Details of Drug Off-Target (DOT)

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

• DOT Name: High affinity immunoglobulin epsilon receptor subunit alpha (FCER1A)
• Synonyms: Fc-epsilon RI-alpha; FcERI; IgE Fc receptor subunit alpha
• Gene Name: FCER1A
• Related Disease:
  Abdominal aortic aneurysm
  Allergic rhinitis
  Asthma
  B-cell neoplasm
  Breast cancer
  Breast carcinoma
  Chronic hepatitis B virus infection
  Chronic idiopathic urticaria
  Glioma
  Leukemia
  Rhinitis
  Systemic lupus erythematosus
  Urticaria
  Atopic dermatitis
  Chronic urticaria
  Hepatitis B virus infection
• UniProt ID: FCERA_HUMAN
• PDB ID: 1F2Q; 1F6A; 1J86; 1J87; 1J88; 1J89; 1RPQ; 2Y7Q; 7SHT; 8C1B; 8C1C
• Pfam ID: PF13895 ; PF13927
• Sequence:
  MAPAMESPTLLCVALLFFAPDGVLAVPQKPKVSLNPPWNRIFKGENVTLTCNGNNFFEVS
  STKWFHNGSLSEETNSSLNIVNAKFEDSGEYKCQHQQVNESEPVYLEVFSDWLLLQASAE
  VVMEGQPLFLRCHGWRNWDVYKVIYYKDGEALKYWYENHNISITNATVEDSGTYYCTGKV
  WQLDYESEPLNITVIKAPREKYWLQFFIPLLVVILFAVDTGLFISTQQQVTFLLKIKRTR
  KGFRLLNPHPKPNPKNN
• Function: High-affinity receptor for immunoglobulin epsilon/IgE. Mediates IgE effector functions in myeloid cells. Upon IgE binding and antigen/allergen cross-linking initiates signaling pathways that lead to myeloid cell activation and differentiation. On mast cells, basophils and eosinophils stimulates the secretion of vasoactive amines, lipid mediators and cytokines that contribute to inflammatory response, tissue remodeling and cytotoxicity against microbes. Triggers the immediate hypersensitivity response to allergens as a host defense mechanism against helminth parasites, pathogenic bacteria and venom toxicity. When dysregulated, it can elicit harmful life-threatening allergic and anaphylactic reactions.
• Tissue Specificity: Expressed in eosinophils.
• 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

16 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Abdominal aortic aneurysm	DISD06OF	Strong	Biomarker	[1]
Allergic rhinitis	DIS3U9HN	Strong	Genetic Variation	[2]
Asthma	DISW9QNS	Strong	Genetic Variation	[3]
B-cell neoplasm	DISVY326	Strong	Altered Expression	[4]
Breast cancer	DIS7DPX1	Strong	Genetic Variation	[5]
Breast carcinoma	DIS2UE88	Strong	Genetic Variation	[5]
Chronic hepatitis B virus infection	DISHL4NT	Strong	Genetic Variation	[6]
Chronic idiopathic urticaria	DISZA5CE	Strong	Genetic Variation	[7]
Glioma	DIS5RPEH	Strong	Biomarker	[8]
Leukemia	DISNAKFL	Strong	Biomarker	[9]
Rhinitis	DISKLMN7	Strong	Biomarker	[10]
Systemic lupus erythematosus	DISI1SZ7	Strong	Genetic Variation	[11]
Urticaria	DIS9WQAI	moderate	Biomarker	[12]
Atopic dermatitis	DISTCP41	Limited	Genetic Variation	[13]
Chronic urticaria	DISMBYB0	Limited	Genetic Variation	[13]
Hepatitis B virus infection	DISLQ2XY	Limited	Genetic Variation	[6]

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 alpha (FCER1A) affects the response to substance of Aspirin.	[12]

This DOT Affected the Regulation of Drug Effects of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Ergotidine	DM78IME	Approved	High affinity immunoglobulin epsilon receptor subunit alpha (FCER1A) affects the secretion of Ergotidine.	[20]

2 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the methylation of High affinity immunoglobulin epsilon receptor subunit alpha (FCER1A).	[14]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of High affinity immunoglobulin epsilon receptor subunit alpha (FCER1A).	[17]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic decreases the expression of High affinity immunoglobulin epsilon receptor subunit alpha (FCER1A).	[15]
Diphenylpyraline	DMW4X37	Approved	Diphenylpyraline decreases the expression of High affinity immunoglobulin epsilon receptor subunit alpha (FCER1A).	[16]
Butanoic acid	DMTAJP7	Investigative	Butanoic acid decreases the expression of High affinity immunoglobulin epsilon receptor subunit alpha (FCER1A).	[18]

References

• [1] IgE actions on CD4+ T cells, mast cells, and macrophages participate in the pathogenesis of experimental abdominal aortic aneurysms.EMBO Mol Med. 2014 Jul;6(7):952-69. doi: 10.15252/emmm.201303811.
• [2] SNPs in the FCER1A gene region show no association with allergic rhinitis in a Han Chinese population.PLoS One. 2010 Dec 31;5(12):e15792. doi: 10.1371/journal.pone.0015792.
• [3] Different FCER1A polymorphisms influence IgE levels in asthmatics and non-asthmatics.Pediatr Allergy Immunol. 2013 Aug;24(5):441-9. doi: 10.1111/pai.12083. Epub 2013 Jun 3.
• [4] Deficiency of FcR1 Increases Body Weight Gain but Improves Glucose Tolerance in Diet-Induced Obese Mice.Endocrinology. 2015 Nov;156(11):4047-58. doi: 10.1210/en.2015-1184. Epub 2015 Aug 21.
• [5] Candidate gene approach evaluates association between innate immunity genes and breast cancer risk in Korean women.Carcinogenesis. 2009 Sep;30(9):1528-31. doi: 10.1093/carcin/bgp084. Epub 2009 Apr 16.
• [6] Genetic variation in FCER1A predicts peginterferon alfa-2a-induced hepatitis B surface antigen clearance in East Asian patients with chronic hepatitis B.J Viral Hepat. 2019 Sep;26(9):1040-1049. doi: 10.1111/jvh.13107. Epub 2019 Jul 23.
• [7] Association of FCER1A genetic polymorphisms with risk for chronic spontaneous urticaria and efficacy of nonsedating H1-antihistamines in Chinese patients.Arch Dermatol Res. 2015 Mar;307(2):183-90. doi: 10.1007/s00403-014-1525-z. Epub 2014 Nov 21.
• [8] Single-nucleotide polymorphisms of allergy-related genes and risk of adult glioma.J Neurooncol. 2013 Jun;113(2):229-38. doi: 10.1007/s11060-013-1122-6. Epub 2013 Mar 25.
• [9] Regulation of FcepsilonRI-mediated degranulation by an adaptor protein 3BP2 in rat basophilic leukemia RBL-2H3 cells.Blood. 2002 Sep 15;100(6):2138-44. doi: 10.1182/blood-2001-12-0340.
• [10] Enhanced expression of high-affinity IgE receptor (Fc epsilon RI) alpha chain in human allergen-induced rhinitis with co-localization to mast cells, macrophages, eosinophils, and dendritic cells.J Allergy Clin Immunol. 1997 Jul;100(1):78-86. doi: 10.1016/s0091-6749(97)70198-2.
• [11] Sex-specific differences in the relationship between the single-nucleotide polymorphism rs2298804 of FCER1A and the susceptibility to systemic lupus erythematosus in a Chinese Han population.Clin Exp Dermatol. 2013 Jun;38(4):410-6. doi: 10.1111/ced.12035. Epub 2013 Mar 21.
• [12] Genetic and ethnic risk factors associated with drug hypersensitivity. Curr Opin Allergy Clin Immunol. 2010 Aug;10(4):280-90. doi: 10.1097/ACI.0b013e32833b1eb3.
• [13] Association of polymorphisms in the promoter region of FCER1A gene with atopic dermatitis, chronic uticaria, asthma, and serum immunoglobulin E levels in a Han Chinese population.Hum Immunol. 2012 Mar;73(3):301-5. doi: 10.1016/j.humimm.2011.12.001. Epub 2011 Dec 11.
• [14] Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
• [15] Inorganic arsenic exposure promotes malignant progression by HDAC6-mediated down-regulation of HTRA1. J Appl Toxicol. 2023 Aug;43(8):1214-1224. doi: 10.1002/jat.4457. Epub 2023 Mar 11.
• [16] Controlled diesel exhaust and allergen coexposure modulates microRNA and gene expression in humans: Effects on inflammatory lung markers. J Allergy Clin Immunol. 2016 Dec;138(6):1690-1700. doi: 10.1016/j.jaci.2016.02.038. Epub 2016 Apr 24.
• [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] 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.
• [19] Genetic and ethnic risk factors associated with drug hypersensitivity. Curr Opin Allergy Clin Immunol. 2010 Aug;10(4):280-90. doi: 10.1097/ACI.0b013e32833b1eb3.
• [20] Significant association of FcepsilonRIalpha promoter polymorphisms with aspirin-intolerant chronic urticaria. J Allergy Clin Immunol. 2007 Feb;119(2):449-56. doi: 10.1016/j.jaci.2006.10.006. Epub 2006 Nov 27.