Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTJE0NOY)

• DOT Name: Trehalase (TREH)
• Synonyms: EC 3.2.1.28; Alpha,alpha-trehalase; Alpha,alpha-trehalose glucohydrolase
• Gene Name: TREH
• Related Disease:
  Adult glioblastoma
  Advanced cancer
  Autosomal dominant optic atrophy, classic form
  Chromosomal disorder
  Congenital nephrotic syndrome, Finnish type
  Familial nephrotic syndrome
  Glioblastoma multiforme
  Glioma
  Hepatocellular carcinoma
  Herpes simplex infection
  Intestinal obstruction
  Lung cancer
  Lung carcinoma
  Medulloblastoma
  Neoplasm
  Nephropathy
  Non-alcoholic fatty liver disease
  Polyarteritis nodosa
  Vasculitis due to ADA2 deficiency
  Diarrhea-vomiting due to trehalase deficiency
  Non-insulin dependent diabetes
  Non-small-cell lung cancer
• UniProt ID: TREA_HUMAN
• EC Number: 3.2.1.28
• Pfam ID: PF01204
• Sequence:
  MPGRTWELCLLLLLGLGLGSQEALPPPCESEIYCHGELLNQVQMAKLYQDDKQFVDMPLS
  IAPEQVLQTFTELSRDHNHSIPREQLQAFVHEHFQAKGQELQPWTPADWKDSPQFLQKIS
  DAKLRAWAGQLHQLWKKLGKKMKPEVLSHPERFSLIYSEHPFIVPGGRFVEFYYWDSYWV
  MEGLLLSEMAETVKGMLQNFLDLVKTYGHVPNGGRVYYLQRSQPPLLTLMMDCYLTHTND
  TAFLQENIETLALELDFWTKNRTVSVSLEGKNYLLNRYYVPYGGPRPESYSKDVELADTL
  PEGDREALWAELKAGAESGWDFSSRWLIGGPNPNSLSGIRTSKLVPVDLNAFLCQAEELM
  SNFYSRLGNDSQATKYRILRSQRLAALNTVLWDEQTGAWFDYDLEKKKKNREFYPSNLTP
  LWAGCFSDPGVADKALKYLEDNRILTYQYGIPTSLQKTGQQWDFPNAWAPLQDLVIRGLA
  KAPLRRAQEVAFQLAQNWIRTNFDVYSQKSAMYEKYDVSNGGQPGGGGEYEVQEGFGWTN
  GVVLMLLDRYGDRLTSGAKLAFLEPHCLAATLLPSLLLSLLPW
• Function: Intestinal trehalase is probably involved in the hydrolysis of ingested trehalose.
• Tissue Specificity: Expressed in kidney, liver and small intestine. Also more weakly expressed in pancreas.
• KEGG Pathway:
  Starch and sucrose metabolism (hsa00500)
  Metabolic pathways (hsa01100)
• Reactome Pathway: Digestion of dietary carbohydrate (R-HSA-189085)

Molecular Interaction Atlas (MIA) of This DOT

22 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Adult glioblastoma	DISVP4LU	Strong	Genetic Variation	[1]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[2]
Autosomal dominant optic atrophy, classic form	DISXUAV9	Strong	Altered Expression	[3]
Chromosomal disorder	DISM5BB5	Strong	Altered Expression	[4]
Congenital nephrotic syndrome, Finnish type	DIS8P7EH	Strong	Biomarker	[5]
Familial nephrotic syndrome	DISADF8G	Strong	Altered Expression	[5]
Glioblastoma multiforme	DISK8246	Strong	Genetic Variation	[1]
Glioma	DIS5RPEH	Strong	Genetic Variation	[6]
Hepatocellular carcinoma	DIS0J828	Strong	Biomarker	[7]
Herpes simplex infection	DISL1SAV	Strong	Genetic Variation	[8]
Intestinal obstruction	DISE52WH	Strong	Altered Expression	[4]
Lung cancer	DISCM4YA	Strong	Altered Expression	[9]
Lung carcinoma	DISTR26C	Strong	Altered Expression	[9]
Medulloblastoma	DISZD2ZL	Strong	Biomarker	[10]
Neoplasm	DISZKGEW	Strong	Biomarker	[7]
Nephropathy	DISXWP4P	Strong	Altered Expression	[4]
Non-alcoholic fatty liver disease	DISDG1NL	Strong	Biomarker	[11]
Polyarteritis nodosa	DISRQ5X8	Strong	Altered Expression	[12]
Vasculitis due to ADA2 deficiency	DIS1UHPY	Strong	Altered Expression	[12]
Diarrhea-vomiting due to trehalase deficiency	DISQXEG3	Supportive	Autosomal dominant	[13]
Non-insulin dependent diabetes	DISK1O5Z	Limited	Altered Expression	[14]
Non-small-cell lung cancer	DIS5Y6R9	Limited	Altered Expression	[15]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Trehalase (TREH).	[16]
Hydrocortisone	DMGEMB7	Approved	Hydrocortisone decreases the activity of Trehalase (TREH).	[17]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Trehalase (TREH).	[18]

References

• [1] Association between RTEL1, PHLDB1, and TREH Polymorphisms and Glioblastoma Risk: A Case-Control Study.Med Sci Monit. 2015 Jul 9;21:1983-8. doi: 10.12659/MSM.893723.
• [2] Adeno-associated virus-mediated doxycycline-regulatable TRAIL expression suppresses growth of human breast carcinoma in nude mice.BMC Cancer. 2012 Apr 24;12:153. doi: 10.1186/1471-2407-12-153.
• [3] Proteasome dysfunction induces excessive proteome instability and loss of mitostasis that can be mitigated by enhancing mitochondrial fusion or autophagy.Autophagy. 2019 Oct;15(10):1757-1773. doi: 10.1080/15548627.2019.1596477. Epub 2019 Apr 19.
• [4] Amniotic fluid microvillar enzyme activity in fetal malformations.Clin Genet. 1990 Nov;38(5):340-5. doi: 10.1111/j.1399-0004.1990.tb03592.x.
• [5] Prenatal detection of the congenital nephrotic syndrome (Finnish type) by trehalase assay in amniotic fluid.Prenat Diagn. 1984 Jul-Aug;4(4):257-60. doi: 10.1002/pd.1970040404.
• [6] Polymorphisms of TREH, IL4R and CCDC26 genes associated with risk of glioma.Cancer Epidemiol. 2012 Jun;36(3):283-7. doi: 10.1016/j.canep.2011.12.011. Epub 2012 Feb 26.
• [7] Reversion of tumor hepatocytes to normal hepatocytes during liver tumor regression in an oncogene-expressing transgenic zebrafish model.Dis Model Mech. 2019 Oct 17;12(10):dmm039578. doi: 10.1242/dmm.039578.
• [8] Regulated Mesenchymal Stem Cells Mediated Colon Cancer Therapy Assessed by Reporter Gene Based Optical Imaging.Int J Mol Sci. 2018 Mar 27;19(4):1002. doi: 10.3390/ijms19041002.
• [9] An improved Tet-On regulatable FasL-adenovirus vector system for lung cancer therapy.J Mol Med (Berl). 2006 Mar;84(3):215-25. doi: 10.1007/s00109-005-0009-1. Epub 2005 Dec 31.
• [10] Loss of Pin1 Suppresses Hedgehog-Driven Medulloblastoma Tumorigenesis.Neoplasia. 2017 Mar;19(3):216-225. doi: 10.1016/j.neo.2017.01.002. Epub 2017 Feb 3.
• [11] Lactotrehalose, an Analog of Trehalose, Increases Energy Metabolism Without Promoting Clostridioides difficile Infection in Mice.Gastroenterology. 2020 Apr;158(5):1402-1416.e2. doi: 10.1053/j.gastro.2019.11.295. Epub 2019 Dec 12.
• [12] Induction of podocyte-derived VEGF ameliorates podocyte injury and subsequent abnormal glomerular development caused by puromycin aminonucleoside.Pediatr Res. 2011 Jul;70(1):83-9. doi: 10.1203/PDR.0b013e31821bdf1c.
• [13] Clinical Practice Guidelines for Rare Diseases: The Orphanet Database. PLoS One. 2017 Jan 18;12(1):e0170365. doi: 10.1371/journal.pone.0170365. eCollection 2017.
• [14] Identification of genetic variation that determines human trehalase activity and its association with type 2 diabetes.Hum Genet. 2013 Jun;132(6):697-707. doi: 10.1007/s00439-013-1278-3. Epub 2013 Mar 7.
• [15] Transition from SCLC to NSCLC phenotype is accompanied by an increased TRE-binding activity and recruitment of specific AP-1 proteins.Oncogene. 1998 Jun 11;16(23):3057-68. doi: 10.1038/sj.onc.1201845.
• [16] 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.
• [17] Effect of hydrocortisone on the maturation of human foetal kidney explants in serum-free organ culture. Biochem Cell Biol. 1989 Feb-Mar;67(2-3):121-7. doi: 10.1139/o89-019.
• [18] Identification of a transcriptomic signature of food-relevant genotoxins in human HepaRG hepatocarcinoma cells. Food Chem Toxicol. 2020 Jun;140:111297. doi: 10.1016/j.fct.2020.111297. Epub 2020 Mar 28.