Details of Drug Off-Target (DOT)

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

• DOT Name: dTDP-D-glucose 4,6-dehydratase (TGDS)
• Synonyms: EC 4.2.1.46
• Gene Name: TGDS
• Related Disease:
  Catel-Manzke syndrome
  Dementia
  Temtamy preaxial brachydactyly syndrome
  Depression
• UniProt ID: TGDS_HUMAN
• EC Number: 4.2.1.46
• Pfam ID: PF16363
• Sequence:
  MSAACWEEPWGLPGGFAKRVLVTGGAGFIASHMIVSLVEDYPNYMIINLDKLDYCASLKN
  LETISNKQNYKFIQGDICDSHFVKLLFETEKIDIVLHFAAQTHVDLSFVRAFEFTYVNVY
  GTHVLVSAAHEARVEKFIYVSTDEVYGGSLDKEFDESSPKQPTNPYASSKAAAECFVQSY
  WEQYKFPVVITRSSNVYGPHQYPEKVIPKFISLLQHNRKCCIHGSGLQTRNFLYATDVVE
  AFLTVLKKGKPGEIYNIGTNFEMSVVQLAKELIQLIKETNSESEMENWVDYVNDRPTNDM
  RYPMKSEKIHGLGWRPKVPWKEGIKKTIEWYRENFHNWKNVEKALEPFPV
• KEGG Pathway:
  Metabolic pathways (hsa01100)
  Biosynthesis of nucleotide sugars (hsa01250)

Molecular Interaction Atlas (MIA) of This DOT

4 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Catel-Manzke syndrome	DISY1VBO	Definitive	Autosomal recessive	[1]
Dementia	DISXL1WY	Strong	Biomarker	[2]
Temtamy preaxial brachydactyly syndrome	DISBN663	Strong	Genetic Variation	[3]
Depression	DIS3XJ69	Limited	Genetic Variation	[4]

This DOT Affected the Drug Response of 2 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Etoposide	DMNH3PG	Approved	dTDP-D-glucose 4,6-dehydratase (TGDS) affects the response to substance of Etoposide.	[11]
Mitomycin	DMH0ZJE	Approved	dTDP-D-glucose 4,6-dehydratase (TGDS) affects the response to substance of Mitomycin.	[11]

5 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 dTDP-D-glucose 4,6-dehydratase (TGDS).	[5]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of dTDP-D-glucose 4,6-dehydratase (TGDS).	[6]
Phenobarbital	DMXZOCG	Approved	Phenobarbital affects the expression of dTDP-D-glucose 4,6-dehydratase (TGDS).	[7]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of dTDP-D-glucose 4,6-dehydratase (TGDS).	[9]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of dTDP-D-glucose 4,6-dehydratase (TGDS).	[10]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of dTDP-D-glucose 4,6-dehydratase (TGDS).	[8]

References

• [1] Homozygous and compound-heterozygous mutations in TGDS cause Catel-Manzke syndrome. Am J Hum Genet. 2014 Dec 4;95(6):763-70. doi: 10.1016/j.ajhg.2014.11.004.
• [2] DUPLICATE: The effectiveness of a cognitive training program in people with mild cognitive impairment: A study in urban community.Asian J Psychiatr. 2018 Jun;35:61-66. doi: 10.1016/j.ajp.2018.05.019. Epub 2018 May 26.
• [3] Mutations in TGDS associated with additional malformations of the middle fingers and halluces: Atypical Catel-Manzke syndrome in a fetus.Am J Med Genet A. 2017 Jun;173(6):1694-1697. doi: 10.1002/ajmg.a.38209. Epub 2017 Apr 19.
• [4] The evaluation and design of a short depression screening tool in Turkish older adults.Int Psychogeriatr. 2018 Oct;30(10):1541-1548. doi: 10.1017/S1041610218000236. Epub 2018 Mar 21.
• [5] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [6] Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
• [7] Reproducible chemical-induced changes in gene expression profiles in human hepatoma HepaRG cells under various experimental conditions. Toxicol In Vitro. 2009 Apr;23(3):466-75. doi: 10.1016/j.tiv.2008.12.018. Epub 2008 Dec 30.
• [8] Air pollution and DNA methylation alterations in lung cancer: A systematic and comparative study. Oncotarget. 2017 Jan 3;8(1):1369-1391. doi: 10.18632/oncotarget.13622.
• [9] Cell-based two-dimensional morphological assessment system to predict cancer drug-induced cardiotoxicity using human induced pluripotent stem cell-derived cardiomyocytes. Toxicol Appl Pharmacol. 2019 Nov 15;383:114761. doi: 10.1016/j.taap.2019.114761. Epub 2019 Sep 15.
• [10] Bisphenol A and bisphenol S induce distinct transcriptional profiles in differentiating human primary preadipocytes. PLoS One. 2016 Sep 29;11(9):e0163318.
• [11] 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.