gene

AQP4

Entity Detail — Knowledge Graph Node

Understanding Entity Pages

This page aggregates everything SciDEX knows about AQP4: 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.

1873Connections

25Hypotheses

14Analyses

50Outgoing

50Incoming

9Experiments

16Debates

Summary

AQP4 is a gene implicated in neurodegeneration research. Key relationships include: associated with, co discussed, activates. Associated with AD, ALI, ALS. Connected to 576 entities in the SciDEX knowledge graph.

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🧬 Gene Info

Gene Symbol	AQP4
Chromosome	18q11.2
Protein Family	Aquaporin (AQP) family
Target Class	Ion Channel
Mechanism of Action	Water channel inhibitor or modulator
Primary Expression	Astrocytes (perivascular endfeet), Ependyma, Kidney collecting duct
Subcellular Localization	Astrocyte end-feet, perivascular, ependymal
Druggability	Low (0.35)
Clinical Stage	Phase I
Molecular Weight	34 kDa
Amino Acids	323 aa
Pathways	Adaptive Immunity, Apoptosis, Blood-Brain Barrier, Chaperone, Glymphatic Pathway
UniProt ID	P55064
Ensembl ID	ENSG00000171885
GeneCards	AQP4
Human Protein Atlas	AQP4
Associated Diseases	AD, Aging, ALI, Als, Alzheimer
Known Drugs/Compounds	Astragaloside IV, dasatinib, MELATONIN, quercetin, riluzole, TGN-020
Interactions	ABCA1, ALPHA-SYNUCLEIN, ALS, ALZHEIMER, ALZHEIMER'S DISEASE, AMYLOID
SciDEX Target	View Target Profile (1 clinical trials)
SciDEX Hypotheses	SASP-Driven Aquaporin-4 Dysregulation Aquaporin-4 Polarization Rescue Loss of AQP4 Polarization Impairs Glymphatic Periv (+5 more)
KG Connections	1872 knowledge graph edges
Databases	GeneCards NCBI Gene HPA STRING

🧬 3D Structure Comparison — AQP4 Experimental (PDB) vs Predicted (AlphaFold) — click to expand

📄 Experimental Structure

7O3C — X-ray / Cryo-EM

🔮 AI Predicted Structure

P55064 — AlphaFold

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

Wiki Pages (4)

Knowledge base pages for this entity

Canonical Page

Pathway Diagram

flowchart TD
    AQP4(["AQP4"])
    NMOSD["NMOSD"]
    Glymphatic_System("Glymphatic System")
    Central_Nervous_System["Central Nervous System"]
    Neuromyelitis_Optica_Spectrum_Disorder["Neuromyelitis Optica Spectrum Di..."]
    Glymphatic_Pathway["Glymphatic Pathway"]
    Water_Flux("Water Flux")
    Sepsis_Associated_Encephalopathy["Sepsis-Associated Encephalopathy"]
    GLYMPHATIC_SYSTEM["GLYMPHATIC SYSTEM"]
    COMPLEMENT_CASCADE["COMPLEMENT CASCADE"]
    NEUROMYELITIS_OPTICA_SPECTRUM_DISORDER["NEUROMYELITIS OPTICA SPECTRUM DI..."]
    AQP4_Ab(["AQP4-Ab"])
    Neuromyelitis_Optica["Neuromyelitis Optica"]
    Central_Nervous_System_Disorders["Central Nervous System Disorders"]

    AQP4 -->|"biomarker for"| NMOSD
    AQP4 -->|"involved in"| Glymphatic_System
    AQP4 -->|"expressed in"| Central_Nervous_System
    AQP4 -->|"biomarker for"| Neuromyelitis_Optica_Spectrum_Disorder
    AQP4 -->|"involved in"| Glymphatic_Pathway
    AQP4 -->|"mediates"| Water_Flux
    AQP4 -->|"associated with"| Sepsis_Associated_Encephalopathy
    AQP4 -->|"associated with"| Glymphatic_System
    AQP4 -->|"involved in"| GLYMPHATIC_SYSTEM
    AQP4 -->|"activates"| COMPLEMENT_CASCADE
    AQP4 -->|"associated with"| NEUROMYELITIS_OPTICA_SPECTRUM_DISORDER
    AQP4 -->|"biomarker for"| NEUROMYELITIS_OPTICA_SPECTRUM_DISORDER
    AQP4_Ab -->|"binds"| AQP4
    AQP4 -->|"associated with"| Neuromyelitis_Optica
    AQP4 -->|"associated with"| Central_Nervous_System_Disorders

    style AQP4 fill:#006494,stroke:#4fc3f7,stroke-width:3px,color:#e0e0e0

Outgoing (1424)

Target	Relation	Type	Str
ds-f2c28aed24a7	provides_data_for	dataset	1.00
GLYMPHATIC SYSTEM	involved_in	entity	0.95
Glymphatic Pathway	component_of	pathway	0.95
Neuromyelitis Optica Spectrum Disorder	biomarker_for	disease	0.95
NMOSD	biomarker_for	disease	0.95
Tau Clearance	regulates	process	0.95
CSF-ISF Exchange	associated_with	process	0.95
COMPLEMENT CASCADE	activates	entity	0.95
Glymphatic Dysfunction	involved_in	mechanism	0.95
Glymphatic Pathway	involved_in	pathway	0.95
Perivascular Water Transport	mediates	process	0.95
NEUROMYELITIS OPTICA SPECTRUM DISORDER	associated_with	entity	0.95
NEUROMYELITIS OPTICA SPECTRUM DISORDER	biomarker_for	entity	0.95
Astrocyte Endfeet	expressed_in	cell_type	0.95
CSF-ISF Exchange	mediates	process	0.95
Amyloid Beta Clearance	regulates	process	0.95
Glymphatic Clearance	mediates	process	0.95
Astrocytic Endfeet	expressed_in	cell_type	0.95
Neuromyelitis Optica	biomarker_for	disease	0.95
Neuromyelitis Optica Spectrum Disorder	associated_with	disease	0.95
Glymphatic System	component_of	process	0.95
Aquaporin-4-IgG	binds	biomarker	0.95
Glymphatic Transport	mediates	process	0.95
Water Flux	mediates	process	0.95
glymphatic pathway	mediates	pathway	0.95
Glymphatic System	involved_in	process	0.95
Central Nervous System	expressed_in	cell_type	0.95
Sepsis-Associated Encephalopathy	associated_with	disease	0.95
Glymphatic System	associated_with	process	0.95
Astrocytic Autophagy	inhibits	process	0.90
astrocytes	associated_with	cell_type	0.90
Tau Aggregation	protects_against	process	0.90
CHI3L1	regulates	protein	0.90
Central Nervous System Disorders	associated_with	disease	0.90
demyelination	implicated_in	process	0.90
brain edema	promotes	phenotype	0.90
astrocytes	inhibits	cell_type	0.90
Amyloid Beta	associated_with	protein	0.90
NMOSD	markers	disease	0.90
MULTIPLE SCLEROSIS	associated_with	entity	0.90
Metabolic waste clearance	mediates	process	0.90
Beta-Amyloid Clearance	involved_in	process	0.90
Neuromyelitis Optica	markers	disease	0.90
Tau clearance	mediates	process	0.90
NF-κB Pathway	inhibits	pathway	0.90
BRAIN TISSUE HOMEOSTASIS	involved_in	entity	0.90
β-amyloid clearance	mediates	process	0.90
Central Nervous System Injury	involved_in	disease	0.90
Cerebrospinal fluid influx	modulates	process	0.90
Cerebral Edema	associated_with	phenotype	0.90

Incoming (449)

Source	Relation	Type	Str
ds-f2c28aed24a7	data_in	dataset	1.00
IGG AUTOANTIBODY	binds	protein	0.95
AQP4-Ab	binds	protein	0.95
AQP4-ANTIBODY	binds	protein	0.95
TGN-020	targets	drug	0.95
B Cells	regulates	cell_type	0.90
h-c8ccbee8	targets_gene	hypothesis	0.90
h-62e56eb9	targets_gene	hypothesis	0.90
h-807d7a82	targets_gene	hypothesis	0.90
Cecal Ligation and Perforation	upregulates	process	0.90
TGN-020	inhibits	drug	0.90
B cells	regulates	cell_type	0.90
Testosterone	upregulates	compound	0.85
Plasmablast/Plasma Cell	associated_with	cell_type	0.85
Progesterone	upregulates	compound	0.85
Estrogen	upregulates	compound	0.85
SDA-2026-04-01-gap-013	targets	analysis	0.85
B Cells	modulates	cell_type	0.85
B Cells	interacts_with	cell_type	0.85
Musk	downregulates	drug	0.80
MMP9	inhibits	gene	0.80
IFN	modulates	gene	0.80
AQP1	co_mentioned_with	gene	0.80
TMAO	downregulates	drug	0.80
P38MAPK	regulates	pathway	0.80
h-c8ccbee8	targets	hypothesis	0.80
TDP-43	downregulates	protein	0.80
GFAP	co-regulated_with	protein	0.80
h-62e56eb9	targets	hypothesis	0.80
BHB	regulates	compound	0.80
B Cells	associated_with	cell_type	0.80
h-807d7a82	targets	hypothesis	0.80
MTNR1A	regulates_expression	gene	0.80
IL1B	downregulates	gene	0.80
TNF	downregulates	gene	0.80
Reactive Astrogliosis	modulates	process	0.75
Microglia	involved_in	cell_type	0.75
RILUZOLE	causes	drug	0.70
ALZHEIMER'S DISEASE	causes	disease	0.70
MELATONIN	regulates	drug	0.70
MELATONIN	activates	drug	0.70
GABA	causes	phenotype	0.70
SENESCENCE	stabilizes	phenotype	0.70
SULFORAPHANE	regulates	drug	0.65
ASTROCYTE	targets	cell_type	0.65
STROKE	targets	disease	0.65
SULFORAPHANE	protects_against	drug	0.65
CSF	activates	phenotype	0.65
ASTROCYTE	treats	cell_type	0.65
ALPHA-SYNUCLEIN	associated_with	concept	0.65

Targeting Hypotheses (25)

Hypotheses where this entity is a therapeutic target

Hypothesis	Score	Disease	Analysis
Targeting the Mechanistic Link Between AQP4 Dysfunction and	0.803	neurodegeneration	View
SASP-Driven Aquaporin-4 Dysregulation	0.782	neurodegeneration	Senolytic therapy for age-related neurod
Aquaporin-4 Polarization Rescue	0.732	neurodegeneration	4R-tau strain-specific spreading pattern
TREM2-Dependent Microglial Surveillance Controls AQP4-Mediat	0.691	neuroscience	Circuit-level neural dynamics in neurode
Loss of AQP4 Polarization Impairs Glymphatic Perivascular In	0.690	neurodegeneration	What are the specific molecular mechanis

Time-Limited AQP4 Inhibition for Acute Cytotoxic Edema Follo	0.690	neurodegeneration	How can AQP4 be effectively targeted the
Aryl Hydrocarbon Receptor (AHR) Activation in B Cells Determ	0.683	neuroinflammation	How do B cells mechanistically orchestra
AQP4 Dysregulation Promotes Neuroinflammation Through Impair	0.680	neurodegeneration	What are the specific molecular mechanis
AQP4-Dependent Astrocyte Swelling Exacerbates Excitotoxic Ne	0.670	neurodegeneration	What are the specific molecular mechanis
Restore AQP4 Perivascular Polarization by Stabilizing DAPC/S	0.670	neurodegeneration	How can AQP4 be effectively targeted the
Pharmacologically Boost AQP4X Readthrough to Restore Perivas	0.650	neurodegeneration	How can AQP4 be effectively targeted the
IL-10-Producing B10 Cells Establish AQP4-Specific Peripheral	0.648	neuroinflammation	How do B cells mechanistically orchestra
Treat Glymphatic Failure by Coupling AQP4-Targeted Therapy t	0.630	neurodegeneration	How can AQP4 be effectively targeted the
Combine Anti-AQP4 Autoimmunity Control with Astrocyte-Endfoo	0.630	neurodegeneration	How can AQP4 be effectively targeted the
AQP4 Missorting in Reactive Astrocytes Drives Glymphatic Fai	0.580	neurodegeneration	What are the specific molecular mechanis
Disrupted AQP4-Mediated K+ Spatial Buffering Causes Neuronal	0.580	neurodegeneration	What are the specific molecular mechanis
Closed-loop transcranial focused ultrasound to restore hippo	0.564	Alzheimer's disease	Circuit-level neural dynamics in neurode
AQP4 Autoantibodies in NMOSD Cause Bystander Oligodendrocyte	0.560	neurodegeneration	What are the specific molecular mechanis
Closed-loop transcranial focused ultrasound to restore hippo	0.551	Alzheimer's disease	Circuit-level neural dynamics in neurode
Glymphatic System-Enhanced Antibody Clearance Reversal	0.537	neurodegeneration	Blood-brain barrier transport mechanisms
Restoring AQP4 Astrocyte Polarization Enhances Glymphatic Ta	0.520	neurodegeneration	Investigate prion-like spreading of tau
Selectively Inhibit Maladaptive AQP4-Driven Astrocyte-Microg	0.500	neurodegeneration	How can AQP4 be effectively targeted the
Shift AQP4 Isoform/OAP Assembly Toward Clearance-Competent A	0.500	neurodegeneration	How can AQP4 be effectively targeted the
Targeting AQP4 Sumoylation to Enhance Glymphatic Clearance a	0.490	neurodegeneration	What are the specific molecular mechanis
AQP4 Water Channel Normalization as Surrogate Marker and The	0.105	neurodegeneration	Neuroinflammation Biomarker Panel for Ea

Mentioning Analyses (14)

Scientific analyses that reference this entity

Experiments (9)

Experimental studies targeting or related to this entity

Experiment	Type	Disease	Score	Feasibility	Model	Status	Est. Cost
CSF Dynamic Biomarkers for Differential Diagnosis of NPH vs AD with Co	clinical	Alzheimer's Disease	0.900	0.50	aortic endothelial cells	proposed	$6,550,000
IL-10 deficiency and VLC ceramide accumulation in inflammatory bowel d	validation	inflammatory bowel disease	0.900	0.00	IL-10 knockout mice	proposed	N/A
s:** - Test tau spreading in AQP4 knockout vs wild-type mice with PSP/	falsification	Neurodegeneration	0.400	0.50	mouse	proposed	$260,000
Proposed experiment from debate on Perivascular spaces and glymphatic	falsification	Neurodegeneration	0.400	0.50	mouse	proposed	$240,000
Proposed experiment from debate on Perivascular spaces and glymphatic	falsification	Neurodegeneration	0.400	0.50	cell_line	proposed	$100,000
Glymphatic-Circadian Axis Enhancement Therapy for Parkinson's Disease	clinical	Parkinson's Disease	0.400	0.50	human	proposed	$5,460,000
CSF Dynamic Biomarkers for Differential Diagnosis of NPH vs AD with Co	clinical	Alzheimer's Disease	0.400	0.50	human	proposed	$5,460,000
NPH Glymphatic System Interaction Experiment	clinical	Neurodegeneration	0.400	0.50	human	proposed	$5,460,000
Vascular Contributions to Alzheimer Disease and Mixed Pathology	clinical	Alzheimer'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
Aquaporin-4 in glymphatic system, and its implication for central nervous system [PMID:36796590]	Peng S, Liu J, Liang C, Yang L, Wang G	Neurobiol Dis	2023	2
Uncommon inflammatory/immune-related myelopathies. [PMID:34715593]	Valencia-Sanchez C, Flanagan EP	J Neuroimmunol	2021	2
B cells orchestrate tolerance to the neuromyelitis optica autoantigen AQP4. [PMID:38383779]	Afzali AM, Nirschl L, Sie C, Pfaller M,	Nature	2024	1
Glymphatic System Impairment in Alzheimer's Disease and Idiopathic Normal Pressu [PMID:31959516]	Reeves BC, Karimy JK, Kundishora AJ, Mes	Trends Mol Med	2020	1
Inebilizumab-cdon. [PMID:32936251]	Unknown	American journal of health-sys	2020	1
The glymphatic pathway in neurological disorders. [PMID:30353860]	Rasmussen MK, Mestre H, Nedergaard M	Lancet Neurol	2018	1
Sleep drives metabolite clearance from the adult brain. [PMID:24136970]	Xie L, Kang H, Xu Q, Chen MJ, Liao Y, Th	Science	2013	1
β-Hydroxybutyrate improves glymphatic system function and alleviates cerebral ed [PMID:41535708]	Yu MJ, Xiong RQ, Wu JW, Li YC, Xie JX et	Acta Pharmacol Sin	2026	0
NRF2 deficit prevents pathologic Tau seeding and spreading in an induced tauopat [PMID:41650822]	López-Sampere Y, Mengod Soler P, Roca-Pe	Redox Biol	2026	0
Neutrophil-microglia interaction drives motor dysfunction in a neuromyelitis opt [PMID:41665955]	Qi F, Lennon VA, Zhao S, Guo Y, Ding H e	J Clin Invest	2026	0
ACSL4-mediated astrocyte ferroptosis augments neuroinflammation and exacerbates [PMID:41776085]	Wen H, Zi Y, Liu Z, Bai Y, Lin J et al.	Cell Death Differ	2026	0
Safety and efficacy of ravulizumab in patients with NMOSD previously treated wit [PMID:41782198]	Bennett JL, Bhattacharyya S, Zabeti A, L	Mult Scler	2026	0
Therapeutic updates in NMOSD and MOGAD: From present practice to future promise. [PMID:41927387]	Elosua-Bayés I, Cobo-Calvo A	Rev Neurol (Paris)	2026	0
Multimodal MR Imaging Reveals the Mechanisms of Post-Cardiac-Arrest Brain edema: [PMID:41933462]	Tan Y, Ye H, Ge Q, Wang P, Liu Z et al.	J Magn Reson Imaging	2026	0
Recurrent aquaporin 4-immunoglobulin G-positive neuromyelitis optica spectrum di [PMID:41915816]	Jiang X, Chen J, Wen Y, Yuan L, Zhang J	The Journal of international m	2026	0
Astragaloside IV alleviates post-traumatic cytotoxic edema via inhibition of AQP [PMID:41916121]	Shen W, Jiang C, Liu X, Wang D, Li G, Hu	Phytomedicine : international	2026	0
Glymphatic System Dysfunction in Central Nervous System Diseases. [PMID:41792880]	Zahran A, Abu-Khazneh O, Bdair M, Hajjeh	CNS neuroscience & therapeutic	2026	0
The postnatal expression of transcripts and proteins in the corpus callosum, as [PMID:41915271]	Mayo F, González-Vinceiro L, Hiraldo-Gon	Journal of physiology and bioc	2026	0
Diagnostic Value of the Kappa Free Light Chain Index to Distinguish MOGAD, NMOSD [PMID:41921124]	Tournier A, Gavoille A, Pique J, Levraut	Neurology	2026	0
Mapping the Brain's Glymphatic System. [PMID:41751308]	Voumvourakis K, Thomaidis NS, Tsiodras S	Biomedicines	2026	0

Debates (16)

Multi-agent debates referencing this entity

AQP4

Understanding Entity Pages

Summary

Wiki Pages (4)

AQP4 (Aquaporin-4 Gene)

Aquaporin-4 (AQP4) - Glymphatic System Biomarker

AQP4 Protein — Aquaporin 4

AQP4 Protein

Pathway Diagram

Outgoing (1424)

Incoming (449)

Targeting Hypotheses (25)

Mentioning Analyses (14)

Can ferroptosis inhibitors prevent BBB disruption and edema formation after card

How do B cells mechanistically orchestrate tolerance to AQP4 and prevent autoimm

Why do systemic anti-inflammatory drugs fail in AD despite cardiovascular effica

How do non-cell autonomous effects of autophagy dysfunction contribute to ALS pa

What are the specific molecular mechanisms by which AQP4 dysfunction contributes

How can AQP4 be effectively targeted therapeutically to improve neurological out

Circuit-level neural dynamics in neurodegeneration

SEA-AD Gene Expression Profiling — Allen Brain Cell Atlas

Sleep disruption as cause and consequence of neurodegeneration

Perivascular spaces and glymphatic clearance failure in AD

Senolytic therapy for age-related neurodegeneration

Astrocyte reactivity subtypes in neurodegeneration

4R-tau strain-specific spreading patterns in PSP vs CBD

Blood-brain barrier transport mechanisms for antibody therapeutics

Experiments (9)

Related Papers (20)

Debates (16)

Can ferroptosis inhibitors prevent BBB disruption and edema formation after card

While the abstract identifies AQP4 as a 'potential and promising target' and men

The abstract states that AQP4 'is part of the pathogenesis' of CNS disorders and

The title suggests B cells actively maintain tolerance to AQP4, but the specific

The title suggests B cells actively maintain tolerance to AQP4, but the specific

PSP and CBD both involve 4R-tau but produce distinct neuropathological patterns

PSP and CBD both involve 4R-tau but produce distinct neuropathological patterns

How do non-cell autonomous effects of autophagy dysfunction contribute to ALS pa

Astrocyte reactivity subtypes in neurodegeneration

The debate noted clinical failures of TNF-α and IL-6 inhibitors in AD despite th