Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTXSUD8R)

• DOT Name: Guanine nucleotide-binding protein subunit beta-like protein 1 (GNB1L)
• Synonyms: G protein subunit beta-like protein 1; DGCRK3; WD repeat-containing protein 14; WD40 repeat-containing protein deleted in VCFS; WDVCF
• Gene Name: GNB1L
• Related Disease:
  Autism
  Autism spectrum disorder
  Bipolar disorder
  DiGeorge syndrome
  Isolated cleft lip
  Psychotic disorder
  Shprintzen-Goldberg syndrome
  Schizophrenia
  Mental disorder
• UniProt ID: GNB1L_HUMAN
• Pfam ID: PF00400
• Sequence:
  MTAPCPPPPPDPQFVLRGTQSPVHALHFCEGAQAQGRPLLFSGSQSGLVHIWSLQTRRAV
  TTLDGHGGQCVTWLQTLPQGRQLLSQGRDLKLCLWDLAEGRSAVVDSVCLESVGFCRSSI
  LAGGQPRWTLAVPGRGSDEVQILEMPSKTSVCALKPKADAKLGMPMCLRLWQADCSSRPL
  LLAGYEDGSVVLWDVSEQKVCSRIACHEEPVMDLDFDSQKARGISGSAGKALAVWSLDWQ
  QALQVRGTHELTNPGIAEVTIRPDRKILATAGWDHRIRVFHWRTMQPLAVLAFHSAAVQC
  VAFTADGLLAAGSKDQRISLWSLYPRA
• Function: Acts as a critical regulator of DNA damage response (DDR) signaling via specifically regulating phosphatidylinositol 3-kinase-related protein kinase (PIKK) family proteins.
• Tissue Specificity: Ubiquitous. Highly expressed in heart, liver, skeletal muscle, kidney, spleen, thymus and pancreas. Detected at low levels in lung, placenta and brain.

Molecular Interaction Atlas (MIA) of This DOT

9 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Autism	DISV4V1Z	Strong	Biomarker	[1]
Autism spectrum disorder	DISXK8NV	Strong	Biomarker	[1]
Bipolar disorder	DISAM7J2	Strong	Biomarker	[2]
DiGeorge syndrome	DIST1RKO	Strong	Biomarker	[3]
Isolated cleft lip	DIS2O2JV	Strong	Genetic Variation	[4]
Psychotic disorder	DIS4UQOT	Strong	Biomarker	[2]
Shprintzen-Goldberg syndrome	DISQH6P3	Strong	Biomarker	[3]
Schizophrenia	DISSRV2N	Disputed	Biomarker	[5]
Mental disorder	DIS3J5R8	Limited	Biomarker	[2]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Guanine nucleotide-binding protein subunit beta-like protein 1 (GNB1L).	[6]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Guanine nucleotide-binding protein subunit beta-like protein 1 (GNB1L).	[7]
Phenobarbital	DMXZOCG	Approved	Phenobarbital affects the expression of Guanine nucleotide-binding protein subunit beta-like protein 1 (GNB1L).	[8]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Guanine nucleotide-binding protein subunit beta-like protein 1 (GNB1L).	[9]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Guanine nucleotide-binding protein subunit beta-like protein 1 (GNB1L).	[10]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Guanine nucleotide-binding protein subunit beta-like protein 1 (GNB1L).	[11]

References

• [1] Evidence for involvement of GNB1L in autism.Am J Med Genet B Neuropsychiatr Genet. 2012 Jan;159B(1):61-71. doi: 10.1002/ajmg.b.32002. Epub 2011 Nov 16.
• [2] Association study between GNB1L and three major mental disorders in Chinese Han populations.Psychiatry Res. 2011 May 30;187(3):457-9. doi: 10.1016/j.psychres.2010.04.019. Epub 2010 Jun 9.
• [3] GNB1L, a gene deleted in the critical region for DiGeorge syndrome on 22q11, encodes a G-protein beta-subunit-like polypeptide.Biochim Biophys Acta. 2000 Nov 15;1494(1-2):185-8. doi: 10.1016/s0167-4781(00)00189-5.
• [4] Genome-wide analyses of non-syndromic cleft lip with palate identify 14 novel loci and genetic heterogeneity.Nat Commun. 2017 Feb 24;8:14364. doi: 10.1038/ncomms14364.
• [5] Functional gene-expression analysis shows involvement of schizophrenia-relevant pathways in patients with 22q11 deletion syndrome.PLoS One. 2012;7(3):e33473. doi: 10.1371/journal.pone.0033473. Epub 2012 Mar 22.
• [6] The thioxotriazole copper(II) complex A0 induces endoplasmic reticulum stress and paraptotic death in human cancer cells. J Biol Chem. 2009 Sep 4;284(36):24306-19.
• [7] 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.
• [8] Reproducible chemical-induced changes in gene expression profiles in human hepatoma HepaRG cells under various experimental conditions. Toxicol In Vitro. 2009 Apr;23(3):466-75. doi: 10.1016/j.tiv.2008.12.018. Epub 2008 Dec 30.
• [9] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [10] Transcriptional signature of human macrophages exposed to the environmental contaminant benzo(a)pyrene. Toxicol Sci. 2010 Apr;114(2):247-59.
• [11] 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.