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Gene | BRAF |
Variant | G464E |
Impact List | missense |
Protein Effect | gain of function |
Gene Variant Descriptions | BRAF G464E (also reported as G463E) lies within the protein kinase domain of the Braf protein (UniProt.org). G464E results in increased Braf kinase activity and activation of MEK and ERK (PMID: 15035987, PMID: 23680146), and in one of two cell lines, increased cell proliferation and cell viability compared to wild-type Braf in culture (PMID: 29533785). |
Associated Drug Resistance | |
Category Variants Paths |
BRAF mutant BRAF act mut BRAF G464E BRAF mutant BRAF G464X BRAF G464E |
Transcript | NM_004333.6 |
gDNA | chr7:g.140781617C>T |
cDNA | c.1391G>A |
Protein | p.G464E |
Source Database | RefSeq |
Genome Build | GRCh38/hg38 |
Transcript | gDNA | cDNA | Protein | Source Database | Genome Build |
---|---|---|---|---|---|
NM_004333.5 | chr7:g.140781617C>T | c.1391G>A | p.G464E | RefSeq | GRCh38/hg38 |
NM_001354609.1 | chr7:g.140781617C>T | c.1391G>A | p.G464E | RefSeq | GRCh38/hg38 |
NM_001378468.1 | chr7:g.140781617C>T | c.1391G>A | p.G464E | RefSeq | GRCh38/hg38 |
NM_001378474.1 | chr7:g.140781617C>T | c.1391G>A | p.G464E | RefSeq | GRCh38/hg38 |
XM_005250045 | chr7:g.140781617C>T | c.1391G>A | p.G464E | RefSeq | GRCh38/hg38 |
XM_047420769.1 | chr7:g.140781617C>T | c.1391G>A | p.G464E | RefSeq | GRCh38/hg38 |
NM_004333.6 | chr7:g.140781617C>T | c.1391G>A | p.G464E | RefSeq | GRCh38/hg38 |
NM_001354609.2 | chr7:g.140781617C>T | c.1391G>A | p.G464E | RefSeq | GRCh38/hg38 |
NM_004333 | chr7:g.140781617C>T | c.1391G>A | p.G464E | RefSeq | GRCh38/hg38 |
Molecular Profile | Indication/Tumor Type | Response Type | Therapy Name | Approval Status | Evidence Type | Efficacy Evidence | References |
---|---|---|---|---|---|---|---|
BRAF G464E | sarcomatoid carcinoma | 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 stable disease with a progression-free survival of 6.9 months in a patient with spindle cell carcinoma harboring a BRAF G464E (PMID: 31924734; NCT02465060). | 31924734 |
BRAF G464E | 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 G464E (PMID: 26343582). | 26343582 |
BRAF G464E | melanoma | predicted - sensitive | PHI-501 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, PHI-501 inhibited growth and migration and induced apoptosis in a melanoma cell line harboring BRAF G464E in culture and inhibited tumor growth in a cell line xenograft model (Cancer Res (2023) 83 (7_Supplement): 1627). | detail... |
BRAF G464E | melanoma | sensitive | SIJ777 | Preclinical - Cell culture | Actionable | In a preclinical study, SIJ777 inhibited Mek, Erk, and Akt phosphorylation, proliferation, migration, invasion, and colony formation, and induced apoptosis in a melanoma cell line harboring BRAF G464E in culture (PMID: 33917428). | 33917428 |