Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT7NG5MJ)

• DOT Name: Homeobox protein EMX1 (EMX1)
• Synonyms: Empty spiracles homolog 1; Empty spiracles-like protein 1
• Gene Name: EMX1
• Related Disease:
  Intellectual disability
  Hypogonadotropic hypogonadism 7 with or without anosmia
  Kallmann syndrome
  Neoplasm
  Schizophrenia
  Spinal muscular atrophy
• UniProt ID: EMX1_HUMAN
• Pfam ID: PF00046
• Sequence:
  MCLAGCTPRKAAAPGRGALPRARLPRTAPAAATMFQPAAKRGFTIESLVAKDGGTGGGTG
  GGGAGSHLLAAAASEEPLRPTALNYPHPSAAEAAFVSGFPAAAAAGAGRSLYGGPELVFP
  EAMNHPALTVHPAHQLGASPLQPPHSFFGAQHRDPLHFYPWVLRNRFFGHRFQASDVPQD
  GLLLHGPFARKPKRIRTAFSPSQLLRLERAFEKNHYVVGAERKQLAGSLSLSETQVKVWF
  QNRRTKYKRQKLEEEGPESEQKKKGSHHINRWRIATKQANGEDIDVTSND
• Function: Transcription factor, which in cooperation with EMX2, acts to generate the boundary between the roof and archipallium in the developing brain. May function in combinations with OTX1/2 to specify cell fates in the developing central nervous system.
• Tissue Specificity: Cerebral cortex.

Molecular Interaction Atlas (MIA) of This DOT

6 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Intellectual disability	DISMBNXP	Definitive	Biomarker	[1]
Hypogonadotropic hypogonadism 7 with or without anosmia	DISPBWEU	Strong	Genetic Variation	[2]
Kallmann syndrome	DISO3HDG	Strong	Genetic Variation	[2]
Neoplasm	DISZKGEW	Strong	Altered Expression	[3]
Schizophrenia	DISSRV2N	Strong	Genetic Variation	[4]
Spinal muscular atrophy	DISTLKOB	Strong	Biomarker	[5]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Homeobox protein EMX1 (EMX1).	[6]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Homeobox protein EMX1 (EMX1).	[7]
Testosterone	DM7HUNW	Approved	Testosterone increases the expression of Homeobox protein EMX1 (EMX1).	[9]
Triclosan	DMZUR4N	Approved	Triclosan increases the expression of Homeobox protein EMX1 (EMX1).	[10]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Homeobox protein EMX1 (EMX1).	[11]

2 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 Homeobox protein EMX1 (EMX1).	[8]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Homeobox protein EMX1 (EMX1).	[12]

References

• [1] Brpf1 Haploinsufficiency Impairs Dendritic Arborization and Spine Formation, Leading to Cognitive Deficits.Front Cell Neurosci. 2019 Jun 4;13:249. doi: 10.3389/fncel.2019.00249. eCollection 2019.
• [2] WDR11, a WD protein that interacts with transcription factor EMX1, is mutated in idiopathic hypogonadotropic hypogonadism and Kallmann syndrome. Am J Hum Genet. 2010 Oct 8;87(4):465-79. doi: 10.1016/j.ajhg.2010.08.018.
• [3] miRNA-mRNA Associated With Survival in Endometrial Cancer.Front Genet. 2019 Aug 20;10:743. doi: 10.3389/fgene.2019.00743. eCollection 2019.
• [4] Genome-Wide Association Study Detected Novel Susceptibility Genes for Schizophrenia and Shared Trans-Populations/Diseases Genetic Effect.Schizophr Bull. 2019 Jun 18;45(4):824-834. doi: 10.1093/schbul/sby140.
• [5] Restoration of SMN to Emx-1 expressing cortical neurons is not sufficient to provide benefit to a severe mouse model of Spinal Muscular Atrophy.Transgenic Res. 2013 Oct;22(5):1029-36. doi: 10.1007/s11248-013-9702-y. Epub 2013 Mar 20.
• [6] Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
• [7] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [8] 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.
• [9] 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.
• [10] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [11] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [12] 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.