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7 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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RGL4
ral guanine nucleotide dissociation stimulator like 4
Chromosome 22 · 22q11.23
NCBI Gene: 266747Ensembl: ENSG00000159496.15HGNC: HGNC:31911UniProt: Q3ZCN2
15PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
guanyl-nucleotide exchange factor activityRas protein signal transductionplasma membranesmall GTPase-mediated signal transductionadolescent idiopathic scoliosisSepsisosteosarcomaseptic shock
✦AI Summary

RGL4 (ral guanine nucleotide dissociation stimulator like 4) is a guanyl-nucleotide exchange factor that functions in Ras protein signal transduction at the plasma membrane. While direct mechanistic studies are limited in the provided literature, RGL4 appears to play roles in immune cell regulation and inflammatory responses across multiple disease contexts. In septic shock, RGL4 is upregulated and serves as a diagnostic biomarker with strong predictive value (ROC = 0.914) 1. Single-cell transcriptomics identified RGL4 as a marker of Neu1 neutrophil subtype, which is associated with septic shock severity and SOFA scores 2. In pediatric sepsis, RGL4 demonstrates causal associations with disease risk through Mendelian randomization analysis, suggesting an inflammatory role 3. In bronchopulmonary dysplasia, RGL4 was identified as one of eight hub genes potentially involved in mitophagy and immune-mediated inflammatory responses 4. Conversely, in lung adenocarcinoma, low RGL4 expression correlates with poor prognosis and altered tumor-infiltrating immune cell infiltration, including memory B cells, CD8+ T cells, and neutrophils 5. In acute myeloid leukemia, RGL4 is a survival-related gene with reduced expression in patient samples compared to healthy controls 2. RGL4 expression changes post-treatment, suggesting potential therapeutic relevance 2. These findings position RGL4 as a multifunctional biomarker in inflammatory and malignant diseases, though mechanistic studies are needed to clarify its precise molecular functions beyond its role as a guanine nucleotide exchange factor.

Sources cited
1
RGL4 is one of six hub genes upregulated in septic shock with ROC = 0.914 for diagnostic prediction
PMID: 37359526
2
RGL4 is a survival-related hub gene in acute myeloid leukemia with lower expression in AML samples and increased expression post-treatment
PMID: 36212177
3
RGL4 shows causal associations with pediatric sepsis risk through Mendelian randomization and plays an inflammatory role
PMID: 39871218
4
RGL4 is identified as one of eight hub genes in bronchopulmonary dysplasia potentially involved in mitophagy and immune-mediated inflammation
PMID: 40783597
5
Low RGL4 expression is associated with poor prognosis and altered tumor-infiltrating immune cells in lung adenocarcinoma
PMID: 32259700
6
RGL4 is a marker of Neu1 neutrophil subtype associated with septic shock and SOFA score severity
PMID: 36304125
Disease Associationsⓘ20
adolescent idiopathic scoliosisOpen Targets
0.20Weak
SepsisOpen Targets
0.06Suggestive
osteosarcomaOpen Targets
0.02Suggestive
septic shockOpen Targets
0.02Suggestive
lung adenocarcinomaOpen Targets
0.02Suggestive
acute lymphoblastic leukemiaOpen Targets
0.01Suggestive
neoplasmOpen Targets
0.01Suggestive
cutaneous lupus erythematosusOpen Targets
0.01Suggestive
T-cell and NK-cell neoplasmOpen Targets
0.01Suggestive
cancerOpen Targets
0.01Suggestive
T-cell acute lymphoblastic leukemiaOpen Targets
0.01Suggestive
meningococcal infectionOpen Targets
0.01Suggestive
colorectal carcinomaOpen Targets
0.01Suggestive
mature T-cell and NK-cell non-Hodgkin lymphomaOpen Targets
0.01Suggestive
acute myeloid leukemiaOpen Targets
0.00Suggestive
hematopoietic and lymphoid cell neoplasmOpen Targets
0.00Suggestive
adult T-cell leukemia/lymphomaOpen Targets
0.00Suggestive
muscle tissue disorderOpen Targets
0.00Suggestive
mycosis fungoidesOpen Targets
0.00Suggestive
Timothy syndromeOpen Targets
0.00Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
RGL2Shared pathway100%RALGDSShared pathway100%RGL1Shared pathway100%RGL3Shared pathway100%RASGEF1BShared pathway100%RASGEF1CShared pathway100%
Tissue Expression6 tissues
Bone Marrow
100%
Lung
10%
Ovary
7%
Heart
3%
Liver
3%
Brain
1%
Gene Interaction Network
Click a node to explore
RGL4RGL2RALGDSRGL1RGL3RASGEF1BRASGEF1C
PROTEIN STRUCTURE
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AlphaFoldAI-predicted · UniProt Q3ZCN2
View on AlphaFold ↗
Constraintⓘ
LOEUFⓘ
1.04LoF Tolerant
pLIⓘ
0.00Tolerant
Observed/Expected LoF0.78 [0.60–1.04]
RankingsWhere RGL4 stands among ~20K protein-coding genes
  • #15,676of 20,598
    Most Researched15
  • #10,304of 17,882
    Most Constrained (LOEUF)1.04
Genes detectedRGL4
Sources retrieved7 papers
Response time—
📄 Sources
7▼
1
Six potential biomarkers in septic shock: a deep bioinformatics and prospective observational study.
PMID: 37359526
Front Immunol · 2023
1.00
2
Investigating mitophagy mechanisms in bronchopulmonary dysplasia through bioinformatics.
PMID: 40783597
Pediatr Res · 2026
0.86
3
Integration of Mendelian Randomization to explore the genetic influences of pediatric sepsis: a focus on RGL4, ATP9A, MAP3K7CL, and DDX11L2.
PMID: 39871218
BMC Pediatr · 2025
0.71
4
Single-cell transcriptome profiling reveals heterogeneous neutrophils with prognostic values in sepsis.
PMID: 36304125
iScience · 2022
0.57
5
Low expression of RGL4 is associated with a poor prognosis and immune infiltration in lung adenocarcinoma patients.
PMID: 32259700
Int Immunopharmacol · 2020
0.43