Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTLOBJL2)

• DOT Name: Glutamine amidotransferase-like class 1 domain-containing protein 1 (GATD1)
• Synonyms: Parkinson disease 7 domain-containing protein 1
• Gene Name: GATD1
• Related Disease: Fuchs' endothelial dystrophy
• UniProt ID: GALD1_HUMAN
• PDB ID: 7ND2; 8A3P
• Sequence:
  MASERLPNRPACLLVASGAAEGVSAQSFLHCFTMASTAFNLQVATPGGKAMEFVDVTESN
  ARWVQDFRLKAYASPAKLESIDGARYHALLIPSCPGALTDLASSGSLARILQHFHSESKP
  ICAVGHGVAALCCATNEDRSWVFDSYSLTGPSVCELVRAPGFARLPLVVEDFVKDSGACF
  SASEPDAVHVVLDRHLVTGQNASSTVPAVQNLLFLCGSRK

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Fuchs' endothelial dystrophy	DISL7TXC	Strong	Genetic Variation	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of Glutamine amidotransferase-like class 1 domain-containing protein 1 (GATD1).	[2]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Glutamine amidotransferase-like class 1 domain-containing protein 1 (GATD1).	[7]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Glutamine amidotransferase-like class 1 domain-containing protein 1 (GATD1).	[3]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Glutamine amidotransferase-like class 1 domain-containing protein 1 (GATD1).	[4]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Glutamine amidotransferase-like class 1 domain-containing protein 1 (GATD1).	[5]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Glutamine amidotransferase-like class 1 domain-containing protein 1 (GATD1).	[6]

References

• [1] Genome-wide association study identifies three novel loci in Fuchs endothelial corneal dystrophy.Nat Commun. 2017 Mar 30;8:14898. doi: 10.1038/ncomms14898.
• [2] 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.
• [3] Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
• [4] 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.
• [5] Low doses of cisplatin induce gene alterations, cell cycle arrest, and apoptosis in human promyelocytic leukemia cells. Biomark Insights. 2016 Aug 24;11:113-21.
• [6] Quantitative proteomics reveals a broad-spectrum antiviral property of ivermectin, benefiting for COVID-19 treatment. J Cell Physiol. 2021 Apr;236(4):2959-2975. doi: 10.1002/jcp.30055. Epub 2020 Sep 22.
• [7] 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.