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10 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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RALGAPA2
Ral GTPase activating protein catalytic subunit alpha 2
Chromosome 20 · 20p11.23
NCBI Gene: 57186Ensembl: ENSG00000188559.17HGNC: HGNC:16207UniProt: Q2PPJ7
39PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
cytosolprotein bindingGO:0005615cytoplasmrheumatic diseaseresponse to xenobiotic stimuluspoisoningliver disease
✦AI Summary

RALGAPA2 encodes the catalytic alpha subunit of the RalGAP2 complex, which functions as a GTPase activating protein that negatively regulates RalA and RalB small GTPases 1. The protein forms an obligatory heterodimer with RalGAPβ, and these heterodimers assemble into extended tetrameric complexes that are essential for in vivo function 2. As a tumor suppressor, RALGAPA2 inhibits oncogenic Ras signaling pathways by promoting GTP hydrolysis in RalA/B GTPases 13. Loss or downregulation of RALGAPA2 has significant clinical implications across multiple cancers. In hepatocellular carcinoma, RALGAPA2 downregulation combined with RalA upregulation correlates with aggressive tumor behavior, venous invasion, advanced staging, and poor overall survival 1. Similarly, reduced RALGAPA2 expression in prostate cancer promotes cellular invasion and progression from intraepithelial neoplasia to invasive adenocarcinoma 3. Forward genetic screens have validated RALGAPA2 as a bona fide tumor suppressor, with knockdown enhancing proliferation in multiple cancer cell lines 4. The therapeutic potential of targeting this pathway is supported by studies showing that Ral inhibition sensitizes cancer cells to existing treatments like sorafenib 14.

Sources cited
1
RALGAPA2 functions as GTPase activating protein for RalA/B and its downregulation in HCC correlates with aggressive tumor behavior
PMID: 34767674
2
RALGAPA2 forms obligatory heterodimers with RalGAPβ that assemble into tetrameric complexes essential for in vivo function
PMID: 40738882
3
RALGAPA2 downregulation in prostate cancer promotes invasion and progression from intraepithelial neoplasia to adenocarcinoma
PMID: 31058283
4
Forward genetic screens validated RALGAPA2 as tumor suppressor and showed Ral inhibition sensitizes cells to sorafenib
PMID: 27178121
⚠Limited data available — This gene has 4 indexed publications. Summary and analysis may be incomplete.
Disease Associationsⓘ20
rheumatic diseaseOpen Targets
0.31Weak
response to xenobiotic stimulusOpen Targets
0.30Weak
poisoningOpen Targets
0.28Weak
liver diseaseOpen Targets
0.28Weak
ovarian neoplasmOpen Targets
0.27Weak
alcohol drinkingOpen Targets
0.26Weak
benign urinary system neoplasmOpen Targets
0.25Weak
Abruptio PlacentaeOpen Targets
0.23Weak
DNA methylationOpen Targets
0.20Weak
sensory perception of smellOpen Targets
0.19Weak
corneal degenerationOpen Targets
0.19Weak
diaphragm diseaseOpen Targets
0.17Weak
pericarditisOpen Targets
0.17Weak
hepatocellular carcinomaOpen Targets
0.08Suggestive
neoplasmOpen Targets
0.07Suggestive
atrial heart septal defectOpen Targets
0.07Suggestive
autosomal dominant polycystic kidney disease type 1 with tuberous sclerosisOpen Targets
0.04Suggestive
septic shockOpen Targets
0.03Suggestive
breast cancerOpen Targets
0.03Suggestive
poliovirus infectionOpen Targets
0.01Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
RALAProtein interaction85%NKIRAS2Protein interaction79%RALGAPBProtein interaction77%AKT2Protein interaction75%GFOD1Protein interaction73%RALGAPA1Shared pathway67%
Tissue Expression6 tissues
Liver
100%
Lung
94%
Bone Marrow
75%
Ovary
27%
Heart
27%
Brain
19%
Gene Interaction Network
Click a node to explore
RALGAPA2RALANKIRAS2RALGAPBAKT2GFOD1RALGAPA1
PROTEIN STRUCTURE
Preparing viewer…
PDB9QU1 · 2.72 Å · X-ray
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
0.74LoF Tolerant
pLIⓘ
0.00Tolerant
Observed/Expected LoF0.63 [0.54–0.74]
RankingsWhere RALGAPA2 stands among ~20K protein-coding genes
  • #10,382of 20,598
    Most Researched39
  • #5,775of 17,882
    Most Constrained (LOEUF)0.74
Genes detectedRALGAPA2
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
Autophagy in colitis-associated colon cancer: exploring its potential role in reducing initiation and preventing IBD-Related CAC development.
PMID: 37723664
Autophagy · 2024
1.00
2
Dysregulation of RalA signaling through dual regulatory mechanisms exerts its oncogenic functions in hepatocellular carcinoma.
PMID: 34767674
Hepatology · 2022
0.90
3
Two-Step Forward Genetic Screen in Mice Identifies Ral GTPase-Activating Proteins as Suppressors of Hepatocellular Carcinoma.
PMID: 27178121
Gastroenterology · 2016
0.80
4
The interaction between MALAT1 target, miR-143-3p, and RALGAPA2 is affected by functional SNP rs3827693 in breast cancer.
PMID: 32880825
Hum Cell · 2020
0.70
5
Transcriptome analysis of human cumulus cells reveals hypoxia as the main determinant of follicular senescence.
PMID: 27268410
Mol Hum Reprod · 2016
0.60