Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTMCAS2D)

• DOT Name: High affinity immunoglobulin epsilon receptor subunit beta (MS4A2)
• Synonyms: FcERI; Fc epsilon receptor I beta-chain; IgE Fc receptor subunit beta; Membrane-spanning 4-domains subfamily A member 2
• Gene Name: MS4A2
• Related Disease:
  Cockayne syndrome type 1
  Allergic asthma
  Allergic rhinitis
  Alzheimer disease
  Asthma
  Bacillary dysentery
  Food allergy
  Helminth infection
  Keratoconjunctivitis
  Respiratory disease
  Vitamin D deficiency
  Advanced cancer
  Atopic dermatitis
  Lung cancer
  Lung carcinoma
  Pneumonia
  Vitelliform macular dystrophy
  IgE responsiveness, atopic
• UniProt ID: FCERB_HUMAN
• Pfam ID: PF04103
• Sequence:
  MDTESNRRANLALPQEPSSVPAFEVLEISPQEVSSGRLLKSASSPPLHTWLTVLKKEQEF
  LGVTQILTAMICLCFGTVVCSVLDISHIEGDIFSSFKAGYPFWGAIFFSISGMLSIISER
  RNATYLVRGSLGANTASSIAGGTGITILIINLKKSLAYIHIHSCQKFFETKCFMASFSTE
  IVVMMLFLTILGLGSAVSLTICGAGEELKGNKVPEDRVYEELNIYSATYSELEDPGEMSP
  PIDL
• Function: High affinity receptor that binds to the Fc region of immunoglobulins epsilon. Aggregation of FCER1 by multivalent antigens is required for the full mast cell response, including the release of preformed mediators (such as histamine) by degranulation and de novo production of lipid mediators and cytokines. Also mediates the secretion of important lymphokines. Binding of allergen to receptor-bound IgE leads to cell activation and the release of mediators responsible for the manifestations of allergy.
• Tissue Specificity: Found on the surface of mast cells and basophils.
• KEGG Pathway:
  Sphingolipid sig.ling pathway (hsa04071)
  Phospholipase D sig.ling pathway (hsa04072)
  Fc epsilon RI sig.ling pathway (hsa04664)
  Asthma (hsa05310)
• Reactome Pathway:
  Role of LAT2/NTAL/LAB on calcium mobilization (R-HSA-2730905)
  FCERI mediated MAPK activation (R-HSA-2871796)
  FCERI mediated Ca+2 mobilization (R-HSA-2871809)
  FCERI mediated NF-kB activation (R-HSA-2871837)
  Fc epsilon receptor (FCERI) signaling (R-HSA-2454202)

Molecular Interaction Atlas (MIA) of This DOT

18 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Cockayne syndrome type 1	DIS9JFVY	Definitive	Biomarker	[1]
Allergic asthma	DISHF0H3	Strong	Genetic Variation	[2]
Allergic rhinitis	DIS3U9HN	Strong	Genetic Variation	[3]
Alzheimer disease	DISF8S70	Strong	Biomarker	[4]
Asthma	DISW9QNS	Strong	Biomarker	[5]
Bacillary dysentery	DISFZHKN	Strong	Biomarker	[6]
Food allergy	DISMQ1BP	Strong	Genetic Variation	[7]
Helminth infection	DIS7CGKY	Strong	Biomarker	[8]
Keratoconjunctivitis	DISOYCQC	Strong	Genetic Variation	[6]
Respiratory disease	DISGGAGJ	Strong	Genetic Variation	[9]
Vitamin D deficiency	DISAWKYI	Strong	Genetic Variation	[10]
Advanced cancer	DISAT1Z9	Limited	Biomarker	[11]
Atopic dermatitis	DISTCP41	Limited	Biomarker	[12]
Lung cancer	DISCM4YA	Limited	Biomarker	[11]
Lung carcinoma	DISTR26C	Limited	Biomarker	[11]
Pneumonia	DIS8EF3M	Limited	Biomarker	[13]
Vitelliform macular dystrophy	DISEFYYN	Limited	Biomarker	[14]
IgE responsiveness, atopic	DISAE27V	No Known	Unknown	[15]

This DOT Affected the Drug Response of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Aspirin	DM672AH	Approved	High affinity immunoglobulin epsilon receptor subunit beta (MS4A2) affects the response to substance of Aspirin.	[18]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Methotrexate	DM2TEOL	Approved	Methotrexate increases the expression of High affinity immunoglobulin epsilon receptor subunit beta (MS4A2).	[16]

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 High affinity immunoglobulin epsilon receptor subunit beta (MS4A2).	[17]

References

• [1] Effectiveness of a school-based intervention to prevent child sexual abuse-Evaluation of the German IGEL program.Child Abuse Negl. 2018 Dec;86:109-122. doi: 10.1016/j.chiabu.2018.08.023. Epub 2018 Oct 1.
• [2] Association of the MS4A2 gene promoter C-109T or the 7th exon E237G polymorphisms with asthma risk: a meta-analysis.Clin Biochem. 2014 May;47(7-8):605-11. doi: 10.1016/j.clinbiochem.2014.01.022. Epub 2014 Feb 1.
• [3] A Nonsynonymous FCER1B SNP is Associated with Risk of Developing Allergic Rhinitis and with IgE Levels.Sci Rep. 2016 Jan 21;6:19724. doi: 10.1038/srep19724.
• [4] MS4A Cluster in Alzheimer's Disease.Mol Neurobiol. 2015;51(3):1240-8. doi: 10.1007/s12035-014-8800-z. Epub 2014 Jul 1.
• [5] MS4A2-rs573790 Is Associated With Aspirin-Exacerbated Respiratory Disease: Replicative Study Using a Candidate Gene Strategy.Front Genet. 2018 Sep 11;9:363. doi: 10.3389/fgene.2018.00363. eCollection 2018.
• [6] Alteration in apyrase enzyme attenuated virulence of Shigella flexneri.Microb Pathog. 2016 Feb;91:123-8. doi: 10.1016/j.micpath.2015.12.004. Epub 2015 Dec 17.
• [7] Influence of SNPs in cytokine-related genes on the severity of food allergy and atopic eczema in children.Pediatr Allergy Immunol. 2006 Dec;17(8):583-90. doi: 10.1111/j.1399-3038.2006.00463.x.
• [8] Variants in the CYSLTR2 are associated with asthma, atopy markers and helminths infections in the Brazilian population.Prostaglandins Leukot Essent Fatty Acids. 2019 Jun;145:15-22. doi: 10.1016/j.plefa.2019.05.003. Epub 2019 May 7.
• [9] Update on recent advances in the management of aspirin exacerbated respiratory disease.Yonsei Med J. 2009 Dec 31;50(6):744-50. doi: 10.3349/ymj.2009.50.6.744. Epub 2009 Dec 18.
• [10] Evidence for a genetic interaction in allergy-related responsiveness to vitamin D deficiency.Allergy. 2012 Aug;67(8):1033-40. doi: 10.1111/j.1398-9995.2012.02856.x. Epub 2012 Jun 12.
• [11] Role for High-Affinity IgE Receptor in Prognosis of Lung Adenocarcinoma Patients.Cancer Immunol Res. 2017 Sep;5(9):821-829. doi: 10.1158/2326-6066.CIR-16-0392. Epub 2017 Aug 3.
• [12] Prediction of atopic dermatitis in 2-yr-old children by cord blood IgE, genetic polymorphisms in cytokine genes, and maternal mentality during pregnancy.Pediatr Allergy Immunol. 2011 Nov;22(7):695-703. doi: 10.1111/j.1399-3038.2011.01177.x. Epub 2011 May 4.
• [13] FcgammaRIV is a mouse IgE receptor that resembles macrophage FcepsilonRI in humans and promotes IgE-induced lung inflammation.J Clin Invest. 2008 Nov;118(11):3738-50. doi: 10.1172/JCI36452. Epub 2008 Oct 23.
• [14] Linkage study of Best's vitelliform macular dystrophy (VMD2) in a large North American family.Hum Hered. 1996 Jul-Aug;46(4):211-20. doi: 10.1159/000154356.
• [15] Screening of the Fc epsilon RI-beta-gene in a Swiss population of asthmatic children: no association with E237G and identification of new sequence variations. Dis Markers. 1998 Nov;14(3):177-86. doi: 10.1155/1998/940356.
• [16] Global molecular effects of tocilizumab therapy in rheumatoid arthritis synovium. Arthritis Rheumatol. 2014 Jan;66(1):15-23.
• [17] 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.
• [18] A polymorphism of MS4A2 (- 109T > C) encoding the beta-chain of the high-affinity immunoglobulin E receptor (FcepsilonR1beta) is associated with a susceptibility to aspirin-intolerant asthma. Clin Exp Allergy. 2006 Jul;36(7):877-83. doi: 10.1111/j.1365-2222.2006.02443.x.