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.

1734Connections
27Hypotheses
18Analyses
50Outgoing
50Incoming
9Experiments
20Debates

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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AI portrait of AQP4

AI-generated illustration

Regenerate portrait ↻
🧬 Gene Info
Gene SymbolAQP4
Chromosome18q11.2
Protein FamilyAquaporin (AQP) family
Target ClassIon Channel
Mechanism of ActionWater channel inhibitor or modulator
Primary ExpressionAstrocytes (perivascular endfeet), Ependyma, Kidney collecting duct
Subcellular LocalizationAstrocyte end-feet, perivascular, ependymal
DruggabilityLow (0.35)
Clinical StagePhase I
Molecular Weight34 kDa
Amino Acids323 aa
PathwaysAdaptive Immunity, Apoptosis, Blood-Brain Barrier, Chaperone, Glymphatic Pathway
UniProt IDP55064
Ensembl IDENSG00000171885
GeneCardsAQP4
Human Protein AtlasAQP4
Associated DiseasesAD, Aging, ALI, Als, Alzheimer
Known Drugs/CompoundsAstragaloside IV, dasatinib, MELATONIN, quercetin, riluzole, TGN-020
InteractionsABCA1, ALPHA-SYNUCLEIN, ALS, ALZHEIMER, ALZHEIMER'S DISEASE, AMYLOID
SciDEX TargetView Target Profile (1 clinical trials)
SciDEX HypothesesSASP-Driven Aquaporin-4 Dysregulation
Aquaporin-4 Polarization Rescue
Loss of AQP4 Polarization Impairs Glymphatic Periv (+7 more)
KG Connections1732 knowledge graph edges
DatabasesGeneCardsNCBI GeneHPASTRING
🧬 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

AQP4 (Aquaporin-4 Gene)

gene · 1866 words

Aquaporin-4 (AQP4) - Glymphatic System Biomarker

biomarker · 1020 words

AQP4 Protein — Aquaporin 4

protein · 766 words

AQP4 Protein

protein · 534 words

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 (1314)

TargetRelationTypeStr
AQP4encodesprotein0.00
ds-f2c28aed24a7provides_data_fordataset1.00
NMOSDbiomarker_fordisease0.95
Neuromyelitis Optica Spectrum Disorderbiomarker_fordisease0.95
GLYMPHATIC SYSTEMinvolved_inentity0.95

Incoming (420)

SourceRelationTypeStr
H2enhances_functionhypothesis0.00
AQP4encodesgene0.00
H5_AQP4detects_glymphatic_dysfunctionbiomarker0.00
ds-f2c28aed24a7data_indataset1.00
AQP4-ANTIBODYbindsprotein0.95

Targeting Hypotheses (27)

Hypotheses where this entity is a therapeutic target

HypothesisScoreDiseaseAnalysis
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
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
CSF/Plasma AQP4 Polarization Index as a Novel Biomarker of A 0.680 - What blood-brain barrier permeability ch
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
Blood Astrocyte-Derived Exosomal AQP4 Mislocalization Predic 0.660 - What blood-brain barrier permeability ch
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
TREM2-Dependent Microglial Surveillance Controls AQP4-Mediat 0.569 neuroscience Circuit-level neural dynamics in neurode
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 (18)

Scientific analyses that reference this entity

What is the minimum effective dose of trazodone required for disease-modifying e

neurodegeneration | 2026-04-26 | 7 hypotheses Top: 0.580

Can CSF p-tau217 normalization serve as a reliable surrogate endpoint for determ

neurodegeneration | 2026-04-26 | 7 hypotheses Top: 0.560

What blood-brain barrier permeability changes serve as early biomarkers for neur

neurodegeneration | 2026-04-26 | 8 hypotheses Top: 0.915

What blood-brain barrier permeability changes serve as early biomarkers for neur

neurodegeneration | 2026-04-26 | 8 hypotheses Top: 0.720

Can ferroptosis inhibitors prevent BBB disruption and edema formation after card

neurodegeneration | 2026-04-25 | 7 hypotheses Top: 0.760

Experiments (9)

Experimental studies targeting or related to this entity

ExperimentTypeDiseaseScoreFeasibilityModelStatusEst. 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 & PMIDAuthorsJournalYearCitations
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 (20)

Multi-agent debates referencing this entity

What is the minimum effective dose of trazodone required for disease-modifying e

closed · Rounds: 4 · Score: 1.00 · 2026-04-26

Can CSF p-tau217 normalization serve as a reliable surrogate endpoint for determ

closed · Rounds: 4 · Score: 1.00 · 2026-04-26

What blood-brain barrier permeability changes serve as early biomarkers for neur

closed · Rounds: 4 · Score: 1.00 · 2026-04-26

What blood-brain barrier permeability changes serve as early biomarkers for neur

closed · Rounds: 4 · Score: 1.00 · 2026-04-26

Hypothesis debate: Closed-loop optogenetic targeting PV interneurons to restore

closed · Rounds: 4 · Score: 0.50 · 2026-04-26

Hypothesis debate: Closed-loop transcranial focused ultrasound targeting EC-II S

closed · Rounds: 4 · Score: 0.50 · 2026-04-26

Hypothesis debate: Closed-loop transcranial focused ultrasound with 40Hz gamma e

closed · Rounds: 4 · Score: 0.50 · 2026-04-26

Can ferroptosis inhibitors prevent BBB disruption and edema formation after card

closed · Rounds: 4 · Score: 0.73 · 2026-04-25

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

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

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

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

Related Research

Hypotheses and analyses mentioning AQP4 in their description or question text

Aryl Hydrocarbon Receptor (AHR) Activation in B Cells Determines AQP4 Tolerance

Score: 0.683 · neuroinflammation · 2026-04-13

**Molecular Mechanism and Rationale** The aryl hydrocarbon receptor (AHR) represents a ligand-activated transcription f

AQP4 Dysregulation Promotes Neuroinflammation Through Impaired CNS-Peripheral Im

Score: 0.680 · neurodegeneration · 2026-04-21

**Molecular Mechanism and Rationale** The molecular mechanism underlying AQP4-mediated neuroinflammation centers on the

CSF/Plasma AQP4 Polarization Index as a Novel Biomarker of Astrocyte Glymphatic

Score: 0.680 · unknown disease · 2026-04-26

Aquaporin-4 (AQP4) water channels are normally concentrated at astrocyte end-feet ensheathing cerebral microvessels. Ear

AQP4-Dependent Astrocyte Swelling Exacerbates Excitotoxic Neuronal Death via Dys

Score: 0.670 · neurodegeneration · 2026-04-21

## **Molecular Mechanism and Rationale** The aquaporin-4 (AQP4) water channel represents a critical nexus between astro

Restore AQP4 Perivascular Polarization by Stabilizing DAPC/SNTA1/DAG1 Anchoring

Score: 0.670 · neurodegeneration · 2026-04-21

**Molecular Mechanism and Rationale** The aquaporin-4 (AQP4) water channel represents the most abundant water channel i

Blood Astrocyte-Derived Exosomal AQP4 Mislocalization Predicts Early Glymphatic

Score: 0.660 · unknown disease · 2026-04-26

Aquaporin-4 (AQP4) is normally highly polarized to astrocyte end-feet surrounding blood vessels, critical for glymphatic

Pharmacologically Boost AQP4X Readthrough to Restore Perivascular Clearance

Score: 0.650 · neurodegeneration · 2026-04-21

## **Molecular Mechanism and Rationale** The aquaporin-4 (AQP4) water channel represents a critical component of the br

IL-10-Producing B10 Cells Establish AQP4-Specific Peripheral Tolerance Through M

Score: 0.648 · neuroinflammation · 2026-04-13

## Mechanistic Overview IL-10-Producing B10 Cells Establish AQP4-Specific Peripheral Tolerance Through Macrophage Reprog

Treat Glymphatic Failure by Coupling AQP4-Targeted Therapy to Sleep/Noradrenergi

Score: 0.630 · neurodegeneration · 2026-04-21

**Molecular Mechanism and Rationale** The glymphatic system represents a critical brain-wide clearance pathway that fac

Combine Anti-AQP4 Autoimmunity Control with Astrocyte-Endfoot Repair in NMOSD

Score: 0.630 · neurodegeneration · 2026-04-21

**Molecular Mechanism and Rationale** The pathophysiology of neuromyelitis optica spectrum disorder (NMOSD) centers on

AQP4 Missorting in Reactive Astrocytes Drives Glymphatic Failure in Chronic Neur

Score: 0.580 · neurodegeneration · 2026-04-21

**Molecular Mechanism and Rationale** The aquaporin-4 (AQP4) water channel represents a critical component of brain hom

Disrupted AQP4-Mediated K+ Spatial Buffering Causes Neuronal Hyperexcitability a

Score: 0.580 · neurodegeneration · 2026-04-21

**Molecular Mechanism and Rationale** The molecular foundation of AQP4-mediated potassium spatial buffering involves a

TREM2-Dependent Microglial Surveillance Controls AQP4-Mediated Tau Clearance Thr

Score: 0.569 · neuroscience · 2026-04-12

**Molecular Mechanism and Rationale** The TREM2-dependent microglial surveillance hypothesis centers on a sophisticated

Closed-loop transcranial focused ultrasound to restore hippocampal gamma oscilla

Score: 0.564 · Alzheimer's disease · 2026-04-17

## Mechanistic Overview Closed-loop transcranial focused ultrasound to restore hippocampal gamma oscillations via glymph

AQP4 Autoantibodies in NMOSD Cause Bystander Oligodendrocyte Injury via Metaboli

Score: 0.560 · neurodegeneration · 2026-04-21

## Mechanistic Overview AQP4 Autoantibodies in NMOSD Cause Bystander Oligodendrocyte Injury via Metabolic Coupling Disru