Details of Drug Off-Target (DOT)

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

• DOT Name: Osteomodulin (OMD)
• Synonyms: Keratan sulfate proteoglycan osteomodulin; KSPG osteomodulin; Osteoadherin; OSAD
• Gene Name: OMD
• Related Disease:
  Advanced cancer
  Dermatofibrosarcoma protuberans
  Aromatic L-amino acid decarboxylase deficiency
  Malaria
  Obsessive compulsive disorder
  Osteoarthritis
  Meningioma
  Neoplasm
• UniProt ID: OMD_HUMAN
• PDB ID: 5YQ5
• Pfam ID: PF13855
• Sequence:
  MGFLSPIYVIFFFFGVKVHCQYETYQWDEDYDQEPDDDYQTGFPFRQNVDYGVPFHQYTL
  GCVSECFCPTNFPSSMYCDNRKLKTIPNIPMHIQQLYLQFNEIEAVTANSFINATHLKEI
  NLSHNKIKSQKIDYGVFAKLPNLLQLHLEHNNLEEFPFPLPKSLERLLLGYNEISKLQTN
  AMDGLVNLTMLDLCYNYLHDSLLKDKIFAKMEKLMQLNLCSNRLESMPPGLPSSLMYLSL
  ENNSISSIPEKYFDKLPKLHTLRMSHNKLQDIPYNIFNLPNIVELSVGHNKLKQAFYIPR
  NLEHLYLQNNEIEKMNLTVMCPSIDPLHYHHLTYIRVDQNKLKEPISSYIFFCFPHIHTI
  YYGEQRSTNGQTIQLKTQVFRRFPDDDDESEDHDDPDNAHESPEQEGAEGHFDLHYYENQ
  E
• Function: May be implicated in biomineralization processes. Has a function in binding of osteoblasts via the alpha(V)beta(3)-integrin.
• Tissue Specificity: Bone specific.
• Reactome Pathway:
  Keratan sulfate degradation (R-HSA-2022857)
  Defective CHST6 causes MCDC1 (R-HSA-3656225)
  Defective ST3GAL3 causes MCT12 and EIEE15 (R-HSA-3656243)
  Defective B4GALT1 causes B4GALT1-CDG (CDG-2d) (R-HSA-3656244)
  Keratan sulfate biosynthesis (R-HSA-2022854)

Molecular Interaction Atlas (MIA) of This DOT

8 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Advanced cancer	DISAT1Z9	Definitive	Altered Expression	[1]
Dermatofibrosarcoma protuberans	DIS4OCQM	Definitive	Altered Expression	[1]
Aromatic L-amino acid decarboxylase deficiency	DIS3C407	Strong	Biomarker	[2]
Malaria	DISQ9Y50	Strong	Biomarker	[3]
Obsessive compulsive disorder	DIS1ZMM2	Strong	Altered Expression	[4]
Osteoarthritis	DIS05URM	Strong	Biomarker	[5]
Meningioma	DISPT4TG	moderate	Biomarker	[6]
Neoplasm	DISZKGEW	Limited	Genetic Variation	[7]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Osteomodulin (OMD).	[8]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Osteomodulin (OMD).	[9]
Progesterone	DMUY35B	Approved	Progesterone increases the expression of Osteomodulin (OMD).	[10]
Berberine	DMC5Q8X	Phase 4	Berberine increases the expression of Osteomodulin (OMD).	[11]

References

• [1] Aneurysmal bone cyst variant translocations upregulate USP6 transcription by promoter swapping with the ZNF9, COL1A1, TRAP150, and OMD genes.Oncogene. 2005 May 12;24(21):3419-26. doi: 10.1038/sj.onc.1208506.
• [2] High throughput newborn screening for aromatic -amino-acid decarboxylase deficiency by analysis of concentrations of 3-O-methyldopa from dried blood spots.J Inherit Metab Dis. 2020 May;43(3):602-610. doi: 10.1002/jimd.12208. Epub 2020 Jan 6.
• [3] Malaria transmission through the mosquito requires the function of the OMD protein.PLoS One. 2019 Sep 25;14(9):e0222226. doi: 10.1371/journal.pone.0222226. eCollection 2019.
• [4] Reduced 3-O-methyl-dopa levels in OCD patients and their unaffected parents is associated with the low activity M158 COMT allele. Am J Med Genet B Neuropsychiatr Genet. 2010 Mar 5;153B(2):542-548.
• [5] Comparison of secretome from osteoblasts derived from sclerotic versus non-sclerotic subchondral bone in OA: A pilot study.PLoS One. 2018 Mar 16;13(3):e0194591. doi: 10.1371/journal.pone.0194591. eCollection 2018.
• [6] Genetic alterations in meningiomas of different textures.Gene. 2016 Oct 30;592(1):134-139. doi: 10.1016/j.gene.2016.07.057. Epub 2016 Jul 27.
• [7] Gene fusions PAFAH1B1-USP6 and RUNX2-USP6 in aneurysmal bone cysts identified by next generation sequencing.Cancer Genet. 2017 Apr;212-213:13-18. doi: 10.1016/j.cancergen.2017.03.007. Epub 2017 Mar 24.
• [8] Bringing in vitro analysis closer to in vivo: studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling. Toxicol Lett. 2018 Sep 15;294:184-192.
• [9] Bisphenol A effects on gene expression in adipocytes from children: association with metabolic disorders. J Mol Endocrinol. 2015 Jun;54(3):289-303.
• [10] Unique transcriptome, pathways, and networks in the human endometrial fibroblast response to progesterone in endometriosis. Biol Reprod. 2011 Apr;84(4):801-15.
• [11] Berberine promotes bone marrow-derived mesenchymal stem cells osteogenic differentiation via canonical Wnt/-catenin signaling pathway. Toxicol Lett. 2016 Jan 5;240(1):68-80. doi: 10.1016/j.toxlet.2015.10.007. Epub 2015 Oct 22.