BRAF Gene: Function, Mutations, and Associated Diseases
A comprehensive guide to the BRAF gene, its protein product, signaling pathways, clinical significance, and mutation landscape.
Gene Information Card
| Symbol | BRAF |
|---|---|
| Full Name | B-Raf proto-oncogene, serine/threonine kinase |
| Gene Type | Protein coding |
| Chromosomal Location | 7q34 |
| NCBI Gene ID | 673 ncbi.nlm.nih.gov/gene/673 |
| Ensembl ID | ENSG00000157764 |
| UniProt ID | P15056 |
| OMIM ID | 164757 |
| HGNC ID | 1097 |
| Aliases | B-RAF, BRAF1, RAFB1, NS7 |
Description
The BRAF gene encodes a serine/threonine kinase that is a critical component of the RAS-RAF-MEK-ERK (MAPK) signaling pathway, which regulates cell division, differentiation, and secretion. Somatic mutations in BRAF, particularly the V600E substitution, are among the most common oncogenic drivers in human cancers, including melanoma, colorectal cancer, and thyroid cancer. Germline mutations cause cardio-facio-cutaneous syndrome and other RASopathies. BRAF inhibitors (e.g., vemurafenib, dabrafenib) are used in targeted therapy for BRAF-mutant tumors.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Melanoma | Activating mutations (V600E) constitutively activate MAPK signaling, promoting proliferation and survival. | COSMIC, ClinVar |
| Colorectal cancer | V600E mutation leads to constitutive kinase activity, driving tumorigenesis; associated with poor prognosis. | COSMIC, ClinVar |
| Thyroid cancer (papillary) | V600E mutation is frequent and correlates with aggressive features and recurrence. | COSMIC, ClinVar |
| Non-small cell lung cancer | BRAF mutations (V600E and non-V600) activate MAPK pathway; targeted therapy approved. | COSMIC, ClinVar |
| Cardio-facio-cutaneous syndrome | Germline mutations (e.g., Q257R) cause dysregulation of RAS-MAPK signaling during development. | OMIM, ClinVar |
| Langerhans cell histiocytosis | Recurrent BRAF V600E mutations found in lesions, activating MAPK pathway. | COSMIC, ClinVar |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 12.6 | Medium |
| Thyroid | 10.2 | Medium |
| Lung | 8.5 | Low |
| Colon | 7.9 | Low |
| Skin | 6.8 | Low |
| Testis | 5.4 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| A549 (lung) | 15.3 | High expression |
| MCF7 (breast) | 12.1 | Medium |
| HeLa (cervical) | 10.8 | Medium |
| HepG2 (liver) | 9.2 | Low |
| K562 (leukemia) | 7.5 | Low |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| V600E | Missense | ~50% in melanoma; 8-10% in solid tumors | Constitutive kinase activation, increased MEK/ERK signaling |
| V600K | Missense | 5-10% of BRAF-mutant melanomas | Similar to V600E, but with different clinical features |
| G469A | Missense | Rare (<1%) | Elevated kinase activity, oncogenic |
| D594G | Missense | Rare (<1%) | Kinase-impaired, but can signal via CRAF dimerization |
| K601E | Missense | Rare (<1%) | Activating, seen in some cancers |
Mutation functional classification
Loss of Function (LOF)
Kinase-dead mutations (e.g., D594G) reduce BRAF kinase activity but can still promote tumorigenesis through paradoxical activation of CRAF and MAPK signaling.
Gain of Function (GOF)
Class I mutations (e.g., V600E) result in constitutive kinase activity independent of RAS, driving uncontrolled cell proliferation.
Dominant Negative (DN)
Some BRAF mutations (e.g., G466E) can act as dominant-negative inhibitors of wild-type BRAF, impairing normal signaling.
View complete mutation data：
Gene Ontology (GO)
| • protein serine/threonine kinase activity | • MAP kinase kinase kinase activity |
| • ATP binding | • signal transduction |
| • cell proliferation | • regulation of cell cycle |
| • apoptosis |
Pathways
• MAPK signaling pathway
• RAS-RAF-MEK-ERK cascade
• VEGF signaling pathway
• Fc epsilon RI signaling pathway
• T cell receptor signaling pathway
Protein Summary
The BRAF protein is a 766-amino acid serine/threonine kinase with three conserved domains: the RAS-binding domain (RBD), the cysteine-rich domain (CRD), and the kinase domain. In the inactive state, BRAF is autoinhibited by intramolecular interactions. Upon RAS activation, BRAF translocates to the membrane, dimerizes, and phosphorylates MEK1/2, which then activates ERK1/2. The V600E mutation in the activation segment disrupts the autoinhibitory interaction, leading to constitutive kinase activity. BRAF is a key therapeutic target; inhibitors such as vemurafenib and dabrafenib selectively block the mutant kinase, while MEK inhibitors (trametinib) are used in combination to enhance efficacy and reduce resistance.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| BRAF Knockout HEK293 Cell Line | EDJ-KQ17804 | Human | 673 | Details Get a Quote |
| BRAF Knockout HCT 116 Cell Line | EDJ-KQ18183 | Human | 673 | Details Get a Quote |
| BRAF Knockout A-549 Cell Line | EDC07532 | Human | 673 | Details Get a Quote |
| BRAF Knockout HeLa Cell Line | EDJ-KQ19077 | Human | 673 | Details Get a Quote |
| BRAF (p.G643=) Point Mutation in HAP1 Cell Line | EDC03413 | Human | 673 | Details Get a Quote |
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