This report describes epilepsy, familial focal, with variable foci 3 (FFEVF3); FFEVF3 exhibits autosomal dominant inheritance. The human gene implicated in this disease is NPRL3, which encodes a component of the GATOR1 complex; the GATOR1 complex is involved in cellular response to amino acid starvation and negative regulation of TORC1 signaling. There is a single orthologous gene in Drosophila, Dmel\Nprl3, for which a number genetic reagents have been generated, including an amorphic allele, RNAi-targeting constructs, and overexpression constructs.
The human NPRL3 gene has not been introduced into flies.
Animals homozygous for an amorphic allele of Dmel\Nprl3 typically die as pharate adults; surviving adults show reduced climbing ability. Systemic knockdown of Nprl3, effected by RNAi, results in epileptic-like behaviors in adults, as assayed by the bang-sensitive test. Abnormal synaptic morphology is observed at larval neuromuscular junctions.
[updated Mar. 2025 by FlyBase; FBrf0222196]
Familial focal epilepsy with variable foci (FFEVF) is an uncommon form of recurrent seizures (epilepsy) that runs in families. Seizures associated with FFEVF can begin at any time from infancy to adulthood. The seizures are described as focal or partial, which means they begin in one region of the brain and do not cause a loss of consciousness. [MedlinePlus, Familial focal epilepsy with variable foci; 2025.02.19]
Familial focal epilepsy with variable foci (FFEVF) is a form of epilepsy characterized by focal seizures arising from different cortical regions, including the temporal, frontal, parietal, and occipital lobes. A subset of patients have structural brain abnormalities, particularly focal cortical dysplasia (FCD) (summary by Ricos et al., 2016; pubmed:26505888). [from MIM:617118; 2025.02.19]
[EPILEPSY, FAMILIAL FOCAL, WITH VARIABLE FOCI 3; FFEVF3](https://omim.org/entry/617118)
[NITROGEN PERMEASE REGULATOR-LIKE 3; NPRL3](https://omim.org/entry/600928)
Familial focal epilepsy with variable foci 2 (FFEVF2) is characterized by focal seizures arising from different cortical regions, including the temporal, frontal, parietal, and occipital lobes. Seizure types commonly include temporal lobe epilepsy (TLE), frontal lobe epilepsy (FLE), and nocturnal frontal lobe epilepsy (NFLE). [from MIM:617118; 2025.02.24]
Familial focal epilepsy with variable foci-3 (FFEVF3) is caused by heterozygous mutation in the NPRL3 gene. [from MIM:617118; 2025.02.24]
NPRL3 encodes a component of the GATOR1 complex; involved in cellular response to amino acid starvation and negative regulation of TORC1 signaling. [GeneCards, NPRL3; 2025.03.02]
One to one: 1 human gene to 1 Drosophila gene.
High-scoring ortholog of human NPRL3 (1 Drosophila to 1 human).
