The two other SCA44 causing mGluR1 missense mutations showed increased receptor activity compared to wild type mGluR1, suggesting that increased activity of mGluR1 leads to increased ligand sensitivity and ligand-independent activation, which is related to the fact that both missense mutations are closely located in the area of mGluR1 activation, resulting in excessive mGluR1 signaling by positive feedback with increased intracellular calcium levels [54]. This evidence concerns the gene GRM1 and spinocerebellar ataxia 44.