Aliases: BRAF1, BRAF-1.
BRAF (B-Raf proto-oncogene, serine/threonine kinase) is named by 26 disorder entries.
ai-gene-review gives BRAF's core molecular functions as MAP kinase kinase kinase activity; and protein serine/threonine kinase activity, acting in MAPK cascade; and positive regulation of ERK1 and ERK2 cascade. The KB's BRAF nodes share MAPK cascade with those core functions.
10 entries type BRAF as a somatic driver, among them BRAF V600 Mutant Melanoma; Langerhans Cell Histiocytosis; Pilocytic Astrocytoma; and Anaplastic Thyroid Carcinoma. In Pilocytic Astrocytoma the gene sits on BRAF Fusion Oncogene Formation; Constitutive MAPK Cascade Activation; and Oncogene-Induced Senescence. Nodes naming BRAF conform to rtk_grb2_signaling_adaptation; senescence_tumor_suppression; and sustaining_proliferative_signaling.
The entries named for a BRAF mutation record the gene differently. BRAF V600 Mutant Melanoma and BRAF V600E-Mutant Non-Small Cell Lung Cancer type it somatic driver and somatic driver, each with a dedicated driver node such as Somatic BRAF p.Val600Glu Driver. BRAF V600E-Mutant Colorectal Cancer and BRAF-Mutant Papillary Thyroid Cancer leave it untyped and untyped, although the colorectal entry does name the gene on 1 node, BRAF V600E Constitutive Activation, while the thyroid entry names it on 0.
Two entries type BRAF as causative: Cardiofaciocutaneous Syndrome; and Cushing Disease. Neither record gives a variant origin (Cardiofaciocutaneous Syndrome; and Cushing Disease), so nothing in the KB that a claim can check says whether these are germline or somatic; the Cushing Disease entry's prose describes its BRAF variant as somatic, which its genetic record does not yet carry. ClinGen rates BRAF definitive for cardiofaciocutaneous syndrome. For the Noonan Syndrome entry it has two assertions, matched through the entry's own term and its subtype for Noonan syndrome with multiple lentigines: limited and moderate.
Of the disorders that name BRAF,
14
have a genetic record with no relationship_type. The entries ClinGen
supports BRAF for that do not type it are
Noonan Syndrome.
Underlined values are claims re-computed from the knowledge base each time this page is built. The tables below are the source of truth.
BRAF encodes a RAF-family serine/threonine protein kinase (EC 2.7.11.1) that is the canonical mitogen-activated protein kinase kinase kinase (MAP3K) of the RAS-RAF-MEK-ERK signaling cascade. In quiescent cells BRAF is autoinhibited by an intramolecular interaction between its N-terminal regulatory region and the C-terminal kinase domain. Mitogenic stimulation generates GTP-loaded RAS, which binds the BRAF RAS-binding domain (RBD), relieves autoinhibition, and recruits BRAF to the plasma membrane. Activation requires side-to-side dimerization — BRAF homodimers and, most potently, BRAF-RAF1 (CRAF) heterodimers — stabilized by 14-3-3 proteins and the HSP90/CDC37 chaperone system. Activated BRAF phosphorylates and activates MAP2K1/MAP2K2 (MEK1/MEK2), the committed step that propagates mitogenic signaling through ERK1/ERK2 to control proliferation, differentiation and survival. BRAF localizes to the cytoplasm/cytosol and to the plasma membrane in its active RAS-bound state. It is a major oncogenic driver: the V600E activating mutation, which renders the kinase constitutively active as a RAS-independent monomer, is recurrent in melanoma, papillary thyroid carcinoma, colorectal cancer, hairy-cell leukemia and other tumors, and germline BRAF mutations cause cardiofaciocutaneous syndrome.
Relationship is the entry's genetic[].relationship_type. untyped means the entry has a genetic record for the gene but does not type it; its free-text association is shown instead.
| Disorder | Relationship | Where the gene appears |
|---|---|---|
| Ameloblastoma | somatic driver somatic |
mechanism: Somatic RTK-RAS-MAPK Driver Alterations
|
| Anaplastic Thyroid Carcinoma | somatic driver somatic |
mechanism: MAPK-Activating Truncal Driver Alteration
|
| BRAF V600 Mutant Melanoma | somatic driver somatic |
mechanism: Somatic BRAF Codon-600 Driver
animal model: Danio rerio; Mus musculus
|
| BRAF V600E-Mutant Non-Small Cell Lung Cancer | somatic driver somatic |
mechanism: Somatic BRAF p.Val600Glu Driver
animal model: Mus musculus
|
| Brain arteriovenous malformation | somatic driver somatic | |
| Cardiofaciocutaneous Syndrome | causative |
mechanism: B-Raf Kinase Dysregulation by Germline BRAF Variants
subtype: CFC1
scoped to subtype: CFC1
|
| Cushing Disease | causative | |
| Langerhans Cell Histiocytosis | somatic driver somatic | |
| Mixed Neuronal-Glial Tumor | somatic driver somatic |
mechanism: MAPK Pathway Activation
|
| Ocular Melanoma | somatic driver somatic |
mechanism: UV-Associated BRAF/NRAS/NF1 Driver Activation
subtype: Conjunctival Melanoma
scoped to subtype: Conjunctival Melanoma
|
| Pilocytic Astrocytoma | somatic driver somatic |
mechanism: BRAF Fusion Oncogene Formation; Constitutive MAPK Cascade Activation; Oncogene-Induced Senescence
|
| Pseudomyxoma Peritonei | somatic driver somatic | |
| BRAF V600E-Mutant Colorectal Cancer |
untyped
Somatic Activating Mutation
somatic
gain of function
|
mechanism: BRAF V600E Constitutive Activation
|
| BRAF-Mutant Papillary Thyroid Cancer |
untyped
Somatic Activating Mutations
|
|
| Colon Adenocarcinoma |
untyped
Somatic activating mutation
|
|
| Craniopharyngioma |
untyped
Somatic BRAF V600E mutation in papillary craniopharyngioma
|
mechanism: BRAF V600E MAPK PCP Tumor Signaling
|
| Cutaneous Melanoma |
untyped
Somatic activating mutation
|
|
| Erdheim-Chester Disease |
untyped
Associated
|
|
| Glomus Tumor | untyped somatic |
mechanism: Constitutive Mitogenic Pathway Activation
|
| Hairy Cell Leukemia |
untyped
Defining somatic driver
|
|
| Melanoma_in_Congenital_Melanocytic_Nevus |
untyped
Mutations
somatic
|
mechanism: Genetic Mutations
|
| MSI-High Colorectal Cancer |
untyped
Somatic Activating Mutation (Sporadic MSI-H)
|
|
| Noonan Syndrome |
untyped
Pathogenic Variants
|
mechanism: Additional RAS-MAPK Signal-Amplifying Variants
subtype: NS7
scoped to subtype: NS7
|
| Noonan Syndrome with Multiple Lentigines |
untyped
Pathogenic Variants
|
mechanism: RAF1/BRAF Kinase Gain-of-Function
subtype: LPRD3
|
| Papillary Thyroid Carcinoma |
untyped
Somatic Activating Mutations
|
|
| Pleuropulmonary Blastoma |
untyped
Occasional Somatic Activating Mutation
|
mechanism: RAS Pathway Activation
|
An entry matches when ClinGen's MONDO disease is the entry's own disease term, a subtype term, or an exact-match mapping. An amber status marks an entry ClinGen supports the gene for (Definitive, Strong or Moderate) whose own record does not type it. A Limited, Disputed or Refuted tier on such an entry is not a gap.
| ClinGen disease | MOI | Classification | dismech entry |
|---|---|---|---|
| Noonan syndrome with multiple lentigines MONDO:0007893 | AD | Limited 2018-07-24 |
Noonan Syndrome
untyped
|
| Costello syndrome MONDO:0009026 | AD | Disputed 2018-07-24 |
Costello Syndrome
not named
|
| cardiofaciocutaneous syndrome MONDO:0015280 | AD | Definitive 2018-07-24 |
Cardiofaciocutaneous Syndrome
causative
|
| Noonan syndrome MONDO:0018997 | AD | Moderate 2018-07-24 |
Noonan Syndrome
untyped
|
Identity from HGNC (snapshot 2026-10-01). Page layers are described in the gene pages documentation.