gene

G3BP1

Entity Detail — Knowledge Graph Node

Understanding Entity Pages

This page aggregates everything SciDEX knows about G3BP1: its mechanistic relationships (Knowledge Graph edges), hypotheses targeting it, analyses mentioning it, and supporting scientific papers. The interactive graph below shows its immediate neighbors. All content is AI-synthesized from peer-reviewed literature.

1194Connections

24Hypotheses

11Analyses

50Outgoing

50Incoming

13Experiments

14Debates

Summary

G3BP1 is a gene implicated in neurodegeneration research. Key relationships include: interacts with, activates, regulates. Associated with AD, ALI, ALS. Connected to 448 entities in the SciDEX knowledge graph.

View on Wiki →

No AI portrait yet

🧬 Gene Info

Gene Symbol	G3BP1
Full Name	Ras-GTPase-Activating Protein-Binding Protein 1
Chromosome	5q33.1
Protein Type	Signaling Protein
Target Class	Signaling Protein
Function	SG Nucleation: G3BP1 acts as a scaffold for SG assembly, recruiting other SG components
Mechanism of Action	G3BP1 inhibitors would prevent stress granule assembly and stabilization by disrupting the interaction between G3BP1 and its binding partners, potentially reducing pathological aggregation of TDP-43 and FUS proteins. This mechanism could alleviate neurodegeneration in conditions characterized by aberrant stress granule formation and RNA metabolism dysfunction.
Primary Expression	Ubiquitous, high in brain (neurons, glia)
Druggability	Medium (0.47)
Clinical Stage	Phase II
Molecular Weight	~52 kDa
Pathways	Apoptosis, Autophagy, Er Stress, Immune Response, Mtor
UniProt ID	A0A7I2V3C4
NCBI Gene ID	9973
Ensembl ID	ENSG00000130830
GeneCards	G3BP1
Human Protein Atlas	G3BP1
Associated Diseases	AD, ALI, Als, Alzheimer, AMI, amyotrophic lateral sclerosis
Known Drugs/Compounds	axonal mRNA, EGCG, Intracellular Free Rna, rapamycin, trehalose
Interactions	ABCD3, ACTB, Actin, Akt, AKT, ALS
SciDEX Target	View Target Profile (7 clinical trials)
SciDEX Hypotheses	Ubiquitin-Mediated Liquid-to-Solid Transition Prev Phase-Separated Organelle Targeting Autophagic Receptor Sequestration via K63-Ub 'Sign (+11 more)
KG Connections	1194 knowledge graph edges
Databases	GeneCards HPA STRING

🧬 3D Structure Comparison — G3BP1 Experimental (PDB) vs Predicted (AlphaFold) — click to expand

📄 Experimental Structure

4FCJ — X-ray / Cryo-EM

🔮 AI Predicted Structure

A0A7I2V3C4 — AlphaFold

Left: Experimental structure from RCSB PDB | Right: AI-predicted structure from AlphaFold | Powered by Mol*

Wiki Pages (2)

Knowledge base pages for this entity

Canonical Page

G3BP1

gene · 1167 words

→

G3BP1 Protein — Ras-GTPase-Activating Protein-Binding Protein 1

protein · 792 words

→

Pathway Diagram

graph TD
    G3BP1["G3BP1"] -->|"associated"| neurodegeneration["neurodegeneration"]
    G3BP1["G3BP1"] -->|"co discussed"| SRPK1["SRPK1"]
    TGM2["TGM2"] -->|"co discussed"| G3BP1["G3BP1"]
    PRMT1["PRMT1"] -->|"co discussed"| G3BP1["G3BP1"]
    PARP1["PARP1"] -->|"co discussed"| G3BP1["G3BP1"]
    HSPA1A["HSPA1A"] -->|"co discussed"| G3BP1["G3BP1"]
    style G3BP1 fill:#4a1a6b,stroke:#4fc3f7,stroke-width:2px,color:#e0e0e0

Outgoing (766)

Target	Relation	Type	Str
Stress Granule Formation	involved_in	process	0.95
STRESS GRANULE DISASSEMBLY	involved_in	entity	0.95
Liquid-Liquid Phase Separation	mediates	process	0.95
Stress Granule Disassembly	mediates	process	0.95
Stress Granules	associated_with	process	0.95
stress granule formation	involved_in	process	0.95
STRESS GRANULE ASSEMBLY	regulates	entity	0.95
stress granule-like structures	involved_in	process	0.95
Stress Granule Formation	mediates	process	0.95
Stress Granule	component_of	organelle	0.95
LIQUID-LIQUID PHASE SEPARATION	mediates	entity	0.95
PI3K/Akt signaling	activates	pathway	0.95
immune evasion	promotes	process	0.94
SLU7	interacts_with	protein	0.92
Stress Granule Assembly	mediates	process	0.92
axonal mRNA translation	inhibits	process	0.90
AUTOPHAGY	associated_with	entity	0.90
stress granules	activates	process	0.90
LINC00599	interacts_with	gene	0.90
Stress Granule	interacts_with	cell_type	0.90
STRESS GRANULE	associated_with	biological_process	0.90
Ribonucleoprotein Granules	regulates	process	0.90
Stress Granule	involved_in	process	0.90
anti-PD-1 therapy response	risk_factor_for	phenotype	0.90
STRESS GRANULE-SPECIFIC INTERACTION NETWORK	regulates	entity	0.90
Stress Granules	component_of	structure	0.90
Stress Granules	activates	process	0.90
Stress Granules	mediates	process	0.90
Liquid-Liquid Phase Separation	involved_in	process	0.90
Intrinsically Disordered Regions	involved_in	mechanism	0.88
ALS	associated_with	entity	0.85
axonal mRNA	binds	compound	0.85
NEURODEGENERATIVE DISEASES	implicated_in	entity	0.85
Stress Granule Interaction Network	regulates	pathway	0.85
Prostate Cancer	upregulates	disease	0.85
MYH9	interacts_with	protein	0.85
MULTISYSTEM PROTEINOPATHY	implicated_in	entity	0.85
FTD	implicated_in	entity	0.85
FAF2	interacts_with	protein	0.85
cell apoptosis	regulates	process	0.80
Stress Response	involved_in	process	0.80
neural stem cells	regulates	cell_type	0.80
autophagy pathway	participates_in	pathway	0.80
ubiquitin-proteasome	participates_in	pathway	0.80
stress_granules	associated_with	entity	0.80
NF-κB	regulates	pathway	0.80
axonal mRNA translation	limits	process	0.80
nerve regeneration	limits	process	0.80
stress_granule_formation	nucleates	pathway	0.80
stress_granule_formation	controls	pathway	0.80

Incoming (428)

Source	Relation	Type	Str
Ubiquitination	modulates	process	0.95
hiPSC-derived lung organoid	expressed_in	cell_type	0.95
Nsp3	binds	protein	0.95
UBIQUITIN	mediates	entity	0.95
UBIQUITINATION	modulates	entity	0.95
TRIM21	phosphorylates	protein	0.95
TRIM21	associated_with	gene	0.90
Intracellular Free Rna	activates	compound	0.90
h-ec731b7a	targets	hypothesis	0.90
h-97aa8486	targets	hypothesis	0.90
LINC00599	interacts_with	gene	0.90
h-27bc0569	targets_gene	hypothesis	0.90
h-fffd1a74	targets	hypothesis	0.90
ubiquitination	regulates	process	0.90
PHOSPHORYLATION	modulates	entity	0.90
EGCG	inhibits	drug	0.89
Phosphorylation	modulates	process	0.85
Prrc2B	interacts_with	protein	0.85
Prrc2C	interacts_with	protein	0.85
Prrc2A	interacts_with	protein	0.85
Heat Shock	associated_with	phenotype	0.85
axotomy	modulates	process	0.85
SQSTM1/p62	interacts_with	protein	0.80
SQSTM1	binds	gene	0.80
CALCOCO2/NDP52	interacts_with	protein	0.80
STING	interacts_with	gene	0.80
CALCOCO2	regulates	gene	0.70
ALS	regulates	gene	0.70
ATG	activates	gene	0.70
ATG	regulates	gene	0.70
BECN1	regulates	gene	0.70
MITOCHONDRIA	interacts_with	gene	0.60
ATP	interacts_with	gene	0.60
AMYOTROPHIC LATERAL SCLEROSIS	regulates	gene	0.60
NEURODEGENERATIVE DISEASES	interacts_with	gene	0.60
PARKINSON	interacts_with	gene	0.60
NF-ΚB	activates	gene	0.60
NIX	interacts_with	gene	0.60
DNA	interacts_with	gene	0.60
CANCER	activates	gene	0.60
GFP	interacts_with	gene	0.60
LGALS8	interacts_with	gene	0.60
ALS	interacts_with	gene	0.60
MTORC1	regulates	gene	0.60
AUTOPHAGY	activates	gene	0.60
RIP3	interacts_with	gene	0.60
PRESENILIN	interacts_with	gene	0.60
HIF	activates	gene	0.60
NEURON	activates	gene	0.60
TRIM21	interacts_with	gene	0.60

Targeting Hypotheses (24)

Hypotheses where this entity is a therapeutic target

Hypothesis	Score	Disease	Analysis
H3: G3BP1 as Nucleation Hub for TDP-43/FUS Seeding	0.743	neurodegeneration	How do pathological stress granules tran
H2: Impaired Autophagy Receptor Recruitment Traps G3BP1 Gran	0.737	neurodegeneration	How do pathological stress granules tran
Ubiquitin-Mediated Liquid-to-Solid Transition Prevention	0.730	neurodegeneration	How does TRIM21-mediated K63 ubiquitinat
Phase-Separated Organelle Targeting	0.729	neurodegeneration	Microglia-astrocyte crosstalk amplificat
Autophagic Receptor Sequestration via K63-Ub 'Signalone' Rec	0.720	neurodegeneration	How does TRIM21-mediated K63 ubiquitinat

Stress Granule Phase Separation Modulators	0.720	neurodegeneration	RNA binding protein dysregulation across
Ataxin-2 Polyglutamine Expansions Hijack G3BP1 to Form Toxic	0.700	neurodegeneration	How do disease-associated mutations in G
H5: C9orf72 DPR Dipeptides Corrupt G3BP1 Condensate Properti	0.698	neurodegeneration	How do pathological stress granules tran
RNA Granule Nucleation Site Modulation	0.662	neurodegeneration	TDP-43 phase separation therapeutics for
H1: CK2 Hyperphosphorylation Locks G3BP1 in Hyper-condensed	0.637	neurodegeneration	How do pathological stress granules tran
G3BP1 NTF2L Domain-Mediated mRNP Scaffold Creates Core Exclu	0.633	neurodegeneration	What determines the spatial organization
Steric Occlusion of G3BP1 Oligomerization Interface	0.630	neurodegeneration	How does TRIM21-mediated K63 ubiquitinat
ALS-Associated G3BP1 Mutations Shift Phase Separation Equili	0.610	neurodegeneration	How do disease-associated mutations in G
Displacement of G3BP1 RGG Box from Target RNA via Ubiquitin-	0.600	neurodegeneration	How does TRIM21-mediated K63 ubiquitinat
Competition with G3BP1-Caprin1/FMRP Scaffold Formation	0.590	neurodegeneration	How does TRIM21-mediated K63 ubiquitinat
G3BP1 Haploinsufficiency Reveals a Therapeutic Window for SG	0.590	neurodegeneration	How do disease-associated mutations in G
ALS-Associated G3BP1/2 Mutations Disrupt TRIM21 Binding Inte	0.585	neurodegeneration	How do pathological stress granules in n
Dysregulated G3BP1 Signaling Impairs Local Translation in Ne	0.580	neurodegeneration	How do disease-associated mutations in G
Liquid-Liquid Phase Separation Modifier Therapy	0.551	neurodegeneration	Protein aggregation cross-seeding across
Modulation of G3BP1 Intrinsically Disordered Region Solvatio	0.500	neurodegeneration	How does TRIM21-mediated K63 ubiquitinat
G3BP1-TDP-43 Cross-Seeding Drives Co-Aggregation That Prion-	0.490	neurodegeneration	How do disease-associated mutations in G
Casein Kinase 2 (CK2)-Mediated Hyperphosphorylation of G3BP1	0.440	neurodegeneration	How do pathological stress granules in n
FUS Mutations Impede G3BP1's Chaperone Function, Exposing Ne	0.430	neurodegeneration	How do disease-associated mutations in G
Small-Molecule Modulation of G3BP1 Condensate Dynamics via P	0.400	neurodegeneration	How do disease-associated mutations in G

Mentioning Analyses (11)

Scientific analyses that reference this entity

What determines the spatial organization of autophagy receptors at stress granul

neurodegeneration | 2026-04-08 | 5 hypotheses Top: 0.633

What determines the specificity of RNA-protein interactions that drive distinct

neurodegeneration | 2026-04-07 | 7 hypotheses Top: 0.710

How does TRIM21-mediated K63 ubiquitination of G3BP1 mechanistically inhibit liq

neurodegeneration | 2026-04-07 | 7 hypotheses Top: 0.730

How do pathological stress granules transition from reversible to persistent in

neurodegeneration | 2026-04-06 | 7 hypotheses Top: 0.834

How do pathological stress granules in neurodegeneration escape TRIM21/autophagy

neurodegeneration | 2026-04-06 | 7 hypotheses Top: 0.717

Experiments (13)

Experimental studies targeting or related to this entity

Experiment	Type	Disease	Score	Feasibility	Model	Status	Est. Cost
TRIM21-mediated K63-linked ubiquitination of G3BP1	exploratory		0.950	0.00	in vitro biochemical assays, c	proposed	N/A
G3BP1-mediated stress granule assembly via liquid-liquid phase separat	exploratory		0.900	0.00	eukaryotic cells	proposed	N/A
G3BP1 intrinsically disordered region analysis and phosphorylation eff	exploratory		0.850	0.00	in vitro protein analysis syst	proposed	N/A
G3BP1-binding factor cooperativity in stress granule network regulatio	exploratory		0.800	0.00	cell culture systems with prot	proposed	N/A
Proposed experiment from debate on TDP-43 undergoes liquid-liquid phas	falsification	Neurodegeneration	0.400	0.50	cell_line	proposed	$80,000
Mechanism: C9orf72 Hexanucleotide Repeat Expansion in ALS/FTD	validation	ALS	0.400	0.50	human	proposed	$2,730,000
C9orf72 Phenotype Divergence: ALS vs FTD Mechanism Study	clinical	ALS	0.400	0.50	human	proposed	$6,550,000
Pre-Symptomatic Detection and Intervention Timing in Genetic Prion Dis	validation	ALS	0.400	0.50	human	proposed	$2,280,000
Stress Granule Dysfunction Validation in Parkinson's Disease	clinical	Parkinson's Disease	0.400	0.50	human	proposed	$5,460,000
Experiment Validation: In vitro ThT Assay	validation	Alzheimer's Disease	0.400	0.50	cell_line	proposed	$160,000
Mutant Huntingtin (mHTT) Clearance Mechanisms — Therapeutic Target Val	validation	Neurodegeneration	0.400	0.50	human	proposed	$3,000,000
Multiscale Computational Modeling of Protein Aggregation Kinetics	validation	Parkinson's Disease	0.400	0.50	human	proposed	$2,280,000
Protein Aggregation Kinetic Validation Results	validation	Neurodegeneration	0.400	0.50	in_silico	proposed	$120,000

Related Papers (20)

Scientific publications cited in analyses involving this entity

Title & PMID	Authors	Journal	Year	Citations
Stress granule homeostasis is modulated by TRIM21-mediated ubiquitination of G3B [PMID:36692217]	Yang C, Wang Z, Kang Y, Yi Q, Wang T, Ba	Autophagy	2023	3
G3BP1 Is a Tunable Switch that Triggers Phase Separation to Assemble Stress Gran [PMID:32302571]	Yang P, Mathieu C, Kolaitis RM, Zhang P,	Cell	2020	3
Organelle-specific autophagy in inflammatory diseases: a potential therapeutic t [PMID:32048886]	Yao RQ, Ren C, Xia ZF, Yao YM	Autophagy	2021	2
Hypoxia-driven phase separation of the PABP1/eIF4B complex forms stress granules [PMID:41780839]	Lin Z, Gao Y, Zhang Q, Yang S, Chen Y, D	Cancer Lett	2026	1
LINC00599 Promotes Pulmonary Hypertension via Liquid-Liquid Phase Separation Wit [PMID:40693377]	Wang Y, Yin L, Zheng S, Liu A, Liu C, Ba	Hypertension	2025	1
The important role of stress granules in prostate cancer development, progressio [PMID:40972860]	Xu Z, You H, Gu J, Jiang J, Yan Z, Jin X	Gene	2025	1
Membrane Atg8ylation, stress granule formation, and MTOR regulation during lysos [PMID:36394332]	Jia J, Wang F, Bhujabal Z, Peters R, Mud	Autophagy	2023	1
Role of stress granules in modulating senescence and promoting cancer progressio [PMID:34460104]	Chatterjee D, Chakrabarti O	Int J Cancer	2022	1
Ubiquitination of G3BP1 mediates stress granule disassembly in a context-specifi [PMID:34739333]	Gwon Y, Maxwell BA, Kolaitis RM, Zhang P	Science	2021	1
Proof of concept: targeted protein degradation of the stress granules component [PMID:41586493]	Unknown	Antimicrobial agents and chemo	2026	0
STING is the scaffold protein for stress granule pre-condensation at the ER. [PMID:41917183]	Eom E, Kim J, Kim J, Kang SJ	Cell death and differentiation	2026	0
Stress granules: Guardians of cellular health and triggers of disease. [PMID:39995077]	["Desai M", "Gulati K", "Agrawal M", "Gh	Neural regeneration research	2026	0
WFDC21P is essential for G3BP1-mediated RIG-I activation and antitumor immunity [PMID:41915747]	Li Z, Wang Y, Chen Z, Liu R, Lai ZH, Li	Proceedings of the National Ac	2026	0
NUP93 facilitates the nuclear import of SOX2 to activate G3BP1 transcription and [PMID:41896201]	Sun H, Yang C, Du J, Xu C, Chen Y, Chen	Cell death & disease	2026	0
Implications of virus-induced stress granules in tauopathies. [PMID:41673769]	Sharma S, Vandenakker A, Cortés-Pérez C,	Translational neurodegeneratio	2026	0
Evolution of a truncated nucleocapsid protein enhances SARS-CoV-2 fitness by sup [PMID:41920932]	Mulloy RP, Evseev D, Sharlin N, Bui-Mari	PLoS biology	2026	0
PRRC2A, PRRC2B and PRRC2C are Stress Granule Proteins that Promote Translation T [PMID:41808986]	["Huang J", "Kadijk E", "Schreiber K", "	bioRxiv : the preprint server	2026	0
Rainbow trout (Oncorhynchus mykiss) G3BP1 function as an antiviral molecule agai [PMID:41831384]	["Zhao J", "Shao Y", "Liu W", "Lu T", "X	Fish & shellfish immunology	2026	0
Stress granules: Guardians of cellular health and triggers of disease. [PMID:39995077]	Desai M, Gulati K, Agrawal M, Ghumra S,	Neural Regen Res	2026	0
Uridine analogs prevent stress granule formation, not by blocking PKR recognitio [PMID:41571440]	Ihn SJ, Jiang E, Kejiou NS, Wang YE, Far	RNA	2026	0

Debates (14)

Multi-agent debates referencing this entity

The study establishes G3BP1's role as a tunable switch for stress granule assemb

closed · Rounds: 4 · Score: 0.69 · 2026-04-22

The study shows TRIM21 and autophagy receptors can eliminate both physiological

closed · Rounds: 4 · Score: 0.75 · 2026-04-22

The study shows stress granules are dynamic and reversible assemblies, but in ne

closed · Rounds: 4 · Score: 0.84 · 2026-04-22

The study shows that G3BP1 ubiquitination inhibits LLPS in vitro, but the molecu

closed · Rounds: 4 · Score: 0.79 · 2026-04-21

While the study identifies G3BP1 as a central node triggering phase separation,

closed · Rounds: 4 · Score: 0.76 · 2026-04-21

SQSTM1 and CALCOCO2 specifically localize to SG periphery rather than throughout

closed · Rounds: 4 · Score: 0.69 · 2026-04-21

Protein aggregation cross-seeding across neurodegenerative diseases?

closed · Rounds: 4 · Score: 0.70 · 2026-04-12

RNA binding protein dysregulation across ALS FTD and AD

closed · Rounds: 4 · Score: 0.72 · 2026-04-12

TDP-43 undergoes liquid-liquid phase separation that becomes pathological. Small

closed · Rounds: 6 · Score: 0.84 · 2026-04-12

TDP-43 phase separation therapeutics for ALS-FTD

closed · Rounds: 4 · Score: 0.95 · 2026-04-11

Related Research

Hypotheses and analyses mentioning G3BP1 in their description or question text

G3BP1

Understanding Entity Pages

Summary

Wiki Pages (2)

G3BP1

G3BP1 Protein — Ras-GTPase-Activating Protein-Binding Protein 1

Pathway Diagram

Outgoing (766)

Incoming (428)

Targeting Hypotheses (24)

Mentioning Analyses (11)

What determines the spatial organization of autophagy receptors at stress granul

What determines the specificity of RNA-protein interactions that drive distinct

How does TRIM21-mediated K63 ubiquitination of G3BP1 mechanistically inhibit liq

How do pathological stress granules transition from reversible to persistent in

How do pathological stress granules in neurodegeneration escape TRIM21/autophagy

How do disease-associated mutations in G3BP1 or its binding partners alter stres

RNA binding protein dysregulation across ALS FTD and AD

Microglia-astrocyte crosstalk amplification loops in neurodegeneration

TDP-43 phase separation therapeutics for ALS-FTD

Protein aggregation cross-seeding across neurodegenerative diseases

Protein aggregation cross-seeding across neurodegenerative diseases

Experiments (13)

Related Papers (20)

Debates (14)

The study establishes G3BP1's role as a tunable switch for stress granule assemb

The study shows TRIM21 and autophagy receptors can eliminate both physiological

The study shows stress granules are dynamic and reversible assemblies, but in ne

The study shows that G3BP1 ubiquitination inhibits LLPS in vitro, but the molecu

While the study identifies G3BP1 as a central node triggering phase separation,

SQSTM1 and CALCOCO2 specifically localize to SG periphery rather than throughout

Protein aggregation cross-seeding across neurodegenerative diseases?

RNA binding protein dysregulation across ALS FTD and AD

TDP-43 undergoes liquid-liquid phase separation that becomes pathological. Small

TDP-43 phase separation therapeutics for ALS-FTD

Related Research

Stress Granule Phase Separation Modulators

Ataxin-2 Polyglutamine Expansions Hijack G3BP1 to Form Toxic, Irreversible Stres

H5: C9orf72 DPR Dipeptides Corrupt G3BP1 Condensate Properties

RNA Granule Nucleation Site Modulation

H1: CK2 Hyperphosphorylation Locks G3BP1 in Hyper-condensed State

G3BP1 NTF2L Domain-Mediated mRNP Scaffold Creates Core Exclusion Zone for Autoph

Steric Occlusion of G3BP1 Oligomerization Interface

ALS-Associated G3BP1 Mutations Shift Phase Separation Equilibrium Toward Aberran

Displacement of G3BP1 RGG Box from Target RNA via Ubiquitin-Mediated Allostery

Competition with G3BP1-Caprin1/FMRP Scaffold Formation

G3BP1 Haploinsufficiency Reveals a Therapeutic Window for SG-Targeting Intervent

ALS-Associated G3BP1/2 Mutations Disrupt TRIM21 Binding Interfaces

Dysregulated G3BP1 Signaling Impairs Local Translation in Neuronal Processes, Co

Liquid-Liquid Phase Separation Modifier Therapy

Modulation of G3BP1 Intrinsically Disordered Region Solvation Free Energy