RASA1 Gene
RAS p21 Protein Activator 1
Gene Information Card
| Symbol | RASA1 |
|---|---|
| Full Name | RAS p21 protein activator 1 |
| Gene Type | protein-coding |
| Chromosomal Location | 5q14.3 |
| NCBI Gene ID | 5921 ncbi.nlm.nih.gov/gene/5921 |
| Ensembl ID | ENSG00000145715 |
| UniProt ID | P20936 |
| OMIM ID | 139150 |
| HGNC ID | 9871 |
| Aliases | GAP, p120GAP, RASGAP, CM-AVM |
Description
RASA1 encodes the RAS p21 protein activator 1 (p120RasGAP), a GTPase-activating protein (GAP) that negatively regulates RAS signaling by accelerating GTP hydrolysis on RAS proteins. It acts as a tumor suppressor and is critical for vascular development. Loss-of-function mutations cause capillary malformation-arteriovenous malformation (CM-AVM) syndrome and are implicated in various cancers.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Capillary malformation-arteriovenous malformation (CM-AVM) | Loss-of-function mutations in RASA1 impair RAS inactivation, leading to abnormal vascular morphogenesis and arteriovenous shunting. | ClinVar, OMIM #608354 |
| Parkes Weber syndrome | Heterozygous germline RASA1 mutations cause localized arteriovenous malformations with limb overgrowth. | OMIM #608355 |
| Hereditary hemorrhagic telangiectasia (HHT)-like phenotype | RASA1 variants disrupt endothelial cell signaling, mimicking HHT vascular lesions. | NCBI Gene, ClinVar |
| Breast cancer | Somatic RASA1 mutations or reduced expression lead to sustained RAS activation and tumor progression. | COSMIC, NCBI Gene |
| Lung cancer | RASA1 loss-of-function mutations contribute to RAS-driven oncogenesis. | COSMIC |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 12.5 | Medium |
| Heart | 8.3 | Low |
| Lung | 6.7 | Low |
| Liver | 4.2 | Low |
| Kidney | 9.1 | Low |
| Skeletal muscle | 3.5 | Low |
| Adipose tissue | 5.8 | Low |
| Skin | 7.4 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK 293 | 15.2 | Embryonic kidney cells |
| HeLa | 11.8 | Cervical carcinoma cells |
| A549 | 9.6 | Lung carcinoma cells |
| MCF7 | 7.3 | Breast carcinoma cells |
| HUVEC | 14.5 | Endothelial cells |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.2125C>T (p.Arg709*) | Nonsense | <0.1% | Truncation, loss of GAP domain function |
| c.1534G>A (p.Gly512Arg) | Missense | <0.1% | Impaired RAS binding and GAP activity |
| c.2740_2741del (p.Leu914fs) | Frameshift | <0.1% | Premature stop, loss of function |
| c.1A>G (p.Met1?) | Start loss | <0.1% | No protein translation |
Mutation functional classification
Loss of Function (LOF)
Most RASA1 mutations are loss-of-function, leading to reduced RAS-GAP activity and increased RAS-GTP signaling. This is the primary mechanism in CM-AVM and tumorigenesis.
Gain of Function (GOF)
No gain-of-function mutations have been reported for RASA1.
Dominant Negative (DN)
Some missense mutations may act as dominant-negative by sequestering RAS or interfering with wild-type RASA1 function, though evidence is limited.
View complete mutation data：
Gene Ontology (GO)
| • GTPase activator activity (GO:0005096) | • RAS protein binding (GO:0017016) |
| • negative regulation of RAS protein signal transduction (GO:0046580) | • angiogenesis (GO:0001525) |
| • vasculogenesis (GO:0001570) | • cell migration (GO:0016477) |
Pathways
• RAS signaling pathway (Reactome: R-HSA-5673001)
• Signaling by Receptor Tyrosine Kinases (Reactome: R-HSA-9006934)
• VEGF signaling pathway (KEGG: hsa04370)
• MAPK signaling pathway (KEGG: hsa04010)
Protein Summary
The RASA1 protein (p120RasGAP) is a 1,047-amino-acid multidomain protein containing SH2, SH3, PH, and C-terminal GAP domains. It binds directly to activated RAS and accelerates GTP hydrolysis, thereby terminating RAS signaling. It also interacts with p190RhoGAP and other signaling molecules to regulate cytoskeletal dynamics and cell proliferation. Loss of RASA1 function leads to constitutive RAS activation, promoting abnormal vascular development and cancer.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| RASA1 Knockout HEK293 Cell Line | EDJ-KQ744 | Human | 5921 | Details Get a Quote |
| RASA1 Knockout A-549 Cell Line | EDJ-KQ19386 | Human | 5921 | Details Get a Quote |
| RASA1 Knockout HCT 116 Cell Line | EDJ-KQ19387 | Human | 5921 | Details Get a Quote |
| RASA1 Knockout HeLa Cell Line | EDJ-KQ19388 | Human | 5921 | Details Get a Quote |
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