Details of Drug Off-Target (DOT)

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

• DOT Name: Homeobox protein Hox-C5 (HOXC5)
• Synonyms: Homeobox protein CP11; Homeobox protein Hox-3D
• Gene Name: HOXC5
• Related Disease:
  Lymphoma
  Acute erythroid leukemia
  Acute megakaryoblastic leukemia
  Acute monocytic leukemia
  Acute myelogenous leukaemia
  Acute myelomonocytic leukemia M4
  Cardiac disease
  Hydatidiform mole
  Leukemia
  Myeloid leukaemia
  B-cell neoplasm
  Lymphoma, non-Hodgkin, familial
  MALT lymphoma
  Non-hodgkin lymphoma
  Hepatitis E virus infection
  Anaplastic large cell lymphoma
  Lymphoid leukemia
• UniProt ID: HXC5_HUMAN
• Pfam ID: PF00046
• Sequence:
  MSSYVANSFYKQSPNIPAYNMQTCGNYGSASEVQASRYCYGGLDLSITFPPPAPSNSLHG
  VDMAANPRAHPDRPACSAAAAPGHAPGRDEAAPLNPGMYSQKAARPALEERAKSSGEIKE
  EQAQTGQPAGLSQPPAPPQIYPWMTKLHMSHETDGKRSRTSYTRYQTLELEKEFHFNRYL
  TRRRRIEIANNLCLNERQIKIWFQNRRMKWKKDSKMKSKEAL
• 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

17 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Lymphoma	DISN6V4S	Definitive	Altered Expression	[1]
Acute erythroid leukemia	DISZFC1O	Strong	Altered Expression	[2]
Acute megakaryoblastic leukemia	DIS0JX3M	Strong	Altered Expression	[2]
Acute monocytic leukemia	DIS28NEL	Strong	Altered Expression	[2]
Acute myelogenous leukaemia	DISCSPTN	Strong	Altered Expression	[2]
Acute myelomonocytic leukemia M4	DISRRMV2	Strong	Altered Expression	[2]
Cardiac disease	DISVO1I5	Strong	Genetic Variation	[3]
Hydatidiform mole	DISKNP7O	Strong	Altered Expression	[4]
Leukemia	DISNAKFL	Strong	Altered Expression	[2]
Myeloid leukaemia	DISMN944	Strong	Altered Expression	[2]
B-cell neoplasm	DISVY326	moderate	Altered Expression	[1]
Lymphoma, non-Hodgkin, familial	DISCXYIZ	moderate	Altered Expression	[1]
MALT lymphoma	DIS1AVVE	moderate	Altered Expression	[1]
Non-hodgkin lymphoma	DISS2Y8A	moderate	Altered Expression	[1]
Hepatitis E virus infection	DIS0TXIR	Disputed	Biomarker	[5]
Anaplastic large cell lymphoma	DISP4D1R	Limited	Altered Expression	[6]
Lymphoid leukemia	DIS65TYQ	Limited	Altered Expression	[6]

4 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-C5 (HOXC5).	[7]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Homeobox protein Hox-C5 (HOXC5).	[8]
Triclosan	DMZUR4N	Approved	Triclosan increases the expression of Homeobox protein Hox-C5 (HOXC5).	[9]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Homeobox protein Hox-C5 (HOXC5).	[10]

References

• [1] HOXC4, HOXC5, and HOXC6 expression in non-Hodgkin's lymphoma: preferential expression of the HOXC5 gene in primary cutaneous anaplastic T-cell and oro-gastrointestinal tract mucosa-associated B-cell lymphomas.Blood. 1997 Nov 15;90(10):4116-25.
• [2] Differentiation and cell-type-restricted expression of HOXC4, HOXC5 and HOXC6 in myeloid leukemias and normal myeloid cells.Leukemia. 1998 Nov;12(11):1724-32. doi: 10.1038/sj.leu.2401106.
• [3] Analysis of single nucleotide polymorphisms and haplotypes in HOXC gene cluster within susceptible region 12q13 of simple congenital heart disease.Zhonghua Yi Xue Yi Chuan Xue Za Zhi. 2005 Oct;22(5):497-501.
• [4] The three most downstream genes of the Hox-3 cluster are expressed in human extraembryonic tissues including trophoblast of androgenetic origin.Development. 1990 Mar;108(3):471-7. doi: 10.1242/dev.108.3.471.
• [5] Potent Inhibition of Hepatitis E Virus Release by a Cyclic Peptide Inhibitor of the Interaction between Viral Open Reading Frame 3 Protein and Host Tumor Susceptibility Gene 101.J Virol. 2018 Sep 26;92(20):e00684-18. doi: 10.1128/JVI.00684-18. Print 2018 Oct 15.
• [6] HOXC4, HOXC5, and HOXC6 expression in primary cutaneous lymphoid lesions. High expression of HOXC5 in anaplastic large-cell lymphomas.Am J Pathol. 1997 Oct;151(4):1067-74.
• [7] Development of a neural teratogenicity test based on human embryonic stem cells: response to retinoic acid exposure. Toxicol Sci. 2011 Dec;124(2):370-7.
• [8] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [9] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [10] Bisphenol-A and estradiol exert novel gene regulation in human MCF-7 derived breast cancer cells. Mol Cell Endocrinol. 2004 Jun 30;221(1-2):47-55. doi: 10.1016/j.mce.2004.04.010.