G3BP1: A Multifunctional Stress Granule Nucleator and Signaling Hub in Cancer and Neurodegeneration
Explore the genomic architecture, expression landscape, disease associations, and functional impact of G3BP1 mutations, with evidence from authoritative biomedical databases.
Gene Information Card
| Symbol | G3BP1 |
|---|---|
| Full Name | G3BP stress granule assembly factor 1 |
| Gene Type | protein coding |
| Chromosomal Location | 5q13.2 |
| NCBI Gene ID | 10146 ncbi.nlm.nih.gov/gene/10146 |
| Ensembl ID | ENSG00000145907 |
| UniProt ID | Q13283 |
| OMIM ID | 608431 |
| HGNC ID | 30292 |
| Aliases | G3BP, HDH-VIII |
Description
G3BP1 encodes a member of the RasGAP SH3 domain binding protein family. It is a key nucleator of stress granules (SGs), cytoplasmic ribonucleoprotein assemblies that form under stress conditions. G3BP1 also participates in mRNA metabolism, cell signaling, and apoptosis. Its dysregulation is implicated in cancer and neurodegenerative diseases.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Cancer (multiple types) | G3BP1 overexpression promotes tumor cell proliferation, invasion, and chemoresistance via SG formation and signaling pathways (e.g., NF-κB, Ras). | COSMIC; literature evidence from NCBI Gene |
| Neurodegenerative disorders (e.g., ALS, FTD) | Aberrant SG dynamics due to G3BP1 mutations or altered expression contribute to pathological protein aggregation. | ClinVar; literature evidence from NCBI Gene |
| Viral infections | G3BP1 is hijacked by viruses to modulate SG assembly, affecting antiviral responses. | UniProt; literature evidence from NCBI Gene |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | High (e.g., 100+ nTPM) | High expression in cerebral cortex and cerebellum |
| Testis | High (e.g., 80+ nTPM) | Elevated in testicular tissue |
| Liver | Moderate (e.g., 50 nTPM) | Moderate expression |
| Kidney | Moderate (e.g., 40 nTPM) | Moderate expression |
| Lung | Low (e.g., 20 nTPM) | Low expression |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HeLa | High (e.g., 100+ nTPM) | Cervical cancer cell line; strong SG response |
| A549 | Moderate (e.g., 60 nTPM) | Lung carcinoma; used in stress granule studies |
| HEK293 | High (e.g., 90 nTPM) | Embryonic kidney; common for SG research |
| MCF7 | Moderate (e.g., 50 nTPM) | Breast cancer; G3BP1 linked to proliferation |
| K562 | Low (e.g., 20 nTPM) | Chronic myeloid leukemia; lower expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.118A>G (p.Thr40Ala) | Missense | Rare (<0.1%) | May affect SG assembly; clinical significance uncertain |
| c.125C>T (p.Pro42Leu) | Missense | Rare (<0.1%) | Potential impact on protein stability; not well characterized |
| c.145G>A (p.Val49Met) | Missense | Rare (<0.1%) | Reported in cancer; functional impact unknown |
| c.200C>T (p.Pro67Leu) | Missense | Rare (<0.1%) | Observed in COSMIC; likely passenger mutation |
| c.250G>A (p.Asp84Asn) | Missense | Rare (<0.1%) | ClinVar: uncertain significance; no disease association confirmed |
Mutation functional classification
Loss of Function (LOF)
Loss-of-function mutations in G3BP1 are rare and not well documented. Complete knockout in cells impairs SG formation, but no pathogenic germline loss-of-function variants have been reported in ClinVar.
Gain of Function (GOF)
Gain-of-function mutations are not clearly defined. Overexpression of wild-type G3BP1 is oncogenic, but specific activating mutations have not been identified.
Dominant Negative (DN)
Dominant-negative mutations have not been characterized. However, certain missense variants may interfere with SG assembly, but evidence is limited.
View complete mutation data：
Gene Ontology (GO)
| • RNA binding | • protein binding |
| • stress granule assembly | • mRNA processing |
| • cell signaling | • apoptotic process |
| • response to stress |
Pathways
• Stress granule formation
• Ras signaling pathway
• NF-κB signaling
• mRNA surveillance
• Apoptosis
Protein Summary
G3BP1 is a 466-amino acid protein containing an N-terminal nuclear transport factor 2 (NTF2)-like domain, a central acidic domain, a proline-rich region, and C-terminal RNA recognition motifs (RRMs). It dimerizes via the NTF2-like domain and nucleates stress granules by undergoing liquid-liquid phase separation. G3BP1 also interacts with RasGAP, modulating Ras signaling, and is involved in mRNA decay and translational regulation.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| G3BP1 Knockout HEK293 Cell Line | EDJ-KQ13536 | Human | 10146 | Details Get a Quote |
| G3BP1 Knockout A-549 Cell Line | EDJ-KQ43157 | Human | 10146 | Details Get a Quote |
| G3BP1 Knockout HCT 116 Cell Line | EDJ-KQ43158 | Human | 10146 | Details Get a Quote |
| G3BP1 Knockout HeLa Cell Line | EDJ-KQ43159 | Human | 10146 | Details Get a Quote |
| G3BP1 (p.S373G) Point Mutation in A-549 Cell Line | EDC07731 | Human | 10146 | Details Get a Quote |
| GFP-G3BP1 Overexpression U2OS Stable Cell Line | EDC01688 | Human | Details Get a Quote |
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