BRAF (v-raf murine sarcoma viral oncogene homolog B1)

2020-05-01   Enric Domingo 

Oncologia Molecular i Envelliment, Centre dInvestigacions en Bioqumica i Biologia Molecular (CIBBIM) Hospital Universitari Vall dHebron Passeig Vall dHebron 119-129 Barcelona 08035, Catalonia, Spain


Atlas Image
Probe(s) - Courtesy Mariano Rocchi, Resources for Molecular Cytogenetics


Review on BRAF, with data on DNA, on the protein encoded, and where the gene is implicated.



The main isoform of the BRAF gene (NM_004333) is composed of 18 exons spanning in a region of 205601 bp.


The main transcript NM_004333 has 6459 bp.


BRAFP1 (alias BRAF2) in Xq13.3



The real sequence A31 G32 A33 was erroneously considered R31 P32. As the A33 was missing in previous sequences, some articles have erroneously assigned wrong numbers to coding mutations and amino acids (i.e. V599E mutation instead of V600E).
Atlas Image
Figure 1. Diagram of the BRAF protein in scale. Numbers inside the blue boxes indicate the exon from which is translated each part of the protein. The three boxes inside represent the conserved regions of the protein with the ARAF and RAF1 genes (CR1, CR2 and CR3). With green bars are represented three different domains: RBD (Ras binding domain), CRD (Cysteine-rich domain) and KD (Kinase domain). A conserved glycine motif (G-loop) in exon 11 is indicated with a red bar and the activation segment (AS) in exon 15 with a pink bar. The black arrows indicate the major phosphorylation sites of the protein. C: Carboxyl-terminal; N: Amino-terminal.


Amino acids: 766. Molecular Weight: 84437 Daltons. The BRAF gene is a proto-oncogene that belongs to the Serine/Threonine Kinase Family. It is also a member of the RAF Subfamily together with the ARAF and RAF1 genes.


BRAF is expressed in most tissues. Protein expression using antibody staining is not mainly consistent with RNA expression.




BRAF is a serine/threonine kinase that belongs to the RAS/RAF/MEK/ERK/MAPK pathway, which is involved in the transduction of mitogenic signals from the cell membrane to the nucleus. BRAF in its inactive form has region CR1 autoinhibiting region CR3 that contains the Kinase Domain, preventing BRAF kinase abilities. The activated form of BRAF is triggered by Ras proteins. RAS is inactive when bound to GDP, but when it binds to GTP becomes active and promotes phosphorylation and activation of BRAF and the pathway signal. This step is mediated by the Ras Binding Domain (RBD) in CR1 of BRAF, which is released ceasing the kinase inhibition. Several downstream genes have been found to be activated by this pathway, among them, CCND1 (cyclin D1), CCND2 ( cyclin D2) and CCND3 (cyclin D3) (self-sufficiency in growth), VEGF (angiogenesis), MYC (insensitivity to antigrowth signals), ITGB3 (b3-integrin )(tissue invasion and metastasis) and MDM2 (apoptosis evasion, limitless replicative potential and angiogenesis).


BRAF shares three conserved regions (CR1, CR2 and CR3) with the other two RAF genes: ARAF and RAF1 (Figure 1). CR1, which has 131 aa, contains the cysteine-rich domain (CRD) and most of the Ras binding domain (RBD). These two domains bind to RAS-GTP. CR2, which has 16 aa, is rich in serine and threonine residues, including S365 as an inhibitory phosphorylation site. Finally CR3, which has 293 aa and has the kinase domain, contains also the G-loop GXGXXG motif (highly conserved in most of the human kinases), the activation segment and the regulatory phosphorylation sites S446, S447, D448, D449, T599 and S602. The other two RAF genes do not show pathogenic mutations for unclear reasons.



BRAF contains several single nucleotide polymorphisms, both synonymous and non-synonymous. It is unclear whether any of them may impact BRAF function.
Atlas Image
Figure 2. Frequency of BRAF mutations in several tumour types. Data and plot taken from pancancer TCGA in cbioportal.
Atlas Image
Figure 3. Somatic mutations found in BRAF (taken from cbioportal). The low panel shows the same data decreasing the highest mutation number to better visualise atypical BRAF mutations. Location of cancer hotspot mutations are show in the line below.
Atlas Image
Figure 4. Mutations in BRAF, KRAS, NRAS and HRAS genes do not overlap (taken from cbioportal).


No germinal mutations described. BRAF germline mutations result in a large proportion of cardiofaciocutaneous syndrome cases, a rare but serious genetic disorder characterised by distinctive craniofacial malformations. A few other germline mutations in BRAF have also been described in similar developmental disorders like Costello, Noonan or Leopard syndromes. These germline mutations are mostly located in exons 6, 12, 15 and 16 affecting residues in the Cysteine-rich or Kinase domains. They have minimal overlap with somatic mutations described in cancer. In addition, carriers of these germline mutations do not seem to show high risk of developing cancer.


BRAF presents somatic mutations in different sort of tumours like thyroid cancer, malignant melanoma, sporadic colorectal tumors showing mismatch repair defects in microsatellites (MSI) and low-grade ovarian serous carcinoma (Figure 2). A majority of these mutations correspond to the hotspot transversion mutation T1799A that causes the amino acidic substitution V600E, which is the most common single nucleotide change in cancer (Figure 3a). The other atypical ones account for a wide variable range of missense mutations residing in the glycines of the G-loop in exon 11 or in the activation segment in exon 15 near the V600 residue (Figure 3b). The mutation V600E confers transformant activity to the cells because it mimics the phosphorylation of T599 and/or S602 in the activation segment so BRAF rests constitutively active in a RAS independent manner.
BRAF mutations can be classified into 3 subtypes depending on their effect on BRAF activity. Class 1 mutations function as an active monomer and are Ras-independent as they do not require any upstream signaling from Ras. Mutations in codon 600 like the main hotspot are examples of Class 1 mutations. Class 2 mutations are also Ras-independent but they act as dimers (eg K601E, K601N, K601T, L597Q, L597V, G469A, G469V, G469R, G464V). Class 3 are mutations that inactivate the kinase domain but strikingly result in higher MAPK signalling. This is because these are Ras-dependent mutations that also provide higher affinity to both Ras and RAF1 (CRAF), resulting in increased downstream signalling. Examples of Class 3 mutations are D287H, V459L, G466V, G466E, G466A, S467L, G469E, N581S, N581I, D594N, D594G, D594A, D594H, F595L, G596D.
Mutations in the Ras genes HRAS, KRAS or NRAS are not concomitant with BRAF mutations (Figure 4), strongly suggesting same pathway activation. The exception are Class 3 BRAF mutations, probably because they benefit from upstream pathway overactivation by Ras mutations.
BRAF-V600E is not present in other tumours like high-grade ovarian serous carcinoma, gastric cancer, esophageal cancer, endometrial cancer, uveal melanoma, biliary tract cancer or hepatocellular carcinoma.. Gene fusions retaining an intact kinase domain of BRAF have been found in different tumour types at frequencies below 3%.


BRAF has some CpG sites from upstream the transcription start site to the first exon but no methylation has ever been described.

Implicated in

Entity name
BRAF is mutated in about 60% of malignant melanomas. The mutation V600E is an early event and an oncogenic driver upregulating cellular proliferation. However, BRAF V600E alone is insufficient for the development of melanoma as it is present in 80% of benign and dysplastic melanocytic nevi, which are the first lesions associated with this tumour type. Other alterations might be required to induce malignant transformation. No BRAF mutations are associated with uveal melanoma.
BRAF mutations in melanoma are associated with younger age at diagnosis, superficial spreading or nodular histology, anatomical regions without chronic sun damage and higher chances to metastasise to the brain.
Metastatic melanoma patients with mutations in BRAF show worse overall survival than BRAF wild types. BRAF inhibition has also been tested to treat melanoma patients given the relevance of MAPK pathway and the high frequency of BRAF mutations. As a result, some BRAF inhibitors have been implemented clinically and have improved outcome recently in melanoma. Sorafenib is a multitargeted tyrosine kinase inhibitor for different genes including BRAF (wild type and mutant) and RAF1 (CRAF). However, several studies found it ineffective in melanoma both as single agent or combined with cytotoxic chemotherapy. However, vemurafenib (for V600E mutated BRAF inhibition) is an inhibitor specific for BRAF V600E (and also V600K) that proved to increase survival and response rates. More recently, it has been shown that the combination of BRAF and MEK inhibitors (eg dabrafenib + trametinib or vemurafenib + cobimetinib) provides even better outcomes as it better prevents resistance compared to BRAF inhibition monotherapy. These combinational treatments are currently used as part of the standard of care of BRAF mutant melanoma patients, usually when they are advanced, metastatic or unresectable. Nevertheless, resistance may eventually occur by both unknown and known molecular alterations (eg recovery of MAPK signaling by secondary Ras/Raf mutations, BRAF amplification or changes in RNA expression).
Entity name
Colorectal cancer
BRAF mutation V600E is associated with mismatch repair deficiency (MSI) and found in 40% of the cases while in mismatch repair proficient tumors (MSS) the frequency is around 5%. Gastric and endometrial MSI and MSS tumors do not have BRAF mutations. In sporadic MSI colon cases this mutation is found in proximal colon tumors with MLH1 methylation (80% of cases), while in tumors from the hereditary nonpolyposis colorectal cancer (HNPCC), either with MLH1, MSH2 or MSH6 germline mutations or none, no BRAF mutations are detected. Because of this BRAF V600E mutation is used for HNPCC diagnostic as an exclusion criteria for germline mutation in mismatch repair genes. BRAF V600E associations with MLH1 methylation and MSI are secondary to the main association with CpG Island Methylator Phenotype (CIMP), a form of genome-wide global methylation. These are common features in sessile serrated adenomas, strongly suggesting these may be the precursors of their counterparts in colorectal carcinomas. Due to strong association with MSI, BRAF V600E is also associated with older age, female gender, poor differentiation and mucinous phenotype. The primary reasons for all these associations are unclear. Interestingly, they do not seem to have been identified in other tumour types.
Recently, it has been suggested that BRAF V600E colorectal cancers may be classified in two distinct subtypes based on their RNA expression patterns: BM1 (KRAS/AKT pathway activation, mTOR/4EBP deregulation, epithelial-mesenchymal transition) and BM2 (cell cycle deregulation).
Due to its high association with MSI, a very well-known biomarker for good prognosis, BRAF V600E mutation is more frequent in stages I/II/III (about 10%) than in stage IV (about 5%). However, BRAF V600E mutation provides poor prognosis in the metastatic setting and also in the subset of MSS patients in stage III. This may be due to chemoresistance in these patients routinely treated with adjuvant cytotoxic chemotherapy. Strikingly, BRAF mutations have been linked to nodal and peritoneal metastases but not to lung or liver metastases, suggesting specific biological behavior depending on BRAF status. Surprisingly, atypical non-V600E BRAF mutations may provide longer overall survival than both BRAF-V600E mutants and wild types in the metastatic setting.
Although mutations in the upstream genes KRAS and NRAS are good biomarkers for lack of response to EGFR inhibition, BRAF V600E mutation does not seem to provide such information. Conversely, atypical non-V600E BRAF mutations do seem to be associated with resistance to EGFR inhibition.
Unlike melanoma, BRAF inhibitors in colorectal cancer have not proved to be effective due to rapid feedback activation of the EGFR pathway by a wide range of different molecular alterations. However, the first results of the BEACON clinical trial suggest that combining encorafenib (BRAF inhibitor) and cetuximab (EGFR inhibitor) with or without binimetinib (MEK inhibitor) may improve response and survival than standard therapy in BRAF-V600E metastatic colorectal cancer patients.
Entity name
Ovarian cancer
The only BRAF mutation is V600E which is found in 30% of low-grade serous carcinoma and borderline tumors. The mutation seems to occur very early in the development. High-grade tumors do not show BRAF mutations.
There is evidence that BRAF mutation provides good prognosis in early stage low-grade serous ovarian cancer.
Entity name
Thyroid cancer
In thyroid papillary cancer the only BRAF mutation present is V600E with a frequency around 60%, making it the most common molecular alteration of this tumour type. The K601E mutation has also been found in some cases of the follicular variant of thyroid cancer.
In thyroid papillary cancer BRAF V600E mutation is associated with advanced tumour stage at diagnosis, lymph nodes, distant metastases, high rate of recurrence and shorter overall and disease-free survival. However, it has been suggested it may not be an independent biomarker of poor outcome and its effect should be put in context with other prognostic factors.
Inhibition of BRAF by two multikinase inhibitors, sorafenib and levantinib, are established therapeutic options for papillary thyroid tumours refractory to radioiodine therapy. Single agent inhibition specific for BRAF V600E mutation by vemurafenib and dabrafenib is not used as the clinical benefit was not considered reasonable compared to the toxicity provided. These two agents improved progression free survival but did not have much effect on overall survival. Several clinical trials are underway testing different combinations of BRAF inhibition with other agents targeting pathways related with resistance.
Entity name
Non-Small Cell Lung cancer
This tumour type shows a modest frequency of BRAF mutations (1-4%). Unlike all the other tumour types, atypical BRAF mutations account for half of all BRAF mutations, the other half being V600E mutations.
BRAF V600E mutation is a marker for worse prognosis in patients treated with platinum-based agents. This outcome is consistent with chemoresistance as suggested in other tumour types. Similarly, dual inhibition of BRAF and MEK by dabrafenib and trametinib respectively improves outcome compared to standard chemotherapy and single agent BRAF inhibition.
Entity name
cell lines
Table 1. BRAF mutational status in cell lines from colorectal, ovarian, skin, thyroid and lung cancer. Data taken from the Cancer Cell Line Encyclopedia in April 2020.
LARGE INTESTINEHT55N581YLUNGNCIH2405L485_P490delinsF P490Yfs*11 L485Yfs*14


Pubmed IDLast YearTitleAuthors
254171142014Integrated genomic characterization of papillary thyroid carcinoma.
273544682017BRAF V600E Mutant Colorectal Cancer Subtypes Based on Gene Expression.Barras D et al
126978562003BRAF mutation in papillary thyroid carcinoma.Cohen Y et al
315404062019BRAF Inhibitors in Thyroid Cancer: Clinical Impact, Mechanisms of Resistance and Future Perspectives.Crispo F et al
120683082002Mutations of the BRAF gene in human cancer.Davies H et al
300420652018Mutation burden and other molecular markers of prognosis in colorectal cancer treated with curative intent: results from the QUASAR 2 clinical trial and an Australian community-based series.Domingo E et al
146959932004Activated BRAF targets proximal colon tumors with mismatch repair deficiency and MLH1 inactivation.Domingo E et al
153426962004BRAF screening as a low-cost effective strategy for simplifying HNPCC genetic testing.Domingo E et al
157821182005BRAF-V600E is not involved in the colorectal tumorigenesis of HNPCC in patients with functional MLH1 and MSH2 genes.Domingo E et al
231654472013Use of multivariate analysis to suggest a new molecular classification of colorectal cancer.Domingo E et al
235502102013Integrative analysis of complex cancer genomics and clinical profiles using the cBioPortal.Gao J et al
310687002019Next-generation characterization of the Cancer Cell Line Encyclopedia.Ghandi M et al
284860442017(Non-V600) BRAF Mutations Define a Clinically Distinct Molecular Subtype of Metastatic Colorectal Cancer.Jones JC et al
315663092019Encorafenib, Binimetinib, and Cetuximab in BRAF V600E-Mutated Colorectal Cancer.Kopetz S et al
213435592011Prognostic and clinicopathologic associations of oncogenic BRAF in metastatic melanoma.Long GV et al
127813692003Raf proteins and cancer: B-Raf is identified as a mutational target.Mercer KE et al
320105892019Targeting BRAF mutations in non-small cell lung cancer.O'Leary CG et al
169532332007KRAS and BRAF oncogenic mutations in MSS colorectal carcinoma progression.Oliveira C et al
193833132008Human cutaneous melanoma; a review of NRAS and BRAF mutation frequencies in relation to histogenetic subclass and body site.Platz A et al
124473722003High frequency of BRAF mutations in nevi.Pollock PM et al
263145512016The distribution of BRAF gene fusions in solid tumors and response to targeted therapy.Ross JS et al
192061692009Germline BRAF mutations in Noonan, LEOPARD, and cardiofaciocutaneous syndromes: molecular diversity and associated phenotypic spectrum.Sarkozy A et al
279938002017Investigating the poor outcomes of BRAF-mutant advanced colorectal cancer: analysis from 2530 patients in randomised clinical trials.Seligmann JF et al
237410672013Somatic profiling of the epidermal growth factor receptor pathway in tumors from patients with advanced colorectal cancer treated with chemotherapy ± cetuximab.Smith CG et al
313533652019Exploring the best treatment options for BRAF-mutant metastatic colon cancer.Taieb J et al
208021812010BRAF mutation is rare in advanced-stage low-grade ovarian serous carcinomas.Wong KK et al
287837192017Tumours with class 3 BRAF mutants are sensitive to the inhibition of activated RAS.Yao Z et al
314264192019Targeting Oncogenic BRAF: Past, Present, and Future.Zaman A et al

Other Information

Locus ID:

NCBI: 673
MIM: 164757
HGNC: 1097
Ensembl: ENSG00000157764


dbSNP: 673
ClinVar: 673
TCGA: ENSG00000157764


Gene IDTranscript IDUniprot

Expression (GTEx)



PathwaySourceExternal ID
MAPK signaling pathwayKEGGko04010
ErbB signaling pathwayKEGGko04012
mTOR signaling pathwayKEGGko04150
Dorso-ventral axis formationKEGGko04320
Focal adhesionKEGGko04510
Natural killer cell mediated cytotoxicityKEGGko04650
Long-term potentiationKEGGko04720
Long-term depressionKEGGko04730
Regulation of actin cytoskeletonKEGGko04810
Insulin signaling pathwayKEGGko04910
Progesterone-mediated oocyte maturationKEGGko04914
Colorectal cancerKEGGko05210
Renal cell carcinomaKEGGko05211
Pancreatic cancerKEGGko05212
Endometrial cancerKEGGko05213
Prostate cancerKEGGko05215
Thyroid cancerKEGGko05216
Bladder cancerKEGGko05219
Chronic myeloid leukemiaKEGGko05220
Acute myeloid leukemiaKEGGko05221
Non-small cell lung cancerKEGGko05223
MAPK signaling pathwayKEGGhsa04010
ErbB signaling pathwayKEGGhsa04012
mTOR signaling pathwayKEGGhsa04150
Focal adhesionKEGGhsa04510
Natural killer cell mediated cytotoxicityKEGGhsa04650
Long-term potentiationKEGGhsa04720
Long-term depressionKEGGhsa04730
Regulation of actin cytoskeletonKEGGhsa04810
Insulin signaling pathwayKEGGhsa04910
Pathways in cancerKEGGhsa05200
Colorectal cancerKEGGhsa05210
Renal cell carcinomaKEGGhsa05211
Pancreatic cancerKEGGhsa05212
Endometrial cancerKEGGhsa05213
Prostate cancerKEGGhsa05215
Thyroid cancerKEGGhsa05216
Bladder cancerKEGGhsa05219
Chronic myeloid leukemiaKEGGhsa05220
Acute myeloid leukemiaKEGGhsa05221
Non-small cell lung cancerKEGGhsa05223
Vascular smooth muscle contractionKEGGhsa04270
Chemokine signaling pathwayKEGGko04062
Vascular smooth muscle contractionKEGGko04270
Chemokine signaling pathwayKEGGhsa04062
Neurotrophin signaling pathwayKEGGko04722
Neurotrophin signaling pathwayKEGGhsa04722
Dorso-ventral axis formationKEGGhsa04320
Progesterone-mediated oocyte maturationKEGGhsa04914
Hepatitis CKEGGko05160
Hepatitis CKEGGhsa05160
Serotonergic synapseKEGGhsa04726
Proteoglycans in cancerKEGGhsa05205
Proteoglycans in cancerKEGGko05205
Rap1 signaling pathwayKEGGhsa04015
Rap1 signaling pathwayKEGGko04015
FoxO signaling pathwayKEGGhsa04068
cAMP signaling pathwayKEGGhsa04024
cAMP signaling pathwayKEGGko04024
MAPK (ERK1/2) signalingKEGGhsa_M00687
MAPK (ERK1/2) signalingKEGGM00687
Neuronal SystemREACTOMER-HSA-112316
Transmission across Chemical SynapsesREACTOMER-HSA-112315
Neurotransmitter Receptor Binding And Downstream Transmission In The Postsynaptic CellREACTOMER-HSA-112314
Activation of NMDA receptor upon glutamate binding and postsynaptic eventsREACTOMER-HSA-442755
Post NMDA receptor activation eventsREACTOMER-HSA-438064
CREB phosphorylation through the activation of RasREACTOMER-HSA-442742
Diseases of signal transductionREACTOMER-HSA-5663202
Immune SystemREACTOMER-HSA-168256
Innate Immune SystemREACTOMER-HSA-168249
DAP12 interactionsREACTOMER-HSA-2172127
DAP12 signalingREACTOMER-HSA-2424491
RAF/MAP kinase cascadeREACTOMER-HSA-5673001
RAF activationREACTOMER-HSA-5673000
MAP2K and MAPK activationREACTOMER-HSA-5674135
Negative regulation of MAPK pathwayREACTOMER-HSA-5675221
Negative feedback regulation of MAPK pathwayREACTOMER-HSA-5674499
Fc epsilon receptor (FCERI) signalingREACTOMER-HSA-2454202
FCERI mediated MAPK activationREACTOMER-HSA-2871796
Cytokine Signaling in Immune systemREACTOMER-HSA-1280215
Signaling by InterleukinsREACTOMER-HSA-449147
Interleukin-2 signalingREACTOMER-HSA-451927
Interleukin receptor SHC signalingREACTOMER-HSA-912526
Interleukin-3, 5 and GM-CSF signalingREACTOMER-HSA-512988
Signal TransductionREACTOMER-HSA-162582
Signaling by EGFRREACTOMER-HSA-177929
GRB2 events in EGFR signalingREACTOMER-HSA-179812
SHC1 events in EGFR signalingREACTOMER-HSA-180336
Signaling by FGFRREACTOMER-HSA-190236
Signaling by FGFR1REACTOMER-HSA-5654736
Negative regulation of FGFR1 signalingREACTOMER-HSA-5654726
Spry regulation of FGF signalingREACTOMER-HSA-1295596
Signaling by FGFR2REACTOMER-HSA-5654738
Negative regulation of FGFR2 signalingREACTOMER-HSA-5654727
Signaling by FGFR3REACTOMER-HSA-5654741
Negative regulation of FGFR3 signalingREACTOMER-HSA-5654732
Signaling by FGFR4REACTOMER-HSA-5654743
Negative regulation of FGFR4 signalingREACTOMER-HSA-5654733
Signaling by Insulin receptorREACTOMER-HSA-74752
Insulin receptor signalling cascadeREACTOMER-HSA-74751
IRS-mediated signallingREACTOMER-HSA-112399
SOS-mediated signallingREACTOMER-HSA-112412
Signalling by NGFREACTOMER-HSA-166520
NGF signalling via TRKA from the plasma membraneREACTOMER-HSA-187037
Signalling to ERKsREACTOMER-HSA-187687
Signalling to RASREACTOMER-HSA-167044
Signalling to p38 via RIT and RINREACTOMER-HSA-187706
Prolonged ERK activation eventsREACTOMER-HSA-169893
Frs2-mediated activationREACTOMER-HSA-170968
ARMS-mediated activationREACTOMER-HSA-170984
Signaling by PDGFREACTOMER-HSA-186797
Downstream signal transductionREACTOMER-HSA-186763
Signaling by VEGFREACTOMER-HSA-194138
VEGFR2 mediated cell proliferationREACTOMER-HSA-5218921
Signaling by SCF-KITREACTOMER-HSA-1433557
MAPK family signaling cascadesREACTOMER-HSA-5683057
MAPK1/MAPK3 signalingREACTOMER-HSA-5684996
Signaling by GPCRREACTOMER-HSA-372790
Gastrin-CREB signalling pathway via PKC and MAPKREACTOMER-HSA-881907
Signaling by Type 1 Insulin-like Growth Factor 1 Receptor (IGF1R)REACTOMER-HSA-2404192
IGF1R signaling cascadeREACTOMER-HSA-2428924
IRS-related events triggered by IGF1RREACTOMER-HSA-2428928
Signaling by LeptinREACTOMER-HSA-2586552
Developmental BiologyREACTOMER-HSA-1266738
Axon guidanceREACTOMER-HSA-422475
NCAM signaling for neurite out-growthREACTOMER-HSA-375165
EGFR tyrosine kinase inhibitor resistanceKEGGko01521
Endocrine resistanceKEGGko01522
EGFR tyrosine kinase inhibitor resistanceKEGGhsa01521
Endocrine resistanceKEGGhsa01522
RET signalingREACTOMER-HSA-8853659
Breast cancerKEGGko05224
Breast cancerKEGGhsa05224
Oncogenic MAPK signalingREACTOMER-HSA-6802957
Signaling by RAS mutantsREACTOMER-HSA-6802949
Signaling by high-kinase activity BRAF mutantsREACTOMER-HSA-6802948
Signaling by moderate kinase activity BRAF mutantsREACTOMER-HSA-6802946
Paradoxical activation of RAF signaling by kinase inactive BRAFREACTOMER-HSA-6802955
Signaling by BRAF and RAF fusionsREACTOMER-HSA-6802952

Protein levels (Protein atlas)

Not detected


Entity IDNameTypeEvidenceAssociationPKPDPMIDs
PA165946873vemurafenibChemicalLabelAnnotation, Pathway, VipGeneassociated
PA166114911dabrafenibChemicalLabelAnnotation, VariantAnnotation, VipGeneassociatedPD
PA166157522rs113488022VariantLabelAnnotation, VipGeneassociated22535154, 23116250, 12068308
PA30196KRASGeneMultilinkAnnotation, Pathwayassociated14513361, 28362716
PA444903MelanomaDiseaseMultilinkAnnotationassociated12068308, 12957284
PA446108Colorectal NeoplasmsDiseaseMultilinkAnnotationassociated12198537


Pubmed IDYearTitleCitations
120683082002Mutations of the BRAF gene in human cancer.2717
211073232010Melanomas acquire resistance to B-RAF(V600E) inhibition by RTK or N-RAS upregulation.818
160798502005BRAFE600-associated senescence-like cell cycle arrest of human naevi.685
168045442006CpG island methylator phenotype underlies sporadic microsatellite instability and is tightly associated with BRAF mutation in colorectal cancer.673
206197392010Effects of KRAS, BRAF, NRAS, and PIK3CA mutations on the efficacy of cetuximab plus chemotherapy in chemotherapy-refractory metastatic colorectal cancer: a retrospective consortium analysis.666
166187172006KRAS mutation status is predictive of response to cetuximab therapy in colorectal cancer.634
240248392013Panitumumab-FOLFOX4 treatment and RAS mutations in colorectal cancer.629
211073202010COT drives resistance to RAF inhibition through MAP kinase pathway reactivation.557
190013202008Wild-type BRAF is required for response to panitumumab or cetuximab in metastatic colorectal cancer.506
190013202008Wild-type BRAF is required for response to panitumumab or cetuximab in metastatic colorectal cancer.506


Enric Domingo

BRAF (v-raf murine sarcoma viral oncogene homolog B1)

Atlas Genet Cytogenet Oncol Haematol. 2020-05-01

Online version:

Historical Card

2004-09-01 BRAF (v-raf murine sarcoma viral oncogene homolog B1) by  Enric Domingo,Simo Schwartz Jr 

Oncologia Molecular i Envelliment, Centre dInvestigacions en Bioqumica i Biologia Molecular (CIBBIM) Hospital Universitari Vall dHebron Passeig Vall dHebron 119-129 Barcelona 08035, Catalonia, Spain