NPRL3 gene

NPR3 like, GATOR1 complex subunit

The NPRL3 gene provides instructions for making a protein that is one piece of a group of proteins (complex) called GATOR1. This complex is found in cells throughout the body, where it regulates a signaling pathway called the mTOR pathway. The mTOR pathway is involved in cell growth and division (proliferation), the survival of cells, and the creation (synthesis) of new proteins. The role of the GATOR1 complex is to block this pathway by inhibiting (stopping) the activity of a complex called mTOR complex 1 (mTORC1) that is integral to the mTOR pathway.

In the brain, the mTOR pathway regulates many processes, including the growth and development of nerve cells and their ability to change and adapt over time (plasticity).

At least ten NPRL3 gene mutations have been found to cause familial focal epilepsy with variable foci (FFEVF), which is an uncommon form of recurrent seizures (epilepsy) that runs in families. Most of these mutations lead to the production of an abnormally short, nonfunctional protein. As a result, formation of normal GATOR1 complex is reduced, leading to overactivity of mTORC1 and excessive signaling of the mTOR pathway. It is not clear how an abnormally active mTOR pathway leads to the seizures of FFEVF. Research suggests that increased mTOR pathway signaling in the brain leads to changes in the connections between nerve cells (synapses) and increased activation (excitation) of nerve cells, which can cause seizures.

Cytogenetic Location: 16p13.3, which is the short (p) arm of chromosome 16 at position 13.3

Molecular Location: base pairs 85,801 to 138,698 on chromosome 16 (Homo sapiens Annotation Release 108, GRCh38.p7) (NCBI)

Cytogenetic Location: 16p13.3, which is the short (p) arm of chromosome 16 at position 13.3
  • alpha-globin regulatory element-containing gene protein
  • C16orf35
  • conserved gene telomeric to alpha globin cluster
  • HS-40
  • MARE
  • NPR3
  • RMD11