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 1–50 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 Fusion1
Trametinib	Cutaneous MelanomaALIAS	Predictive	C	Supports Sensitivity Response	2	accepted

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 1–25 of 142 publications · bibliographic data as recorded by PubMed; abstracts are not reproduced.

Improved survival with vemurafenib in melanoma with BRAF V600E mutation.
· N Engl J Med · 2011 · PMID 21639808 · validated civic_curation pubmed
Improved overall survival in melanoma with combined dabrafenib and trametinib.
· N Engl J Med · 2015 · PMID 25399551 · validated civic_curation pubmed
Cobimetinib combined with vemurafenib in advanced BRAF(V600)-mutant melanoma (coBRIM): updated efficacy results from a randomised, double-blind, phase 3 trial.
· Lancet Oncol · 2016 · PMID 27480103 · validated civic_curation pubmed
Encorafenib plus binimetinib versus vemurafenib or encorafenib in patients with BRAF-mutant melanoma (COLUMBUS): a multicentre, open-label, randomised phase 3 trial.
· Lancet Oncol · 2018 · PMID 29573941 · validated

BRAF Fusion2
(diagnostic)	Thyroid Gland Papillary CarcinomaALIAS	Diagnostic	B	Supports Positive	4	accepted	EID462 The AKAP9-BRAF fusion gene was found in 3/28 tumor samples of radiation-associated papillary thyroid carcinoma, and no samples of non-radiation associated papillary thyroid carcinoma. This fusion was … (full text at CIViC) PMID 15630448 · Ciampi et al., 2005 · Open in CIViC	civic
Trametinib	Large Congenital Melanocytic NevusUNRESOLVED	Predictive	C	Supports Sensitivity Response	3	submitted	EID7759 Case report of a 7-year-old girl with a giant congenital melanocytic nevus that had an AKAP9-BRAF fusion and was treated with trametinib, which resulted in rapid resolution of the patient's pain and p… (full text at CIViC) PMID 30792255 · Mir et al., 2019 · Open in CIViC	civic

BRAF Asn486_Pro490del2
(oncogenic)	Malignant NeoplasmALIAS	Oncogenic	D	Supports Oncogenicity	5	submitted	EID12993 BRAF p.Asn486_Pro490del (NM_004333.6:c.1457_1471del15) causes increased colony formation (triplicates). Class 2 BRAF variant. PMID 26732095 · Chen et al., 2016 · Open in CIViC	civic
(functional)	—UNRESOLVED	Functional	D	Supports Gain Of Function	5	submitted	EID12994 BRAF p.Asn486_Pro490del (NM_004333.6:c.1457_1471del15) causes increased ratio of pERK/ERK. Class 2 BRAF variant. PMID 26732095 · Chen et al., 2016 · Open in CIViC	civic

BRAF D594G10
(prognostic)	Malignant Colorectal NeoplasmCURATED_BROADER	Prognostic	B	Supports Poor Outcome	2	accepted	EID1553 In a study of 908 patients with colorectal cancer (CRC), 7 patients had BRAF D595G mutations and 589 patients were BRAF wild type. The survival rate of CRC patients at 3 years was significantly poorer… (full text at CIViC) PMID 27404270 · Amaki-Takao et al., 2016 · Open in CIViC	civic
〃	Malignant Colorectal NeoplasmCURATED_BROADER	Prognostic	B	Supports Poor Outcome	1	accepted	EID1551 In a study of 908 patients with colorectal cancer, 7 patients had BRAF (D594G) mutations and 45 patients had BRAF (V600E) mutations. Overall clinicopathological implications of BRAF V600E and D594G mu… (full text at CIViC) PMID 27404270 · Amaki-Takao et al., 2016 · Open in CIViC	civic
Cetuximab + IrinotecanCombination	Malignant Colorectal NeoplasmCURATED_BROADER	Predictive	C	Does Not Support Resistance	3	accepted	EID2201 One patient participating in a large retrospective study of cetuximab in metastatic, treatment refractory colorectal cancer had a tumor which harbored BRAF D594G and was wildtype for KRAS, NRAS and PI… (full text at CIViC) PMID 20619739 · De Roock et al., 2010 · Open in CIViC	civic
〃	Malignant Colorectal NeoplasmCURATED_BROADER	Predictive	C	Supports Resistance	3	accepted	EID4472 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
Cetuximab + PanitumumabSubstitutes	Malignant Colorectal NeoplasmCURATED_BROADER	Predictive	C	Does Not Support Resistance	1	accepted	EID1554 Two patients with stage IV BRAF (D594G) mutations received anti-EGFR antibody therapy (cetuximab and panitumumab). The first patient was on FOLFOX plus bevacizumab and showed no signs of progression f… (full text at CIViC) PMID 27404270 · Amaki-Takao et al., 2016 · Open in CIViC	civic
Sorafenib	Cutaneous MelanomaALIAS	Predictive	D	Supports Sensitivity Response	3	accepted	EID6001 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	Malignant NeoplasmALIAS	Predictive	D	Supports Sensitivity Response	3	rejected	EID12453 Cell lines were treated with varying concentrations of trametinib for 3 days. Viability was measured by ATP-Glo. The melanoma cell line, SK-MEL-264 (BRAF D594G), was sensitive with low IC50 values (<5… (full text at CIViC) PMID 28783719 · Yao et al., 2017 · Open in CIViC	civic
〃	Malignant NeoplasmALIAS	Predictive	D	Supports Sensitivity Response	2	submitted	EID7760 In a BRAF-mutation inducible model in the NIH3T3 cell line, class 3 BRAF mutations (G466V, G466E, D594G, D594N, and G596R) were resistant to vemurafenib but sensitive to MEK-inhibitor trametinib. PMID 28783719 · Yao et al., 2017 · Open in CIViC	civic
U0126	Cutaneous MelanomaALIAS	Predictive	D	Supports Resistance	3	accepted	EID6002 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
Vemurafenib	Malignant NeoplasmALIAS	Predictive	D	Does Not Support Sensitivity Response	3	accepted	EID7556 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

BRAF D594K2
Irinotecan	Malignant Colorectal NeoplasmCURATED_BROADER	Predictive	B	Supports Resistance	3	accepted	EID6402 The presence of BRAF V600E or D594K was associated with reduced progression-free survival in 5 patients with metastatic colorectal cancer treated with irinotecan-based first line therapy (3.5mo vs. 12… (full text at CIViC) PMID 19603024 · Souglakos et al., 2009 · Open in CIViC	civic
Oxaliplatin	Malignant Colorectal NeoplasmCURATED_BROADER	Predictive	B	Supports Resistance	3	accepted	EID6403 Of 100 metastatic colorectal cancer patients treated with oxaliplatin-based first-line therapy, the 6 patients with either BRAF V600E or D594K had reduced progression-free survival compared to 94 pati… (full text at CIViC) PMID 19603024 · Souglakos et al., 2009 · Open in CIViC	civic

BRAF D594N8
(functional)	—UNRESOLVED	Functional	D	Supports Gain Of Function	5	submitted	EID12985 BRAF p.Asp594Asn (NM_004333.6:c.1780G>A) causes increased MEK phosphorylation, increased ratio of pERK/ERK, increased signaling through RAF1 (CRAF), it has loss of kinase activity. Class 3 BRAF varian… (full text at CIViC) PMID 28783719 · Yao et al., 2017 · Open in CIViC	civic
Dabrafenib	Cutaneous MelanomaALIAS	Predictive	B	Supports Sensitivity Response	—	rejected	EID2813 Patients were treated with a specific RAF inhibitor (dabrafenib), which improved overall survival of patients with BRAF mutations (P<0.003), compared to non-treated patients with BRAF mutations. Patie… (full text at CIViC) PMID 21343559 · Long et al., 2011 · Open in CIViC	civic
〃	Cutaneous MelanomaALIAS	Predictive	D	Supports Sensitivity Response	—	rejected	EID2814 An inducible BRAF-V600E mouse melanoma model shows a tight correlation between activated BRAF and disease progression. PMID 16424035 · Hoeflich et al., 2006 · Open in CIViC	civic
〃	Cutaneous MelanomaALIAS	Predictive	D	Supports Sensitivity Response	—	rejected	EID2815 Acquired resistance to vemurafenib in BRAF-V600E positive melanomas frequently confound vemurafenib therapy. Proposed resistance mechanisms include PDGFRbeta upregulation or NRAS mutations resulting i… (full text at CIViC) PMID 20818844 · Flaherty et al., 2010 · Open in CIViC	civic
〃	Cutaneous MelanomaALIAS	Predictive	D	Supports Sensitivity Response	—	rejected	EID2816 Acquired resistance to vemurafenib in BRAF-V600E positive melanomas frequently confound vemurafenib therapy. Proposed resistance mechanisms include PDGFRbeta upregulation or NRAS mutations resulting i… (full text at CIViC) PMID 21107320 · Johannessen et al., 2010 · Open in CIViC	civic
〃	Cutaneous MelanomaALIAS	Predictive	D	Supports Sensitivity Response	—	rejected	EID2817 Acquired resistance to vemurafenib in BRAF-V600E positive melanomas frequently confound vemurafenib therapy. Proposed resistance mechanisms include PDGFRbeta upregulation or NRAS mutations resulting i… (full text at CIViC) PMID 21107323 · Nazarian et al., 2010 · Open in CIViC	civic
Dabrafenib + TrametinibCombination	Lung Non-Small Cell CarcinomaCURATED_BROADER	Predictive	D	Supports Sensitivity Response	2	submitted	EID8820 Non-V600 BRAF mutations occur frequently in NSCLC. While BRAF D594N results in impaired kinase activity, it can induce MEK/ERK activation when expressed in HEK293T cells in the presence of RAF1 (CRAF)… (full text at CIViC) PMID 28947956 · Noeparast et al., 2017 · Open in CIViC	civic
Vemurafenib	Malignant NeoplasmALIAS	Predictive	D	Does Not Support Sensitivity Response	3	submitted	EID7557 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

BRAF Fusion3
Belvarafenib	Melanoma	Predictive	C	Supports Sensitivity Response	3	accepted	EID13151 A patient with metastatic melanoma of unknown primary harboring an AGK-BRAF fusion with an intact BRAF kinase domain received belvarafenib 450 mg twice daily after progression on pembrolizumab, dacarb… (full text at CIViC) PMID 38470950 · Kim et al., 2024 · Open in CIViC	civic
Sorafenib	Melanoma	Predictive	C	Supports Sensitivity Response	2	accepted	EID723 BRAF fusion AGK-BRAF was associated with decreased sensitivity to vemurafenib and increased sensitivity to sorafenib in-vitro. A single patient with this fusion showed durable response to sorafenib. PMID 23890088 · Botton et al., 2013 · Open in CIViC	civic
Vemurafenib	Melanoma	Predictive	D	Supports Resistance	2	accepted	EID724 A melanoma cell line with AGK-BRAF in-frame fusion showed decreased sensitivity towards Vemurafenib in comparison with BRAF mutated (V600E) cell lines. PMID 23890088 · Botton et al., 2013 · Open in CIViC	civic

AKT1 E17K + BRAF V600EAKT1 BRAF2
Uprosertib	Melanoma	Predictive	D	Supports Sensitivity Response	2	accepted	EID707 A melanoma cell line (M262) with AKT E17K mutation was found to be sensitive to AKT inhibition with GSK2141795B in this study. PMID 24735930 · Lassen et al., 2014 · Open in CIViC	civic
Dabrafenib + UprosertibCombination	Melanoma	Predictive	D	Supports Sensitivity Response	2	submitted	EID13115 A BRAF V600E-positive melanoma cell line (M262) with AKT E17K mutation was found to have a similar level of sensitivity to combination dabrafenib plus AKT inhibitor GSK2141795B (IC50 < 1nM) as to dabr… (full text at CIViC) PMID 24735930 · Lassen et al., 2014 · Open in CIViC	civic

BRAF D594N + BRAF G466A2
Cetuximab	Malignant NeoplasmALIAS	Predictive	D	Does Not Support Sensitivity Response	3	submitted	EID12448 A patient with a metastatic collecting duct carcinoma of the kidney was treated with combination chemotherapy and responded except for one ovarian lesion. A PDX was generated from the ovarian lesion. … (full text at CIViC) PMID 28783719 · Yao et al., 2017 · Open in CIViC	civic
Capmatinib + CrizotinibSubstitutes	Malignant NeoplasmALIAS	Predictive	D	Supports Sensitivity Response	3	submitted	EID12449 A patient with a metastatic collecting duct carcinoma of the kidney was treated with combination chemotherapy and responded except for one ovarian lesion. A PDX was generated from the ovarian lesion. … (full text at CIViC) PMID 28783719 · Yao et al., 2017 · Open in CIViC	civic

BRAF Exon 15 Mutation2
Regorafenib Anhydrous	Gastrointestinal Stromal Tumor	Predictive	C	Does Not Support Sensitivity Response	2	accepted	EID4121 This phase II clinical trial of regorafenib (NCT01068769) examined the long term safety and efficacy of regorafenib monotherapy in patients with metastatic and/or unresectable gastrointestinal stromal… (full text at CIViC) PMID 27371698 · Ben-Ami et al., 2016 · Open in CIViC	civic
〃	Gastrointestinal Stromal Tumor	Predictive	C	Supports Resistance	1	accepted	EID4605 This retrospective study of a phase 2 clinical trial (NCT01068769) examined regorafenib safety and efficacy in advanced gastrointestinal stromal tumor (GIST) patients refractory to at least imatinib a… (full text at CIViC) PMID 22614970 · George et al., 2012 · Open in CIViC	civic