LZTR1 NM_006767.4:c.2412dup, Lys805GlnfsTer46

"This variant has been reported in ClinVar as Likely pathogenic (2 clinical laboratories) and as Pathogenic (1 clinical laboratories)."

Error in OpenAI Consolidation. OncoKB: LZTR1K805Qfs*46LZTR1K805Qfs*46SomaticNCBI Gene:8216|Show additional gene information Variant OverviewLZTR1, a ubiquitin ligase adaptor protein, is recurrently altered by mutation in glioblastoma, Noonan syndrome, and schwannomatosis.The LZTR1 K805Qfs*46 is a truncating mutation in a tumor suppressor gene, and therefore is likely oncogenic.Hide mutation effect description The mutation effect description for truncating mutations in LZTR1 is: Truncating mutations in LZTR1 occur throughout the coding region of the protein and tend to result in loss of heterozygosity (PMID: 24362817, 23917401, 30442762). Loss-of-function truncating variants are found in patients with Noonan Syndrome, schwannomatosis, and glioblastoma (PMID: 24362817, 23917401). Inactivation of LZTR1 in hematopoietic cell lines results in increased RAS plasma membrane localization due to reduced CUL3-mediated ubiquitination degradation of RAS (PMID: 30442762). Loss of LZTR1 in HEK293T and HeLa cells results in increased expression of RIT1 and an increased MAPK response to serum stimulation (PMID: 30872527). In vitro studies with LZTR1-knockout in HeLa cells demonstrated that loss of LZTR1 results in loss of EGFR and AXL degradation, leading to aberrant growth factor signaling (PMID: 36445254). LZTR1-deleted mouse embryonic fibroblasts (MEFs) have an enhanced response to growth factors compared to wildtype MEFs (PMID: 30872527). In addition, loss of LZTR1 activity leads to imatinib, rebastinib, and ponatinib resistance but sensitivity to trametinib in cell growth assays (PMID: 30442762). Preclinical studies with E0954 schwannoma-like cells and LZTR1-knockdown mice demonstrated sensitivity to combination treatment of EGFR inhibitors afatinib or osimertinib plus AXL-specific inhibitor bemcentinib as measured by reduced clonogenicity and tumor growth (PMID: 36445254). JAX-CKB: No results found