Details of Drug Off-Target (DOT)

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

• DOT Name: Phytanoyl-CoA dioxygenase domain-containing protein 1 (PHYHD1)
• Synonyms: Protein PHYHD1; EC 1.14.11.-
• Gene Name: PHYHD1
• Related Disease:
  Alzheimer disease
  Lewy body dementia
  Parkinson disease
• UniProt ID: PHYD1_HUMAN
• PDB ID: 2OPW; 3OBZ
• EC Number: 1.14.11.-
• Pfam ID: PF05721
• Sequence:
  MACLSPSQLQKFQQDGFLVLEGFLSAEECVAMQQRIGEIVAEMDVPLHCRTEFSTQEEEQ
  LRAQGSTDYFLSSGDKIRFFFEKGVFDEKGNFLVPPEKSINKIGHALHAHDPVFKSITHS
  FKVQTLARSLGLQMPVVVQSMYIFKQPHFGGEVSPHQDASFLYTEPLGRVLGVWIAVEDA
  TLENGCLWFIPGSHTSGVSRRMVRAPVGSAPGTSFLGSEPARDNSLFVPTPVQRGALVLI
  HGEVVHKSKQNLSDRSRQAYTFHLMEASGTTWSPENWLQPTAELPFPQLYT
• Function: 2-oxoglutarate(2OG)-dependent dioxygenase that catalyzes the conversion of 2-oxoglutarate to succinate and CO(2) in an iron-dependent manner. However, does not couple 2OG turnover to the hydroxylation of acyl-coenzyme A derivatives, implying that it is not directly involved in phytanoyl coenzyme-A metabolism. Does not show detectable activity towards fatty acid CoA thioesters ; [Isoform 2]: Isoform 2 probably lacks enzyme activity; [Isoform 3]: Isoform 3 probably lacks enzyme activity.

Molecular Interaction Atlas (MIA) of This DOT

3 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Alzheimer disease	DISF8S70	Limited	Biomarker	[1]
Lewy body dementia	DISAE66J	Limited	Altered Expression	[1]
Parkinson disease	DISQVHKL	Limited	Altered Expression	[1]

9 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 Phytanoyl-CoA dioxygenase domain-containing protein 1 (PHYHD1).	[2]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Phytanoyl-CoA dioxygenase domain-containing protein 1 (PHYHD1).	[3]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Phytanoyl-CoA dioxygenase domain-containing protein 1 (PHYHD1).	[4]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Phytanoyl-CoA dioxygenase domain-containing protein 1 (PHYHD1).	[5]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Phytanoyl-CoA dioxygenase domain-containing protein 1 (PHYHD1).	[6]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Phytanoyl-CoA dioxygenase domain-containing protein 1 (PHYHD1).	[7]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Phytanoyl-CoA dioxygenase domain-containing protein 1 (PHYHD1).	[8]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Phytanoyl-CoA dioxygenase domain-containing protein 1 (PHYHD1).	[9]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Phytanoyl-CoA dioxygenase domain-containing protein 1 (PHYHD1).	[10]

References

• [1] Genes associated with the progression of neurofibrillary tangles in Alzheimer's disease.Transl Psychiatry. 2014 Jun 10;4(6):e396. doi: 10.1038/tp.2014.35.
• [2] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [3] 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.
• [4] Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
• [5] 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.
• [6] Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
• [7] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [8] 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.
• [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.