NF1, also known as the neurofibromatosis type 1 gene, is of great significance as its product, neurofibromin, mainly functions to downregulate RAS, thus regulating the RAS/MAPK pathway [2]. This pathway is involved in numerous biological processes, and the regulation by NF1 is crucial for normal cellular function. Mutations in NF1 can lead to neurofibromatosis type 1, an autosomal dominantly inherited tumour predisposition syndrome.

Most NF1 patients have private loss-of-function mutations scattered along the NF1 gene. A significant proportion of NF1 missense mutations (30%) were found to be deleterious by affecting pre-mRNA splicing [1]. Heritable constitutional mutations in NF1 result in dysregulation of the RAS/MAPK pathway, causing NF1, which is characterized by benign cutaneous lesions like neurofibromas and café-au-lait macules, as well as a predisposition to various malignancies [2]. Also, acquired somatic NF1 mutations are found in a wide variety of malignant neoplasms not associated with NF1, and these somatic mutations may be critical drivers in multiple cancers [2].

In conclusion, NF1 is essential for regulating the RAS/MAPK pathway, and its malfunction due to mutations is closely related to the development of neurofibromatosis type 1 and various malignancies. The study of NF1 gene mutations helps in understanding the pathophysiology of related diseases, potentially leading to better diagnostic and therapeutic strategies.

References:

1. Sabbagh, Audrey, Pasmant, Eric, Imbard, Apolline, Parfait, Béatrice, Wolkenstein, Pierre. 2013. NF1 molecular characterization and neurofibromatosis type I genotype-phenotype correlation: the French experience. In Human mutation, 34, 1510-8. doi:10.1002/humu.22392. https://pubmed.ncbi.nlm.nih.gov/23913538/

2. Philpott, Charlotte, Tovell, Hannah, Frayling, Ian M, Cooper, David N, Upadhyaya, Meena. 2017. The NF1 somatic mutational landscape in sporadic human cancers. In Human genomics, 11, 13. doi:10.1186/s40246-017-0109-3. https://pubmed.ncbi.nlm.nih.gov/28637487/