BRAF
Chr 7ADB-Raf proto-oncogene, serine/threonine kinase
Also known as: B-RAF1, B-raf, BRAF-1, BRAF1, NS7, RAFB1
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]
Moderate evidence — consider for supplementary testing
4 total gene-disease associations curated
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Highly LoF-intolerant (top ~10% of genes)
Highly missense-constrained (top ~0.1%)
This gene — mechanism propensity
This gene has evidence for multiple mechanisms of pathogenicity (loss-of-function and gain-of-function). Both the Badonyi & Marsh prediction and the broader genomic evidence point to loss-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.
Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.
Literature Evidence
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.
References
ClinVar Variant Classifications
1566 submitted variants in ClinVar
Classification Summary
Curated Variants Distribution
Classified variants from ClinVar · 5 ACMG categories
| Classification | LoF | Missense + Inframe | Non-coding | Synonymous | Total |
|---|---|---|---|---|---|
Pathogenic | 2 | 58 | 0 | 0 | 60 |
Likely Pathogenic | 0 | 69 | 0 | 0 | 69 |
VUS | 50 | 465 | 129 | 17 | 661 |
Likely Benign | 2 | 9 | 275 | 278 | 564 |
Benign | 0 | 4 | 88 | 12 | 104 |
Conflicting | — | 70 | |||
| Total | 54 | 605 | 492 | 307 | 1,528 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →47 pathogenic / likely-pathogenic (of 57) ClinVar copy-number / structural variants overlap BRAF — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →
Protein Context — Lollipop Plot
BRAF · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
Biology of Young Lung Cancer Study: The YOUNG LUNG Study
RECRUITINGA Study of Participants in China With Non-Small-Cell Lung Cancer That is Unable to be Treated With Surgery
ACTIVE NOT RECRUITINGRET-US Study - Ultrasound-Based Prediction of RET Alterations and Lateral-Neck Metastasis in Thyroid Cancer
NOT YET RECRUITINGA Retrospective and Prospective Real-world Study of Molecular Typing in the Treatment of Advanced Thyroid Cancer
RECRUITINGAtezolizumab and Cobimetinib in Treating Patients With Metastatic, Recurrent, or Refractory Non-small Cell Lung Cancer
ACTIVE NOT RECRUITINGObservational Prospective Study of Quality of Life in Unresectable TNM Stage III NSCLC (OBSTINATE)
ACTIVE NOT RECRUITINGDabrafenib and Trametinib for BRAF V600 Mutant Low-Grade Gliomas
RECRUITINGPOTENT - Tepotinib in Combination With Pembrolizumab in NSCLC
ACTIVE NOT RECRUITINGFirst-line Therapy With Nivolumab Plus Ipilimumab in Combination With Chemotherapy for Metatastatic NSCLC (NICReWo Trial)
RECRUITINGPembrolizumab, Dabrafenib, and Trametinib Before Surgery for the Treatment of BRAF-Mutated Anaplastic Thyroid Cancer
ACTIVE NOT RECRUITINGTreatment Strategies and Survival Outcome for Non-small Cell Lung Cancer With Oncogenic Mutation
RECRUITINGTrametinib for Pediatric Neuro-oncology Patients With Refractory Tumor and Activation of the MAPK/ERK Pathway.
ACTIVE NOT RECRUITINGExternal Resources
Links to major genomics databases and tools