesoderm development protein; Renal carcinoma antigen NY-REN-61
• Gene Name: MESD
• Related Disease:
  Adult teratoma
  Osteogenesis imperfecta, type 20
  Teratoma
  Triple negative breast cancer
  Osteogenesis imperfecta
  Osteogenesis imperfecta type 2
• UniProt ID: MESD_HUMAN
• Pfam ID: PF10185
• Sequence:
  MAASRWARKAVVLLCASDLLLLLLLLPPPGSCAAEGSPGTPDESTPPPRKKKKDIRDYND
  ADMARLLEQWEKDDDIEEGDLPEHKRPSAPVDFSKIDPSKPESILKMTKKGKTLMMFVTV
  SGSPTEKETEEITSLWQGSLFNANYDVQRFIVGSDRAIFMLRDGSYAWEIKDFLVGQDRC
  ADVTLEGQVYPGKGGGSKEKNKTKQDKGKKKKEGDLKSRSSKEENRAGNKREDL
• Function: Chaperone specifically assisting the folding of beta-propeller/EGF modules within the family of low-density lipoprotein receptors (LDLRs). Acts as a modulator of the Wnt pathway through chaperoning the coreceptors of the canonical Wnt pathway, LRP5 and LRP6, to the plasma membrane. Essential for specification of embryonic polarity and mesoderm induction. Plays an essential role in neuromuscular junction (NMJ) formation by promoting cell-surface expression of LRP4. May regulate phagocytosis of apoptotic retinal pigment epithelium (RPE) cells.

Molecular Interaction Atlas (MIA) of This DOT

6 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Adult teratoma	DISBY81U	Strong	Genetic Variation	[1]
Osteogenesis imperfecta, type 20	DIS1VTDS	Strong	Autosomal recessive	[2]
Teratoma	DIS6ICY4	Strong	Genetic Variation	[1]
Triple negative breast cancer	DISAMG6N	Strong	Altered Expression	[3]
Osteogenesis imperfecta	DIS7XQSD	moderate	Genetic Variation	[2]
Osteogenesis imperfecta type 2	DISMGSS3	Supportive	Autosomal dominant	[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 LRP chaperone MESD (MESD).	[5]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of LRP chaperone MESD (MESD).	[6]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of LRP chaperone MESD (MESD).	[7]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of LRP chaperone MESD (MESD).	[8]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of LRP chaperone MESD (MESD).	[9]
Okadaic acid	DM47CO1	Investigative	Okadaic acid decreases the expression of LRP chaperone MESD (MESD).	[10]

References

• [1] Fusion of the SUMO/Sentrin-specific protease 1 gene SENP1 and the embryonic polarity-related mesoderm development gene MESDC2 in a patient with an infantile teratoma and a constitutional t(12;15)(q13;q25).Hum Mol Genet. 2005 Jul 15;14(14):1955-63. doi: 10.1093/hmg/ddi200. Epub 2005 May 25.
• [2] Autosomal-Recessive Mutations in MESD Cause Osteogenesis Imperfecta. Am J Hum Genet. 2019 Oct 3;105(4):836-843. doi: 10.1016/j.ajhg.2019.08.008. Epub 2019 Sep 26.
• [3] Role of Wnt Co-Receptor LRP6 in Triple Negative Breast Cancer Cell Migration and Invasion.J Cell Biochem. 2017 Sep;118(9):2968-2976. doi: 10.1002/jcb.25956. Epub 2017 May 30.
• [4] Compound Heterozygous Frameshift Mutations in MESD Cause a Lethal Syndrome Suggestive of Osteogenesis Imperfecta Type XX. J Bone Miner Res. 2021 Jun;36(6):1077-1087. doi: 10.1002/jbmr.4277. Epub 2021 Mar 19.
• [5] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [6] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [7] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [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] Bisphenol A induces DSB-ATM-p53 signaling leading to cell cycle arrest, senescence, autophagy, stress response, and estrogen release in human fetal lung fibroblasts. Arch Toxicol. 2018 Apr;92(4):1453-1469.
• [10] Proteomic analysis reveals multiple patterns of response in cells exposed to a toxin mixture. Chem Res Toxicol. 2009 Jun;22(6):1077-85.