Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTEU00OH)

• DOT Name: Transmembrane protein 17 (TMEM17)
• Gene Name: TMEM17
• Related Disease:
  Advanced cancer
  Breast cancer
  Breast carcinoma
  Gastrointestinal stromal tumour
  Lung cancer
  Lung carcinoma
  Neoplasm
  Non-small-cell lung cancer
  Prostate cancer
  Prostate carcinoma
  Triple negative breast cancer
• UniProt ID: TMM17_HUMAN
• Pfam ID: PF09799
• Sequence:
  MELPDPVRQRLGNFSRAVFSDSNRTGPESNEGPENEMVSSLALQMSLYFNTYYFPLWWVS
  SIMMLHMKYSILPDYYKFIVITVIILITLIEAIRLYLGYVGNLQEKVPELAGFWLLSLLL
  QLPLILFLLFNEGLTNLPLEKAIHIIFTLFLAFQVVAAFLTLRKMVNQLAVRFHLQDFDR
  LSANRGDMRRMRSCIEEI
• Function: Transmembrane component of the tectonic-like complex, a complex localized at the transition zone of primary cilia and acting as a barrier that prevents diffusion of transmembrane proteins between the cilia and plasma membranes. Required for ciliogenesis and sonic hedgehog/SHH signaling.

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	Altered Expression	[1]
Breast cancer	DIS7DPX1	Strong	Altered Expression	[1]
Breast carcinoma	DIS2UE88	Strong	Altered Expression	[1]
Gastrointestinal stromal tumour	DIS6TJYS	Strong	Biomarker	[2]
Lung cancer	DISCM4YA	Strong	Altered Expression	[3]
Lung carcinoma	DISTR26C	Strong	Altered Expression	[3]
Neoplasm	DISZKGEW	Strong	Altered Expression	[1]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Biomarker	[3]
Prostate cancer	DISF190Y	Strong	Genetic Variation	[4]
Prostate carcinoma	DISMJPLE	Strong	Genetic Variation	[4]
Triple negative breast cancer	DISAMG6N	Strong	Altered Expression	[1]

4 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 Transmembrane protein 17 (TMEM17).	[5]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Transmembrane protein 17 (TMEM17).	[6]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Transmembrane protein 17 (TMEM17).	[7]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Transmembrane protein 17 (TMEM17).	[8]

References

• [1] TMEM17 promotes malignant progression of breast cancer via AKT/GSK3 signaling.Cancer Manag Res. 2018 Aug 2;10:2419-2428. doi: 10.2147/CMAR.S168723. eCollection 2018.
• [2] Hedgehog pathway dysregulation contributes to the pathogenesis of human gastrointestinal stromal tumors via GLI-mediated activation of KIT expression. Oncotarget. 2016 Nov 29;7(48):78226-78241. doi: 10.18632/oncotarget.12909.
• [3] TMEM17 depresses invasion and metastasis in lung cancer cells via ERK signaling pathway.Oncotarget. 2017 Aug 7;8(41):70685-70694. doi: 10.18632/oncotarget.19977. eCollection 2017 Sep 19.
• [4] 12 new susceptibility loci for prostate cancer identified by genome-wide association study in Japanese population.Nat Commun. 2019 Sep 27;10(1):4422. doi: 10.1038/s41467-019-12267-6.
• [5] A transcriptome-based classifier to identify developmental toxicants by stem cell testing: design, validation and optimization for histone deacetylase inhibitors. Arch Toxicol. 2015 Sep;89(9):1599-618.
• [6] Integrative "-Omics" analysis in primary human hepatocytes unravels persistent mechanisms of cyclosporine A-induced cholestasis. Chem Res Toxicol. 2016 Dec 19;29(12):2164-2174.
• [7] Temozolomide induces activation of Wnt/-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278. doi: 10.1007/s10565-019-09502-7. Epub 2019 Nov 22.
• [8] Gene Expression Regulation and Pathway Analysis After Valproic Acid and Carbamazepine Exposure in a Human Embryonic Stem Cell-Based Neurodevelopmental Toxicity Assay. Toxicol Sci. 2015 Aug;146(2):311-20. doi: 10.1093/toxsci/kfv094. Epub 2015 May 15.