Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTPVAX04)

DOT Name Transcriptional regulator QRICH1 (QRICH1)
Synonyms Glutamine-rich protein 1
Gene Name QRICH1
Related Disease
Syndromic intellectual disability ( )
Ververi-Brady syndrome ( )
Alzheimer disease ( )
Intellectual disability ( )
Neuroblastoma ( )
Coronary heart disease ( )
Schizophrenia ( )
UniProt ID
QRIC1_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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Pfam ID
PF12012
Sequence
MNNSLENTISFEEYIRVKARSVPQHRMKEFLDSLASKGPEALQEFQQTATTTMVYQQGGN
CIYTDSTEVAGSLLELACPVTTSVQPQTQQEQQIQVQQPQQVQVQVQVQQSPQQVSAQLS
PQLTVHQPTEQPIQVQVQIQGQAPQSAAPSIQTPSLQSPSPSQLQAAQIQVQHVQAAQQI
QAAEIPEEHIPHQQIQAQLVAGQSLAGGQQIQIQTVGALSPPPSQQGSPREGERRVGTAS
VLQPVKKRKVDMPITVSYAISGQPVATVLAIPQGQQQSYVSLRPDLLTVDSAHLYSATGT
ITSPTGETWTIPVYSAQPRGDPQQQSITHIAIPQEAYNAVHVSGSPTALAAVKLEDDKEK
MVGTTSVVKNSHEEVVQTLANSLFPAQFMNGNIHIPVAVQAVAGTYQNTAQTVHIWDPQQ
QPQQQTPQEQTPPPQQQQQQLQVTCSAQTVQVAEVEPQSQPQPSPELLLPNSLKPEEGLE
VWKNWAQTKNAELEKDAQNRLAPIGRRQLLRFQEDLISSAVAELNYGLCLMTREARNGEG
EPYDPDVLYYIFLCIQKYLFENGRVDDIFSDLYYVRFTEWLHEVLKDVQPRVTPLGYVLP
SHVTEEMLWECKQLGAHSPSTLLTTLMFFNTKYFLLKTVDQHMKLAFSKVLRQTKKNPSN
PKDKSTSIRYLKALGIHQTGQKVTDDMYAEQTENPENPLRCPIKLYDFYLFKCPQSVKGR
NDTFYLTPEPVVAPNSPIWYSVQPISREQMGQMLTRILVIREIQEAIAVANASTMH
Function
Transcriptional regulator that acts as a mediator of the integrated stress response (ISR) through transcriptional control of protein homeostasis under conditions of ER stress. Controls the outcome of the unfolded protein response (UPR) which is an ER-stress response pathway. ER stress induces QRICH1 translation by a ribosome translation re-initiation mechanism in response to EIF2S1/eIF-2-alpha phosphorylation, and stress-induced QRICH1 regulates a transcriptional program associated with protein translation, protein secretion-mediated proteotoxicity and cell death during the terminal UPR. May cooperate with ATF4 transcription factor signaling to regulate ER homeostasis which is critical for cell viability. Up-regulates CASP3/caspase-3 activity in epithelial cells under ER stress. Central regulator of proteotoxicity associated with ER stress-mediated inflammatory diseases in the intestines and liver. Involved in chondrocyte hypertrophy, a process required for normal longitudinal bone growth.

Molecular Interaction Atlas (MIA) of This DOT

7 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Syndromic intellectual disability DISH7SDF Definitive Autosomal dominant [1]
Ververi-Brady syndrome DISARDLU Definitive Autosomal dominant [2]
Alzheimer disease DISF8S70 Strong Biomarker [3]
Intellectual disability DISMBNXP Strong Biomarker [4]
Neuroblastoma DISVZBI4 Strong Altered Expression [3]
Coronary heart disease DIS5OIP1 moderate Genetic Variation [5]
Schizophrenia DISSRV2N No Known Unknown [6]
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⏷ Show the Full List of 7 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
5 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 Transcriptional regulator QRICH1 (QRICH1). [7]
Paclitaxel DMLB81S Approved Paclitaxel increases the phosphorylation of Transcriptional regulator QRICH1 (QRICH1). [3]
Vinblastine DM5TVS3 Approved Vinblastine increases the phosphorylation of Transcriptional regulator QRICH1 (QRICH1). [3]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene increases the methylation of Transcriptional regulator QRICH1 (QRICH1). [10]
TAK-243 DM4GKV2 Phase 1 TAK-243 increases the sumoylation of Transcriptional regulator QRICH1 (QRICH1). [11]
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2 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Ivermectin DMDBX5F Approved Ivermectin decreases the expression of Transcriptional regulator QRICH1 (QRICH1). [8]
Trichostatin A DM9C8NX Investigative Trichostatin A affects the expression of Transcriptional regulator QRICH1 (QRICH1). [12]
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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 Classification of Genes: Standardized Clinical Validity Assessment of Gene-Disease Associations Aids Diagnostic Exome Analysis and Reclassifications. Hum Mutat. 2017 May;38(5):600-608. doi: 10.1002/humu.23183. Epub 2017 Feb 13.
3 Amyloid beta protein-related death-inducing protein induces G2/M arrest: Implications for neurodegeneration in Alzheimer's disease. J Neurosci Res. 2007 Aug 1;85(10):2262-71. doi: 10.1002/jnr.21351.
4 Genetic diagnosis of developmental disorders in the DDD study: a scalable analysis of genome-wide research data.Lancet. 2015 Apr 4;385(9975):1305-14. doi: 10.1016/S0140-6736(14)61705-0. Epub 2014 Dec 17.
5 Identification of 64 Novel Genetic Loci Provides an Expanded View on the Genetic Architecture of Coronary Artery Disease.Circ Res. 2018 Feb 2;122(3):433-443. doi: 10.1161/CIRCRESAHA.117.312086. Epub 2017 Dec 6.
6 Increased burden of ultra-rare protein-altering variants among 4,877 individuals with schizophrenia. Nat Neurosci. 2016 Nov;19(11):1433-1441. doi: 10.1038/nn.4402. Epub 2016 Oct 3.
7 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.
8 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.
9 Amyloid beta protein-related death-inducing protein induces G2/M arrest: Implications for neurodegeneration in Alzheimer's disease. J Neurosci Res. 2007 Aug 1;85(10):2262-71. doi: 10.1002/jnr.21351.
10 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.
11 Inhibiting ubiquitination causes an accumulation of SUMOylated newly synthesized nuclear proteins at PML bodies. J Biol Chem. 2019 Oct 18;294(42):15218-15234. doi: 10.1074/jbc.RA119.009147. Epub 2019 Jul 8.
12 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.