Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT43YF6N)

• DOT Name: Diencephalon/mesencephalon homeobox protein 1 (DMBX1)
• Synonyms: Orthodenticle homolog 3; Paired-like homeobox protein DMBX1
• Gene Name: DMBX1
• Related Disease:
  Cataract
  Lung adenocarcinoma
  Neoplasm
  Complex neurodevelopmental disorder
  Malignant rhabdoid tumour
  Medulloblastoma
  Proliferative vitreoretinopathy
• UniProt ID: DMBX1_HUMAN
• Pfam ID: PF00046 ; PF03826
• Sequence:
  MQHYGVNGYSLHAMNSLSAMYNLHQQAAQQAQHAPDYRPSVHALTLAERLAGCTFQDIIL
  EARYGSQHRKQRRSRTAFTAQQLEALEKTFQKTHYPDVVMRERLAMCTNLPEARVQVWFK
  NRRAKFRKKQRSLQKEQLQKQKEAEGSHGEGKAEAPTPDTQLDTEQPPRLPGSDPPAELH
  LSLSEQSASESAPEDQPDREEDPRAGAEDPKAEKSPGADSKGLGCKRGSPKADSPGSLTI
  TPVAPGGGLLGPSHSYSSSPLSLFRLQEQFRQHMAATNNLVHYSSFEVGGPAPAAAAAAA
  AVPYLGVNMAPLGSLHCQSYYQSLSAAAAAHQGVWGSPLLPAPPAGLAPASATLNSKTTS
  IENLRLRAKQHAASLGLDTLPN
• Function: Functions as a transcriptional repressor. May repress OTX2-mediated transactivation by forming a heterodimer with OTX2 on the P3C (5'-TAATCCGATTA-3') sequence. Required for brain development.

Molecular Interaction Atlas (MIA) of This DOT

7 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Cataract	DISUD7SL	Strong	Biomarker	[1]
Lung adenocarcinoma	DISD51WR	Strong	Biomarker	[2]
Neoplasm	DISZKGEW	Strong	Altered Expression	[2]
Complex neurodevelopmental disorder	DISB9AFI	Limited	Autosomal recessive	[3]
Malignant rhabdoid tumour	DIS46HZU	Limited	Biomarker	[4]
Medulloblastoma	DISZD2ZL	Limited	Biomarker	[4]
Proliferative vitreoretinopathy	DISZTEK1	Limited	Biomarker	[5]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of Diencephalon/mesencephalon homeobox protein 1 (DMBX1).	[6]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Diencephalon/mesencephalon homeobox protein 1 (DMBX1).	[10]

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 Diencephalon/mesencephalon homeobox protein 1 (DMBX1).	[7]
Calcitriol	DM8ZVJ7	Approved	Calcitriol decreases the expression of Diencephalon/mesencephalon homeobox protein 1 (DMBX1).	[8]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of Diencephalon/mesencephalon homeobox protein 1 (DMBX1).	[8]
Troglitazone	DM3VFPD	Approved	Troglitazone decreases the expression of Diencephalon/mesencephalon homeobox protein 1 (DMBX1).	[9]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Diencephalon/mesencephalon homeobox protein 1 (DMBX1).	[11]

References

• [1] Mutational analysis of the human MBX gene in four Korean families demonstrating microphthalmia with congenital cataract.Turk J Pediatr. 2007 Jul-Sep;49(3):334-6.
• [2] DMBX1 promotes tumor proliferation and regulates cell cycle progression via repressing OTX2-mediated transcription of p21 in lung adenocarcinoma cell.Cancer Lett. 2019 Jul 1;453:45-56. doi: 10.1016/j.canlet.2019.03.045. Epub 2019 Mar 27.
• [3] Classification of Genes: Standardized Clinical Validity Assessment of Gene-Disease Associations Aids Diagnostic Exome Analysis and Reclassifications. Hum Mutat. 2017 May;38(5):600-608. doi: 10.1002/humu.23183. Epub 2017 Feb 13.
• [4] CRX/OTX3: a useful marker in the differential diagnosis of tumors of the pineal region and indicator of photoreceptor differentiation in medulloblastomas and atypical teratoid rhabdoid tumors.Appl Immunohistochem Mol Morphol. 2013 May;21(3):248-53. doi: 10.1097/PAI.0b013e3182649dad.
• [5] Expression of VEGF-A, Otx homeobox and p53 family genes in proliferative vitreoretinopathy.Mediators Inflamm. 2013;2013:857380. doi: 10.1155/2013/857380. Epub 2013 Oct 21.
• [6] 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.
• [7] Predictive toxicology using systemic biology and liver microfluidic "on chip" approaches: application to acetaminophen injury. Toxicol Appl Pharmacol. 2012 Mar 15;259(3):270-80.
• [8] Effects of 1alpha,25 dihydroxyvitamin D3 and testosterone on miRNA and mRNA expression in LNCaP cells. Mol Cancer. 2011 May 18;10:58.
• [9] Effects of ciglitazone and troglitazone on the proliferation of human stomach cancer cells. World J Gastroenterol. 2009 Jan 21;15(3):310-20.
• [10] 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.
• [11] Characterization of the Molecular Alterations Induced by the Prolonged Exposure of Normal Colon Mucosa and Colon Cancer Cells to Low-Dose Bisphenol A. Int J Mol Sci. 2022 Oct 1;23(19):11620. doi: 10.3390/ijms231911620.