Reviewed April 2011
What is the official name of the RAF1 gene?
The official name of this gene is “Raf-1 proto-oncogene, serine/threonine kinase.”
RAF1 is the gene's official symbol. The RAF1 gene is also known by other names, listed below.
What is the normal function of the RAF1 gene?
The RAF1 gene provides instructions for making a protein that is part of a signaling pathway called the RAS/MAPK pathway, which transmits chemical signals from outside the cell to the cell's nucleus. RAS/MAPK signaling helps control the growth and division (proliferation) of cells, the process by which cells mature to carry out specific functions (differentiation), cell movement (migration), and the self-destruction of cells (apoptosis).
The RAF1 gene belongs to a class of genes known as oncogenes. When mutated, oncogenes have the potential to cause normal cells to become cancerous.
How are changes in the RAF1 gene related to health conditions?
- multiple lentigines syndrome - caused by mutations in the RAF1 gene
At least two mutations in the RAF1 gene have been found to cause multiple lentigines syndrome (formerly called LEOPARD syndrome). This condition is characterized by multiple brown skin spots (lentigines), heart defects, short stature, genital abnormalities, hearing loss, and distinctive facial features. These mutations change single protein building blocks (amino acids) in the RAF1 protein. One mutation replaces the amino acid serine with the amino acid leucine at position 257 in the RAF1 protein (written Ser257Leu or S257L). The other mutation replaces the amino acid leucine with the amino acid valine at position 613 in the RAF1 protein (written Leu613Val or L613V).
The known RAF1 gene changes that cause multiple lentigines syndrome are believed to abnormally activate the RAF1 protein, which disrupts the regulation of the RAS/MAPK signaling pathway that controls cell functions such as growth and division. This misregulation can result in the various features of multiple lentigines syndrome.
- Noonan syndrome - caused by mutations in the RAF1 gene
More than 10 mutations causing Noonan syndrome have been identified in the RAF1 gene. These mutations change single amino acids in the RAF1 protein. These changes interrupt the normal processes of the RAF1 protein, causing problems with cell division, apoptosis, cell differentiation, and cell migration. Researchers believe that this disruption in normal cell processes plays a role in the signs and symptoms of Noonan syndrome, specifically cardiac abnormalities. It has been noted that people with Noonan syndrome caused by a RAF1 gene mutation have a greater incidence of heart defects than other people with Noonan syndrome, specifically a condition called hypertrophic cardiomyopathy, which is a thickening of the heart muscle that forces the heart to work harder to pump blood.
- cancers - increased risk from variations of the RAF1 gene
Some gene mutations are acquired during a person's lifetime and are present only in certain cells. These changes are called somatic mutations and are not inherited. Somatic mutations in the RAF1 gene are involved in the development of several types of cancer. These mutations lead to a RAF1 protein that is always active and can direct cells to grow and divide uncontrollably. Studies suggest that RAF1 gene mutations may be found in ovarian, lung, and colorectal cancers. Somatic mutations in the RAF1 gene are a rare cause of cancer.
For reasons that are unclear, inherited mutations in the RAF1 gene do not appear to increase the risk of cancer in people with multiple lentigines syndrome or Noonan syndrome.
Where is the RAF1 gene located?
Cytogenetic Location: 3p25
Molecular Location on chromosome 3: base pairs 12,583,600 to 12,664,200
The RAF1 gene is located on the short (p) arm of chromosome 3 at position 25.
More precisely, the RAF1 gene is located from base pair 12,583,600 to base pair 12,664,200 on chromosome 3.
See How do geneticists indicate the location of a gene? (http://ghr.nlm.nih.gov/handbook/howgeneswork/genelocation) in the Handbook.
Where can I find additional information about RAF1?
You and your healthcare professional may find the following resources about RAF1 helpful.
Educational resources - Information pages
- The Cell: A Molecular Approach (second edition, 2000): Ras, Raf, and the MAP Kinase Pathway (http://www.ncbi.nlm.nih.gov/books/NBK9870/)
- The Cell: A Molecular Approach (second edition, 2000): The Raf Onocgene Protein (http://www.ncbi.nlm.nih.gov/books/NBK9840/?rendertype=figure&id=A2642)
Gene Reviews - Clinical summary
- Gene Review: Noonan Syndrome (http://www.ncbi.nlm.nih.gov/books/NBK1124)
- Gene Review: Noonan Syndrome with Multiple Lentigines (http://www.ncbi.nlm.nih.gov/books/NBK1383)
Genetic Testing Registry - Repository of genetic test information
- GTR: Genetic tests for RAF1 (http://www.ncbi.nlm.nih.gov/gtr/tests/?term=5894%5Bgeneid%5D)
You may also be interested in these resources, which are designed for genetics professionals and researchers.
- PubMed - Recent literature (http://www.ncbi.nlm.nih.gov/pubmed?term=%28RAF1%5BTI%5D%29%20AND%20%28%28Genes%5BMH%5D%29%20OR%20%28Genetic%20Phenomena%5BMH%5D%29%29%20AND%20english%5Bla%5D%20AND%20human%5Bmh%5D%20AND%20%22last%201800%20days%22%5Bdp%5D)
- OMIM - Genetic disorder catalog (http://omim.org/entry/164760)
Research Resources - Tools for researchers
- Atlas of Genetics and Cytogenetics in Oncology and Haematology (http://atlasgeneticsoncology.org/Genes/RAF1ID42032ch3p25.html)
- HGNC Gene Family: Mitogen-activated protein kinase kinase kinases (http://www.genenames.org/cgi-bin/genefamilies/set/654)
- HGNC Gene Symbol Report (http://www.genenames.org/cgi-bin/gene_symbol_report?q=data/hgnc_data.php&hgnc_id=9829)
- NCBI Gene (http://www.ncbi.nlm.nih.gov/gene/5894)
What other names do people use for the RAF1 gene or gene products?
- Oncogene RAF1
- raf proto-oncogene serine/threonine protein kinase
See How are genetic conditions and genes named? (http://ghr.nlm.nih.gov/handbook/mutationsanddisorders/naming) in the Handbook.
What glossary definitions help with understanding RAF1?
amino acid ;
cell division ;
short stature ;
threonine kinase ;
You may find definitions for these and many other terms in the Genetics Home Reference
- Emuss V, Garnett M, Mason C, Marais R. Mutations of C-RAF are rare in human cancer because C-RAF has a low basal kinase activity compared with B-RAF. Cancer Res. 2005 Nov 1;65(21):9719-26. (http://www.ncbi.nlm.nih.gov/pubmed/16266992?dopt=Abstract)
- Kobayashi T, Aoki Y, Niihori T, Cavé H, Verloes A, Okamoto N, Kawame H, Fujiwara I, Takada F, Ohata T, Sakazume S, Ando T, Nakagawa N, Lapunzina P, Meneses AG, Gillessen-Kaesbach G, Wieczorek D, Kurosawa K, Mizuno S, Ohashi H, David A, Philip N, Guliyeva A, Narumi Y, Kure S, Tsuchiya S, Matsubara Y. Molecular and clinical analysis of RAF1 in Noonan syndrome and related disorders: dephosphorylation of serine 259 as the essential mechanism for mutant activation. Hum Mutat. 2010 Mar;31(3):284-94. doi: 10.1002/humu.21187. (http://www.ncbi.nlm.nih.gov/pubmed/20052757?dopt=Abstract)
- McPhillips F, Mullen P, MacLeod KG, Sewell JM, Monia BP, Cameron DA, Smyth JF, Langdon SP. Raf-1 is the predominant Raf isoform that mediates growth factor-stimulated growth in ovarian cancer cells. Carcinogenesis. 2006 Apr;27(4):729-39. Epub 2005 Dec 6. (http://www.ncbi.nlm.nih.gov/pubmed/16332724?dopt=Abstract)
- Mhawech-Fauceglia P, Cheney RT, Schwaller J. Genetic alterations in urothelial bladder carcinoma: an updated review. Cancer. 2006 Mar 15;106(6):1205-16. Review. (http://www.ncbi.nlm.nih.gov/pubmed/16470587?dopt=Abstract)
- NCBI Gene (http://www.ncbi.nlm.nih.gov/gene/5894)
- Pandit B, Sarkozy A, Pennacchio LA, Carta C, Oishi K, Martinelli S, Pogna EA, Schackwitz W, Ustaszewska A, Landstrom A, Bos JM, Ommen SR, Esposito G, Lepri F, Faul C, Mundel P, López Siguero JP, Tenconi R, Selicorni A, Rossi C, Mazzanti L, Torrente I, Marino B, Digilio MC, Zampino G, Ackerman MJ, Dallapiccola B, Tartaglia M, Gelb BD. Gain-of-function RAF1 mutations cause Noonan and LEOPARD syndromes with hypertrophic cardiomyopathy. Nat Genet. 2007 Aug;39(8):1007-12. Epub 2007 Jul 1. (http://www.ncbi.nlm.nih.gov/pubmed/17603483?dopt=Abstract)
- Razzaque MA, Nishizawa T, Komoike Y, Yagi H, Furutani M, Amo R, Kamisago M, Momma K, Katayama H, Nakagawa M, Fujiwara Y, Matsushima M, Mizuno K, Tokuyama M, Hirota H, Muneuchi J, Higashinakagawa T, Matsuoka R. Germline gain-of-function mutations in RAF1 cause Noonan syndrome. Nat Genet. 2007 Aug;39(8):1013-7. Epub 2007 Jul 1. (http://www.ncbi.nlm.nih.gov/pubmed/17603482?dopt=Abstract)
- Romano AA, Allanson JE, Dahlgren J, Gelb BD, Hall B, Pierpont ME, Roberts AE, Robinson W, Takemoto CM, Noonan JA. Noonan syndrome: clinical features, diagnosis, and management guidelines. Pediatrics. 2010 Oct;126(4):746-59. doi: 10.1542/peds.2009-3207. Epub 2010 Sep 27. Review. (http://www.ncbi.nlm.nih.gov/pubmed/20876176?dopt=Abstract)
- Yokoyama T, Takano K, Yoshida A, Katada F, Sun P, Takenawa T, Andoh T, Endo T. DA-Raf1, a competent intrinsic dominant-negative antagonist of the Ras-ERK pathway, is required for myogenic differentiation. J Cell Biol. 2007 Jun 4;177(5):781-93. Epub 2007 May 29. (http://www.ncbi.nlm.nih.gov/pubmed/17535970?dopt=Abstract)
The resources on this site should not be used as a substitute for
professional medical care or advice. Users seeking information about
a personal genetic disease, syndrome, or condition should consult with a qualified
See How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.