Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTN0YIS3)

• DOT Name: Proline-rich transmembrane protein 1 (PRRT1)
• Synonyms: Dispanin subfamily D member 1; DSPD1; Synapse differentiation-induced protein 4; SynDIG4
• Gene Name: PRRT1
• Related Disease:
  Breast cancer
  Breast carcinoma
  Colon cancer
  Colon carcinoma
  Rheumatoid arthritis
  Type-1 diabetes
• UniProt ID: PRRT1_HUMAN
• Pfam ID: PF04505
• Sequence:
  MSSEKSGLPDSVPHTSPPPYNAPQPPAEPPAPPPQAAPSSHHHHHHHYHQSGTATLPRLG
  AGGLASSAATAQRGPSSSATLPRPPHHAPPGPAAGAPPPGCATLPRMPPDPYLQETRFEG
  PLPPPPPAAAAPPPPAPAQTAQAPGFVVPTHAGTVGTLPLGGYVAPGYPLQLQPCTAYVP
  VYPVGTPYAGGTPGGTGVTSTLPPPPQGPGLALLEPRRPPHDYMPIAVLTTICCFWPTGI
  IAIFKAVQVRTALARGDMVSAEIASREARNFSFISLAVGIAAMVLCTILTVVIIIAAQHH
  ENYWDP
• Function: Required to maintain a pool of extrasynaptic AMPA-regulated glutamate receptors (AMPAR) which is necessary for synapse development and function. Regulates basal AMPAR function and synaptic transmission during development but is dispensable at mature hippocampal synapses. Plays a role in regulating basal phosphorylation levels of glutamate receptor GRIA1 and promotes GRIA1 and GRIA2 cell surface expression.

Molecular Interaction Atlas (MIA) of This DOT

6 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Breast cancer	DIS7DPX1	Strong	Biomarker	[1]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[1]
Colon cancer	DISVC52G	Strong	Biomarker	[1]
Colon carcinoma	DISJYKUO	Strong	Biomarker	[1]
Rheumatoid arthritis	DISTSB4J	Strong	Genetic Variation	[2]
Type-1 diabetes	DIS7HLUB	Strong	Genetic Variation	[3]

7 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 Proline-rich transmembrane protein 1 (PRRT1).	[4]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Proline-rich transmembrane protein 1 (PRRT1).	[5]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of Proline-rich transmembrane protein 1 (PRRT1).	[7]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of Proline-rich transmembrane protein 1 (PRRT1).	[8]
Folic acid	DMEMBJC	Approved	Folic acid decreases the expression of Proline-rich transmembrane protein 1 (PRRT1).	[9]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Proline-rich transmembrane protein 1 (PRRT1).	[10]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Proline-rich transmembrane protein 1 (PRRT1).	[11]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Proline-rich transmembrane protein 1 (PRRT1).	[6]

References

• [1] The identification of specific methylation patterns across different cancers.PLoS One. 2015 Mar 16;10(3):e0120361. doi: 10.1371/journal.pone.0120361. eCollection 2015.
• [2] A genome-wide association study suggests contrasting associations in ACPA-positive versus ACPA-negative rheumatoid arthritis.Ann Rheum Dis. 2011 Feb;70(2):259-65. doi: 10.1136/ard.2009.126821. Epub 2010 Dec 14.
• [3] A genome-wide association study identifies KIAA0350 as a type 1 diabetes gene.Nature. 2007 Aug 2;448(7153):591-4. doi: 10.1038/nature06010. Epub 2007 Jul 15.
• [4] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [5] 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.
• [6] Prenatal arsenic exposure and the epigenome: identifying sites of 5-methylcytosine alterations that predict functional changes in gene expression in newborn cord blood and subsequent birth outcomes. Toxicol Sci. 2015 Jan;143(1):97-106. doi: 10.1093/toxsci/kfu210. Epub 2014 Oct 10.
• [7] Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
• [8] The exosome-like vesicles derived from androgen exposed-prostate stromal cells promote epithelial cells proliferation and epithelial-mesenchymal transition. Toxicol Appl Pharmacol. 2021 Jan 15;411:115384. doi: 10.1016/j.taap.2020.115384. Epub 2020 Dec 25.
• [9] Folic acid supplementation dysregulates gene expression in lymphoblastoid cells--implications in nutrition. Biochem Biophys Res Commun. 2011 Sep 9;412(4):688-92. doi: 10.1016/j.bbrc.2011.08.027. Epub 2011 Aug 16.
• [10] Definition of transcriptome-based indices for quantitative characterization of chemically disturbed stem cell development: introduction of the STOP-Toxukn and STOP-Toxukk tests. Arch Toxicol. 2017 Feb;91(2):839-864.
• [11] Benzo[a]pyrene-induced changes in microRNA-mRNA networks. Chem Res Toxicol. 2012 Apr 16;25(4):838-49.