Details of Drug Off-Target (DOT)

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

• DOT Name: B-lymphocyte antigen CD20 (MS4A1)
• Synonyms: B-lymphocyte surface antigen B1; Bp35; Leukocyte surface antigen Leu-16; Membrane-spanning 4-domains subfamily A member 1; CD antigen CD20
• Gene Name: MS4A1
• Related Disease:
  Common variable immunodeficiency
  Immunodeficiency, common variable, 5
• UniProt ID: CD20_HUMAN
• PDB ID: 2OSL; 3BKY; 3PP4; 6VJA; 6Y90; 6Y92; 6Y97; 6Y9A
• Pfam ID: PF04103
• Sequence:
  MTTPRNSVNGTFPAEPMKGPIAMQSGPKPLFRRMSSLVGPTQSFFMRESKTLGAVQIMNG
  LFHIALGGLLMIPAGIYAPICVTVWYPLWGGIMYIISGSLLAATEKNSRKCLVKGKMIMN
  SLSLFAAISGMILSIMDILNIKISHFLKMESLNFIRAHTPYINIYNCEPANPSEKNSPST
  QYCYSIQSLFLGILSVMLIFAFFQELVIAGIVENEWKRTCSRPKSNIVLLSAEEKKEQTI
  EIKEEVVGLTETSSQPKNEEDIEIIPIQEEEEEETETNFPEPPQDQESSPIENDSSP
• Function: B-lymphocyte-specific membrane protein that plays a role in the regulation of cellular calcium influx necessary for the development, differentiation, and activation of B-lymphocytes. Functions as a store-operated calcium (SOC) channel component promoting calcium influx after activation by the B-cell receptor/BCR.
• Tissue Specificity: Expressed on B-cells.
• KEGG Pathway: Hematopoietic cell lineage (hsa04640)

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Common variable immunodeficiency	DISHE7JQ	Supportive	Autosomal dominant	[1]
Immunodeficiency, common variable, 5	DISLLQGK	Limited	Autosomal recessive	[2]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Capecitabine	DMTS85L	Approved	Capecitabine decreases the expression of B-lymphocyte antigen CD20 (MS4A1).	[3]
Curcumin	DMQPH29	Phase 3	Curcumin decreases the expression of B-lymphocyte antigen CD20 (MS4A1).	[4]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of B-lymphocyte antigen CD20 (MS4A1).	[6]

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 increases the methylation of B-lymphocyte antigen CD20 (MS4A1).	[5]

References

• [1] CD20 deficiency in humans results in impaired T cell-independent antibody responses. J Clin Invest. 2010 Jan;120(1):214-22. doi: 10.1172/JCI40231. Epub 2009 Dec 21.
• [2] 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.
• [3] Gene expression responses reflecting 5-FU-induced toxicity: Comparison between patient colon tissue and 3D human colon organoids. Toxicol Lett. 2022 Dec 1;371:17-24. doi: 10.1016/j.toxlet.2022.09.013. Epub 2022 Sep 29.
• [4] Gene-expression profiling during curcumin-induced apoptosis reveals downregulation of CXCR4. Exp Hematol. 2007 Jan;35(1):84-95.
• [5] 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.
• [6] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.