Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTZW1WVQ)

DOT Name	Parvalbumin alpha (PVALB)
Gene Name	PVALB
Related Disease	Mood disorder ( ) Multiple sclerosis ( ) Neuroblastoma ( ) Adenoma ( ) Alzheimer disease ( ) Amyloidosis ( ) Anxiety ( ) Anxiety disorder ( ) Autism ( ) Autism spectrum disorder ( ) Bipolar depression ( ) Bipolar disorder ( ) Classic Hodgkin lymphoma ( ) Cognitive impairment ( ) Fragile X syndrome ( ) HIV infectious disease ( ) Huntington disease ( ) Major depressive disorder ( ) Mental disorder ( ) Neuralgia ( ) Neurodevelopmental disorder ( ) Non-insulin dependent diabetes ( ) Papillary renal cell carcinoma ( ) Parkinson disease ( ) Pervasive developmental disorder ( ) Psychotic disorder ( ) Renal cell carcinoma ( ) Rhabdomyosarcoma ( ) Schizoaffective disorder ( ) Status epilepticus seizure ( ) Stroke ( ) Temporal lobe epilepsy ( ) Absence epilepsy ( ) Amyotrophic lateral sclerosis ( ) Cardiac failure ( ) Congestive heart failure ( ) Dravet syndrome ( ) Obesity ( ) Angelman syndrome ( ) leukaemia ( ) Leukemia ( ) Neoplasm ( ) Nervous system disease ( )
UniProt ID	PRVA_HUMAN
3D Structure	Download 2D Sequence (FASTA) Download 3D Structure (PDB) Download
PDB ID	1RJV; 1RK9
Pfam ID	PF13499
Sequence	MSMTDLLNAEDIKKAVGAFSATDSFDHKKFFQMVGLKKKSADDVKKVFHMLDKDKSGFIE EDELGFILKGFSPDARDLSAKETKMLMAAGDKDGDGKIGVDEFSTLVAES
Function	In muscle, parvalbumin is thought to be involved in relaxation after contraction. It binds two calcium ions.
Reactome Pathway	Transcriptional Regulation by MECP2 (R-HSA-8986944 )

Molecular Interaction Atlas (MIA) of This DOT

43 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance
Mood disorder	DISLVMWO	Definitive	Biomarker	[1]
Multiple sclerosis	DISB2WZI	Definitive	Biomarker	[2]
Neuroblastoma	DISVZBI4	Definitive	Biomarker	[3]
Adenoma	DIS78ZEV	Strong	Biomarker	[4]
Alzheimer disease	DISF8S70	Strong	Biomarker	[5]
Amyloidosis	DISHTAI2	Strong	Biomarker	[5]
Anxiety	DISIJDBA	Strong	Biomarker	[6]
Anxiety disorder	DISBI2BT	Strong	Biomarker	[6]
Autism	DISV4V1Z	Strong	Biomarker	[7]
Autism spectrum disorder	DISXK8NV	Strong	Altered Expression	[8]
Bipolar depression	DISA75FU	Strong	Biomarker	[9]
Bipolar disorder	DISAM7J2	Strong	Altered Expression	[10]
Classic Hodgkin lymphoma	DISV1LU6	Strong	Biomarker	[11]
Cognitive impairment	DISH2ERD	Strong	Biomarker	[12]
Fragile X syndrome	DISE8W3A	Strong	Biomarker	[13]
HIV infectious disease	DISO97HC	Strong	Altered Expression	[14]
Huntington disease	DISQPLA4	Strong	Biomarker	[15]
Major depressive disorder	DIS4CL3X	Strong	Posttranslational Modification	[16]
Mental disorder	DIS3J5R8	Strong	Genetic Variation	[17]
Neuralgia	DISWO58J	Strong	Biomarker	[18]
Neurodevelopmental disorder	DIS372XH	Strong	Biomarker	[12]
Non-insulin dependent diabetes	DISK1O5Z	Strong	Biomarker	[19]
Papillary renal cell carcinoma	DIS25HBV	Strong	Biomarker	[20]
Parkinson disease	DISQVHKL	Strong	Biomarker	[21]
Pervasive developmental disorder	DIS51975	Strong	Altered Expression	[8]
Psychotic disorder	DIS4UQOT	Strong	Biomarker	[22]
Renal cell carcinoma	DISQZ2X8	Strong	Biomarker	[20]
Rhabdomyosarcoma	DISNR7MS	Strong	Altered Expression	[23]
Schizoaffective disorder	DISLBW6B	Strong	Biomarker	[9]
Status epilepticus seizure	DISY3BIC	Strong	Biomarker	[24]
Stroke	DISX6UHX	Strong	Biomarker	[25]
Temporal lobe epilepsy	DISNOPXX	Strong	Biomarker	[26]
Absence epilepsy	DISJPOUD	moderate	Biomarker	[27]
Amyotrophic lateral sclerosis	DISF7HVM	moderate	Biomarker	[28]
Cardiac failure	DISDC067	moderate	Biomarker	[29]
Congestive heart failure	DIS32MEA	moderate	Biomarker	[29]
Dravet syndrome	DISJF7LY	moderate	Biomarker	[30]
Obesity	DIS47Y1K	moderate	Biomarker	[25]
Angelman syndrome	DIS4QVXO	Disputed	Biomarker	[31]
leukaemia	DISS7D1V	Limited	Biomarker	[32]
Leukemia	DISNAKFL	Limited	Biomarker	[32]
Neoplasm	DISZKGEW	Limited	Biomarker	[33]
Nervous system disease	DISJ7GGT	Limited	Posttranslational Modification	[34]
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⏷ Show the Full List of 43 Disease(s)

Molecular Interaction Atlas (MIA)

MIA Detail

Jump to Detail Molecular Interaction Atlas of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate affects the expression of Parvalbumin alpha (PVALB).	[35]
Testosterone enanthate	DMB6871	Approved	Testosterone enanthate affects the expression of Parvalbumin alpha (PVALB).	[36]
Cocaine	DMSOX7I	Approved	Cocaine decreases the expression of Parvalbumin alpha (PVALB).	[37]
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1 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Parvalbumin alpha (PVALB).	[38]
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References

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2	Distribution of parvalbumin and calretinin immunoreactive interneurons in motor cortex from multiple sclerosis post-mortem tissue.Exp Brain Res. 2008 May;187(3):459-65. doi: 10.1007/s00221-008-1317-9. Epub 2008 Feb 23.
3	Alpha-parvalbumin reduces depolarization-induced elevations of cytosolic free calcium in human neuroblastoma cells.Cell Calcium. 1996 Jun;19(6):527-33. doi: 10.1016/s0143-4160(96)90062-7.
4	PVALB, a new Hrthle adenoma diagnostic marker identified through gene expression.J Clin Endocrinol Metab. 2011 Jan;96(1):E151-60. doi: 10.1210/jc.2010-1318. Epub 2010 Oct 6.
5	Early restoration of parvalbumin interneuron activity prevents memory loss and network hyperexcitability in a mouse model of Alzheimer's disease.Mol Psychiatry. 2020 Dec;25(12):3380-3398. doi: 10.1038/s41380-019-0483-4. Epub 2019 Aug 20.
6	Interneuronal -GABA(A) receptors regulate binge drinking and are necessary for the behavioral effects of early withdrawal.Neuropsychopharmacology. 2019 Jan;44(2):425-434. doi: 10.1038/s41386-018-0164-z. Epub 2018 Jul 28.
7	Embryonic stem cell transplants as a therapeutic strategy in a rodent model of autism.Neuropsychopharmacology. 2018 Jul;43(8):1789-1798. doi: 10.1038/s41386-018-0021-0. Epub 2018 Feb 7.
8	Inducible and reversible silencing of the Pvalb gene in mice: An in vitro and in vivo study.Eur J Neurosci. 2019 Aug;50(4):2694-2706. doi: 10.1111/ejn.14404. Epub 2019 Jun 17.
9	Molecular abnormalities of the hippocampus in severe psychiatric illness: postmortem findings from the Stanley Neuropathology Consortium.Mol Psychiatry. 2004 Jun;9(6):609-20, 544. doi: 10.1038/sj.mp.4001471.
10	The thalamic reticular nucleus in schizophrenia and bipolar disorder: role of parvalbumin-expressing neuron networks and oxidative stress.Mol Psychiatry. 2018 Oct;23(10):2057-2065. doi: 10.1038/mp.2017.230. Epub 2017 Nov 28.
11	Simultaneous intrinsic signal imaging of auditory and visual cortex reveals profound effects of acute hearing loss on visual processing.Neuroimage. 2017 Oct 1;159:459-472. doi: 10.1016/j.neuroimage.2017.07.037. Epub 2017 Jul 20.
12	Downregulation of Npas4 in parvalbumin interneurons and cognitive deficits after neonatal NMDA receptor blockade: relevance for schizophrenia.Transl Psychiatry. 2019 Feb 21;9(1):99. doi: 10.1038/s41398-019-0436-3.
13	Beneficial effects of sound exposure on auditory cortex development in a mouse model of Fragile X Syndrome.Neurobiol Dis. 2020 Feb;134:104622. doi: 10.1016/j.nbd.2019.104622. Epub 2019 Nov 5.
14	Quantitation of parvalbumin+ neurons and human immunodeficiency virus type 1 (HIV-1) regulatory gene expression in the HIV-1 transgenic rat: effects of vitamin A deficiency and morphine.J Neurovirol. 2010 Feb;16(1):33-40. doi: 10.3109/13550280903555712.
15	Striatal Vulnerability in Huntington's Disease: Neuroprotection Versus Neurotoxicity.Brain Sci. 2017 Jun 7;7(6):63. doi: 10.3390/brainsci7060063.
16	Parvalbumin Promoter Methylation Altered in Major Depressive Disorder.Int J Med Sci. 2019 Aug 14;16(9):1207-1214. doi: 10.7150/ijms.36131. eCollection 2019.
17	Alterations of GABAergic Neuron-Associated Extracellular Matrix and Synaptic Responses in Gad1-Heterozygous Mice Subjected to Prenatal Stress.Front Cell Neurosci. 2018 Sep 5;12:284. doi: 10.3389/fncel.2018.00284. eCollection 2018.
18	Neuropathic Pain Creates an Enduring Prefrontal Cortex Dysfunction Corrected by the Type II Diabetic Drug Metformin But Not by Gabapentin.J Neurosci. 2018 Aug 15;38(33):7337-7350. doi: 10.1523/JNEUROSCI.0713-18.2018. Epub 2018 Jul 20.
19	Impact of obesity-induced type 2 diabetes on long-term outcomes following stroke.Clin Sci (Lond). 2019 Jul 22;133(14):1603-1607. doi: 10.1042/CS20190492. Print 2019 Jul 31.
20	Diagnostic value of cytokeratin 7 and parvalbumin in differentiating chromophobe renal cell carcinoma from renal oncocytoma.Anal Quant Cytol Histol. 2006 Aug;28(4):228-36.
21	Novel application of the gray-level co-occurrence matrix analysis in the parvalbumin stained hippocampal gyrus dentatus in distinct rat models of Parkinson's disease.Comput Biol Med. 2019 Dec;115:103482. doi: 10.1016/j.compbiomed.2019.103482. Epub 2019 Oct 4.
22	Parvalbumin promoter hypermethylation in postmortem brain in schizophrenia.Epigenomics. 2018 May;10(5):519-524. doi: 10.2217/epi-2017-0159. Epub 2018 Apr 24.
23	Expression of memory, differentiation, and repression of c-myc and p53 genes in human RD/TE-671 cells induced by a ureido-derivative of pyridine (UDP-4).Cell Growth Differ. 1996 Jun;7(6):797-809.
24	Paradoxical effects of optogenetic stimulation in mesial temporal lobe epilepsy.Ann Neurol. 2019 Nov;86(5):714-728. doi: 10.1002/ana.25572. Epub 2019 Aug 27.
25	Obesity-induced type 2 diabetes impairs neurological recovery after stroke in correlation with decreased neurogenesis and persistent atrophy of parvalbumin-positive interneurons.Clin Sci (Lond). 2019 Jul 1;133(13):1367-1386. doi: 10.1042/CS20190180. Print 2019 Jul 15.
26	Proportional loss of parvalbumin-immunoreactive synaptic boutons and granule cells from the hippocampus of sea lions with temporal lobe epilepsy.J Comp Neurol. 2019 Oct 1;527(14):2341-2355. doi: 10.1002/cne.24680. Epub 2019 Mar 22.
27	Sensory coding is impaired in rat absence epilepsy.J Physiol. 2019 Feb;597(3):951-966. doi: 10.1113/JP277297. Epub 2019 Jan 4.
28	Deletion of the endogenous TrkB.T1 receptor isoform restores the number of hippocampal CA1 parvalbumin-positive neurons and rescues long-term potentiation in pre-symptomatic mSOD1(G93A) ALS mice.Mol Cell Neurosci. 2018 Jun;89:33-41. doi: 10.1016/j.mcn.2018.03.010. Epub 2018 Mar 24.
29	Ca(2+)-Binding Proteins of the EF-Hand Superfamily: Diagnostic and Prognostic Biomarkers and Novel Therapeutic Targets.Methods Mol Biol. 2019;1929:157-186. doi: 10.1007/978-1-4939-9030-6_11.
30	Discovery of novel 4-phenyl-2-(pyrrolidinyl)nicotinamide derivatives as potent Na(v)1.1 activators.Bioorg Med Chem Lett. 2019 Mar 15;29(6):815-820. doi: 10.1016/j.bmcl.2019.01.023. Epub 2019 Jan 23.
31	Down-Regulation of miRNA-708 Promotes Aberrant Calcium Signaling by Targeting Neuronatin in a Mouse Model of Angelman Syndrome.Front Mol Neurosci. 2019 Feb 13;12:35. doi: 10.3389/fnmol.2019.00035. eCollection 2019.
32	Effect of tyrosinase and caffeic acid crosslinking of turbot parvalbumin on the digestibility, and release of mediators and cytokines from activated RBL-2H3 cells.Food Chem. 2019 Dec 1;300:125209. doi: 10.1016/j.foodchem.2019.125209. Epub 2019 Jul 20.
33	Renal oncocytoma with and without intravascular extension into the branches of renal vein have the same morphological, immunohistochemical, and genetic features.Virchows Arch. 2008 Feb;452(2):193-200. doi: 10.1007/s00428-007-0541-1. Epub 2007 Dec 8.
34	The Perineuronal 'Safety' Net? Perineuronal Net Abnormalities in Neurological Disorders.Front Mol Neurosci. 2018 Aug 3;11:270. doi: 10.3389/fnmol.2018.00270. eCollection 2018.
35	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.
36	Transcriptional profiling of testosterone-regulated genes in the skeletal muscle of human immunodeficiency virus-infected men experiencing weight loss. J Clin Endocrinol Metab. 2007 Jul;92(7):2793-802. doi: 10.1210/jc.2006-2722. Epub 2007 Apr 17.
37	Cytosolic proteomic alterations in the nucleus accumbens of cocaine overdose victims. Mol Psychiatry. 2007 Jan;12(1):55-73. doi: 10.1038/sj.mp.4001914. Epub 2006 Oct 31.
38	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.