Details of Drug Off-Target (DOT)

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

DOT Name Proline-rich transmembrane protein 2 (PRRT2)
Synonyms Dispanin subfamily B member 3; DSPB3
Gene Name PRRT2
Related Disease
Infantile convulsions and choreoathetosis ( )
Melanoma ( )
Non-alcoholic fatty liver disease ( )
Acute myelogenous leukaemia ( )
Benign neonatal seizures ( )
Bone osteosarcoma ( )
Breast cancer ( )
Breast carcinoma ( )
Cardiac failure ( )
Choreatic disease ( )
Clear cell renal carcinoma ( )
Colon carcinoma ( )
Colorectal carcinoma ( )
Congestive heart failure ( )
Dystonia ( )
Episodic kinesigenic dyskinesia ( )
Episodic kinesigenic dyskinesia 1 ( )
Gastrointestinal stromal tumour ( )
Hyperglycemia ( )
Myotonic dystrophy ( )
Neuroblastoma ( )
Non-insulin dependent diabetes ( )
Obesity ( )
Obsolete episodic kinesigenic dyskinesia 1 ( )
Osteosarcoma ( )
Rheumatoid arthritis ( )
Seizures, benign familial infantile, 2 ( )
Squamous cell carcinoma ( )
Type-1/2 diabetes ( )
Focal epilepsy ( )
Glioma ( )
Intellectual disability ( )
Movement disorder ( )
Neuralgia ( )
Non-small-cell lung cancer ( )
Benign familial infantile epilepsy ( )
Childhood onset GLUT1 deficiency syndrome 2 ( )
Familial or sporadic hemiplegic migraine ( )
Obsolete paroxysmal nonkinesigenic dyskinesia 1 ( )
Glioblastoma multiforme ( )
Adult glioblastoma ( )
Advanced cancer ( )
Alzheimer disease ( )
Asthma ( )
Colon cancer ( )
Hereditary episodic ataxia ( )
Nervous system disease ( )
Pancreatic cancer ( )
Paroxysmal dyskinesia ( )
Prostate cancer ( )
Prostate carcinoma ( )
Stomach cancer ( )
UniProt ID
PRRT2_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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Pfam ID
PF04505
Sequence
MAASSSEISEMKGVEESPKVPGEGPGHSEAETGPPQVLAGVPDQPEAPQPGPNTTAAPVD
SGPKAGLAPETTETPAGASETAQATDLSLSPGGESKANCSPEDPCQETVSKPEVSKEATA
DQGSRLESAAPPEPAPEPAPQPDPRPDSQPTPKPALQPELPTQEDPTPEILSESVGEKQE
NGAVVPLQAGDGEEGPAPEPHSPPSKKSPPANGAPPRVLQQLVEEDRMRRAHSGHPGSPR
GSLSRHPSSQLAGPGVEGGEGTQKPRDYIILAILSCFCPMWPVNIVAFAYAVMSRNSLQQ
GDVDGAQRLGRVAKLLSIVALVGGVLIIIASCVINLGVYK
Function
As a component of the outer core of AMPAR complex, may be involved in synaptic transmission in the central nervous system. In hippocampal neurons, in presynaptic terminals, plays an important role in the final steps of neurotransmitter release, possibly by regulating Ca(2+)-sensing. In the cerebellum, may inhibit SNARE complex formation and down-regulate short-term facilitation.

Molecular Interaction Atlas (MIA) of This DOT

52 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Infantile convulsions and choreoathetosis DIS0H0JE Definitive Autosomal dominant [1]
Melanoma DIS1RRCY Definitive Altered Expression [2]
Non-alcoholic fatty liver disease DISDG1NL Definitive Altered Expression [3]
Acute myelogenous leukaemia DISCSPTN Strong Biomarker [4]
Benign neonatal seizures DISWNBHF Strong Genetic Variation [5]
Bone osteosarcoma DIST1004 Strong Biomarker [6]
Breast cancer DIS7DPX1 Strong Altered Expression [7]
Breast carcinoma DIS2UE88 Strong Altered Expression [7]
Cardiac failure DISDC067 Strong Altered Expression [8]
Choreatic disease DISH8K3M Strong Genetic Variation [9]
Clear cell renal carcinoma DISBXRFJ Strong Biomarker [10]
Colon carcinoma DISJYKUO Strong Altered Expression [11]
Colorectal carcinoma DIS5PYL0 Strong Biomarker [12]
Congestive heart failure DIS32MEA Strong Altered Expression [8]
Dystonia DISJLFGW Strong Genetic Variation [13]
Episodic kinesigenic dyskinesia DIS65CHB Strong Genetic Variation [14]
Episodic kinesigenic dyskinesia 1 DISGVQMP Strong Autosomal dominant [15]
Gastrointestinal stromal tumour DIS6TJYS Strong Biomarker [16]
Hyperglycemia DIS0BZB5 Strong Altered Expression [17]
Myotonic dystrophy DISNBEMX Strong Biomarker [18]
Neuroblastoma DISVZBI4 Strong Biomarker [19]
Non-insulin dependent diabetes DISK1O5Z Strong Biomarker [20]
Obesity DIS47Y1K Strong Biomarker [21]
Obsolete episodic kinesigenic dyskinesia 1 DISRYM2O Strong Autosomal dominant [22]
Osteosarcoma DISLQ7E2 Strong Altered Expression [23]
Rheumatoid arthritis DISTSB4J Strong Altered Expression [24]
Seizures, benign familial infantile, 2 DIS6LZ05 Strong Autosomal dominant [22]
Squamous cell carcinoma DISQVIFL Strong Biomarker [25]
Type-1/2 diabetes DISIUHAP Strong Altered Expression [17]
Focal epilepsy DIS4LY5L moderate Genetic Variation [26]
Glioma DIS5RPEH moderate Biomarker [27]
Intellectual disability DISMBNXP moderate Genetic Variation [28]
Movement disorder DISOJJ2D moderate Biomarker [9]
Neuralgia DISWO58J moderate Altered Expression [29]
Non-small-cell lung cancer DIS5Y6R9 moderate Altered Expression [30]
Benign familial infantile epilepsy DISFYXOW Supportive Autosomal dominant [31]
Childhood onset GLUT1 deficiency syndrome 2 DISXPRXM Supportive Autosomal dominant [32]
Familial or sporadic hemiplegic migraine DISOSL2O Supportive Autosomal dominant [33]
Obsolete paroxysmal nonkinesigenic dyskinesia 1 DIS5U9J8 Supportive Autosomal dominant [32]
Glioblastoma multiforme DISK8246 Disputed Altered Expression [34]
Adult glioblastoma DISVP4LU Limited Altered Expression [34]
Advanced cancer DISAT1Z9 Limited Altered Expression [35]
Alzheimer disease DISF8S70 Limited Biomarker [36]
Asthma DISW9QNS Limited Biomarker [37]
Colon cancer DISVC52G Limited Altered Expression [11]
Hereditary episodic ataxia DISC4ZQW Limited Genetic Variation [38]
Nervous system disease DISJ7GGT Limited Genetic Variation [39]
Pancreatic cancer DISJC981 Limited Biomarker [40]
Paroxysmal dyskinesia DIS5XVXE Limited Genetic Variation [41]
Prostate cancer DISF190Y Limited Biomarker [42]
Prostate carcinoma DISMJPLE Limited Biomarker [42]
Stomach cancer DISKIJSX Limited Biomarker [43]
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⏷ Show the Full List of 52 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
2 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 Proline-rich transmembrane protein 2 (PRRT2). [44]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene decreases the methylation of Proline-rich transmembrane protein 2 (PRRT2). [49]
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7 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Tretinoin DM49DUI Approved Tretinoin decreases the expression of Proline-rich transmembrane protein 2 (PRRT2). [45]
Cisplatin DMRHGI9 Approved Cisplatin increases the expression of Proline-rich transmembrane protein 2 (PRRT2). [46]
Estradiol DMUNTE3 Approved Estradiol affects the expression of Proline-rich transmembrane protein 2 (PRRT2). [47]
Hydrogen peroxide DM1NG5W Approved Hydrogen peroxide affects the expression of Proline-rich transmembrane protein 2 (PRRT2). [48]
(+)-JQ1 DM1CZSJ Phase 1 (+)-JQ1 increases the expression of Proline-rich transmembrane protein 2 (PRRT2). [50]
PMID28460551-Compound-2 DM4DOUB Patented PMID28460551-Compound-2 decreases the expression of Proline-rich transmembrane protein 2 (PRRT2). [51]
Trichostatin A DM9C8NX Investigative Trichostatin A decreases the expression of Proline-rich transmembrane protein 2 (PRRT2). [52]
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⏷ Show the Full List of 7 Drug(s)

References

1 Technical standards for the interpretation and reporting of constitutional copy-number variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics (ACMG) and the Clinical Genome Resource (ClinGen). Genet Med. 2020 Feb;22(2):245-257. doi: 10.1038/s41436-019-0686-8. Epub 2019 Nov 6.
2 Recent insights into apoptosis and toxic autophagy: The roles of MDA-7/IL-24, a multidimensional anti-cancer therapeutic.Semin Cancer Biol. 2020 Nov;66:140-154. doi: 10.1016/j.semcancer.2019.07.013. Epub 2019 Jul 26.
3 Resveratrol protects against hepatic insulin resistance in a rat's model of non-alcoholic fatty liver disease by down-regulation of GPAT-1 and DGAT2 expression and inhibition of PKC membranous translocation.Clin Exp Pharmacol Physiol. 2019 Jun;46(6):545-555. doi: 10.1111/1440-1681.13074. Epub 2019 Apr 4.
4 Protein Kinase C Epsilon Is a Key Regulator of Mitochondrial Redox Homeostasis in Acute Myeloid Leukemia.Clin Cancer Res. 2018 Feb 1;24(3):608-618. doi: 10.1158/1078-0432.CCR-17-2684. Epub 2017 Nov 10.
5 Severe phenotypic spectrum of biallelic mutations in PRRT2 gene.J Neurol Neurosurg Psychiatry. 2015 Jul;86(7):782-5. doi: 10.1136/jnnp-2014-309025. Epub 2015 Jan 16.
6 Spinal PKC activation - Induced neuronal HMGB1 translocation contributes to hyperalgesia in a bone cancer pain model in rats.Exp Neurol. 2018 May;303:80-94. doi: 10.1016/j.expneurol.2018.02.003. Epub 2018 Feb 8.
7 CCR2 Chemokine Receptors Enhance Growth and Cell-Cycle Progression of Breast Cancer Cells through SRC and PKC Activation.Mol Cancer Res. 2019 Feb;17(2):604-617. doi: 10.1158/1541-7786.MCR-18-0750. Epub 2018 Nov 16.
8 Increased free Zn(2+) correlates induction of sarco(endo)plasmic reticulum stress via altered expression levels of Zn(2+) -transporters in heart failure.J Cell Mol Med. 2018 Mar;22(3):1944-1956. doi: 10.1111/jcmm.13480. Epub 2018 Jan 15.
9 Movement disorders phenomenology in focal motor seizures.Parkinsonism Relat Disord. 2019 Apr;61:161-165. doi: 10.1016/j.parkreldis.2018.10.021. Epub 2018 Oct 16.
10 CCL2 as a potential therapeutic target for clear cell renal cell carcinoma.Cancer Med. 2016 Oct;5(10):2920-2933. doi: 10.1002/cam4.886. Epub 2016 Sep 26.
11 Aberrant methylation of ERBB pathway genes in sporadic colorectal cancer.J Appl Genet. 2015 May;56(2):185-92. doi: 10.1007/s13353-014-0253-6. Epub 2014 Nov 1.
12 Atypical Protein Kinase-C inhibitors exhibit a synergistic effect in facilitating DNA damaging effect of 5-fluorouracil in colorectal cancer cells.Biomed Pharmacother. 2020 Jan;121:109665. doi: 10.1016/j.biopha.2019.109665. Epub 2019 Nov 22.
13 Paroxysmal kinesigenic dyskinesia: Clinical and genetic analyses of 110 patients.Neurology. 2015 Nov 3;85(18):1546-53. doi: 10.1212/WNL.0000000000002079. Epub 2015 Oct 7.
14 PRRT2 frameshift mutation reduces its mRNA stability resulting loss of function in paroxysmal kinesigenic dyskinesia.Biochem Biophys Res Commun. 2020 Feb 12;522(3):553-559. doi: 10.1016/j.bbrc.2019.11.025. Epub 2019 Nov 27.
15 Familial Paroxysmal Kinesigenic Dyskinesia C RETIRED CHAPTER, FOR HISTORICAL REFERENCE ONLY. 2005 Jun 24 [updated 2013 Jun 27]. In: Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE, Bean LJH, Gripp KW, Amemiya A, editors. GeneReviews(?) [Internet]. Seattle (WA): University of Washington, Seattle; 1993C2024.
16 Sustained Mutant KIT Activation in the Golgi Complex Is Mediated by PKC- in Gastrointestinal Stromal Tumors.Clin Cancer Res. 2017 Feb 1;23(3):845-856. doi: 10.1158/1078-0432.CCR-16-0521. Epub 2016 Jul 20.
17 Relationship between aldose reductase enzyme and the signaling pathway of protein kinase C in an in vitro diabetic retinopathy model.Can J Physiol Pharmacol. 2020 Apr;98(4):243-251. doi: 10.1139/cjpp-2019-0211. Epub 2019 Nov 19.
18 LDB3 splicing abnormalities are specific to skeletal muscles of patients with myotonic dystrophy type 1 and alter its PKC binding affinity.Neurobiol Dis. 2014 Sep;69:200-5. doi: 10.1016/j.nbd.2014.05.026. Epub 2014 May 27.
19 A novel PKC- inhibitor abrogates cell proliferation and induces apoptosis in neuroblastoma. Int J Biochem Cell Biol. 2011 May;43(5):784-94.
20 Potential Nexus of Non-alcoholic Fatty Liver Disease and Type 2 Diabetes Mellitus: Insulin Resistance Between Hepatic and Peripheral Tissues.Front Pharmacol. 2019 Jan 14;9:1566. doi: 10.3389/fphar.2018.01566. eCollection 2018.
21 Swimming training reduces glucose-amplifying pathway and cholinergic responses in islets from lean- and MSG-obese rats.Clin Exp Pharmacol Physiol. 2020 Feb;47(2):286-293. doi: 10.1111/1440-1681.13197. Epub 2019 Nov 12.
22 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.
23 miR-486 suppresses the development of osteosarcoma by regulating PKC- pathway.Int J Oncol. 2017 May;50(5):1590-1600. doi: 10.3892/ijo.2017.3928. Epub 2017 Mar 22.
24 Protein kinase C-theta inhibitors: a novel therapy for inflammatory disorders.Curr Pharm Des. 2012;18(30):4725-46. doi: 10.2174/138161212802651625.
25 Induction of endonuclease G-mediated apopotosis in human oral squamous cell carcinoma cells by protein kinase C inhibitor safingol.Apoptosis. 2006 Jan;11(1):47-56. doi: 10.1007/s10495-005-3348-z.
26 Mutation screening of the PRRT2 gene for benign epilepsy with centrotemporal spikes in Chinese mainland population.Int J Neurosci. 2017 Jan;127(1):10-13. doi: 10.3109/00207454.2015.1136886. Epub 2016 Apr 6.
27 PRRT2 inhibits the proliferation of glioma cells by modulating unfolded protein response pathway.Biochem Biophys Res Commun. 2017 Apr 1;485(2):454-460. doi: 10.1016/j.bbrc.2017.02.052. Epub 2017 Feb 10.
28 The evolving spectrum of PRRT2-associated paroxysmal diseases.Brain. 2015 Dec;138(Pt 12):3476-95. doi: 10.1093/brain/awv317. Epub 2015 Nov 23.
29 Activation of enkephalinergic (Enk) interneurons in the central amygdala (CeA) buffers the behavioral effects of persistent pain.Neurobiol Dis. 2019 Apr;124:364-372. doi: 10.1016/j.nbd.2018.12.005. Epub 2018 Dec 17.
30 Protein kinase C-iota-mediated glycolysis promotes non-small-cell lung cancer progression.Onco Targets Ther. 2019 Jul 18;12:5835-5848. doi: 10.2147/OTT.S207211. eCollection 2019.
31 PRRT2 mutations cause benign familial infantile epilepsy and infantile convulsions with choreoathetosis syndrome. Am J Hum Genet. 2012 Jan 13;90(1):152-60. doi: 10.1016/j.ajhg.2011.12.003.
32 Phenotypic overlap among paroxysmal dyskinesia subtypes: Lesson from a family with PRRT2 gene mutation. Brain Dev. 2013 Aug;35(7):664-6. doi: 10.1016/j.braindev.2012.07.018. Epub 2012 Aug 16.
33 PRRT2 mutations cause hemiplegic migraine. Neurology. 2012 Nov 20;79(21):2122-4. doi: 10.1212/WNL.0b013e3182752cb8. Epub 2012 Oct 17.
34 Oncogenic Role of MicroRNA-30b-5p in Glioblastoma Through Targeting Proline-Rich Transmembrane Protein 2.Oncol Res. 2018 Mar 5;26(2):219-230. doi: 10.3727/096504017X14944585873659. Epub 2017 May 17.
35 Expression of TMBIM6 in Cancers: The Involvement of Sp1 and PKC.Cancers (Basel). 2019 Jul 11;11(7):974. doi: 10.3390/cancers11070974.
36 Loss in PKC Epsilon Causes Downregulation of MnSOD and BDNF Expression in Neurons of Alzheimer's Disease Hippocampus.J Alzheimers Dis. 2018;63(3):1173-1189. doi: 10.3233/JAD-171008.
37 Participation of Antidiuretic Hormone (ADH) in Asthma Exacerbations Induced by Psychological Stress via PKA/PKC Signal Pathway in Airway-Related Vagal Preganglionic Neurons (AVPNs).Cell Physiol Biochem. 2017;41(6):2230-2241. doi: 10.1159/000475638. Epub 2017 Apr 25.
38 Acute-Onset Ataxia and Transient Cerebellar Diffusion Restriction Associated with a PRRT2 Mutation.J Stroke Cerebrovasc Dis. 2019 Feb;28(2):e3-e4. doi: 10.1016/j.jstrokecerebrovasdis.2018.10.021. Epub 2018 Nov 28.
39 PRRT2 missense mutations cluster near C-terminus and frequently lead to protein mislocalization.Epilepsia. 2019 May;60(5):807-817. doi: 10.1111/epi.14725. Epub 2019 Apr 13.
40 Protein kinase C isoforms in the normal pancreas and in pancreatic disease.Cell Signal. 2017 Dec;40:1-9. doi: 10.1016/j.cellsig.2017.08.005. Epub 2017 Aug 18.
41 Paroxysmal movement disorders - practical update on diagnosis and management.Expert Rev Neurother. 2019 Sep;19(9):807-822. doi: 10.1080/14737175.2019.1648211. Epub 2019 Aug 8.
42 The role of PKC and PKD in CXCL12 directed prostate cancer migration.Biochem Biophys Res Commun. 2019 Oct 29;519(1):86-92. doi: 10.1016/j.bbrc.2019.08.134. Epub 2019 Aug 30.
43 Sotrastaurin attenuates the stemness of gastric cancer cells by targeting PKC.Biomed Pharmacother. 2019 Sep;117:109165. doi: 10.1016/j.biopha.2019.109165. Epub 2019 Jun 28.
44 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.
45 Development of a neural teratogenicity test based on human embryonic stem cells: response to retinoic acid exposure. Toxicol Sci. 2011 Dec;124(2):370-7.
46 Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
47 Identification of novel low-dose bisphenol a targets in human foreskin fibroblast cells derived from hypospadias patients. PLoS One. 2012;7(5):e36711. doi: 10.1371/journal.pone.0036711. Epub 2012 May 4.
48 Global gene expression analysis reveals differences in cellular responses to hydroxyl- and superoxide anion radical-induced oxidative stress in caco-2 cells. Toxicol Sci. 2010 Apr;114(2):193-203. doi: 10.1093/toxsci/kfp309. Epub 2009 Dec 31.
49 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.
50 CCAT1 is an enhancer-templated RNA that predicts BET sensitivity in colorectal cancer. J Clin Invest. 2016 Feb;126(2):639-52.
51 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.
52 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.