Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT42C4HF)

• DOT Name: Homeobox protein Hox-A11 (HOXA11)
• Synonyms: Homeobox protein Hox-1I
• Gene Name: HOXA11
• Related Disease:
  Radioulnar synostosis with amegakaryocytic thrombocytopenia 1
  Radio-ulnar synostosis-amegakaryocytic thrombocytopenia syndrome
• UniProt ID: HXA11_HUMAN
• Pfam ID: PF12045 ; PF00046
• Sequence:
  MDFDERGPCSSNMYLPSCTYYVSGPDFSSLPSFLPQTPSSRPMTYSYSSNLPQVQPVREV
  TFREYAIEPATKWHPRGNLAHCYSAEELVHRDCLQAPSAAGVPGDVLAKSSANVYHHPTP
  AVSSNFYSTVGRNGVLPQAFDQFFETAYGTPENLASSDYPGDKSAEKGPPAATATSAAAA
  AAATGAPATSSSDSGGGGGCRETAAAAEEKERRRRPESSSSPESSSGHTEDKAGGSSGQR
  TRKKRCPYTKYQIRELEREFFFSVYINKEKRLQLSRMLNLTDRQVKIWFQNRRMKEKKIN
  RDRLQYYSANPLL
• Function: Sequence-specific transcription factor which is part of a developmental regulatory system that provides cells with specific positional identities on the anterior-posterior axis.
• KEGG Pathway: Transcriptio.l misregulation in cancer (hsa05202)

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Radioulnar synostosis with amegakaryocytic thrombocytopenia 1	DIS18K7L	Strong	Autosomal dominant	[1]
Radio-ulnar synostosis-amegakaryocytic thrombocytopenia syndrome	DISBKMHA	Supportive	Autosomal dominant	[1]

2 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 Homeobox protein Hox-A11 (HOXA11).	[2]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the methylation of Homeobox protein Hox-A11 (HOXA11).	[9]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Homeobox protein Hox-A11 (HOXA11).	[3]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Homeobox protein Hox-A11 (HOXA11).	[4]
Methotrexate	DM2TEOL	Approved	Methotrexate decreases the expression of Homeobox protein Hox-A11 (HOXA11).	[5]
Decitabine	DMQL8XJ	Approved	Decitabine increases the expression of Homeobox protein Hox-A11 (HOXA11).	[6]
Bortezomib	DMNO38U	Approved	Bortezomib decreases the expression of Homeobox protein Hox-A11 (HOXA11).	[7]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol increases the expression of Homeobox protein Hox-A11 (HOXA11).	[8]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Homeobox protein Hox-A11 (HOXA11).	[6]

References

• [1] Amegakaryocytic thrombocytopenia and radio-ulnar synostosis are associated with HOXA11 mutation. Nat Genet. 2000 Dec;26(4):397-8. doi: 10.1038/82511.
• [2] 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.
• [3] 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.
• [4] Endocrine regulation of HOX genes. Endocr Rev. 2006 Jun;27(4):331-55. doi: 10.1210/er.2005-0018. Epub 2006 Apr 21.
• [5] Global molecular effects of tocilizumab therapy in rheumatoid arthritis synovium. Arthritis Rheumatol. 2014 Jan;66(1):15-23.
• [6] 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.
• [7] The proapoptotic effect of zoledronic acid is independent of either the bone microenvironment or the intrinsic resistance to bortezomib of myeloma cells and is enhanced by the combination with arsenic trioxide. Exp Hematol. 2011 Jan;39(1):55-65.
• [8] Selenium and vitamin E: cell type- and intervention-specific tissue effects in prostate cancer. J Natl Cancer Inst. 2009 Mar 4;101(5):306-20.
• [9] DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.