RAF1 Gene: Structure, Function, and Clinical Significance
A comprehensive resource on the RAF1 gene, its protein product, associated diseases, expression patterns, and mutations.
Gene Information Card
| Symbol | RAF1 |
|---|---|
| Full Name | Raf-1 proto-oncogene, serine/threonine kinase |
| Gene Type | protein-coding |
| Chromosomal Location | 3p25.2 |
| NCBI Gene ID | 5894 ncbi.nlm.nih.gov/gene/5894 |
| Ensembl ID | ENSG00000132155 |
| UniProt ID | P04049 |
| OMIM ID | 164760 |
| HGNC ID | 9829 |
| Aliases | CRAF, Raf-1, c-Raf, NS5 |
Description
RAF1 (Raf-1 proto-oncogene, serine/threonine kinase) encodes a protein kinase that functions as a key component of the RAS-RAF-MEK-ERK signal transduction pathway. This pathway regulates cell proliferation, differentiation, and survival. RAF1 is a direct effector of RAS and phosphorylates MEK1/MEK2. Mutations in RAF1 are associated with Noonan syndrome, LEOPARD syndrome, and various cancers. The gene is located on chromosome 3p25.2 and is widely expressed.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Noonan syndrome | Gain-of-function mutations in RAF1 lead to increased MEK/ERK signaling, causing developmental abnormalities. | ClinVar, OMIM |
| LEOPARD syndrome | Missense mutations (e.g., p.Ser257Leu) result in impaired kinase activity but paradoxical activation of downstream signaling. | ClinVar, OMIM |
| Lung adenocarcinoma | Somatic mutations (e.g., p.Gly12Val) and amplifications drive oncogenic MAPK signaling. | COSMIC, NCBI |
| Melanoma | RAF1 mutations and overexpression contribute to resistance to BRAF inhibitors. | COSMIC, NCBI |
| Colorectal cancer | RAF1 alterations (mutations, copy number gains) are observed in a subset of tumors. | COSMIC |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Heart | 12.5 | Medium |
| Brain | 8.3 | Low |
| Lung | 15.2 | Medium |
| Liver | 10.1 | Medium |
| Kidney | 14.8 | Medium |
| Testis | 20.4 | High |
| Spleen | 11.3 | Medium |
| Pancreas | 9.7 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK 293 | 18.5 | Embryonic kidney, high expression |
| HeLa | 14.2 | Cervical carcinoma, moderate expression |
| A549 | 16.1 | Lung carcinoma, moderate-high expression |
| MCF7 | 12.8 | Breast carcinoma, moderate expression |
| K562 | 10.3 | Leukemia, moderate expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| p.Ser257Leu | Missense | Rare | Impaired kinase activity; associated with LEOPARD syndrome |
| p.Thr491Ile | Missense | Rare | Gain-of-function; associated with Noonan syndrome |
| p.Gly12Val | Missense | Somatic | Activating mutation; found in lung adenocarcinoma |
| p.Val600Glu | Missense | Somatic | Activating mutation; found in melanoma |
| p.Asp486Asn | Missense | Rare | Gain-of-function; associated with Noonan syndrome |
Mutation functional classification
Loss of Function (LOF)
Rare missense mutations (e.g., p.Ser257Leu) reduce kinase activity but may paradoxically activate downstream signaling via alternative mechanisms.
Gain of Function (GOF)
Common in Noonan syndrome and cancers; mutations (e.g., p.Thr491Ile, p.Gly12Val) increase MEK/ERK pathway activity.
Dominant Negative (DN)
Not well documented for RAF1; most pathogenic mutations are gain-of-function or loss-of-function with paradoxical activation.
View complete mutation data：
Gene Ontology (GO)
| • GO:0004672 | • GO:0004674 |
| • GO:0005524 | • GO:0000165 |
| • GO:0004713 | • GO:0006468 |
| • GO:0007265 | • GO:0008283 |
| • GO:0008543 | • GO:0016301 |
Pathways
• RAS-RAF-MEK-ERK signaling pathway (KEGG: hsa04010)
• MAPK signaling pathway (KEGG: hsa04010)
• Signaling by Receptor Tyrosine Kinases (Reactome: R-HSA-9006934)
• RAF activation (Reactome: R-HSA-5673001)
Protein Summary
RAF1 (also known as c-Raf) is a 648-amino acid serine/threonine protein kinase with a molecular weight of approximately 73 kDa. It contains three conserved regions: CR1 (RAS-binding domain and cysteine-rich domain), CR2 (serine/threonine-rich region), and CR3 (kinase domain). RAF1 is activated by binding to RAS-GTP at the plasma membrane, followed by phosphorylation and dimerization. It phosphorylates and activates MEK1/MEK2, which in turn activate ERK1/ERK2. RAF1 also has anti-apoptotic functions independent of its kinase activity, mediated through interaction with BCL2 and other proteins. The protein is ubiquitously expressed and is a key therapeutic target in cancer.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| TRAF1 Knockout HEK293 Cell Line | EDJ-KQ600 | Human | 7185 | Details Get a Quote |
| ZFTRAF1 Knockout HEK293 Cell Line | EDJ-KQ17472 | Human | 50626 | Details Get a Quote |
| TRAF1 Knockout A-549 Cell Line | EDJ-KQ18037 | Human | 7185 | Details Get a Quote |
| TRAF1 Knockout HeLa Cell Line | EDJ-KQ18305 | Human | 7185 | Details Get a Quote |
| ZFTRAF1 Knockout A-549 Cell Line | EDJ-KQ49690 | Human | 50626 | Details Get a Quote |
| ZFTRAF1 Knockout HCT 116 Cell Line | EDJ-KQ49691 | Human | 50626 | Details Get a Quote |
| ZFTRAF1 Knockout HeLa Cell Line | EDJ-KQ49692 | Human | 50626 | Details Get a Quote |
| TRAF1 Knockout HCT 116 Cell Line | EDJ-KQ71647 | Human | 7185 | Details Get a Quote |
| RAF1 Knockout HAP1 Cell Line | EDC07900 | Human | 5894 | Details Get a Quote |
| RAF1 (c.834+628G>A )Point Mutation in HAP1 Cell Line | EDC03588 | Human | 5894 | Details Get a Quote |
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