Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTJ3WIKC)

• DOT Name: Glutamate receptor ionotropic, delta-1 (GRID1)
• Synonyms: GluD1; GluR delta-1 subunit
• Gene Name: GRID1
• Related Disease:
  Colorectal carcinoma
  Bipolar disorder
  Breast cancer
  Depression
  Mental disorder
  Narcolepsy
  Schizoaffective disorder
  Acute myelogenous leukaemia
  Colorectal neoplasm
  Asthma
• UniProt ID: GRID1_HUMAN
• PDB ID: 8BLJ; 8BN2; 8BN5
• Pfam ID: PF01094 ; PF00060 ; PF10613
• Sequence:
  MEALTLWLLPWICQCVSVRADSIIHIGAIFEENAAKDDRVFQLAVSDLSLNDDILQSEKI
  TYSIKVIEANNPFQAVQEACDLMTQGILALVTSTGCASANALQSLTDAMHIPHLFVQRNP
  GGSPRTACHLNPSPDGEAYTLASRPPVRLNDVMLRLVTELRWQKFVMFYDSEYDIRGLQS
  FLDQASRLGLDVSLQKVDKNISHVFTSLFTTMKTEELNRYRDTLRRAILLLSPQGAHSFI
  NEAVETNLASKDSHWVFVNEEISDPEILDLVHSALGRMTVVRQIFPSAKDNQKCTRNNHR
  ISSLLCDPQEGYLQMLQISNLYLYDSVLMLANAFHRKLEDRKWHSMASLNCIRKSTKPWN
  GGRSMLDTIKKGHITGLTGVMEFREDSSNPYVQFEILGTTYSETFGKDMRKLATWDSEKG
  LNGSLQERPMGSRLQGLTLKVVTVLEEPFVMVAENILGQPKRYKGFSIDVLDALAKALGF
  KYEIYQAPDGRYGHQLHNTSWNGMIGELISKRADLAISAITITPERESVVDFSKRYMDYS
  VGILIKKPEEKISIFSLFAPFDFAVWACIAAAIPVVGVLIFVLNRIQAVRAQSAAQPRPS
  ASATLHSAIWIVYGAFVQQGGESSVNSMAMRIVMGSWWLFTLIVCSSYTANLAAFLTVSR
  MDNPIRTFQDLSKQVEMSYGTVRDSAVYEYFRAKGTNPLEQDSTFAELWRTISKNGGADN
  CVSSPSEGIRKAKKGNYAFLWDVAVVEYAALTDDDCSVTVIGNSISSKGYGIALQHGSPY
  RDLFSQRILELQDTGDLDVLKQKWWPHMGRCDLTSHASAQADGKSLKLHSFAGVFCILAI
  GLLLACLVAALELWWNSNRCHQETPKEDKEVNLEQVHRRMNSLMDEDIAHKQISPASIEL
  SALEMGGLAPTQTLEPTREYQNTQLSVSTFLPEQSSHGTSRTLSSGPSSNLPLPLSSSAT
  MPSMQCKHRSPNGGLFRQSPVKTPIPMSFQPVPGGVLPEALDTSHGTSI
• Function: Receptor for glutamate. L-glutamate acts as an excitatory neurotransmitter at many synapses in the central nervous system. The postsynaptic actions of Glu are mediated by a variety of receptors that are named according to their selective agonists.
• KEGG Pathway: Neuroactive ligand-receptor interaction (hsa04080)

Molecular Interaction Atlas (MIA) of This DOT

10 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Colorectal carcinoma	DIS5PYL0	Definitive	Biomarker	[1]
Bipolar disorder	DISAM7J2	Strong	Biomarker	[2]
Breast cancer	DIS7DPX1	Strong	Genetic Variation	[3]
Depression	DIS3XJ69	Strong	Biomarker	[4]
Mental disorder	DIS3J5R8	Strong	Genetic Variation	[5]
Narcolepsy	DISLCNLI	Strong	Genetic Variation	[6]
Schizoaffective disorder	DISLBW6B	Strong	Biomarker	[7]
Acute myelogenous leukaemia	DISCSPTN	moderate	Genetic Variation	[8]
Colorectal neoplasm	DISR1UCN	Disputed	Biomarker	[1]
Asthma	DISW9QNS	Limited	Genetic Variation	[9]

6 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 Glutamate receptor ionotropic, delta-1 (GRID1).	[10]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Glutamate receptor ionotropic, delta-1 (GRID1).	[11]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Glutamate receptor ionotropic, delta-1 (GRID1).	[12]
Menadione	DMSJDTY	Approved	Menadione affects the expression of Glutamate receptor ionotropic, delta-1 (GRID1).	[13]
Permethrin	DMZ0Q1G	Approved	Permethrin increases the expression of Glutamate receptor ionotropic, delta-1 (GRID1).	[15]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Glutamate receptor ionotropic, delta-1 (GRID1).	[17]

3 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Fulvestrant	DM0YZC6	Approved	Fulvestrant increases the methylation of Glutamate receptor ionotropic, delta-1 (GRID1).	[14]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Glutamate receptor ionotropic, delta-1 (GRID1).	[16]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the methylation of Glutamate receptor ionotropic, delta-1 (GRID1).	[14]

References

• [1] Genomic and epigenomic integration identifies a prognostic signature in colon cancer.Clin Cancer Res. 2011 Mar 15;17(6):1535-45. doi: 10.1158/1078-0432.CCR-10-2509. Epub 2011 Jan 28.
• [2] Deletion of glutamate delta-1 receptor in mouse leads to aberrant emotional and social behaviors.PLoS One. 2012;7(3):e32969. doi: 10.1371/journal.pone.0032969. Epub 2012 Mar 7.
• [3] A locus on 19p13 modifies risk of breast cancer in BRCA1 mutation carriers and is associated with hormone receptor-negative breast cancer in the general population.Nat Genet. 2010 Oct;42(10):885-92. doi: 10.1038/ng.669. Epub 2010 Sep 19.
• [4] Deletion of glutamate delta-1 receptor in mouse leads to enhanced working memory and deficit in fear conditioning.PLoS One. 2013;8(4):e60785. doi: 10.1371/journal.pone.0060785. Epub 2013 Apr 3.
• [5] Exome sequencing of a large family identifies potential candidate genes contributing risk to bipolar disorder. Gene. 2018 Mar 1;645:119-123. doi: 10.1016/j.gene.2017.12.025. Epub 2017 Dec 14.
• [6] Genome-wide association database developed in the Japanese Integrated Database Project.J Hum Genet. 2009 Sep;54(9):543-6. doi: 10.1038/jhg.2009.68. Epub 2009 Jul 24.
• [7] Bipolar I disorder and schizophrenia: a 440-single-nucleotide polymorphism screen of 64 candidate genes among Ashkenazi Jewish case-parent trios.Am J Hum Genet. 2005 Dec;77(6):918-36. doi: 10.1086/497703. Epub 2005 Oct 28.
• [8] Genome-wide haplotype association study identify the FGFR2 gene as a risk gene for acute myeloid leukemia.Oncotarget. 2017 Jan 31;8(5):7891-7899. doi: 10.18632/oncotarget.13631.
• [9] Identification of Four Novel Loci in Asthma in European American and African American Populations.Am J Respir Crit Care Med. 2017 Feb 15;195(4):456-463. doi: 10.1164/rccm.201604-0861OC.
• [10] Stem cell transcriptome responses and corresponding biomarkers that indicate the transition from adaptive responses to cytotoxicity. Chem Res Toxicol. 2017 Apr 17;30(4):905-922.
• [11] Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
• [12] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [13] 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.
• [14] 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.
• [15] Exposure to Insecticides Modifies Gene Expression and DNA Methylation in Hematopoietic Tissues In Vitro. Int J Mol Sci. 2023 Mar 26;24(7):6259. doi: 10.3390/ijms24076259.
• [16] 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.
• [17] 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.