Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT2VP73H)

• DOT Name: Homeobox protein BarH-like 1 (BARX1)
• Gene Name: BARX1
• Related Disease:
  Anterior segment dysgenesis 4
  Barrett esophagus
  Esophageal squamous cell carcinoma
  Familial multiple trichoepithelioma
  Gastroesophageal reflux disease
  Intestinal disorder
  Isolated cleft lip
  Hepatocellular carcinoma
  Esophageal adenocarcinoma
• UniProt ID: BARX1_HUMAN
• PDB ID: 2DMT
• Pfam ID: PF00046
• Sequence:
  MQRPGEPGAARFGPPEGCADHRPHRYRSFMIEEILTEPPGPKGAAPAAAAAAAGELLKFG
  VQALLAARPFHSHLAVLKAEQAAVFKFPLAPLGCSGLSSALLAAGPGLPGAAGAPHLPLE
  LQLRGKLEAAGPGEPGTKAKKGRRSRTVFTELQLMGLEKRFEKQKYLSTPDRIDLAESLG
  LSQLQVKTWYQNRRMKWKKIVLQGGGLESPTKPKGRPKKNSIPTSEQLTEQERAKDAEKP
  AEVPGEPSDRSRED
• Function: Transcription factor, which is involved in craniofacial development, in odontogenesis and in stomach organogenesis. May have a role in the differentiation of molars from incisors. Plays a role in suppressing endodermal Wnt activity. Binds to a regulatory module of the NCAM promoter.
• Tissue Specificity: Widely expressed. Expressed at higher levels in testis and heart. Detected in craniofacial tissue and adult iris, but not in lymphocytes, fibroblasts, choroid retina, retinal pigment epithelium, kidney, or fetal liver.

Molecular Interaction Atlas (MIA) of This DOT

9 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Anterior segment dysgenesis 4	DISSZ066	Strong	Altered Expression	[1]
Barrett esophagus	DIS416Y7	Strong	Genetic Variation	[2]
Esophageal squamous cell carcinoma	DIS5N2GV	Strong	Biomarker	[3]
Familial multiple trichoepithelioma	DISKZAUY	Strong	Genetic Variation	[4]
Gastroesophageal reflux disease	DISQ8G5S	Strong	Genetic Variation	[5]
Intestinal disorder	DISGPMUQ	Strong	Genetic Variation	[2]
Isolated cleft lip	DIS2O2JV	Strong	Altered Expression	[6]
Hepatocellular carcinoma	DIS0J828	moderate	Altered Expression	[7]
Esophageal adenocarcinoma	DISODWFP	Limited	Genetic Variation	[3]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of Homeobox protein BarH-like 1 (BARX1).	[8]
Acetaldehyde	DMJFKG4	Investigative	Acetaldehyde increases the expression of Homeobox protein BarH-like 1 (BARX1).	[10]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Homeobox protein BarH-like 1 (BARX1).	[9]

References

• [1] Cloning, characterization, localization, and mutational screening of the human BARX1 gene.Genomics. 2000 Sep 15;68(3):336-42. doi: 10.1006/geno.2000.6307.
• [2] A genome-wide association study identifies new susceptibility loci for esophageal adenocarcinoma and Barrett's esophagus.Nat Genet. 2013 Dec;45(12):1487-93. doi: 10.1038/ng.2796. Epub 2013 Oct 13.
• [3] An esophageal adenocarcinoma susceptibility locus at 9q22 also confers risk to esophageal squamous cell carcinoma by regulating the function of BARX1.Cancer Lett. 2018 May 1;421:103-111. doi: 10.1016/j.canlet.2018.02.019. Epub 2018 Feb 14.
• [4] Supportive evidence for FOXP1, BARX1, and FOXF1 as genetic risk loci for the development of esophageal adenocarcinoma.Cancer Med. 2015 Nov;4(11):1700-4. doi: 10.1002/cam4.500. Epub 2015 Aug 15.
• [5] Polymorphisms of the BARX1 and ADAMTS17 Locus Genes in Individuals With Gastroesophageal Reflux Disease.J Neurogastroenterol Motil. 2019 Jul 1;25(3):436-441. doi: 10.5056/jnm18183.
• [6] Barx1, growth factors and apoptosis in facial tissue of children with clefts.Stomatologija. 2008;10(2):62-6.
• [7] Loss of Barx1 promotes hepatocellular carcinoma metastasis through up-regulating MGAT5 and MMP9 expression and indicates poor prognosis.Oncotarget. 2017 May 30;8(42):71867-71880. doi: 10.18632/oncotarget.18288. eCollection 2017 Sep 22.
• [8] Large-scale in silico and microarray-based identification of direct 1,25-dihydroxyvitamin D3 target genes. Mol Endocrinol. 2005 Nov;19(11):2685-95.
• [9] 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.
• [10] Transcriptome profile analysis of saturated aliphatic aldehydes reveals carbon number-specific molecules involved in pulmonary toxicity. Chem Res Toxicol. 2014 Aug 18;27(8):1362-70.