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HGNC Approved Gene Symbol: GMPS
Cytogenetic location: 3q25.31 Genomic coordinates (GRCh38): 3:155,869,430-155,944,020 (from NCBI)
In the de novo synthesis of purine nucleotides, IMP is the branch point metabolite at which point the pathway diverges to the synthesis of either guanine or adenine nucleotides. In the guanine nucleotide pathway, there are 2 enzymes involved in converting IMP to GMP, namely IMP dehydrogenase (IMPD1; 146690), which catalyzes the oxidation of IMP to XMP, and GMP synthetase (EC 6.3.5.2), which catalyzes the amination of XMP to GMP. Both IMP dehydrogenase and GMP synthetase exhibit elevated levels of activity in rapidly proliferating cells such as neoplastic and regenerating tissues (summary by Hirst et al., 1994).
Hirst et al. (1994) purified human GMP synthetase to homogeneity and isolated a cDNA encoding the enzyme from a T-lymphoblastoma cell line. The open reading frame encoded a protein of 693 amino acids with a predicted molecular mass of 76,725. The cDNA complemented a guaA mutant of Escherichia coli. A single 2.4-kb mRNA was demonstrated. DNA hybridization analysis suggested that human GMP synthetase is encoded by 1 gene.
By fluorescence in situ hybridization, Fedorova et al. (1997) mapped the GMPS gene to 3q24.
In a patient with treatment-related acute myeloid leukemia and the karyotype t(3;11)(q25;q23), Pegram et al. (2000) identified GMPS to be the partner gene of MLL (159550). The authors stated that GMPS was the first partner gene of MLL to be identified on 3q and the first gene of this type to be found in leukemia-associated translocations.
Fedorova, L., Kost-Alimova, M., Gizatullin, R. Z., Alimov, A., Zabarovska, V. I., Szeles, A., Protopopov, A. I., Vorobieva, N. V., Kashuba, V. I., Klein, G., Zelenin, A. V., Sheer, D., Zabarovsky, E. R. Assignment and ordering of twenty-three unique NotI-linking clones containing expressed genes including the guanosine 5-prime-monophosphate synthetase gene to human chromosome 3. Europ. J. Hum. Genet. 5: 110-116, 1997. [PubMed: 9195163]
Hirst, M., Haliday, E., Nakamura, J., Lou, L. Human GMP synthetase: protein purification, cloning, and functional expression of cDNA. J. Biol. Chem. 269: 23830-23837, 1994. [PubMed: 8089153]
Pegram, L. D., Megonigal, M. D., Lange, B. J., Nowell, P. C., Rowley, J. D., Rappaport, E. F., Felix, C. A. t(3;11) translocation in treatment-related acute myeloid leukemia fuses MLL with the GMPS (guanosine 5-prime monophosphate synthetase) gene. Blood 96: 4360-4362, 2000. [PubMed: 11110714]