biostudies-literatureMo J- Neurofibromatosis Therapeutic Acceleration Program - NF1 Research Consortium Fund - Giorgio FoundationU.S. Department of Health & Human Services | NIH | National Cancer InstituteNCI NIH HHS1235-1251https://www.ebi.ac.uk/biostudies/studies/S-EPMC9063229biostudies-literatureUnknown41(9)Neurofibromatosis type 1 (NF1) is an autosomal dominant genetic disease and one of the most common inherited tumor predisposition syndromes, affecting 1 in 3000 individuals worldwide. The NF1 gene encodes neurofibromin, a large protein with RAS GTP-ase activating (RAS-GAP) activity, and loss of NF1 results in increased RAS signaling. Neurofibromin contains many other domains, and there is considerable evidence that these domains play a role in some manifestations of NF1. Investigating the role of these domains as well as the various signaling pathways that neurofibromin regulates and interacts with will provide a better understanding of how neurofibromin acts to suppress tumor development and potentially open new therapeutic avenues. In this review, we discuss what is known about the strucOncogeneNeurofibromin and suppression of tumorigenesis: beyond the GAP.PMC9063229R01 CA166593U54 CA196519Le LQMcKay RMMo JMoye SLfalseNeurofibromin and suppression of tumorigenesis: beyond the GAP.Neurofibromatosis type 1 (NF1) is an autosomal dominant genetic disease and one of the most common inherited tumor predisposition syndromes, affecting 1 in 3000 individuals worldwide. The NF1 gene encodes neurofibromin, a large protein with RAS GTP-ase activating (RAS-GAP) activity, and loss of NF1 results in increased RAS signaling. Neurofibromin contains many other domains, and there is considerable evidence that these domains play a role in some manifestations of NF1. Investigating the role of these domains as well as the various signaling pathways that neurofibromin regulates and interacts with will provide a better understanding of how neurofibromin acts to suppress tumor development and potentially open new therapeutic avenues. In this review, we discuss what is known about the struc2022-01-01T00:00:00Z2022 Feb2025-05-18T12:06:09.277Z2025-04-05T20:40:52.056ZS-EPMC90632293506657410.1038/s41388-021-02156-y