Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT8CSNU2)

• DOT Name: CD320 antigen (CD320)
• Synonyms: 8D6 antigen; FDC-signaling molecule 8D6; FDC-SM-8D6; Transcobalamin receptor; TCblR; CD antigen CD320
• Gene Name: CD320
• Related Disease: Methylmalonic acidemia due to transcobalamin receptor defect
• UniProt ID: CD320_HUMAN
• PDB ID: 4ZRP; 4ZRQ; 7QBD; 7QBE; 7QBF; 7QBG
• Pfam ID: PF00057
• Sequence:
  MSGGWMAQVGAWRTGALGLALLLLLGLGLGLEAAASPLSTPTSAQAAGPSSGSCPPTKFQ
  CRTSGLCVPLTWRCDRDLDCSDGSDEEECRIEPCTQKGQCPPPPGLPCPCTGVSDCSGGT
  DKKLRNCSRLACLAGELRCTLSDDCIPLTWRCDGHPDCPDSSDELGCGTNEILPEGDATT
  MGPPVTLESVTSLRNATTMGPPVTLESVPSVGNATSSSAGDQSGSPTAYGVIAAAAVLSA
  SLVTATLLLLSWLRAQERLRPLGLLVAMKESLLLSEQKTSLP
• Function: Receptor for transcobalamin saturated with cobalamin (TCbl). Plays an important role in cobalamin uptake. Plasma membrane protein that is expressed on follicular dendritic cells (FDC) and mediates interaction with germinal center B cells. Functions as costimulator to promote B cell responses to antigenic stimuli; promotes B cell differentiation and proliferation. Germinal center-B (GC-B) cells differentiate into memory B-cells and plasma cells (PC) through interaction with T-cells and follicular dendritic cells (FDC). CD320 augments the proliferation of PC precursors generated by IL-10.
• Tissue Specificity: Detected in the germinal center (GC) of lymphoid follicles (at protein level) . Expressed abundantly on follicular dendritic cells (FDCs) .
• KEGG Pathway: Cobalamin transport and metabolism (hsa04980)
• Reactome Pathway:
  Transport of RCbl within the body (R-HSA-9758890)
  Defective CD320 causes MMATC (R-HSA-3359485)

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Methylmalonic acidemia due to transcobalamin receptor defect	DIS7B024	Definitive	Autosomal recessive	[1]

10 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 CD320 antigen (CD320).	[2]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of CD320 antigen (CD320).	[3]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of CD320 antigen (CD320).	[4]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of CD320 antigen (CD320).	[5]
Amiodarone	DMUTEX3	Phase 2/3 Trial	Amiodarone increases the expression of CD320 antigen (CD320).	[6]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of CD320 antigen (CD320).	[7]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of CD320 antigen (CD320).	[8]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of CD320 antigen (CD320).	[9]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of CD320 antigen (CD320).	[10]
Coumestrol	DM40TBU	Investigative	Coumestrol increases the expression of CD320 antigen (CD320).	[11]

References

• [1] Technical standards for the interpretation and reporting of constitutional copy-number variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics (ACMG) and the Clinical Genome Resource (ClinGen). Genet Med. 2020 Feb;22(2):245-257. doi: 10.1038/s41436-019-0686-8. Epub 2019 Nov 6.
• [2] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [3] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [4] Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
• [5] 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.
• [6] Identification by automated screening of a small molecule that selectively eliminates neural stem cells derived from hESCs but not dopamine neurons. PLoS One. 2009 Sep 23;4(9):e7155.
• [7] Identification of a transcriptomic signature of food-relevant genotoxins in human HepaRG hepatocarcinoma cells. Food Chem Toxicol. 2020 Jun;140:111297. doi: 10.1016/j.fct.2020.111297. Epub 2020 Mar 28.
• [8] Bromodomain-containing protein 4 (BRD4) regulates RNA polymerase II serine 2 phosphorylation in human CD4+ T cells. J Biol Chem. 2012 Dec 14;287(51):43137-55.
• [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] Identification of mechanisms of action of bisphenol a-induced human preadipocyte differentiation by transcriptional profiling. Obesity (Silver Spring). 2014 Nov;22(11):2333-43.
• [11] Pleiotropic combinatorial transcriptomes of human breast cancer cells exposed to mixtures of dietary phytoestrogens. Food Chem Toxicol. 2009 Apr;47(4):787-95.