RASA2: RAS p21 Protein Activator 2
A GTPase-activating protein (GAP) that negatively regulates RAS signaling and is implicated in cancer and Noonan syndrome.
Gene Information Card
| Symbol | RASA2 |
|---|---|
| Full Name | RAS p21 protein activator 2 |
| Gene Type | protein-coding |
| Chromosomal Location | 3q23 |
| NCBI Gene ID | 5922 ncbi.nlm.nih.gov/gene/5922 |
| Ensembl ID | ENSG00000114013 |
| UniProt ID | Q15283 |
| OMIM ID | 601589 |
| HGNC ID | 9872 |
| Aliases | GAP1M, RASAL2, RAS p21 protein activator 2 |
Description
RASA2 encodes a member of the GTPase-activating protein (GAP) family that stimulates the intrinsic GTPase activity of RAS proteins, thereby converting active RAS-GTP to inactive RAS-GDP. This negative regulation of RAS signaling is critical for controlling cell proliferation, differentiation, and survival. Mutations in RASA2 are associated with Noonan syndrome and various cancers, including melanoma and lung adenocarcinoma.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Noonan syndrome | Loss-of-function mutations in RASA2 impair RAS-GAP activity, leading to increased RAS-GTP levels and hyperactive RAS-MAPK signaling during development. | ClinVar, OMIM |
| Melanoma | Somatic missense mutations (e.g., p.Gly125Arg) reduce GAP activity, promoting RAS-driven tumorigenesis. | COSMIC, ClinVar |
| Lung adenocarcinoma | Recurrent mutations in RASA2 are associated with aberrant RAS signaling and poor prognosis. | COSMIC, NCBI |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 12.5 | Medium |
| Lung | 8.3 | Low |
| Heart | 6.1 | Low |
| Liver | 4.7 | Low |
| Kidney | 9.2 | Low |
| Testis | 15.8 | Medium |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK 293 | 11.2 | Embryonic kidney cells; moderate expression |
| A549 | 7.8 | Lung carcinoma; low expression |
| SK-MEL-28 | 14.5 | Melanoma; high expression |
| MCF7 | 6.3 | Breast cancer; low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.373G>A (p.Gly125Arg) | Missense | Somatic (melanoma) | Loss of GAP activity; increased RAS-GTP |
| c.1060C>T (p.Arg354Trp) | Missense | Germline (Noonan syndrome) | Impaired RAS binding and GAP function |
| c.1438G>A (p.Gly480Arg) | Missense | Somatic (lung adenocarcinoma) | Reduced catalytic activity |
Mutation functional classification
Loss of Function (LOF)
Most RASA2 mutations (e.g., p.Gly125Arg, p.Arg354Trp) reduce or abolish GAP activity, leading to sustained RAS-GTP signaling.
Gain of Function (GOF)
No confirmed gain-of-function mutations reported in RASA2.
Dominant Negative (DN)
Some missense variants may act in a dominant-negative manner by competing with wild-type RASA2 for RAS binding without effective GAP activity.
View complete mutation data：
Gene Ontology (GO)
| • GTPase activator activity (GO:0005096) | • RAS GTPase binding (GO:0017016) |
| • Negative regulation of RAS protein signal transduction (GO:0046580) | • Cytoplasm (GO:0005737) |
| • Plasma membrane (GO:0005886) |
Pathways
• RAS signaling pathway (Reactome: R-HSA-5673001)
• MAPK signaling pathway (KEGG: hsa04010)
• Signaling by RAS mutants (Reactome: R-HSA-6802948)
Protein Summary
RASA2 (GAP1m) is a 1046-amino-acid protein containing a PH domain, C2 domain, and a RasGAP domain. It localizes to the plasma membrane and cytoplasm, where it negatively regulates RAS by accelerating GTP hydrolysis. Loss of RASA2 function leads to constitutive RAS activation, contributing to developmental disorders and oncogenesis.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| RASA2 Knockout HEK293 Cell Line | EDJ-KQ227 | Human | 5922 | Details Get a Quote |
| RASA2 Knockout A-549 Cell Line | EDJ-KQ19389 | Human | 5922 | Details Get a Quote |
| RASA2 Knockout HCT 116 Cell Line | EDJ-KQ19391 | Human | 5922 | Details Get a Quote |
| RASA2 Knockout HeLa Cell Line | EDJ-KQ19392 | Human | 5922 | Details Get a Quote |
