Details of Drug Off-Target (DOT)

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

• DOT Name: Lysophospholipase D GDPD1 (GDPD1)
• Synonyms: EC 3.1.4.-; Glycerophosphodiester phosphodiesterase 4; Glycerophosphodiester phosphodiesterase domain-containing protein 1
• Gene Name: GDPD1
• Related Disease: Retinitis pigmentosa
• UniProt ID: GDPD1_HUMAN
• EC Number: 3.1.4.-
• Pfam ID: PF03009
• Sequence:
  MSSTAAFYLLSTLGGYLVTSFLLLKYPTLLHQRKKQRFLSKHISHRGGAGENLENTMAAF
  QHAVKIGTDMLELDCHITKDEQVVVSHDENLKRATGVNVNISDLKYCELPPYLGKLDVSF
  QRACQCEGKDNRIPLLKEVFEAFPNTPINIDIKVNNNVLIKKVSELVKRYNREHLTVWGN
  ANYEIVEKCYKENSDIPILFSLQRVLLILGLFFTGLLPFVPIREQFFEIPMPSIILKLKE
  PHTMSRSQKFLIWLSDLLLMRKALFDHLTARGIQVYIWVLNEEQEYKRAFDLGATGVMTD
  YPTKLRDFLHNFSA
• Function: Hydrolyzes lysoglycerophospholipids to produce lysophosphatidic acid (LPA) and the corresponding amines. Shows a preference for 1-O-alkyl-sn-glycero-3-phosphocholine (lyso-PAF), lysophosphatidylethanolamine (lyso-PE) and lysophosphatidylcholine (lyso-PC). May be involved in bioactive N-acylethanolamine biosynthesis from both N-acyl-lysoplasmenylethanolamin (N-acyl-lysoPlsEt) and N-acyl-lysophosphatidylethanolamin (N-acyl-lysoPE). In addition, hydrolyzes glycerophospho-N-acylethanolamine to N-acylethanolamine. Does not display glycerophosphodiester phosphodiesterase activity, since it cannot hydrolyze either glycerophosphoinositol or glycerophosphocholine.
• Tissue Specificity: Widely expressed with high expression level in testis.
• KEGG Pathway:
  Ether lipid metabolism (hsa00565)
  Metabolic pathways (hsa01100)
• Reactome Pathway: Glycerophospholipid catabolism (R-HSA-6814848)

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Retinitis pigmentosa	DISCGPY8	Limited	Autosomal dominant	[1]

10 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 Lysophospholipase D GDPD1 (GDPD1).	[2]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Lysophospholipase D GDPD1 (GDPD1).	[3]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Lysophospholipase D GDPD1 (GDPD1).	[4]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Lysophospholipase D GDPD1 (GDPD1).	[5]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Lysophospholipase D GDPD1 (GDPD1).	[7]
Phenobarbital	DMXZOCG	Approved	Phenobarbital increases the expression of Lysophospholipase D GDPD1 (GDPD1).	[8]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 increases the expression of Lysophospholipase D GDPD1 (GDPD1).	[10]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Lysophospholipase D GDPD1 (GDPD1).	[12]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Lysophospholipase D GDPD1 (GDPD1).	[13]
Acetaldehyde	DMJFKG4	Investigative	Acetaldehyde increases the expression of Lysophospholipase D GDPD1 (GDPD1).	[14]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Lysophospholipase D GDPD1 (GDPD1).	[6]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of Lysophospholipase D GDPD1 (GDPD1).	[9]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the methylation of Lysophospholipase D GDPD1 (GDPD1).	[11]

References

• [1] Structural Variants Create New Topological-Associated Domains and Ectopic Retinal Enhancer-Gene Contact in Dominant Retinitis Pigmentosa. Am J Hum Genet. 2020 Nov 5;107(5):802-814. doi: 10.1016/j.ajhg.2020.09.002. Epub 2020 Oct 5.
• [2] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [3] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [4] Predictive toxicology using systemic biology and liver microfluidic "on chip" approaches: application to acetaminophen injury. Toxicol Appl Pharmacol. 2012 Mar 15;259(3):270-80.
• [5] 17-Estradiol Activates HSF1 via MAPK Signaling in ER-Positive Breast Cancer Cells. Cancers (Basel). 2019 Oct 11;11(10):1533. doi: 10.3390/cancers11101533.
• [6] Prenatal arsenic exposure and the epigenome: identifying sites of 5-methylcytosine alterations that predict functional changes in gene expression in newborn cord blood and subsequent birth outcomes. Toxicol Sci. 2015 Jan;143(1):97-106. doi: 10.1093/toxsci/kfu210. Epub 2014 Oct 10.
• [7] Minimal peroxide exposure of neuronal cells induces multifaceted adaptive responses. PLoS One. 2010 Dec 17;5(12):e14352. doi: 10.1371/journal.pone.0014352.
• [8] Dose- and time-dependent effects of phenobarbital on gene expression profiling in human hepatoma HepaRG cells. Toxicol Appl Pharmacol. 2009 Feb 1;234(3):345-60.
• [9] Effect of aflatoxin B(1), benzo[a]pyrene, and methapyrilene on transcriptomic and epigenetic alterations in human liver HepaRG cells. Food Chem Toxicol. 2018 Nov;121:214-223. doi: 10.1016/j.fct.2018.08.034. Epub 2018 Aug 26.
• [10] Inhibition of BRD4 attenuates tumor cell self-renewal and suppresses stem cell signaling in MYC driven medulloblastoma. Oncotarget. 2014 May 15;5(9):2355-71.
• [11] 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.
• [12] From transient transcriptome responses to disturbed neurodevelopment: role of histone acetylation and methylation as epigenetic switch between reversible and irreversible drug effects. Arch Toxicol. 2014 Jul;88(7):1451-68.
• [13] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [14] Transcriptome profile analysis of saturated aliphatic aldehydes reveals carbon number-specific molecules involved in pulmonary toxicity. Chem Res Toxicol. 2014 Aug 18;27(8):1362-70.