We found that five genes encoding the four enzymes that catalyze the irreversible reactions of gluconeogenesis were all downregulated in renal cysts, including pyruvate carboxylase (PC, −3.4×), phosphoenolpyruvate carboxy-kinase (PCK1, −43.4×; PCK2, −3.9×), fructose 1,2-bisphosphatase (FBP1, −7.2×), and glucose 6-phosphate phosphatase (G6PC, −7.3×). This evidence concerns the gene G6PC1 and cystic kidney disease.