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10 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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RAP2A
RAP2A, member of RAS oncogene family
Chromosome 13 · 13q32.1
NCBI Gene: 5911Ensembl: ENSG00000125249.7HGNC: HGNC:9861UniProt: P10114
85PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
establishment of protein localizationmagnesium ion bindingGTPase activityG protein activitydrug allergyosteitis deformansmacular holesactinic keratosis
✦AI Summary

RAP2A (RAP2A, member of RAS oncogene family) is a small GTPase that functions as a molecular switch cycling between GDP-bound inactive and GTP-bound active states 1. The protein serves as a key mechanotransducer in the Hippo pathway, where it is activated by low extracellular matrix stiffness and subsequently activates MAP4K kinases to regulate YAP/TAZ transcriptional activity 1. RAP2A integrates cytoskeletal signals and coordinates cellular responses to mechanical cues, including regulation of cell migration, adhesion, and proliferation 2. In metabolic contexts, RAP2A participates in β3-adrenergic receptor desensitization through the EPAC/RAP2A/PI-PLC pathway, contributing to catecholamine resistance in obesity 3. The gene is transcriptionally regulated by p53 following DNA damage and shows aberrant expression in various cancers 4. In cancer contexts, RAP2A enhances cell migration and invasion through Akt pathway activation and MMP regulation 4. However, its expression requires tight regulation, as both overexpression and knockdown impair macrophage NF-κB signaling and inflammatory responses 5. RAP2A also affects chemotherapy sensitivity, with its downregulation enhancing 5-FU sensitivity in gastric cancer cells 6.

Sources cited
1
RAP2A functions as a mechanotransducer in Hippo pathway, activated by low ECM stiffness to control YAP/TAZ activity
PMID: 30135582
2
RAP2A integrates cytoskeletal signals for Hippo signaling and cellular responses to mechanical cues
PMID: 38574891
3
RAP2A participates in β3-adrenergic receptor desensitization and catecholamine resistance in obesity
PMID: 34847077
4
RAP2A is a p53 target gene that enhances cancer cell migration and invasion through Akt/MMP pathways
PMID: 25728512
5
Both overexpression and knockdown of RAP2A impair macrophage NF-κB signaling and inflammatory responses
PMID: 30851634
6
RAP2A knockdown enhances 5-FU sensitivity in gastric cancer cells
PMID: 36046374
Disease Associationsⓘ20
drug allergyOpen Targets
0.24Weak
osteitis deformansOpen Targets
0.21Weak
macular holesOpen Targets
0.12Weak
actinic keratosisOpen Targets
0.11Weak
dermatomycosisOpen Targets
0.11Weak
sleep apneaOpen Targets
0.09Suggestive
gastric cancerOpen Targets
0.09Suggestive
Abnormality of the skeletal systemOpen Targets
0.08Suggestive
atrial fibrillationOpen Targets
0.08Suggestive
renal cell carcinomaOpen Targets
0.08Suggestive
glioblastoma multiformeOpen Targets
0.07Suggestive
mathematical abilityOpen Targets
0.07Suggestive
peripheral arterial diseaseOpen Targets
0.07Suggestive
hepatocellular carcinomaOpen Targets
0.06Suggestive
hypertensionOpen Targets
0.06Suggestive
neoplasmOpen Targets
0.06Suggestive
myocardial infarctionOpen Targets
0.05Suggestive
papillary thyroid carcinomaOpen Targets
0.05Suggestive
breast cancerOpen Targets
0.04Suggestive
gliomaOpen Targets
0.04Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
ARHGAP29Protein interaction96%RAPGEF4Protein interaction93%RAPGEF6Protein interaction90%RUNDC3AProtein interaction90%RAPGEF3Protein interaction89%RAPGEF2Protein interaction89%
Tissue Expression6 tissues
Brain
100%
Heart
37%
Lung
24%
Bone Marrow
19%
Liver
14%
Ovary
13%
Gene Interaction Network
Click a node to explore
RAP2AARHGAP29RAPGEF4RAPGEF6RUNDC3ARAPGEF3RAPGEF2
PROTEIN STRUCTURE
Preparing viewer…
PDB1KAO · 1.70 Å · X-ray
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
0.66LoF Tolerant
pLIⓘ
0.76Intermediate
Observed/Expected LoF0.31 [0.16–0.66]
RankingsWhere RAP2A stands among ~20K protein-coding genes
  • #5,634of 20,598
    Most Researched85
  • #4,806of 17,882
    Most Constrained (LOEUF)0.66
Genes detectedRAP2A
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
RAP2 mediates mechanoresponses of the Hippo pathway.
PMID: 30135582
Nature · 2018
1.00
2
β3-Adrenergic receptor downregulation leads to adipocyte catecholamine resistance in obesity.
PMID: 34847077
J Clin Invest · 2022
0.90
3
Rap2a is a novel target gene of p53 and regulates cancer cell migration and invasion.
PMID: 25728512
Cell Signal · 2015
0.80
4
Transcriptomic analyses of ovarian clear-cell carcinoma with concurrent endometriosis.
PMID: 37621654
Front Endocrinol (Lausanne) · 2023
0.70
5
Impact of periodontitis on type 2 diabetes: a bioinformatic analysis.
PMID: 38811930
BMC Oral Health · 2024
0.60