Alternative titles; symbols
HGNC Approved Gene Symbol: PGD
Cytogenetic location: 1p36.22 Genomic coordinates (GRCh38): 1:10,399,064-10,420,511 (from NCBI)
6-Phosphogluconate dehydrogenase (PGD; EC 1.1.1.44) is the third enzyme in the pentose phosphate pathway. It catalyzes the oxidative decarboxylation of 6-phosphogluconate to ribulose 5-phosphate, with release of carbon dioxide and reduction of NADP+ (summary by Tsui et al., 1996).
Tsui et al. (1996) cloned PGD from a human adult heart cDNA library. The gene encodes a deduced 483-amino acid protein with a calculated molecular mass of 53 kD. Human PGD shares 94.2%, 83.1%, and 71.4% identity with sheep, pig, and Drosophila PGD proteins, respectively.
A possibility of linkage between the Rhesus and 6PGD loci was found by Weitkamp et al. (1970). This has since been fully confirmed (Weitkamp et al., 1971). Weitkamp (1972) gave valid criticism of the conclusions of linkage studies of 2 groups. It is clear, however, that the Rhesus and 6PGD loci are on chromosome 1. Douglas et al. (1973) demonstrated that the PGM1 and 6PGD loci are on the distal end of the short arm of chromosome 1. Assuming that each arm of chromosome 1 is 140 male cM long, Cook et al. (1974) concluded that, measured from the centromere, map positions are as follows: PGD, 1p124; RH, 1p109; PGM1, 1p079; FY, 1p010; PEPC, 1q030. Since the G6PD locus is X-linked, these 2 functionally related genes do not show clustering.
At HGM8, Povey et al. (1985) concluded that the smallest region of overlap for PGD is 1p36.2-p36.13.
From a study of 6PGD enzymes from sheep liver, human erythrocytes, and Trypanosoma brucei, Rippa et al. (1998) found evidence that the activity of 6PGD is subjected to 2-way regulation: NADPH, which regulates the pentose phosphate pathway, inhibits the enzyme, while 6-phosphogluconate, levels of which rise when NADPH inhibition is removed, acts as an activator, ensuring that 6-phosphogluconate is rapidly removed.
Data on gene frequencies of allelic variants were tabulated by Roychoudhury and Nei (1988).
Using starch-gel electrophoresis, Fildes and Parr (1963) detected 2 distinct alleles of human red cell 6-phosphogluconate dehydrogenase. Ten of 150 random blood samples showed 2 broad, less distinct bands in contrast to the single narrow, sharp band in the remainder. Inheritance appeared to be autosomal. Heterozygotes and homozygotes showed no quantitative difference in red blood cell 6PGD activity.
Davidson (1967) noted that the 2 common PGD alleles identified by Fildes and Parr (1963) are designated PGD-A and PGD-C. Davidson (1967) identified a rare PGD variant designated PGD-Friendship.
Other rare PGD variants were reported by Parr (1966), Blake and Kirk (1969), Tariverdian et al. (1970), Benkmann et al. (1986), and Nevo (1989).
Benkmann, H.-G., Paik, Y. K., Chen, L. Z., Goedde, H. W. Polymorphism of 6-PGD in South Korea: a new genetic variant 6-PGD Korea. Hum. Genet. 74: 204-205, 1986. [PubMed: 3770750] [Full Text: https://doi.org/10.1007/BF00282097]
Blake, N. M., Kirk, R. L. New genetic variant of 6-phosphogluconate dehydrogenase in Australian aborigines. Nature 221: 278 only, 1969. [PubMed: 5763087] [Full Text: https://doi.org/10.1038/221278a0]
Bowman, J. E., Carson, P. E., Frischer, H., De Garay, A. L. Genetics of starch-gel electrophoretic variants of human 6-phosphogluconic dehydrogenase: population and family studies in the United States and in Mexico. Nature 210: 811-812, 1966. [PubMed: 5958448] [Full Text: https://doi.org/10.1038/210811a0]
Burgerhout, W., Van Someren, H., Bootsma, D. Cytological mapping of the genes assigned to the human A1 chromosome by use of radiation-induced chromosome breakage in a human-Chinese hamster hybrid cell line. Humangenetik 20: 159-162, 1973. [PubMed: 4785162] [Full Text: https://doi.org/10.1007/BF00284852]
Cook, P. J. L., Robson, E. B., Buckton, K. E., Jacobs, P. A., Polani, P. E. Segregation of genetic markers in families with chromosome polymorphisms and structural rearrangements involving chromosome 1. Ann. Hum. Genet. 37: 261-274, 1974. [PubMed: 4812948] [Full Text: https://doi.org/10.1111/j.1469-1809.1974.tb01834.x]
Davidson, R. G. Electrophoretic variants of human 6-phosphogluconate dehydrogenase: population and family studies and description of a new variant. Ann. Hum. Genet. 30: 355-362, 1967. [PubMed: 5619936] [Full Text: https://doi.org/10.1111/j.1469-1809.1967.tb00037.x]
Douglas, G. R., McAlpine, P. J., Hamerton, J. L. Regional localization of loci for human PGM-1 and 6PGD on human chromosome 1 by use of hybrids of Chinese hamster-human somatic cells. Proc. Nat. Acad. Sci. 70: 2737-2740, 1973. [PubMed: 4517931] [Full Text: https://doi.org/10.1073/pnas.70.10.2737]
Fildes, R. A., Parr, C. W. Human red-cell phosphogluconate dehydrogenases. Nature 200: 890-891, 1963. [PubMed: 14096069] [Full Text: https://doi.org/10.1038/200890a0]
Nelson, M. S. Biochemical and genetic characterization of the Lowell variant: a new phenotype of 6-phosphogluconate dehydrogenase. Hum. Genet. 62: 333-336, 1982. [PubMed: 7166309] [Full Text: https://doi.org/10.1007/BF00304550]
Nevo, S. A new rare PGD variant, PGD Mediterranean. Hum. Genet. 81: 199 only, 1989. [PubMed: 2912891] [Full Text: https://doi.org/10.1007/BF00293905]
Parr, C. W., Fitch, L. I. Inherited quantitative variations of human phosphogluconate dehydrogenase. Ann. Hum. Genet. 30: 339-353, 1967. [PubMed: 5619935] [Full Text: https://doi.org/10.1111/j.1469-1809.1967.tb00036.x]
Parr, C. W. Erythrocyte phosphogluconate dehydrogenase polymorphism. Nature 210: 487-489, 1966. [PubMed: 5960509] [Full Text: https://doi.org/10.1038/210487a0]
Povey, S., Morton, N. E., Sherman, S. L. Report of the committee on the genetic constitution of chromosomes 1 and 2. Cytogenet. Cell Genet. 40: 67-106, 1985. [PubMed: 3864603] [Full Text: https://doi.org/10.1159/000132170]
Rippa, M., Giovannini, P. P., Barrett, M. P., Dallocchio, F., Hanau, S. 6-Phosphogluconate dehydrogenase: the mechanism of action investigated by a comparison of the enzyme from different species. Biochim. Biophys. Acta 1429: 83-92, 1998. [PubMed: 9920387] [Full Text: https://doi.org/10.1016/s0167-4838(98)00222-2]
Ritter, H., Tariverdian, G., Wendt, G. G., Zilch, I. Genetic and linkage analysis on 6-PGD. Humangenetik 14: 73-75, 1971. [PubMed: 5004219] [Full Text: https://doi.org/10.1007/BF00273038]
Roychoudhury, A. K., Nei, M. Human Polymorphic Genes: World Distribution. New York: Oxford Univ. Press (pub.) 1988.
Tariverdian, G., Ropers, H.-H., Op't Hof, J., Ritter, H. Zur Genetik der 6-Phosphogluconatdehydrogenase (EC: 1.1.1.44): Eine neue Variante F (Freiburg). Humangenetik 10: 355-357, 1970. [PubMed: 5493240] [Full Text: https://doi.org/10.1007/BF00278774]
Tsui, S. K. W., Chan, J. Y. W., Waye, M. M. Y., Fung, K. P., Lee, C. Y. Identification of a cDNA encoding 6-phosphogluconate dehydrogenase from a human heart cDNA library. Biochem. Genet. 34: 367-373, 1996. [PubMed: 8978909] [Full Text: https://doi.org/10.1007/BF00554412]
Weitkamp, L. R., Guttormsen, S. A., Greendyke, R. M. Genetic linkage between a locus for 6-PGD and the Rh locus: evaluation of possible heterogeneity in the recombination fraction between sexes and among families. Am. J. Hum. Genet. 23: 462-470, 1971. [PubMed: 4999137]
Weitkamp, L. R., Guttormsen, S. A., Shreffler, D. C., Sing, C. F., Napier, J. A. Genetic linkage relations of the loci for 6-phosphogluconate dehydrogenase and adenosine deaminase in man. Am. J. Hum. Genet. 22: 216-220, 1970. [PubMed: 4985154]
Weitkamp, L. R. Genetic linkage relationships of the ADA and 6-PGD loci in 'Humangenetik'. (Letter) Humangenetik 15: 359-360, 1972. [PubMed: 4634454] [Full Text: https://doi.org/10.1007/BF00281739]
Westerveld, A., Meera Khan, P. Evidence for linkage between human loci for 6-phosphogluconate dehydrogenase and phosphoglucomutase(1) in man-Chinese hamster somatic cell hybrids. Nature 236: 30-32, 1972. [PubMed: 4553635] [Full Text: https://doi.org/10.1038/236030a0]