Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTZG8RC6)

• DOT Name: Suppressor of tumorigenicity 7 protein (ST7)
• Synonyms: Protein FAM4A1; Protein HELG
• Gene Name: ST7
• Related Disease:
  Advanced cancer
  Breast cancer
  Breast carcinoma
  Breast neoplasm
  Carcinoma
  Carcinoma of esophagus
  Colon cancer
  Colon carcinoma
  Hepatocellular carcinoma
  Acute myelogenous leukaemia
  Infantile spasm
• UniProt ID: ST7_HUMAN
• Pfam ID: PF04184
• Sequence:
  MAEAATGFLEQLKSCIVWSWTYLWTVWFFIVLFLVYILRVPLKINDNLSTVSMFLNTLTP
  KFYVALTGTSSLISGLILIFEWWYFRKYGTSFIEQVSVSHLRPLLGGVDNNSSNNSNSSN
  GDSDSNRQSVSECKVWRNPLNLFRGAEYNRYTWVTGREPLTYYDMNLSAQDHQTFFTCDS
  DHLRPADAIMQKAWRERNPQARISAAHEALEINEIRSRVEVPLIASSTIWEIKLLPKCAT
  AYILLAEEEATTIAEAEKLFKQALKAGDGCYRRSQQLQHHGSQYEAQHRRDTNVLVYIKR
  RLAMCARRLGRTREAVKMMRDLMKEFPLLSMFNIHENLLEALLELQAYADVQAVLAKYDD
  ISLPKSATICYTAALLKARAVSDKFSPEAASRRGLSTAEMNAVEAIHRAVEFNPHVPKYL
  LEMKSLILPPEHILKRGDSEAIAYAFFHLAHWKRVEGALNLLHCTWEGTFRMIPYPLEKG
  HLFYPYPICTETADRELLPSFHEVSVYPKKELPFFILFTAGLCSFTAMLALLTHQFPELM
  GVFAKAMIDIFCSAEFRDWNCKSIFMRVEDELEIPPAPQSQHFQN
• Function: May act as a tumor suppressor.
• Tissue Specificity: Ubiquitously expressed, with highest levels in heart, liver and pancreas.

Molecular Interaction Atlas (MIA) of This DOT

11 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Advanced cancer	DISAT1Z9	Strong	Biomarker	[1]
Breast cancer	DIS7DPX1	Strong	Genetic Variation	[2]
Breast carcinoma	DIS2UE88	Strong	Genetic Variation	[2]
Breast neoplasm	DISNGJLM	Strong	Genetic Variation	[3]
Carcinoma	DISH9F1N	Strong	Genetic Variation	[4]
Carcinoma of esophagus	DISS6G4D	Strong	Genetic Variation	[5]
Colon cancer	DISVC52G	Strong	Genetic Variation	[2]
Colon carcinoma	DISJYKUO	Strong	Genetic Variation	[2]
Hepatocellular carcinoma	DIS0J828	Strong	Genetic Variation	[2]
Acute myelogenous leukaemia	DISCSPTN	Limited	Genetic Variation	[6]
Infantile spasm	DISZSKDG	Limited	Autosomal recessive	[7]

This DOT Affected the Drug Response of 3 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Etoposide	DMNH3PG	Approved	Suppressor of tumorigenicity 7 protein (ST7) affects the response to substance of Etoposide.	[20]
Mitomycin	DMH0ZJE	Approved	Suppressor of tumorigenicity 7 protein (ST7) affects the response to substance of Mitomycin.	[20]
Topotecan	DMP6G8T	Approved	Suppressor of tumorigenicity 7 protein (ST7) affects the response to substance of Topotecan.	[20]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of Suppressor of tumorigenicity 7 protein (ST7).	[8]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Suppressor of tumorigenicity 7 protein (ST7).	[9]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Suppressor of tumorigenicity 7 protein (ST7).	[10]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Suppressor of tumorigenicity 7 protein (ST7).	[11]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Suppressor of tumorigenicity 7 protein (ST7).	[12]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Suppressor of tumorigenicity 7 protein (ST7).	[13]
Calcitriol	DM8ZVJ7	Approved	Calcitriol decreases the expression of Suppressor of tumorigenicity 7 protein (ST7).	[14]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of Suppressor of tumorigenicity 7 protein (ST7).	[14]
Testosterone enanthate	DMB6871	Approved	Testosterone enanthate affects the expression of Suppressor of tumorigenicity 7 protein (ST7).	[15]
Epigallocatechin gallate	DMCGWBJ	Phase 3	Epigallocatechin gallate increases the expression of Suppressor of tumorigenicity 7 protein (ST7).	[16]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Suppressor of tumorigenicity 7 protein (ST7).	[17]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A affects the expression of Suppressor of tumorigenicity 7 protein (ST7).	[19]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Suppressor of tumorigenicity 7 protein (ST7).	[18]

References

• [1] Absence of ST7 gene alterations in human cancer.Clin Cancer Res. 2002 Sep;8(9):2939-41.
• [2] Mutations in the ST7/RAY1/HELG locus rarely occur in primary colorectal, gastric, and hepatocellular carcinomas.Br J Cancer. 2003 Jun 16;88(12):1909-13. doi: 10.1038/sj.bjc.6600942.
• [3] Lack of mutations within ST7 gene in tumour-derived cell lines and primary epithelial tumours.Br J Cancer. 2002 Jul 15;87(2):208-11. doi: 10.1038/sj.bjc.6600418.
• [4] Somatic mutation analysis of p53 and ST7 tumor suppressor genes in gastric carcinoma by DHPLC.World J Gastroenterol. 2003 Dec;9(12):2662-5. doi: 10.3748/wjg.v9.i12.2662.
• [5] An LOH and mutational investigation of the ST7 gene locus in human esophageal carcinoma.Oncogene. 2003 Jan 23;22(3):467-70. doi: 10.1038/sj.onc.1206125.
• [6] Mutational analysis of the ST7 gene in human myeloid tumor cell lines.Oncol Rep. 2003 Nov-Dec;10(6):1737-9.
• [7] Classification of Genes: Standardized Clinical Validity Assessment of Gene-Disease Associations Aids Diagnostic Exome Analysis and Reclassifications. Hum Mutat. 2017 May;38(5):600-608. doi: 10.1002/humu.23183. Epub 2017 Feb 13.
• [8] 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.
• [9] Development of a neural teratogenicity test based on human embryonic stem cells: response to retinoic acid exposure. Toxicol Sci. 2011 Dec;124(2):370-7.
• [10] Blood transcript immune signatures distinguish a subset of people with elevated serum ALT from others given acetaminophen. Clin Pharmacol Ther. 2016 Apr;99(4):432-41.
• [11] Bringing in vitro analysis closer to in vivo: studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling. Toxicol Lett. 2018 Sep 15;294:184-192.
• [12] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [13] The thioxotriazole copper(II) complex A0 induces endoplasmic reticulum stress and paraptotic death in human cancer cells. J Biol Chem. 2009 Sep 4;284(36):24306-19.
• [14] Effects of 1alpha,25 dihydroxyvitamin D3 and testosterone on miRNA and mRNA expression in LNCaP cells. Mol Cancer. 2011 May 18;10:58.
• [15] Transcriptional profiling of testosterone-regulated genes in the skeletal muscle of human immunodeficiency virus-infected men experiencing weight loss. J Clin Endocrinol Metab. 2007 Jul;92(7):2793-802. doi: 10.1210/jc.2006-2722. Epub 2007 Apr 17.
• [16] Application of the adverse outcome pathway concept for investigating developmental neurotoxicity potential of Chinese herbal medicines by using human neural progenitor cells in vitro. Cell Biol Toxicol. 2023 Feb;39(1):319-343. doi: 10.1007/s10565-022-09730-4. Epub 2022 Jun 15.
• [17] Transcriptional signature of human macrophages exposed to the environmental contaminant benzo(a)pyrene. Toxicol Sci. 2010 Apr;114(2):247-59.
• [18] DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.
• [19] A trichostatin A expression signature identified by TempO-Seq targeted whole transcriptome profiling. PLoS One. 2017 May 25;12(5):e0178302. doi: 10.1371/journal.pone.0178302. eCollection 2017.
• [20] 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.