BRAF
  • 1
    Haplo
    Score
  • 0
    Triplo
    Score

Gene Facts External Data Attribution

HGNC Symbol
BRAF (HGNC:1097) HGNC Entrez Ensembl OMIM UCSC Uniprot GeneReviews LOVD LSDB ClinVar
HGNC Name
B-Raf proto-oncogene, serine/threonine kinase
Gene type
protein-coding gene
Locus type
gene with protein product
Previous symbols
No previous names found
Alias symbols
BRAF1, BRAF-1
%HI
8.98(Read more about the DECIPHER Haploinsufficiency Index)
pLI
1(Read more about gnomAD pLI score)
LOEUF
0.24(Read more about gnomAD LOEUF score)
Cytoband
7q34
Genomic Coordinates
GRCh37/hg19: chr7:140413128-140624729 NCBI Ensembl UCSC
GRCh38/hg38: chr7:140713328-140924929 NCBI Ensembl UCSC
MANE Select Transcript
NM_004333.6 ENST00000646891.2 (Read more about MANE Select)
MANE Plus Clinical Transcript(s)
NM_001374258.1 ENST00000644969.2 (Read more about MANE Plus Clinical)
Function
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). Phosphorylates PFKFB2 (PubMed:36402789). May play a role in the postsynaptic responses of hippocampal neurons (PubMed:1508179). {ECO:0000269|PubMed:1508179, ECO:0000269|PubMed:21441910, ECO:0000269|PubMed:29433126, ECO:0000269|PubMed:36402789, ECO:0000305}. (Source: Uniprot)

Dosage Sensitivity Summary (Gene)

Dosage ID:
ISCA-3165
ClinGen Curation ID:
CCID:006758
Curation Status:
Complete
Issue Type:
Dosage Curation - Gene
Haploinsufficiency:
Little Evidence for Haploinsufficiency (1)
Read full report...
Triplosensitivity:
No Evidence for Triplosensitivity (0)
Read full report...
Last Evaluated:
08/04/2014

Haploinsufficiency (HI) Score Details

HI Score:
1
HI Evidence Strength:
Little Evidence for Haploinsufficiency (Disclaimer)
HI Evidence:
  • PUBMED: 21862832
    Yu and Graf (2011) report a patient with a history of oligohydramnios, normal birth weight, feeding difficulties and failure to thrive, small hyperpigmented macules, sparse hair, skeletal anomalies, seizures, profound intellectual disability, and hypotonia. The authors note that many of the features present in this patient are not consistent with Cardiofacialcutaneous syndrome (cause by gain of function missense mutations in BRAF). Chromosomal microarray detected a 93 kilobase intragenic deletion in BRAF. Parental specimens were not available for testing. No other genetic studies (other than a normal karyotype) were reported. The authors suggest haploinsufficiency of BRAF as an explanation for the patient's features. Functional studies were not done but, if a truncated protein were stable, it would lack all domains necessary for upstream or downstream activation within the RAS-MAPK pathway and would not be able to heterodimerize.
HI Evidence Comments:
Heterozygous gain of function missense mutations and rare in-frame deletions which lead to elevated kinase activity are a cause of Cardiofacialcutaneous (CFC) syndrome, LEOPARD syndrome, and Noonan syndrome. Some missense mutations can lead to reduced kinase activity, measured by luciferase assays using an ELK-dependent vector (PMID:16474404), and reduced phosphorylation of downstream effectors in transfected cells (PMID:18470943). Yu and Graf (2011) discuss this phenomenon as possible evidence that deletion of BRAF could lead to a viable, abnormal phenotype in human. However, Moretti, et al., 2009 (PMID:19735675) demonstrated that missense mutants, transfected into HEK293T cells, which have reduced kinase activity, are able to heterodimerize with C-Raf and induce its transactivation. Therefore, the functional effects of these BRAF missense mutations are still being elucidated and it is not clear whether a deletion of BRAF might lead to disruption or dysregulation of the RAS-MAPK pathway. BRAF mutations, including point mutations, deletions, and duplications, are frequently found as acquired abnormalities in a variety of tumors.

Triplosensitivity (TS) Score Details

TS Score:
0
TS Evidence Strength:
No Evidence for Triplosensitivity (Disclaimer)
TS Evidence Comments:
While there are rare reports of large duplications of 7q that include BRAF in individuals with a variety of congenital abnormalities and other cytogenetic abnormalities (PMIDs: 22161098, 22482977, 19838731, 2248294, 2319577), to our knowledge, congenital focal whole gene duplications of BRAF have not been reported in the literature. BRAF mutations, including point mutations, deletions, and duplications, are frequently found as acquired abnormalities in a variety of tumors.

Genomic View

Select assembly: (NC_000007.13) (NC_000007.14)