Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTUM65JL)

• DOT Name: Glycerophosphodiester phosphodiesterase domain-containing protein 5 (GDPD5)
• Synonyms: Glycerophosphocholine phosphodiesterase GDPD5; EC 3.1.4.2; Glycerophosphodiester phosphodiesterase 2; Phosphoinositide phospholipase C GDPD5; EC 3.1.4.11
• Gene Name: GDPD5
• Related Disease:
  Colorectal carcinoma
  Familial amyotrophic lateral sclerosis
  Advanced cancer
  Breast cancer
  Breast carcinoma
  Breast neoplasm
  Neoplasm
  Acute myelogenous leukaemia
  Neuroblastoma
  Rheumatoid arthritis
• UniProt ID: GDPD5_HUMAN
• EC Number: 3.1.4.11; 3.1.4.2
• Pfam ID: PF03009 ; PF13653
• Sequence:
  MVRHQPLQYYEPQLCLSCLTGIYGCRWKRYQRSHDDTTPWERLWFLLLTFTFGLTLTWLY
  FWWEVHNDYDEFNWYLYNRMGYWSDWPVPILVTTAAAFAYIAGLLVLALCHIAVGQQMNL
  HWLHKIGLVVILASTVVAMSAVAQLWEDEWEVLLISLQGTAPFLHVGAVAAVTMLSWIVA
  GQFARAERTSSQVTILCTFFTVVFALYLAPLTISSPCIMEKKDLGPKPALIGHRGAPMLA
  PEHTLMSFRKALEQKLYGLQADITISLDGVPFLMHDTTLRRTTNVEEEFPELARRPASML
  NWTTLQRLNAGQWFLKTDPFWTASSLSPSDHREAQNQSICSLAELLELAKGNATLLLNLR
  DPPREHPYRSSFINVTLEAVLHSGFPQHQVMWLPSRQRPLVRKVAPGFQQTSGSKEAVAS
  LRRGHIQRLNLRYTQVSRQELRDYASWNLSVNLYTVNAPWLFSLLWCAGVPSVTSDNSHA
  LSQVPSPLWIMPPDEYCLMWVTADLVSFTLIVGIFVLQKWRLGGIRSYNPEQIMLSAAVR
  RTSRDVSIMKEKLIFSEISDGVEVSDVLSVCSDNSYDTYANSTATPVGPRGGGSHTKTLI
  ERSGR
• Function: Glycerophosphodiester phosphodiesterase that promotes neurite formation and drives spinal motor neuron differentiation. Mediates the cleavage of glycosylphosphatidylinositol (GPI) anchor of target proteins: removes the GPI-anchor of RECK, leading to release RECK from the plasma membrane. May contribute to the osmotic regulation of cellular glycerophosphocholine.
• Reactome Pathway: Glycerophospholipid catabolism (R-HSA-6814848)

Molecular Interaction Atlas (MIA) of This DOT

10 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Colorectal carcinoma	DIS5PYL0	Strong	Altered Expression	[1]
Familial amyotrophic lateral sclerosis	DISWZ9CJ	Strong	Biomarker	[2]
Advanced cancer	DISAT1Z9	moderate	Altered Expression	[3]
Breast cancer	DIS7DPX1	moderate	Altered Expression	[3]
Breast carcinoma	DIS2UE88	moderate	Biomarker	[3]
Breast neoplasm	DISNGJLM	moderate	Altered Expression	[3]
Neoplasm	DISZKGEW	moderate	Altered Expression	[3]
Acute myelogenous leukaemia	DISCSPTN	Limited	Genetic Variation	[4]
Neuroblastoma	DISVZBI4	Limited	Altered Expression	[5]
Rheumatoid arthritis	DISTSB4J	Limited	Altered Expression	[5]

This DOT Affected the Regulation of Drug Effects of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Choline alfoscerate	DMOI1ZF	Approved	Glycerophosphodiester phosphodiesterase domain-containing protein 5 (GDPD5) affects the abundance of Choline alfoscerate.	[24]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of Glycerophosphodiester phosphodiesterase domain-containing protein 5 (GDPD5).	[6]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Glycerophosphodiester phosphodiesterase domain-containing protein 5 (GDPD5).	[7]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Glycerophosphodiester phosphodiesterase domain-containing protein 5 (GDPD5).	[8]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Glycerophosphodiester phosphodiesterase domain-containing protein 5 (GDPD5).	[9]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Glycerophosphodiester phosphodiesterase domain-containing protein 5 (GDPD5).	[10]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Glycerophosphodiester phosphodiesterase domain-containing protein 5 (GDPD5).	[11]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Glycerophosphodiester phosphodiesterase domain-containing protein 5 (GDPD5).	[12]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Glycerophosphodiester phosphodiesterase domain-containing protein 5 (GDPD5).	[13]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of Glycerophosphodiester phosphodiesterase domain-containing protein 5 (GDPD5).	[14]
Triclosan	DMZUR4N	Approved	Triclosan increases the expression of Glycerophosphodiester phosphodiesterase domain-containing protein 5 (GDPD5).	[15]
Menadione	DMSJDTY	Approved	Menadione affects the expression of Glycerophosphodiester phosphodiesterase domain-containing protein 5 (GDPD5).	[16]
Niclosamide	DMJAGXQ	Approved	Niclosamide increases the expression of Glycerophosphodiester phosphodiesterase domain-containing protein 5 (GDPD5).	[17]
Diethylstilbestrol	DMN3UXQ	Approved	Diethylstilbestrol increases the expression of Glycerophosphodiester phosphodiesterase domain-containing protein 5 (GDPD5).	[18]
Azathioprine	DMMZSXQ	Approved	Azathioprine decreases the expression of Glycerophosphodiester phosphodiesterase domain-containing protein 5 (GDPD5).	[19]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Glycerophosphodiester phosphodiesterase domain-containing protein 5 (GDPD5).	[20]
Resveratrol	DM3RWXL	Phase 3	Resveratrol increases the expression of Glycerophosphodiester phosphodiesterase domain-containing protein 5 (GDPD5).	[18]
Genistein	DM0JETC	Phase 2/3	Genistein increases the expression of Glycerophosphodiester phosphodiesterase domain-containing protein 5 (GDPD5).	[18]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Glycerophosphodiester phosphodiesterase domain-containing protein 5 (GDPD5).	[21]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane decreases the expression of Glycerophosphodiester phosphodiesterase domain-containing protein 5 (GDPD5).	[23]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Glycerophosphodiester phosphodiesterase domain-containing protein 5 (GDPD5).	[22]

References

• [1] GDPD5, a target of miR-195-5p, is associated with metastasis and chemoresistance in colorectal cancer.Biomed Pharmacother. 2018 May;101:945-952. doi: 10.1016/j.biopha.2018.03.028. Epub 2018 Mar 22.
• [2] GDE2 is essential for neuronal survival in the postnatal mammalian spinal cord.Mol Neurodegener. 2017 Jan 19;12(1):8. doi: 10.1186/s13024-017-0148-1.
• [3] Glycerophosphodiester phosphodiesterase domain containing 5 (GDPD5) expression correlates with malignant choline phospholipid metabolite profiles in human breast cancer.NMR Biomed. 2012 Sep;25(9):1033-42. doi: 10.1002/nbm.2766. Epub 2012 Jan 26.
• [4] Genome-wide haplotype association study identify the FGFR2 gene as a risk gene for acute myeloid leukemia.Oncotarget. 2017 Jan 31;8(5):7891-7899. doi: 10.18632/oncotarget.13631.
• [5] Involvement of membrane protein GDE2 in retinoic acid-induced neurite formation in Neuro2A cells.FEBS Lett. 2007 Feb 20;581(4):712-8. doi: 10.1016/j.febslet.2007.01.035. Epub 2007 Jan 24.
• [6] Stem cell transcriptome responses and corresponding biomarkers that indicate the transition from adaptive responses to cytotoxicity. Chem Res Toxicol. 2017 Apr 17;30(4):905-922.
• [7] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [8] Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
• [9] Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
• [10] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [11] Genistein and bisphenol A exposure cause estrogen receptor 1 to bind thousands of sites in a cell type-specific manner. Genome Res. 2012 Nov;22(11):2153-62.
• [12] 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.
• [13] Global gene expression analysis reveals differences in cellular responses to hydroxyl- and superoxide anion radical-induced oxidative stress in caco-2 cells. Toxicol Sci. 2010 Apr;114(2):193-203. doi: 10.1093/toxsci/kfp309. Epub 2009 Dec 31.
• [14] The exosome-like vesicles derived from androgen exposed-prostate stromal cells promote epithelial cells proliferation and epithelial-mesenchymal transition. Toxicol Appl Pharmacol. 2021 Jan 15;411:115384. doi: 10.1016/j.taap.2020.115384. Epub 2020 Dec 25.
• [15] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [16] Time series analysis of oxidative stress response patterns in HepG2: a toxicogenomics approach. Toxicology. 2013 Apr 5;306:24-34.
• [17] Mitochondrial Uncoupling Induces Epigenome Remodeling and Promotes Differentiation in Neuroblastoma. Cancer Res. 2023 Jan 18;83(2):181-194. doi: 10.1158/0008-5472.CAN-22-1029.
• [18] Gene expression profiling in Ishikawa cells: a fingerprint for estrogen active compounds. Toxicol Appl Pharmacol. 2009 Apr 1;236(1):85-96.
• [19] A transcriptomics-based in vitro assay for predicting chemical genotoxicity in vivo. Carcinogenesis. 2012 Jul;33(7):1421-9.
• [20] Definition of transcriptome-based indices for quantitative characterization of chemically disturbed stem cell development: introduction of the STOP-Toxukn and STOP-Toxukk tests. Arch Toxicol. 2017 Feb;91(2):839-864.
• [21] 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.
• [22] 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.
• [23] Transcriptome and DNA methylation changes modulated by sulforaphane induce cell cycle arrest, apoptosis, DNA damage, and suppression of proliferation in human liver cancer cells. Food Chem Toxicol. 2020 Feb;136:111047. doi: 10.1016/j.fct.2019.111047. Epub 2019 Dec 12.
• [24] Decrease of an intracellular organic osmolyte contributes to the cytotoxicity of organophosphate in neuroblastoma cells in vitro. Toxicology. 2021 Apr 15;453:152725. doi: 10.1016/j.tox.2021.152725. Epub 2021 Feb 19.