Details of Drug Off-Target (DOT)

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

• DOT Name: Glycerophosphoinositol inositolphosphodiesterase GDPD2 (GDPD2)
• Synonyms: EC 3.1.4.43; Glycerophosphodiester phosphodiesterase 3; Glycerophosphodiester phosphodiesterase domain-containing protein 2; Osteoblast differentiation promoting factor
• Gene Name: GDPD2
• Related Disease:
  Breast cancer
  Breast carcinoma
  Neoplasm
• UniProt ID: GDPD2_HUMAN
• EC Number: 3.1.4.43
• Pfam ID: PF03009 ; PF13653
• Sequence:
  MAESPGCCSVWARCLHCLYSCHWRKCPRERMQTSKCDCIWFGLLFLTFLLSLSWLYIGLV
  LLNDLHNFNEFLFRRWGHWMDWSLAFLLVISLLVTYASLLLVLALLLRLCRQPLHLHSLH
  KVLLLLIMLLVAAGLVGLDIQWQQEWHSLRVSLQATAPFLHIGAAAGIALLAWPVADTFY
  RIHRRGPKILLLLLFFGVVLVIYLAPLCISSPCIMEPRDLPPKPGLVGHRGAPMLAPENT
  LMSLRKTAECGATVFETDVMVSSDGVPFLMHDEHLSRTTNVASVFPTRITAHSSDFSWTE
  LKRLNAGSWFLERRPFWGAKPLAGPDQKEAESQTVPALEELLEEAAALNLSIMFDLRRPP
  QNHTYYDTFVIQTLETVLNARVPQAMVFWLPDEDRANVQRRAPGMRQIYGRQGGNRTERP
  QFLNLPYQDLPLLDIKALHKDNVSVNLFVVNKPWLFSLLWCAGVDSVTTNDCQLLQQMRY
  PIWLITPQTYLIIWVITNCVSTMLLLWTFLLQRRFVKKRGKTGLETAVLLTRINNFMME
• Function: Has glycerophosphoinositol inositolphosphodiesterase activity and specifically hydrolyzes glycerophosphoinositol, with no activity for other substrates such as glycerophosphoinositol 4-phosphate, glycerophosphocholine, glycerophosphoethanolamine, and glycerophosphoserine. Accelerates the program of osteoblast differentiation and growth. May play a role in remodeling of the actin cytoskeleton.

Molecular Interaction Atlas (MIA) of This DOT

3 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Breast cancer	DIS7DPX1	Strong	Altered Expression	[1]
Breast carcinoma	DIS2UE88	Strong	Altered Expression	[1]
Neoplasm	DISZKGEW	Strong	Altered Expression	[1]

5 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 Glycerophosphoinositol inositolphosphodiesterase GDPD2 (GDPD2).	[2]
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of Glycerophosphoinositol inositolphosphodiesterase GDPD2 (GDPD2).	[3]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Glycerophosphoinositol inositolphosphodiesterase GDPD2 (GDPD2).	[4]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Glycerophosphoinositol inositolphosphodiesterase GDPD2 (GDPD2).	[5]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the mutagenesis of Glycerophosphoinositol inositolphosphodiesterase GDPD2 (GDPD2).	[6]

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 Glycerophosphoinositol inositolphosphodiesterase GDPD2 (GDPD2).	[7]

References

• [1] Negative regulation of urokinase receptor activity by a GPI-specific phospholipase C in breast cancer cells.Elife. 2017 Aug 29;6:e23649. doi: 10.7554/eLife.23649.
• [2] 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.
• [3] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [4] Gene Expression Regulation and Pathway Analysis After Valproic Acid and Carbamazepine Exposure in a Human Embryonic Stem Cell-Based Neurodevelopmental Toxicity Assay. Toxicol Sci. 2015 Aug;146(2):311-20. doi: 10.1093/toxsci/kfv094. Epub 2015 May 15.
• [5] A transcriptome-based classifier to identify developmental toxicants by stem cell testing: design, validation and optimization for histone deacetylase inhibitors. Arch Toxicol. 2015 Sep;89(9):1599-618.
• [6] Exome-wide mutation profile in benzo[a]pyrene-derived post-stasis and immortal human mammary epithelial cells. Mutat Res Genet Toxicol Environ Mutagen. 2014 Dec;775-776:48-54. doi: 10.1016/j.mrgentox.2014.10.011. Epub 2014 Nov 4.
• [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.