Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT2GJ7XZ)

DOT Name Glutamine--tRNA ligase (QARS1)
Synonyms EC 6.1.1.18; Glutaminyl-tRNA synthetase; GlnRS
Gene Name QARS1
Related Disease
Diffuse cerebral and cerebellar atrophy - intractable seizures - progressive microcephaly syndrome ( )
Microcephaly-short stature-intellectual disability-facial dysmorphism syndrome ( )
UniProt ID
SYQ_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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PDB ID
4R3Z; 4YE6; 4YE8; 4YE9
EC Number
6.1.1.18
Pfam ID
PF00749 ; PF03950 ; PF20974 ; PF04558 ; PF04557
Sequence
MAALDSLSLFTSLGLSEQKARETLKNSALSAQLREAATQAQQTLGSTIDKATGILLYGLA
SRLRDTRRLSFLVSYIASKKIHTEPQLSAALEYVRSHPLDPIDTVDFERECGVGVIVTPE
QIEEAVEAAINRHRPQLLVERYHFNMGLLMGEARAVLKWADGKMIKNEVDMQVLHLLGPK
LEADLEKKFKVAKARLEETDRRTAKDVVENGETADQTLSLMEQLRGEALKFHKPGENYKT
PGYVVTPHTMNLLKQHLEITGGQVRTRFPPEPNGILHIGHAKAINFNFGYAKANNGICFL
RFDDTNPEKEEAKFFTAICDMVAWLGYTPYKVTYASDYFDQLYAWAVELIRRGLAYVCHQ
RGEELKGHNTLPSPWRDRPMEESLLLFEAMRKGKFSEGEATLRMKLVMEDGKMDPVAYRV
KYTPHHRTGDKWCIYPTYDYTHCLCDSIEHITHSLCTKEFQARRSSYFWLCNALDVYCPV
QWEYGRLNLHYAVVSKRKILQLVATGAVRDWDDPRLFTLTALRRRGFPPEAINNFCARVG
VTVAQTTMEPHLLEACVRDVLNDTAPRAMAVLESLRVIITNFPAAKSLDIQVPNFPADET
KGFHQVPFAPIVFIERTDFKEEPEPGFKRLAWGQPVGLRHTGYVIELQHVVKGPSGCVES
LEVTCRRADAGEKPKAFIHWVSQPLMCEVRLYERLFQHKNPEDPTEVPGGFLSDLNLASL
HVVDAALVDCSVALAKPFDKFQFERLGYFSVDPDSHQGKLVFNRTVTLKEDPGKV
Function Glutamine--tRNA ligase. Plays a critical role in brain development.
Tissue Specificity Highly expressed in fetal cerebral cortex, particularly in the ventricular zone, inner subventricular zone, outer subventricular zone, and cortical plate.
KEGG Pathway
Aminoacyl-tR. biosynthesis (hsa00970 )
Metabolic pathways (hsa01100 )
Reactome Pathway
Cytosolic tRNA aminoacylation (R-HSA-379716 )
Mitochondrial tRNA aminoacylation (R-HSA-379726 )
Selenoamino acid metabolism (R-HSA-2408522 )

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Diffuse cerebral and cerebellar atrophy - intractable seizures - progressive microcephaly syndrome DISOAE2X Definitive Autosomal recessive [1]
Microcephaly-short stature-intellectual disability-facial dysmorphism syndrome DISAHCQX Supportive Autosomal recessive [2]
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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 Glutamine--tRNA ligase (QARS1). [3]
Glyphosate DM0AFY7 Investigative Glyphosate affects the methylation of Glutamine--tRNA ligase (QARS1). [9]
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6 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Tretinoin DM49DUI Approved Tretinoin increases the expression of Glutamine--tRNA ligase (QARS1). [4]
Cisplatin DMRHGI9 Approved Cisplatin increases the expression of Glutamine--tRNA ligase (QARS1). [5]
Ivermectin DMDBX5F Approved Ivermectin decreases the expression of Glutamine--tRNA ligase (QARS1). [6]
Bisphenol A DM2ZLD7 Investigative Bisphenol A increases the expression of Glutamine--tRNA ligase (QARS1). [7]
chloropicrin DMSGBQA Investigative chloropicrin increases the expression of Glutamine--tRNA ligase (QARS1). [8]
Okadaic acid DM47CO1 Investigative Okadaic acid affects the expression of Glutamine--tRNA ligase (QARS1). [10]
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⏷ Show the Full List of 6 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 Severe growth deficiency, microcephaly, intellectual disability, and characteristic facial features are due to a homozygous QARS mutation. Neurogenetics. 2017 Jul;18(3):141-146. doi: 10.1007/s10048-017-0516-6. Epub 2017 Jun 15.
3 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.
4 Pharmacogenomic analysis of acute promyelocytic leukemia cells highlights CYP26 cytochrome metabolism in differential all-trans retinoic acid sensitivity. Blood. 2007 May 15;109(10):4450-60.
5 Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
6 Quantitative proteomics reveals a broad-spectrum antiviral property of ivermectin, benefiting for COVID-19 treatment. J Cell Physiol. 2021 Apr;236(4):2959-2975. doi: 10.1002/jcp.30055. Epub 2020 Sep 22.
7 Alternatives for the worse: Molecular insights into adverse effects of bisphenol a and substitutes during human adipocyte differentiation. Environ Int. 2021 Nov;156:106730. doi: 10.1016/j.envint.2021.106730. Epub 2021 Jun 27.
8 Transcriptomic analysis of human primary bronchial epithelial cells after chloropicrin treatment. Chem Res Toxicol. 2015 Oct 19;28(10):1926-35.
9 Association of Glyphosate Exposure with Blood DNA Methylation in a Cross-Sectional Study of Postmenopausal Women. Environ Health Perspect. 2022 Apr;130(4):47001. doi: 10.1289/EHP10174. Epub 2022 Apr 4.
10 Alterations in metabolism-related genes induced in SHSY5Y cells by okadaic acid exposure. J Toxicol Environ Health A. 2012;75(13-15):844-56. doi: 10.1080/15287394.2012.690703.