As a component of the GATOR1 complex functions as an inhibitor of the amino acid-sensing branch of the TORC1 pathway. The GATOR1 complex strongly increases GTP hydrolysis by RRAGA and RRAGB within RRAGC-containing heterodimers, thereby deactivating RRAGs, releasing mTORC1 from lysosomal surface and inhibiting mTORC1 signaling. The GATOR1 complex is negatively regulated by GATOR2 the other GATOR subcomplex in this amino acid-sensing branch of the TORC1 pathway. {Experimental EvidencePubMed:23723238, Experimental EvidencePubMed:25457612, Experimental EvidencePubMed:29769719}.
Epilepsy, familial focal, with variable foci 1 (FFEVF1) [MIM:604364]: An autosomal dominant form of epilepsy characterized by focal seizures arising from different cortical regions in different family members. Many patients have an aura and show automatisms during the seizures, whereas others may have nocturnal seizures. There is often secondary generalization. Some patients show abnormal interictal EEG, and some patients may have intellectual disability or autism spectrum disorders. Seizure onset usually occurs in the first or second decades, although later onset has been reported, and there is phenotypic variability within families. Penetrance of the disorder is incomplete. {Experimental EvidencePubMed:23542697, Experimental EvidencePubMed:23542701, Experimental EvidencePubMed:24283814, Experimental EvidencePubMed:24591017, Experimental EvidencePubMed:25366275, Experimental EvidencePubMed:26505888, Experimental EvidencePubMed:27173016}. Note=The disease is caused by variants affecting the gene represented in this entry. Note=Inactivating mutations and truncating deletions in the genes encoding GATOR1 proteins, including DEPDC5, are detected in glioblastoma and ovarian tumors and are associated with loss of heterozygosity events. Inactivation of GATOR1 proteins promotes constitutive localization of mTORC1 to the lysosomal membrane and blocks mTORC1 inactivation following amino acid withdrawal (PubMed:23723238). {Experimental EvidencePubMed:23723238}.
National and Kapodistrian University of Athens
Department of Biology
Biophysics & Bioinformatics Laboratory