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Gene Review

NKX6-1  -  NK6 homeobox 1

Homo sapiens

Synonyms: Homeobox protein NK-6 homolog A, Homeobox protein Nkx-6.1, NKX6.1, NKX6A, Nkx6.1
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High impact information on NKX6-1

  • In the absence of Nkx6.1, there are fewer secondary motoneurons and supernumerary ventral interneurons, suggesting Nkx6.1 promotes motoneuron and suppresses interneuron formation [1].
  • Peroxisome Proliferator-Activated Receptor-{gamma} Regulates Expression of PDX-1 and NKX6.1 in INS-1 Cells [2].
  • Among cell lines, both beta- and alpha-cell lines express nkx6.1 mRNA; but no protein can be detected in the alpha-cell lines, suggesting that post-transcriptional regulation contributes to the restriction of Nkx6.1 to beta-cells [3].
  • The nkx6.1 gene has a long 5'-untranslated region (5'-UTR) downstream of a cluster of transcription start sites. nkx6.1 gene sequences from -5.6 to +1.0 kilobase pairs have specific promoter activity in beta-cell lines but not in NIH3T3 cells [3].
  • In this report, we identify a novel beta-cell-specific enhancer element in the nkx6.1 gene between -157 and -30 bp (relative to the transcriptional start site) that harbors a conserved A/T-containing sequence flanked by G/C-rich stretches [4].

Biological context of NKX6-1

  • Analysis of gene expression by RT-PCR showed the presence of islet developmental transcription factors neuroD, Nkx6.1, and PDX-1, as well as mature islet hormones [5].
  • We found that native hMSCs have a pluripotent phenotype (OCT4 expression and high telomere length) and constitutively express NKX6-1 at a low level but lack all other transcription factors implicated in beta-cell differentiation [6].
  • Full-length Nkx6.1 fails to activate this reporter plasmid in spite of robust interaction with the binding site in vitro [7].

Anatomical context of NKX6-1

  • Isolation, characterization, and chromosomal mapping of the human Nkx6.1 gene (NKX6A), a new pancreatic islet homeobox gene [8].
  • The homeodomain (HD) protein Nkx6.1 is the most beta-cell-specific transcription factor known in the pancreas and its function is critical for the formation of the insulin-producing beta-cells [7].
  • However, at E14.5, Nkx6.1 immunoreactivity marks the nuclei of all epithelial cells of the ventral and dorsal pancreatic buds and the only endocrine cell types found at this time point are glucagon and PYY [9].

Analytical, diagnostic and therapeutic context of NKX6-1


  1. Zebrafish and fly Nkx6 proteins have similar CNS expression patterns and regulate motoneuron formation. Cheesman, S.E., Layden, M.J., Von Ohlen, T., Doe, C.Q., Eisen, J.S. Development (2004) [Pubmed]
  2. Peroxisome Proliferator-Activated Receptor-{gamma} Regulates Expression of PDX-1 and NKX6.1 in INS-1 Cells. Moibi, J.A., Gupta, D., Jetton, T.L., Peshavaria, M., Desai, R., Leahy, J.L. Diabetes (2007) [Pubmed]
  3. Transcriptional and translational regulation of beta-cell differentiation factor Nkx6.1. Watada, H., Mirmira, R.G., Leung, J., German, M.S. J. Biol. Chem. (2000) [Pubmed]
  4. The transcriptional repressor Nkx6.1 also functions as a deoxyribonucleic acid context-dependent transcriptional activator during pancreatic beta-cell differentiation: evidence for feedback activation of the nkx6.1 gene by Nkx6.1. Iype, T., Taylor, D.G., Ziesmann, S.M., Garmey, J.C., Watada, H., Mirmira, R.G. Mol. Endocrinol. (2004) [Pubmed]
  5. Enriched human pancreatic ductal cultures obtained from selective death of acinar cells express pancreatic and duodenal homeobox gene-1 age-dependently. Street, C.N., Lakey, J.R., Rajotte, R.V., Shapiro, A.M., Kieffer, T.J., Lyon, J.G., Kin, T., Korbutt, G.S. The review of diabetic studies : RDS (2004) [Pubmed]
  6. Human bone marrow mesenchymal stem cells can express insulin and key transcription factors of the endocrine pancreas developmental pathway upon genetic and/or microenvironmental manipulation in vitro. Moriscot, C., de Fraipont, F., Richard, M.J., Marchand, M., Savatier, P., Bosco, D., Favrot, M., Benhamou, P.Y. Stem Cells (2005) [Pubmed]
  7. Cloning and DNA-binding properties of the rat pancreatic beta-cell-specific factor Nkx6.1. Jørgensen, M.C., Vestergård Petersen, H., Ericson, J., Madsen, O.D., Serup, P. FEBS Lett. (1999) [Pubmed]
  8. Isolation, characterization, and chromosomal mapping of the human Nkx6.1 gene (NKX6A), a new pancreatic islet homeobox gene. Inoue, H., Rudnick, A., German, M.S., Veile, R., Donis-Keller, H., Permutt, M.A. Genomics (1997) [Pubmed]
  9. Developmental Biology of the Psammomys obesus Pancreas: Cloning and Expression of the Neurogenin-3 Gene. Vedtofte, L., B??dvarsd??ttir, T.B., Karlsen, A.E., Heller, R.S. J. Histochem. Cytochem. (2007) [Pubmed]
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