Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTHJP8M2)

• DOT Name: Homeobox protein Hox-A6 (HOXA6)
• Synonyms: Homeobox protein Hox-1B
• Gene Name: HOXA6
• Related Disease:
  Advanced cancer
  B-cell neoplasm
  Clear cell renal carcinoma
  Colon cancer
  Colon carcinoma
  Corpus callosum, agenesis of
  leukaemia
  Leukemia
  Mowat-Wilson syndrome
  Neoplasm
  Chronic obstructive pulmonary disease
  Colorectal carcinoma
  Werner syndrome
  Breast cancer
  Breast carcinoma
• UniProt ID: HXA6_HUMAN
• Pfam ID: PF00046
• Sequence:
  MSSYFVNPTFPGSLPSGQDSFLGQLPLYQAGYDALRPFPASYGASSLPDKTYTSPCFYQQ
  SNSVLACNRASYEYGASCFYSDKDLSGASPSGSGKQRGPGDYLHFSPEQQYKPDSSSGQG
  KALHDEGADRKYTSPVYPWMQRMNSCAGAVYGSHGRRGRQTYTRYQTLELEKEFHFNRYL
  TRRRRIEIANALCLTERQIKIWFQNRRMKWKKENKLINSTQPSGEDSEAKAGE
• 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.

Molecular Interaction Atlas (MIA) of This DOT

15 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Advanced cancer	DISAT1Z9	Strong	Posttranslational Modification	[1]
B-cell neoplasm	DISVY326	Strong	Biomarker	[2]
Clear cell renal carcinoma	DISBXRFJ	Strong	Altered Expression	[3]
Colon cancer	DISVC52G	Strong	Genetic Variation	[4]
Colon carcinoma	DISJYKUO	Strong	Genetic Variation	[4]
Corpus callosum, agenesis of	DISO9P40	Strong	Genetic Variation	[5]
leukaemia	DISS7D1V	Strong	Genetic Variation	[6]
Leukemia	DISNAKFL	Strong	Genetic Variation	[6]
Mowat-Wilson syndrome	DISD1AW7	Strong	Genetic Variation	[5]
Neoplasm	DISZKGEW	Strong	Altered Expression	[2]
Chronic obstructive pulmonary disease	DISQCIRF	moderate	Genetic Variation	[7]
Colorectal carcinoma	DIS5PYL0	moderate	Biomarker	[8]
Werner syndrome	DISZY45W	moderate	Biomarker	[9]
Breast cancer	DIS7DPX1	Limited	Biomarker	[10]
Breast carcinoma	DIS2UE88	Limited	Biomarker	[10]

3 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-A6 (HOXA6).	[11]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Homeobox protein Hox-A6 (HOXA6).	[13]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Homeobox protein Hox-A6 (HOXA6).	[14]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Homeobox protein Hox-A6 (HOXA6).	[12]

References

• [1] Inactivation of HOXA genes by hypermethylation in myeloid and lymphoid malignancy is frequent and associated with poor prognosis.Clin Cancer Res. 2007 Sep 1;13(17):5048-55. doi: 10.1158/1078-0432.CCR-07-0919.
• [2] Effect of HOXA6 on the proliferation, apoptosis, migration and invasion of colorectal cancer cells.Int J Oncol. 2018 Jun;52(6):2093-2100. doi: 10.3892/ijo.2018.4352. Epub 2018 Apr 2.
• [3] MiR-1294 acts as a tumor suppressor in clear cell renal cell carcinoma through targeting HOXA6.Eur Rev Med Pharmacol Sci. 2019 May;23(9):3719-3725. doi: 10.26355/eurrev_201905_17797.
• [4] A novel long non-coding RNA from the HOXA6-HOXA5 locus facilitates colon cancer cell growth.BMC Cancer. 2019 Jun 3;19(1):532. doi: 10.1186/s12885-019-5715-0.
• [5] Frameshift mutation of the zinc finger homeo box 1 B gene in syndromic corpus callosum agenesis (Mowat-Wilson syndrome).Neuropediatrics. 2003 Dec;34(6):322-5. doi: 10.1055/s-2003-44671.
• [6] Lineage and stage specific expression of HOX 1 genes in the human hematopoietic system.Biochem Biophys Res Commun. 1992 Mar 31;183(3):1124-30. doi: 10.1016/s0006-291x(05)80307-9.
• [7] Relationship between COPD and polymorphisms of HOX-1 and mEPH in a Chinese population.Oncol Rep. 2007 Feb;17(2):483-8.
• [8] Study of Promoter Methylation Patterns of HOXA2, HOXA5, and HOXA6 and Its Clinicopathological Characteristics in Colorectal Cancer.Front Oncol. 2019 May 21;9:394. doi: 10.3389/fonc.2019.00394. eCollection 2019.
• [9] Common and cell type-specific responses of human cells to mitochondrial dysfunction.Exp Cell Res. 2005 Jan 15;302(2):270-80. doi: 10.1016/j.yexcr.2004.09.006.
• [10] Analysis of HOX gene expression patterns in human breast cancer.Mol Biotechnol. 2014 Jan;56(1):64-71. doi: 10.1007/s12033-013-9682-4.
• [11] 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.
• [12] Noncoding RNA synthesis and loss of Polycomb group repression accompanies the colinear activation of the human HOXA cluster. RNA. 2007 Feb;13(2):223-39. doi: 10.1261/rna.266707. Epub 2006 Dec 21.
• [13] 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.
• [14] 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.