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Symbol AQP4 contributors: mct/shn - updated : 05-01-2015
HGNC name aquaporin 4
HGNC id 637
Location 18q11.2      Physical location : 24.432.009 - 24.445.716
Synonym name
  • mercurial-insensitive water channel
  • aquaporin type 4 transcript variant c
  • aquaporin type4
  • aquaporin-4
  • Synonym symbol(s) MIWC, HMIWC2, MGC22454, WCH4
    TYPE functioning gene
    STRUCTURE 13.71 kb     5 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    regulatory sequence
    MAPPING cloned Y linked N status provisional
    Map cen - D18S866 - D18S66 - AQP4 - D18S478 - D18S1151 - qter
    TRANSCRIPTS type messenger
  • MIWC1 contains TATA, CAAT, AP-1 regulatory elements PMID:7559426
  • five elements of M1 mRNA clustered within the 286-bp region were found to function as a novel astrocyte-specific enhancer PMID:22225570
  • a consensus sequence of Pit-1/Oct/Unc-86 (POU) transcription factors was indispensable to the astrocyte-specific enhancer of M1 mRNA
  • identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    5 splicing 5216 34.8 323 . astrocytes of fetal archicortex and neocortex PMID:16814974 - 18179769
  • also called M1 or variant a
  • longer AQP4M1 isoform interferes with array formation, presumably due to the additional 22 N-terminal AAs
  • two N-terminal cysteines are palmitoylated, suggesting that palmitoylation of the N-terminal cysteines is the reason for the inability of AQP4M1 to form square arrays
  • 4 splicing 5136 32.2 301 . astrocytes of fetal archicortex and neocortex PMID:16814974 - 18179769
  • also called C2, M23 or variant b
  • only the shorter AQP4M23 isoform assembles into square arrays
    Type widely
       expressed in (based on citations)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Cardiovascularheart   lowly Homo sapiensNM_001650
     vessel     Homo sapiens
    Digestiveintestine   lowly Rattus norvegicus
    Nervousbrainforebraincerebral cortex highly Rattus norvegicus
     brainhindbraincerebellum highly Rattus norvegicus
     brain   highly Rattus norvegicus
     brain   highly Homo sapiensNM_001650
     spinal cord     Homo sapiens
    Respiratorylung   lowly Rattus norvegicus
    Urinarykidneytubulecollecting duct highly Homo sapiensNM_00165
     kidney   lowly Rattus norvegicus
    Visualeye   lowly Rattus norvegicus
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Muscularstriatumskeletal highly Homo sapiensNM_001650
    SystemCellPubmedSpeciesStageRna symbol
    Cardiovascularendothelial cell Homo sapiens
    Muscularmyocyte Homo sapiens
    Nervousastrocyte Homo sapiens
    cell lineage
    cell lines
    at STAGE
  • C terminal unique sorting cassette
  • C-terminal signals determine AQP4 basolateral membrane targeting in epithelial MDCK cells
  • two independent basolateral sorting signals
  • mono polymer homomer , polymer
    interspecies ortholog to Aqp4, Mus musculus
    ortholog to Aqp4, Rattus norvegicus
    ortholog to aqp4, Danio rerio
    ortholog to AQP4, Pan troglodytes
    intraspecies homolog to AQP5
  • water transport proteins
  • CATEGORY transport channel
    SUBCELLULAR LOCALIZATION     plasma membrane
  • specific membrane domains of astrocytes
  • in the sarcolemma of fast -twitch fibers and astrocyte end- feet
  • associated with the transverse tubules of skeletal myofibers (
  • selectively expressed in endfoot membranes and not in other membranes at the blood–brain interface (PMIDS:
  • basic FUNCTION
  • critical role in inner ear fluid homeostasis
  • ‘‘orthodox’’aquaporin, that transport only water molecules
  • hypothalamic osmoreceptor and regulator of vasopressin secretion, in response to brain edema formation
  • playing a role in accommodating the rapid changes in cell volume and hydrostatic forces that occur during muscular contraction in order to prevent damage to the sarcolemma
  • may be playing a role in a role in olfactory function
  • involved in water homeostasis in the mammalian brain
  • plays a protective role after contusion spinal cord injury by facilitating the clearance of excess water
  • play pivotal roles in cerebral water movement as essential mediators during edema and fluid accumulation
  • not only serves as an influx route for water but also is critical for initiating downstream signaling events that may affect and potentially exacerbate the pathological outcome in clinical conditions associated with brain edema
  • AQP4-mediated cell swelling is inextricably coupled with activation of signaling pathways that may profoundly affect the pathological and pathophysiological outcome in clinical conditions associated with brain edema
  • TRPV4 and AQP4 combined possess the essential features expected of a regulatory volume decrease (RVD) activator
  • major brain water channel AQP4 is implicated in water transport at the blood–brain interface
  • the maintenance of water homeostasis under pathological conditions is mediated by the aquaporin-4 (AQP4) channel in astrocytes
  • predominantly contribute to cytotoxic edema following traumatic brain injury (TBI)
    text water channel
    a component
  • TRPV4/AQP4 complex in astrocytes, that constitutes a key element in the brain volume homeostasis by acting as an osmosensor that couples osmotic stress to downstream signaling cascades
    small molecule
  • AP2 adaptor complex
  • TRPV4
  • FOXO3 transcriptionally upregulates AQP4 and induces cerebral edema following traumatic brain injury
  • TEAD1 overexpression restores AQP4 expression, and both TEAD1 and AQP4 overexpression rescue migratory deficits in TEAD1-knockout cells, implicating a direct regulatory role for TEAD1-AQP4 in glioblastoma (GBM) migration
  • cell & other
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional     --low  
    in muscle of DMD and BMD (
    constitutional     --low  
    in mesial temporal lobe epilepsy (MTLE) secundary to a disruption of the dystrophin complex, resulting in a perturbed flux of water through astrocytes and K+ homeostasis with propensity for seizures
    constitutional     --over  
    post-partum in pregnancy and in early lung development
    constitutional     --low  
    in sarcoglycanopathies and dysferlinopathies (LGMD2B, LGMD2C, LGMD2D, LGMD2E, LGMD2F)
  • to cerebral edema
  • to neuromyelitis optica
  • Variant & Polymorphism other variant reduced normalized water permeability of brain
    Candidate gene
    Therapy target
    aquaporins appear to be important for the development of novel drug therapies for Meniere disease and related disorders
    potential role of AQP1 or AQP4 as novel therapeutic targets for the management of lung cancer
    AQP4 inhibition or downregulation as novel early neuroprotective manoeuvres in spinal cord injury
  • AQP4 null mice are deaf
  • Aqp4 knockout mice display cochlear dysfunction that is the primary cause of hearing impairment
  • AQP4-dependent spinal cord swelling following compression injury, resulting in remarkably improved outcome in AQP4-null mice
  • AQP4 expression is reduced in Duchenne muscular dystrophy patients, and is reported to correlate with decreased alpha1-syntrophin and altered osmotic permeability
  • AQP4 was significantly reduced despite normal dystrophin and alpha1-syntrophin in dysferlinopathy patients
  • Mice lacking AQP4 (AQP4(-/-) mice) exhibited significantly impaired locomotor function and prolonged bladder dysfunction after spinal cord injury