ABSTRACT: Using the published protein sequence from a rabbit microsomal glucose-6-phosphate dehydrogenase G6PD we have isolated and sequenced a cDNA clone coding for its human equivalent, which is also known as hexose-6-phosphate dehydrogenase (H6PD) and glucose dehydrogenase. The corresponding genomic sequence is in the databases enabling its localization to chromosome 1p36. The gene spans 37 kb and consists of 5 exons, the fifth of which codes for more than half of the 89kDa protein. The first intron is a 10kb insertion in the 5' untranslated sequence. The predicted mRNA has an exceptionally long (6.5kb) 3' untranslated sequence. The predicted protein shows extensive homology with X-linked G6PD, suggesting the two genes share a common ancestor but no intron positions are conserved between the two genes suggesting the gene duplication was an ancient event. The C-terminal portion of the protein is not homologous with G6PD but shows limited homology with proteins of unknown function found throughout evolution and encoded next to G6PD in various micro-organisms. Intriguingly this C-terminal portion has some homology with the N-terminal sequence of Plasmodium falciparum G6PD.

Keywords: Hexose-6-phosphate dehydrogenase gene, glucose 1- dehydrogenase, microsomal G6PD, chromosome 1p36, long 3' untranslated region, devb.

Reprint requests to: Dr. Philip J. Mason, Department of Haematology, Royal Postgraduate Medical School, Hammersmith Hospital, Ducane Road, London W12 ONN, UNITED KINGDOM, phone: 0181-383-3235, fax: 0181-742-9335, e-mail: pmason@rpms.ac.uk.