Gene

BRAF

B-Raf proto-oncogene, serine/threonine kinase

Explore in graph →CI-GENE-00022038HGNC:1097 ENSG00000157764 NCBI 673 CIViC Cancer geneApproved

Curated evidence

Clinical evidence (574)

CIViC items involving this gene, grouped by molecular profile and therapy, with native levels and directions. 50 items per page.

civicCuratedShowing 51–100 of 574 evidence items · levels, directions and significance as curated at the source; each row links to its CIViC record.

Therapy	Cancer	Type	Level	Direction · significance	Rating (1–5)	Status	Evidence	Source
BRAF F595L1
Vemurafenib	Histiocytoma	Predictive	D	Supports Resistance	—	submitted	EID4426 In an in vitro study, a Plat-E cell line expressing a BRAF F595L mutation was associated with resistance to vemurafenib treatment, as compared to Plat-E cells expressing vector, wild-type BRAF or BRAF…

Cohorts

Alteration frequency by cohort (200)

Frequency = cases affected / cases profiled within one cohort. Cohorts are never pooled.

cbioportalObserved200 cohort rows (showing 50, sorted by frequency) · frequency = affected / profiled, as published by each cohort; cohorts are not pooled. Hover a row badge for its release.

Cohort	Mapped cancer	Alteration	Affected (n)	Profiled (n)	Frequency (%)	Rank in cohort	Source
Metastatic Melanoma (MSK, JCO Precis Oncol 2017) skcm_vanderbilt_mskcc_2015	Cutaneous Melanoma	Ssm	66

Literature

Linked publications (142)

25 per page, newest first.

pubmedPublishedShowing 51–75 of 142 publications · bibliographic data as recorded by PubMed; abstracts are not reproduced.

Vemurafenib for Refractory Multisystem Langerhans Cell Histiocytosis in Children: An International Observational Study.
· J Clin Oncol · 2019 · PMID 31513482 · validated civic_curation pubmed
Trametinib Activity in Patients with Solid Tumors and Lymphomas Harboring BRAF Non-V600 Mutations or Fusions: Results from NCI-MATCH (EAY131).
· Clin Cancer Res · 2020 · PMID 31924734 · validated civic_curation pubmed
Vemurafenib in patients with BRAF(V600E)-positive metastatic or unresectable papillary thyroid cancer refractory to radioactive iodine: a non-randomised, multicentre, open-label, phase 2 trial.
· Lancet Oncol · 2016 · PMID 27460442 · validated civic_curation pubmed
BRAF mutation predicts a poorer clinical prognosis for papillary thyroid cancer.
· J Clin Endocrinol Metab · 2005 · PMID 16174717

BRAF G464V2
Sorafenib	Malignant Breast Neoplasm	Predictive	D	Supports Sensitivity Response	1	submitted	EID2811 In an attempt to block both MAPK and PI3K/Akt pathways, two signaling inhibitors (sorafenib, a BRAF kinase inhibitor, and ceramide, an agent that dephosphorylates Akt) were used in cell culture and mo… (full text at CIViC) PMID 18519791 · Tran et al., 2008 · Open in CIViC	civic
Vemurafenib	Malignant NeoplasmALIAS	Predictive	C	Does Not Support Sensitivity Response	2	accepted	EID5964 The phase 2a MyPathway study assigned patients with HER2, EGFR, BRAF or SHH alterations to treatment with pertuzumab plus trastuzumab, erlotinib, vemurafenib, or vismodegib, respectively. Of 26 patien… (full text at CIViC) PMID 29320312 · Hainsworth et al., 2018 · Open in CIViC	civic

BRAF G466V9
Cetuximab	Malignant Colorectal NeoplasmCURATED_BROADER	Predictive	D	Supports Sensitivity Response	3	submitted	EID12437 In the study with a tumour from a patient with metastatic colorectal cancer BRAF (G466V) and wild-type RAS and NF1. Treament with Panitumumab and irinotecan cause tumour regression. And in tumour cell… (full text at CIViC) PMID 28783719 · Yao et al., 2017 · Open in CIViC	civic
〃	Lung Non-Small Cell CarcinomaCURATED_BROADER	Predictive	D	Supports Sensitivity Response	3	rejected	EID12441 Several BRAF mutant cell lines were analyzed in response to treatment with increasing concentrations of cetuximab (0-300nM). Cell-growth and impact on signalling was measured: ERK signalling by wester… (full text at CIViC) PMID 28783719 · Yao et al., 2017 · Open in CIViC	civic
Irinotecan + PanitumumabCombination	Malignant Colorectal NeoplasmCURATED_BROADER	Predictive	D	Supports Sensitivity Response	3	accepted	EID7552 In the study with a tumor from a patient with metastatic colorectal cancer BRAF (G466V) and wild-type RAS and NF1. Treament with Panitumumab and irinotecan cause tumor regression. And in tumor cells o… (full text at CIViC) PMID 28783719 · Yao et al., 2017 · Open in CIViC	civic
Pan-RAF/MEK Molecular Glue NST-628	Lung Adenocarcinoma	Predictive	D	Supports Sensitivity Response	3	submitted	EID13159 In the BRAF G466V-mutant NCI-H1666 model, NST-628 suppressed MAPK signaling without inducing BRAF–CRAF heterodimer formation. NCI-H1666 was also included in a panel of BRAF class II/III-mutant cell li… (full text at CIViC) PMID 38588399 · Ryan et al., 2024 · Open in CIViC	civic
Trametinib	Malignant NeoplasmALIAS	Predictive	D	Supports Sensitivity Response	3	submitted	EID12452 Cell lines were treated with varying concentrations of trametinib for 3 days. Viability was measured by ATP-Glo. NSCLC cell lines H1666 and CAL-12T bearing the BRAF G466V mutation were sensitive with… (full text at CIViC) PMID 28783719 · Yao et al., 2017 · Open in CIViC	civic
Vemurafenib	Malignant NeoplasmALIAS	Predictive	C	Does Not Support Sensitivity Response	2	accepted	EID5968 The phase 2a MyPathway study assigned patients with HER2, EGFR, BRAF or SHH alterations to treatment with pertuzumab plus trastuzumab, erlotinib, vemurafenib, or vismodegib, respectively. Of 26 patien… (full text at CIViC) PMID 29320312 · Hainsworth et al., 2018 · Open in CIViC	civic
〃	Malignant Colorectal NeoplasmCURATED_BROADER	Predictive	D	Does Not Support Sensitivity Response	3	accepted	EID7553 In the study with a tumor from a patient with metastatic colorectal cancer BRAF (G466V) and wild-type RAS and NF1. Treatment with Panitumumab and irinotecan cause tumor regression. And in tumor cells … (full text at CIViC) PMID 28783719 · Yao et al., 2017 · Open in CIViC	civic
〃	Solid NeoplasmCURATED_BROADER	Predictive	D	Does Not Support Sensitivity Response	3	accepted	EID7554 RAF inhibitor vemurafenib failed to inhibit ERK signaling in tumor cells and NIH3T3 that express class 3 BRAF mutations (G466V, G466E, D594G, D594N, and G596R). PMID 28783719 · Yao et al., 2017 · Open in CIViC	civic
〃	Lung Non-Small Cell CarcinomaCURATED_BROADER	Predictive	D	Supports Resistance	3	rejected	EID12439 Several BRAF mutant cell lines were treated with vemurafenib, A375 (BRAF V600E) was used as a positive control. Two non-small cell cancer cell lines (H1666 and CAL-12T) containing the BRAF G466V mutat… (full text at CIViC) PMID 28783719 · Yao et al., 2017 · Open in CIViC	civic

BRAF G4692
BRAF Inhibitor	Melanoma	Predictive	B	Does Not Support Sensitivity Response	3	submitted	EID7623 In a retrospective study from 20 institutes in 4 countries, the efficacy of BRAF inhibitor and/or MEK inhibitor in patients with melanoma harboring BRAF nonV600E/K mutations were evaluated. Treated wi… (full text at CIViC) PMID 31580757 · Menzer et al., 2019 · Open in CIViC	civic
BRAF Inhibitor + Mitogen-Activated Protein Kinase Kinase InhibitorCombination	Melanoma	Predictive	B	Supports Sensitivity Response	3	accepted	EID7634 In a retrospective study from 20 institutes in 4 countries, the efficacy of BRAF inhibitor and/or MEK inhibitor in patients with melanoma harboring BRAF nonV600E/K mutations were evaluated. Treated wi… (full text at CIViC) PMID 31580757 · Menzer et al., 2019 · Open in CIViC	civic

BRAF G469A8
(functional)	—UNRESOLVED	Functional	D	Supports Gain Of Function	5	submitted	EID12981 BRAF p.Gly469Ala (NM_004333.6:c.1406G>C) causes increased MEK phosphorylation, increased ratio of pERK/ERK. Class 2 BRAF variant. (In PMID: 15035987 AA numbers shifted by one, AA 468 corresponds to AA… (full text at CIViC) PMID 15035987 · Wan et al., 2004 · Open in CIViC	civic
〃	—UNRESOLVED	Functional	D	Supports Gain Of Function	5	submitted	EID12982 BRAF p.Gly469Ala (NM_004333.6:c.1406G>C) causes increased MEK phosphorylation, and increased ratio of pERK/ERK. Class 2 BRAF variant. PMID 28783719 · Yao et al., 2017 · Open in CIViC	civic
Cetuximab	Malignant Colorectal NeoplasmCURATED_BROADER	Predictive	C	Supports Resistance	—	submitted	EID4182 In a retrospective study of 53, KRAS exon 2 wild-type, metastatic colorectal cancer patients, patients harboring BRAF G466A (n=1), G469A (n=2), D594G (n=1), or V600E (n=2) mutations were reported to b… (full text at CIViC) PMID 26989027 · Hsu et al., 2016 · Open in CIViC	civic
Erlotinib	Lung Non-Small Cell CarcinomaCURATED_BROADER	Predictive	D	Supports Resistance	—	submitted	EID4184 In an in vitro study, a PC-9 cell line expressing BRAF G469A mutation demonstrated decreased sensitivity to erlotinib treatment compared to PC-9 cells expressing BRAF wild-type. Sensitivity was determ… (full text at CIViC) PMID 22773810 · Ohashi et al., 2012 · Open in CIViC	civic
Osimertinib	Lung Adenocarcinoma	Predictive	D	Supports Resistance	5	rejected	EID10514 PC9 cells harboring an in-frame deletion in exon 19 of the EGFR gene were cultured in the presence of increasing concentrations of osimertinib. Three clones resistant to osimertinib were isolated and … (full text at CIViC) PMID 31502118 · La Monica et al., 2019 · Open in CIViC	civic
〃	Lung Adenocarcinoma	Predictive	D	Supports Resistance	5	rejected	EID10515 PC9 cells harboring an in-frame deletion in exon 19 of the EGFR gene were cultured in the presence of increasing concentrations of osimertinib. Three clones resistant to osimertinib were isolated and … (full text at CIViC) PMID 31502118 · La Monica et al., 2019 · Open in CIViC	civic
Vemurafenib	Malignant NeoplasmALIAS	Predictive	C	Does Not Support Sensitivity Response	2	accepted	EID5965 The phase 2a MyPathway study assigned patients with HER2, EGFR, BRAF or SHH alterations to treatment with pertuzumab plus trastuzumab, erlotinib, vemurafenib, or vismodegib, respectively. Of 26 patien… (full text at CIViC) PMID 29320312 · Hainsworth et al., 2018 · Open in CIViC	civic
〃	Melanoma	Predictive	D	Supports Resistance	—	submitted	EID4183 In an in vitro study, a MO-1 cell line expressing BRAF G469A demonstrated reduced sensitivity to vemurafenib treatment, similar to LND-1 cells expression BRAF wild-type. Sensitivity was determined by … (full text at CIViC) PMID 26070258 · Porcelli et al., 2015 · Open in CIViC	civic

BRAF G469E5
(functional)	—UNRESOLVED	Functional	D	Supports Gain Of Function	5	submitted	EID12983 BRAF p.Gly469Glu (NM_004333.6:c.1406G>A) causes increased MEK phosphorylation, increased signaling through RAF1 (CRAF), it has low kinase activity. Class 3 BRAF variant. (In PMID: 15035987 AA numbers … (full text at CIViC) PMID 15035987 · Wan et al., 2004 · Open in CIViC	civic
〃	—UNRESOLVED	Functional	D	Supports Gain Of Function	5	submitted	EID12984 BRAF p.Gly469Glu (NM_004333.6:c.1406G>A) causes increased ratio of pERK/ERK, increased signaling through RAF1 (CRAF), it has low kinase activity. Class 3 BRAF variant. PMID 18794803 · Smalley et al., 2009 · Open in CIViC	civic
Sorafenib	Cutaneous MelanomaALIAS	Predictive	D	Supports Sensitivity Response	3	accepted	EID6003 In this preclinical study, melanoma cell lines harboring the kinase-dead G469E- and D594G mutations were identified. These cell lines were resitant to MEK-Inhibition but underwent apoptosis after shRN… (full text at CIViC) PMID 18794803 · Smalley et al., 2009 · Open in CIViC	civic
Trametinib	Breast Ductal Carcinoma	Predictive	C	Supports Sensitivity Response	2	submitted	EID7861 Subprotocol R of the NCI-MATCH study tested the MEK inhibitor trametinib in non-V600 BRAF mutant tumors. 32 patients were eligible and received therapy with trametinib. Of these 1 patient had a confir… (full text at CIViC) PMID 31924734 · Johnson et al., 2020 · Open in CIViC	civic
U0126	Cutaneous MelanomaALIAS	Predictive	D	Supports Resistance	3	accepted	EID6004 In this preclinical study, melanoma cell lines harboring the kinase-dead G469E- and D594G mutations were identified. These cell lines were resitant to MEK-Inhibition (U0126) but underwent apoptosis af… (full text at CIViC) PMID 18794803 · Smalley et al., 2009 · Open in CIViC	civic

BRAF G469S2
(diagnostic)	Multinodular and Vacuolated Neuronal TumorALIAS	Diagnostic	C	Supports Positive	2	submitted	EID12460 In an 11-year-old female presenting with seizures, a mixed MVNT with a ganglioglioma-like component located in the left temporal lobe revealed a BRAF p.G469S mutation (NM_004333.6:c.1405_1406delinsTC;… (full text at CIViC) PMID 29428973 · Pekmezci et al., 2018 · Open in CIViC	civic
Dabrafenib + TrametinibCombination	Lung Non-Small Cell CarcinomaCURATED_BROADER	Predictive	D	Supports Sensitivity Response	3	submitted	EID9515 Non-V600 BRAF mutations occur frequently in NSCLC. BRAF G469S increases kinase activity, as it can induce MEK/ERK activation to higher levels that wild-type BRAF when expressed in HEK293T cells. BEAS-… (full text at CIViC) PMID 28947956 · Noeparast et al., 2017 · Open in CIViC	civic