Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTW680HT)

• DOT Name: Acyl-coenzyme A oxidase-like protein (ACOXL)
• Synonyms: Acyl-CoA oxidase-like protein; EC 1.3.3.-
• Gene Name: ACOXL
• Related Disease:
  Alopecia areata
  Attention deficit hyperactivity disorder
  Classic Hodgkin lymphoma
  Colon cancer
  Colorectal adenocarcinoma
  Colorectal cancer
  Colorectal cancer, susceptibility to, 1
  Colorectal cancer, susceptibility to, 10
  Colorectal cancer, susceptibility to, 12
  Colorectal carcinoma
  Colorectal neoplasm
  Erectile dysfunction
  IgA nephropathy
  Nasopharyngeal carcinoma
  Open-angle glaucoma
  Plasma cell myeloma
  Rheumatoid arthritis
  Type-1 diabetes
  Acute myelogenous leukaemia
  Ovarian neoplasm
  Ovarian serous adenocarcinoma
  Prostate cancer
  Prostate carcinoma
  Small lymphocytic lymphoma
• UniProt ID: ACOXL_HUMAN
• EC Number: 1.3.3.-
• Pfam ID: PF01756 ; PF00441 ; PF02770
• Sequence:
  MRALTVQRVKFAMDLPLLKRAGQDLAEKTKNFVSRSLVIGEVLSMADMATGVKCGIIYWL
  FGGAIRNLGSPEHVTKWFQPLQEQKYTGMFAMTERGHGSNARGIQTEATFDLSAQEFVID
  TPCENAEKMYIGNAMYGNYAAVFAQLIIDGRSQGPHCFIVPVRDENGSLYPGVTAIDMMY
  KEGLHGVDNGILIFDKVRIPRENLLDKFGSVAPDGQYHSPIRNKSARFNAMLAALTPSRL
  AVAFQAMGAMKLGLTIAIRYSHSRRQFGPKTKEEVKIIEHQTQTLRLMPHLATALALTFV
  SRYAGALLDEDVFQGKELVNSRSLQALVAGLKAYSTWENIRCLQDCRECTGGMGYMMENR
  ISGLKCDTDVFATFEGDDVVMLQVVGRELLAQYTKQYEEKPLFGLLQNWAESVGDKLRTS
  FLAFNMDTVDDLAFLLKAVKFRERVLQRGLVARIYYKVKTKKEDFFHAWNSCLHHVASLS
  LAHTHRVTLEQFSLAVKSCPDQEDQTLLMKFCLLYGTKLVFQERAWYLEHKYLTPMASTR
  IRNQERC
• Reactome Pathway: Beta-oxidation of pristanoyl-CoA (R-HSA-389887)

Molecular Interaction Atlas (MIA) of This DOT

24 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Alopecia areata	DIS0XXBJ	Strong	Genetic Variation	[1]
Attention deficit hyperactivity disorder	DISL8MX9	Strong	Genetic Variation	[2]
Classic Hodgkin lymphoma	DISV1LU6	Strong	Genetic Variation	[3]
Colon cancer	DISVC52G	Strong	Genetic Variation	[4]
Colorectal adenocarcinoma	DISPQOUB	Strong	Genetic Variation	[4]
Colorectal cancer	DISNH7P9	Strong	Genetic Variation	[4]
Colorectal cancer, susceptibility to, 1	DISZ794C	Strong	Genetic Variation	[4]
Colorectal cancer, susceptibility to, 10	DISQXMYM	Strong	Genetic Variation	[4]
Colorectal cancer, susceptibility to, 12	DIS4FXJX	Strong	Genetic Variation	[4]
Colorectal carcinoma	DIS5PYL0	Strong	Genetic Variation	[4]
Colorectal neoplasm	DISR1UCN	Strong	Genetic Variation	[4]
Erectile dysfunction	DISD8MTH	Strong	Genetic Variation	[5]
IgA nephropathy	DISZ8MTK	Strong	Genetic Variation	[6]
Nasopharyngeal carcinoma	DISAOTQ0	Strong	Genetic Variation	[7]
Open-angle glaucoma	DISSZEE8	Strong	Genetic Variation	[8]
Plasma cell myeloma	DIS0DFZ0	Strong	Genetic Variation	[3]
Rheumatoid arthritis	DISTSB4J	Strong	Genetic Variation	[9]
Type-1 diabetes	DIS7HLUB	Strong	Genetic Variation	[10]
Acute myelogenous leukaemia	DISCSPTN	Limited	Genetic Variation	[11]
Ovarian neoplasm	DISEAFTY	Limited	Genetic Variation	[12]
Ovarian serous adenocarcinoma	DISSU72Z	Limited	Genetic Variation	[12]
Prostate cancer	DISF190Y	Limited	Biomarker	[13]
Prostate carcinoma	DISMJPLE	Limited	Biomarker	[13]
Small lymphocytic lymphoma	DIS30POX	Limited	Genetic Variation	[14]

3 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 Acyl-coenzyme A oxidase-like protein (ACOXL).	[15]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Acyl-coenzyme A oxidase-like protein (ACOXL).	[17]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Acyl-coenzyme A oxidase-like protein (ACOXL).	[19]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the methylation of Acyl-coenzyme A oxidase-like protein (ACOXL).	[16]
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Acyl-coenzyme A oxidase-like protein (ACOXL).	[18]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Acyl-coenzyme A oxidase-like protein (ACOXL).	[20]

References

• [1] Genome-wide meta-analysis in alopecia areata resolves HLA associations and reveals two new susceptibility loci.Nat Commun. 2015 Jan 22;6:5966. doi: 10.1038/ncomms6966.
• [2] New suggestive genetic loci and biological pathways for attention function in adult attention-deficit/hyperactivity disorder.Am J Med Genet B Neuropsychiatr Genet. 2015 Sep;168(6):459-470. doi: 10.1002/ajmg.b.32341. Epub 2015 Jul 14.
• [3] Genome-wide association analysis of chronic lymphocytic leukaemia, Hodgkin lymphoma and multiple myeloma identifies pleiotropic risk loci.Sci Rep. 2017 Jan 23;7:41071. doi: 10.1038/srep41071.
• [4] Genome-wide diet-gene interaction analyses for risk of colorectal cancer.PLoS Genet. 2014 Apr 17;10(4):e1004228. doi: 10.1371/journal.pgen.1004228. eCollection 2014 Apr.
• [5] Pilot genome-wide association search identifies potential loci for risk of erectile dysfunction in type 1 diabetes using the DCCT/EDIC study cohort.J Urol. 2012 Aug;188(2):514-20. doi: 10.1016/j.juro.2012.04.001. Epub 2012 Jun 15.
• [6] A genome-wide association study in Han Chinese identifies multiple susceptibility loci for IgA nephropathy.Nat Genet. 2011 Dec 25;44(2):178-82. doi: 10.1038/ng.1047.
• [7] A genome-wide association study of nasopharyngeal carcinoma identifies three new susceptibility loci.Nat Genet. 2010 Jul;42(7):599-603. doi: 10.1038/ng.601. Epub 2010 May 30.
• [8] A multiethnic genome-wide association study of primary open-angle glaucoma identifies novel risk loci.Nat Commun. 2018 Jun 11;9(1):2278. doi: 10.1038/s41467-018-04555-4.
• [9] Genetics of rheumatoid arthritis contributes to biology and drug discovery.Nature. 2014 Feb 20;506(7488):376-81. doi: 10.1038/nature12873. Epub 2013 Dec 25.
• [10] Fine mapping of type 1 diabetes susceptibility loci and evidence for colocalization of causal variants with lymphoid gene enhancers.Nat Genet. 2015 Apr;47(4):381-6. doi: 10.1038/ng.3245. Epub 2015 Mar 9.
• [11] 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.
• [12] Identification of 12 new susceptibility loci for different histotypes of epithelial ovarian cancer.Nat Genet. 2017 May;49(5):680-691. doi: 10.1038/ng.3826. Epub 2017 Mar 27.
• [13] Analysis of the Human Prostate-Specific Proteome Defined by Transcriptomics and Antibody-Based Profiling Identifies TMEM79 and ACOXL as Two Putative, Diagnostic Markers in Prostate Cancer.PLoS One. 2015 Aug 3;10(8):e0133449. doi: 10.1371/journal.pone.0133449. eCollection 2015.
• [14] Genome-wide association analysis implicates dysregulation of immunity genes in chronic lymphocytic leukaemia.Nat Commun. 2017 Feb 6;8:14175. doi: 10.1038/ncomms14175.
• [15] 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.
• [16] Integrative "-Omics" analysis in primary human hepatocytes unravels persistent mechanisms of cyclosporine A-induced cholestasis. Chem Res Toxicol. 2016 Dec 19;29(12):2164-2174.
• [17] Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
• [18] 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.
• [19] 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.
• [20] Air pollution and DNA methylation alterations in lung cancer: A systematic and comparative study. Oncotarget. 2017 Jan 3;8(1):1369-1391. doi: 10.18632/oncotarget.13622.