Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTHXRYG3)

• DOT Name: Interferon alpha-17 (IFNA17)
• Synonyms: IFN-alpha-17; Interferon alpha-88; Interferon alpha-I'; LeIF I; Interferon alpha-T
• Gene Name: IFNA17
• Related Disease:
  Adenoma
  Advanced cancer
  Bladder cancer
  Esophageal squamous cell carcinoma
  Familial atypical multiple mole melanoma syndrome
  Gastric adenocarcinoma
  Glioblastoma multiforme
  HIV infectious disease
  Lung neoplasm
  Malignant mesothelioma
  Nasopharyngeal carcinoma
  Neoplasm
  Pancreatic cancer
  Renal carcinoma
  Renal cell carcinoma
  Sarcoidosis
  Systemic lupus erythematosus
  Transitional cell carcinoma
  Undifferentiated carcinoma
  Urothelial carcinoma
  Narcolepsy
  Adenocarcinoma
  Cervical cancer
  Cervical carcinoma
  Lupus nephritis
  Malignant pleural mesothelioma
  Melanocytic nevus
  Melanoma
  Myasthenia gravis
  Non-small-cell lung cancer
  Squamous cell carcinoma
  Tuberculosis
  Type-1 diabetes
• UniProt ID: IFN17_HUMAN
• Pfam ID: PF00143
• Sequence:
  MALSFSLLMAVLVLSYKSICSLGCDLPQTHSLGNRRALILLAQMGRISPFSCLKDRHDFG
  LPQEEFDGNQFQKTQAISVLHEMIQQTFNLFSTEDSSAAWEQSLLEKFSTELYQQLNNLE
  ACVIQEVGMEETPLMNEDSILAVRKYFQRITLYLTEKKYSPCAWEVVRAEIMRSLSFSTN
  LQKILRRKD
• 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

33 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Adenoma	DIS78ZEV	Strong	Biomarker	[1]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[2]
Bladder cancer	DISUHNM0	Strong	Biomarker	[3]
Esophageal squamous cell carcinoma	DIS5N2GV	Strong	Biomarker	[4]
Familial atypical multiple mole melanoma syndrome	DIS2YEKP	Strong	Genetic Variation	[5]
Gastric adenocarcinoma	DISWWLTC	Strong	Genetic Variation	[1]
Glioblastoma multiforme	DISK8246	Strong	Genetic Variation	[6]
HIV infectious disease	DISO97HC	Strong	Altered Expression	[7]
Lung neoplasm	DISVARNB	Strong	Genetic Variation	[8]
Malignant mesothelioma	DISTHJGH	Strong	Genetic Variation	[9]
Nasopharyngeal carcinoma	DISAOTQ0	Strong	Biomarker	[10]
Neoplasm	DISZKGEW	Strong	Biomarker	[11]
Pancreatic cancer	DISJC981	Strong	Biomarker	[12]
Renal carcinoma	DISER9XT	Strong	Genetic Variation	[13]
Renal cell carcinoma	DISQZ2X8	Strong	Genetic Variation	[13]
Sarcoidosis	DISE5B8Z	Strong	Biomarker	[14]
Systemic lupus erythematosus	DISI1SZ7	Strong	Biomarker	[15]
Transitional cell carcinoma	DISWVVDR	Strong	Biomarker	[16]
Undifferentiated carcinoma	DISIAZST	Strong	Biomarker	[1]
Urothelial carcinoma	DISRTNTN	Strong	Biomarker	[16]
Narcolepsy	DISLCNLI	moderate	Genetic Variation	[17]
Adenocarcinoma	DIS3IHTY	Limited	Biomarker	[18]
Cervical cancer	DISFSHPF	Limited	Biomarker	[19]
Cervical carcinoma	DIST4S00	Limited	Biomarker	[19]
Lupus nephritis	DISCVGPZ	Limited	Biomarker	[15]
Malignant pleural mesothelioma	DIST2R60	Limited	Genetic Variation	[20]
Melanocytic nevus	DISYS32D	Limited	Biomarker	[21]
Melanoma	DIS1RRCY	Limited	Genetic Variation	[22]
Myasthenia gravis	DISELRCI	Limited	Biomarker	[23]
Non-small-cell lung cancer	DIS5Y6R9	Limited	Genetic Variation	[20]
Squamous cell carcinoma	DISQVIFL	Limited	Biomarker	[18]
Tuberculosis	DIS2YIMD	Limited	Genetic Variation	[24]
Type-1 diabetes	DIS7HLUB	Limited	Biomarker	[25]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Beta-carotene	DM0RXBT	Approved	Beta-carotene increases the expression of Interferon alpha-17 (IFNA17).	[26]

References

• [1] Loss of heterozygosity on the short arm of chromosome 9 without p16 gene mutation in gastric carcinomas.Jpn J Cancer Res. 1995 Apr;86(4):333-5. doi: 10.1111/j.1349-7006.1995.tb03060.x.
• [2] Genomic cloning of methylthioadenosine phosphorylase: a purine metabolic enzyme deficient in multiple different cancers.Proc Natl Acad Sci U S A. 1996 Jun 11;93(12):6203-8. doi: 10.1073/pnas.93.12.6203.
• [3] Homozygous deletion mapping at 9p21 in bladder carcinoma defines a critical region within 2cM of IFNA.Oncogene. 1994 Sep;9(9):2757-60.
• [4] Frequent microsatellite alterations on chromosome 3p in esophageal squamous cell carcinoma.Cancer Res. 1995 Feb 15;55(4):891-4.
• [5] Haplotype analysis limits the position of the familial melanoma locus on 9p to the D9S169-D9S156 interval.Melanoma Res. 1994 Feb;4(1):29-34. doi: 10.1097/00008390-199402000-00005.
• [6] Loss of heterozygosity of microsatellite loci on chromosome 9p in astrocytic tumors and its prognostic implications.J Neurooncol. 1996 Oct;30(1):19-24. doi: 10.1007/BF00177439.
• [7] Expression Pattern of Individual IFNA Subtypes in Chronic HIV Infection.J Interferon Cytokine Res. 2017 Dec;37(12):541-549. doi: 10.1089/jir.2017.0076.
• [8] Loss of heterozygosity at 9p23 defines a novel locus in non-small cell lung cancer.Oncogene. 1995 Aug 3;11(3):581-5.
• [9] Homozygous deletions within 9p21-p22 identify a small critical region of chromosomal loss in human malignant mesotheliomas.Cancer Res. 1993 Oct 15;53(20):4761-3.
• [10] Interferon-alpha and p53 alleles involved in nasopharyngeal carcinoma.Carcinogenesis. 1997 Apr;18(4):645-7. doi: 10.1093/carcin/18.4.645.
• [11] Molecular evidence supporting field effect in urothelial carcinogenesis.Clin Cancer Res. 2005 Sep 15;11(18):6512-9. doi: 10.1158/1078-0432.CCR-05-0891.
• [12] Pancreatic adenocarcinoma upregulated factor (PAUF) confers resistance to pancreatic cancer cells against oncolytic parvovirus H-1 infection through IFNA receptor-mediated signaling.Biochem Biophys Res Commun. 2015 Apr 3;459(2):313-318. doi: 10.1016/j.bbrc.2015.02.107. Epub 2015 Feb 26.
• [13] Sensitization of renal carcinoma to radiation using alpha interferon (IFNA) gene transfection.Radiat Res. 1997 Nov;148(5):443-8.
• [14] Cystic fibrosis conductance regulator, tumor necrosis factor, interferon alpha-10, interferon alpha-17, and interferon gamma genotyping as potential risk markers in pulmonary sarcoidosis pathogenesis in Greek patients.Genet Test Mol Biomarkers. 2010 Aug;14(4):577-84. doi: 10.1089/gtmb.2009.0198.
• [15] Podocytes and autophagy: a potential therapeutic target in lupus nephritis.Autophagy. 2019 May;15(5):908-912. doi: 10.1080/15548627.2019.1580512. Epub 2019 Feb 17.
• [16] Molecular genetic evidence for a common clonal origin of urinary bladder small cell carcinoma and coexisting urothelial carcinoma.Am J Pathol. 2005 May;166(5):1533-9. doi: 10.1016/S0002-9440(10)62369-3.
• [17] A rare form of narcolepsy (HLA-DR2-) shows possible association with (functionally relevant) alpha-interferon gene polymorphisms.Psychiatr Genet. 2004 Mar;14(1):47-51. doi: 10.1097/00041444-200403000-00008.
• [18] Genetics and lung carcinoma in Okinawa Prefecture, Japan.Anticancer Res. 1999 Nov-Dec;19(6C):5611-4.
• [19] Interferon, alpha 17 (IFNA17) Ile184Arg polymorphism and cervical cancer risk.Cancer Lett. 2003 Jan 28;189(2):183-8. doi: 10.1016/s0304-3835(02)00548-7.
• [20] Molecular deletion of 9p sequences in non-small cell lung cancer and malignant mesothelioma.Genes Chromosomes Cancer. 1993 May;7(1):47-53. doi: 10.1002/gcc.2870070108.
• [21] Melanoma ex naevo: a study of the associated naevus.Melanoma Res. 2003 Apr;13(2):213-7. doi: 10.1097/01.cmr.0000056226.78713.99.
• [22] Low prevalence of RAS-RAF-activating mutations in Spitz melanocytic nevi compared with other melanocytic lesions.J Cutan Pathol. 2007 Jun;34(6):448-55. doi: 10.1111/j.1600-0560.2006.00646.x.
• [23] IFNA-AS1 regulates CD4(+) T cell activation in myasthenia gravis though HLA-DRB1.Clin Immunol. 2017 Oct;183:121-131. doi: 10.1016/j.clim.2017.08.008. Epub 2017 Aug 16.
• [24] Association between IFNA genotype and the risk of sarcoidosis.Hum Genet. 2004 Apr;114(5):503-9. doi: 10.1007/s00439-004-1099-5. Epub 2004 Mar 5.
• [25] Polymorphism discovery and association analyses of the interferon genes in type 1 diabetes.BMC Genet. 2006 Feb 22;7:12. doi: 10.1186/1471-2156-7-12.
• [26] Beta-carotene and apocarotenals promote retinoid signaling in BEAS-2B human bronchioepithelial cells. Arch Biochem Biophys. 2006 Nov 1;455(1):48-60.