Aliases for BRAF Gene
- B-Raf Proto-Oncogene, Serine/Threonine Kinase 2 3 5
- BRAF1 2 3 4
- V-Raf Murine Sarcoma Viral Oncogene Homolog B1 3 4
- V-Raf Murine Sarcoma Viral Oncogene Homolog B 2 3
- Serine/Threonine-Protein Kinase B-Raf 3 4
- Proto-Oncogene B-Raf 3 4
- RAFB1 3 4
- B-Raf Proto-Oncogene Serine/Threonine-Protein Kinase (P94) 3
External Ids for BRAF Gene
Previous GeneCards Identifiers for BRAF Gene
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. Oncogenic BRAF mutations are divided into three categories that determine their sensitivity to inhibitors. Class 1 BRAF mutations (V600) are RAS-independent, signal as monomers and are sensitive to current RAF monomer inhibitors. Class 2 BRAF mutations (K601E, K601N, K601T, L597Q, L597V, G469A, G469V, G469R, G464V, G464E, and fusions) are RAS-independent, signaling as constitutive dimers and are resistant to vemurafenib. Such mutants may be sensitive to novel RAF dimer inhibitors or MEK inhibitors. Class 3 BRAF mutations (D287H, V459L, G466V, G466E, G466A, S467L, G469E, N581S, N581I, D594N, D594G, D594A, D594H, F595L, G596D, and G596R) with low or absent kinase activity are RAS-dependent and they activate ERK by increasing their binding to activated RAS and wild-type CRAF. Class 3 BRAF mutations coexist with mutations in RAS or NF1 in melanoma may be treated with MEK inhibitors. In epithelial tumors such as CRC or NSCLC may be effectively treated with combinations that include inhibitors of receptor tyrosine kinase.
GeneCards Summary for BRAF Gene
BRAF (B-Raf Proto-Oncogene, Serine/Threonine Kinase) is a Protein Coding gene. Diseases associated with BRAF include Cardiofaciocutaneous Syndrome 1 and Noonan Syndrome 7. Among its related pathways are RET signaling and G-protein signaling M-RAS regulation pathway. 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.
UniProtKB/Swiss-Prot Summary for BRAF Gene
Protein kinase involved in the transduction of mitogenic signals from the cell membrane to the nucleus (Probable). Phosphorylates MAP2K1, and thereby activates the MAP kinase signal transduction pathway (PubMed:21441910, PubMed:29433126). May play a role in the postsynaptic responses of hippocampal neurons (PubMed:1508179).
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.