This report describes Noonan syndrome 7 (NS7), which is a subtype of Noonan syndrome; NS7 exhibits autosomal dominant inheritance. The human gene implicated in this disease is BRAF, which encodes one of several RAF serine/threonine-protein kinases that act as links between the membrane-associated RAS GTPases and the MAPK/ERK cascade. There are two additional RAF genes in human, ARAF and RAF1. In Drosophila, there is a single orthologous gene, Dmel\Raf, for which classical amorphic and hypomorphic mutations, RNAi-targeting constructs, and alleles caused by insertional mutagenesis have been generated.
A UAS construct of the human Hsap\BRAF gene carrying a variant implicated in NS7 has been introduced into flies. Variant(s) implicated in human disease tested (as transgenic human gene, BRAF): the W531C variant form has been introduced into flies. Experiments using this variant include assessments of pharmaceutical candidates. Hsap\BRAF has also been used in a fly model of cancer (FBhh0000960).
[updated May 2021 by FlyBase; FBrf0222196]
Noonan syndrome (NS) is an autosomal dominant disorder characterized by short stature, facial dysmorphism, and a wide spectrum of congenital heart defects. The distinctive facial features consist of a broad forehead, hypertelorism, downslanting palpebral fissures, a high-arched palate, and low-set, posteriorly rotated ears. Cardiac involvement is present in up to 90% of patients. Pulmonic stenosis and hypertrophic cardiomyopathy are the most common forms of cardiac disease, but a variety of other lesions are also observed. Additional relatively frequent features include multiple skeletal defects (chest and spine deformities), webbed neck, mental retardation, cryptorchidism, and bleeding diathesis (summary by Tartaglia et al., 2002 pubmed:11992261). [from MIM:163950, 2015.04.14]
Congenital heart disease occurs in 50%-80% of individuals. Pulmonary valve stenosis, often with dysplasia, is the most common heart defect and is found in 20%-50% of individuals. Hypertrophic cardiomyopathy, found in 20%-30% of individuals, may be present at birth or develop in infancy or childhood. [Gene Reviews, Noonan Syndrome, 2020.08.21]
[NOONAN SYNDROME 7; NS7](https://omim.org/entry/613706)
[B-RAF PROTOONCOGENE, SERINE/THREONINE KINASE; BRAF](https://omim.org/entry/164757)
This form of Noonan syndrome (NS7) is caused by heterozygous mutation in the BRAF gene. [from MIM:613706; 2021.05.08]
BRAF 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. [Gene Cards, BRAF; 2021.05.08]
Many to one: 3 human to 1 Drosophila. The three human genes are BRAF, RAF1, and ARAF.
High-scoring ortholog of human BRAF, ARAF, RAF1 (1 Drosophila to 3 human). Dmel\Raf shares 43-47% identity and 56-60% similarity with the human genes.
