Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTRT1UJ7)

DOT Name Low-density lipoprotein receptor-related protein 12 (LRP12)
Synonyms LDLR-related protein 12; LRP-12; Suppressor of tumorigenicity 7 protein
Gene Name LRP12
Related Disease
Adult lymphoma ( )
B-cell neoplasm ( )
Lung adenocarcinoma ( )
Lymphoma ( )
Non-insulin dependent diabetes ( )
Non-small-cell lung cancer ( )
Oculopharyngeal muscular dystrophy ( )
Oculopharyngodistal myopathy 1 ( )
Pediatric lymphoma ( )
UniProt ID
LRP12_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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Pfam ID
PF00431 ; PF00057
Sequence
MACRWSTKESPRWRSALLLLFLAGVYGNGALAEHSENVHISGVSTACGETPEQIRAPSGI
ITSPGWPSEYPAKINCSWFIRANPGEIITISFQDFDIQGSRRCNLDWLTIETYKNIESYR
ACGSTIPPPYISSQDHIWIRFHSDDNISRKGFRLAYFSGKSEEPNCACDQFRCGNGKCIP
EAWKCNNMDECGDSSDEEICAKEANPPTAAAFQPCAYNQFQCLSRFTKVYTCLPESLKCD
GNIDCLDLGDEIDCDVPTCGQWLKYFYGTFNSPNYPDFYPPGSNCTWLIDTGDHRKVILR
FTDFKLDGTGYGDYVKIYDGLEENPHKLLRVLTAFDSHAPLTVVSSSGQIRVHFCADKVN
AARGFNATYQVDGFCLPWEIPCGGNWGCYTEQQRCDGYWHCPNGRDETNCTMCQKEEFPC
SRNGVCYPRSDRCNYQNHCPNGSDEKNCFFCQPGNFHCKNNRCVFESWVCDSQDDCGDGS
DEENCPVIVPTRVITAAVIGSLICGLLLVIALGCTCKLYSLRMFERRSFETQLSRVEAEL
LRREAPPSYGQLIAQGLIPPVEDFPVCSPNQASVLENLRLAVRSQLGFTSVRLPMAGRSS
NIWNRIFNFARSRHSGSLALVSADGDEVVPSQSTSREPERNHTHRSLFSVESDDTDTENE
RRDMAGASGGVAAPLPQKVPPTTAVEATVGACASSSTQSTRGGHADNGRDVTSVEPPSVS
PARHQLTSALSRMTQGLRWVRFTLGRSSSLSQNQSPLRQLDNGVSGREDDDDVEMLIPIS
DGSSDFDVNDCSRPLLDLASDQGQGLRQPYNATNPGVRPSNRDGPCERCGIVHTAQIPDT
CLEVTLKNETSDDEALLLC
Function Probable receptor, which may be involved in the internalization of lipophilic molecules and/or signal transduction. May act as a tumor suppressor.
Tissue Specificity
Widely expressed in heart, skeletal muscle, brain, lung, placenta and pancreas, but not in tissues consisting of a large number of epithelial cells, such as liver and kidney. Expressed at very low levels in a number of tumor-derived cell lines.
Reactome Pathway
Retinoid metabolism and transport (R-HSA-975634 )

Molecular Interaction Atlas (MIA) of This DOT

9 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Adult lymphoma DISK8IZR Strong Posttranslational Modification [1]
B-cell neoplasm DISVY326 Strong Posttranslational Modification [1]
Lung adenocarcinoma DISD51WR Strong Posttranslational Modification [2]
Lymphoma DISN6V4S Strong Posttranslational Modification [1]
Non-insulin dependent diabetes DISK1O5Z Strong Genetic Variation [3]
Non-small-cell lung cancer DIS5Y6R9 Strong Posttranslational Modification [2]
Oculopharyngeal muscular dystrophy DISF4G07 Strong Biomarker [4]
Oculopharyngodistal myopathy 1 DISVM1IO Strong Autosomal dominant [5]
Pediatric lymphoma DIS51BK2 Strong Posttranslational Modification [1]
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⏷ Show the Full List of 9 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 decreases the methylation of Low-density lipoprotein receptor-related protein 12 (LRP12). [6]
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14 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Ciclosporin DMAZJFX Approved Ciclosporin increases the expression of Low-density lipoprotein receptor-related protein 12 (LRP12). [7]
Acetaminophen DMUIE76 Approved Acetaminophen increases the expression of Low-density lipoprotein receptor-related protein 12 (LRP12). [8]
Doxorubicin DMVP5YE Approved Doxorubicin decreases the expression of Low-density lipoprotein receptor-related protein 12 (LRP12). [9]
Cupric Sulfate DMP0NFQ Approved Cupric Sulfate increases the expression of Low-density lipoprotein receptor-related protein 12 (LRP12). [10]
Cisplatin DMRHGI9 Approved Cisplatin increases the expression of Low-density lipoprotein receptor-related protein 12 (LRP12). [11]
Estradiol DMUNTE3 Approved Estradiol increases the expression of Low-density lipoprotein receptor-related protein 12 (LRP12). [12]
Marinol DM70IK5 Approved Marinol decreases the expression of Low-density lipoprotein receptor-related protein 12 (LRP12). [13]
Panobinostat DM58WKG Approved Panobinostat decreases the expression of Low-density lipoprotein receptor-related protein 12 (LRP12). [14]
Urethane DM7NSI0 Phase 4 Urethane increases the expression of Low-density lipoprotein receptor-related protein 12 (LRP12). [15]
PMID28460551-Compound-2 DM4DOUB Patented PMID28460551-Compound-2 increases the expression of Low-density lipoprotein receptor-related protein 12 (LRP12). [16]
Torcetrapib DMDHYM7 Discontinued in Phase 2 Torcetrapib increases the expression of Low-density lipoprotein receptor-related protein 12 (LRP12). [17]
Trichostatin A DM9C8NX Investigative Trichostatin A decreases the expression of Low-density lipoprotein receptor-related protein 12 (LRP12). [18]
Sulforaphane DMQY3L0 Investigative Sulforaphane increases the expression of Low-density lipoprotein receptor-related protein 12 (LRP12). [19]
cinnamaldehyde DMZDUXG Investigative cinnamaldehyde increases the expression of Low-density lipoprotein receptor-related protein 12 (LRP12). [20]
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⏷ Show the Full List of 14 Drug(s)

References

1 A gene panel, including LRP12, is frequently hypermethylated in major types of B-cell lymphoma.PLoS One. 2014 Sep 16;9(9):e104249. doi: 10.1371/journal.pone.0104249. eCollection 2014.
2 Epigenomic profiling of non-small cell lung cancer xenografts uncover LRP12 DNA methylation as predictive biomarker for carboplatin resistance.Genome Med. 2018 Jul 20;10(1):55. doi: 10.1186/s13073-018-0562-1.
3 An Expanded Genome-Wide Association Study of Type 2 Diabetes in Europeans.Diabetes. 2017 Nov;66(11):2888-2902. doi: 10.2337/db16-1253. Epub 2017 May 31.
4 Noncoding CGG repeat expansions in neuronal intranuclear inclusion disease, oculopharyngodistal myopathy and an overlapping disease.Nat Genet. 2019 Aug;51(8):1222-1232. doi: 10.1038/s41588-019-0458-z. Epub 2019 Jul 22.
5 Classification of Genes: Standardized Clinical Validity Assessment of Gene-Disease Associations Aids Diagnostic Exome Analysis and Reclassifications. Hum Mutat. 2017 May;38(5):600-608. doi: 10.1002/humu.23183. Epub 2017 Feb 13.
6 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.
7 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.
8 Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
9 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.
10 Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
11 Low doses of cisplatin induce gene alterations, cell cycle arrest, and apoptosis in human promyelocytic leukemia cells. Biomark Insights. 2016 Aug 24;11:113-21.
12 17-Estradiol Activates HSF1 via MAPK Signaling in ER-Positive Breast Cancer Cells. Cancers (Basel). 2019 Oct 11;11(10):1533. doi: 10.3390/cancers11101533.
13 THC exposure of human iPSC neurons impacts genes associated with neuropsychiatric disorders. Transl Psychiatry. 2018 Apr 25;8(1):89. doi: 10.1038/s41398-018-0137-3.
14 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.
15 Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
16 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.
17 Clarifying off-target effects for torcetrapib using network pharmacology and reverse docking approach. BMC Syst Biol. 2012 Dec 10;6:152.
18 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.
19 Sulforaphane-induced apoptosis in human leukemia HL-60 cells through extrinsic and intrinsic signal pathways and altering associated genes expression assayed by cDNA microarray. Environ Toxicol. 2017 Jan;32(1):311-328.
20 Comparative DNA microarray analysis of human monocyte derived dendritic cells and MUTZ-3 cells exposed to the moderate skin sensitizer cinnamaldehyde. Toxicol Appl Pharmacol. 2009 Sep 15;239(3):273-83.