Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT6MQP3A)

• DOT Name: Atrial natriuretic peptide receptor 3 (NPR3)
• Synonyms: Atrial natriuretic peptide clearance receptor; Atrial natriuretic peptide receptor type C; ANP-C; ANPR-C; NPR-C
• Gene Name: NPR3
• Related Disease: Boudin-Mortier syndrome
• UniProt ID: ANPRC_HUMAN
• PDB ID: 1JDN; 1JDP; 1YK0; 1YK1
• Pfam ID: PF01094
• Sequence:
  MPSLLVLTFSPCVLLGWALLAGGTGGGGVGGGGGGAGIGGGRQEREALPPQKIEVLVLLP
  QDDSYLFSLTRVRPAIEYALRSVEGNGTGRRLLPPGTRFQVAYEDSDCGNRALFSLVDRV
  AAARGAKPDLILGPVCEYAAAPVARLASHWDLPMLSAGALAAGFQHKDSEYSHLTRVAPA
  YAKMGEMMLALFRHHHWSRAALVYSDDKLERNCYFTLEGVHEVFQEEGLHTSIYSFDETK
  DLDLEDIVRNIQASERVVIMCASSDTIRSIMLVAHRHGMTSGDYAFFNIELFNSSSYGDG
  SWKRGDKHDFEAKQAYSSLQTVTLLRTVKPEFEKFSMEVKSSVEKQGLNMEDYVNMFVEG
  FHDAILLYVLALHEVLRAGYSKKDGGKIIQQTWNRTFEGIAGQVSIDANGDRYGDFSVIA
  MTDVEAGTQEVIGDYFGKEGRFEMRPNVKYPWGPLKLRIDENRIVEHTNSSPCKSSGGLE
  ESAVTGIVVGALLGAGLLMAFYFFRKKYRITIERRTQQEESNLGKHRELREDSIRSHFSV
  A
• Function: Receptor for the natriuretic peptide hormones, binding with similar affinities atrial natriuretic peptide NPPA/ANP, brain natriuretic peptide NPPB/BNP, and C-type natriuretic peptide NPPC/CNP. May function as a clearance receptor for NPPA, NPPB and NPPC, regulating their local concentrations and effects. May regulate diuresis, blood pressure and skeletal development. Does not have guanylate cyclase activity.

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Boudin-Mortier syndrome	DISE1QTK	Strong	Autosomal recessive	[1]

3 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 Atrial natriuretic peptide receptor 3 (NPR3).	[2]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Atrial natriuretic peptide receptor 3 (NPR3).	[17]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the methylation of Atrial natriuretic peptide receptor 3 (NPR3).	[21]

22 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Atrial natriuretic peptide receptor 3 (NPR3).	[3]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Atrial natriuretic peptide receptor 3 (NPR3).	[4]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Atrial natriuretic peptide receptor 3 (NPR3).	[5]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Atrial natriuretic peptide receptor 3 (NPR3).	[6]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate affects the expression of Atrial natriuretic peptide receptor 3 (NPR3).	[7]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Atrial natriuretic peptide receptor 3 (NPR3).	[8]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of Atrial natriuretic peptide receptor 3 (NPR3).	[9]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of Atrial natriuretic peptide receptor 3 (NPR3).	[10]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Atrial natriuretic peptide receptor 3 (NPR3).	[11]
Zoledronate	DMIXC7G	Approved	Zoledronate decreases the expression of Atrial natriuretic peptide receptor 3 (NPR3).	[12]
Phenobarbital	DMXZOCG	Approved	Phenobarbital affects the expression of Atrial natriuretic peptide receptor 3 (NPR3).	[13]
Progesterone	DMUY35B	Approved	Progesterone increases the expression of Atrial natriuretic peptide receptor 3 (NPR3).	[14]
Panobinostat	DM58WKG	Approved	Panobinostat increases the expression of Atrial natriuretic peptide receptor 3 (NPR3).	[10]
Folic acid	DMEMBJC	Approved	Folic acid decreases the expression of Atrial natriuretic peptide receptor 3 (NPR3).	[15]
Belinostat	DM6OC53	Phase 2	Belinostat increases the expression of Atrial natriuretic peptide receptor 3 (NPR3).	[10]
DNCB	DMDTVYC	Phase 2	DNCB affects the expression of Atrial natriuretic peptide receptor 3 (NPR3).	[16]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Atrial natriuretic peptide receptor 3 (NPR3).	[18]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Atrial natriuretic peptide receptor 3 (NPR3).	[19]
Geldanamycin	DMS7TC5	Discontinued in Phase 2	Geldanamycin increases the expression of Atrial natriuretic peptide receptor 3 (NPR3).	[20]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Atrial natriuretic peptide receptor 3 (NPR3).	[22]
acrolein	DMAMCSR	Investigative	acrolein affects the expression of Atrial natriuretic peptide receptor 3 (NPR3).	[16]
methyl salicylate	DMKCG8H	Investigative	methyl salicylate affects the expression of Atrial natriuretic peptide receptor 3 (NPR3).	[16]

References

• [1] Bi-allelic Loss-of-Function Mutations in the NPR-C Receptor Result in Enhanced Growth and Connective Tissue Abnormalities. Am J Hum Genet. 2018 Aug 2;103(2):288-295. doi: 10.1016/j.ajhg.2018.06.007. Epub 2018 Jul 19.
• [2] 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.
• [3] 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.
• [4] Retinoic acid receptor alpha amplifications and retinoic acid sensitivity in breast cancers. Clin Breast Cancer. 2013 Oct;13(5):401-8.
• [5] Blood transcript immune signatures distinguish a subset of people with elevated serum ALT from others given acetaminophen. Clin Pharmacol Ther. 2016 Apr;99(4):432-41.
• [6] 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.
• [7] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [8] Genistein and bisphenol A exposure cause estrogen receptor 1 to bind thousands of sites in a cell type-specific manner. Genome Res. 2012 Nov;22(11):2153-62.
• [9] 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.
• [10] 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.
• [11] 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.
• [12] Interleukin-19 as a translational indicator of renal injury. Arch Toxicol. 2015 Jan;89(1):101-6.
• [13] Reproducible chemical-induced changes in gene expression profiles in human hepatoma HepaRG cells under various experimental conditions. Toxicol In Vitro. 2009 Apr;23(3):466-75. doi: 10.1016/j.tiv.2008.12.018. Epub 2008 Dec 30.
• [14] Unique transcriptome, pathways, and networks in the human endometrial fibroblast response to progesterone in endometriosis. Biol Reprod. 2011 Apr;84(4):801-15.
• [15] Folic acid supplementation dysregulates gene expression in lymphoblastoid cells--implications in nutrition. Biochem Biophys Res Commun. 2011 Sep 9;412(4):688-92. doi: 10.1016/j.bbrc.2011.08.027. Epub 2011 Aug 16.
• [16] Gene profiles of THP-1 macrophages after in vitro exposure to respiratory (non-)sensitizing chemicals: identification of discriminating genetic markers and pathway analysis. Toxicol In Vitro. 2009 Sep;23(6):1151-62. doi: 10.1016/j.tiv.2009.06.007. Epub 2009 Jun 13.
• [17] 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.
• [18] CCAT1 is an enhancer-templated RNA that predicts BET sensitivity in colorectal cancer. J Clin Invest. 2016 Feb;126(2):639-52.
• [19] 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.
• [20] 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.
• [21] 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.
• [22] 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.