Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTVGE10W)

DOT Name Neurogranin (NRGN)
Synonyms Ng; RC3
Gene Name NRGN
Related Disease
Parkinson disease ( )
Androgen insensitivity syndrome ( )
Arthritis ( )
Bipolar disorder ( )
Cognitive impairment ( )
Colitis ( )
Congenital hypothyroidism ( )
Creutzfeldt Jacob disease ( )
Dementia ( )
Depression ( )
Familial Alzheimer disease ( )
Huntington disease ( )
Hypothyroidism ( )
Major depressive disorder ( )
Mental disorder ( )
Neuroblastoma ( )
Parkinsonian disorder ( )
Stroke ( )
Alcohol dependence ( )
Frontotemporal dementia ( )
Neoplasm ( )
Amyotrophic lateral sclerosis ( )
HIV infectious disease ( )
Lewy body dementia ( )
Nervous system disease ( )
Pick disease ( )
UniProt ID
NEUG_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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Pfam ID
PF00612
Sequence
MDCCTENACSKPDDDILDIPLDDPGANAAAAKIQASFRGHMARKKIKSGERGRKGPGPGG
PGGAGVARGGAGGGPSGD
Function Acts as a 'third messenger' substrate of protein kinase C-mediated molecular cascades during synaptic development and remodeling. Binds to calmodulin in the absence of calcium.
Tissue Specificity In the cerebral cortex, found in the cell bodies of neurons in layers II-VI, and in apical and basal dendrites of pyramidal neurons. Is not found in the dendrites in patients with Alzheimer disease.
Reactome Pathway
Long-term potentiation (R-HSA-9620244 )

Molecular Interaction Atlas (MIA) of This DOT

26 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Parkinson disease DISQVHKL Definitive Biomarker [1]
Androgen insensitivity syndrome DISUZBBO Strong Biomarker [2]
Arthritis DIST1YEL Strong Genetic Variation [3]
Bipolar disorder DISAM7J2 Strong Genetic Variation [4]
Cognitive impairment DISH2ERD Strong Altered Expression [5]
Colitis DISAF7DD Strong Genetic Variation [6]
Congenital hypothyroidism DISL5XVU Strong Altered Expression [7]
Creutzfeldt Jacob disease DISCB6RX Strong Altered Expression [8]
Dementia DISXL1WY Strong Biomarker [9]
Depression DIS3XJ69 Strong Biomarker [10]
Familial Alzheimer disease DISE75U4 Strong Biomarker [11]
Huntington disease DISQPLA4 Strong Biomarker [12]
Hypothyroidism DISR0H6D Strong Biomarker [13]
Major depressive disorder DIS4CL3X Strong Biomarker [14]
Mental disorder DIS3J5R8 Strong Biomarker [4]
Neuroblastoma DISVZBI4 Strong Altered Expression [15]
Parkinsonian disorder DISHGY45 Strong Biomarker [9]
Stroke DISX6UHX Strong Biomarker [16]
Alcohol dependence DIS4ZSCO moderate Biomarker [17]
Frontotemporal dementia DISKYHXL moderate Biomarker [18]
Neoplasm DISZKGEW Disputed Altered Expression [19]
Amyotrophic lateral sclerosis DISF7HVM Limited Biomarker [18]
HIV infectious disease DISO97HC Limited Biomarker [1]
Lewy body dementia DISAE66J Limited Biomarker [1]
Nervous system disease DISJ7GGT Limited Biomarker [1]
Pick disease DISP6X50 Limited Biomarker [18]
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⏷ Show the Full List of 26 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
10 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Valproate DMCFE9I Approved Valproate increases the expression of Neurogranin (NRGN). [20]
Tretinoin DM49DUI Approved Tretinoin decreases the expression of Neurogranin (NRGN). [21]
Vorinostat DMWMPD4 Approved Vorinostat increases the expression of Neurogranin (NRGN). [22]
Carbamazepine DMZOLBI Approved Carbamazepine affects the expression of Neurogranin (NRGN). [23]
SNDX-275 DMH7W9X Phase 3 SNDX-275 increases the expression of Neurogranin (NRGN). [22]
Nabiximols DMHKJ5I Phase 3 Nabiximols decreases the expression of Neurogranin (NRGN). [24]
OTX-015 DMI8RG1 Phase 1/2 OTX-015 increases the expression of Neurogranin (NRGN). [25]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene increases the expression of Neurogranin (NRGN). [26]
(+)-JQ1 DM1CZSJ Phase 1 (+)-JQ1 decreases the expression of Neurogranin (NRGN). [27]
Trichostatin A DM9C8NX Investigative Trichostatin A affects the expression of Neurogranin (NRGN). [28]
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⏷ Show the Full List of 10 Drug(s)

References

1 Cerebrospinal Fluid Concentrations of the Synaptic Marker Neurogranin in Neuro-HIV and Other Neurological Disorders.Curr HIV/AIDS Rep. 2019 Feb;16(1):76-81. doi: 10.1007/s11904-019-00420-1.
2 Neurogranin and tau in cerebrospinal fluid and plasma of patients with acute ischemic stroke.BMC Neurol. 2017 Aug 30;17(1):170. doi: 10.1186/s12883-017-0945-8.
3 Humanin prevents undesired apoptosis of chondrocytes without interfering with the anti-inflammatory effect of dexamethasone in collagen-induced arthritis.Clin Exp Rheumatol. 2020 Jan-Feb;38(1):129-135. Epub 2019 Jun 6.
4 Polymorphisms in NRGN are associated with schizophrenia, major depressive disorder and bipolar disorder in the Han Chinese population.J Affect Disord. 2016 Apr;194:180-7. doi: 10.1016/j.jad.2016.01.034. Epub 2016 Jan 13.
5 Neurogranin Expression Is Regulated by Synaptic Activity and Promotes Synaptogenesis in Cultured Hippocampal Neurons.Mol Neurobiol. 2019 Nov;56(11):7321-7337. doi: 10.1007/s12035-019-1593-3. Epub 2019 Apr 24.
6 Effects of humanin on experimental colitis induced by 2,4,6-trinitrobenzene sulphonic acid in rats.Saudi J Gastroenterol. 2017 Mar-Apr;23(2):105-111. doi: 10.4103/sjg.SJG_318_16.
7 RC3/neurogranin structure and expression in the caprine brain in relation to congenital hypothyroidism.Brain Res Mol Brain Res. 1995 Mar;29(1):119-30. doi: 10.1016/0169-328x(94)00237-9.
8 CSF neurogranin as a neuronal damage marker in CJD: a comparative study with AD.J Neurol Neurosurg Psychiatry. 2019 Aug;90(8):846-853. doi: 10.1136/jnnp-2018-320155. Epub 2019 May 16.
9 Cerebrospinal fluid levels of neurogranin in Parkinsonian disorders.Mov Disord. 2020 Mar;35(3):513-518. doi: 10.1002/mds.27950. Epub 2019 Dec 13.
10 Biomarkers for Antidepressant Efficacy of Electroconvulsive Therapy: An Exploratory Cerebrospinal Fluid Study.Neuropsychobiology. 2019;77(1):13-22. doi: 10.1159/000491401. Epub 2018 Aug 17.
11 The intact postsynaptic protein neurogranin is reduced in brain tissue from patients with familial and sporadic Alzheimer's disease.Acta Neuropathol. 2019 Jan;137(1):89-102. doi: 10.1007/s00401-018-1910-3. Epub 2018 Sep 22.
12 Cerebrospinal fluid neurogranin and TREM2 in Huntington's disease.Sci Rep. 2018 Mar 9;8(1):4260. doi: 10.1038/s41598-018-21788-x.
13 The nature of the compensatory response to low thyroid hormone in the developing brain.J Neuroendocrinol. 2010 Mar;22(3):153-65. doi: 10.1111/j.1365-2826.2009.01947.x. Epub 2009 Dec 23.
14 Electroconvulsive therapy does not alter the synaptic protein neurogranin in the cerebrospinal fluid of patients with major depression.J Neural Transm (Vienna). 2017 Dec;124(12):1641-1645. doi: 10.1007/s00702-017-1802-z. Epub 2017 Oct 23.
15 Differential expression of MARCKS and other calmodulin-binding protein kinase C substrates in cultured neuroblastoma and glioma cells.J Neurochem. 1994 Dec;63(6):2314-23. doi: 10.1046/j.1471-4159.1994.63062314.x.
16 The effect of DPP-4 inhibition to improve functional outcome after stroke is mediated by the SDF-1/CXCR4 pathway.Cardiovasc Diabetol. 2018 May 19;17(1):60. doi: 10.1186/s12933-018-0702-3.
17 Neurogranin in the nucleus accumbens regulates NMDA receptor tolerance and motivation for ethanol seeking.Neuropharmacology. 2018 Mar 15;131:58-67. doi: 10.1016/j.neuropharm.2017.12.008. Epub 2017 Dec 7.
18 Cerebrospinal fluid neurogranin concentration in neurodegeneration: relation to clinical phenotypes and neuropathology.Acta Neuropathol. 2018 Sep;136(3):363-376. doi: 10.1007/s00401-018-1851-x. Epub 2018 Apr 26.
19 Identification of histological markers for malignant glioma by genome-wide expression analysis: dynein, alpha-PIX and sorcin.Acta Neuropathol. 2006 Jan;111(1):29-38. doi: 10.1007/s00401-005-1085-6. Epub 2005 Nov 30.
20 The neuroprotective action of the mood stabilizing drugs lithium chloride and sodium valproate is mediated through the up-regulation of the homeodomain protein Six1. Toxicol Appl Pharmacol. 2009 Feb 15;235(1):124-34.
21 Effect of retinoic acid on gene expression in human conjunctival epithelium: secretory phospholipase A2 mediates retinoic acid induction of MUC16. Invest Ophthalmol Vis Sci. 2005 Nov;46(11):4050-61.
22 Definition of transcriptome-based indices for quantitative characterization of chemically disturbed stem cell development: introduction of the STOP-Toxukn and STOP-Toxukk tests. Arch Toxicol. 2017 Feb;91(2):839-864.
23 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.
24 Clinical response to Nabiximols correlates with the downregulation of immune pathways in multiple sclerosis. Eur J Neurol. 2018 Jul;25(7):934-e70. doi: 10.1111/ene.13623. Epub 2018 Apr 16.
25 Comprehensive transcriptome profiling of BET inhibitor-treated HepG2 cells. PLoS One. 2022 Apr 29;17(4):e0266966. doi: 10.1371/journal.pone.0266966. eCollection 2022.
26 Identification of a transcriptomic signature of food-relevant genotoxins in human HepaRG hepatocarcinoma cells. Food Chem Toxicol. 2020 Jun;140:111297. doi: 10.1016/j.fct.2020.111297. Epub 2020 Mar 28.
27 Bromodomain-containing protein 4 (BRD4) regulates RNA polymerase II serine 2 phosphorylation in human CD4+ T cells. J Biol Chem. 2012 Dec 14;287(51):43137-55.
28 A trichostatin A expression signature identified by TempO-Seq targeted whole transcriptome profiling. PLoS One. 2017 May 25;12(5):e0178302. doi: 10.1371/journal.pone.0178302. eCollection 2017.