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10 sources retrieved · Most recent: April 2026 · Index updated 15 days ago
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RASAL2
RAS protein activator like 2
Chromosome 1 · 1q25.2
NCBI Gene: 9462Ensembl: ENSG00000075391.18HGNC: HGNC:9874UniProt: A0A8Q3SIU1
93PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
protein bindingGTPase activator activityregulation of intracellular signal transductionsignal transductionblood coagulation diseasebenign neoplasmKeloidHodgkins lymphoma
✦AI Summary

RASAL2 (RAS protein activator like 2) is a RasGAP that inhibits the Ras-cyclic AMP signaling pathway through GTPase activator activity 1. However, RASAL2 exhibits context-dependent and paradoxical roles in cancer biology. In breast cancer, RASAL2 functions as a tumor and metastasis suppressor, with loss associated with metastatic disease and chemoresistance 1. Yet in other malignancies, RASAL2 acts as an oncogene. In gastric cancer, H. pylori infection induces RASAL2 expression via NF-κB, which then activates the AKT/β-catenin axis by inhibiting protein phosphatase 2A, promoting tumorigenesis 2. Similarly, RASAL2 is upregulated in hepatocellular carcinoma and pancreatic ductal adenocarcinoma, where it promotes proliferation and metastasis 3 4. RASQL2 regulates multiple pathways beyond Ras signaling. In astrocytomas, it modulates RHO activity and mesenchymal-amoeboid transition 5. In triple-negative breast cancer, RASAL2 knockout increases autophagic-exosome secretion via Rab27a regulation 6, and RASAL2 confers chemoresistance through CREB1-BCL2-mediated mitochondrial apoptosis resistance 7. In chr1 kidney disease, RASAL2 suppresses angiogenesis and promotes peritubular capillary rarefaction via HIF-1α 8. These findings establish RASAL2 as a multifunctional signaling hub with tissue- and context-specific roles in cancer progression and fibrotic disease.

Sources cited
1
RASAL2 functions as tumor and metastasis suppressor in breast cancer; loss correlates with metastatic disease and recurrence
PMID: 24029233
2
H. pylori induces RASAL2 via NF-κB to activate AKT/β-catenin axis and promote gastric tumorigenesis
PMID: 35134322
3
RASAL2 is upregulated in hepatocellular carcinoma and promotes proliferation and metastasis via AKT phosphorylation
PMID: 28447723
4
RASAL2 upregulation in pancreatic ductal adenocarcinoma promotes malignant phenotypes via YAP1/TIAM1 signaling
PMID: 35844783
5
RASAL2 interacts with ECT2 and regulates RHO activity in astrocytoma mesenchymal-amoeboid transition
PMID: 22683310
6
RASAL2 knockout in triple-negative breast cancer disrupts autophagic flux and promotes autophagic-exosome secretion via Rab27a
PMID: 40369567
7
RASAL2 confers chemoresistance in triple-negative breast cancer through CREB1-BCL2 axis and mitochondrial apoptosis resistance
PMID: 39890967
8
RASAL2 suppresses angiogenesis and promotes peritubular capillary rarefaction in renal interstitial fibrosis via HIF-1α-mediated pathway
PMID: 38453052
Disease Associationsⓘ20
blood coagulation diseaseOpen Targets
0.36Weak
benign neoplasmOpen Targets
0.31Weak
KeloidOpen Targets
0.28Weak
Hodgkins lymphomaOpen Targets
0.25Weak
liver diseaseOpen Targets
0.23Weak
HypercholesterolemiaOpen Targets
0.20Weak
neurodegenerative diseaseOpen Targets
0.19Weak
prostate cancerOpen Targets
0.11Weak
autismOpen Targets
0.11Weak
Familial prostate cancerOpen Targets
0.11Weak
neoplasmOpen Targets
0.11Weak
triple-negative breast cancerOpen Targets
0.11Weak
colorectal carcinomaOpen Targets
0.09Suggestive
posterior cortical atrophyOpen Targets
0.09Suggestive
breast cancerOpen Targets
0.09Suggestive
renal cell carcinomaOpen Targets
0.08Suggestive
ovarian cancerOpen Targets
0.08Suggestive
head and neck squamous cell carcinomaOpen Targets
0.07Suggestive
insomniaOpen Targets
0.06Suggestive
hypotrichosis simplexOpen Targets
0.06Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
HRASProtein interaction99%NRASProtein interaction94%RRAS2Protein interaction91%DAB2IPProtein interaction83%MRASProtein interaction74%GUCA2BShared pathway33%
Tissue Expression6 tissues
Heart
100%
Lung
46%
Brain
40%
Ovary
28%
Liver
17%
Bone Marrow
11%
Gene Interaction Network
Click a node to explore
RASAL2HRASNRASRRAS2DAB2IPMRASGUCA2B
PROTEIN STRUCTURE
Preparing viewer…
AlphaFoldAI-predicted · UniProt Q9UJF2
View on AlphaFold ↗
Constraintⓘ
LOEUFⓘ
0.55Moderately Constrained
pLIⓘ
0.01Tolerant
Observed/Expected LoF0.44 [0.35–0.55]
RankingsWhere RASAL2 stands among ~20K protein-coding genes
  • #5,163of 20,598
    Most Researched93
  • #3,550of 17,882
    Most Constrained (LOEUF)0.55 · top quartile
Genes detectedRASAL2
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
Helicobacter pylori-induced RASAL2 Through Activation of Nuclear Factor-κB Promotes Gastric Tumorigenesis via β-catenin Signaling Axis.
PMID: 35134322
Gastroenterology · 2022
1.00
2
The RasGAP gene, RASAL2, is a tumor and metastasis suppressor.
PMID: 24029233
Cancer Cell · 2013
0.90
3
RAS protein activator-like 2 (RASAL2) initiates peritubular capillary rarefaction in hypoxic renal interstitial fibrosis.
PMID: 38453052
Transl Res · 2024
0.80
4
ECT2 and RASAL2 mediate mesenchymal-amoeboid transition in human astrocytoma cells.
PMID: 22683310
Am J Pathol · 2012
0.70
5
Rasal2 inhibits autophagic-exosomes secretion via regulating Rab27a in triple-negative breast cancer progression.
PMID: 40369567
J Transl Med · 2025
0.60