Nitrogen permease regulator-like 3 (NPRL3)

Nitrogen permease regulator-like 3 (NPRL3) is a protein encoded by the NPRL3 gene that serves as a subunit of the GATOR1 complex, alongside NPRL2 and DEPDC5[1][4][7][8]. The GATOR1 complex is a critical negative regulator of the mechanistic target of rapamycin complex 1 (mTORC1) signaling pathway, particularly in response to amino acid availability[1][2][4][7]. NPRL3, through the GATOR1 complex, exerts GTPase-activating activity that inhibits mTORC1 by promoting GTP hydrolysis on the Rag GTPase heterodimer, thereby blocking mTORC1 activation during amino acid starvation[4][7][8]. The gene is highly expressed in the brain and is important for brain development and neuronal activity[3][7]. Loss-of-function mutations in NPRL3 cause epilepsy syndromes, notably familial focal epilepsy with variable foci, via dysregulated mTOR signaling[1][2][3]. While aberrant mTOR signaling is implicated in cancer, the direct therapeutic targeting of NPRL3 is not established, distinguishing it from conventional drug targets such as receptors or enzymes[3][8]. Key notes: - NPRL3 is not a traditional drug target (e.g., receptor, enzyme), so it is usually not the direct target of approved drugs nor a biomarker for therapy[3]. - Most disease relevance currently centers on inherited forms of epilepsy with GATOR1 complex gene mutations, which may confer drug-resistant epilepsy[3]. - The gene/protein is often referenced in genetic context (epilepsy panels, gene variant interpretation), not as a direct therapeutic or diagnostic target. If structured information for conventional drug target databases is needed, most fields would be set to "null" or "not applicable" for drug/biomarker/safety sections.

Other names

NPRL3C16orf35CGTHBAMARERMD11FFEVF3NPR3HS-40Alpha-globin regulatory element-containing gene proteinconserved gene telomeric to alpha globin cluster-14 gene proteinGATOR1 complex protein NPRL3GATOR complex protein NPRL3