NPRL3

Chr 16

NPR3 like, GATOR1 complex subunit

Also known as: C16orf35, CGTHBA, FFEVF3, HS-40, MARE, NPR3, RMD11

NCBI Gene: 8131 ENSG00000103148 UniProt: Q12980

The protein functions as a component of the GATOR1 complex that inhibits mTORC1 signaling by acting as a GTPase activating protein for Rag complexes in response to amino acid depletion. Mutations cause familial focal epilepsy with variable foci 3, inherited in an autosomal dominant pattern. The pathogenic mechanism involves disruption of the amino acid-sensing mTORC1 pathway regulation at the lysosomal membrane.

GeneReviews ResearchSummary from RefSeq, OMIM, UniProt

Predicted to enable GTPase activator activity. Involved in cellular response to amino acid starvation and negative regulation of TORC1 signaling. Part of GATOR1 complex. Is active in lysosomal membrane. Implicated in familial focal epilepsy with variable foci 3. [provided by Alliance of Genome Resources, Jul 2025]

GeneReviews ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtEpilepsy, familial focal, with variable foci 3

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

—

P/LP missense

0.49

LOEUF

LOF

Mechanism· G2P

📖

GeneReview available — NPRL3