Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT7FI94W)

DOT Name Homeobox protein Nkx-6.2 (NKX6-2)
Synonyms Homeobox protein NK-6 homolog B
Gene Name NKX6-2
Related Disease
Bladder cancer ( )
Brain neoplasm ( )
Chronic kidney disease ( )
Epilepsy ( )
Leukodystrophy ( )
Neoplasm ( )
Pancreatic adenocarcinoma ( )
Pathologic nystagmus ( )
Spastic ataxia ( )
Spastic ataxia 8, autosomal recessive, with hypomyelinating leukodystrophy ( )
Urinary bladder cancer ( )
Urinary bladder neoplasm ( )
UniProt ID
NKX62_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
MDTNRPGAFVLSSAPLAALHNMAEMKTSLFPYALQGPAGFKAPALGGLGAQLPLGTPHGI
SDILGRPVGAAGGGLLGGLPRLNGLASSAGVYFGPAAAVARGYPKPLAELPGRPPIFWPG
VVQGAPWRDPRLAGPAPAGGVLDKDGKKKHSRPTFSGQQIFALEKTFEQTKYLAGPERAR
LAYSLGMTESQVKVWFQNRRTKWRKRHAVEMASAKKKQDSDAEKLKVGGSDAEDDDEYNR
PLDPNSDDEKITRLLKKHKPSNLALVSPCGGGAGDAL
Function
Transcription factor with repressor activity involved in the regulation of axon-glial interactions at myelin paranodes in oligodendrocytes. Binds to the consensus DNA sequence 5'-(A/T)TTAATGA-3'. In oligodendrocytes, binds to MBP and PLP1 promoter regions.
Tissue Specificity Highest expression in brain.

Molecular Interaction Atlas (MIA) of This DOT

12 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Bladder cancer DISUHNM0 Strong Biomarker [1]
Brain neoplasm DISY3EKS Strong Biomarker [2]
Chronic kidney disease DISW82R7 Strong Altered Expression [3]
Epilepsy DISBB28L Strong Altered Expression [4]
Leukodystrophy DISVY1TT Strong Genetic Variation [4]
Neoplasm DISZKGEW Strong Biomarker [2]
Pancreatic adenocarcinoma DISKHX7S Strong Biomarker [5]
Pathologic nystagmus DIS1QSPO Strong Genetic Variation [4]
Spastic ataxia DISIRRA9 Strong Genetic Variation [6]
Spastic ataxia 8, autosomal recessive, with hypomyelinating leukodystrophy DISX8TEG Strong Autosomal recessive [7]
Urinary bladder cancer DISDV4T7 Strong Biomarker [1]
Urinary bladder neoplasm DIS7HACE Strong Biomarker [1]
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⏷ Show the Full List of 12 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 Homeobox protein Nkx-6.2 (NKX6-2). [8]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene increases the methylation of Homeobox protein Nkx-6.2 (NKX6-2). [11]
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2 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Estradiol DMUNTE3 Approved Estradiol affects the expression of Homeobox protein Nkx-6.2 (NKX6-2). [9]
Triclosan DMZUR4N Approved Triclosan decreases the expression of Homeobox protein Nkx-6.2 (NKX6-2). [10]
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References

1 Detection of bladder cancer using novel DNA methylation biomarkers in urine sediments.Cancer Epidemiol Biomarkers Prev. 2011 Jul;20(7):1483-91. doi: 10.1158/1055-9965.EPI-11-0067. Epub 2011 May 17.
2 Cloning, expression and chromosomal location of NKX6B TO 10Q26, a region frequently deleted in brain tumors.Mamm Genome. 2001 Feb;12(2):157-62. doi: 10.1007/s003350010247.
3 Molecular Markers of Tubulointerstitial Fibrosis and Tubular Cell Damage in Patients with Chronic Kidney Disease.PLoS One. 2015 Aug 28;10(8):e0136994. doi: 10.1371/journal.pone.0136994. eCollection 2015.
4 Genetic and phenotypic characterization of NKX6-2-related spastic ataxia and hypomyelination.Eur J Neurol. 2020 Feb;27(2):334-342. doi: 10.1111/ene.14082. Epub 2019 Oct 17.
5 Predictors of Response and Survival in Locally Advanced Adenocarcinoma of the Pancreas Following Neoadjuvant GTX with or Without Radiation Therapy.Oncologist. 2018 Jan;23(1):4-e10. doi: 10.1634/theoncologist.2017-0208. Epub 2017 Dec 6.
6 Mutations in NKX6-2 Cause Progressive Spastic Ataxia and Hypomyelination. Am J Hum Genet. 2017 Jun 1;100(6):969-977. doi: 10.1016/j.ajhg.2017.05.009.
7 Classification of Genes: Standardized Clinical Validity Assessment of Gene-Disease Associations Aids Diagnostic Exome Analysis and Reclassifications. Hum Mutat. 2017 May;38(5):600-608. doi: 10.1002/humu.23183. Epub 2017 Feb 13.
8 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.
9 Identification of novel low-dose bisphenol a targets in human foreskin fibroblast cells derived from hypospadias patients. PLoS One. 2012;7(5):e36711. doi: 10.1371/journal.pone.0036711. Epub 2012 May 4.
10 Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
11 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.