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This gene encodes a protein belonging to the RAF family of serine/threonine protein kinases. This protein plays a role in regulating the MAP kinase/ERK signaling pathway, which affects cell division, differentiation, and secretion. Mutations in this gene, most commonly the V600E mutation, are the most frequently identified cancer-causing mutations in melanoma, and have been identified in various other cancers as well, including non-Hodgkin lymphoma, colorectal cancer, thyroid carcinoma, non-small cell lung carcinoma, hairy cell leukemia and adenocarcinoma of lung. Mutations in this gene are also associated with cardiofaciocutaneous, Noonan, and Costello syndromes, which exhibit overlapping phenotypes. A pseudogene of this gene has been identified on the X chromosome. [provided by RefSeq, Aug 2017]
BRAF mutations are found to be recurrent in many cancer types. Of these, the mutation of valine 600 to glutamic acid (V600E) is the most prevalent. V600E has been determined to be an activating mutation, and cells that harbor it, along with other V600 mutations are sensitive to the BRAF inhibitor dabrafenib. It is also common to use MEK inhibition as a substitute for BRAF inhibitors, and the MEK inhibitor trametinib has seen some success in BRAF mutant melanomas. BRAF mutations have also been correlated with poor prognosis in many cancer types, although there is at least one study that questions this conclusion in papillary thyroid cancer.
BRAF (B-Raf Proto-Oncogene, Serine/Threonine Kinase) is a Protein Coding gene. Diseases associated with BRAF include Cardiofaciocutaneous Syndrome 1 and Lung Cancer. Among its related pathways are MAPK-Erk Pathway and RANK Signaling in Osteoclasts. Gene Ontology (GO) annotations related to this gene include calcium ion binding and transferase activity, transferring phosphorus-containing groups. An important paralog of this gene is RAF1.
Raf kinases, a family of three serine/threonine kinases, are part of the Ras-MAPK signaling cascade and phosphorylate MEK. Upon growth factor stimulation, Raf-1 (c-Raf) is activated by GTP-bound Ras and recruited to the cell membrane. This activation process is tightly regulated.
GO ID | Qualified GO term | Evidence | PubMed IDs |
---|---|---|---|
GO:0000166 | nucleotide binding | IEA | -- |
GO:0004672 | protein kinase activity | IDA,IEA | 17563371 |
GO:0004674 | protein serine/threonine kinase activity | IDA,IEA | 19667065 |
GO:0004709 | MAP kinase kinase kinase activity | IEA | -- |
GO:0004713 | protein tyrosine kinase activity | IEA | -- |
GO ID | Qualified GO term | Evidence | PubMed IDs |
---|---|---|---|
GO:0005634 | nucleus | IEA | -- |
GO:0005737 | cytoplasm | IEA | -- |
GO:0005739 | mitochondrion | IBA | 21873635 |
GO:0005829 | cytosol | TAS | -- |
GO:0005886 | plasma membrane | IBA,TAS | -- |
SuperPathway | Contained pathways | ||
---|---|---|---|
1 | RET signaling |
.92
|
.92
|
2 | Common Cytokine Receptor Gamma-Chain Family Signaling Pathways | ||
3 | Negative regulation of FGFR1 signaling | ||
4 | Endometrial cancer |
.36
.32
|
|
5 | IL-2 Pathway |
ErbB Family Pathway
.59
ErbB4 Pathway
.59
Prolactin Signaling
.54
ErbB2-ErbB3 Heterodimers
.49
|
UVC-Induced MAPK Signaling
.44
TREM1 Pathway
.43
IL-4 Pathway
.34
|
GO ID | Qualified GO term | Evidence | PubMed IDs |
---|---|---|---|
GO:0000165 | MAPK cascade | TAS | -- |
GO:0000186 | activation of MAPKK activity | IEA | -- |
GO:0002318 | myeloid progenitor cell differentiation | IEA | -- |
GO:0006468 | protein phosphorylation | IDA,IEA | 17563371 |
GO:0007165 | signal transduction | IEA | -- |
Name | Status | Disease Links | Group | Role | Mechanism of Action | Clinical Trials |
---|---|---|---|---|---|---|
Sorafenib | Approved, Investigational | Pharma | Target, inhibitor, inhibitors | Raf kinases and tyrosine kinases inhibitor, RAF, VEGFR2, and PDGFR-beta inhibitors, Kinase Inhibitors, Vascular endothelial growth factor (VEGF) and VEGF receptor (VEGFR) inhibitors | 762 | |
Dabrafenib | Approved, Investigational | Pharma | Target, antagonist, inhibitor, Inhibition | BRAF kinase inhibitor, Kinase Inhibitors, Mutant BRAF Kinase | 108 | |
Vemurafenib | Approved | Pharma | Target, inhibitor, Biomarker, activator | BRAF kinase inhibitor, B-RAF Inhibitors, Kinase Inhibitors, BRAF inhibitors | 130 | |
Trametinib | Approved | Pharma | inhibitor, Biomarker | MEK 1/2 inhibitor, MEK Inhibitors, Kinase Inhibitors, Mitogen-activated protein/extracellular signal-regulated kinase (MEK) inhibitors | 179 | |
encorafenib | Approved, Investigational | Pharma | Target, inhibitor | 0 |