Rho GTPases represent a subgroup of the Ras superfamily of small GTP-binding proteins and consist of more than 20 members in mammals. The most widely investigated members of the Rho family in the nervous system are the Ras-related C3 botulinum toxin substrate 1 (Rac1), Ras homologous member A (RhoA), and the cell division cycle 42. In the adult brain, small GTPases regulate biological events of the actin cytoskeleton of the excitatory synapse, thus contributing to synaptic plasticity.
To date only 2 different variants including a splice site and a frame shift variant have been reported in the RAP1GDS1 gene that means loss of function variants (LOF) could be responsible for the disease phenotype. Missense variants have not been reported so far. The splice site variant (c.1444-1G>A; p.?) have been reported in 5 different families (9 patients) representing hotspot mutation. [Asiri et al. 2020; Maddirevula et al. 2020; Bertoli-Avella et al. 2021]
RAP1GDS1