Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT6TU8SE)

• DOT Name: Lipoma-preferred partner (LPP)
• Synonyms: LIM domain-containing preferred translocation partner in lipoma
• Gene Name: LPP
• Related Disease:
  Chronic renal failure
  Cutaneous squamous cell carcinoma
  Acute myelogenous leukaemia
  Advanced cancer
  Alopecia areata
  Anxiety disorder
  Arteriosclerosis
  Atherosclerosis
  Autoimmune disease
  Autoimmune disease, susceptibility to, 6
  Autoimmune thyroid disease
  B-cell lymphoma
  Breast cancer
  Breast carcinoma
  Classic Hodgkin lymphoma
  Colorectal carcinoma
  Depression
  Epithelial ovarian cancer
  Graves disease
  Hamartoma
  Hashimoto thyroiditis
  Hypothyroidism
  Lung adenocarcinoma
  Lung cancer
  Lung carcinoma
  Multiple sclerosis
  Neoplasm of mature B-cells
  Open-angle glaucoma
  Ovarian cancer
  Ovarian neoplasm
  Post-traumatic stress disorder
  Schizophrenia
  Small lymphocytic lymphoma
  Squamous cell carcinoma
  STAT3-related early-onset multisystem autoimmune disease
  Vitiligo
  Allergic rhinitis
  Asthma
  Immune system disorder
  Neoplasm
  Basal cell carcinoma
  Basal cell neoplasm
  Crohn disease
  Inflammatory bowel disease
  Non-insulin dependent diabetes
  Systemic lupus erythematosus
• UniProt ID: LPP_HUMAN
• Pfam ID: PF00412
• Sequence:
  MSHPSWLPPKSTGEPLGHVPARMETTHSFGNPSISVSTQQPPKKFAPVVAPKPKYNPYKQ
  PGGEGDFLPPPPPPLDDSSALPSISGNFPPPPPLDEEAFKVQGNPGGKTLEERRSSLDAE
  IDSLTSILADLECSSPYKPRPPQSSTGSTASPPVSTPVTGHKRMVIPNQPPLTATKKSTL
  KPQPAPQAGPIPVAPIGTLKPQPQPVPASYTTASTSSRPTFNVQVKSAQPSPHYMAAPSS
  GQIYGSGPQGYNTQPVPVSGQCPPPSTRGGMDYAYIPPPGLQPEPGYGYAPNQGRYYEGY
  YAAGPGYGGRNDSDPTYGQQGHPNTWKREPGYTPPGAGNQNPPGMYPVTGPKKTYITDPV
  SAPCAPPLQPKGGHSGQLGPSSVAPSFRPEDELEHLTKKMLYDMENPPADEYFGRCARCG
  ENVVGEGTGCTAMDQVFHVDCFTCIICNNKLRGQPFYAVEKKAYCEPCYINTLEQCNVCS
  KPIMERILRATGKAYHPHCFTCVMCHRSLDGIPFTVDAGGLIHCIEDFHKKFAPRCSVCK
  EPIMPAPGQEETVRIVALDRDFHVHCYRCEDCGGLLSEGDNQGCYPLDGHILCKTCNSAR
  IRVLTAKASTDL
• Function: May play a structural role at sites of cell adhesion in maintaining cell shape and motility. In addition to these structural functions, it may also be implicated in signaling events and activation of gene transcription. May be involved in signal transduction from cell adhesion sites to the nucleus allowing successful integration of signals arising from soluble factors and cell-cell adhesion sites. Also suggested to serve as a scaffold protein upon which distinct protein complexes are assembled in the cytoplasm and in the nucleus.
• Tissue Specificity: Expressed in a wide variety of tissues but no or very low expression in brain and peripheral leukocytes.

Molecular Interaction Atlas (MIA) of This DOT

46 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Chronic renal failure	DISGG7K6	Definitive	Genetic Variation	[1]
Cutaneous squamous cell carcinoma	DIS3LXUG	Definitive	Genetic Variation	[2]
Acute myelogenous leukaemia	DISCSPTN	Strong	Biomarker	[3]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[4]
Alopecia areata	DIS0XXBJ	Strong	Genetic Variation	[5]
Anxiety disorder	DISBI2BT	Strong	Biomarker	[6]
Arteriosclerosis	DISK5QGC	Strong	Biomarker	[7]
Atherosclerosis	DISMN9J3	Strong	Biomarker	[7]
Autoimmune disease	DISORMTM	Strong	Genetic Variation	[8]
Autoimmune disease, susceptibility to, 6	DISHNUXI	Strong	Genetic Variation	[8]
Autoimmune thyroid disease	DISIHC6A	Strong	Genetic Variation	[9]
B-cell lymphoma	DISIH1YQ	Strong	Genetic Variation	[10]
Breast cancer	DIS7DPX1	Strong	Posttranslational Modification	[11]
Breast carcinoma	DIS2UE88	Strong	Posttranslational Modification	[11]
Classic Hodgkin lymphoma	DISV1LU6	Strong	Genetic Variation	[12]
Colorectal carcinoma	DIS5PYL0	Strong	Biomarker	[13]
Depression	DIS3XJ69	Strong	Biomarker	[14]
Epithelial ovarian cancer	DIS56MH2	Strong	Biomarker	[4]
Graves disease	DISU4KOQ	Strong	Genetic Variation	[9]
Hamartoma	DIS0I87H	Strong	Altered Expression	[15]
Hashimoto thyroiditis	DIS77CDF	Strong	Genetic Variation	[9]
Hypothyroidism	DISR0H6D	Strong	Genetic Variation	[8]
Lung adenocarcinoma	DISD51WR	Strong	Genetic Variation	[16]
Lung cancer	DISCM4YA	Strong	Genetic Variation	[16]
Lung carcinoma	DISTR26C	Strong	Genetic Variation	[16]
Multiple sclerosis	DISB2WZI	Strong	Genetic Variation	[17]
Neoplasm of mature B-cells	DISKAXO0	Strong	Genetic Variation	[18]
Open-angle glaucoma	DISSZEE8	Strong	Genetic Variation	[19]
Ovarian cancer	DISZJHAP	Strong	Biomarker	[4]
Ovarian neoplasm	DISEAFTY	Strong	Biomarker	[4]
Post-traumatic stress disorder	DISHL1EY	Strong	Biomarker	[20]
Schizophrenia	DISSRV2N	Strong	Genetic Variation	[21]
Small lymphocytic lymphoma	DIS30POX	Strong	Genetic Variation	[12]
Squamous cell carcinoma	DISQVIFL	Strong	Genetic Variation	[22]
STAT3-related early-onset multisystem autoimmune disease	DISAXTN7	Strong	Genetic Variation	[8]
Vitiligo	DISR05SL	Strong	Genetic Variation	[23]
Allergic rhinitis	DIS3U9HN	moderate	Genetic Variation	[24]
Asthma	DISW9QNS	moderate	Genetic Variation	[25]
Immune system disorder	DISAEGPH	moderate	Genetic Variation	[26]
Neoplasm	DISZKGEW	moderate	Altered Expression	[11]
Basal cell carcinoma	DIS7PYN3	Limited	Genetic Variation	[22]
Basal cell neoplasm	DIS37IXW	Limited	Genetic Variation	[22]
Crohn disease	DIS2C5Q8	Limited	Genetic Variation	[27]
Inflammatory bowel disease	DISGN23E	Limited	Genetic Variation	[27]
Non-insulin dependent diabetes	DISK1O5Z	Limited	Genetic Variation	[28]
Systemic lupus erythematosus	DISI1SZ7	Limited	Genetic Variation	[29]

5 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 Lipoma-preferred partner (LPP).	[30]
Fulvestrant	DM0YZC6	Approved	Fulvestrant increases the methylation of Lipoma-preferred partner (LPP).	[41]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Lipoma-preferred partner (LPP).	[45]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of Lipoma-preferred partner (LPP).	[48]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Lipoma-preferred partner (LPP).	[41]

21 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 Lipoma-preferred partner (LPP).	[31]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Lipoma-preferred partner (LPP).	[32]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Lipoma-preferred partner (LPP).	[33]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Lipoma-preferred partner (LPP).	[34]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Lipoma-preferred partner (LPP).	[35]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Lipoma-preferred partner (LPP).	[36]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Lipoma-preferred partner (LPP).	[37]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Lipoma-preferred partner (LPP).	[38]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Lipoma-preferred partner (LPP).	[39]
Calcitriol	DM8ZVJ7	Approved	Calcitriol decreases the expression of Lipoma-preferred partner (LPP).	[32]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Lipoma-preferred partner (LPP).	[40]
Troglitazone	DM3VFPD	Approved	Troglitazone increases the expression of Lipoma-preferred partner (LPP).	[42]
Resveratrol	DM3RWXL	Phase 3	Resveratrol decreases the expression of Lipoma-preferred partner (LPP).	[43]
Genistein	DM0JETC	Phase 2/3	Genistein decreases the expression of Lipoma-preferred partner (LPP).	[44]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Lipoma-preferred partner (LPP).	[46]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide increases the expression of Lipoma-preferred partner (LPP).	[47]
Geldanamycin	DMS7TC5	Discontinued in Phase 2	Geldanamycin increases the expression of Lipoma-preferred partner (LPP).	[49]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Lipoma-preferred partner (LPP).	[50]
3R14S-OCHRATOXIN A	DM2KEW6	Investigative	3R14S-OCHRATOXIN A decreases the expression of Lipoma-preferred partner (LPP).	[51]
GALLICACID	DM6Y3A0	Investigative	GALLICACID decreases the expression of Lipoma-preferred partner (LPP).	[52]
crotylaldehyde	DMTWRQI	Investigative	crotylaldehyde decreases the expression of Lipoma-preferred partner (LPP).	[53]

References

• [1] Identification of CDC42BPG as a novel susceptibility locus for hyperuricemia in a Japanese population.Mol Genet Genomics. 2018 Apr;293(2):371-379. doi: 10.1007/s00438-017-1394-1. Epub 2017 Nov 9.
• [2] Genome-wide association study identifies novel susceptibility loci for cutaneous squamous cell carcinoma.Nat Commun. 2016 Jul 18;7:12048. doi: 10.1038/ncomms12048.
• [3] A novel LPP fusion gene indicates the crucial role of truncated LPP proteins in lipomas and pulmonary chondroid hamartomas.Cytogenet Cell Genet. 2001;95(3-4):153-6. doi: 10.1159/000059338.
• [4] Cancer-associated fibroblasts regulate endothelial adhesion protein LPP to promote ovarian cancer chemoresistance.J Clin Invest. 2018 Feb 1;128(2):589-606. doi: 10.1172/JCI95200. Epub 2017 Dec 18.
• [5] 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.
• [6] Facial gender but not emotion distinguishes neural responses of 10- to 13-year-old children with social anxiety disorder from healthy and clinical controls.Biol Psychol. 2018 May;135:36-46. doi: 10.1016/j.biopsycho.2018.02.004. Epub 2018 Feb 13.
• [7] MicroRNA 28-5p regulates ATP-binding cassette transporter A1 via inhibiting extracellular signal-regulated kinase 2.Mol Med Rep. 2016 Jan;13(1):433-40. doi: 10.3892/mmr.2015.4563. Epub 2015 Nov 12.
• [8] Leveraging Polygenic Functional Enrichment to Improve GWAS Power.Am J Hum Genet. 2019 Jan 3;104(1):65-75. doi: 10.1016/j.ajhg.2018.11.008. Epub 2018 Dec 27.
• [9] Seven newly identified loci for autoimmune thyroid disease.Hum Mol Genet. 2012 Dec 1;21(23):5202-8. doi: 10.1093/hmg/dds357. Epub 2012 Aug 24.
• [10] Genome-wide association study of B cell non-Hodgkin lymphoma identifies 3q27 as a susceptibility locus in the Chinese population.Nat Genet. 2013 Jul;45(7):804-7. doi: 10.1038/ng.2666. Epub 2013 Jun 9.
• [11] LPP is a Src substrate required for invadopodia formation and efficient breast cancer lung metastasis.Nat Commun. 2017 Apr 24;8:15059. doi: 10.1038/ncomms15059.
• [12] 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.
• [13] LIM protein JUB promotes epithelial-mesenchymal transition in colorectal cancer.Cancer Sci. 2014 Jun;105(6):660-6. doi: 10.1111/cas.12404. Epub 2014 May 10.
• [14] Neurophysiological Markers of Emotion Processing in Burnout Syndrome.Front Psychol. 2017 Dec 13;8:2155. doi: 10.3389/fpsyg.2017.02155. eCollection 2017.
• [15] Expression patterns of the LPP-HMGA2 fusion transcript in pulmonary chondroid hamartomas with t(3;12)(q27 approximately 28;q14 approximately 15).Cancer Genet Cytogenet. 2005 Nov;163(1):68-70. doi: 10.1016/j.cancergencyto.2005.02.023.
• [16] Single nucleotide polymorphism in the 3' untranslated region of LPP is a risk factor for lung cancer: a case-control study.BMC Cancer. 2019 Jan 8;19(1):35. doi: 10.1186/s12885-018-5241-5.
• [17] Analysis of immune-related loci identifies 48 new susceptibility variants for multiple sclerosis.Nat Genet. 2013 Nov;45(11):1353-60. doi: 10.1038/ng.2770. Epub 2013 Sep 29.
• [18] Genome-wide association study identifies five susceptibility loci for follicular lymphoma outside the HLA region.Am J Hum Genet. 2014 Oct 2;95(4):462-71. doi: 10.1016/j.ajhg.2014.09.004.
• [19] 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.
• [20] Differential impact of post-deployment stress and PTSD on neural reactivity to emotional stimuli in Iraq and Afghanistan veterans.J Psychiatr Res. 2018 Jan;96:9-14. doi: 10.1016/j.jpsychires.2017.09.019. Epub 2017 Sep 20.
• [21] Late electrophysiological potentials and emotion in schizophrenia: A meta-analytic review.Schizophr Res. 2019 Sep;211:21-31. doi: 10.1016/j.schres.2019.07.013. Epub 2019 Jul 17.
• [22] Combined analysis of keratinocyte cancers identifies novel genome-wide loci.Hum Mol Genet. 2019 Sep 15;28(18):3148-3160. doi: 10.1093/hmg/ddz121.
• [23] Genome-wide association studies of autoimmune vitiligo identify 23 new risk loci and highlight key pathways and regulatory variants.Nat Genet. 2016 Nov;48(11):1418-1424. doi: 10.1038/ng.3680. Epub 2016 Oct 10.
• [24] Genome-wide association and HLA fine-mapping studies identify risk loci and genetic pathways underlying allergic rhinitis.Nat Genet. 2018 Aug;50(8):1072-1080. doi: 10.1038/s41588-018-0157-1. Epub 2018 Jul 16.
• [25] Genetic Architectures of Childhood- and Adult-Onset Asthma Are Partly Distinct.Am J Hum Genet. 2019 Apr 4;104(4):665-684. doi: 10.1016/j.ajhg.2019.02.022. Epub 2019 Mar 28.
• [26] Meta-analysis of genome-wide association studies in celiac disease and rheumatoid arthritis identifies fourteen non-HLA shared loci.PLoS Genet. 2011 Feb;7(2):e1002004. doi: 10.1371/journal.pgen.1002004. Epub 2011 Feb 24.
• [27] Genome-wide association study implicates immune activation of multiple integrin genes in inflammatory bowel disease.Nat Genet. 2017 Feb;49(2):256-261. doi: 10.1038/ng.3760. Epub 2017 Jan 9.
• [28] Variants associated with type 2 diabetes identified by the transethnic meta-analysis study: assessment in American Indians and evidence for a new signal in LPP.Diabetologia. 2014 Nov;57(11):2334-8. doi: 10.1007/s00125-014-3351-4. Epub 2014 Aug 12.
• [29] Genome-wide association meta-analysis in Chinese and European individuals identifies ten new loci associated with systemic lupus erythematosus.Nat Genet. 2016 Aug;48(8):940-946. doi: 10.1038/ng.3603. Epub 2016 Jul 11.
• [30] 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.
• [31] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [32] Comparison of the gene expression profiles of monocytic versus granulocytic lineages of HL-60 leukemia cell differentiation by DNA microarray analysis. Life Sci. 2003 Aug 15;73(13):1705-19. doi: 10.1016/s0024-3205(03)00515-0.
• [33] Gene expression analysis of precision-cut human liver slices indicates stable expression of ADME-Tox related genes. Toxicol Appl Pharmacol. 2011 May 15;253(1):57-69.
• [34] 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.
• [35] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [36] The thioxotriazole copper(II) complex A0 induces endoplasmic reticulum stress and paraptotic death in human cancer cells. J Biol Chem. 2009 Sep 4;284(36):24306-19.
• [37] Pleiotropic combinatorial transcriptomes of human breast cancer cells exposed to mixtures of dietary phytoestrogens. Food Chem Toxicol. 2009 Apr;47(4):787-95.
• [38] 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.
• [39] Temozolomide induces activation of Wnt/-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278. doi: 10.1007/s10565-019-09502-7. Epub 2019 Nov 22.
• [40] 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.
• [41] 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.
• [42] Effects of ciglitazone and troglitazone on the proliferation of human stomach cancer cells. World J Gastroenterol. 2009 Jan 21;15(3):310-20.
• [43] A novel long noncoding RNA AK001796 acts as an oncogene and is involved in cell growth inhibition by resveratrol in lung cancer. Toxicol Appl Pharmacol. 2015 Jun 1;285(2):79-88.
• [44] Quantitative proteomics and transcriptomics addressing the estrogen receptor subtype-mediated effects in T47D breast cancer cells exposed to the phytoestrogen genistein. Mol Cell Proteomics. 2011 Jan;10(1):M110.002170.
• [45] 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.
• [46] Inhibition of BRD4 attenuates tumor cell self-renewal and suppresses stem cell signaling in MYC driven medulloblastoma. Oncotarget. 2014 May 15;5(9):2355-71.
• [47] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [48] Quantitative phosphoproteomics reveal cellular responses from caffeine, coumarin and quercetin in treated HepG2 cells. Toxicol Appl Pharmacol. 2022 Aug 15;449:116110. doi: 10.1016/j.taap.2022.116110. Epub 2022 Jun 7.
• [49] Identification of transcriptome signatures and biomarkers specific for potential developmental toxicants inhibiting human neural crest cell migration. Arch Toxicol. 2016 Jan;90(1):159-80.
• [50] 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.
• [51] Persistence of epigenomic effects after recovery from repeated treatment with two nephrocarcinogens. Front Genet. 2018 Dec 3;9:558.
• [52] Gene expression profile analysis of gallic acid-induced cell death process. Sci Rep. 2021 Aug 18;11(1):16743. doi: 10.1038/s41598-021-96174-1.
• [53] Gene expression profile and cytotoxicity of human bronchial epithelial cells exposed to crotonaldehyde. Toxicol Lett. 2010 Aug 16;197(2):113-22.