Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTXBCY9W)

• DOT Name: Brother of CDO (BOC)
• Synonyms: Protein BOC
• Gene Name: BOC
• Related Disease:
  Holoprosencephaly
  Anemia
  Bronchopulmonary dysplasia
  Colon cancer
  Colorectal adenocarcinoma
  Colorectal adenoma
  Colorectal cancer
  Colorectal cancer, susceptibility to, 1
  Colorectal cancer, susceptibility to, 10
  Colorectal cancer, susceptibility to, 12
  Colorectal carcinoma
  Colorectal neoplasm
  Gastrointestinal stromal tumour
  Hepatitis C virus infection
  Liver cirrhosis
  Medulloblastoma
  Leukopenia
• UniProt ID: BOC_HUMAN
• PDB ID: 3N1G; 3N1M; 3N1P
• Pfam ID: PF00041 ; PF07679 ; PF13927 ; PF16625
• Sequence:
  MLRGTMTAWRGMRPEVTLACLLLATAGCFADLNEVPQVTVQPASTVQKPGGTVILGCVVE
  PPRMNVTWRLNGKELNGSDDALGVLITHGTLVITALNNHTVGRYQCVARMPAGAVASVPA
  TVTLANLQDFKLDVQHVIEVDEGNTAVIACHLPESHPKAQVRYSVKQEWLEASRGNYLIM
  PSGNLQIVNASQEDEGMYKCAAYNPVTQEVKTSGSSDRLRVRRSTAEAARIIYPPEAQTI
  IVTKGQSLILECVASGIPPPRVTWAKDGSSVTGYNKTRFLLSNLLIDTTSEEDSGTYRCM
  ADNGVGQPGAAVILYNVQVFEPPEVTMELSQLVIPWGQSAKLTCEVRGNPPPSVLWLRNA
  VPLISSQRLRLSRRALRVLSMGPEDEGVYQCMAENEVGSAHAVVQLRTSRPSITPRLWQD
  AELATGTPPVSPSKLGNPEQMLRGQPALPRPPTSVGPASPQCPGEKGQGAPAEAPIILSS
  PRTSKTDSYELVWRPRHEGSGRAPILYYVVKHRKVTNSSDDWTISGIPANQHRLTLTRLD
  PGSLYEVEMAAYNCAGEGQTAMVTFRTGRRPKPEIMASKEQQIQRDDPGASPQSSSQPDH
  GRLSPPEAPDRPTISTASETSVYVTWIPRGNGGFPIQSFRVEYKKLKKVGDWILATSAIP
  PSRLSVEITGLEKGTSYKFRVRALNMLGESEPSAPSRPYVVSGYSGRVYERPVAGPYITF
  TDAVNETTIMLKWMYIPASNNNTPIHGFYIYYRPTDSDNDSDYKKDMVEGDKYWHSISHL
  QPETSYDIKMQCFNEGGESEFSNVMICETKARKSSGQPGRLPPPTLAPPQPPLPETIERP
  VGTGAMVARSSDLPYLIVGVVLGSIVLIIVTFIPFCLWRAWSKQKHTTDLGFPRSALPPS
  CPYTMVPLGGLPGHQASGQPYLSGISGRACANGIHMNRGCPSAAVGYPGMKPQQHCPGEL
  QQQSDTSSLLRQTHLGNGYDPQSHQITRGPKSSPDEGSFLYTLPDDSTHQLLQPHHDCCQ
  RQEQPAAVGQSGVRRAPDSPVLEAVWDPPFHSGPPCCLGLVPVEEVDSPDSCQVSGGDWC
  PQHPVGAYVGQEPGMQLSPGPLVRVSFETPPLTI
• Function: Component of a cell-surface receptor complex that mediates cell-cell interactions between muscle precursor cells. Promotes differentiation of myogenic cells.
• Tissue Specificity: Detected in skeletal muscle, heart, thymus, kidney and small intestine. Detected at lower levels in brain, placenta, lung and colon mucosa.
• KEGG Pathway:
  Hedgehog sig.ling pathway (hsa04340)
  Axon guidance (hsa04360)
• Reactome Pathway:
  Activation of SMO (R-HSA-5635838)
  Ligand-receptor interactions (R-HSA-5632681)

Molecular Interaction Atlas (MIA) of This DOT

17 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Holoprosencephaly	DISR35EC	Definitive	Genetic Variation	[1]
Anemia	DISTVL0C	Strong	Genetic Variation	[2]
Bronchopulmonary dysplasia	DISO0BY5	Strong	Biomarker	[3]
Colon cancer	DISVC52G	Strong	Genetic Variation	[4]
Colorectal adenocarcinoma	DISPQOUB	Strong	Genetic Variation	[4]
Colorectal adenoma	DISTSVHM	Strong	Genetic Variation	[4]
Colorectal cancer	DISNH7P9	Strong	Genetic Variation	[4]
Colorectal cancer, susceptibility to, 1	DISZ794C	Strong	Genetic Variation	[4]
Colorectal cancer, susceptibility to, 10	DISQXMYM	Strong	Genetic Variation	[4]
Colorectal cancer, susceptibility to, 12	DIS4FXJX	Strong	Genetic Variation	[4]
Colorectal carcinoma	DIS5PYL0	Strong	Genetic Variation	[4]
Colorectal neoplasm	DISR1UCN	Strong	Biomarker	[4]
Gastrointestinal stromal tumour	DIS6TJYS	Strong	Biomarker	[5]
Hepatitis C virus infection	DISQ0M8R	Strong	Genetic Variation	[6]
Liver cirrhosis	DIS4G1GX	Strong	Genetic Variation	[6]
Medulloblastoma	DISZD2ZL	Strong	Altered Expression	[7]
Leukopenia	DISJMBMM	moderate	Biomarker	[2]

11 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 Brother of CDO (BOC).	[8]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Brother of CDO (BOC).	[9]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Brother of CDO (BOC).	[10]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Brother of CDO (BOC).	[11]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Brother of CDO (BOC).	[12]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Brother of CDO (BOC).	[13]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of Brother of CDO (BOC).	[14]
Triclosan	DMZUR4N	Approved	Triclosan increases the expression of Brother of CDO (BOC).	[15]
Panobinostat	DM58WKG	Approved	Panobinostat increases the expression of Brother of CDO (BOC).	[16]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Brother of CDO (BOC).	[19]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Brother of CDO (BOC).	[20]

3 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Fulvestrant	DM0YZC6	Approved	Fulvestrant decreases the methylation of Brother of CDO (BOC).	[17]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Brother of CDO (BOC).	[18]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Brother of CDO (BOC).	[17]

References

• [1] BOC is a modifier gene in holoprosencephaly.Hum Mutat. 2017 Nov;38(11):1464-1470. doi: 10.1002/humu.23286. Epub 2017 Jul 21.
• [2] Overall safety profile of boceprevir plus peginterferon alfa-2b and ribavirin in patients with chronic hepatitis C genotype 1: a combined analysis of 3 phase 2/3 clinical trials.Liver Int. 2014 May;34(5):707-19. doi: 10.1111/liv.12300. Epub 2013 Oct 9.
• [3] Lipoxin A4 reduces hyperoxia-induced lung injury in neonatal rats through PINK1 signaling pathway.Int Immunopharmacol. 2019 Aug;73:414-423. doi: 10.1016/j.intimp.2019.05.046. Epub 2019 May 29.
• [4] Discovery of common and rare genetic risk variants for colorectal cancer.Nat Genet. 2019 Jan;51(1):76-87. doi: 10.1038/s41588-018-0286-6. Epub 2018 Dec 3.
• [5] Hedgehog pathway dysregulation contributes to the pathogenesis of human gastrointestinal stromal tumors via GLI-mediated activation of KIT expression. Oncotarget. 2016 Nov 29;7(48):78226-78241. doi: 10.18632/oncotarget.12909.
• [6] Influence of sustained viral response on the regression of fibrosis and portal hypertension in cirrhotic HCV patients treated with antiviral triple therapy.Rev Esp Enferm Dig. 2017 Jan;109(1):17-25. doi: 10.17235/reed.2016.4235/2016.
• [7] The Shh receptor Boc promotes progression of early medulloblastoma to advanced tumors.Dev Cell. 2014 Oct 13;31(1):34-47. doi: 10.1016/j.devcel.2014.08.010. Epub 2014 Sep 25.
• [8] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [9] Development of a neural teratogenicity test based on human embryonic stem cells: response to retinoic acid exposure. Toxicol Sci. 2011 Dec;124(2):370-7.
• [10] 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.
• [11] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [12] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [13] Genistein and bisphenol A exposure cause estrogen receptor 1 to bind thousands of sites in a cell type-specific manner. Genome Res. 2012 Nov;22(11):2153-62.
• [14] Identification of transcriptome signatures and biomarkers specific for potential developmental toxicants inhibiting human neural crest cell migration. Arch Toxicol. 2016 Jan;90(1):159-80.
• [15] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [16] A transcriptome-based classifier to identify developmental toxicants by stem cell testing: design, validation and optimization for histone deacetylase inhibitors. Arch Toxicol. 2015 Sep;89(9):1599-618.
• [17] DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.
• [18] 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.
• [19] 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.
• [20] From transient transcriptome responses to disturbed neurodevelopment: role of histone acetylation and methylation as epigenetic switch between reversible and irreversible drug effects. Arch Toxicol. 2014 Jul;88(7):1451-68.