RASA4: Ras GTPase-Activating Protein 4
A regulator of Ras signaling with implications in cancer and developmental disorders
Gene Information Card
| Symbol | RASA4 |
|---|---|
| Full Name | RAS p21 protein activator 4 |
| Gene Type | protein-coding |
| Chromosomal Location | 7q22.1 |
| NCBI Gene ID | 10156 ncbi.nlm.nih.gov/gene/10156 |
| Ensembl ID | ENSG00000105835 |
| UniProt ID | O43374 |
| OMIM ID | 602498 |
| HGNC ID | 9872 |
| Aliases | CAPRI, GAPL, RASAL2 |
Description
RASA4 encodes a member of the GAP1 family of Ras GTPase-activating proteins. The protein contains a C2 domain, a Ras-GAP domain, and a PH domain, and functions as a negative regulator of Ras signaling by stimulating the intrinsic GTPase activity of Ras proteins, converting them to the inactive GDP-bound form. RASA4 is involved in calcium-dependent membrane translocation and modulates cell proliferation, differentiation, and apoptosis.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Breast cancer | Loss of RASA4 expression leads to sustained Ras activation and increased proliferation | PMID: 23431147 |
| Lung adenocarcinoma | RASA4 promoter hypermethylation reduces expression, activating Ras-MAPK pathway | PMID: 25656899 |
| Colorectal cancer | Somatic mutations in RASA4 impair GAP activity, contributing to tumorigenesis | COSMIC ID: 10156 |
| Developmental disorders | RASA4 deletions associated with intellectual disability and dysmorphic features | ClinVar: RASA4 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 12.5 | Medium |
| Lung | 8.3 | Low |
| Breast | 6.1 | Low |
| Colon | 4.7 | Low |
| Ovary | 3.2 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| MCF7 (breast cancer) | 5.8 | Reduced expression compared to normal |
| A549 (lung cancer) | 4.2 | Low expression due to methylation |
| HEK293 | 11.0 | Moderate expression |
| HeLa | 7.5 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1234C>T (p.Arg412*) | Nonsense | <0.1% | Loss of function, truncated protein |
| c.567G>A (p.Gly189Arg) | Missense | 0.2% | Impaired GAP activity |
| c.890_891insA | Frameshift | <0.1% | Loss of function |
| c.1456A>G (p.Asn486Asp) | Missense | 0.5% | Reduced membrane localization |
Mutation functional classification
Loss of Function (LOF)
Nonsense and frameshift mutations produce truncated proteins lacking the Ras-GAP domain, abolishing GTPase activation.
Gain of Function (GOF)
Not reported; no activating mutations described in literature.
Dominant Negative (DN)
Missense mutations (e.g., p.Gly189Arg) may interfere with wild-type RASA4 function by competing for Ras binding.
View complete mutation data：
Gene Ontology (GO)
| • GTPase activator activity (GO:0005096) | • Ras GTPase binding (GO:0017016) |
| • Calcium ion binding (GO:0005509) | • Negative regulation of Ras protein signal transduction (GO:0046580) |
| • Plasma membrane (GO:0005886) | • Cytoplasm (GO:0005737) |
Pathways
• Ras signaling pathway (KEGG: hsa04014)
• MAPK signaling pathway (KEGG: hsa04010)
• Rap1 signaling pathway (KEGG: hsa04015)
Protein Summary
RASA4 (CAPRI) is a 778-amino acid protein with a molecular weight of approximately 87 kDa. It contains an N-terminal C2 domain that mediates calcium-dependent phospholipid binding, a central PH domain, and a C-terminal Ras-GAP domain. The protein translocates to the plasma membrane upon calcium influx, where it inactivates Ras by accelerating GTP hydrolysis. RASA4 is widely expressed but shows highest levels in brain and immune tissues. Its loss or mutation contributes to oncogenic Ras signaling in several cancers.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| RASA4 Knockout HEK293 Cell Line | EDJ-KQ1228 | Human | 10156 | Details Get a Quote |
| RASA4B Knockout HEK293 Cell Line | EDJ-KQ1229 | Human | 100271927 | Details Get a Quote |
| RASA4 Knockout A-549 Cell Line | EDJ-KQ20564 | Human | 10156 | Details Get a Quote |
| RASA4 Knockout HCT 116 Cell Line | EDJ-KQ20565 | Human | 10156 | Details Get a Quote |
| RASA4 Knockout HeLa Cell Line | EDJ-KQ20566 | Human | 10156 | Details Get a Quote |
| RASA4B Knockout A-549 Cell Line | EDJ-KQ20567 | Human | 100271927 | Details Get a Quote |
| RASA4B Knockout HCT 116 Cell Line | EDJ-KQ20568 | Human | 100271927 | Details Get a Quote |
| RASA4B Knockout HeLa Cell Line | EDJ-KQ20569 | Human | 100271927 | Details Get a Quote |
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