Details of Drug Off-Target (DOT)

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

• DOT Name: Homeobox protein Nkx-2.6 (NKX2-6)
• Synonyms: Homeobox protein NK-2 homolog F
• Gene Name: NKX2-6
• Related Disease:
  Atrial fibrillation
  DiGeorge syndrome
  Persistent truncus arteriosus
  Shprintzen-Goldberg syndrome
  Conotruncal heart malformations
  Tetralogy of fallot
  Congenital heart disease
• UniProt ID: NKX26_HUMAN
• Pfam ID: PF00046
• Sequence:
  MLLSPVTSTPFSVKDILRLERERSCPAASPHPRVRKSPENFQYLRMDAEPRGSEVHNAGG
  GGGDRKLDGSEPPGGPCEAVLEMDAERMGEPQPGLNAASPLGGGTRVPERGVGNSGDSVR
  GGRSEQPKARQRRKPRVLFSQAQVLALERRFKQQRYLSAPEREHLASALQLTSTQVKIWF
  QNRRYKCKRQRQDKSLELAGHPLTPRRVAVPVLVRDGKPCLGPGPGAPAFPSPYSAAVSP
  YSCYGGYSGAPYGAGYGTCYAGAPSGPAPHTPLASAGFGHGGQNATPQGHLAATLQGVRA
  W
• Function: Acts as a transcriptional activator. In conjunction with NKX2-5, may play a role in both pharyngeal and cardiac embryonic development.

Molecular Interaction Atlas (MIA) of This DOT

7 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Atrial fibrillation	DIS15W6U	Strong	Biomarker	[1]
DiGeorge syndrome	DIST1RKO	Strong	Biomarker	[2]
Persistent truncus arteriosus	DISRZ8EA	Strong	SusceptibilityMutation	[3]
Shprintzen-Goldberg syndrome	DISQH6P3	Strong	Biomarker	[2]
Conotruncal heart malformations	DIS7FMIG	Moderate	Autosomal recessive	[4]
Tetralogy of fallot	DISMHFNW	moderate	SusceptibilityMutation	[3]
Congenital heart disease	DISQBA23	Limited	Autosomal recessive	[5]

2 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic increases the methylation of Homeobox protein Nkx-2.6 (NKX2-6).	[6]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Homeobox protein Nkx-2.6 (NKX2-6).	[8]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of Homeobox protein Nkx-2.6 (NKX2-6).	[7]

References

• [1] NKX2-6 mutation predisposes to familial atrial fibrillation.Int J Mol Med. 2014 Dec;34(6):1581-90. doi: 10.3892/ijmm.2014.1971. Epub 2014 Oct 16.
• [2] Conotruncal malformations and absent thymus due to a deleterious NKX2-6 mutation.J Med Genet. 2014 Apr;51(4):268-70. doi: 10.1136/jmedgenet-2013-102100. Epub 2014 Jan 13.
• [3] Prevalence and spectrum of Nkx2.6 mutations in patients with congenital heart disease.Eur J Med Genet. 2014 Oct;57(10):579-86. doi: 10.1016/j.ejmg.2014.08.005. Epub 2014 Sep 3.
• [4] 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.
• [5] Technical standards for the interpretation and reporting of constitutional copy-number variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics (ACMG) and the Clinical Genome Resource (ClinGen). Genet Med. 2020 Feb;22(2):245-257. doi: 10.1038/s41436-019-0686-8. Epub 2019 Nov 6.
• [6] Epigenetic changes in individuals with arsenicosis. Chem Res Toxicol. 2011 Feb 18;24(2):165-7. doi: 10.1021/tx1004419. Epub 2011 Feb 4.
• [7] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [8] 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.