Gmpr-KO Mouse

GMPR, guanosine monophosphate reductase, is a nucleotide metabolism enzyme that converts GMP to IMP, thus decreasing GTP pools [3]. It belongs to the IMPDH/GMPR family of (β/α)(8) barrel enzymes, where reaction specificity is controlled by differences in dynamics [1]. GMPR is involved in maintaining the cellular balance of adenine and guanine nucleotides [4].

In a patient with late-onset disorder of mitochondrial DNA maintenance, a novel heterozygous c.547G>C variant in GMPR was identified. This variant caused aberrant splicing, decreased GMPR protein levels, and was associated with subtle changes in nucleotide homeostasis and disturbed mtDNA maintenance in skeletal muscle [4]. In exome sequencing of 49,960 individuals in the UK Biobank, novel LOF variants in GMPR were found to have large effects on blood cell traits [2].

In conclusion, GMPR is crucial for nucleotide metabolism and maintaining nucleotide homeostasis. Studies on GMPR, such as the identification of variants in patients with mitochondrial DNA-related disorders and the discovery of its impact on blood cell traits, contribute to understanding related biological processes and disease mechanisms.