Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTRB4S6X)

• DOT Name: Acylphosphatase-2 (ACYP2)
• Synonyms: EC 3.6.1.7; Acylphosphatase, muscle type isozyme; Acylphosphate phosphohydrolase 2
• Gene Name: ACYP2
• Related Disease:
  Advanced cancer
  Brain neoplasm
  Carcinoma of esophagus
  Carcinoma of liver and intrahepatic biliary tract
  Cardiovascular disease
  Glioma
  IgA nephropathy
  Liver cancer
  Liver cirrhosis
  Matthew-Wood syndrome
  Neoplasm
  Gastric cancer
  Kidney cancer
  Laryngeal squamous cell carcinoma
  Renal cell carcinoma
  Stomach cancer
  Breast cancer
  Breast carcinoma
  Bone osteosarcoma
  Lung cancer
  Lung carcinoma
  Osteosarcoma
• UniProt ID: ACYP2_HUMAN
• EC Number: 3.6.1.7
• Pfam ID: PF00708
• Sequence:
  MSTAQSLKSVDYEVFGRVQGVCFRMYTEDEARKIGVVGWVKNTSKGTVTGQVQGPEDKVN
  SMKSWLSKVGSPSSRIDRTNFSNEKTISKLEYSNFSIRY
• Function: Its physiological role is not yet clear.
• KEGG Pathway:
  Pyruvate metabolism (hsa00620)
  Metabolic pathways (hsa01100)

Molecular Interaction Atlas (MIA) of This DOT

22 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Advanced cancer	DISAT1Z9	Strong	Genetic Variation	[1]
Brain neoplasm	DISY3EKS	Strong	Genetic Variation	[2]
Carcinoma of esophagus	DISS6G4D	Strong	Genetic Variation	[3]
Carcinoma of liver and intrahepatic biliary tract	DIS8WA0W	Strong	Genetic Variation	[1]
Cardiovascular disease	DIS2IQDX	Strong	Genetic Variation	[4]
Glioma	DIS5RPEH	Strong	Genetic Variation	[5]
IgA nephropathy	DISZ8MTK	Strong	Genetic Variation	[6]
Liver cancer	DISDE4BI	Strong	Genetic Variation	[1]
Liver cirrhosis	DIS4G1GX	Strong	Genetic Variation	[1]
Matthew-Wood syndrome	DISA7HR7	Strong	Genetic Variation	[7]
Neoplasm	DISZKGEW	Strong	Genetic Variation	[1]
Gastric cancer	DISXGOUK	moderate	Genetic Variation	[8]
Kidney cancer	DISBIPKM	moderate	Genetic Variation	[9]
Laryngeal squamous cell carcinoma	DIS9UUVF	moderate	Genetic Variation	[10]
Renal cell carcinoma	DISQZ2X8	moderate	Genetic Variation	[9]
Stomach cancer	DISKIJSX	moderate	Genetic Variation	[8]
Breast cancer	DIS7DPX1	Disputed	Genetic Variation	[11]
Breast carcinoma	DIS2UE88	Disputed	Genetic Variation	[11]
Bone osteosarcoma	DIST1004	Limited	Genetic Variation	[2]
Lung cancer	DISCM4YA	Limited	Genetic Variation	[12]
Lung carcinoma	DISTR26C	Limited	Genetic Variation	[12]
Osteosarcoma	DISLQ7E2	Limited	Genetic Variation	[2]

This DOT Affected the Drug Response of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Cisplatin	DMRHGI9	Approved	Acylphosphatase-2 (ACYP2) increases the response to substance of Cisplatin.	[25]

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 Acylphosphatase-2 (ACYP2).	[13]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the methylation of Acylphosphatase-2 (ACYP2).	[24]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Acylphosphatase-2 (ACYP2).	[14]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Acylphosphatase-2 (ACYP2).	[15]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Acylphosphatase-2 (ACYP2).	[16]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Acylphosphatase-2 (ACYP2).	[17]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Acylphosphatase-2 (ACYP2).	[18]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of Acylphosphatase-2 (ACYP2).	[19]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of Acylphosphatase-2 (ACYP2).	[20]
Demecolcine	DMCZQGK	Approved	Demecolcine increases the expression of Acylphosphatase-2 (ACYP2).	[21]
Dihydrotestosterone	DM3S8XC	Phase 4	Dihydrotestosterone increases the expression of Acylphosphatase-2 (ACYP2).	[22]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Acylphosphatase-2 (ACYP2).	[23]

References

• [1] Associations between polymorphisms of the ACYP2 gene and Liver cancer risk: A case-control study and meta-analysis.Mol Genet Genomic Med. 2019 Jul;7(7):e00716. doi: 10.1002/mgg3.716. Epub 2019 May 23.
• [2] Replication of a genetic variant in ACYP2 associated with cisplatin-induced hearing loss in patients with osteosarcoma.Pharmacogenet Genomics. 2016 May;26(5):243-7. doi: 10.1097/FPC.0000000000000212.
• [3] Leukocyte telomere length-related genetic variants in ACYP2 contribute to the risk of esophageal carcinoma in Chinese Han population.Oncotarget. 2017 Apr 11;8(15):25564-25570. doi: 10.18632/oncotarget.16071.
• [4] GWAS for discovery and replication of genetic loci associated with sudden cardiac arrest in patients with coronary artery disease.BMC Cardiovasc Disord. 2011 Jun 10;11:29. doi: 10.1186/1471-2261-11-29.
• [5] The effects of gene polymorphisms on glioma prognosis.J Gene Med. 2017 Nov;19(11):345-352. doi: 10.1002/jgm.2989. Epub 2017 Nov 8.
• [6] Association between the ACYP2 Polymorphisms and IgAN Risk in the Chinese Han Population.Kidney Blood Press Res. 2019;44(4):810-822. doi: 10.1159/000501703. Epub 2019 Jul 10.
• [7] Genetic determinants of telomere length and risk of pancreatic cancer: A PANDoRA study.Int J Cancer. 2019 Mar 15;144(6):1275-1283. doi: 10.1002/ijc.31928. Epub 2018 Nov 12.
• [8] Association analysis of telomere length related gene ACYP2 with the gastric cancer risk in the northwest Chinese Han population.Oncotarget. 2017 May 9;8(19):31144-31152. doi: 10.18632/oncotarget.16097.
• [9] Association between ACYP2 polymorphisms and the risk of renal cell cancer.Mol Genet Genomic Med. 2019 Nov;7(11):e966. doi: 10.1002/mgg3.966. Epub 2019 Sep 5.
• [10] Assessment of the association between ACYP2 and laryngeal squamous cell carcinoma risk in Chinese males.Mol Genet Genomic Med. 2019 Jul;7(7):e00731. doi: 10.1002/mgg3.731. Epub 2019 May 29.
• [11] Single Nucleotide Polymorphisms in the Acylphosphatase 2 Gene and The SNP-SNP Interactions on the Risk of Breast Cancer in Chinese Han Women.Clin Breast Cancer. 2018 Jun;18(3):e329-e333. doi: 10.1016/j.clbc.2017.09.003. Epub 2017 Sep 19.
• [12] Association of polymorphisms in the telomere-related gene ACYP2 with lung cancer risk in the Chinese Han population.Oncotarget. 2016 Dec 27;7(52):87473-87478. doi: 10.18632/oncotarget.13870.
• [13] 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.
• [14] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [15] 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.
• [16] 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.
• [17] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [18] 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.
• [19] Gene expression profile induced by arsenic trioxide in chronic lymphocytic leukemia cells reveals a central role for heme oxygenase-1 in apoptosis and regulation of matrix metalloproteinase-9. Oncotarget. 2016 Dec 13;7(50):83359-83377.
• [20] 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.
• [21] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [22] Differentially expressed genes in the prostate cancer cell line LNCaP after exposure to androgen and anti-androgen. Cancer Genet Cytogenet. 2006 Apr 15;166(2):130-8. doi: 10.1016/j.cancergencyto.2005.09.012.
• [23] 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.
• [24] 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.
• [25] Common variants in ACYP2 influence susceptibility to cisplatin-induced hearing loss. Nat Genet. 2015 Mar;47(3):263-6. doi: 10.1038/ng.3217. Epub 2015 Feb 9.