NPRL2

Chr 3AD

NPR2 like, GATOR1 complex subunit

Also known as: FFEVF2, NPR2, NPR2L, TUSC4

NCBI Gene: 10641 ENSG00000114388 UniProt: Q8WTW4 OMIM: 607072

The protein functions as a GTPase activator within the GATOR1 complex at the lysosomal membrane, where it negatively regulates TORC1 signaling and kinase activity during cellular amino acid starvation responses. Mutations cause familial focal epilepsy with variable foci 2, inherited in an autosomal dominant pattern. The pathogenic mechanism involves disruption of the mTORC1 signaling pathway regulation at lysosomes.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt

Enables GTPase activator activity. Involved in cellular response to amino acid starvation; negative regulation of TORC1 signaling; and negative regulation of kinase activity. Part of GATOR1 complex. Is active in lysosomal membrane. Implicated in familial focal epilepsy with variable foci 2. [provided by Alliance of Genome Resources, Jul 2025]

GeneReviews OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Epilepsy, familial focal, with variable foci 2MIM #617116

Clinical highlights

Gene-disease validity (ClinGen)

focal epilepsy · ADDefinitivesufficient evidence for diagnostic panels

Interpreting a novel variant

Loss of function is the curated mechanism (Gene2Phenotype) and the gene is intolerant of it in the population — truncating, frameshift and canonical splice variants carry more prior weight here than missense.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

—

P/LP submissions

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P/LP missense

0.47

LOEUF

LOF

Mechanism· G2P

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GeneReview available — NPRL2