Gene Variant Detail

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Gene BRAF
Variant G466V
Impact List missense
Protein Effect loss of function
Gene Variant Descriptions BRAF G466V lies within the protein kinase domain of the Braf protein (UniProt.org). G466V results in impaired Braf kinase activity, but paradoxically activates MEK and ERK through transactivation of CRAF in cell culture (PMID: 22649091, PMID: 28783719), and in one of two cell lines, G466V decreased cell proliferation and cell viability as compared to wild-type Braf (PMID: 29533785).
Associated Drug Resistance
Category Variants Paths

BRAF mutant BRAF G466X BRAF G466V

BRAF mutant BRAF inact mut BRAF G466V

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Transcript NM_004333.6
gDNA chr7:g.140781611C>A
cDNA c.1397G>T
Protein p.G466V
Source Database RefSeq
Genome Build GRCh38/hg38
Transcript gDNA cDNA Protein Source Database Genome Build
NM_004333 chr7:g.140781611C>A c.1397G>T p.G466V RefSeq GRCh38/hg38
XM_047420766.1 chr7:g.140778075C>A c.1397G>T p.G466V RefSeq GRCh38/hg38
NM_001378468.1 chr7:g.140781611C>A c.1397G>T p.G466V RefSeq GRCh38/hg38
XM_047420769.1 chr7:g.140781611C>A c.1397G>T p.G466V RefSeq GRCh38/hg38
NM_004333.6 chr7:g.140781611C>A c.1397G>T p.G466V RefSeq GRCh38/hg38
NM_001378472.1 chr7:g.140777053C>A c.1397G>T p.G466V RefSeq GRCh38/hg38
NM_001378474.1 chr7:g.140781611C>A c.1397G>T p.G466V RefSeq GRCh38/hg38
NM_001378471.1 chr7:g.140778000C>A c.1397G>T p.G466V RefSeq GRCh38/hg38
NM_001378473.1 chr7:g.140777053C>A c.1397G>T p.G466V RefSeq GRCh38/hg38
NM_001354609.2 chr7:g.140781611C>A c.1397G>T p.G466V RefSeq GRCh38/hg38
NM_001354609.1 chr7:g.140781611C>A c.1397G>T p.G466V RefSeq GRCh38/hg38
NM_004333.5 chr7:g.140781611C>A c.1397G>T p.G466V RefSeq GRCh38/hg38
XM_005250045 chr7:g.140781611C>A c.1397G>T p.G466V RefSeq GRCh38/hg38

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Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
BRAF G466V lung non-small cell carcinoma sensitive Trametinib Preclinical - Cell culture Actionable In a preclinical study, Mekinist (trametinib) reduced ERK signaling and inhibited proliferation of non-small cell lung cancer cell lines harboring BRAF G466V in culture (PMID: 28783719). 28783719
BRAF G466V lung adenocarcinoma no benefit Trametinib Case Reports/Case Series Actionable In a Phase II trial (NCI-MATCH), Mekinist (trametinib) treatment did not demonstrate clinical activity in patients with advanced solid tumors or lymphoma harboring BRAF fusion or non-V600 mutations, resulted in progressive disease in a patient with lung adenocarcinoma harboring BRAF G466V (PMID: 31924734; NCT02465060). 31924734
BRAF G466V colorectal cancer sensitive Trametinib Preclinical - Pdx Actionable In a preclinical study, treatment with Mekinist (trametinib) delayed tumor growth in a colorectal cancer patient-derived xenograft (PDX) model harboring BRAF G466V, and wild-type RAS and NF1 (PMID: 28783719). 28783719
BRAF G466V Advanced Solid Tumor no benefit Trametinib Case Reports/Case Series Actionable In a Phase II trial (NCI-MATCH), Mekinist (trametinib) treatment did not demonstrate clinical activity in patients with advanced solid tumors or lymphoma harboring BRAF fusion or non-V600 mutations, resulted in progressive disease in a patient with tumor of unknown primary harboring BRAF G466V (PMID: 31924734; NCT02465060). 31924734
BRAF G466V lung non-small cell carcinoma no benefit Vemurafenib Case Reports/Case Series Actionable In a Phase II trial, Zelboraf (vemurafenib) treatment did not result in response in the cohort of 15 non-small cell lung cancer patients with non-V600 BRAF mutations, which included 3 patients harboring BRAF G466V, and enrollment in this cohort was discontinued (PMID: 31959346; NCT02304809). 31959346
BRAF G466V lung non-small cell carcinoma no benefit Vemurafenib Preclinical - Cell culture Actionable In a preclinical study, non-small cell lung cancer cells harboring BRAF G466V demonstrated decreased sensitivity to Zelboraf (vemurafenib) in culture (PMID: 27523909). 27523909
BRAF G466V colorectal cancer predicted - resistant Vemurafenib Preclinical - Pdx Actionable In a preclinical study, Zelboraf (vemurafenib) did not inhibit ERK signaling or tumor growth in a colorectal cancer patient-derived xenograft (PDX) model harboring BRAF G466V, and wild-type RAS and NF1 (PMID: 28783719). 28783719
BRAF G466V colorectal cancer predicted - resistant Vemurafenib Preclinical - Pdx Actionable In a preclinical study, Zelboraf (vemurafenib) treatment did not inhibit Erk signaling or reduce tumor growth in a patient-derived xenograft (PDX) model of colorectal cancer harboring BRAF G466V (PMID: 30559419). 30559419
BRAF G466V Advanced Solid Tumor no benefit Vemurafenib Clinical Study - Cohort Actionable In a Phase II trial (MyPathway), Zelboraf (vemurafenib) treatment resulted in an objective response in only 4% (1/23) of patient with advanced solid tumors harboring non-V600 BRAF mutations, 1 of the non-responding patients harbored BRAF G466V (PMID: 29320312; NCT02091141). 29320312
BRAF G466V colorectal cancer sensitive Cetuximab Preclinical - Pdx Actionable In a preclinical study, Erbitux (cetuximab) treatment inhibited Erk signaling and reduced tumor growth in a patient-derived xenograft (PDX) model of colorectal cancer harboring BRAF G466V (PMID: 30559419). 30559419
BRAF G466V colorectal cancer sensitive Cetuximab Preclinical - Pdx Actionable In a preclinical study, treatment with Erbitux (cetuximab) reduced ERK signaling and resulted in tumor regression in a colorectal cancer patient-derived xenograft (PDX) model harboring BRAF G466V, and wild-type RAS and NF1 (PMID: 28783719). 28783719
BRAF G466V lung non-small cell carcinoma sensitive Dasatinib Preclinical - Cell culture Actionable In a preclinical study, Sprycel (dasatinib) induced apoptosis in non-small cell lung cancer cells expressing BRAF G466V in culture (PMID: 22649091). 22649091
BRAF G466V lung cancer predicted - sensitive PLX8394 Preclinical - Cell culture Actionable In a preclinical study, lung cancer cells harboring BRAF G466V demonstrated sensitivity to PLX8394 treatment in culture (PMID: 30559419). 30559419
BRAF G466V lung adenocarcinoma sensitive PLX8394 Preclinical - Cell culture Actionable In a preclinical study, PLX8394 decreased growth of lung adenocarcinoma cell lines harboring BRAF G466V in culture (PMID: 27834212). 27834212
BRAF G466V colorectal cancer resistant PLX8394 Preclinical - Pdx Actionable In a preclinical study, PLX8394 treatment did not inhibit Erk signaling or reduce tumor growth in a patient-derived xenograft (PDX) model of colorectal cancer harboring BRAF G466V (PMID: 30559419). 30559419
BRAF G466V lung non-small cell carcinoma sensitive Dabrafenib + Trametinib Preclinical - Cell culture Actionable In a preclinical study, treatment with the combination of Mekinist (trametinib) and Tafinlar (dabrafenib) resulted in decreased proliferation and increased apoptosis, and enhanced ERK inhibition compared to either agent alone in a non-small cell lung cancer cell line harboring BRAF G466V in culture (PMID: 28947956). 28947956
BRAF G466V lung adenocarcinoma predicted - sensitive Dabrafenib + Trametinib Case Reports/Case Series Actionable In a clinical case study, first-line treatment with the combination of Mekinist (trametinib) and Tafinlar (dabrafenib) resulted in a partial response after 3 months in a patient with metastatic lung adenocarcinoma harboring BRAF G466V (PMID: 38283732). 38283732
BRAF G466V colorectal cancer sensitive Cetuximab + Vemurafenib Preclinical - Pdx Actionable In a preclinical study, Zelboraf (vemurafenib) treatment in combination with Erbitux (cetuximab) inhibited tumor growth in a patient-derived xenograft (PDX) model of colorectal cancer harboring BRAF G466V, but did not improve efficacy compared to Erbitux (cetuximab) treatment alone (PMID: 30559419). 30559419
BRAF G466V lung non-small cell carcinoma sensitive TAE226 Preclinical Actionable In a preclinical study, TAE226 treatment inhibited proliferation of non-small cell lung carcinoma cell lines harboring BRAF G466V mutation in culture (PMID: 26090892). 26090892
BRAF G466V lung non-small cell carcinoma sensitive TAK-632 Preclinical - Cell culture Actionable In a preclinical study, TAK-632 inhibited proliferation of non-small cell lung cancer cells harboring BRAF G466V in culture (PMID: 27523909). 27523909
BRAF G466V colorectal cancer not predictive Irinotecan + Panitumumab Case Reports/Case Series Actionable In a clinical case study, a patient with metastatic colorectal cancer harboring BRAF G466V, and with wild-type RAS and NF1, demonstrated tumor regression following treatment with Vectibix (panitumumab) plus Camptosar (irinotecan) (PMID: 28783719). 28783719
BRAF G466V colorectal cancer not predictive Irinotecan + Panitumumab Case Reports/Case Series Actionable In a clinical study, the combination of Vectibix (panitumumab) with Camptosar (irinotecan) as a third-line therapy resulted in a partial response with 6.1 months progression-free survival in a patient with metastatic colorectal cancer harboring BRAF G466V (PMID: 31515458). 31515458
BRAF G466V lung cancer predicted - sensitive RMC-4550 Preclinical - Cell culture Actionable In a preclinical study, RMC-4550 inhibited Erk phosphorylation and proliferation of lung cancer cells harboring BRAF G466V in culture (PMID: 30104724). 30104724
BRAF G466V colorectal cancer sensitive Cetuximab + PLX8394 Preclinical - Pdx Actionable In a preclinical study, PLX8394 treatment in combination with Erbitux (cetuximab) inhibited tumor growth in a patient-derived xenograft (PDX) model of colorectal cancer harboring BRAF G466V, but did not improve efficacy compared to Erbitux (cetuximab) treatment alone (PMID: 30559419). 30559419
BRAF G466V lung non-small cell carcinoma predicted - sensitive PF-07799933 Preclinical - Biochemical Actionable In a preclinical study, PF-07799933 inhibited Erk phosphorylation in non-small cell lung cancer cells harboring BRAF G466V in culture (PMID: 38691346). 38691346
BRAF G466V lung cancer predicted - sensitive CFT1946 Preclinical - Cell culture Actionable In a preclinical study, CFT1946 treatment inhibited proliferation of a lung cancer cell line harboring heterozygous BRAF G466V in culture (Cancer Res 2022;82(12_Suppl):Abstract nr 2158). detail...
BRAF G466V lung non-small cell carcinoma sensitive IHMT-RAF-128 Preclinical - Cell culture Actionable In a preclinical study, IHMT-RAF-128 inhibited proliferation in a non-small cell lung cancer cell line harboring BRAF G466V in culture (PMID: 37164118). 37164118
BRAF G466V lung non-small cell carcinoma sensitive SIJ777 Preclinical - Cell culture Actionable In a preclinical study, SIJ777 inhibited proliferation of a non-small cell lung cancer cell line harboring BRAF G466V in culture (PMID: 33917428). 33917428