ArticleHuman molecular genetics2008
Novel variants in human Aquaporin-4 reduce cellular water permeability.
Article in Human molecular genetics, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
35 citing papers in PubMed, 75 citations in OpenAlex.
- Genetic Architecture of Perivascular Space Morphology in the Pediatric Brain.bioRxiv : the preprint server for biology · 2026Article
- A Bioinformatic Study of Genetics Involved in Determining Mild Traumatic Brain Injury Severity and Recovery.Biomedicines · 2025Article
- Brain water content in sudden unexpected infant death.Forensic science, medicine, and pathology · 2023Article
- dbAQP-SNP: a database of missense single-nucleotide polymorphisms in human aquaporins.Database : the journal of biological databases and curation · 2023Article
- Aquaporin splice variation differentially modulates channel function during marine teleost egg hydration.PloS one · 2023Article
- Cerebral Microcirculation, Perivascular Unit, and Glymphatic System: Role of Aquaporin-4 as the Gatekeeper for Water Homeostasis.Frontiers in neurology · 2021Review
- Ageing and genetic background influence anaesthetic effects in a D. melanogaster model of blunt trauma with brain injuryBritish journal of anaesthesia · 2020Article
- Haplotype of the astrocytic water channel AQP4 is associated with slow wave energy regulation in human NREM sleep.PLoS biology · 2020Article
- Role of Sulfonylurea Receptor 1 and Glibenclamide in Traumatic Brain Injury: A Review of the Evidence.International journal of molecular sciences · 2020Review
- Polymorphisms in the Human Aquaporin 4 Gene Are Associated With Schizophrenia in the Southern Chinese Han Population: A Case-Control Study.Frontiers in psychiatry · 2020Article
- Predictive Value of Serum Antibodies and Point Mutations of AQP4, AQP1 and MOG in A Cohort of Spanish Patients with Neuromyelitis Optica Spectrum Disorders.International journal of molecular sciences · 2019Article
- Aquaporin 4 Blockade Attenuates Acute Lung Injury Through Inhibition of Th17 Cell Proliferation in Mice.Inflammation · 2019Article
- Altered Waste Disposal System in Aging and Alzheimer's Disease: Focus on Astrocytic Aquaporin-4.Frontiers in pharmacology · 2019Review
- Blockade of Aquaporin 4 Inhibits Irradiation-Induced Pulmonary Inflammation and Modulates Macrophage Polarization in Mice.Inflammation · 2018Article
- Genetic defects disrupting glial ion and water homeostasis in the brain.Brain pathology (Zurich, Switzerland) · 2018Review
- Genetic variation in Aquaporin-4 moderates the relationship between sleep and brain Aβ-amyloid burden.Translational psychiatry · 2018Observational
- The Glymphatic System in Diabetes-Induced Dementia.Frontiers in neurology · 2018Review
- The single nucleotide polymorphism site of aquaporin-4 gene in patients with neuromyelitis optica.Experimental and therapeutic medicine · 2017Article
- Astaxanthin protects astrocytes against trauma-induced apoptosis through inhibition of NKCC1 expression via the NF-κB signaling pathway.BMC neuroscience · 2017Article
- Aquaporin Water Channels and Hydrocephalus.Pediatric neurosurgery · 2017Review
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
Abstract
Cerebral edema contributes significantly to morbidity and mortality after brain injury and stroke. Aquaporin-4 (AQP4), a water channel expressed in astrocytes, plays a key role in brain water homeostasis. Genetic variants in other aquaporin family members have been associated with disease phenotypes. However, in human AQP4, only one non-synonymous single-nucleotide polymorphism (nsSNP) has been reported, with no characterization of protein function or disease phenotype. We analyzed DNA from an ethnically diverse cohort of 188 individuals to identify novel AQP4 variants. AQP4 variants were constructed by site-directed mutagenesis and expressed in cells. Water permeability assays in the cells were used to measure protein function. We identified 24 variants in AQP4 including four novel nsSNPs (I128T, D184E, I205L and M224T). We did not observe the previously documented M278T in our sample. The nsSNPs found were rare ( approximately 1-2% allele frequency) and heterozygous. Computational analysis predicted reduced function mutations. Protein expression and membrane localization were similar for reference AQP4 and the five AQP4 mutants. Cellular assays confirmed that four variant AQP4 channels reduced normalized water permeability to between 26 and 48% of the reference (P < 0.001), while the M278T mutation increased normalized water permeability (P < 0.001). We identified multiple novel AQP4 SNPs and showed that four nsSNPs reduced water permeability. The previously reported M278T mutation resulted in gain of function. Our experiments provide insight into the function of the AQP4 protein. These nsSNPs may have clinical implications for patients with cerebral edema and related disorders.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.