Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT6G9UXN)

DOT Name Probable hydrolase PNKD (PNKD)
Synonyms EC 3.-.-.-; Myofibrillogenesis regulator 1; MR-1; Paroxysmal nonkinesiogenic dyskinesia protein; Trans-activated by hepatitis C virus core protein 2
Gene Name PNKD
Related Disease
Advanced cancer ( )
Arteriosclerosis ( )
Atherosclerosis ( )
Breast cancer ( )
Breast carcinoma ( )
Cardiovascular disease ( )
Clear cell renal carcinoma ( )
Colon cancer ( )
Colorectal adenocarcinoma ( )
Colorectal adenoma ( )
Colorectal cancer ( )
Colorectal cancer, susceptibility to, 1 ( )
Colorectal cancer, susceptibility to, 10 ( )
Colorectal cancer, susceptibility to, 12 ( )
Colorectal carcinoma ( )
Colorectal neoplasm ( )
Convulsion ( )
Dystonia ( )
Dystonia 12 ( )
Familial hemiplegic migraine ( )
Hereditary episodic ataxia ( )
Movement disorder ( )
Neoplasm ( )
Obsolete paroxysmal nonkinesigenic dyskinesia 1 ( )
Papillary renal cell carcinoma ( )
Paroxysmal dyskinesia ( )
Renal cell carcinoma ( )
Crohn disease ( )
Matthew-Wood syndrome ( )
Pancreatic ductal carcinoma ( )
Ulcerative colitis ( )
Bjornstad syndrome ( )
Epithelial ovarian cancer ( )
Hepatocellular carcinoma ( )
Inflammatory bowel disease ( )
Ovarian cancer ( )
Ovarian neoplasm ( )
Parkinsonian disorder ( )
Paroxysmal dystonia ( )
Tourette syndrome ( )
UniProt ID
PNKD_HUMAN
3D Structure
Download
2D Sequence (FASTA)
Download
3D Structure (PDB)
Download
EC Number
3.-.-.-
Pfam ID
PF16123 ; PF00753
Sequence
MAAVVAATALKGRGARNARVLRGILAGATANKASHNRTRALQSHSSPEGKEEPEPLSPEL
EYIPRKRGKNPMKAVGLAWYSLYTRTWLGYLFYRQQLRRARNRYPKGHSKTQPRLFNGVK
VLPIPVLSDNYSYLIIDTQAQLAVAVDPSDPRAVQASIEKEGVTLVAILCTHKHWDHSGG
NRDLSRRHRDCRVYGSPQDGIPYLTHPLCHQDVVSVGRLQIRALATPGHTQGHLVYLLDG
EPYKGPSCLFSGDLLFLSGCGRTFEGNAETMLSSLDTVLGLGDDTLLWPGHEYAEENLGF
AGVVEPENLARERKMQWVQRQRLERKGTCPSTLGEERSYNPFLRTHCLALQEALGPGPGP
TGDDDYSRAQLLEELRRLKDMHKSK
Function Probable hydrolase that plays an aggravative role in the development of cardiac hypertrophy via activation of the NF-kappa-B signaling pathway.
Tissue Specificity
Isoform 1 is only expressed in the brain. Isoform 2 is ubiquitously detected with highest expression in skeletal muscle and detected in myocardial myofibrils. Variant Val-7 and Val-9 are detected in the brain only.

Molecular Interaction Atlas (MIA) of This DOT

40 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Advanced cancer DISAT1Z9 Strong Biomarker [1]
Arteriosclerosis DISK5QGC Strong Biomarker [2]
Atherosclerosis DISMN9J3 Strong Biomarker [2]
Breast cancer DIS7DPX1 Strong Altered Expression [1]
Breast carcinoma DIS2UE88 Strong Altered Expression [1]
Cardiovascular disease DIS2IQDX Strong Genetic Variation [3]
Clear cell renal carcinoma DISBXRFJ Strong Biomarker [4]
Colon cancer DISVC52G Strong Genetic Variation [5]
Colorectal adenocarcinoma DISPQOUB Strong Genetic Variation [5]
Colorectal adenoma DISTSVHM Strong Genetic Variation [6]
Colorectal cancer DISNH7P9 Strong Genetic Variation [5]
Colorectal cancer, susceptibility to, 1 DISZ794C Strong Genetic Variation [5]
Colorectal cancer, susceptibility to, 10 DISQXMYM Strong Genetic Variation [5]
Colorectal cancer, susceptibility to, 12 DIS4FXJX Strong Genetic Variation [5]
Colorectal carcinoma DIS5PYL0 Strong Genetic Variation [5]
Colorectal neoplasm DISR1UCN Strong Genetic Variation [5]
Convulsion DIS1CYA2 Strong Biomarker [7]
Dystonia DISJLFGW Strong Genetic Variation [8]
Dystonia 12 DISNX38R Strong Biomarker [9]
Familial hemiplegic migraine DISYVMKL Strong Biomarker [10]
Hereditary episodic ataxia DISC4ZQW Strong Genetic Variation [10]
Movement disorder DISOJJ2D Strong Genetic Variation [10]
Neoplasm DISZKGEW Strong Biomarker [1]
Obsolete paroxysmal nonkinesigenic dyskinesia 1 DIS5U9J8 Strong Autosomal dominant [11]
Papillary renal cell carcinoma DIS25HBV Strong Biomarker [4]
Paroxysmal dyskinesia DIS5XVXE Strong Genetic Variation [10]
Renal cell carcinoma DISQZ2X8 Strong Biomarker [4]
Crohn disease DIS2C5Q8 moderate Genetic Variation [12]
Matthew-Wood syndrome DISA7HR7 moderate Altered Expression [13]
Pancreatic ductal carcinoma DIS26F9Q moderate Altered Expression [13]
Ulcerative colitis DIS8K27O moderate Genetic Variation [12]
Bjornstad syndrome DISO267N Limited Biomarker [14]
Epithelial ovarian cancer DIS56MH2 Limited Biomarker [15]
Hepatocellular carcinoma DIS0J828 Limited Altered Expression [1]
Inflammatory bowel disease DISGN23E Limited Genetic Variation [16]
Ovarian cancer DISZJHAP Limited Biomarker [15]
Ovarian neoplasm DISEAFTY Limited Biomarker [15]
Parkinsonian disorder DISHGY45 Limited Biomarker [8]
Paroxysmal dystonia DISV0MSQ Limited Genetic Variation [9]
Tourette syndrome DISX9D54 Limited Autosomal dominant [7]
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⏷ Show the Full List of 40 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
3 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 Probable hydrolase PNKD (PNKD). [17]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene affects the methylation of Probable hydrolase PNKD (PNKD). [28]
Bisphenol A DM2ZLD7 Investigative Bisphenol A decreases the methylation of Probable hydrolase PNKD (PNKD). [29]
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11 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 Probable hydrolase PNKD (PNKD). [18]
Tretinoin DM49DUI Approved Tretinoin increases the expression of Probable hydrolase PNKD (PNKD). [19]
Acetaminophen DMUIE76 Approved Acetaminophen decreases the expression of Probable hydrolase PNKD (PNKD). [20]
Cupric Sulfate DMP0NFQ Approved Cupric Sulfate decreases the expression of Probable hydrolase PNKD (PNKD). [21]
Cisplatin DMRHGI9 Approved Cisplatin affects the expression of Probable hydrolase PNKD (PNKD). [22]
Estradiol DMUNTE3 Approved Estradiol increases the expression of Probable hydrolase PNKD (PNKD). [23]
Calcitriol DM8ZVJ7 Approved Calcitriol decreases the expression of Probable hydrolase PNKD (PNKD). [24]
Decitabine DMQL8XJ Approved Decitabine affects the expression of Probable hydrolase PNKD (PNKD). [22]
Zoledronate DMIXC7G Approved Zoledronate increases the expression of Probable hydrolase PNKD (PNKD). [25]
Dihydrotestosterone DM3S8XC Phase 4 Dihydrotestosterone increases the expression of Probable hydrolase PNKD (PNKD). [26]
Genistein DM0JETC Phase 2/3 Genistein decreases the expression of Probable hydrolase PNKD (PNKD). [27]
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⏷ Show the Full List of 11 Drug(s)

References

1 Myofibrillogenesis regulator 1 (MR-1): a potential therapeutic target for cancer and PNKD.J Drug Target. 2018 Sep;26(8):643-648. doi: 10.1080/1061186X.2017.1401077. Epub 2017 Nov 15.
2 Silencing MR-1 attenuates atherosclerosis in ApoE(-/-) mice induced by angiotensin II through FAK-Akt-mTOR-NF-kappaB signaling pathway.Korean J Physiol Pharmacol. 2018 Mar;22(2):127-134. doi: 10.4196/kjpp.2018.22.2.127. Epub 2018 Feb 23.
3 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.
4 Spectrum of diverse genomic alterations define non-clear cell renal carcinoma subtypes.Nat Genet. 2015 Jan;47(1):13-21. doi: 10.1038/ng.3146. Epub 2014 Nov 17.
5 Novel Common Genetic Susceptibility Loci for Colorectal Cancer.J Natl Cancer Inst. 2019 Feb 1;111(2):146-157. doi: 10.1093/jnci/djy099.
6 Discovery of common and rare genetic risk variants for colorectal cancer.Nat Genet. 2019 Jan;51(1):76-87. doi: 10.1038/s41588-018-0286-6. Epub 2018 Dec 3.
7 The PNKD gene is associated with Tourette Disorder or Tic disorder in a multiplex family. Mol Psychiatry. 2018 Jun;23(6):1487-1495. doi: 10.1038/mp.2017.179. Epub 2017 Sep 12.
8 Genetics of dystonia: what's known? What's new? What's next?.Mov Disord. 2013 Jun 15;28(7):899-905. doi: 10.1002/mds.25536.
9 Genetics of primary dystonia.Semin Neurol. 1999;19(3):271-80. doi: 10.1055/s-2008-1040843.
10 The clinical and genetic heterogeneity of paroxysmal dyskinesias.Brain. 2015 Dec;138(Pt 12):3567-80. doi: 10.1093/brain/awv310. Epub 2015 Nov 23.
11 The Gene Curation Coalition: A global effort to harmonize gene-disease evidence resources. Genet Med. 2022 Aug;24(8):1732-1742. doi: 10.1016/j.gim.2022.04.017. Epub 2022 May 4.
12 Association analyses identify 38 susceptibility loci for inflammatory bowel disease and highlight shared genetic risk across populations.Nat Genet. 2015 Sep;47(9):979-986. doi: 10.1038/ng.3359. Epub 2015 Jul 20.
13 Clinicopathological and prognostic significance of myofibrillogenesis regulator-1 protein expression in pancreatic ductal adenocarcinoma.Tumour Biol. 2013 Oct;34(5):2983-7. doi: 10.1007/s13277-013-0862-4. Epub 2013 May 22.
14 Genetics of dystonia.Semin Neurol. 2011 Nov;31(5):441-8. doi: 10.1055/s-0031-1299783. Epub 2012 Jan 21.
15 Myofibrillogenesis regulator 1 (MR-1) is a novel biomarker and potential therapeutic target for human ovarian cancer.BMC Cancer. 2011 Jun 25;11:270. doi: 10.1186/1471-2407-11-270.
16 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.
17 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.
18 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.
19 Retinoic acid receptor alpha amplifications and retinoic acid sensitivity in breast cancers. Clin Breast Cancer. 2013 Oct;13(5):401-8.
20 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.
21 Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
22 Acute hypersensitivity of pluripotent testicular cancer-derived embryonal carcinoma to low-dose 5-aza deoxycytidine is associated with global DNA Damage-associated p53 activation, anti-pluripotency and DNA demethylation. PLoS One. 2012;7(12):e53003. doi: 10.1371/journal.pone.0053003. Epub 2012 Dec 27.
23 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.
24 Large-scale in silico and microarray-based identification of direct 1,25-dihydroxyvitamin D3 target genes. Mol Endocrinol. 2005 Nov;19(11):2685-95.
25 Interleukin-19 as a translational indicator of renal injury. Arch Toxicol. 2015 Jan;89(1):101-6.
26 LSD1 activates a lethal prostate cancer gene network independently of its demethylase function. Proc Natl Acad Sci U S A. 2018 May 1;115(18):E4179-E4188.
27 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.
28 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.
29 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.