Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTII5O0G)

• DOT Name: Interferon alpha-4 (IFNA4)
• Synonyms: IFN-alpha-4; Interferon alpha-4B; Interferon alpha-76; Interferon alpha-M1
• Gene Name: IFNA4
• Related Disease:
  Crohn disease
  Hepatitis C virus infection
  Addison disease
  Neoplasm
• UniProt ID: IFNA4_HUMAN
• Pfam ID: PF00143
• Sequence:
  MALSFSLLMAVLVLSYKSICSLGCDLPQTHSLGNRRALILLAQMGRISHFSCLKDRHDFG
  FPEEEFDGHQFQKAQAISVLHEMIQQTFNLFSTEDSSAAWEQSLLEKFSTELYQQLNDLE
  ACVIQEVGVEETPLMNEDSILAVRKYFQRITLYLTEKKYSPCAWEVVRAEIMRSLSFSTN
  LQKRLRRKD
• Function: Produced by macrophages, IFN-alpha have antiviral activities. Interferon stimulates the production of two enzymes: a protein kinase and an oligoadenylate synthetase.
• KEGG Pathway:
  Cytokine-cytokine receptor interaction (hsa04060)
  PI3K-Akt sig.ling pathway (hsa04151)
  Necroptosis (hsa04217)
  Toll-like receptor sig.ling pathway (hsa04620)
  NOD-like receptor sig.ling pathway (hsa04621)
  RIG-I-like receptor sig.ling pathway (hsa04622)
  Cytosolic D.-sensing pathway (hsa04623)
  JAK-STAT sig.ling pathway (hsa04630)
  .tural killer cell mediated cytotoxicity (hsa04650)
  Alcoholic liver disease (hsa04936)
  Tuberculosis (hsa05152)
  Hepatitis C (hsa05160)
  Hepatitis B (hsa05161)
  Measles (hsa05162)
  Human cytomegalovirus infection (hsa05163)
  Influenza A (hsa05164)
  Human papillomavirus infection (hsa05165)
  Kaposi sarcoma-associated herpesvirus infection (hsa05167)
  Herpes simplex virus 1 infection (hsa05168)
  Epstein-Barr virus infection (hsa05169)
  Human immunodeficiency virus 1 infection (hsa05170)
  Coro.virus disease - COVID-19 (hsa05171)
  Pathways in cancer (hsa05200)
  Autoimmune thyroid disease (hsa05320)
  Lipid and atherosclerosis (hsa05417)
• Reactome Pathway:
  Regulation of IFNA/IFNB signaling (R-HSA-912694)
  TRAF6 mediated IRF7 activation (R-HSA-933541)
  SARS-CoV-2 activates/modulates innate and adaptive immune responses (R-HSA-9705671)
  Factors involved in megakaryocyte development and platelet production (R-HSA-983231)
  Interferon alpha/beta signaling (R-HSA-909733)

Molecular Interaction Atlas (MIA) of This DOT

4 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Crohn disease	DIS2C5Q8	Strong	Genetic Variation	[1]
Hepatitis C virus infection	DISQ0M8R	Strong	Biomarker	[2]
Addison disease	DIS7HNOH	moderate	Biomarker	[3]
Neoplasm	DISZKGEW	Disputed	Altered Expression	[4]

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 Interferon alpha-4 (IFNA4).	[5]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Glyphosate	DM0AFY7	Investigative	Glyphosate increases the expression of Interferon alpha-4 (IFNA4).	[6]

References

• [1] Exome sequencing identifies novel compound heterozygous IFNA4 and IFNA10 mutations as a cause of impaired function in Crohn's disease patients.Sci Rep. 2015 May 22;5:10514. doi: 10.1038/srep10514.
• [2] Detection of interferon-alpha expression by PCR in patients with chronic hepatitis C and hepatitis non-A, non-B.J Gastroenterol Hepatol. 1994 Jul-Aug;9(4):373-80. doi: 10.1111/j.1440-1746.1994.tb01258.x.
• [3] Cytokine Autoantibody Screening in the Swedish Addison Registry Identifies Patients With Undiagnosed APS1.J Clin Endocrinol Metab. 2018 Jan 1;103(1):179-186. doi: 10.1210/jc.2017-01957.
• [4] Anti-IL-10-mediated Enhancement of Antitumor Efficacy of a Dendritic Cell-targeting MIP3-gp100 Vaccine in the B16F10 Mouse Melanoma Model Is Dependent on Type I Interferons.J Immunother. 2018 May;41(4):181-189. doi: 10.1097/CJI.0000000000000212.
• [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] Glyphosate-based herbicides at low doses affect canonical pathways in estrogen positive and negative breast cancer cell lines. PLoS One. 2019 Jul 11;14(7):e0219610. doi: 10.1371/journal.pone.0219610. eCollection 2019.