Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTDQ0KW7)

DOT Name	Glycine receptor subunit alpha-2 (GLRA2)
Gene Name	GLRA2
Related Disease	Hepatocellular carcinoma ( ) Neoplasm ( ) Autism ( ) Dementia ( ) Epilepsy ( ) Intellectual developmental disorder, X-linked, syndromic, Pilorge type ( ) Myocardial infarction ( ) X-linked dominant hypophosphatemic rickets ( ) Autism spectrum disorder ( ) Nervous system disease ( ) Rett syndrome ( ) Wilms tumor ( )
UniProt ID	GLRA2_HUMAN
3D Structure	Download 2D Sequence (FASTA) Download 3D Structure (PDB) Download
PDB ID	5BKF; 5BKG; 7KUY; 7L31
Pfam ID	PF02931 ; PF02932
Sequence	MNRQLVNILTALFAFFLETNHFRTAFCKDHDSRSGKQPSQTLSPSDFLDKLMGRTSGYDA RIRPNFKGPPVNVTCNIFINSFGSVTETTMDYRVNIFLRQQWNDSRLAYSEYPDDSLDLD PSMLDSIWKPDLFFANEKGANFHDVTTDNKLLRISKNGKVLYSIRLTLTLSCPMDLKNFP MDVQTCTMQLESFGYTMNDLIFEWLSDGPVQVAEGLTLPQFILKEEKELGYCTKHYNTGK FTCIEVKFHLERQMGYYLIQMYIPSLLIVILSWVSFWINMDAAPARVALGITTVLTMTTQ SSGSRASLPKVSYVKAIDIWMAVCLLFVFAALLEYAAVNFVSRQHKEFLRLRRRQKRQNK EEDVTRESRFNFSGYGMGHCLQVKDGTAVKATPANPLPQPPKDGDAIKKKFVDRAKRIDT ISRAAFPLAFLIFNIFYWITYKIIRHEDVHKK
Function	Glycine receptors are ligand-gated chloride channels. Channel opening is triggered by extracellular glycine. Channel opening is also triggered by taurine and beta-alanine. Plays a role in synaptic plasticity. Contributes to the generation of inhibitory postsynaptic currents, and is involved in the down-regulation of neuronal excitability. Plays a role in cellular responses to ethanol.
KEGG Pathway	Neuroactive ligand-receptor interaction (hsa04080 )
Reactome Pathway	Neurotransmitter receptors and postsynaptic signal transmission (R-HSA-112314 )

Molecular Interaction Atlas (MIA) of This DOT

12 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance
Hepatocellular carcinoma	DIS0J828	Definitive	Biomarker	[1]
Neoplasm	DISZKGEW	Definitive	Biomarker	[1]
Autism	DISV4V1Z	Strong	Genetic Variation	[2]
Dementia	DISXL1WY	Strong	Biomarker	[3]
Epilepsy	DISBB28L	Strong	Biomarker	[4]
Intellectual developmental disorder, X-linked, syndromic, Pilorge type	DISF038C	Strong	X-linked	[2]
Myocardial infarction	DIS655KI	Strong	Biomarker	[5]
X-linked dominant hypophosphatemic rickets	DISU3OP6	Strong	Biomarker	[6]
Autism spectrum disorder	DISXK8NV	Limited	Biomarker	[7]
Nervous system disease	DISJ7GGT	Limited	Genetic Variation	[8]
Rett syndrome	DISGG5UV	Limited	Biomarker	[8]
Wilms tumor	DISB6T16	Limited	Biomarker	[9]
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Molecular Interaction Atlas (MIA)

MIA Detail

Jump to Detail Molecular Interaction Atlas of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Lindane	DMB8CNL	Approved	Lindane decreases the activity of Glycine receptor subunit alpha-2 (GLRA2).	[10]
[3H]methyltrienolone	DMTSGOW	Investigative	[3H]methyltrienolone decreases the expression of Glycine receptor subunit alpha-2 (GLRA2).	[12]
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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 Glycine receptor subunit alpha-2 (GLRA2).	[11]
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References

1	Prognostic Value of Gamma-Glutamyl Transpeptidase to Lymphocyte Count Ratio in Patients With Single Tumor Size ?5 cm Hepatocellular Carcinoma After Radical Resection.Front Oncol. 2019 May 21;9:347. doi: 10.3389/fonc.2019.00347. eCollection 2019.
2	Genetic and functional analyses demonstrate a role for abnormal glycinergic signaling in autism. Mol Psychiatry. 2016 Jul;21(7):936-45. doi: 10.1038/mp.2015.139. Epub 2015 Sep 15.
3	Balance between innate versus adaptive immune system and the risk of dementia: a population-based cohort study.J Neuroinflammation. 2019 Mar 30;16(1):68. doi: 10.1186/s12974-019-1454-z.
4	Epigenetic mechanisms underlying human epileptic disorders and the process of epileptogenesis.Neurobiol Dis. 2010 Jul;39(1):53-60. doi: 10.1016/j.nbd.2010.02.005. Epub 2010 Feb 24.
5	Identification of risk genes associated with myocardial infarction based on the recursive feature elimination algorithm and support vector machine classifier.Mol Med Rep. 2018 Jan;17(1):1555-1560. doi: 10.3892/mmr.2017.8044. Epub 2017 Nov 14.
6	Fine structure mapping of the human X-linked hypophosphatemic rickets gene locus.J Clin Endocrinol Metab. 1994 Nov;79(5):1351-4. doi: 10.1210/jcem.79.5.7962329.
7	2-glycine receptors modulate adult hippocampal neurogenesis and spatial memory.Dev Neurobiol. 2017 Dec;77(12):1430-1441. doi: 10.1002/dneu.22549. Epub 2017 Oct 26.
8	Analysis of the genomic structure of the human glycine receptor alpha2 subunit gene and exclusion of this gene as a candidate for Rett syndrome.Am J Med Genet. 1998 Jun 30;78(2):176-8.
9	Predicted Markers of Overall Survival in Pancreatic Cancer Patients Receiving Dendritic Cell Vaccinations Targeting WT1.Oncology. 2019;97(3):135-148. doi: 10.1159/000500359. Epub 2019 Jun 19.
10	Mechanism of action of the insecticides, lindane and fipronil, on glycine receptor chloride channels. Br J Pharmacol. 2012 Apr;165(8):2707-20. doi: 10.1111/j.1476-5381.2011.01722.x.
11	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.
12	Gene expression signature-based chemical genomic prediction identifies a novel class of HSP90 pathway modulators. Cancer Cell. 2006 Oct;10(4):321-30.