Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT0CEJOO)

• DOT Name: Membrane-spanning 4-domains subfamily A member 3 (MS4A3)
• Synonyms: CD20 antigen-like protein; Hematopoietic-specific transmembrane protein 4; HTm4
• Gene Name: MS4A3
• Related Disease:
  Acute myelogenous leukaemia
  Alzheimer disease
  leukaemia
  Leukemia
  Lung squamous cell carcinoma
  Neoplasm
  Asthma
  Adenocarcinoma
  Advanced cancer
• UniProt ID: MS4A3_HUMAN
• Pfam ID: PF04103
• Sequence:
  MASHEVDNAELGSASAHGTPGSEAGPEELNTSVYQPIDGSPDYQKAKLQVLGAIQILNAA
  MILALGVFLGSLQYPYHFQKHFFFFTFYTGYPIWGAVFFCSSGTLSVVAGIKPTRTWIQN
  SFGMNIASATIALVGTAFLSLNIAVNIQSLRSCHSSSESPDLCNYMGSISNGMVSLLLIL
  TLLELCVTISTIAMWCNANCCNSREEISSPPNSV
• Function: Hematopoietic modulator for the G1-S cell cycle transition. Modulates the level of phosphorylation of cyclin-dependent kinase 2 (CDK2) through its direct binding to cyclin-dependent kinase inhibitor 3 (CDKN3/KAP).
• Tissue Specificity: Expressed specifically in hematopoietic cells and tissues.
• Reactome Pathway: Neutrophil degranulation (R-HSA-6798695)

Molecular Interaction Atlas (MIA) of This DOT

9 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Acute myelogenous leukaemia	DISCSPTN	Strong	Biomarker	[1]
Alzheimer disease	DISF8S70	Strong	Biomarker	[2]
leukaemia	DISS7D1V	Strong	Biomarker	[1]
Leukemia	DISNAKFL	Strong	Biomarker	[1]
Lung squamous cell carcinoma	DISXPIBD	Strong	Biomarker	[3]
Neoplasm	DISZKGEW	Strong	Altered Expression	[4]
Asthma	DISW9QNS	moderate	Genetic Variation	[5]
Adenocarcinoma	DIS3IHTY	Limited	Altered Expression	[6]
Advanced cancer	DISAT1Z9	Limited	Altered Expression	[6]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide decreases the expression of Membrane-spanning 4-domains subfamily A member 3 (MS4A3).	[7]
Decitabine	DMQL8XJ	Approved	Decitabine increases the expression of Membrane-spanning 4-domains subfamily A member 3 (MS4A3).	[8]
Cyclophosphamide	DM4O2Z7	Approved	Cyclophosphamide decreases the expression of Membrane-spanning 4-domains subfamily A member 3 (MS4A3).	[9]
Butanoic acid	DMTAJP7	Investigative	Butanoic acid increases the expression of Membrane-spanning 4-domains subfamily A member 3 (MS4A3).	[7]

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 Membrane-spanning 4-domains subfamily A member 3 (MS4A3).	[10]

References

• [1] Ecotropic viral integration site 1 regulates the progression of acute myeloid leukemia via MS4A3-mediated TGF/EMT signaling pathway.Oncol Lett. 2018 Aug;16(2):2701-2708. doi: 10.3892/ol.2018.8890. Epub 2018 Jun 4.
• [2] Gene-based aggregate SNP associations between candidate AD genes and cognitive decline.Age (Dordr). 2016 Apr;38(2):41. doi: 10.1007/s11357-016-9885-2. Epub 2016 Mar 22.
• [3] Whole-exome sequencing to identify novel somatic mutations in squamous cell lung cancers.Int J Oncol. 2013 Sep;43(3):755-64. doi: 10.3892/ijo.2013.1991. Epub 2013 Jun 25.
• [4] EVI1 promotes tumor growth via transcriptional repression of MS4A3.J Hematol Oncol. 2015 Mar 21;8:28. doi: 10.1186/s13045-015-0124-6.
• [5] Asthma susceptible genes in Chinese population: a meta-analysis.Respir Res. 2010 Sep 24;11(1):129. doi: 10.1186/1465-9921-11-129.
• [6] Characterization of the expression of HTm4 (MS4A3), a cell cycle regulator, in human peripheral blood cells and normal and malignant tissues.J Cell Mol Med. 2011 Jan;15(1):86-93. doi: 10.1111/j.1582-4934.2009.00925.x.
• [7] MS4A3-HSP27 target pathway reveals potential for haematopoietic disorder treatment in alimentary toxic aleukia. Cell Biol Toxicol. 2023 Feb;39(1):201-216. doi: 10.1007/s10565-021-09639-4. Epub 2021 Sep 28.
• [8] The DNA methyltransferase inhibitors azacitidine, decitabine and zebularine exert differential effects on cancer gene expression in acute myeloid leukemia cells. Leukemia. 2009 Jun;23(6):1019-28.
• [9] Comparative gene expression analysis of a chronic myelogenous leukemia cell line resistant to cyclophosphamide using oligonucleotide arrays and response to tyrosine kinase inhibitors. Leuk Res. 2007 Nov;31(11):1511-20.
• [10] 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.