Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTKH7U5Q)

• DOT Name: Pyridoxal-dependent decarboxylase domain-containing protein 1 (PDXDC1)
• Synonyms: EC 4.1.1.-
• Gene Name: PDXDC1
• Related Disease:
  Chronic kidney disease
  Chronic renal failure
  Clear cell renal carcinoma
  Glioma
  Papillary renal cell carcinoma
  Renal cell carcinoma
  Schizophrenia
• UniProt ID: PDXD1_HUMAN
• EC Number: 4.1.1.-
• Pfam ID: PF00282
• Sequence:
  MDASLEKIADPTLAEMGKNLKEAVKMLEDSQRRTEEENGKKLISGDIPGPLQGSGQDMVS
  ILQLVQNLMHGDEDEEPQSPRIQNIGEQGHMALLGHSLGAYISTLDKEKLRKLTTRILSD
  TTLWLCRIFRYENGCAYFHEEEREGLAKICRLAIHSRYEDFVVDGFNVLYNKKPVIYLSA
  AARPGLGQYLCNQLGLPFPCLCRVPCNTVFGSQHQMDVAFLEKLIKDDIERGRLPLLLVA
  NAGTAAVGHTDKIGRLKELCEQYGIWLHVEGVNLATLALGYVSSSVLAAAKCDSMTMTPG
  PWLGLPAVPAVTLYKHDDPALTLVAGLTSNKPTDKLRALPLWLSLQYLGLDGFVERIKHA
  CQLSQRLQESLKKVNYIKILVEDELSSPVVVFRFFQELPGSDPVFKAVPVPNMTPSGVGR
  ERHSCDALNRWLGEQLKQLVPASGLTVMDLEAEGTCLRFSPLMTAAVLGTRGEDVDQLVA
  CIESKLPVLCCTLQLREEFKQEVEATAGLLYVDDPNWSGIGVVRYEHANDDKSSLKSDPE
  GENIHAGLLKKLNELESDLTFKIGPEYKSMKSCLYVGMASDNVDAAELVETIAATAREIE
  ENSRLLENMTEVVRKGIQEAQVELQKASEERLLEEGVLRQIPVVGSVLNWFSPVQALQKG
  RTFNLTAGSLESTEPIYVYKAQGAGVTLPPTPSGSRTKQRLPGQKPFKRSLRGSDALSET
  SSVSHIEDLEKVERLSSGPEQITLEASSTEGHPGAPSPQHTDQTEAFQKGVPHPEDDHSQ
  VEGPESLR

Molecular Interaction Atlas (MIA) of This DOT

7 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Chronic kidney disease	DISW82R7	Definitive	Genetic Variation	[1]
Chronic renal failure	DISGG7K6	Definitive	Genetic Variation	[1]
Clear cell renal carcinoma	DISBXRFJ	Strong	Biomarker	[2]
Glioma	DIS5RPEH	Strong	Genetic Variation	[3]
Papillary renal cell carcinoma	DIS25HBV	Strong	Biomarker	[2]
Renal cell carcinoma	DISQZ2X8	Strong	Biomarker	[2]
Schizophrenia	DISSRV2N	Limited	Genetic Variation	[4]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the methylation of Pyridoxal-dependent decarboxylase domain-containing protein 1 (PDXDC1).	[5]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Pyridoxal-dependent decarboxylase domain-containing protein 1 (PDXDC1).	[15]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 affects the phosphorylation of Pyridoxal-dependent decarboxylase domain-containing protein 1 (PDXDC1).	[16]
Coumarin	DM0N8ZM	Investigative	Coumarin affects the phosphorylation of Pyridoxal-dependent decarboxylase domain-containing protein 1 (PDXDC1).	[16]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Pyridoxal-dependent decarboxylase domain-containing protein 1 (PDXDC1).	[6]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Pyridoxal-dependent decarboxylase domain-containing protein 1 (PDXDC1).	[7]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Pyridoxal-dependent decarboxylase domain-containing protein 1 (PDXDC1).	[8]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Pyridoxal-dependent decarboxylase domain-containing protein 1 (PDXDC1).	[9]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Pyridoxal-dependent decarboxylase domain-containing protein 1 (PDXDC1).	[10]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Pyridoxal-dependent decarboxylase domain-containing protein 1 (PDXDC1).	[11]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of Pyridoxal-dependent decarboxylase domain-containing protein 1 (PDXDC1).	[12]
Marinol	DM70IK5	Approved	Marinol decreases the expression of Pyridoxal-dependent decarboxylase domain-containing protein 1 (PDXDC1).	[13]
Menadione	DMSJDTY	Approved	Menadione affects the expression of Pyridoxal-dependent decarboxylase domain-containing protein 1 (PDXDC1).	[14]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A affects the expression of Pyridoxal-dependent decarboxylase domain-containing protein 1 (PDXDC1).	[17]
[3H]methyltrienolone	DMTSGOW	Investigative	[3H]methyltrienolone increases the expression of Pyridoxal-dependent decarboxylase domain-containing protein 1 (PDXDC1).	[18]

References

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• [2] Spectrum of diverse genomic alterations define non-clear cell renal carcinoma subtypes.Nat Genet. 2015 Jan;47(1):13-21. doi: 10.1038/ng.3146. Epub 2014 Nov 17.
• [3] Genotype-based gene signature of glioma risk.Neuro Oncol. 2017 Jul 1;19(7):940-950. doi: 10.1093/neuonc/now288.
• [4] Pleiotropic Meta-Analysis of Cognition, Education, and Schizophrenia Differentiates Roles of Early Neurodevelopmental and Adult Synaptic Pathways.Am J Hum Genet. 2019 Aug 1;105(2):334-350. doi: 10.1016/j.ajhg.2019.06.012.
• [5] 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.
• [6] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [7] Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
• [8] Gene expression analysis of precision-cut human liver slices indicates stable expression of ADME-Tox related genes. Toxicol Appl Pharmacol. 2011 May 15;253(1):57-69.
• [9] Bringing in vitro analysis closer to in vivo: studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling. Toxicol Lett. 2018 Sep 15;294:184-192.
• [10] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [11] 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.
• [12] Chronic occupational exposure to arsenic induces carcinogenic gene signaling networks and neoplastic transformation in human lung epithelial cells. Toxicol Appl Pharmacol. 2012 Jun 1;261(2):204-16.
• [13] THC exposure of human iPSC neurons impacts genes associated with neuropsychiatric disorders. Transl Psychiatry. 2018 Apr 25;8(1):89. doi: 10.1038/s41398-018-0137-3.
• [14] 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.
• [15] 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.
• [16] Quantitative phosphoproteomics reveal cellular responses from caffeine, coumarin and quercetin in treated HepG2 cells. Toxicol Appl Pharmacol. 2022 Aug 15;449:116110. doi: 10.1016/j.taap.2022.116110. Epub 2022 Jun 7.
• [17] Comprehensive analysis of transcriptomic changes induced by low and high doses of bisphenol A in HepG2 spheroids in vitro and rat liver in vivo. Environ Res. 2019 Jun;173:124-134. doi: 10.1016/j.envres.2019.03.035. Epub 2019 Mar 18.
• [18] Evaluation of an in vitro model of androgen ablation and identification of the androgen responsive proteome in LNCaP cells. Proteomics. 2007 Jan;7(1):47-63.