Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTPB5C0O)

• DOT Name: G antigen 4 (GAGE4)
• Synonyms: Cancer/testis antigen 4.4; CT4.4
• Gene Name: GAGE4
• Related Disease:
  Neoplasm
  Hepatocellular carcinoma
  Lung cancer
  Melorheostosis
  Urinary bladder neoplasm
  Epstein barr virus infection
  Melanoma
  Thyroid gland papillary carcinoma
• UniProt ID: GAGE4_HUMAN
• Pfam ID: PF05831
• Sequence:
  MSWRGRSTYYWPRPRRYVQPPEMIGPMRPEQFSDEVEPATPEEGEPATQRQDPAAAQEGE
  DEGASAGQGPKPEADSQEQGHPQTGCECEDGPDGQEMDPPNPEEVKTPEEGEKQSQC
• Function: Antigen, recognized on melanoma by autologous cytolytic T-lymphocytes.
• Tissue Specificity: Expressed in a variety of tumor tissues but not in normal tissues, except testis.

Molecular Interaction Atlas (MIA) of This DOT

8 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Neoplasm	DISZKGEW	Definitive	Altered Expression	[1]
Hepatocellular carcinoma	DIS0J828	Strong	Genetic Variation	[2]
Lung cancer	DISCM4YA	Strong	Altered Expression	[3]
Melorheostosis	DISIMCL3	Strong	Biomarker	[4]
Urinary bladder neoplasm	DIS7HACE	Strong	Altered Expression	[3]
Epstein barr virus infection	DISOO0WT	moderate	Altered Expression	[1]
Melanoma	DIS1RRCY	moderate	Biomarker	[5]
Thyroid gland papillary carcinoma	DIS48YMM	Limited	Altered Expression	[6]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Mitoxantrone	DMM39BF	Approved	G antigen 4 (GAGE4) affects the response to substance of Mitoxantrone.	[9]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Decitabine	DMQL8XJ	Approved	Decitabine increases the expression of G antigen 4 (GAGE4).	[7]
Zoledronate	DMIXC7G	Approved	Zoledronate decreases the expression of G antigen 4 (GAGE4).	[8]

References

• [1] Relationship between GAGE-1/-2 expression, EBV infection and interferon-gamma expression in undifferentiated carcinoma of nasopharyngeal type.Anticancer Res. 2000 May-Jun;20(3A):1727-32.
• [2] Different gene expression of MDM2, GAGE-1, -2 and FHIT in hepatocellular carcinoma and focal nodular hyperplasia.Br J Cancer. 1999 Apr;80(1-2):73-8. doi: 10.1038/sj.bjc.6690324.
• [3] A new family of genes coding for an antigen recognized by autologous cytolytic T lymphocytes on a human melanoma.J Exp Med. 1995 Sep 1;182(3):689-98. doi: 10.1084/jem.182.3.689.
• [4] A testicular antigen aberrantly expressed in human cancers detected by autologous antibody screening.Proc Natl Acad Sci U S A. 1997 Mar 4;94(5):1914-8. doi: 10.1073/pnas.94.5.1914.
• [5] Characterization of the GAGE genes that are expressed in various human cancers and in normal testis.Cancer Res. 1999 Jul 1;59(13):3157-65.
• [6] MAGE-1, GAGE-1/-2 gene expression in FNAB of classic variant of papillary thyroid carcinoma and papillary hyperplasia in nodular goiter.Int J Mol Med. 1999 Oct;4(4):445-8. doi: 10.3892/ijmm.4.4.445.
• [7] Treatment of chronic lymphocytic leukemia with a hypomethylating agent induces expression of NXF2, an immunogenic cancer testis antigen. Clin Cancer Res. 2009 May 15;15(10):3406-15. doi: 10.1158/1078-0432.CCR-08-2099. Epub 2009 Apr 28.
• [8] Interleukin-19 as a translational indicator of renal injury. Arch Toxicol. 2015 Jan;89(1):101-6.
• [9] Gene expression profiling of 30 cancer cell lines predicts resistance towards 11 anticancer drugs at clinically achieved concentrations. Int J Cancer. 2006 Apr 1;118(7):1699-712. doi: 10.1002/ijc.21570.