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10 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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RRAS
RAS related
Chromosome 19 · 19q13.33
NCBI Gene: 6237Ensembl: ENSG00000126458.5HGNC: HGNC:10447UniProt: P10301
98PubMed Papers
20Diseases
0Drugs
1Pathogenic Variants
FUNCTIONAL ROLE
Hub Gene
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
GTPase activitypositive regulation of angiogenesisregulation of phosphatidylinositol 3-kinase/protein kinase B signal transductionface morphogenesisNoonan syndromeNoonan syndrome and Noonan-related syndromeneurodegenerative diseasegenetic disorder
✦AI Summary

RRAS is a small GTPase that functions as a molecular switch regulating multiple cellular processes through activation of MAPK and PI3K-mTOR signaling pathways 1. The protein controls cell adhesion, migration, and actin cytoskeleton organization 2, with documented roles in integrin beta-1 modulation [UniProt]. In normal physiology, RRAS expression is transcriptionally regulated by FOXF1 in lung endothelial cells, where it suppresses fibroblast activation and pulmonary inflammation—processes dysregulated in idiopathic pulmonary fibrosis 3. Clinically, RRAS mutations drive disease through two distinct mechanisms: (1) Germline mutations cause RASopathies, particularly Noonan syndrome, as rare but pathogenic variants affecting the RAS/MAPK pathway 4; (2) Somatic mutations, specifically RRAS Q87L (homologous to KRAS Q61), represent recurrent oncogenic drivers in ~0.45% of non-small cell lung cancers and oral squamous cell carcinomas, activating canonical growth signaling and conferring sensitivity to pan-RAS inhibitor RMC-6236 15. In acute megakaryoblastic leukemia, elevated RRAS promotes immune escape via enhanced ERK signaling and reduced CD8+ T cell anti-tumor immunity 2. Therapeutically, RRAS shows promise as a therapeutic target for glucose regulation in diabetes when enhanced PI3Kα binding is pharmacologically modulated 6, while emerging as a prognostic marker for treatment response and recurrence risk in multiple cancer types 7.

Sources cited
1
RRAS Q87L mutations are oncogenic drivers found in ~0.45% of NSCLC, activate MAPK and PI3K-mTOR signaling, and are sensitive to RMC-6236 pan-RAS inhibitor
PMID: 41292901
2
RRAS Q87L and RRAS2 Q72L are recurrent oncogenic drivers in lung cancer responsive to pan-RAS inhibitor RMC-6236
PMID: 41543339
3
FOXF1 transcriptionally activates RRAS gene promoter in lung endothelial cells; RRAS signaling impairment increases collagen deposition and inflammation in pulmonary fibrosis
PMID: 37137915
4
RRAS encodes a small GTPase controlling cell adhesion and migration; elevated RRAS in AMKL enhances ERK phosphorylation and promotes immune escape from CD8+ T cells
PMID: 41428087
5
RRAS mutations identified as rare pathogenic variants in Noonan syndrome patients within the RASopathy disease spectrum
PMID: 39725732
6
RRAS enhances PI3Kα binding affinity through molecular glue compounds, promoting glucose uptake independent of insulin signaling
PMID: 40705882
7
High RRAS expression in oral squamous cell carcinoma associates with radiotherapy and cisplatin resistance through EGFR/RRAS/AKT/ERK pathway and is a prognostic marker for recurrence
PMID: 39842500
Disease Associationsⓘ20
Noonan syndromeOpen Targets
0.42Moderate
Noonan syndrome and Noonan-related syndromeOpen Targets
0.37Weak
neurodegenerative diseaseOpen Targets
0.29Weak
genetic disorderOpen Targets
0.27Weak
hypertensionOpen Targets
0.25Weak
Increased blood pressureOpen Targets
0.18Weak
cardiovascular diseaseOpen Targets
0.17Weak
hereditary cancerOpen Targets
0.12Weak
neoplasmOpen Targets
0.10Weak
lung cancerOpen Targets
0.10Suggestive
prostate cancerOpen Targets
0.08Suggestive
peripheral arterial diseaseOpen Targets
0.07Suggestive
malignant peripheral nerve sheath tumorOpen Targets
0.07Suggestive
melanomaOpen Targets
0.06Suggestive
nasopharyngeal carcinomaOpen Targets
0.06Suggestive
Rare genetic vascular diseaseOpen Targets
0.05Suggestive
Huntington diseaseOpen Targets
0.05Suggestive
non-small cell lung carcinomaOpen Targets
0.05Suggestive
colorectal carcinomaOpen Targets
0.05Suggestive
lung adenocarcinomaOpen Targets
0.05Suggestive
Pathogenic Variants1
NM_006270.5(RRAS):c.107GCG[5] (p.Gly39dup)Likely pathogenic
Inborn genetic diseases
★☆☆☆2017→ Residue 39
View on ClinVar ↗
Related Genes
PIK3R3Protein interaction100%PIK3R1Protein interaction100%RALGDSProtein interaction100%PLXNB1Protein interaction99%RASA1Protein interaction98%RASSF5Protein interaction97%
Tissue Expression6 tissues
Heart
100%
Lung
95%
Ovary
37%
Liver
20%
Brain
6%
Bone Marrow
3%
Gene Interaction Network
Click a node to explore
RRASPIK3R3PIK3R1RALGDSPLXNB1RASA1RASSF5
PROTEIN STRUCTURE
Preparing viewer…
PDB2FN4 · 1.65 Å · X-ray
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
1.18LoF Tolerant
pLIⓘ
0.00Tolerant
Observed/Expected LoF0.75 [0.49–1.18]
RankingsWhere RRAS stands among ~20K protein-coding genes
  • #4,908of 20,598
    Most Researched98 · top quartile
  • #4,895of 5,498
    Most Pathogenic Variants1
  • #12,302of 17,882
    Most Constrained (LOEUF)1.18
Genes detectedRRAS
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
Lung endothelial cells regulate pulmonary fibrosis through FOXF1/R-Ras signaling.
PMID: 37137915
Nat Commun · 2023
1.00
2
Molecular glues that facilitate RAS binding to PI3Kα promote glucose uptake without insulin.
PMID: 40705882
Science · 2025
0.90
3
Immune Characteristics of eQTL and Gene Risk Model and the Inhibitory Effect of DCTD and RRAS on Ferroptosis in Glioblastoma.
PMID: 40917066
Front Biosci (Landmark Ed) · 2025
0.80
4
Clinical features and molecular genetics of patients with RASopathies: expanding the phenotype with rare genes and novel variants.
PMID: 39725732
Eur J Pediatr · 2024
0.70
5
PMID: 41292901
bioRxiv · 2025
0.60