Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT7DTH46)

DOT Name H2.0-like homeobox protein (HLX)
Synonyms Homeobox protein HB24; Homeobox protein HLX1
Gene Name HLX
Related Disease
Acute leukaemia ( )
Acute lymphocytic leukaemia ( )
Advanced cancer ( )
B-cell lymphoma ( )
Classic Hodgkin lymphoma ( )
Hepatocellular carcinoma ( )
Neoplasm ( )
Asthma ( )
Fetal growth restriction ( )
Acute myelogenous leukaemia ( )
Congenital diaphragmatic hernia ( )
UniProt ID
HLX_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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Pfam ID
PF00046
Sequence
MFAAGLAPFYASNFSLWSAAYCSSAGPGGCSFPLDPAAVKKPSFCIADILHAGVGDLGAA
PEGLAGASAAALTAHLGSVHPHASFQAAARSPLRPTPVVAPSEVPAGFPQRLSPLSAAYH
HHHPQQQQQQQQPQQQQPPPPPRAGALQPPASGTRVVPNPHHSGSAPAPSSKDLKFGIDR
ILSAEFDPKVKEGNTLRDLTSLLTGGRPAGVHLSGLQPSAGQFFASLDPINEASAILSPL
NSNPRNSVQHQFQDTFPGPYAVLTKDTMPQTYKRKRSWSRAVFSNLQRKGLEKRFEIQKY
VTKPDRKQLAAMLGLTDAQVKVWFQNRRMKWRHSKEAQAQKDKDKEAGEKPSGGAPAADG
EQDERSPSRSEGEAESESSDSESLDMAPSDTERTEGSERSLHQTTVIKAPVTGALITASS
AGSGGSSGGGGNSFSFSSASSLSSSSTSAGCASSLGGGGASELLPATQPTASSAPKSPEP
AQGALGCL
Function Transcription factor required for TBX21/T-bet-dependent maturation of Th1 cells as well as maintenance of Th1-specific gene expression. Involved in embryogenesis and hematopoiesis.
Tissue Specificity Low level in normal B and T-cells, high level in activated lymphocytes and monocytes. Also found in thymus, tonsil, bone marrow, developing vessels, and fetal brain.

Molecular Interaction Atlas (MIA) of This DOT

11 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Acute leukaemia DISDQFDI Strong Altered Expression [1]
Acute lymphocytic leukaemia DISPX75S Strong Altered Expression [1]
Advanced cancer DISAT1Z9 Strong Biomarker [2]
B-cell lymphoma DISIH1YQ Strong Altered Expression [3]
Classic Hodgkin lymphoma DISV1LU6 Strong Altered Expression [4]
Hepatocellular carcinoma DIS0J828 Strong Biomarker [5]
Neoplasm DISZKGEW Strong Biomarker [5]
Asthma DISW9QNS moderate Genetic Variation [6]
Fetal growth restriction DIS5WEJ5 moderate Altered Expression [7]
Acute myelogenous leukaemia DISCSPTN Limited Genetic Variation [8]
Congenital diaphragmatic hernia DIS0IPVU Limited Biomarker [9]
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⏷ Show the Full List of 11 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
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 H2.0-like homeobox protein (HLX). [10]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene increases the methylation of H2.0-like homeobox protein (HLX). [18]
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9 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Ciclosporin DMAZJFX Approved Ciclosporin decreases the expression of H2.0-like homeobox protein (HLX). [11]
Tretinoin DM49DUI Approved Tretinoin affects the expression of H2.0-like homeobox protein (HLX). [12]
Doxorubicin DMVP5YE Approved Doxorubicin decreases the expression of H2.0-like homeobox protein (HLX). [13]
Cisplatin DMRHGI9 Approved Cisplatin decreases the expression of H2.0-like homeobox protein (HLX). [14]
Triclosan DMZUR4N Approved Triclosan increases the expression of H2.0-like homeobox protein (HLX). [15]
Rosiglitazone DMILWZR Approved Rosiglitazone decreases the expression of H2.0-like homeobox protein (HLX). [16]
SNDX-275 DMH7W9X Phase 3 SNDX-275 decreases the expression of H2.0-like homeobox protein (HLX). [17]
Tamibarotene DM3G74J Phase 3 Tamibarotene affects the expression of H2.0-like homeobox protein (HLX). [12]
PMID27336223-Compound-5 DM6E50A Patented PMID27336223-Compound-5 decreases the expression of H2.0-like homeobox protein (HLX). [16]
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⏷ Show the Full List of 9 Drug(s)

References

1 High expression of two diverged homeobox genes, HB24 and HB9, in acute leukemias: molecular markers of hematopoietic cell immaturity.Leukemia. 1993 Mar;7(3):446-51.
2 Co-regulation of senescence-associated genes by oncogenic homeobox proteins and polycomb repressive complexes.Cell Cycle. 2013 Jul 15;12(14):2194-9. doi: 10.4161/cc.25331.
3 Epstein-Barr virus (EBV) activates NKL homeobox gene HLX in DLBCL.PLoS One. 2019 May 29;14(5):e0216898. doi: 10.1371/journal.pone.0216898. eCollection 2019.
4 Aberrant expression of NKL homeobox gene HLX in Hodgkin lymphoma.Oncotarget. 2018 Feb 16;9(18):14338-14353. doi: 10.18632/oncotarget.24512. eCollection 2018 Mar 6.
5 H2.0-like homeobox 1 acts as a tumor suppressor in hepatocellular carcinoma.Tumour Biol. 2016 May;37(5):6419-28. doi: 10.1007/s13277-015-4490-z. Epub 2015 Dec 2.
6 TBX21 and HLX1 polymorphisms influence cytokine secretion at birth.PLoS One. 2012;7(1):e31069. doi: 10.1371/journal.pone.0031069. Epub 2012 Jan 30.
7 Expression of Homeobox Gene HLX and its Downstream Target Genes are Altered in Placentae From Discordant Twin Pregnancies.Twin Res Hum Genet. 2018 Feb;21(1):42-50. doi: 10.1017/thg.2017.66. Epub 2017 Dec 7.
8 Polymorphisms in human homeobox HLX1 and DNA repair RAD51 genes increase the risk of therapy-related acute myeloid leukemia.Blood. 2006 Dec 1;108(12):3916-8. doi: 10.1182/blood-2006-05-022921. Epub 2006 Aug 10.
9 HLX is a candidate gene for a pattern of anomalies associated with congenital diaphragmatic hernia, short bowel, and asplenia.Am J Med Genet A. 2017 Nov;173(11):3070-3074. doi: 10.1002/ajmg.a.38354. Epub 2017 Sep 12.
10 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.
11 Integrative "-Omics" analysis in primary human hepatocytes unravels persistent mechanisms of cyclosporine A-induced cholestasis. Chem Res Toxicol. 2016 Dec 19;29(12):2164-2174.
12 Differential modulation of PI3-kinase/Akt pathway during all-trans retinoic acid- and Am80-induced HL-60 cell differentiation revealed by DNA microarray analysis. Biochem Pharmacol. 2004 Dec 1;68(11):2177-86.
13 Bringing in vitro analysis closer to in vivo: studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling. Toxicol Lett. 2018 Sep 15;294:184-192.
14 Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
15 Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
16 PPARgamma controls CD1d expression by turning on retinoic acid synthesis in developing human dendritic cells. J Exp Med. 2006 Oct 2;203(10):2351-62.
17 Definition of transcriptome-based indices for quantitative characterization of chemically disturbed stem cell development: introduction of the STOP-Toxukn and STOP-Toxukk tests. Arch Toxicol. 2017 Feb;91(2):839-864.
18 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.