Abstract: Glucocorticoids are widely used as potent anti-inflammatory drugs. Glucocorticoids exert their pharmacological effects by binding to glucocorticoid receptor (GR), which promotes expression of its target genes, or suppresses transcription mediated by other transcriptional factors, such as nuclear factor-κB (NF-κB). We had recently found one novel single nucleotide polymorphism, 420G>T (K140N), in the glucocorticoid receptor gene in Japanese subjects. In transiently transfected COS-7 cells, the expression of the K140N variant protein was approximately 14% of the wild type protein, although their mRNA levels were almost equivalent. When the transfected COS-7 cells were treated with a proteasome inhibitor MG-132, the K140N variant protein levels were increased 3-fold whereas those of the wild type were increased by 1.5-fold. Immunocytochemistry revealed that the K140N variant protein was localized similar to the wild type protein. The luciferase reporter assay in COS-7 cells treated with 100 nM dexamethasone showed that the overall luciferase activity of the K140N variant was reduced to approximately 67% of the wild type. Thus, the K140N variation was suggested to influence the response to glucocorticoid treatment.