Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT6Q3DJ0)

DOT Name	Homeobox protein Nkx-2.8 (NKX2-8)
Synonyms	Homeobox protein NK-2 homolog H
Gene Name	NKX2-8
Related Disease	Neural tube defect ( ) Advanced cancer ( ) Carcinoma of esophagus ( ) Epithelial ovarian cancer ( ) Esophageal cancer ( ) Esophageal squamous cell carcinoma ( ) Lung cancer ( ) Lung carcinoma ( ) Neoplasm ( ) Neoplasm of esophagus ( ) Non-small-cell lung cancer ( )
UniProt ID	NKX28_HUMAN
3D Structure	Download 2D Sequence (FASTA) Download 3D Structure (PDB) Download
Pfam ID	PF00046
Sequence	MATSGRLSFTVRSLLDLPEQDAQHLPRREPEPRAPQPDPCAAWLDSERGHYPSSDESSLE TSPPDSSQRPSARPASPGSDAEKRKKRRVLFSKAQTLELERRFRQQRYLSAPEREQLASL LRLTPTQVKIWFQNHRYKLKRARAPGAAESPDLAASAELHAAPGLLRRVVVPVLVRDGQP CGGGGGGEVGTAAAQEKCGAPPAAACPLPGYPAFGPGSALGLFPAYQHLASPALVSWNW

Molecular Interaction Atlas (MIA) of This DOT

11 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance
Neural tube defect	DIS5J95E	Definitive	Genetic Variation	[1]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[2]
Carcinoma of esophagus	DISS6G4D	Strong	Altered Expression	[3]
Epithelial ovarian cancer	DIS56MH2	Strong	Biomarker	[4]
Esophageal cancer	DISGB2VN	Strong	Altered Expression	[3]
Esophageal squamous cell carcinoma	DIS5N2GV	Strong	Biomarker	[3]
Lung cancer	DISCM4YA	Strong	Biomarker	[5]
Lung carcinoma	DISTR26C	Strong	Biomarker	[5]
Neoplasm	DISZKGEW	Strong	Genetic Variation	[4]
Neoplasm of esophagus	DISOLKAQ	Strong	Altered Expression	[3]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Genetic Variation	[6]
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Molecular Interaction Atlas (MIA)

MIA Detail

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 Homeobox protein Nkx-2.8 (NKX2-8).	[7]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Homeobox protein Nkx-2.8 (NKX2-8).	[10]
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2 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Triclosan	DMZUR4N	Approved	Triclosan increases the expression of Homeobox protein Nkx-2.8 (NKX2-8).	[8]
Decitabine	DMQL8XJ	Approved	Decitabine increases the expression of Homeobox protein Nkx-2.8 (NKX2-8).	[9]
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References

1	Genome-wide association mapping in dogs enables identification of the homeobox gene, NKX2-8, as a genetic component of neural tube defects in humans.PLoS Genet. 2013;9(7):e1003646. doi: 10.1371/journal.pgen.1003646. Epub 2013 Jul 18.
2	The tumor-suppressor gene Nkx2.8 suppresses bladder cancer proliferation through upregulation of FOXO3a and inhibition of the MEK/ERK signaling pathway.Carcinogenesis. 2012 Mar;33(3):678-86. doi: 10.1093/carcin/bgr321. Epub 2012 Jan 4.
3	Nkx2-8 downregulation promotes angiogenesis and activates NF-B in esophageal cancer.Cancer Res. 2013 Jun 15;73(12):3638-48. doi: 10.1158/0008-5472.CAN-12-4028. Epub 2013 Apr 19.
4	NKX2-8 deletion-induced reprogramming of fatty acid metabolism confers chemoresistance in epithelial ovarian cancer.EBioMedicine. 2019 May;43:238-252. doi: 10.1016/j.ebiom.2019.04.041. Epub 2019 Apr 29.
5	Both gene amplification and allelic loss occur at 14q13.3 in lung cancer.Clin Cancer Res. 2011 Feb 15;17(4):690-9. doi: 10.1158/1078-0432.CCR-10-1892. Epub 2010 Dec 10.
6	One allele's loss is another's gain: alterations of NKX2-8 in non-small cell lung cancer.Clin Cancer Res. 2011 Feb 15;17(4):638-9. doi: 10.1158/1078-0432.CCR-10-3081. Epub 2010 Dec 16.
7	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.
8	Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
9	Gene induction and apoptosis in human hepatocellular carci-noma cells SMMC-7721 exposed to 5-aza-2'-deoxycytidine. Chin Med J (Engl). 2007 Sep 20;120(18):1626-31.
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.