Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTI4H30Z)

• DOT Name: Sodium/potassium-transporting ATPase subunit beta-1-interacting protein 2 (NKAIN2)
• Synonyms: Na(+)/K(+)-transporting ATPase subunit beta-1-interacting protein 2; Protein FAM77B; T-cell lymphoma breakpoint-associated target protein 1
• Gene Name: NKAIN2
• Related Disease:
  Neoplasm
  Neurotic disorder
  Prostate cancer
  Prostate carcinoma
  Alcohol dependence
  Alzheimer disease
  Chromosomal disorder
  Coeliac disease
  Leukemia
  Narcolepsy
  T-cell lymphoma
  Pancreatic cancer
  Periodontitis
  Neuroblastoma
• UniProt ID: NKAI2_HUMAN
• Pfam ID: PF05640
• Sequence:
  MGYCSGRCTLIFICGMQLVCVLERQIFDFLGYQWAPILANFVHIIIVILGLFGTIQYRPR
  YITGYAVWLVLWVTWNVFVICFYLEAGDLSKETDLILTFNISMHRSWWMENGPGCTVTSV
  TPAPDWAPEDHRYITVSGCLLEYQYIEVAHSSLQIVLALAGFIYACYVVKCITEEEDSFD
  FIGGFDSYGYQGPQKTSHLQLQPMYMSK
• Tissue Specificity: Expressed in fetal brain. Weakly expressed in adult brain and thymus. Not expressed in any other normal tissue examined.

Molecular Interaction Atlas (MIA) of This DOT

14 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Neoplasm	DISZKGEW	Definitive	Genetic Variation	[1]
Neurotic disorder	DIS1YCE9	Definitive	Genetic Variation	[2]
Prostate cancer	DISF190Y	Definitive	Altered Expression	[1]
Prostate carcinoma	DISMJPLE	Definitive	Altered Expression	[1]
Alcohol dependence	DIS4ZSCO	Strong	Biomarker	[3]
Alzheimer disease	DISF8S70	Strong	Genetic Variation	[4]
Chromosomal disorder	DISM5BB5	Strong	Biomarker	[5]
Coeliac disease	DISIY60C	Strong	Genetic Variation	[6]
Leukemia	DISNAKFL	Strong	Biomarker	[7]
Narcolepsy	DISLCNLI	Strong	Genetic Variation	[8]
T-cell lymphoma	DISSXRTQ	Strong	Biomarker	[7]
Pancreatic cancer	DISJC981	moderate	Biomarker	[9]
Periodontitis	DISI9JOI	moderate	Genetic Variation	[10]
Neuroblastoma	DISVZBI4	Limited	Biomarker	[11]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of Sodium/potassium-transporting ATPase subunit beta-1-interacting protein 2 (NKAIN2).	[12]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Sodium/potassium-transporting ATPase subunit beta-1-interacting protein 2 (NKAIN2).	[13]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Sodium/potassium-transporting ATPase subunit beta-1-interacting protein 2 (NKAIN2).	[14]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Sodium/potassium-transporting ATPase subunit beta-1-interacting protein 2 (NKAIN2).	[15]
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of Sodium/potassium-transporting ATPase subunit beta-1-interacting protein 2 (NKAIN2).	[17]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Sodium/potassium-transporting ATPase subunit beta-1-interacting protein 2 (NKAIN2).	[19]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Sodium/potassium-transporting ATPase subunit beta-1-interacting protein 2 (NKAIN2).	[16]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Sodium/potassium-transporting ATPase subunit beta-1-interacting protein 2 (NKAIN2).	[18]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A affects the methylation of Sodium/potassium-transporting ATPase subunit beta-1-interacting protein 2 (NKAIN2).	[20]

References

• [1] NKAIN2 functions as a novel tumor suppressor in prostate cancer.Oncotarget. 2016 Sep 27;7(39):63793-63803. doi: 10.18632/oncotarget.11690.
• [2] A genome-wide association study of neuroticism in a population-based sample.PLoS One. 2010 Jul 9;5(7):e11504. doi: 10.1371/journal.pone.0011504.
• [3] Family-based association analysis of alcohol dependence in the COGA sample and replication in the Australian twin-family study.J Neural Transm (Vienna). 2011 Sep;118(9):1293-9. doi: 10.1007/s00702-011-0628-3. Epub 2011 Mar 29.
• [4] Genome-wide association study of the rate of cognitive decline in Alzheimer's disease.Alzheimers Dement. 2014 Jan;10(1):45-52. doi: 10.1016/j.jalz.2013.01.008. Epub 2013 Mar 25.
• [5] Molecular cytogenetic analysis of the breakpoint region at 6q21-22 in T-cell lymphoma/leukemia cell lines.Genes Chromosomes Cancer. 2002 Jun;34(2):175-85. doi: 10.1002/gcc.10057.
• [6] Genome-wide association study of celiac disease in North America confirms FRMD4B as new celiac locus.PLoS One. 2014 Jul 7;9(7):e101428. doi: 10.1371/journal.pone.0101428. eCollection 2014.
• [7] Disruption of TCBA1 associated with a de novo t(1;6)(q32.2;q22.3) presenting in a child with developmental delay and recurrent infections.J Med Genet. 2006 Feb;43(2):143-7. doi: 10.1136/jmg.2004.029660. Epub 2005 May 20.
• [8] Genome-wide association database developed in the Japanese Integrated Database Project.J Hum Genet. 2009 Sep;54(9):543-6. doi: 10.1038/jhg.2009.68. Epub 2009 Jul 24.
• [9] Downregulation of microRNA-181d had suppressive effect on pancreatic cancer development through inverse regulation of KNAIN2.Tumour Biol. 2017 Apr;39(4):1010428317698364. doi: 10.1177/1010428317698364.
• [10] Genome-wide association study of chronic periodontitis in a general German population.J Clin Periodontol. 2013 Nov;40(11):977-85. doi: 10.1111/jcpe.12154. Epub 2013 Sep 11.
• [11] High-resolution array CGH profiling identifies Na/K transporting ATPase interacting 2 (NKAIN2) as a predisposing candidate gene in neuroblastoma.PLoS One. 2013 Oct 25;8(10):e78481. doi: 10.1371/journal.pone.0078481. eCollection 2013.
• [12] 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.
• [13] Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
• [14] 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.
• [15] Blood transcript immune signatures distinguish a subset of people with elevated serum ALT from others given acetaminophen. Clin Pharmacol Ther. 2016 Apr;99(4):432-41.
• [16] Prenatal arsenic exposure and the epigenome: identifying sites of 5-methylcytosine alterations that predict functional changes in gene expression in newborn cord blood and subsequent birth outcomes. Toxicol Sci. 2015 Jan;143(1):97-106. doi: 10.1093/toxsci/kfu210. Epub 2014 Oct 10.
• [17] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [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.
• [19] Cell-based two-dimensional morphological assessment system to predict cancer drug-induced cardiotoxicity using human induced pluripotent stem cell-derived cardiomyocytes. Toxicol Appl Pharmacol. 2019 Nov 15;383:114761. doi: 10.1016/j.taap.2019.114761. Epub 2019 Sep 15.
• [20] DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.