NF1/A0196

Neurofibromin 1, also known as NF1 or A0196, is a multifunctional protein, which acts as an inhibitory element on Ras signaling.

Neurofibromin 1, also known as NF1 or A0196, is a multifunctional protein, which acts as an inhibitory element on Ras signaling. This protein stimulates the GTPase activity of Ras and consequently negatively regulates Ras activity. Mouse models of neurofibromatosis have been generated and complete loss of NF1 is lethal in mice because of defects in cardiac development. However, mice heterozygous for functional deletion of the NF1 gene also exhibit compromized spatial learning, and deficits in early-stage hippocampal long-term potentiation (LTP). The deficits in early-stage LTP and spatial learning have been linked to Ras hyperactivation and increased gamma-amino butyric acid (GABA)-mediated inhibition. Mutations in NF1 cause neurofibromatosis type 1, a common genetic disease that affects about 1 in 3000 children. NF1 is characterized by hyperpigmented skin macules, iris tumors, and benign tumors of nerve cells (neurofibromas). However more than 50% of patients with NF1 have neurobehavioral impairments, which include attention deficit/hyperactivity disorder (ADHD), spatial learning disabilities, and other cognitive developmental problems. It has been estimated that approximately 1% of children with autism spectrum disorders have mutations in the NF1 gene.