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Gene | BRAF |
Variant | N486_P490del |
Impact List | deletion |
Protein Effect | gain of function |
Gene Variant Descriptions | BRAF N486_P490del results in the deletion of five amino acids within the alphaC-helix region in the protein kinase domain of the Braf protein from amino acids 486 to 490 (PMID: 26732095). N486_P490del confers a gain of function to the Braf protein as indicated by activation of the MAPK signaling pathway and increased cell proliferation and transformation, and has been demonstrated to confer Braf inhibitor resistance in cell culture (PMID: 37656784, PMID: 26732095). |
Associated Drug Resistance | Y |
Category Variants Paths |
BRAF mutant BRAF act mut BRAF N486_P490del |
Transcript | NM_004333.6 |
gDNA | chr7:g.140778038_140778052del15 |
cDNA | c.1457_1471del15 |
Protein | p.N486_P490delNVTAP |
Source Database | RefSeq |
Genome Build | GRCh38/hg38 |
Transcript | gDNA | cDNA | Protein | Source Database | Genome Build |
---|---|---|---|---|---|
XM_017012558 | chr7:g.140781658_140781672del15 | c.1456_1470del15 | p.S486_W490delSSDDW | RefSeq | GRCh38/hg38 |
NM_001354609.1 | chr7:g.140778038_140778052del15 | c.1457_1471del15 | p.N486_P490delNVTAP | RefSeq | GRCh38/hg38 |
XM_047420770.1 | chr7:g.140734715_140734729del15 | c.1456_1470del15 | p.I486_A490delIHRSA | RefSeq | GRCh38/hg38 |
NM_001378470.1 | chr7:g.140777034_140777048del15 | c.1456_1470del15 | p.S486_Q490delSTKPQ | RefSeq | GRCh38/hg38 |
NM_001378469.1 | chr7:g.140777070_140777084del15 | c.1457_1471del15 | p.T486_N490delTRHVN | RefSeq | GRCh38/hg38 |
NM_001378472.1 | chr7:g.140776980_140776994del15 | c.1456_1470del15 | p.Y486_H490delYHHLH | RefSeq | GRCh38/hg38 |
NM_001374244.1 | chr7:g.140781658_140781672del15 | c.1456_1470del15 | p.S486_W490delSSDDW | RefSeq | GRCh38/hg38 |
NM_001378468.1 | chr7:g.140778038_140778052del15 | c.1457_1471del15 | p.N486_P490delNVTAP | RefSeq | GRCh38/hg38 |
NM_004333.5 | chr7:g.140778038_140778052del15 | c.1457_1471del15 | p.N486_P490delNVTAP | RefSeq | GRCh38/hg38 |
XM_017012559.2 | chr7:g.140781658_140781672del15 | c.1456_1470del15 | p.S486_W490delSSDDW | RefSeq | GRCh38/hg38 |
XM_017012558.1 | chr7:g.140781658_140781672del15 | c.1456_1470del15 | p.S486_W490delSSDDW | RefSeq | GRCh38/hg38 |
NM_001378475.1 | chr7:g.140754194_140754208del15 | c.1456_1470del15 | p.H486_K490delHRDLK | RefSeq | GRCh38/hg38 |
NM_004333.6 | chr7:g.140778038_140778052del15 | c.1457_1471del15 | p.N486_P490delNVTAP | RefSeq | GRCh38/hg38 |
XM_047420769.1 | chr7:g.140778038_140778052del15 | c.1457_1471del15 | p.N486_P490delNVTAP | RefSeq | GRCh38/hg38 |
XM_047420766.1 | chr7:g.140778002_140778016del15 | c.1456_1470del15 | p.F486_V490delFKNEV | RefSeq | GRCh38/hg38 |
XM_005250045 | chr7:g.140778038_140778052del15 | c.1457_1471del15 | p.N486_P490delNVTAP | RefSeq | GRCh38/hg38 |
NM_001378471.1 | chr7:g.140777025_140777039del15 | c.1456_1470del15 | p.P486_I490delPQLAI | RefSeq | GRCh38/hg38 |
NM_001378474.1 | chr7:g.140778038_140778052del15 | c.1457_1471del15 | p.N486_P490delNVTAP | RefSeq | GRCh38/hg38 |
XM_017012559 | chr7:g.140781658_140781672del15 | c.1456_1470del15 | p.S486_W490delSSDDW | RefSeq | GRCh38/hg38 |
NM_001378467.1 | chr7:g.140778050_140778064del15 | c.1457_1471del15 | p.K486_V490delKMLNV | RefSeq | GRCh38/hg38 |
NM_001378473.1 | chr7:g.140776980_140776994del15 | c.1456_1470del15 | p.Y486_H490delYHHLH | RefSeq | GRCh38/hg38 |
NM_001374258.1 | chr7:g.140781658_140781672del15 | c.1456_1470del15 | p.S486_W490delSSDDW | RefSeq | GRCh38/hg38 |
XM_047420767.1 | chr7:g.140781658_140781672del15 | c.1456_1470del15 | p.S486_W490delSSDDW | RefSeq | GRCh38/hg38 |
NM_001354609.2 | chr7:g.140778038_140778052del15 | c.1457_1471del15 | p.N486_P490delNVTAP | RefSeq | GRCh38/hg38 |
XM_017012559.1 | chr7:g.140781658_140781672del15 | c.1456_1470del15 | p.S486_W490delSSDDW | RefSeq | GRCh38/hg38 |
XM_047420768.1 | chr7:g.140781658_140781672del15 | c.1456_1470del15 | p.S486_W490delSSDDW | RefSeq | GRCh38/hg38 |
NM_004333 | chr7:g.140778038_140778052del15 | c.1457_1471del15 | p.N486_P490delNVTAP | RefSeq | GRCh38/hg38 |
Molecular Profile | Indication/Tumor Type | Response Type | Therapy Name | Approval Status | Evidence Type | Efficacy Evidence | References |
---|---|---|---|---|---|---|---|
BRAF N486_P490del | ovarian cancer | sensitive | LY3009120 | Preclinical | Actionable | In a preclinical study, an ovarian cancer cell line harboring BRAF N486_P490del was sensitive to LY3009120, resulting in inhibition of cell growth and decreased phosphorylation of MEK and ERK in culture (PMID: 26732095). | 26732095 |
BRAF N486_P490del | ovarian cancer | sensitive | Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, Mekinist (trametinib) inhibited growth of an ovarian cancer cell line harboring BRAF N486_P490del in culture (PMID: 26732095). | 26732095 |
BRAF N486_P490del | ovarian cancer | sensitive | Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, Mekinist (trametinib) inhibited MAPK signaling and colony formation in an ovarian cancer cell line harboring BRAF N486_P490del in culture (PMID: 37656784). | 37656784 |
BRAF N486_P490del | ovarian cancer | resistant | Vemurafenib | Preclinical | Actionable | In a preclinical study, an ovarian cancer cell line harboring BRAF N486_P490del was resistant to Zelboraf (vemurafenib), resulting in minimal inhibition of both cell growth and phosphorylation of MEK and ERK in culture (PMID: 26732095). | 26732095 |
BRAF N486_P490del | ovarian cancer | resistant | Vemurafenib | Preclinical - Cell culture | Actionable | In a preclinical study, Zelboraf (vemurafenib) failed to reduce phosphorylation of Mek and Erk and did not inhibit viability of an ovarian cancer cell line harboring BRAF N486_P490del in culture (PMID: 26996308). | 26996308 |
BRAF N486_P490del | ovarian cancer | conflicting | Dabrafenib | Preclinical - Cell culture | Actionable | In a preclinical study, Tafinlar (dabrafenib) inhibited MAPK signaling and colony formation in an ovarian cancer cell line harboring BRAF N486_P490del in culture (PMID: 37656784). | 37656784 |
BRAF N486_P490del | ovarian cancer | conflicting | Dabrafenib | Preclinical | Actionable | In a preclinical study, Tafinlar (dabrafenib) resulted in minimal growth inhibitory activity of an ovarian cancer cell line harboring BRAF N486_P490del (PMID: 26732095). | 26732095 |
BRAF N486_P490del | pancreatic ductal adenocarcinoma | sensitive | Trametinib | Case Reports/Case Series | Actionable | In a clinical case study, Mekinist (trametinib) treatment resulted in partial response in a patient with pancreatic ductal adenocarcinoma harboring BRAF N486_P490del 8 weeks after initiation of treatment and lasted for 6 months (PMID: 29903880). | 29903880 |
BRAF N486_P490del | pancreatic ductal adenocarcinoma | sensitive | Trametinib | Preclinical - Patient cell culture | Actionable | In a preclinical study, a pancreatic ductal adenocarcinoma patient-derived organoid model harboring BRAF N486_P490del was sensitive to treatment with Mekinist (trametinib) in culture, demonstrating decreased cell viability (PMID: 37463056). | 37463056 |
BRAF N486_P490del | pancreatic ductal adenocarcinoma | sensitive | Trametinib | Preclinical - Pdx | Actionable | In a preclinical study, a patient-derived xenograft (PDX) model with pancreatic ductal adenocarcinoma harboring BRAF N486_P490del demonstrated partial inhibition of Erk phosphorylation and moderate inhibition of tumor growth when treated with Mekinist (trametinib) (PMID: 34011980). | 34011980 |
BRAF N486_P490del | pancreatic ductal adenocarcinoma | sensitive | Trametinib | Preclinical - Patient cell culture | Actionable | In a preclinical study, Mekinist (trametinib) inhibited growth of organoids derived from pancreatic ductal adenocarcinoma patients harboring BRAF N486_P490del in culture (PMID: 37656784). | 37656784 |
BRAF N486_P490del | pancreatic cancer | predicted - sensitive | Dabrafenib | Case Reports/Case Series | Actionable | In a clinical case study, a patient with pancreatic cancer harboring BRAF N486_P490del had a partial response when treated with Tafinlar (dabrafenib), demonstrating a decrease in both the size of the primary and metastatic lesions and response duration of 6 months (PMID: 31519698). | 31519698 |
BRAF N486_P490del | lymphatic system cancer | predicted - sensitive | Trametinib | Case Reports/Case Series | Actionable | In a clinical case study, Mekinist (trametinib) treatment in two patients with Langerhans cell histiocytosis harboring BRAF N486_P490del resulted in a complete response with no disease reactivation over 18 months of treatment in one patient and a partial response with stable disease in the lungs maintained over 12 months of treatment in a second patient (PMID: 32991018). | 32991018 |
BRAF N486_P490del | pancreatic ductal adenocarcinoma | predicted - sensitive | LY3009120 | Preclinical - Pdx & cell culture | Actionable | In a preclinical study, a patient-derived xenograft (PDX) model with pancreatic ductal adenocarcinoma harboring BRAF N486_P490del demonstrated partial inhibition of Erk phosphorylation and moderate inhibition of tumor growth when treated with LY3009120 (PMID: 34011980). | 34011980 |
BRAF N486_P490del | pancreatic ductal adenocarcinoma | sensitive | LY3009120 + Trametinib | Preclinical - Pdx | Actionable | In a preclinical study, a patient-derived xenograft (PDX) model with pancreatic ductal adenocarcinoma harboring BRAF N486_P490del demonstrated inhibition of Erk phosphorylation and greater inhibition of tumor growth when treated with the combination of Mekinist (trametinib) and LY3009120 compared to either agent alone (PMID: 34011980). | 34011980 |
BRAF N486_P490del | ovarian cancer | sensitive | Cobimetinib | Preclinical - Cell culture | Actionable | In a preclinical study, an ovarian cancer cell line harboring BRAF N486_P490del demonstrated sensitivity to Cotellic (cobimetinib), resulting in decreased cell viability in culture (PMID: 26996308). | 26996308 |
BRAF N486_P490del | melanoma | sensitive | Cobimetinib | Preclinical - Cell culture | Actionable | In a preclinical study, a melanoma cell line harboring BRAF N486_P490del demonstrated sensitivity to Cotellic (cobimetinib), resulting in decreased cell viability in culture (PMID: 26996308). | 26996308 |
BRAF N486_P490del | ovarian cancer | sensitive | PD-0325901 | Preclinical - Cell culture | Actionable | In a preclinical study, an ovarian cancer cell line harboring BRAF N486_P490del demonstrated sensitivity to PD-0325901, resulting in decreased cell viability in culture (PMID: 26996308). | 26996308 |
BRAF N486_P490del | melanoma | sensitive | PD-0325901 | Preclinical - Cell culture | Actionable | In a preclinical study, a melanoma cell line harboring BRAF N486_P490del demonstrated sensitivity to PD-0325901, resulting in decreased cell viability in culture (PMID: 26996308). | 26996308 |
BRAF N486_P490del | ovarian cancer | predicted - sensitive | GDC0879 | Preclinical - Cell culture | Actionable | In a preclinical study, an ovarian cancer cell line harboring BRAF N486_P490del demonstrated partial sensitivity to GDC0879 in culture (PMID: 26996308). | 26996308 |
BRAF N486_P490del | melanoma | predicted - sensitive | GDC0879 | Preclinical - Cell culture | Actionable | In a preclinical study, a melanoma cell line harboring BRAF N486_P490del demonstrated partial sensitivity to GDC0879 in culture (PMID: 26996308). | 26996308 |
BRAF N486_P490del | melanoma | sensitive | AZ628 | Preclinical - Cell culture | Actionable | In a preclinical study, a melanoma cell line harboring BRAF N486_P490del demonstrated sensitivity to AZ628, resulting in decreased cell viability and inhibition of Mek and Erk phosphorylation in culture (PMID: 26996308). | 26996308 |
BRAF N486_P490del | ovarian cancer | sensitive | AZ628 | Preclinical - Cell culture | Actionable | In a preclinical study, an ovarian cancer cell line harboring BRAF N486_P490del demonstrated sensitivity to AZ628, resulting in decreased cell viability and inhibition of Mek and Erk phosphorylation in culture (PMID: 26996308). | 26996308 |
BRAF N486_P490del | melanoma | resistant | Vemurafenib | Preclinical - Cell culture | Actionable | In a preclinical study, Zelboraf (vemurafenib) failed to reduce phosphorylation of Mek and Erk and did not inhibit viability of a melanoma cell line harboring BRAF N486_P490del in culture (PMID: 26996308). | 26996308 |
BRAF N486_P490del | pancreatic ductal adenocarcinoma | predicted - sensitive | Dabrafenib + Trametinib | Case Reports/Case Series | Actionable | In a clinical case study, the combination of Tafinlar (dabrafenib) and Mekinist (trametinib) resulted in a partial response after 8 weeks of treatment in a patient with metastatic pancreatic ductal adenocarcinoma harboring BRAF N486_P490del (PMID: 36505826). | 36505826 |
BRAF N486_P490del | pancreatic ductal adenocarcinoma | predicted - sensitive | Dabrafenib + Trametinib | Case Reports/Case Series | Actionable | In a retrospective analysis, third-line treatment with the combination of Tafinlar (dabrafenib) and Mekinist (trametinib) resulted in a partial response lasting 18 months in a patient with KRAS wild-type, metastatic pancreatic ductal adenocarcinoma harboring BRAF N486_P490del (PMID: 38770091). | 38770091 |
BRAF N486_P490del | pancreatic ductal adenocarcinoma | sensitive | Ulixertinib | Preclinical - Patient cell culture | Actionable | In a preclinical study, a pancreatic ductal adenocarcinoma patient-derived organoid model harboring BRAF N486_P490del was sensitive to treatment with Ulixertinib (BVD-523) in culture, demonstrating decreased cell viability (PMID: 37463056). | 37463056 |
BRAF N486_P490del | Advanced Solid Tumor | predicted - sensitive | Trametinib | Preclinical - Biochemical | Actionable | In a preclinical study, Mekinist (trametinib) inhibited Mek and Erk phosphorylation in cells expressing BRAF N486_P490del in culture (PMID: 37656784). | 37656784 |
BRAF N486_P490del | Advanced Solid Tumor | predicted - resistant | Vemurafenib | Preclinical - Biochemical | Actionable | In a preclinical study, Zelboraf (vemurafenib) did not inhibit Mek and Erk phosphorylation in cells expressing BRAF N486_P490del in culture (PMID: 37656784). | 37656784 |
BRAF N486_P490del | Advanced Solid Tumor | predicted - sensitive | Dabrafenib | Preclinical - Biochemical | Actionable | In a preclinical study, Tafinlar (dabrafenib) inhibited Mek and Erk phosphorylation in cells expressing BRAF N486_P490del in culture (PMID: 37656784). | 37656784 |
BRAF N486_P490del | Advanced Solid Tumor | predicted - sensitive | LXH 254 | Preclinical - Biochemical | Actionable | In a preclinical study, LXH 254 inhibited Mek and Erk phosphorylation in cells expressing BRAF N486_P490del in culture (PMID: 37656784). | 37656784 |
BRAF N486_P490del | ovarian cancer | sensitive | LXH 254 | Preclinical - Cell culture | Actionable | In a preclinical study, LXH 254 inhibited MAPK signaling and colony formation in an ovarian cancer cell line harboring BRAF N486_P490del in culture (PMID: 37656784). | 37656784 |
BRAF N486_P490del | ovarian cancer | decreased response | Encorafenib | Preclinical - Cell culture | Actionable | In a preclinical study, an ovarian cancer cell line harboring BRAF N486_P490del was less sensitive to Braftovi (encorafenib) treatment compared to type II RAF inhibitors in culture (PMID: 37656784). | 37656784 |
BRAF N486_P490del | ovarian cancer | sensitive | Sorafenib | Preclinical - Cell culture | Actionable | In a preclinical study, Nexavar (sorafenib) inhibited colony formation in an ovarian cancer cell line harboring BRAF N486_P490del in culture (PMID: 37656784). | 37656784 |
BRAF N486_P490del | ovarian cancer | predicted - sensitive | Ulixertinib | Preclinical - Biochemical | Actionable | In a preclinical study, Ulixertinib (BVD-523) inhibited metabolic activity in an ovarian cancer cell line harboring BRAF N486_P490del in culture (PMID: 37656784). | 37656784 |
BRAF N486_P490del | ovarian cancer | predicted - sensitive | LXH 254 + Trametinib | Preclinical - Biochemical | Actionable | In a preclinical study, combination of Mekinist (trametinib) and LXH 254 resulted in enhanced inhibition of metabolic activity in an ovarian cancer cell line harboring BRAF N486_P490del in culture (PMID: 37656784). | 37656784 |
BRAF N486_P490del | ovarian cancer | predicted - sensitive | Sorafenib + Trametinib | Preclinical - Biochemical | Actionable | In a preclinical study, combination of Mekinist (trametinib) and Nexavar (sorafenib) resulted in enhanced inhibition of metabolic activity in an ovarian cancer cell line harboring BRAF N486_P490del in culture (PMID: 37656784). | 37656784 |
BRAF N486_P490del | pancreatic ductal adenocarcinoma | sensitive | Binimetinib | Preclinical - Patient cell culture | Actionable | In a preclinical study, Mektovi (binimetinib) inhibited growth of organoids derived from pancreatic ductal adenocarcinoma patients harboring BRAF N486_P490del in culture (PMID: 37656784). | 37656784 |
BRAF N486_P490del | pancreatic ductal adenocarcinoma | sensitive | SCH772984 | Preclinical - Patient cell culture | Actionable | In a preclinical study, SCH772984 inhibited growth of organoids derived from pancreatic ductal adenocarcinoma patients harboring BRAF N486_P490del in culture (PMID: 37656784). | 37656784 |
BRAF N486_P490del | pancreatic ductal adenocarcinoma | sensitive | Sorafenib | Preclinical - Patient cell culture | Actionable | In a preclinical study, Nexavar (sorafenib) inhibited growth of organoids derived from pancreatic ductal adenocarcinoma patients harboring BRAF N486_P490del in culture (PMID: 37656784). | 37656784 |
BRAF N486_P490del | pancreatic ductal adenocarcinoma | sensitive | LXH 254 | Preclinical - Patient cell culture | Actionable | In a preclinical study, LXH 254 inhibited growth of organoids derived from pancreatic ductal adenocarcinoma patients harboring BRAF N486_P490del in culture (PMID: 37656784). | 37656784 |
BRAF N486_P490del | lung adenocarcinoma | predicted - sensitive | Dabrafenib + Trametinib | Case Reports/Case Series | Actionable | In a clinical case study, treatment with the combination of Tafinlar (dabrafenib) and Mekinist (trametinib) resulted in complete resolution of the pulmonary lesions and ongoing response after 6 months in a patient with metastatic lung adenocarcinoma harboring BRAF N486_P490del, who remained on treatment at 9 months (PMID: 38479107). | 38479107 |