Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT8QPRVJ)

• DOT Name: Glycerophosphocholine cholinephosphodiesterase ENPP6 (ENPP6)
• Synonyms: GPC-Cpde; EC 3.1.4.-; EC 3.1.4.38; Choline-specific glycerophosphodiester phosphodiesterase; Ectonucleotide pyrophosphatase/phosphodiesterase family member 6; E-NPP 6; NPP-6
• Gene Name: ENPP6
• UniProt ID: ENPP6_HUMAN
• EC Number: 3.1.4.-; 3.1.4.38
• Pfam ID: PF01663
• Sequence:
  MAVKLGTLLLALALGLAQPASARRKLLVFLLDGFRSDYISDEALESLPGFKEIVSRGVKV
  DYLTPDFPSLSYPNYYTLMTGRHCEVHQMIGNYMWDPTTNKSFDIGVNKDSLMPLWWNGS
  EPLWVTLTKAKRKVYMYYWPGCEVEILGVRPTYCLEYKNVPTDINFANAVSDALDSFKSG
  RADLAAIYHERIDVEGHHYGPASPQRKDALKAVDTVLKYMTKWIQERGLQDRLNVIIFSD
  HGMTDIFWMDKVIELNKYISLNDLQQVKDRGPVVSLWPAPGKHSEIYNKLSTVEHMTVYE
  KEAIPSRFYYKKGKFVSPLTLVADEGWFITENREMLPFWMNSTGRREGWQRGWHGYDNEL
  MDMRGIFLAFGPDFKSNFRAAPIRSVDVYNVMCNVVGITPLPNNGSWSRVMCMLKGRAST
  APPVWPSHCALALILLFLLA
• Function: Choline-specific glycerophosphodiesterase that hydrolyzes glycerophosphocholine (GPC) and lysophosphatidylcholine (LPC) and contributes to supplying choline to the cells. Has a preference for LPC with short (12:0 and 14:0) or polyunsaturated (18:2 and 20:4) fatty acids. In vitro, hydrolyzes only choline-containing lysophospholipids, such as sphingosylphosphorylcholine (SPC), platelet-activating factor (PAF) and lysoPAF, but not other lysophospholipids.
• Tissue Specificity: Predominantly expressed in kidney and brain. In the kidney, expressed specifically in the proximal tubules and thin descending limbs of Henle (at protein level).
• KEGG Pathway:
  Ether lipid metabolism (hsa00565)
  Metabolic pathways (hsa01100)
• Reactome Pathway: Glycerophospholipid catabolism (R-HSA-6814848)

Molecular Interaction Atlas (MIA) of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate affects the expression of Glycerophosphocholine cholinephosphodiesterase ENPP6 (ENPP6).	[1]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Glycerophosphocholine cholinephosphodiesterase ENPP6 (ENPP6).	[2]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Glycerophosphocholine cholinephosphodiesterase ENPP6 (ENPP6).	[3]
Zoledronate	DMIXC7G	Approved	Zoledronate increases the expression of Glycerophosphocholine cholinephosphodiesterase ENPP6 (ENPP6).	[4]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Glycerophosphocholine cholinephosphodiesterase ENPP6 (ENPP6).	[5]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Glycerophosphocholine cholinephosphodiesterase ENPP6 (ENPP6).	[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 affects the methylation of Glycerophosphocholine cholinephosphodiesterase ENPP6 (ENPP6).	[7]

References

• [1] 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.
• [2] 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.
• [3] Blood transcript immune signatures distinguish a subset of people with elevated serum ALT from others given acetaminophen. Clin Pharmacol Ther. 2016 Apr;99(4):432-41.
• [4] Interleukin-19 as a translational indicator of renal injury. Arch Toxicol. 2015 Jan;89(1):101-6.
• [5] 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.
• [6] 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.
• [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.