Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT6DVD2Q)

DOT Name Alpha-2-macroglobulin receptor-associated protein (LRPAP1)
Synonyms Alpha-2-MRAP; Low density lipoprotein receptor-related protein-associated protein 1; RAP
Gene Name LRPAP1
Related Disease
Congenital heart disease ( )
Nervous system disease ( )
Pancreatic ductal carcinoma ( )
Advanced cancer ( )
Androgen insensitivity syndrome ( )
Atrial septal defect ( )
Biliary tract cancer ( )
Bladder cancer ( )
Cardiovascular disease ( )
Chronic kidney disease ( )
Clear cell renal carcinoma ( )
Craniosynostosis ( )
Dementia ( )
Duchenne muscular dystrophy ( )
Epithelial ovarian cancer ( )
Gastric cancer ( )
Hepatocellular carcinoma ( )
High blood pressure ( )
Kidney neoplasm ( )
Lung cancer ( )
Lung carcinoma ( )
Membranous glomerulonephritis ( )
Metabolic disorder ( )
Metastatic malignant neoplasm ( )
Myocardial infarction ( )
Myopia ( )
Myopia 23, autosomal recessive ( )
Neoplasm ( )
Neuralgia ( )
Non-alcoholic steatohepatitis ( )
Osteoarthritis ( )
Ovarian cancer ( )
Ovarian neoplasm ( )
Renal cell carcinoma ( )
Rheumatoid arthritis ( )
Tetralogy of fallot ( )
Thyroid tumor ( )
Transitional cell carcinoma ( )
Ventricular septal defect ( )
Diabetic kidney disease ( )
Subarachnoid hemorrhage ( )
Anemia ( )
Kaposi sarcoma ( )
Parkinson disease ( )
Psychotic disorder ( )
Renal fibrosis ( )
Type-1/2 diabetes ( )
Venous thromboembolism ( )
UniProt ID
AMRP_HUMAN
3D Structure
Download
2D Sequence (FASTA)
Download
3D Structure (PDB)
Download
PDB ID
1LRE; 1NRE; 1OP1; 1OV2; 2FCW; 2FTU; 2FYL; 2P01; 2P03
Pfam ID
PF06401 ; PF06400
Sequence
MAPRRVRSFLRGLPALLLLLLFLGPWPAASHGGKYSREKNQPKPSPKRESGEEFRMEKLN
QLWEKAQRLHLPPVRLAELHADLKIQERDELAWKKLKLDGLDEDGEKEARLIRNLNVILA
KYGLDGKKDARQVTSNSLSGTQEDGLDDPRLEKLWHKAKTSGKFSGEELDKLWREFLHHK
EKVHEYNVLLETLSRTEEIHENVISPSDLSDIKGSVLHSRHTELKEKLRSINQGLDRLRR
VSHQGYSTEAEFEEPRVIDLWDLAQSANLTDKELEAFREELKHFEAKIEKHNHYQKQLEI
AHEKLRHAESVGDGERVSRSREKHALLEGRTKELGYTVKKHLQDLSGRISRARHNEL
Function Molecular chaperone for LDL receptor-related proteins that may regulate their ligand binding activity along the secretory pathway.
KEGG Pathway
Cholesterol metabolism (hsa04979 )

Molecular Interaction Atlas (MIA) of This DOT

48 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Congenital heart disease DISQBA23 Definitive Genetic Variation [1]
Nervous system disease DISJ7GGT Definitive Genetic Variation [1]
Pancreatic ductal carcinoma DIS26F9Q Definitive Biomarker [2]
Advanced cancer DISAT1Z9 Strong Biomarker [3]
Androgen insensitivity syndrome DISUZBBO Strong Biomarker [4]
Atrial septal defect DISJT76B Strong Genetic Variation [5]
Biliary tract cancer DISBNYQL Strong Biomarker [6]
Bladder cancer DISUHNM0 Strong Biomarker [7]
Cardiovascular disease DIS2IQDX Strong Genetic Variation [8]
Chronic kidney disease DISW82R7 Strong Biomarker [9]
Clear cell renal carcinoma DISBXRFJ Strong Biomarker [10]
Craniosynostosis DIS6J405 Strong Biomarker [11]
Dementia DISXL1WY Strong Genetic Variation [12]
Duchenne muscular dystrophy DISRQ3NV Strong Biomarker [13]
Epithelial ovarian cancer DIS56MH2 Strong Biomarker [14]
Gastric cancer DISXGOUK Strong Biomarker [7]
Hepatocellular carcinoma DIS0J828 Strong Biomarker [15]
High blood pressure DISY2OHH Strong Biomarker [16]
Kidney neoplasm DISBNZTN Strong Altered Expression [17]
Lung cancer DISCM4YA Strong Biomarker [18]
Lung carcinoma DISTR26C Strong Biomarker [18]
Membranous glomerulonephritis DISFSUKQ Strong Biomarker [19]
Metabolic disorder DIS71G5H Strong Biomarker [20]
Metastatic malignant neoplasm DIS86UK6 Strong Biomarker [21]
Myocardial infarction DIS655KI Strong Genetic Variation [22]
Myopia DISK5S60 Strong GermlineCausalMutation [23]
Myopia 23, autosomal recessive DISBT35O Strong Autosomal recessive [23]
Neoplasm DISZKGEW Strong Biomarker [24]
Neuralgia DISWO58J Strong Biomarker [25]
Non-alcoholic steatohepatitis DIST4788 Strong Biomarker [20]
Osteoarthritis DIS05URM Strong Biomarker [26]
Ovarian cancer DISZJHAP Strong Biomarker [14]
Ovarian neoplasm DISEAFTY Strong Biomarker [14]
Renal cell carcinoma DISQZ2X8 Strong Biomarker [27]
Rheumatoid arthritis DISTSB4J Strong Biomarker [26]
Tetralogy of fallot DISMHFNW Strong Biomarker [5]
Thyroid tumor DISLVKMD Strong Biomarker [28]
Transitional cell carcinoma DISWVVDR Strong Biomarker [29]
Ventricular septal defect DISICO41 Strong Genetic Variation [5]
Diabetic kidney disease DISJMWEY moderate Altered Expression [30]
Subarachnoid hemorrhage DISI7I8Y Disputed Biomarker [31]
Anemia DISTVL0C Limited Biomarker [32]
Kaposi sarcoma DISC1H1Z Limited Altered Expression [33]
Parkinson disease DISQVHKL Limited Genetic Variation [34]
Psychotic disorder DIS4UQOT Limited Biomarker [35]
Renal fibrosis DISMHI3I Limited Biomarker [36]
Type-1/2 diabetes DISIUHAP Limited Biomarker [36]
Venous thromboembolism DISUR7CR Limited Genetic Variation [37]
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⏷ Show the Full List of 48 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
1 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 Alpha-2-macroglobulin receptor-associated protein (LRPAP1). [38]
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8 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Tretinoin DM49DUI Approved Tretinoin increases the expression of Alpha-2-macroglobulin receptor-associated protein (LRPAP1). [39]
Acetaminophen DMUIE76 Approved Acetaminophen increases the expression of Alpha-2-macroglobulin receptor-associated protein (LRPAP1). [40]
Doxorubicin DMVP5YE Approved Doxorubicin increases the expression of Alpha-2-macroglobulin receptor-associated protein (LRPAP1). [41]
Cupric Sulfate DMP0NFQ Approved Cupric Sulfate decreases the expression of Alpha-2-macroglobulin receptor-associated protein (LRPAP1). [42]
Ivermectin DMDBX5F Approved Ivermectin decreases the expression of Alpha-2-macroglobulin receptor-associated protein (LRPAP1). [43]
Carbamazepine DMZOLBI Approved Carbamazepine affects the expression of Alpha-2-macroglobulin receptor-associated protein (LRPAP1). [44]
Diethylstilbestrol DMN3UXQ Approved Diethylstilbestrol decreases the expression of Alpha-2-macroglobulin receptor-associated protein (LRPAP1). [45]
Bisphenol A DM2ZLD7 Investigative Bisphenol A decreases the expression of Alpha-2-macroglobulin receptor-associated protein (LRPAP1). [46]
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⏷ Show the Full List of 8 Drug(s)

References

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3 Frequent overexpression, but not activation by point mutation, of ras genes in primary human gastric cancers.Gastroenterology. 1987 Dec;93(6):1339-45. doi: 10.1016/0016-5085(87)90264-2.
4 Pooling data from different populations: should there be regional differences in cerebral haemodynamics?.BMC Neurol. 2018 Sep 27;18(1):156. doi: 10.1186/s12883-018-1155-8.
5 Isolation of differentially expressed genes in human heart tissues.Biochim Biophys Acta. 2002 Dec 12;1588(3):241-6. doi: 10.1016/s0925-4439(02)00171-0.
6 Cholesterol metabolism gene polymorphisms and the risk of biliary tract cancers and stones: a population-based case-control study in Shanghai, China.Carcinogenesis. 2011 Jan;32(1):58-62. doi: 10.1093/carcin/bgq194. Epub 2010 Nov 9.
7 Histologic demonstration of antigens reactive with anti-p21 ras monoclonal antibody (RAP-5) in human stomach cancers.J Natl Cancer Inst. 1986 Aug;77(2):379-85.
8 Determination of alpha-2-MRAP gene polymorphisms in nephrolithiasis patients.Int J Biol Macromol. 2017 Dec;105(Pt 1):1324-1327. doi: 10.1016/j.ijbiomac.2017.07.167. Epub 2017 Jul 29.
9 The activin receptor is stimulated in the skeleton, vasculature, heart, and kidney during chronic kidney disease.Kidney Int. 2018 Jan;93(1):147-158. doi: 10.1016/j.kint.2017.06.016. Epub 2017 Aug 23.
10 Hepatitis A virus receptor blocks cell differentiation and is overexpressed in clear cell renal cell carcinoma.Kidney Int. 2004 May;65(5):1761-73. doi: 10.1111/j.1523-1755.2004.00601.x.
11 The role of ICP overnight monitoring (ONM) in children with suspected craniostenosis.Childs Nerv Syst. 2020 Jan;36(1):87-94. doi: 10.1007/s00381-019-04288-9. Epub 2019 Jul 4.
12 LRP-associated protein gene (LRPAP1) and susceptibility to degenerative dementia.Genes Brain Behav. 2008 Nov;7(8):943-50. doi: 10.1111/j.1601-183X.2008.00436.x. Epub 2008 Aug 21.
13 Postnatal Hyperplasic Effects of ActRIIB Blockade in a Severely Dystrophic Muscle.J Cell Physiol. 2017 Jul;232(7):1774-1793. doi: 10.1002/jcp.25694. Epub 2017 Feb 16.
14 Immunohistochemical detection of the ras oncogene product p21 in advanced ovarian cancer. Lack of correlation with clinical outcome.Arch Pathol Lab Med. 1988 Feb;112(2):151-4.
15 Immunohistochemical detection of ras oncogene p21 product in liver cirrhosis and hepatocellular carcinoma.Am J Gastroenterol. 1987 Jun;82(6):512-8.
16 Intracranial pressure variability: relation to clinical outcome, intracranial pressure-volume index, cerebrovascular reactivity and blood pressure variability.J Clin Monit Comput. 2020 Aug;34(4):733-741. doi: 10.1007/s10877-019-00387-9. Epub 2019 Sep 19.
17 Quantitation of enhanced expression of ras-oncogene product (p21) in childhood renal tumours.Anticancer Res. 1991 Jul-Aug;11(4):1657-62.
18 Stromal LRP1 in lung adenocarcinoma predicts clinical outcome.Clin Cancer Res. 2011 Apr 15;17(8):2426-33. doi: 10.1158/1078-0432.CCR-10-2385. Epub 2011 Feb 15.
19 Role of receptor-associated 39/45 kD protein in active Heymann nephritis.Kidney Int. 1995 Feb;47(2):432-41. doi: 10.1038/ki.1995.56.
20 Rapeseed Protein-Derived Antioxidant Peptide RAP Ameliorates Nonalcoholic Steatohepatitis and Related Metabolic Disorders in Mice.Mol Pharm. 2019 Jan 7;16(1):371-381. doi: 10.1021/acs.molpharmaceut.8b01030. Epub 2018 Dec 21.
21 Validation of RNA arbitrarily primed PCR probes hybridized to glass cDNA microarrays: application to the analysis of limited samples.Clin Chem. 2005 Jan;51(1):93-101. doi: 10.1373/clinchem.2004.036236.
22 Association of a polymorphism of BTN2A1 with myocardial infarction in East Asian populations.Atherosclerosis. 2011 Mar;215(1):145-52. doi: 10.1016/j.atherosclerosis.2010.12.005. Epub 2010 Dec 15.
23 Mutations in LRPAP1 are associated with severe myopia in humans. Am J Hum Genet. 2013 Aug 8;93(2):313-20. doi: 10.1016/j.ajhg.2013.06.002. Epub 2013 Jul 3.
24 RAS-related GTPases DIRAS1 and DIRAS2 induce autophagic cancer cell death and are required for autophagy in murine ovarian cancer cells.Autophagy. 2018;14(4):637-653. doi: 10.1080/15548627.2018.1427022. Epub 2018 Mar 21.
25 Neuropathic pain inhibitor, RAP-103, is a potent inhibitor of microglial CCL1/CCR8.Neurochem Int. 2018 Oct;119:184-189. doi: 10.1016/j.neuint.2017.12.005. Epub 2017 Dec 14.
26 Evaluation of differentially expressed genes by a combination of cDNA array and RAP-PCR using the AtlasImage 2.0 software.J Autoimmun. 2003 Sep;21(2):161-6. doi: 10.1016/s0896-8411(03)00088-x.
27 Increased glyceraldehyde-3-phosphate dehydrogenase expression in renal cell carcinoma identified by RNA-based, arbitrarily primed polymerase chain reaction.Cancer. 2000 Jul 1;89(1):152-64.
28 RAP1GAP inhibits cytoskeletal remodeling and motility in thyroid cancer cells.Endocr Relat Cancer. 2012 Jul 22;19(4):575-88. doi: 10.1530/ERC-12-0086. Print 2012 Aug.
29 Immunocytochemical demonstration of p21ras in normal and transitional cell carcinoma urothelium.J Pathol. 1988 Sep;156(1):59-65. doi: 10.1002/path.1711560112.
30 Huangkui capsule alleviates renal tubular epithelial-mesenchymal transition in diabetic nephropathy via inhibiting NLRP3 inflammasome activation and TLR4/NF-B signaling.Phytomedicine. 2019 Apr;57:203-214. doi: 10.1016/j.phymed.2018.12.021. Epub 2018 Dec 17.
31 Impaired cerebral compensatory reserve is associated with admission imaging characteristics of diffuse insult in traumatic brain injury.Acta Neurochir (Wien). 2018 Dec;160(12):2277-2287. doi: 10.1007/s00701-018-3681-y. Epub 2018 Sep 24.
32 Modified activin receptor IIB ligand trap mitigates ineffective erythropoiesis and disease complications in murine -thalassemia.Blood. 2014 Jun 19;123(25):3864-72. doi: 10.1182/blood-2013-06-511238. Epub 2014 May 2.
33 Role of CCAAT/enhancer-binding protein alpha (C/EBPalpha) in activation of the Kaposi's sarcoma-associated herpesvirus (KSHV) lytic-cycle replication-associated protein (RAP) promoter in cooperation with the KSHV replication and transcription activator (RTA) and RAP.J Virol. 2003 Jan;77(1):600-23. doi: 10.1128/jvi.77.1.600-623.2003.
34 APOE and LRPAP1 gene polymorphism and risk of Parkinson's disease.Neurol Sci. 2014 Jul;35(7):1075-81. doi: 10.1007/s10072-014-1651-6. Epub 2014 Feb 7.
35 The Role of Cognition and Social Functioning as Predictors in the Transition to Psychosis for Youth With Attenuated Psychotic Symptoms.Schizophr Bull. 2017 Jan;43(1):57-63. doi: 10.1093/schbul/sbw152. Epub 2016 Oct 25.
36 Rapeseed protein-derived antioxidant peptide RAP alleviates renal fibrosis through MAPK/NF-B signaling pathways in diabetic nephropathy.Drug Des Devel Ther. 2018 May 15;12:1255-1268. doi: 10.2147/DDDT.S162288. eCollection 2018.
37 Low-density lipoprotein receptor-related protein polymorphisms in patients with elevated factor VIII coagulant activity and venous thrombosis.Blood Coagul Fibrinolysis. 2005 Oct;16(7):465-8. doi: 10.1097/01.mbc.0000178831.45049.aa.
38 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.
39 Systems analysis of transcriptome and proteome in retinoic acid/arsenic trioxide-induced cell differentiation/apoptosis of promyelocytic leukemia. Proc Natl Acad Sci U S A. 2005 May 24;102(21):7653-8.
40 Predictive toxicology using systemic biology and liver microfluidic "on chip" approaches: application to acetaminophen injury. Toxicol Appl Pharmacol. 2012 Mar 15;259(3):270-80.
41 Identification of novel biomarkers for doxorubicin-induced toxicity in human cardiomyocytes derived from pluripotent stem cells. Toxicology. 2015 Feb 3;328:102-11. doi: 10.1016/j.tox.2014.12.018. Epub 2014 Dec 18.
42 Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
43 Quantitative proteomics reveals a broad-spectrum antiviral property of ivermectin, benefiting for COVID-19 treatment. J Cell Physiol. 2021 Apr;236(4):2959-2975. doi: 10.1002/jcp.30055. Epub 2020 Sep 22.
44 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.
45 Identification of biomarkers and outcomes of endocrine disruption in human ovarian cortex using In Vitro Models. Toxicology. 2023 Feb;485:153425. doi: 10.1016/j.tox.2023.153425. Epub 2023 Jan 5.
46 Alternatives for the worse: Molecular insights into adverse effects of bisphenol a and substitutes during human adipocyte differentiation. Environ Int. 2021 Nov;156:106730. doi: 10.1016/j.envint.2021.106730. Epub 2021 Jun 27.