cDNA sequence and localization of polymorphic human cytosolic phosphoenolpyruvate carboxykinase gene (PCK1) to chromosome 20, band q13.31: PCK1 is not tightly linked to maturity-onset diabetes of the young.

Complementary DNA clones encoding human cytosolic phosphoenolpyruvate carboxykinase (GTP) [GTP: oxaloacetate carboxy-lyase (transphosphorylating), EC 4.1.1.32) (PEPCK)] were isolated from a human kidney cDNA library. The nucleotide sequence of the 2.7 kb insert of one of these clones indicates that human PEPCK is a protein of 622 amino acids whose sequence shows 90% identity with that of the cognate rat enzyme. The human PEPCK gene (PCK1) was isolated by hybridization using a fragment of the hPEPCK cDNA as a probe. PCK1 was mapped to human chromosome 20 using DNA from a panel of reduced human-hamster somatic cell hybrids. This assignment was confirmed using fluorescence in situ chromosomal hybridization which localized PCK1 to chromosome 20, band q13.31. A simple tandem repeat DNA polymorphism in the 3'-untranslated region of the mRNA was characterized and used to localize PCK1 relative to the gene responsible for a form of non-insulin-dependent (Type 2) diabetes mellitus called maturity-onset diabetes of the young (MODY). Linkage studies showed that PCK1 is not tightly linked to MODY in one large pedigree and exclude this diabetes candidate gene as the cause of MODY in this family.