RAS signaling downstream of NF1 loss-of-function variants

Stable Identifier
Homo sapiens
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NF1 is a RAS GAP that stimulates the intrinsic RAS GTPase activity, thereby shifting the RAS pathway towards the inactive state (reviewed in King et al, 2013). Loss-of-function mutations in NF1 have been identified both in germline diseases like neurofibromatosis 1 and in a range of sporadically occurring cancers. These mutations, which range from complete gene deletions to missense or frameshift mutations, generally decrease NF1 protein levels and abrogate RAS GAP activity in the cells, resulting in constitutive RAS pathway activation (reviewed in Maertens and Cichowski, 2014; Tidyman and Rauen, 2009; Ratner and Miller, 2015).

Literature References
PubMed ID Title Journal Year
19467855 The RASopathies: developmental syndromes of Ras/MAPK pathway dysregulation

Tidyman, WE, Rauen, KA

Curr. Opin. Genet. Dev. 2009
23443682 Nonredundant functions for Ras GTPase-activating proteins in tissue homeostasis

Lapinski, PE, Lubeck, BA, King, PD

Sci Signal 2013
24814062 An expanding role for RAS GTPase activating proteins (RAS GAPs) in cancer

Cichowski, K, Maertens, O

Adv Biol Regul 2014
25877329 A RASopathy gene commonly mutated in cancer: the neurofibromatosis type 1 tumour suppressor

Miller, SJ, Ratner, N

Nat. Rev. Cancer 2015
Name Identifier Synonyms
neurofibromatosis DOID:8712 Neurofibromatosis 1, neurofibromatosis type IV, Acoustic neurofibromatosis, Recklinghausen's neurofibromatosis, neurofibromatosis type 4, central Neurofibromatosis, type IV neurofibromatosis of riccardi, neurofibromatosis type 1, neurofibromatosis type 2, peripheral Neurofibromatosis, von Reklinghausen disease
cancer DOID:162 malignant tumor, malignant neoplasm, primary cancer
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