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    AQP4 aquaporin 4 [ Homo sapiens (human) ]

    Gene ID: 361, updated on 28-Oct-2024

    Summary

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    Official Symbol
    AQP4provided by HGNC
    Official Full Name
    aquaporin 4provided by HGNC
    Primary source
    HGNC:HGNC:637
    See related
    Ensembl:ENSG00000171885 MIM:600308; AllianceGenome:HGNC:637
    Gene type
    protein coding
    RefSeq status
    REVIEWED
    Organism
    Homo sapiens
    Lineage
    Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
    Also known as
    MIWC; MLC4; WCH4; hAQP4
    Summary
    This gene encodes a member of the aquaporin family of intrinsic membrane proteins that function as water-selective channels in the plasma membranes of many cells. This protein is the predominant aquaporin found in brain and has an important role in brain water homeostasis. Alternatively spliced transcript variants encoding different isoforms have been described for this gene. Additional isoforms, resulting from the use of alternative in-frame translation initiation codons, have also been described. Recent studies provided evidence for translational readthrough in this gene, and expression of C-terminally extended isoforms via the use of an alternative in-frame translation termination codon. [provided by RefSeq, Jun 2018]
    Expression
    Biased expression in brain (RPKM 248.2) and lung (RPKM 72.5) See more
    Orthologs
    mouse all
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    Genomic context

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    See AQP4 in Genome Data Viewer
    Location:
    18q11.2
    Exon count:
    5
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 18 NC_000018.10 (26852038..26865803, complement)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 18 NC_060942.1 (27046091..27059856, complement)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 18 NC_000018.9 (24432002..24445767, complement)

    Chromosome 18 - NC_000018.10Genomic Context describing neighboring genes Neighboring gene uncharacterized LOC105372035 Neighboring gene ubiquitin recognition factor in ER associated degradation 1 pseudogene Neighboring gene H3K4me1 hESC enhancer GRCh37_chr18:24442920-24443420 Neighboring gene AQP4 antisense RNA 1 Neighboring gene OCT4-NANOG hESC enhancer GRCh37_chr18:24507672-24508283 Neighboring gene carbohydrate sulfotransferase 9 Neighboring gene OCT4-NANOG hESC enhancer GRCh37_chr18:24536524-24537111 Neighboring gene OCT4-NANOG hESC enhancer GRCh37_chr18:24537112-24537698 Neighboring gene ATPase H+ transporting V1 subunit E1 pseudogene 2 Neighboring gene uncharacterized LOC124904275 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 13194 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 13195

    Genomic regions, transcripts, and products

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    Go to nucleotide: Graphics FASTA GenBank

    Expression

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    • Project title: HPA RNA-seq normal tissues HPA RNA-seq normal tissues
    • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
    • BioProject: PRJEB4337
    • Publication: PMID 24309898
    • Analysis date: Wed Apr 4 07:08:55 2018

    Bibliography

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    Related articles in PubMed

    1. Osmotic stress decreases aquaporin-4 expression in the human retinal pigment epithelial cell line, ARPE-19. Willermain F, et al. Int J Mol Med, 2014 Aug. PMID 24888368
    2. Mutagenesis of the aquaporin 4 extracellular domains defines restricted binding patterns of pathogenic neuromyelitis optica IgG. Owens GP, et al. J Biol Chem, 2015 May 8. PMID 25792738, Free PMC Article
    3. Diagnostic value of aquaporin 4 antibody in assessing idiopathic inflammatory demyelinating central nervous system diseases in Egyptian patients. Kishk NA, et al. J Clin Neurosci, 2015 Apr. PMID 25677878
    4. Reduction in serum aquaporin-4 antibody titers during development of a tumor-like brain lesion in a patient with neuromyelitis optica: a serum antibody-consuming effect? Aboulenein-Djamshidian F, et al. J Neuropathol Exp Neurol, 2015 Mar. PMID 25668569, Free PMC Article
    5. Differential expression of aquaporin-4 isoforms localizes with neuromyelitis optica disease activity. Saini H, et al. J Neuroimmunol, 2010 Apr 15. PMID 20227773

    See all (367) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. Shifting from ependyma to choroid plexus epithelium and the changing expressions of aquaporin-1 and aquaporin-4.
      Title: Shifting from ependyma to choroid plexus epithelium and the changing expressions of aquaporin-1 and aquaporin-4.
    2. Macroscopic changes in aquaporin-4 underlie blast traumatic brain injury-related impairment in glymphatic function.
      Title: Macroscopic changes in aquaporin-4 underlie blast traumatic brain injury-related impairment in glymphatic function.
    3. Differentiated pattern of complement system activation between MOG-IgG-associated disease and AQP4-IgG-positive neuromyelitis optica spectrum disorder.
      Title: Differentiated pattern of complement system activation between MOG-IgG-associated disease and AQP4-IgG-positive neuromyelitis optica spectrum disorder.
    4. B cells orchestrate tolerance to the neuromyelitis optica autoantigen AQP4.
      Title: B cells orchestrate tolerance to the neuromyelitis optica autoantigen AQP4.
    5. Aquaporin-4 and Parkinson's Disease.
      Title: Aquaporin-4 and Parkinson's Disease.
    6. Non-coding RNAs and Aquaporin 4: Their Role in the Pathogenesis of Neurological Disorders.
      Title: Non-coding RNAs and Aquaporin 4: Their Role in the Pathogenesis of Neurological Disorders.
    7. Glymphatic system and aquaporin-4 in epilepsy.
      Title: Glymphatic system and aquaporin‑4 in epilepsy.
    8. The Expression and Role of Aquaporin 4 in Colon Cancer.
      Title: The Expression and Role of Aquaporin 4 in Colon Cancer.
    9. Renal dysfunction in AQP4 NMOSD and MS; a potential predictor of relapse and prognosis.
      Title: Renal dysfunction in AQP4 NMOSD and MS; a potential predictor of relapse and prognosis.
    10. Readthrough isoform of aquaporin-4 (AQP4) as a therapeutic target for Alzheimer's disease and other proteinopathies.
      Title: Readthrough isoform of aquaporin-4 (AQP4) as a therapeutic target for Alzheimer's disease and other proteinopathies.
    Submit: New GeneRIF Correction See all GeneRIFs (309)

    Phenotypes

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    Find tests for this gene in the NIH Genetic Testing Registry (GTR)

    Review eQTL and phenotype association data in this region using PheGenI

    Associated conditions

    Description Tests
    Megalencephalic leukoencephalopathy with subcortical cysts 4, remitting
    MedGen: C5830628 OMIM: 620448 GeneReviews: Not available
    		not available

    Variation

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    See variants in ClinVar

    See studies and variants in dbVar

    See Variation Viewer (GRCh37.p13)

    See Variation Viewer (GRCh38)

    Genotypes

    Pathways from PubChem

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    Interactions

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    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

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    Markers

    Homology

    Clone Names

    • MGC22454

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables identical protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables water channel activity EXP
    Inferred from Experiment
    more info
    		 PubMed 
    enables water channel activity IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables water channel activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables water channel activity IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    Process Evidence Code Pubs
    involved_in cellular response to type II interferon IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in cerebrospinal fluid circulation ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    involved_in intracellular water homeostasis IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in intracellular water homeostasis ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    involved_in multicellular organismal-level water homeostasis IEP
    Inferred from Expression Pattern
    more info
    		 PubMed 
    involved_in multicellular organismal-level water homeostasis ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    involved_in protein homotetramerization IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in renal water homeostasis TAS
    Traceable Author Statement
    more info
    		  
    involved_in transmembrane transport IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in water transport IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in water transport IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    Component Evidence Code Pubs
    located_in astrocyte end-foot ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    is_active_in basolateral plasma membrane IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    located_in basolateral plasma membrane ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    located_in cytoplasm IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in endosome membrane IEA
    Inferred from Electronic Annotation
    more info
    		  
    located_in external side of plasma membrane IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in extracellular region IEA
    Inferred from Electronic Annotation
    more info
    		  
    is_active_in plasma membrane IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    located_in plasma membrane IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in plasma membrane TAS
    Traceable Author Statement
    more info
    		  
    located_in sarcolemma IDA
    Inferred from Direct Assay
    more info
    		 PubMed 

    General protein information

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    Preferred Names
    aquaporin-4
    Names
    aquaporin type4
    mercurial-insensitive water channel

    NCBI Reference Sequences (RefSeq)

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    NEW Try the new Transcript table

    RefSeqs maintained independently of Annotated Genomes

    These reference sequences exist independently of genome builds. Explain

    These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

    Genomic

    1. NG_029560.1 RefSeqGene

      Range
      5046..18710
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. NM_001317384.3 → NP_001304313.1  aquaporin-4 isoform M1x

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1, also known as hMIWC2) represents the predominant transcript and encodes four isoforms, resulting from the use of two alternative in-frame translation initiation codons and two alternative in-frame translation termination codons. This RefSeq represents the longest, C-terminally extended isoform (M1x, also known as M1ex), which results from the use of the upstream AUG start codon and readthrough of the upstream UGA stop codon to the downstream UAA stop codon. As the UGA stop codon has been reported to specify several alternative amino acids (tryptophan, cysteine, arginine and serine), its location in this isoform is denoted by an 'X'.
      Source sequence(s)
      AC018371, AK222684, BU687682, DA244620, DT220791, HQ901095
      Consensus CDS
      CCDS92445.1
      UniProtKB/TrEMBL
      A0A5F9ZHR4, Q53H97
      Related
      ENSP00000500598.2, ENST00000672981.2
      Conserved Domains (1) summary
      pfam00230
      Location:31 → 248
      MIP; Major intrinsic protein

    2. NM_001317387.3 → NP_001304316.1  aquaporin-4 isoform delta4

      Status: REVIEWED

      Description
      Transcript Variant: This variant (3) lacks an in-frame coding exon compared to variant 1, and encodes a shorter isoform (delta4) missing an internal protein segment compared to isoform M1. This isoform exhibits no water transport properties, and downregulates the expression and water channel activity of isoform M1; thus, appears to function as a regulator of water permeability (PMID:24356448).
      Source sequence(s)
      AC018371, AK222684, BU687682, DA244620, DT220791, HQ901095
      Consensus CDS
      CCDS82244.1
      UniProtKB/TrEMBL
      Q53H97, V9PBN7
      Related
      ENSP00000502364.1, ENST00000675739.1
      Conserved Domains (1) summary
      cl00200
      Location:31 → 221
      MIP; Major intrinsic protein (MIP) superfamily. Members of the MIP superfamily function as membrane channels that selectively transport water, small neutral molecules, and ions out of and between cells. The channel proteins share a common fold: the N-terminal ...

    3. NM_001364286.1 → NP_001351215.1  aquaporin-4 isoform M23

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1, also known as hMIWC2) represents the predominant transcript and encodes four isoforms, resulting from the use of two alternative in-frame translation initiation codons and two alternative in-frame translation termination codons. This RefSeq represents isoform M23, which results from the use of the downstream in-frame AUG start codon and the upstream UGA stop codon. Isoform M23 has a shorter N-terminus compared to isoform M1. An alternatively spliced transcript variant (NM_004028.4) encodes the same isoform.
      Source sequence(s)
      AC018371, AK222684, BU687682, DA244620, DT220791, HQ901095
      Consensus CDS
      CCDS58617.1
      UniProtKB/TrEMBL
      Q53H97
      Conserved Domains (1) summary
      pfam00230
      Location:9 → 226
      MIP; Major intrinsic protein

    4. NM_001364287.1 → NP_001351216.1  aquaporin-4 isoform M23x

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1, also known as hMIWC2) represents the predominant transcript and encodes four isoforms, resulting from the use of two alternative in-frame translation initiation codons and two alternative in-frame translation termination codons. This RefSeq represents a C-terminally extended isoform (M23x, also known as M23ex), which results from the use of the downstream in-frame AUG start codon and readthrough of the upstream UGA stop codon to the downstream UAA stop codon. As the UGA stop codon has been reported to specify several alternative amino acids (tryptophan, cysteine, arginine and serine), its location in this isoform is denoted by an 'X'. An alternatively spliced transcript variant (NM_001364289.1) encodes the same isoform.
      Source sequence(s)
      AC018371, AK222684, BU687682, DA244620, DT220791, HQ901095
      UniProtKB/TrEMBL
      Q53H97
      Conserved Domains (1) summary
      pfam00230
      Location:9 → 226
      MIP; Major intrinsic protein

    5. NM_001364289.2 → NP_001351218.1  aquaporin-4 isoform M23x

      Status: REVIEWED

      Description
      Transcript Variant: This variant (2, also known as hMIWC1) is alternatively spliced at the 5' end, which causes translation initiation from an in-frame, downstream start codon, compared to variant 1. Variant 2 encodes two isoforms, resulting from the use of alternative in-frame translation termination codons. The encoded isoform (M23x, also known as M23ex), which results from readthrough of the upstream UGA stop codon to the downstream UAA stop codon, has a shorter N-terminus and a longer C-terminus compared to isoform M1. As the UGA stop codon has been reported to specify several alternative amino acids (tryptophan, cysteine, arginine and serine), its location in isoform M23x is denoted by an 'X'. This isoform is the same as that represented in NM_001364287.1.
      Source sequence(s)
      AC018371, BC030745, HQ901095, U34845
      UniProtKB/TrEMBL
      Q53H97
      Conserved Domains (1) summary
      pfam00230
      Location:9 → 226
      MIP; Major intrinsic protein

    6. NM_001650.7 → NP_001641.1  aquaporin-4 isoform M1

      See identical proteins and their annotated locations for NP_001641.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1, also known as hMIWC2) represents the predominant transcript and encodes four isoforms, resulting from the use of two alternative in-frame translation initiation codons and two alternative in-frame translation termination codons. This RefSeq represents isoform M1, which results from the use of the upstream AUG start codon and the upstream UGA stop codon.
      Source sequence(s)
      AC018371, AK222684, BU687682, DA244620, DT220791, HQ901095
      Consensus CDS
      CCDS11889.1
      UniProtKB/Swiss-Prot
      P55087, P78564
      UniProtKB/TrEMBL
      F1DSG4, Q53H97
      Related
      ENSP00000372654.4, ENST00000383168.9
      Conserved Domains (1) summary
      pfam00230
      Location:31 → 248
      MIP; Major intrinsic protein

    7. NM_004028.5 → NP_004019.1  aquaporin-4 isoform M23

      See identical proteins and their annotated locations for NP_004019.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (2, also known as hMIWC1) is alternatively spliced at the 5' end, which causes translation initiation from an in-frame, downstream start codon, compared to variant 1. Variant 2 encodes two isoforms, resulting from the use of alternative in-frame translation termination codons. The encoded isoform (M23), which results from the use of the upstream UGA stop codon, has a shorter N-terminus compared to isoform M1. This isoform is the same as that represented in NM_001364286.1.
      Source sequence(s)
      AC018371, BC030745, HQ901095, U34845
      Consensus CDS
      CCDS58617.1
      UniProtKB/TrEMBL
      Q53H97
      Related
      ENSP00000462597.1, ENST00000581374.5
      Conserved Domains (1) summary
      pfam00230
      Location:9 → 226
      MIP; Major intrinsic protein

    RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

    The following sections contain reference sequences that belong to a specific genome build. Explain

    Reference GRCh38.p14 Primary Assembly

    Genomic

    1. NC_000018.10 Reference GRCh38.p14 Primary Assembly

      Range
      26852038..26865803 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_011525942.4 → XP_011524244.1  aquaporin-4 isoform X1

      UniProtKB/TrEMBL
      Q53H97
      Conserved Domains (1) summary
      pfam00230
      Location:24 → 241
      MIP; Major intrinsic protein

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060942.1 Alternate T2T-CHM13v2.0

      Range
      27046091..27059856 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)
    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    P55087.2 GenPept UniProtKB/Swiss-Prot:P55087

    Gene LinkOut

    The following LinkOut resources are supplied by external providers. These providers are responsible for maintaining the links.

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