Entity Detail — Knowledge Graph Node
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.
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.
AI-generated illustration
Regenerate portrait ↻| 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 (+7 more) |
| KG Connections | 1732 knowledge graph edges |
| Databases | GeneCardsNCBI GeneHPASTRING |
Knowledge base pages for this entity
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| Target | Relation | Type | Str |
|---|---|---|---|
| AQP4 | encodes | protein | 0.00 |
| ds-f2c28aed24a7 | provides_data_for | dataset | 1.00 |
| NMOSD | biomarker_for | disease | 0.95 |
| Neuromyelitis Optica Spectrum Disorder | biomarker_for | disease | 0.95 |
| GLYMPHATIC SYSTEM | involved_in | entity | 0.95 |
| Glymphatic Pathway | component_of | pathway | 0.95 |
| Astrocyte Endfeet | expressed_in | cell_type | 0.95 |
| Amyloid Beta Clearance | regulates | process | 0.95 |
| NEUROMYELITIS OPTICA SPECTRUM DISORDER | associated_with | entity | 0.95 |
| Glymphatic Dysfunction | involved_in | mechanism | 0.95 |
| Aquaporin-4-IgG | binds | biomarker | 0.95 |
| Glymphatic Clearance | mediates | process | 0.95 |
| NEUROMYELITIS OPTICA SPECTRUM DISORDER | biomarker_for | entity | 0.95 |
| CSF-ISF Exchange | associated_with | process | 0.95 |
| CSF-ISF Exchange | mediates | process | 0.95 |
| Perivascular Water Transport | mediates | process | 0.95 |
| Tau Clearance | regulates | process | 0.95 |
| Glymphatic System | associated_with | process | 0.95 |
| Astrocytic Endfeet | expressed_in | cell_type | 0.95 |
| Central Nervous System | expressed_in | cell_type | 0.95 |
| Glymphatic Transport | mediates | process | 0.95 |
| COMPLEMENT CASCADE | activates | entity | 0.95 |
| Neuromyelitis Optica | biomarker_for | disease | 0.95 |
| Neuromyelitis Optica Spectrum Disorder | associated_with | disease | 0.95 |
| Water Flux | mediates | process | 0.95 |
| Glymphatic System | component_of | process | 0.95 |
| Sepsis-Associated Encephalopathy | associated_with | disease | 0.95 |
| glymphatic pathway | mediates | pathway | 0.95 |
| Glymphatic Pathway | involved_in | pathway | 0.95 |
| CHI3L1 | regulates | protein | 0.90 |
| Neuromyelitis Optica | associated_with | disease | 0.90 |
| β-amyloid Transport | associated_with | process | 0.90 |
| MULTIPLE SCLEROSIS | associated_with | entity | 0.90 |
| BRAIN TISSUE HOMEOSTASIS | involved_in | entity | 0.90 |
| demyelination | implicated_in | process | 0.90 |
| Cerebral Edema | associated_with | phenotype | 0.90 |
| Amyloid Beta | associated_with | protein | 0.90 |
| brain edema | promotes | phenotype | 0.90 |
| astrocytes | activates | cell_type | 0.90 |
| glymphatic clearance | participates_in | pathway | 0.90 |
| CSF FLOW | facilitates | process | 0.90 |
| Blood-Brain Barrier | component_of | process | 0.90 |
| EXTRACELLULAR TAU CLEARANCE | facilitates | process | 0.90 |
| Tau clearance | mediates | process | 0.90 |
| Metabolic waste clearance | mediates | process | 0.90 |
| Cerebrospinal fluid influx | modulates | process | 0.90 |
| THERAPEUTIC_TARGET | therapeutic_target | entity | 0.90 |
| Glymphatic Function | associated_with | process | 0.90 |
| Beta-Amyloid Clearance | involved_in | process | 0.90 |
| NF-κB Pathway | inhibits | pathway | 0.90 |
| Source | Relation | Type | Str |
|---|---|---|---|
| H2 | enhances_function | hypothesis | 0.00 |
| AQP4 | encodes | gene | 0.00 |
| H5_AQP4 | detects_glymphatic_dysfunction | biomarker | 0.00 |
| ds-f2c28aed24a7 | data_in | dataset | 1.00 |
| AQP4-ANTIBODY | binds | protein | 0.95 |
| TGN-020 | targets | drug | 0.95 |
| IGG AUTOANTIBODY | binds | protein | 0.95 |
| AQP4-Ab | binds | protein | 0.95 |
| B cells | regulates | cell_type | 0.90 |
| B Cells | regulates | cell_type | 0.90 |
| Cecal Ligation and Perforation | upregulates | process | 0.90 |
| h-c8ccbee8 | targets | hypothesis | 0.90 |
| h-62e56eb9 | targets | hypothesis | 0.90 |
| h-807d7a82 | targets | hypothesis | 0.90 |
| TGN-020 | inhibits | drug | 0.90 |
| SDA-2026-04-01-gap-013 | targets | analysis | 0.85 |
| B Cells | interacts_with | cell_type | 0.85 |
| B Cells | associated_with | cell_type | 0.85 |
| Testosterone | upregulates | compound | 0.85 |
| Estrogen | upregulates | compound | 0.85 |
| Progesterone | upregulates | compound | 0.85 |
| Plasmablast/Plasma Cell | associated_with | cell_type | 0.85 |
| TDP-43 | downregulates | protein | 0.80 |
| Musk | downregulates | drug | 0.80 |
| AQP1 | associated_with | gene | 0.80 |
| MMP9 | inhibits | gene | 0.80 |
| TMAO | downregulates | drug | 0.80 |
| IFN | modulates | gene | 0.80 |
| GFAP | associated_with | protein | 0.80 |
| BHB | regulates | compound | 0.80 |
| P38MAPK | regulates | pathway | 0.80 |
| TNF | downregulates | gene | 0.80 |
| IL1B | downregulates | gene | 0.80 |
| MTNR1A | regulates_expression | gene | 0.80 |
| Microglia | involved_in | cell_type | 0.75 |
| Reactive Astrogliosis | modulates | process | 0.75 |
| MELATONIN | activates | drug | 0.70 |
| MELATONIN | regulates | drug | 0.70 |
| ALZHEIMER'S DISEASE | causes | disease | 0.70 |
| RILUZOLE | causes | drug | 0.70 |
| SENESCENCE | stabilizes | phenotype | 0.70 |
| GABA | causes | phenotype | 0.70 |
| SULFORAPHANE | regulates | drug | 0.65 |
| STROKE | targets | disease | 0.65 |
| ASTROCYTE | targets | cell_type | 0.65 |
| CSF | activates | phenotype | 0.65 |
| SULFORAPHANE | protects_against | drug | 0.65 |
| MICROGLIA | causes | cell_type | 0.65 |
| TH | interacts_with | gene | 0.65 |
| GLYMPHATIC CLEARANCE | interacts_with | phenotype | 0.65 |
Hypotheses where this entity is a therapeutic target
Scientific analyses that reference this entity
neurodegeneration | 2026-04-26 | 7 hypotheses Top: 0.580
neurodegeneration | 2026-04-26 | 7 hypotheses Top: 0.560
neurodegeneration | 2026-04-26 | 8 hypotheses Top: 0.915
neurodegeneration | 2026-04-26 | 8 hypotheses Top: 0.720
neurodegeneration | 2026-04-25 | 7 hypotheses Top: 0.760
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 |
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 |
Multi-agent debates referencing this entity
closed · Rounds: 4 · Score: 1.00 · 2026-04-26
closed · Rounds: 4 · Score: 1.00 · 2026-04-26
closed · Rounds: 4 · Score: 1.00 · 2026-04-26
closed · Rounds: 4 · Score: 1.00 · 2026-04-26
closed · Rounds: 4 · Score: 0.50 · 2026-04-26
closed · Rounds: 4 · Score: 0.50 · 2026-04-26
closed · Rounds: 4 · Score: 0.50 · 2026-04-26
closed · Rounds: 4 · Score: 0.73 · 2026-04-25
closed · Rounds: 4 · Score: 0.76 · 2026-04-21
closed · Rounds: 4 · Score: 0.76 · 2026-04-21
Hypotheses and analyses mentioning AQP4 in their description or question text
Score: 0.683 · neuroinflammation · 2026-04-13
**Molecular Mechanism and Rationale** The aryl hydrocarbon receptor (AHR) represents a ligand-activated transcription f
Score: 0.680 · neurodegeneration · 2026-04-21
**Molecular Mechanism and Rationale** The molecular mechanism underlying AQP4-mediated neuroinflammation centers on the
Score: 0.680 · unknown disease · 2026-04-26
Aquaporin-4 (AQP4) water channels are normally concentrated at astrocyte end-feet ensheathing cerebral microvessels. Ear
Score: 0.670 · neurodegeneration · 2026-04-21
## **Molecular Mechanism and Rationale** The aquaporin-4 (AQP4) water channel represents a critical nexus between astro
Score: 0.670 · neurodegeneration · 2026-04-21
**Molecular Mechanism and Rationale** The aquaporin-4 (AQP4) water channel represents the most abundant water channel i
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
Score: 0.650 · neurodegeneration · 2026-04-21
## **Molecular Mechanism and Rationale** The aquaporin-4 (AQP4) water channel represents a critical component of the br
Score: 0.648 · neuroinflammation · 2026-04-13
## Mechanistic Overview IL-10-Producing B10 Cells Establish AQP4-Specific Peripheral Tolerance Through Macrophage Reprog
Score: 0.630 · neurodegeneration · 2026-04-21
**Molecular Mechanism and Rationale** The glymphatic system represents a critical brain-wide clearance pathway that fac
Score: 0.630 · neurodegeneration · 2026-04-21
**Molecular Mechanism and Rationale** The pathophysiology of neuromyelitis optica spectrum disorder (NMOSD) centers on
Score: 0.580 · neurodegeneration · 2026-04-21
**Molecular Mechanism and Rationale** The aquaporin-4 (AQP4) water channel represents a critical component of brain hom
Score: 0.580 · neurodegeneration · 2026-04-21
**Molecular Mechanism and Rationale** The molecular foundation of AQP4-mediated potassium spatial buffering involves a
Score: 0.569 · neuroscience · 2026-04-12
**Molecular Mechanism and Rationale** The TREM2-dependent microglial surveillance hypothesis centers on a sophisticated
Score: 0.564 · Alzheimer's disease · 2026-04-17
## Mechanistic Overview Closed-loop transcranial focused ultrasound to restore hippocampal gamma oscillations via glymph
Score: 0.560 · neurodegeneration · 2026-04-21
## Mechanistic Overview AQP4 Autoantibodies in NMOSD Cause Bystander Oligodendrocyte Injury via Metabolic Coupling Disru