Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTI2XGIT)

• DOT Name: Interferon alpha-inducible protein 27, mitochondrial (IFI27)
• Synonyms: p27; Interferon alpha-induced 11.5 kDa protein; Interferon-stimulated gene 12a protein; ISG12(a); ISG12A
• Gene Name: IFI27
• Related Disease:
  Multiple endocrine neoplasia type 1
  Adenoma
  B-cell neoplasm
  Bladder cancer
  Bone osteosarcoma
  Carcinoma of liver and intrahepatic biliary tract
  Cholangiocarcinoma
  Classic Hodgkin lymphoma
  Colon cancer
  Endometrial carcinoma
  Epithelial ovarian cancer
  Glioblastoma multiforme
  Glioma
  Hepatocellular carcinoma
  Influenza
  Leukemia
  Liver cancer
  Lung cancer
  Lung carcinoma
  Mantle cell lymphoma
  Metastatic malignant neoplasm
  Neuroblastoma
  Non-small-cell lung cancer
  Osteosarcoma
  Ovarian cancer
  Ovarian neoplasm
  Plasma cell myeloma
  Psoriasis
  Renal cell carcinoma
  Small lymphocytic lymphoma
  Thyroid tumor
  Triple negative breast cancer
  Urinary bladder cancer
  Urinary bladder neoplasm
  Acute myelogenous leukaemia
  Adult glioblastoma
  Liver cirrhosis
  Esophageal squamous cell carcinoma
  Melanoma
  Thyroid cancer
  Thyroid gland carcinoma
  Carcinoma
  Clear cell renal carcinoma
  Coeliac disease
  Colon carcinoma
  leukaemia
  Nasopharyngeal carcinoma
  Uterine fibroids
• UniProt ID: IFI27_HUMAN
• Pfam ID: PF06140
• Sequence:
  MEASALTSSAVTSVAKVVRVASGSAVVLPLARIATVVIGGVVAMAAVPMVLSAMGFTAAG
  IASSSIAAKMMSAAAIANGGGVASGSLVATLQSLGATGLSGLTKFILGSIGSAIAAVIAR
  FY
• Function: Probable adapter protein involved in different biological processes. Part of the signaling pathways that lead to apoptosis. Involved in type-I interferon-induced apoptosis characterized by a rapid and robust release of cytochrome C from the mitochondria and activation of BAX and caspases 2, 3, 6, 8 and 9. Also functions in TNFSF10-induced apoptosis. May also have a function in the nucleus, where it may be involved in the interferon-induced negative regulation of the transcriptional activity of NR4A1, NR4A2 and NR4A3 through the enhancement of XPO1-mediated nuclear export of these nuclear receptors. May thereby play a role in the vascular response to injury. In the innate immune response, has an antiviral activity towards hepatitis C virus/HCV. May prevent the replication of the virus by recruiting both the hepatitis C virus non-structural protein 5A/NS5A and the ubiquitination machinery via SKP2, promoting the ubiquitin-mediated proteasomal degradation of NS5A. Promotes also virus-induced pyroptosis by activating CASP3 in the mitochondria after 'Lys-6'-linked ubiquitination by TRIM21.
• Reactome Pathway: Interferon alpha/beta signaling (R-HSA-909733)

Molecular Interaction Atlas (MIA) of This DOT

48 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Multiple endocrine neoplasia type 1	DIS0RJRK	Definitive	Genetic Variation	[1]
Adenoma	DIS78ZEV	Strong	Biomarker	[2]
B-cell neoplasm	DISVY326	Strong	Altered Expression	[3]
Bladder cancer	DISUHNM0	Strong	Altered Expression	[4]
Bone osteosarcoma	DIST1004	Strong	Posttranslational Modification	[5]
Carcinoma of liver and intrahepatic biliary tract	DIS8WA0W	Strong	Altered Expression	[6]
Cholangiocarcinoma	DIS71F6X	Strong	Altered Expression	[7]
Classic Hodgkin lymphoma	DISV1LU6	Strong	Altered Expression	[8]
Colon cancer	DISVC52G	Strong	Biomarker	[9]
Endometrial carcinoma	DISXR5CY	Strong	Biomarker	[10]
Epithelial ovarian cancer	DIS56MH2	Strong	Biomarker	[11]
Glioblastoma multiforme	DISK8246	Strong	Biomarker	[12]
Glioma	DIS5RPEH	Strong	Biomarker	[13]
Hepatocellular carcinoma	DIS0J828	Strong	Altered Expression	[14]
Influenza	DIS3PNU3	Strong	Biomarker	[15]
Leukemia	DISNAKFL	Strong	Genetic Variation	[16]
Liver cancer	DISDE4BI	Strong	Altered Expression	[6]
Lung cancer	DISCM4YA	Strong	Altered Expression	[17]
Lung carcinoma	DISTR26C	Strong	Altered Expression	[17]
Mantle cell lymphoma	DISFREOV	Strong	Biomarker	[18]
Metastatic malignant neoplasm	DIS86UK6	Strong	Biomarker	[19]
Neuroblastoma	DISVZBI4	Strong	Altered Expression	[20]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Biomarker	[21]
Osteosarcoma	DISLQ7E2	Strong	Posttranslational Modification	[5]
Ovarian cancer	DISZJHAP	Strong	Biomarker	[11]
Ovarian neoplasm	DISEAFTY	Strong	Biomarker	[11]
Plasma cell myeloma	DIS0DFZ0	Strong	Posttranslational Modification	[22]
Psoriasis	DIS59VMN	Strong	Biomarker	[23]
Renal cell carcinoma	DISQZ2X8	Strong	Altered Expression	[24]
Small lymphocytic lymphoma	DIS30POX	Strong	Altered Expression	[25]
Thyroid tumor	DISLVKMD	Strong	Biomarker	[26]
Triple negative breast cancer	DISAMG6N	Strong	Altered Expression	[27]
Urinary bladder cancer	DISDV4T7	Strong	Altered Expression	[4]
Urinary bladder neoplasm	DIS7HACE	Strong	Altered Expression	[4]
Acute myelogenous leukaemia	DISCSPTN	moderate	Altered Expression	[28]
Adult glioblastoma	DISVP4LU	moderate	Biomarker	[12]
Liver cirrhosis	DIS4G1GX	moderate	Biomarker	[29]
Esophageal squamous cell carcinoma	DIS5N2GV	Disputed	Altered Expression	[30]
Melanoma	DIS1RRCY	Disputed	Biomarker	[31]
Thyroid cancer	DIS3VLDH	Disputed	Biomarker	[26]
Thyroid gland carcinoma	DISMNGZ0	Disputed	Biomarker	[26]
Carcinoma	DISH9F1N	Limited	Biomarker	[32]
Clear cell renal carcinoma	DISBXRFJ	Limited	Altered Expression	[24]
Coeliac disease	DISIY60C	Limited	Biomarker	[33]
Colon carcinoma	DISJYKUO	Limited	Biomarker	[9]
leukaemia	DISS7D1V	Limited	Biomarker	[34]
Nasopharyngeal carcinoma	DISAOTQ0	Limited	Altered Expression	[35]
Uterine fibroids	DISBZRMJ	Limited	Biomarker	[36]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of Interferon alpha-inducible protein 27, mitochondrial (IFI27).	[37]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Interferon alpha-inducible protein 27, mitochondrial (IFI27).	[56]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Interferon alpha-inducible protein 27, mitochondrial (IFI27).	[38]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Interferon alpha-inducible protein 27, mitochondrial (IFI27).	[39]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Interferon alpha-inducible protein 27, mitochondrial (IFI27).	[40]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Interferon alpha-inducible protein 27, mitochondrial (IFI27).	[41]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Interferon alpha-inducible protein 27, mitochondrial (IFI27).	[42]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Interferon alpha-inducible protein 27, mitochondrial (IFI27).	[43]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Interferon alpha-inducible protein 27, mitochondrial (IFI27).	[44]
Calcitriol	DM8ZVJ7	Approved	Calcitriol decreases the expression of Interferon alpha-inducible protein 27, mitochondrial (IFI27).	[45]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of Interferon alpha-inducible protein 27, mitochondrial (IFI27).	[46]
Methotrexate	DM2TEOL	Approved	Methotrexate decreases the expression of Interferon alpha-inducible protein 27, mitochondrial (IFI27).	[47]
Decitabine	DMQL8XJ	Approved	Decitabine increases the expression of Interferon alpha-inducible protein 27, mitochondrial (IFI27).	[48]
Zoledronate	DMIXC7G	Approved	Zoledronate increases the expression of Interferon alpha-inducible protein 27, mitochondrial (IFI27).	[49]
Demecolcine	DMCZQGK	Approved	Demecolcine increases the expression of Interferon alpha-inducible protein 27, mitochondrial (IFI27).	[50]
Azathioprine	DMMZSXQ	Approved	Azathioprine decreases the expression of Interferon alpha-inducible protein 27, mitochondrial (IFI27).	[47]
Testosterone enanthate	DMB6871	Approved	Testosterone enanthate affects the expression of Interferon alpha-inducible protein 27, mitochondrial (IFI27).	[51]
Diclofenac	DMPIHLS	Approved	Diclofenac decreases the expression of Interferon alpha-inducible protein 27, mitochondrial (IFI27).	[47]
Nicotine	DMWX5CO	Approved	Nicotine increases the expression of Interferon alpha-inducible protein 27, mitochondrial (IFI27).	[52]
Piroxicam	DMTK234	Approved	Piroxicam decreases the expression of Interferon alpha-inducible protein 27, mitochondrial (IFI27).	[47]
Prednisolone	DMQ8FR2	Approved	Prednisolone decreases the expression of Interferon alpha-inducible protein 27, mitochondrial (IFI27).	[47]
Methylprednisolone	DM4BDON	Approved	Methylprednisolone decreases the expression of Interferon alpha-inducible protein 27, mitochondrial (IFI27).	[47]
Tofacitinib	DMBS370	Approved	Tofacitinib decreases the expression of Interferon alpha-inducible protein 27, mitochondrial (IFI27).	[53]
Amantadine	DMS3YE9	Approved	Amantadine increases the expression of Interferon alpha-inducible protein 27, mitochondrial (IFI27).	[54]
Epigallocatechin gallate	DMCGWBJ	Phase 3	Epigallocatechin gallate decreases the expression of Interferon alpha-inducible protein 27, mitochondrial (IFI27).	[55]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Interferon alpha-inducible protein 27, mitochondrial (IFI27).	[57]
cinnamaldehyde	DMZDUXG	Investigative	cinnamaldehyde decreases the expression of Interferon alpha-inducible protein 27, mitochondrial (IFI27).	[58]

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