NRAS NM_002524.4:c.71T>A, Ile24Asn

"This variant has been reported in ClinVar as Pathogenic (1 clinical laboratories) and as Likely Pathogenic by ClinGen RASopathy Variant Curation Expert Panel expert panel."

Error in OpenAI Consolidation. OncoKB: NRASI24NNRASI24NSomaticNCBI Gene:4893|Show additional gene information Variant OverviewNRAS, a GTPase, is mutated in a diverse range of cancers, most frequently in melanoma and thyroid cancer.The NRAS I24N mutation is likely oncogenic.Hide mutation effect description The NRAS I24N mutation is located in the catalytic GTP-binding domain of the protein. In vitro studies using a Novellus FACT assay with Ba/F3 cells expressing NRAS I24N demonstrate that the mutation is activating as measured by increased MAPK signaling compared to wildtype (PMID: 34117033). JAX-CKB: NRAS I24N lies within the G domain of the Nras protein (PMID: 17384584). I24N results in autoactivation of Sos comparable to wild-type Nras under an autoinhibitory-free condition of Sos, but leads to deregulation of Sos activation under an autoinhibitory condition of Sos in an in vitro assay (PMID: 32753483), and results in increased GTP-bound Nras and activation of downstream signaling in cell culture, demonstrated by increased phosphorylation of Mek, and impaired cell migration in a zebrafish model (PMID: 21263000), and therefore, is predicted to lead to a loss of Nras protein function.