Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT7WZRD0)

• DOT Name: Probable phosphoglycerate mutase 4 (PGAM4)
• Synonyms: EC 5.4.2.11; EC 5.4.2.4
• Gene Name: PGAM4
• Related Disease: Male infertility
• UniProt ID: PGAM4_HUMAN
• EC Number: 5.4.2.11; 5.4.2.4
• Pfam ID: PF00300
• Sequence:
  MAAYKLVLIRHGESTWNLENRFSCWYDADLSPAGHEEAKRGGQALRDAGYEFDICLTSVQ
  KRVIRTLWTVLDAIDQMWLPVVRTWRLNERHYGGLTGLNKAETAAKHGEAQVKIWRRSYD
  VPPPPMEPDHPFYSNISKDRRYADLTEDQLPSYESPKDTIARALPFWNEEIVPQIKEGKR
  VLIAAHGNSLQGIAKHVEGLSEEAIMELNLPTGIPIVYELDKNLKPIKPMQFLGDEETVC
  KAIEAVAAQGKAKK
• KEGG Pathway:
  Glycolysis / Gluconeogenesis (hsa00010)
  Glycine, serine and threonine metabolism (hsa00260)
  Metabolic pathways (hsa01100)
  Carbon metabolism (hsa01200)
  Biosynthesis of amino acids (hsa01230)
  Glucagon sig.ling pathway (hsa04922)
  Central carbon metabolism in cancer (hsa05230)

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Male infertility	DISY3YZZ	Strong	Altered Expression	[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 Probable phosphoglycerate mutase 4 (PGAM4).	[2]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Probable phosphoglycerate mutase 4 (PGAM4).	[7]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Probable phosphoglycerate mutase 4 (PGAM4).	[3]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Probable phosphoglycerate mutase 4 (PGAM4).	[4]
Marinol	DM70IK5	Approved	Marinol decreases the expression of Probable phosphoglycerate mutase 4 (PGAM4).	[5]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Probable phosphoglycerate mutase 4 (PGAM4).	[6]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN decreases the expression of Probable phosphoglycerate mutase 4 (PGAM4).	[8]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A affects the expression of Probable phosphoglycerate mutase 4 (PGAM4).	[9]
chloropicrin	DMSGBQA	Investigative	chloropicrin decreases the expression of Probable phosphoglycerate mutase 4 (PGAM4).	[10]

References

• [1] A single nucleotide polymorphism within the novel sex-linked testis-specific retrotransposed PGAM4 gene influences human male fertility.PLoS One. 2012;7(5):e35195. doi: 10.1371/journal.pone.0035195. Epub 2012 May 9.
• [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] Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
• [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] THC exposure of human iPSC neurons impacts genes associated with neuropsychiatric disorders. Transl Psychiatry. 2018 Apr 25;8(1):89. doi: 10.1038/s41398-018-0137-3.
• [6] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [7] 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.
• [8] Endoplasmic reticulum stress impairs insulin signaling through mitochondrial damage in SH-SY5Y cells. Neurosignals. 2012;20(4):265-80.
• [9] Comprehensive analysis of transcriptomic changes induced by low and high doses of bisphenol A in HepG2 spheroids in vitro and rat liver in vivo. Environ Res. 2019 Jun;173:124-134. doi: 10.1016/j.envres.2019.03.035. Epub 2019 Mar 18.
• [10] Molecular targets of chloropicrin in human airway epithelial cells. Toxicol In Vitro. 2017 Aug;42:247-254.