concept

PHASE SEPARATION

Entity Detail — Knowledge Graph Node

Understanding Entity Pages

This page aggregates everything SciDEX knows about PHASE SEPARATION: 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.

23Connections

9Hypotheses

1Analyses

12Outgoing

11Incoming

11Experiments

1Debates

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💡 Concept Info

Name	PHASE SEPARATION

Pathway Diagram

graph TD
    PHASE_SEPARATION[PHASE SEPARATION]
    PHASE_SEPARATION -->|involved_in| Normal_Cell_Function[Normal Cell Function]
    PHASE_SEPARATION -->|mediates| stress_granule_formation[stress granule formation]
    PHASE_SEPARATION -->|involved_in| Stress_Granules[Stress Granules]
    PHASE_SEPARATION -->|involved_in| Stress_Granule_Formation[Stress Granule Formation]
    PHASE_SEPARATION -->|mediates| Condensate_Formation[Condensate Formation]
    PHASE_SEPARATION -->|contributes to| TDP_43_Aggregation[TDP-43 Aggregation]
    PHASE_SEPARATION -->|drives| DDR_foci_formation[DDR foci formation]
    PHASE_SEPARATION -->|mediates| stress_granules[stress granules]
    PHASE_SEPARATION -->|drives| protein_aggregation[protein aggregation]
    PHASE_SEPARATION -->|involved_in| STAU1_Condensate_Formation[STAU1 Condensate Formation]
    DNAJB6[DNAJB6] -->|regulates| PHASE_SEPARATION
    Repeat_Rna[Repeat Rna] -->|modulates| PHASE_SEPARATION
    TDP_43_Misfolding[TDP-43 Misfolding] -->|mediates| PHASE_SEPARATION
    RNA_G_quadruplexes[RNA G-quadruplexes] -->|regulates| PHASE_SEPARATION
    Tdp43_Low_Complexity_Domain[Tdp43 Low-Complexity Domain] -->|mediates| PHASE_SEPARATION
    SYNCRIP[SYNCRIP] -->|mediates| PHASE_SEPARATION
    Tp53Bp1[Tp53Bp1] -->|involved_in| PHASE_SEPARATION
    UBQLN2[UBQLN2] -->|involved_in| PHASE_SEPARATION
    Chemical_Modulators[Chemical Modulators] -->|modulates| PHASE_SEPARATION

Outgoing (12)

Target	Relation	Type	Str
Normal Cell Function	involved_in	phenotype	0.95
stress granule formation	mediates	process	0.94
Stress Granules	involved_in	process	0.90
Condensate Formation	mediates	mechanism	0.90
TDP-43 Aggregation	contributes_to	mechanism	0.90
DDR foci formation	drives	process	0.90
Stress Granule Formation	associated_with	process	0.90
stress granules	mediates	process	0.90
protein aggregation	drives	process	0.90
STAU1 Condensate Formation	involved_in	mechanism	0.85
PABP1	associated_with	protein	0.85
biomolecular condensates	forms	structure	0.70

Incoming (11)

Source	Relation	Type	Str
DNAJB6	regulates	protein	0.93
Repeat Rna	modulates	compound	0.90
TDP-43 Misfolding	mediates	mechanism	0.90
RNA G-quadruplexes	regulates	process	0.90
Tdp43 Low-Complexity Domain	mediates	protein	0.90
Phosphorylation	associated_with	process	0.85
Tp53Bp1	involved_in	protein	0.85
UBQLN2	involved_in	protein	0.85
SYNCRIP	mediates	protein	0.85
Chemical Modulators	modulates	compound	0.80
FUS	drives	gene	0.70

Targeting Hypotheses (9)

Hypotheses where this entity is a therapeutic target

Hypothesis	Score	Disease	Analysis
HSPB1 Phosphorylation Mimetics to Promote Protective TDP-43	0.820	neurodegeneration	What is the therapeutic window between i
Stress Granule Phase Separation Modulators	0.720	neurodegeneration	RNA binding protein dysregulation across
TRIM21 as a 'Phase Separation Thermostat' via Catalytic Reve	0.700	neurodegeneration	How does TRIM21-mediated K63 ubiquitinat
p62 Liquid-Liquid Phase Separation Nucleates Cross-Organelle	0.649	neurodegeneration	How do different organelle-specific auto
Small Molecule Modulation of Phase Separation	0.640	neurodegeneration	What determines the specificity of RNA-p

Hierarchical Phase Separation with Scaffold Cores	0.630	neurodegeneration	What determines the specificity of RNA-p
ALS-Associated G3BP1 Mutations Shift Phase Separation Equili	0.610	neurodegeneration	How do disease-associated mutations in G
Liquid-Liquid Phase Separation Modifier Therapy	0.551	neurodegeneration	Protein aggregation cross-seeding across
Liquid-Liquid Phase Separation (LLPS) Saturation Partitionin	0.461	neurodegeneration	What determines the spatial organization

Mentioning Analyses (1)

Scientific analyses that reference this entity

How do host cell factors influence the conformation and propagation properties o

neurodegeneration | 2026-04-08 | 0 hypotheses

Experiments (11)

Experimental studies targeting or related to this entity

Experiment	Type	Disease	Score	Feasibility	Model	Status	Est. Cost
G3BP1-mediated stress granule assembly via liquid-liquid phase separat	exploratory		0.900	0.00	eukaryotic cells	proposed	N/A
TRIM21 E3 ubiquitin ligase screen for stress granule regulation	exploratory	neurodegenerative diseases	0.900	0.00	cultured 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
C9orf72 Phenotype Divergence: ALS vs FTD Mechanism Study	clinical	ALS	0.400	0.50	human	proposed	$6,550,000
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
Pre-Symptomatic Detection and Intervention Timing in Genetic Prion Dis	validation	ALS	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
Stress Granule Dysfunction Validation in Parkinson's Disease	clinical	Parkinson's Disease	0.400	0.50	human	proposed	$5,460,000

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
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
Ubiquitination of G3BP1 mediates stress granule disassembly in a context-specifi [PMID:34739333]	Gwon Y, Maxwell BA, Kolaitis RM, Zhang P	Science	2021	1
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
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
Implications of virus-induced stress granules in tauopathies. [PMID:41673769]	Sharma S, Vandenakker A, Cortés-Pérez C,	Transl Neurodegener	2026	0
Pharmacological modulation of stress granules via G3BP1/2: A pathway to treat ca [PMID:41924133]	Yang J, Gao F	Front Pharmacol	2026	0
Stress granules at the crossroads of retroviral replication and antiviral immuni [PMID:41931190]	Akbarin MM, Farjami Z, Álvarez HR	Mol Biol Rep	2026	0
Pharmacological modulation of stress granules via G3BP1/2: A pathway to treat ca [PMID:41924133]	Yang J, Gao F	Frontiers in pharmacology	2026	0
Disruption of G3BP1 granules promotes mammalian CNS and PNS axon regeneration. [PMID:40014573]	["Sahoo P", "Agrawal M", "Hanovice N", "	Proceedings of the National Ac	2025	0
RIOK1 phase separation restricts PTEN translation via stress granules activating [PMID:40467995]	["Meng F", "Li H", "Huang Y", "Wang C",	Nature cancer	2025	0
β-propeller protein-associated neurodegeneration protein WDR45 regulates stress [PMID:40473629]	["Li Y", "Fang J", "Ding Y", "Zhang X",	Nature communications	2025	0
Identification of small molecule inhibitors of G3BP-driven stress granule format [PMID:38284934]	["Freibaum B", "Messing J", "Nakamura H"	The Journal of cell biology	2024	0

Debates (1)

Multi-agent debates referencing this entity

How do host cell factors influence the conformation and propagation properties o

closed · Rounds: 4 · Score: 0.95 · 2026-04-10

Related Research

Hypotheses and analyses mentioning PHASE SEPARATION in their description or question text

Hierarchical Phase Separation with Scaffold Cores

Score: 0.630 · neurodegeneration · 2026-04-21

**Molecular Mechanism and Rationale** The hierarchical phase separation model proposes a sophisticated two-tier mechani

ALS-Associated G3BP1 Mutations Shift Phase Separation Equilibrium Toward Aberran

Score: 0.610 · neurodegeneration · 2026-04-22

## Mechanistic Overview ALS-Associated G3BP1 Mutations Shift Phase Separation Equilibrium Toward Aberrant Condensate Sta

Liquid-Liquid Phase Separation Modifier Therapy

Score: 0.551 · neurodegeneration · 2026-04-02

Compounds that modulate the surface tension and composition of biomolecular condensates could prevent the aberrant mixin

Liquid-Liquid Phase Separation (LLPS) Saturation Partitioning Excludes Autophagy

Score: 0.461 · neurodegeneration · 2026-04-21

## Mechanistic Overview Liquid-Liquid Phase Separation (LLPS) Saturation Partitioning Excludes Autophagy Receptors from