BRAF

Chr 7AD

B-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]

GeneReviewsOMIMResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Adenocarcinoma of lung, somaticMIM #211980
Cardiofaciocutaneous syndromeMIM #115150
AD
Colorectal cancer, somaticMIM #114500
LEOPARD syndrome 3MIM #613707
AD
Melanoma, malignant, somaticMIM #155600
Nonsmall cell lung cancer, somaticMIM #211980
Noonan syndrome 7MIM #613706
AD
UniProtFamilial non-Hodgkin lymphoma

Clinical highlights

Gene-disease validity (ClinGen)
Noonan syndrome · ADModerateconsider for supplementary testing4 gene-disease associations curated in total
Interpreting a novel variant
Gain of function is the curated mechanism (Gene2Phenotype), so a variant that simply removes the protein may not be the pathogenic class here — missense variants in functional domains often carry more weight.Curated gene-level mechanism — a prior for triage, not a per-variant call.
12
Active trials
3529
Pubs (1 yr)
P/LP submissions
P/LP missense
0.21
LOEUF· LoF intol.
GOF*
Mechanism· G2P
📖
GeneReview available — BRAF
Authoritative clinical overview · Recommended first read
Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Dual constrained — LoF & missense intolerant
LoF Constraint?
0.21LOEUF
pLI 1.000
Z-score 5.91
OE 0.10 (0.050.21)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint?
3.72Z-score
OE missense 0.49 (0.430.55)
203 obs / 416.7 exp
Constrained

Highly missense-constrained (top ~0.1%)

Observed / Expected Ratios?
LoF OE?0.10 (0.050.21)
00.351.4
Missense OE?0.49 (0.430.55)
00.61.4
Synonymous OE?1.02
01.21.6
LoF obs/exp: 5 / 50.2Missense obs/exp: 203 / 416.7Syn Z: -0.22

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

BRAF · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

VCEP specificationsRASopathyReleased
Specifications ↗Panel ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

Lung CancerTKI ResistanceEGFR Sensitive Mutation

A Single Center, Single Arm Clinical Study on the Treatment of Advanced Non-small Cell Lung Cancer With Positive EGFR Sensitive Mutations and Failed EGFR TKIs With the Combination of Enrotinib and Paclitaxel Monoclonal Antibody

NOT YET RECRUITING
NCT06048315Phase PHASE3Degan LuStarted 2023-09
AnlotinibPenpulimab
Colon CancerPancreas CancerDigestive Cancer

CEND-1 in Combination with Neoadjuvant FOLFIRINOX with or Without Panitumumab

ACTIVE NOT RECRUITING
NCT05121038Phase PHASE1, PHASE2Anup KasiStarted 2021-10-20
CEND-1PanitumumabFolfirinox
Haematological MalignancySolid Tumour

DETERMINE (Determining Extended Therapeutic Indications for Existing Drugs in Rare Molecularly Defined Indications Using a National Evaluation Platform Trial) - Master Screening Protocol

RECRUITING
NCT05722886Phase PHASE2, PHASE3Cancer Research UKStarted 2023-03-01
AlectinibAtezolizumabEntrectinib
Carcinoma, Non-Small-Cell Lung

MYLUNG Consortium Study Protocol 2

ACTIVE NOT RECRUITING
NCT05644808US Oncology ResearchStarted 2020-12-29
Lung Adenocarcinoma

PHOENIX: QL1706 Plus Chemotherapy and Bevacizumab in AGA-Resistant, PD-L1 ≥50% Non-Squamous NSCLC

NOT YET RECRUITING
NCT07416058Phase PHASE2Guangdong Association of Clinical TrialsStarted 2026-01-31
QL1706 (bispecific antibody targeting PD-1 and CLTA-4)
BRAF NP_004324.2:p.V600EMetastatic Colon AdenocarcinomaMetastatic Microsatellite Stable Colorectal Carcinoma

Encorafenib, Cetuximab, and Nivolumab in Treating Patients With Microsatellite Stable, BRAFV600E Mutated Unresectable or Metastatic Colorectal Cancer

ACTIVE NOT RECRUITING
NCT04017650Phase PHASE1, PHASE2M.D. Anderson Cancer CenterStarted 2019-06-14
CetuximabEncorafenibNivolumab
Low-grade GliomaPlexiform NeurofibromaCentral Nervous System Glioma

Trametinib for Pediatric Neuro-oncology Patients With Refractory Tumor and Activation of the MAPK/ERK Pathway.

ACTIVE NOT RECRUITING
NCT03363217Phase PHASE2St. Justine's HospitalStarted 2018-08-16
Trametinib
Non Small Cell Lung CancerEGFR Gene MutationALK Gene Mutation

Treatment Strategies and Survival Outcome for Non-small Cell Lung Cancer With Oncogenic Mutation

RECRUITING
NCT04322890Phase PHASE2Hunan Province Tumor HospitalStarted 2020-04-16
OsimertinibAlectinib 150 MGCrizotinib 250 MG
Non Small Cell Lung Cancer Metastatic

First-line Therapy With Nivolumab Plus Ipilimumab in Combination With Chemotherapy for Metatastatic NSCLC (NICReWo Trial)

RECRUITING
NCT07190677Fondazione IRCCS Policlinico San Matteo di PaviaStarted 2025-01-17
Melanoma

Effects of Anti-PD1 Adjuvant Checkpoint Blockade Immunotherapy on Atypical/Dysplastic Nevi

RECRUITING
NCT06599619John KirkwoodStarted 2025-02-20
Single agent, adjuvant anti-PD1 therapy
GliomaGlioblastoma (GBM)MGMT-Methylated Glioblastoma

STUPP Regimen With or Without Lenvatinib for Newly Diagnosed Glioblastoma With MGMT Promoter Methylation

NOT YET RECRUITING
NCT07754734Phase PHASE2Dongguan People's HospitalStarted 2026-08-10
LenvatinibTMZ (Temozolomide)radiotherapy
Metastatic Colon AdenocarcinomaMetastatic Rectal AdenocarcinomaStage III Colon Cancer AJCC v8

Testing the Addition of Nivolumab to Standard Treatment for Patients With Metastatic or Unresectable Colorectal Cancer That Have a BRAF Mutation

ACTIVE NOT RECRUITING
NCT05308446Phase PHASE2National Cancer Institute (NCI)Started 2022-07-19
CetuximabEncorafenibNivolumab