Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTWV82RP)

• DOT Name: Membrane-spanning 4-domains subfamily A member 4A (MS4A4A)
• Synonyms: CD20 antigen-like 1; Four-span transmembrane protein 1
• Gene Name: MS4A4A
• Related Disease:
  Familial Alzheimer disease
  Juvenile idiopathic arthritis
  Prion disease
  Mantle cell lymphoma
  Plasma cell myeloma
  Alzheimer disease
• UniProt ID: M4A4A_HUMAN
• Pfam ID: PF04103
• Sequence:
  MHQTYSRHCRPEESTFSAAMTTMQGMEQAMPGAGPGVPQLGNMAVIHSHLWKGLQEKFLK
  GEPKVLGVVQILTALMSLSMGITMMCMASNTYGSNPISVYIGYTIWGSVMFIISGSLSIA
  AGIRTTKGLVRGSLGMNITSSVLAASGILINTFSLAFYSFHHPYCNYYGNSNNCHGTMSI
  LMGLDGMVLLLSVLEFCIAVSLSAFGCKVLCCTPGGVVLILPSHSHMAETASPTPLNEV
• Function: May be involved in signal transduction as a component of a multimeric receptor complex.
• Tissue Specificity: Variable expression in multiple hemopoietic cell lines.

Molecular Interaction Atlas (MIA) of This DOT

6 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Familial Alzheimer disease	DISE75U4	Strong	Biomarker	[1]
Juvenile idiopathic arthritis	DISQZGBV	Strong	Biomarker	[2]
Prion disease	DISOUMB0	Strong	Genetic Variation	[3]
Mantle cell lymphoma	DISFREOV	moderate	Biomarker	[4]
Plasma cell myeloma	DIS0DFZ0	moderate	Biomarker	[4]
Alzheimer disease	DISF8S70	Limited	Genetic Variation	[5]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Membrane-spanning 4-domains subfamily A member 4A (MS4A4A).	[6]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Membrane-spanning 4-domains subfamily A member 4A (MS4A4A).	[7]
Calcitriol	DM8ZVJ7	Approved	Calcitriol decreases the expression of Membrane-spanning 4-domains subfamily A member 4A (MS4A4A).	[8]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Membrane-spanning 4-domains subfamily A member 4A (MS4A4A).	[10]

1 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 Membrane-spanning 4-domains subfamily A member 4A (MS4A4A).	[9]

References

• [1] Common variants at MS4A4/MS4A6E, CD2AP, CD33 and EPHA1 are associated with late-onset Alzheimer's disease.Nat Genet. 2011 May;43(5):436-41. doi: 10.1038/ng.801. Epub 2011 Apr 3.
• [2] Gene expression signatures in polyarticular juvenile idiopathic arthritis demonstrate disease heterogeneity and offer a molecular classification of disease subsets.Arthritis Rheum. 2009 Jul;60(7):2113-23. doi: 10.1002/art.24534.
• [3] Genome-wide association study in multiple human prion diseases suggests genetic risk factors additional to PRNP.Hum Mol Genet. 2012 Apr 15;21(8):1897-906. doi: 10.1093/hmg/ddr607. Epub 2011 Dec 30.
• [4] MS4A4A: a novel cell surface marker for M2 macrophages and plasma cells.Immunol Cell Biol. 2017 Aug;95(7):611-619. doi: 10.1038/icb.2017.18. Epub 2017 Mar 17.
• [5] Genome-wide meta-analysis identifies new loci and functional pathways influencing Alzheimer's disease risk.Nat Genet. 2019 Mar;51(3):404-413. doi: 10.1038/s41588-018-0311-9. Epub 2019 Jan 7.
• [6] Gene expression analysis of precision-cut human liver slices indicates stable expression of ADME-Tox related genes. Toxicol Appl Pharmacol. 2011 May 15;253(1):57-69.
• [7] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [8] Identification of vitamin D3 target genes in human breast cancer tissue. J Steroid Biochem Mol Biol. 2016 Nov;164:90-97.
• [9] 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.
• [10] Transcriptional signature of human macrophages exposed to the environmental contaminant benzo(a)pyrene. Toxicol Sci. 2010 Apr;114(2):247-59.