ARAF Gene - Serine/Threonine Kinase A-Raf
Comprehensive gene card for ARAF (A-Raf proto-oncogene, serine/threonine kinase) with genomic, transcriptomic, and clinical annotations.
Gene Information Card
| Symbol | ARAF |
|---|---|
| Full Name | A-Raf proto-oncogene, serine/threonine kinase |
| Gene Type | protein-coding |
| Chromosomal Location | Xp11.3 |
| NCBI Gene ID | 369 ncbi.nlm.nih.gov/gene/369 |
| Ensembl ID | ENSG00000078061 |
| UniProt ID | P10398 |
| OMIM ID | 311010 |
| HGNC ID | 646 |
| Aliases | A-Raf, PKS2, ARAF1, RAFA1 |
Description
ARAF (A-Raf proto-oncogene, serine/threonine kinase) is a member of the RAF family of kinases (ARAF, BRAF, RAF1). It encodes a protein that functions in the MAPK/ERK signaling pathway, transducing signals from RAS to MEK. ARAF is involved in cell growth, differentiation, and survival. Mutations in ARAF are associated with various cancers and developmental disorders such as Noonan syndrome and cardiofaciocutaneous syndrome.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Noonan syndrome | Gain-of-function mutations in ARAF lead to increased MAPK pathway activity, causing developmental abnormalities. | ClinVar, OMIM |
| Cardiofaciocutaneous syndrome | Activating ARAF mutations dysregulate RAS-MAPK signaling, resulting in characteristic facial, cardiac, and skin features. | ClinVar, OMIM |
| Lung adenocarcinoma | Somatic mutations (e.g., p.S214A) in ARAF promote oncogenic signaling. | COSMIC, NCBI |
| Melanoma | ARAF amplifications and mutations contribute to MAPK pathway hyperactivation. | COSMIC |
| Colorectal cancer | ARAF mutations and overexpression are implicated in tumor progression. | COSMIC |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 12.5 | Medium |
| Heart | 8.3 | Low |
| Lung | 6.1 | Low |
| Liver | 4.2 | Low |
| Kidney | 7.8 | Low |
| Testis | 15.2 | Medium |
| Spleen | 5.9 | Low |
| Pancreas | 3.1 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK 293 | 14.0 | Embryonic kidney; moderate expression |
| HeLa | 9.5 | Cervical carcinoma; low expression |
| A549 | 7.2 | Lung carcinoma; low expression |
| MCF7 | 6.8 | Breast carcinoma; low expression |
| K562 | 5.1 | Leukemia; low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| p.S214A | Missense | <1% | Gain-of-function; increases kinase activity |
| p.D447V | Missense | <1% | Gain-of-function; associated with Noonan syndrome |
| p.P261S | Missense | <1% | Gain-of-function; cardiofaciocutaneous syndrome |
| p.G361V | Missense | <1% | Likely gain-of-function; reported in cancer |
| p.V222M | Missense | <1% | Uncertain significance; observed in melanoma |
Mutation functional classification
Loss of Function (LOF)
No well-characterized loss-of-function mutations reported in ARAF; most pathogenic variants are gain-of-function.
Gain of Function (GOF)
Yes; missense mutations (e.g., p.S214A, p.D447V) increase kinase activity and MAPK pathway signaling.
Dominant Negative (DN)
Not reported for ARAF.
View complete mutation data：
Gene Ontology (GO)
Pathways
• MAPK signaling pathway (KEGG: hsa04010)
• RAS signaling pathway (KEGG: hsa04014)
• Signaling by Receptor Tyrosine Kinases (Reactome: R-HSA-9006925)
• RAF activation (Reactome: R-HSA-5673001)
Protein Summary
The ARAF protein (UniProt P10398) is a 606-amino-acid serine/threonine kinase with conserved domains: an N-terminal RAS-binding domain (RBD), a cysteine-rich domain (CRD), and a C-terminal kinase domain. It localizes to the cytoplasm and plasma membrane. ARAF is activated by RAS-GTP and phosphorylates MEK1/2. Unlike BRAF, ARAF has lower basal kinase activity but can be potently activated by mutations. Post-translational modifications include phosphorylation at Ser214, Ser299, and Tyr302, which regulate activity and stability.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| ARAF Knockout HEK293 Cell Line | EDJ-KQ221 | Human | 369 | Details Get a Quote |
| ARAF Knockout A-549 Cell Line | EDJ-KQ21180 | Human | 369 | Details Get a Quote |
| ARAF Knockout HCT 116 Cell Line | EDJ-KQ21181 | Human | 369 | Details Get a Quote |
| ARAF Knockout HeLa Cell Line | EDJ-KQ21182 | Human | 369 | Details Get a Quote |
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