Gene: RAF1
Alternate names for this Gene: CMD1NN|CRAF|NS5|Raf-1|c-Raf
Gene Summary: This gene is the cellular homolog of viral raf gene (v-raf). The encoded protein is a MAP kinase kinase kinase (MAP3K), which functions downstream of the Ras family of membrane associated GTPases to which it binds directly. Once activated, the cellular RAF1 protein can phosphorylate to activate the dual specificity protein kinases MEK1 and MEK2, which in turn phosphorylate to activate the serine/threonine specific protein kinases, ERK1 and ERK2. Activated ERKs are pleiotropic effectors of cell physiology and play an important role in the control of gene expression involved in the cell division cycle, apoptosis, cell differentiation and cell migration. Mutations in this gene are associated with Noonan syndrome 5 and LEOPARD syndrome 2.
Gene is located in Chromosome: 3
Location in Chromosome : 3p25.2
Description of this Gene: Raf-1 proto-oncogene, serine/threonine kinase
Type of Gene: protein-coding
rs80338796 in
RAF1 gene and
Adenocarcinoma of lung (disorder)
PMID 26619011 2016 Identifying recurrent mutations in cancer reveals widespread lineage diversity and mutational specificity.
rs11713601 in
RAF1 gene and
Body Height
PMID 30595370 2019 Leveraging Polygenic Functional Enrichment to Improve GWAS Power.
rs1553609795 in
RAF1 gene and
CARDIOMYOPATHY, DILATED, 1NN
PMID 24777450 2014 RAF1 mutations in childhood-onset dilated cardiomyopathy.
rs3729931 in
RAF1 gene and
Cardiac Hypertrophy
PMID 21348951 2011 Hypertrophy-associated polymorphisms ascertained in a founder cohort applied to heart failure risk and mortality.
PMID 17603482 2007 Germline gain-of-function mutations in RAF1 cause Noonan syndrome.
PMID 17603483 2007 Gain-of-function RAF1 mutations cause Noonan and LEOPARD syndromes with hypertrophic cardiomyopathy.
rs3729931 in
RAF1 gene and
Cardiomegaly
PMID 21348951 2011 Hypertrophy-associated polymorphisms ascertained in a founder cohort applied to heart failure risk and mortality.
rs121434594 in
RAF1 gene and
Cardiomyopathy, Hypertrophic, Familial
PMID 17603482 2007 Germline gain-of-function mutations in RAF1 cause Noonan syndrome.
PMID 17603483 2007 Gain-of-function RAF1 mutations cause Noonan and LEOPARD syndromes with hypertrophic cardiomyopathy.
rs80338796 in
RAF1 gene and
Colorectal Neoplasms
PMID 26619011 2016 Identifying recurrent mutations in cancer reveals widespread lineage diversity and mutational specificity.
rs80338796 in
RAF1 gene and
Cutaneous Melanoma
PMID 26619011 2016 Identifying recurrent mutations in cancer reveals widespread lineage diversity and mutational specificity.
rs80338796 in
RAF1 gene and
Disorders of both mitral and tricuspid valves
PMID 17603483 2007 Gain-of-function RAF1 mutations cause Noonan and LEOPARD syndromes with hypertrophic cardiomyopathy.
PMID 17603482 2007 Germline gain-of-function mutations in RAF1 cause Noonan syndrome.
rs80338796 in
RAF1 gene and
Downward slant of palpebral fissure
PMID 17603482 2007 Germline gain-of-function mutations in RAF1 cause Noonan syndrome.
PMID 17603483 2007 Gain-of-function RAF1 mutations cause Noonan and LEOPARD syndromes with hypertrophic cardiomyopathy.
rs80338796 in
RAF1 gene and
Dysmorphic features
PMID 21784453 2011 Spectrum of mutations in Noonan syndrome and their correlation with phenotypes.
PMID 24777450 2014 RAF1 mutations in childhood-onset dilated cardiomyopathy.
PMID 23877478 2014 Unique cerebrovascular anomalies in Noonan syndrome with RAF1 mutation.
PMID 20876176 2010 Noonan syndrome: clinical features, diagnosis, and management guidelines.
PMID 16523510 2006 LEOPARD syndrome: clinical diagnosis in the first year of life.
PMID 17603483 2007 Gain-of-function RAF1 mutations cause Noonan and LEOPARD syndromes with hypertrophic cardiomyopathy.
PMID 26446362 2016 Recent advances in RASopathies.
PMID 21396583 2011 Noonan syndrome and clinically related disorders.
PMID 19437094 2009 Noonan syndrome: crossed fused ectopic kidneys and focal segmental glomerulosclerosis-a rare association.
PMID 17603482 2007 Germline gain-of-function mutations in RAF1 cause Noonan syndrome.
PMID 26903553 2016 Growth patterns of patients with Noonan syndrome: correlation with age and genotype.
PMID 20052757 2010 Molecular and clinical analysis of RAF1 in Noonan syndrome and related disorders: dephosphorylation of serine 259 as the essential mechanism for mutant activation.
PMID 23613113 2013 A boy with Burkitt lymphoma associated with Noonan syndrome due to a mutation in RAF1.
PMID 22389993 2012 Two cases of LEOPARD syndrome--RAF1 mutations firstly described in children.
PMID 22826437 2012 Increased BRAF heterodimerization is the common pathogenic mechanism for noonan syndrome-associated RAF1 mutants.
rs80338796 in
RAF1 gene and
Gastric Adenocarcinoma
PMID 26619011 2016 Identifying recurrent mutations in cancer reveals widespread lineage diversity and mutational specificity.
rs80338796 in
RAF1 gene and
Gastroesophageal reflux disease
PMID 17603483 2007 Gain-of-function RAF1 mutations cause Noonan and LEOPARD syndromes with hypertrophic cardiomyopathy.
PMID 17603482 2007 Germline gain-of-function mutations in RAF1 cause Noonan syndrome.
rs80338796 in
RAF1 gene and
Global developmental delay
PMID 17603483 2007 Gain-of-function RAF1 mutations cause Noonan and LEOPARD syndromes with hypertrophic cardiomyopathy.
PMID 17603482 2007 Germline gain-of-function mutations in RAF1 cause Noonan syndrome.
rs80338796 in
RAF1 gene and
Hypertrophic Cardiomyopathy
PMID 17603482 2007 Germline gain-of-function mutations in RAF1 cause Noonan syndrome.
PMID 17603483 2007 Gain-of-function RAF1 mutations cause Noonan and LEOPARD syndromes with hypertrophic cardiomyopathy.
rs80338796 in
RAF1 gene and
Intellectual Disability
PMID 17603483 2007 Gain-of-function RAF1 mutations cause Noonan and LEOPARD syndromes with hypertrophic cardiomyopathy.
PMID 17603482 2007 Germline gain-of-function mutations in RAF1 cause Noonan syndrome.
rs80338796 in
RAF1 gene and
LEOPARD SYNDROME 2
PMID 17603483 2007 Gain-of-function RAF1 mutations cause Noonan and LEOPARD syndromes with hypertrophic cardiomyopathy.
rs80338796 in
RAF1 gene and
LEOPARD Syndrome
PMID 25706034 2015 Neonatal pulmonary arterial hypertension and Noonan syndrome: two fatal cases with a specific RAF1 mutation.
PMID 17603483 2007 Gain-of-function RAF1 mutations cause Noonan and LEOPARD syndromes with hypertrophic cardiomyopathy.
PMID 17603482 2007 Germline gain-of-function mutations in RAF1 cause Noonan syndrome.
PMID 20052757 2010 Molecular and clinical analysis of RAF1 in Noonan syndrome and related disorders: dephosphorylation of serine 259 as the essential mechanism for mutant activation.
PMID 19953625 2010 Tumor spectrum in children with Noonan syndrome and SOS1 or RAF1 mutations.
PMID 19933846 2010 Impact of feedback phosphorylation and Raf heterodimerization on normal and mutant B-Raf signaling.
rs80338796 in
RAF1 gene and
Multiple congenital anomalies
PMID 23613113 2013 A boy with Burkitt lymphoma associated with Noonan syndrome due to a mutation in RAF1.
PMID 22826437 2012 Increased BRAF heterodimerization is the common pathogenic mechanism for noonan syndrome-associated RAF1 mutants.
PMID 17603483 2007 Gain-of-function RAF1 mutations cause Noonan and LEOPARD syndromes with hypertrophic cardiomyopathy.
PMID 21784453 2011 Spectrum of mutations in Noonan syndrome and their correlation with phenotypes.
PMID 22389993 2012 Two cases of LEOPARD syndrome--RAF1 mutations firstly described in children.
PMID 17603482 2007 Germline gain-of-function mutations in RAF1 cause Noonan syndrome.
PMID 19437094 2009 Noonan syndrome: crossed fused ectopic kidneys and focal segmental glomerulosclerosis-a rare association.
PMID 16523510 2006 LEOPARD syndrome: clinical diagnosis in the first year of life.
PMID 21396583 2011 Noonan syndrome and clinically related disorders.
PMID 20876176 2010 Noonan syndrome: clinical features, diagnosis, and management guidelines.
PMID 26446362 2016 Recent advances in RASopathies.
PMID 26903553 2016 Growth patterns of patients with Noonan syndrome: correlation with age and genotype.
PMID 23877478 2014 Unique cerebrovascular anomalies in Noonan syndrome with RAF1 mutation.
PMID 20052757 2010 Molecular and clinical analysis of RAF1 in Noonan syndrome and related disorders: dephosphorylation of serine 259 as the essential mechanism for mutant activation.
PMID 24777450 2014 RAF1 mutations in childhood-onset dilated cardiomyopathy.
rs80338796 in
RAF1 gene and
Muscle hypotonia
PMID 21784453 2011 Spectrum of mutations in Noonan syndrome and their correlation with phenotypes.
PMID 26903553 2016 Growth patterns of patients with Noonan syndrome: correlation with age and genotype.
PMID 24777450 2014 RAF1 mutations in childhood-onset dilated cardiomyopathy.
PMID 26446362 2016 Recent advances in RASopathies.
PMID 22826437 2012 Increased BRAF heterodimerization is the common pathogenic mechanism for noonan syndrome-associated RAF1 mutants.
PMID 23613113 2013 A boy with Burkitt lymphoma associated with Noonan syndrome due to a mutation in RAF1.
PMID 22389993 2012 Two cases of LEOPARD syndrome--RAF1 mutations firstly described in children.
PMID 16523510 2006 LEOPARD syndrome: clinical diagnosis in the first year of life.
PMID 20876176 2010 Noonan syndrome: clinical features, diagnosis, and management guidelines.
PMID 23877478 2014 Unique cerebrovascular anomalies in Noonan syndrome with RAF1 mutation.
PMID 17603483 2007 Gain-of-function RAF1 mutations cause Noonan and LEOPARD syndromes with hypertrophic cardiomyopathy.
PMID 21396583 2011 Noonan syndrome and clinically related disorders.
PMID 19437094 2009 Noonan syndrome: crossed fused ectopic kidneys and focal segmental glomerulosclerosis-a rare association.
PMID 17603482 2007 Germline gain-of-function mutations in RAF1 cause Noonan syndrome.
PMID 20052757 2010 Molecular and clinical analysis of RAF1 in Noonan syndrome and related disorders: dephosphorylation of serine 259 as the essential mechanism for mutant activation.
rs397516830 in
RAF1 gene and
NOONAN SYNDROME 3
PMID 22821648 2012 Prenatal diagnosis of hypoplastic left heart syndrome associated with Noonan Syndrome and de novo RAF1 mutation.
rs121434594 in
RAF1 gene and
Noonan Syndrome
PMID 17603487 2007 Selective loading of high-affinity peptides onto major histocompatibility complex class I molecules by the tapasin-ERp57 heterodimer.
PMID 17603482 2007 Germline gain-of-function mutations in RAF1 cause Noonan syndrome.
PMID 23885229 2013 Noonan syndrome: comparing mutation-positive with mutation-negative dutch patients.
PMID 17603486 2007 Mast cell lineage diversion of T lineage precursors by the essential T cell transcription factor GATA-3.
PMID 17603483 2007 Gain-of-function RAF1 mutations cause Noonan and LEOPARD syndromes with hypertrophic cardiomyopathy.
PMID 20683980 2010 Noonan syndrome associated with both a new Jnk-activating familial SOS1 and a de novo RAF1 mutations.
PMID 19020799 2008 PTPN11, SOS1, KRAS, and RAF1 gene analysis, and genotype-phenotype correlation in Korean patients with Noonan syndrome.
PMID 24732797 2014 RASSF1A inactivation unleashes a tumor suppressor/oncogene cascade with context-dependent consequences on cell cycle progression.
PMID 20052757 2010 Molecular and clinical analysis of RAF1 in Noonan syndrome and related disorders: dephosphorylation of serine 259 as the essential mechanism for mutant activation.
PMID 12675918 2003 Protein kinase and protein phosphatase expression in the central nervous system of G93A mSOD over-expressing mice.
PMID 23321623 2013 Prenatal diagnostic testing of the Noonan syndrome genes in fetuses with abnormal ultrasound findings.
PMID 17603484 2007 Common variants in WFS1 confer risk of type 2 diabetes.
PMID 17603485 2007 Two variants on chromosome 17 confer prostate cancer risk, and the one in TCF2 protects against type 2 diabetes.
PMID 25862627 2015 External ear anomalies and hearing impairment in Noonan Syndrome.
PMID 26266034 2015 A Novel Noonan Syndrome RAF1 Mutation: Lethal Course in a Preterm Infant.
PMID 11933072 2002 Mutations in conserved regions 1, 2, and 3 of Raf-1 that activate transforming activity.
PMID 17603488 2007 Redox regulation of peptide receptivity of major histocompatibility complex class I molecules by ERp57 and tapasin.
PMID 12077328 2002 14-3-3 antagonizes Ras-mediated Raf-1 recruitment to the plasma membrane to maintain signaling fidelity.
PMID 1760348 1992 Downgrading of arts-centered education in state schools.
PMID 29084544 2017 Targeted/exome sequencing identified mutations in ten Chinese patients diagnosed with Noonan syndrome and related disorders.
PMID 23877478 2014 Unique cerebrovascular anomalies in Noonan syndrome with RAF1 mutation.
PMID 29493581 2018 ClinGen's RASopathy Expert Panel consensus methods for variant interpretation.
PMID 25706034 2015 We present two infants with Noonan syndrome and an identical RAF1 mutation, p.Ser257Leu (c.770C>T), who developed severe pulmonary arterial hypertension (PAH) that proved to be fatal.
PMID 22389993 2012 Two cases of LEOPARD syndrome--RAF1 mutations firstly described in children.
PMID 24775816 2013 LEOPARD syndrome: a variant of Noonan syndrome strongly associated with hypertrophic cardiomyopathy.
PMID 17603489 2007 A GaN bulk crystal with improved structural quality grown by the ammonothermal method.
PMID 19933846 2010 Impact of feedback phosphorylation and Raf heterodimerization on normal and mutant B-Raf signaling.
PMID 19953625 2010 Tumor spectrum in children with Noonan syndrome and SOS1 or RAF1 mutations.
PMID 22826437 2012 Increased BRAF heterodimerization is the common pathogenic mechanism for noonan syndrome-associated RAF1 mutants.
rs121434594 in
RAF1 gene and
Noonan Syndrome 5
PMID 20683980 2010 Noonan syndrome associated with both a new Jnk-activating familial SOS1 and a de novo RAF1 mutations.
PMID 17603482 2007 Germline gain-of-function mutations in RAF1 cause Noonan syndrome.
PMID 20876176 2010 Noonan syndrome: clinical features, diagnosis, and management guidelines.
PMID 17603483 2007 Gain-of-function RAF1 mutations cause Noonan and LEOPARD syndromes with hypertrophic cardiomyopathy.
rs80338796 in
RAF1 gene and
Nystagmus
PMID 17603482 2007 Germline gain-of-function mutations in RAF1 cause Noonan syndrome.
PMID 17603483 2007 Gain-of-function RAF1 mutations cause Noonan and LEOPARD syndromes with hypertrophic cardiomyopathy.
rs80338796 in
RAF1 gene and
Pediatric failure to thrive
PMID 17603483 2007 Gain-of-function RAF1 mutations cause Noonan and LEOPARD syndromes with hypertrophic cardiomyopathy.
PMID 17603482 2007 Germline gain-of-function mutations in RAF1 cause Noonan syndrome.
rs80338796 in
RAF1 gene and
Polyhydramnios
PMID 17603483 2007 Gain-of-function RAF1 mutations cause Noonan and LEOPARD syndromes with hypertrophic cardiomyopathy.
PMID 17603482 2007 Germline gain-of-function mutations in RAF1 cause Noonan syndrome.
rs5746193 in
RAF1 gene and
Red Blood Cell Count measurement
PMID 30595370 2019 Leveraging Polygenic Functional Enrichment to Improve GWAS Power.
rs80338796 in
RAF1 gene and
Relative macrocephaly
PMID 17603482 2007 Germline gain-of-function mutations in RAF1 cause Noonan syndrome.
PMID 17603483 2007 Gain-of-function RAF1 mutations cause Noonan and LEOPARD syndromes with hypertrophic cardiomyopathy.
rs2290159 in
RAF1 gene and
Serum total cholesterol measurement
PMID 20686565 2010 Biological, clinical and population relevance of 95 loci for blood lipids.
PMID 24097068 2013 Discovery and refinement of loci associated with lipid levels.
rs80338796 in
RAF1 gene and
Short stature
PMID 17603483 2007 Gain-of-function RAF1 mutations cause Noonan and LEOPARD syndromes with hypertrophic cardiomyopathy.
PMID 17603482 2007 Germline gain-of-function mutations in RAF1 cause Noonan syndrome.
rs80338796 in
RAF1 gene and
Ventricular Septal Defects
PMID 17603483 2007 Gain-of-function RAF1 mutations cause Noonan and LEOPARD syndromes with hypertrophic cardiomyopathy.
PMID 17603482 2007 Germline gain-of-function mutations in RAF1 cause Noonan syndrome.
rs1057519815 in
RAF1 gene and
melanoma
PMID 23737487 2013 C-RAF mutations confer resistance to RAF inhibitors.