Developmentally-regulated GTP-binding protein 1

DRG1 (developmentally-regulated GTP-binding protein 1) is a 40.5 kDa GTPase that catalyzes GTP hydrolysis and contains intrinsic GTPase activity stimulated by DFRP1 binding (UniProt: Q9Y295). When hydroxylated by JMJD7, it may bind RNA and participate in translation. Additionally, DRG1 binds to microtubules and promotes their polymerization and stability during mitotic spindle assembly, functions independent of its GTPase activity.

DRG1 is involved in both cytoskeletal dynamics and translational regulation. Pathogenic mutations in DRG1 cause Tan-Almurshedi syndrome (TANALS), an autosomal recessive neurodevelopmental disorder marked by global developmental delay, intellectual disability, speech deficits, failure to thrive, and craniofacial anomalies (UniProt: Q9Y295).

In Alzheimer's disease, DRG1 is significantly downregulated in post-mortem AD brain tissue compared to age-matched controls, with a mean log2 fold-change of −0.92 (Chaparral AD proteomics). This reduction was detected across subcellular fractions in a TMT-labeled quantitative proteomics study, suggesting impaired GTPase and microtubule-stabilizing functions may contribute to AD pathology.