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Gene | BRAF |
Variant | G464V |
Impact List | missense |
Protein Effect | gain of function |
Gene Variant Descriptions | BRAF G464V (also reported as G463V) lies within the protein kinase domain of the Braf protein (UniProt.org). G464V results in increased Braf kinase activity and increased downstream Mek and Erk activation (PMID: 12068308, PMID: 26343582), and in one of two cell lines, increased cell proliferation and viability compared to wild-type Braf in culture (PMID: 29533785). |
Associated Drug Resistance | |
Category Variants Paths |
BRAF mutant BRAF act mut BRAF G464V BRAF mutant BRAF G464X BRAF G464V |
Transcript | NM_004333.6 |
gDNA | chr7:g.140781617C>A |
cDNA | c.1391G>T |
Protein | p.G464V |
Source Database | RefSeq |
Genome Build | GRCh38/hg38 |
Transcript | gDNA | cDNA | Protein | Source Database | Genome Build |
---|---|---|---|---|---|
NM_001354609.2 | chr7:g.140781617C>A | c.1391G>T | p.G464V | RefSeq | GRCh38/hg38 |
XM_047420769.1 | chr7:g.140781617C>A | c.1391G>T | p.G464V | RefSeq | GRCh38/hg38 |
XM_005250045 | chr7:g.140781617C>A | c.1391G>T | p.G464V | RefSeq | GRCh38/hg38 |
NM_001354609.1 | chr7:g.140781617C>A | c.1391G>T | p.G464V | RefSeq | GRCh38/hg38 |
NM_001378474.1 | chr7:g.140781617C>A | c.1391G>T | p.G464V | RefSeq | GRCh38/hg38 |
NM_001378468.1 | chr7:g.140781617C>A | c.1391G>T | p.G464V | RefSeq | GRCh38/hg38 |
NM_004333.6 | chr7:g.140781617C>A | c.1391G>T | p.G464V | RefSeq | GRCh38/hg38 |
NM_004333.5 | chr7:g.140781617C>A | c.1391G>T | p.G464V | RefSeq | GRCh38/hg38 |
NM_004333 | chr7:g.140781617C>A | c.1391G>T | p.G464V | RefSeq | GRCh38/hg38 |
Molecular Profile | Indication/Tumor Type | Response Type | Therapy Name | Approval Status | Evidence Type | Efficacy Evidence | References |
---|---|---|---|---|---|---|---|
BRAF G464V | 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 G464V (PMID: 31924734; NCT02465060). | 31924734 |
BRAF G464V | Advanced Solid Tumor | resistant | 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, 2 of the non-responding patients harbored BRAF G464V (PMID: 29320312; NCT02091141). | 29320312 |
BRAF G464V | Advanced Solid Tumor | resistant | Vemurafenib | Preclinical - Cell culture | Actionable | In a preclinical study, Zelboraf (vemurafenib) did not inhibit MEK and ERK activation in transformed cells over expressing the constitutively dimerized BRAF G464V (PMID: 26343582). | 26343582 |
BRAF G464V | triple-receptor negative breast cancer | sensitive | SIJ777 | Preclinical - Cell culture | Actionable | In a preclinical study, SIJ777 inhibited proliferation of a triple-negative breast cancer cell line harboring BRAF G464V in culture (PMID: 33917428). | 33917428 |