NF1 encodes neurofibromin 1, a GTPase-activating protein (GAP) that is a key negative regulator of the RAS and PI3K signaling pathway (Figure 2).[23] The NF1 R1241* mutation leads to a nonsense codon, resulting in truncation of the NF1 protein within the GAP-related domain, which is likely to negate tumor suppressing activity. The gene discussed is PIK3CA; the disease is neoplasm.