Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTI3FQQC)

• DOT Name: Apolipoprotein M (APOM)
• Synonyms: Apo-M; ApoM; Protein G3a
• Gene Name: APOM
• Related Disease:
  Acute coronary syndrome
  Advanced cancer
  Alzheimer disease
  Arteriosclerosis
  Atherosclerosis
  Chronic kidney disease
  Colorectal carcinoma
  Coronary atherosclerosis
  Diabetic kidney disease
  Fatty liver disease
  Hepatitis B virus infection
  Hepatitis C virus infection
  Hyperlipidemia
  IgA nephropathy
  Lung adenocarcinoma
  Lung cancer
  Lupus
  Maturity-onset diabetes of the young
  Nasopharyngeal carcinoma
  Neoplasm
  Nephropathy
  Nephrotic syndrome
  Non-small-cell lung cancer
  Obesity
  Obstructive sleep apnea
  Rheumatoid arthritis
  Sarcoidosis
  Type-1 diabetes
  Vascular disease
  Chronic obstructive pulmonary disease
  Maturity-onset diabetes of the young type 3
  Pulmonary emphysema
  Systemic lupus erythematosus
  Lung carcinoma
  Lung squamous cell carcinoma
  Metabolic disorder
  Myocardial infarction
  Type-1/2 diabetes
• UniProt ID: APOM_HUMAN
• PDB ID: 2WEW; 2WEX; 2YG2
• Pfam ID: PF11032
• Sequence:
  MFHQIWAALLYFYGIILNSIYQCPEHSQLTTLGVDGKEFPEVHLGQWYFIAGAAPTKEEL
  ATFDPVDNIVFNMAAGSAPMQLHLRATIRMKDGLCVPRKWIYHLTEGSTDLRTEGRPDMK
  TELFSSSCPGGIMLNETGQGYQRFLLYNRSPHPPEKCVEEFKSLTSCLDSKAFLLTPRNQ
  EACELSNN
• Function: Probably involved in lipid transport. Can bind sphingosine-1-phosphate, myristic acid, palmitic acid and stearic acid, retinol, all-trans-retinoic acid and 9-cis-retinoic acid.
• Tissue Specificity: Plasma protein. Expressed in liver and kidney.
• Reactome Pathway: Retinoid metabolism and transport (R-HSA-975634)

Molecular Interaction Atlas (MIA) of This DOT

38 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Acute coronary syndrome	DIS7DYEW	Strong	Biomarker	[1]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[2]
Alzheimer disease	DISF8S70	Strong	Biomarker	[3]
Arteriosclerosis	DISK5QGC	Strong	Biomarker	[4]
Atherosclerosis	DISMN9J3	Strong	Biomarker	[4]
Chronic kidney disease	DISW82R7	Strong	Biomarker	[5]
Colorectal carcinoma	DIS5PYL0	Strong	Biomarker	[2]
Coronary atherosclerosis	DISKNDYU	Strong	Genetic Variation	[6]
Diabetic kidney disease	DISJMWEY	Strong	Biomarker	[7]
Fatty liver disease	DIS485QZ	Strong	Biomarker	[8]
Hepatitis B virus infection	DISLQ2XY	Strong	Altered Expression	[9]
Hepatitis C virus infection	DISQ0M8R	Strong	Biomarker	[10]
Hyperlipidemia	DIS61J3S	Strong	Altered Expression	[11]
IgA nephropathy	DISZ8MTK	Strong	Biomarker	[12]
Lung adenocarcinoma	DISD51WR	Strong	Genetic Variation	[13]
Lung cancer	DISCM4YA	Strong	Biomarker	[14]
Lupus	DISOKJWA	Strong	Altered Expression	[15]
Maturity-onset diabetes of the young	DISG75M5	Strong	Biomarker	[16]
Nasopharyngeal carcinoma	DISAOTQ0	Strong	Genetic Variation	[17]
Neoplasm	DISZKGEW	Strong	Biomarker	[18]
Nephropathy	DISXWP4P	Strong	Biomarker	[12]
Nephrotic syndrome	DISSPSC2	Strong	Altered Expression	[11]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Altered Expression	[14]
Obesity	DIS47Y1K	Strong	Altered Expression	[19]
Obstructive sleep apnea	DIS0SVD1	Strong	Biomarker	[20]
Rheumatoid arthritis	DISTSB4J	Strong	Genetic Variation	[21]
Sarcoidosis	DISE5B8Z	Strong	Genetic Variation	[22]
Type-1 diabetes	DIS7HLUB	Strong	Biomarker	[23]
Vascular disease	DISVS67S	Strong	Altered Expression	[1]
Chronic obstructive pulmonary disease	DISQCIRF	moderate	Genetic Variation	[24]
Maturity-onset diabetes of the young type 3	DISMFSO5	moderate	Altered Expression	[25]
Pulmonary emphysema	DIS5M7HZ	moderate	Genetic Variation	[26]
Systemic lupus erythematosus	DISI1SZ7	Disputed	Biomarker	[27]
Lung carcinoma	DISTR26C	Limited	Genetic Variation	[28]
Lung squamous cell carcinoma	DISXPIBD	Limited	Genetic Variation	[28]
Metabolic disorder	DIS71G5H	Limited	Biomarker	[19]
Myocardial infarction	DIS655KI	Limited	Altered Expression	[29]
Type-1/2 diabetes	DISIUHAP	Limited	Biomarker	[30]

11 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 Apolipoprotein M (APOM).	[31]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Apolipoprotein M (APOM).	[32]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Apolipoprotein M (APOM).	[33]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Apolipoprotein M (APOM).	[34]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Apolipoprotein M (APOM).	[35]
Simvastatin	DM30SGU	Approved	Simvastatin decreases the expression of Apolipoprotein M (APOM).	[36]
Chenodiol	DMQ8JIK	Approved	Chenodiol decreases the expression of Apolipoprotein M (APOM).	[37]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol increases the expression of Apolipoprotein M (APOM).	[38]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Apolipoprotein M (APOM).	[39]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Apolipoprotein M (APOM).	[40]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Apolipoprotein M (APOM).	[41]

References

• [1] Vehicle-dependent Effects of Sphingosine 1-phosphate on Plasminogen Activator Inhibitor-1 Expression.J Atheroscler Thromb. 2017 Sep 1;24(9):954-969. doi: 10.5551/jat.37663. Epub 2017 Mar 17.
• [2] Apolipoprotein M increases the expression of vitamin D receptor mRNA in colorectal cancer cells detected with duplex fluorescence reverse transcription-quantitative polymerase chain reaction.Mol Med Rep. 2017 Aug;16(2):1167-1172. doi: 10.3892/mmr.2017.6716. Epub 2017 Jun 7.
• [3] Exclusion of CYP46 and APOM as candidate genes for Alzheimer's disease in a French population.Neurosci Lett. 2004 Jun 10;363(2):139-43. doi: 10.1016/j.neulet.2004.03.066.
• [4] ApoM-S1P Modulates Ox-LDL-Induced Inflammation Through the PI3K/Akt Signaling Pathway in HUVECs.Inflammation. 2019 Apr;42(2):606-617. doi: 10.1007/s10753-018-0918-0.
• [5] Apolipoprotein M in patients with chronic kidney disease.Atherosclerosis. 2018 Aug;275:304-311. doi: 10.1016/j.atherosclerosis.2018.06.815. Epub 2018 Jun 15.
• [6] Correlation analysis between ApoM gene-promoter polymorphisms and coronary heart disease.Cardiovasc J Afr. 2016 Jul/Aug;27(4):228-237. doi: 10.5830/CVJA-2016-001.
• [7] ApoM/HDL-C and apoM/apoA-I ratios are indicators of diabetic nephropathy in healthy controls and type 2 diabetes mellitus.Clin Chim Acta. 2017 Mar;466:31-37. doi: 10.1016/j.cca.2017.01.006. Epub 2017 Jan 7.
• [8] Autophagy dysregulation caused by ApoM deficiency plays an important role in liver lipid metabolic disorder.Biochem Biophys Res Commun. 2018 Jan 22;495(4):2643-2648. doi: 10.1016/j.bbrc.2017.12.148. Epub 2017 Dec 27.
• [9] Enchanced levels of apolipoprotein M during HBV infection feedback suppresses HBV replication.Lipids Health Dis. 2011 Aug 29;10:154. doi: 10.1186/1476-511X-10-154.
• [10] Antiviral activity of boceprevir monotherapy in treatment-naive subjects with chronic hepatitis C genotype 2/3.J Hepatol. 2013 Jul;59(1):31-7. doi: 10.1016/j.jhep.2013.02.018. Epub 2013 Feb 27.
• [11] Characteristics of lipid metabolism including serum apolipoprotein M levels in patients with primary nephrotic syndrome.Lipids Health Dis. 2017 Sep 6;16(1):167. doi: 10.1186/s12944-017-0556-9.
• [12] Apolipoprotein M/sphingosine-1-phosphate: novel effects on lipids, inflammation and kidney biology.Curr Opin Lipidol. 2019 Jun;30(3):212-217. doi: 10.1097/MOL.0000000000000606.
• [13] A genome-wide association study of lung cancer identifies a region of chromosome 5p15 associated with risk for adenocarcinoma.Am J Hum Genet. 2009 Nov;85(5):679-91. doi: 10.1016/j.ajhg.2009.09.012. Epub 2009 Oct 15.
• [14] Apolipoprotein M promotes proliferation and invasion in non-small cell lung cancers via upregulating S1PR1 and activating the ERK1/2 and PI3K/AKT signaling pathways.Biochem Biophys Res Commun. 2018 Jun 22;501(2):520-526. doi: 10.1016/j.bbrc.2018.05.029.
• [15] Low apolipoprotein M serum levels correlate with Systemic lupus erythematosus disease activity and apolipoprotein M gene polymorphisms with Lupus.Lipids Health Dis. 2017 May 5;16(1):88. doi: 10.1186/s12944-017-0476-8.
• [16] Apolipoprotein M can discriminate HNF1A-MODY from Type 1 diabetes.Diabet Med. 2013 Feb;30(2):246-50. doi: 10.1111/dme.12066.
• [17] 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.
• [18] Apolipoprotein M could inhibit growth and metastasis of SMMC7721 cells via vitamin D receptor signaling.Cancer Manag Res. 2019 Apr 30;11:3691-3701. doi: 10.2147/CMAR.S202799. eCollection 2019.
• [19] Apolipoprotein M: new connections with diet, adipose tissue and metabolic syndrome.Curr Opin Lipidol. 2020 Feb;31(1):8-14. doi: 10.1097/MOL.0000000000000654.
• [20] Serum high-density lipoprotein correlates with serum apolipoprotein M and A5 in obstructive sleep apnea hypopnea syndrome.Sleep Breath. 2017 Mar;21(1):37-44. doi: 10.1007/s11325-016-1357-5. Epub 2016 May 21.
• [21] Apolipoprotein m (APOM) levels and APOM rs805297 G/T polymorphism are associated with increased risk of rheumatoid arthritis.Joint Bone Spine. 2014 Jan;81(1):32-6. doi: 10.1016/j.jbspin.2013.03.017. Epub 2013 May 6.
• [22] High-Density Genetic Mapping Identifies New Susceptibility Variants in Sarcoidosis Phenotypes and Shows Genomic-driven Phenotypic Differences.Am J Respir Crit Care Med. 2016 May 1;193(9):1008-22. doi: 10.1164/rccm.201507-1372OC.
• [23] A Shift in ApoM/S1P Between HDL-Particles in Women With Type 1 Diabetes Mellitus Is Associated With Impaired Anti-Inflammatory Effects of the ApoM/S1P Complex.Arterioscler Thromb Vasc Biol. 2017 Jun;37(6):1194-1205. doi: 10.1161/ATVBAHA.117.309275. Epub 2017 Apr 6.
• [24] Apolipoprotein M gene single nucleotide polymorphisms discovery in patients with chronic obstructive pulmonary disease and determined by the base-quenched probe technique.Gene. 2017 Dec 30;637:9-13. doi: 10.1016/j.gene.2017.09.029. Epub 2017 Sep 18.
• [25] Regulation of apolipoprotein M gene expression by MODY3 gene hepatocyte nuclear factor-1alpha: haploinsufficiency is associated with reduced serum apolipoprotein M levels.Diabetes. 2003 Dec;52(12):2989-95. doi: 10.2337/diabetes.52.12.2989.
• [26] APOM and high-density lipoprotein cholesterol are associated with lung function and per cent emphysema.Eur Respir J. 2014 Apr;43(4):1003-17. doi: 10.1183/09031936.00147612. Epub 2013 Jul 30.
• [27] Low plasma concentrations of apolipoprotein M are associated with disease activity and endothelial dysfunction in systemic lupus erythematosus.Arthritis Res Ther. 2019 May 2;21(1):110. doi: 10.1186/s13075-019-1890-2.
• [28] Large-scale association analysis identifies new lung cancer susceptibility loci and heterogeneity in genetic susceptibility across histological subtypes.Nat Genet. 2017 Jul;49(7):1126-1132. doi: 10.1038/ng.3892. Epub 2017 Jun 12.
• [29] A single-nucleotide polymorphism C-724 /del in the proter region of the apolipoprotein M gene is associated with type 2 diabetes mellitus.Lipids Health Dis. 2016 Aug 30;15(1):142. doi: 10.1186/s12944-016-0307-3.
• [30] Apolipoprotein M: a novel adipokine decreasing with obesity and upregulated by calorie restriction.Am J Clin Nutr. 2019 Jun 1;109(6):1499-1510. doi: 10.1093/ajcn/nqy331.
• [31] 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.
• [32] 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.
• [33] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [34] 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.
• [35] 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.
• [36] Effects of simvastatin on apolipoprotein M in vivo and in vitro. Lipids Health Dis. 2011 Jul 5;10:112. doi: 10.1186/1476-511X-10-112.
• [37] Chenodeoxycholic acid significantly impacts the expression of miRNAs and genes involved in lipid, bile acid and drug metabolism in human hepatocytes. Life Sci. 2016 Jul 1;156:47-56.
• [38] Selenium and vitamin E: cell type- and intervention-specific tissue effects in prostate cancer. J Natl Cancer Inst. 2009 Mar 4;101(5):306-20.
• [39] 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.
• [40] Cell-based two-dimensional morphological assessment system to predict cancer drug-induced cardiotoxicity using human induced pluripotent stem cell-derived cardiomyocytes. Toxicol Appl Pharmacol. 2019 Nov 15;383:114761. doi: 10.1016/j.taap.2019.114761. Epub 2019 Sep 15.
• [41] Isobaric tags for relative and absolute quantitation-based proteomics analysis of the effect of ginger oil on bisphenol A-induced breast cancer cell proliferation. Oncol Lett. 2021 Feb;21(2):101. doi: 10.3892/ol.2020.12362. Epub 2020 Dec 8.