Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTQL6F4R)

• DOT Name: Biorientation of chromosomes in cell division protein 1 (BOD1)
• Synonyms: Biorientation defective protein 1; Protein FAM44B
• Gene Name: BOD1
• Related Disease:
  Breast cancer
  Breast carcinoma
  Herpes zoster
  Intellectual disability
  Syndromic intellectual disability
• UniProt ID: BOD1_HUMAN
• Pfam ID: PF05205
• Sequence:
  MADGGGGGGTGAVGGGGTSQASAGAATGATGASGGGGPINPASLPPGDPQLIALIVEQLK
  SRGLFDSFRRDCLADVDTKPAYQNLRQKVDNFVSTHLDKQEWNPTMNKNQLRNGLRQSVV
  QSGMLEAGVDRIISQVVDPKLNHIFRPQIERAIHEFLAAQKKAAVPAPPPEPEGQDPPAP
  SQDTS
• Function: Required for proper chromosome biorientation through the detection or correction of syntelic attachments in mitotic spindles.
• Reactome Pathway: Formation of WDR5-containing histone-modifying complexes (R-HSA-9772755)

Molecular Interaction Atlas (MIA) of This DOT

5 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Breast cancer	DIS7DPX1	Strong	Altered Expression	[1]
Breast carcinoma	DIS2UE88	Strong	Altered Expression	[1]
Herpes zoster	DISNSMNY	Strong	Biomarker	[2]
Intellectual disability	DISMBNXP	Limited	Autosomal recessive	[3]
Syndromic intellectual disability	DISH7SDF	Limited	Autosomal recessive	[4]

5 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 Biorientation of chromosomes in cell division protein 1 (BOD1).	[5]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Biorientation of chromosomes in cell division protein 1 (BOD1).	[6]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Biorientation of chromosomes in cell division protein 1 (BOD1).	[7]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Biorientation of chromosomes in cell division protein 1 (BOD1).	[9]
chloropicrin	DMSGBQA	Investigative	chloropicrin decreases the expression of Biorientation of chromosomes in cell division protein 1 (BOD1).	[10]

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 decreases the methylation of Biorientation of chromosomes in cell division protein 1 (BOD1).	[8]

References

• [1] miR-142-3p attenuates breast cancer stem cell characteristics and decreases radioresistance in vitro.Tumour Biol. 2018 Aug;40(8):1010428318791887. doi: 10.1177/1010428318791887.
• [2] Disease burden of varicella versus other vaccine-preventable diseases before introduction of vaccination into the national immunisation programme in the Netherlands.Euro Surveill. 2019 May;24(18):1800363. doi: 10.2807/1560-7917.ES.2019.24.18.1800363.
• [3] Classification of Genes: Standardized Clinical Validity Assessment of Gene-Disease Associations Aids Diagnostic Exome Analysis and Reclassifications. Hum Mutat. 2017 May;38(5):600-608. doi: 10.1002/humu.23183. Epub 2017 Feb 13.
• [4] A homozygous stop gain mutation in BOD1 gene in a Lebanese patient with syndromic intellectual disability. Clin Genet. 2020 Sep;98(3):288-292. doi: 10.1111/cge.13799.
• [5] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [6] Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
• [7] High-throughput ectopic expression screen for tamoxifen resistance identifies an atypical kinase that blocks autophagy. Proc Natl Acad Sci U S A. 2011 Feb 1;108(5):2058-63.
• [8] 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.
• [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.
• [10] Transcriptomic analysis of human primary bronchial epithelial cells after chloropicrin treatment. Chem Res Toxicol. 2015 Oct 19;28(10):1926-35.