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    P2RX4 purinergic receptor P2X 4 [ Homo sapiens (human) ]

    Gene ID: 5025, updated on 2-Nov-2024

    Summary

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    Official Symbol
    P2RX4provided by HGNC
    Official Full Name
    purinergic receptor P2X 4provided by HGNC
    Primary source
    HGNC:HGNC:8535
    See related
    Ensembl:ENSG00000135124 MIM:600846; AllianceGenome:HGNC:8535
    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
    P2X4; P2X4R
    Summary
    The product of this gene belongs to the family of purinoceptors for ATP. This receptor functions as a ligand-gated ion channel with high calcium permeability. The main pharmacological distinction between the members of the purinoceptor family is the relative sensitivity to the antagonists suramin and PPADS. The product of this gene has the lowest sensitivity for these antagonists. Multiple alternatively spliced transcript variants, some protein-coding and some not protein-coding, have been found for this gene. [provided by RefSeq, Feb 2012]
    Expression
    Ubiquitous expression in placenta (RPKM 18.6), colon (RPKM 15.4) and 25 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    See P2RX4 in Genome Data Viewer
    Location:
    12q24.31
    Exon count:
    14
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 12 NC_000012.12 (121210129..121234106)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 12 NC_060936.1 (121200899..121224872)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 12 NC_000012.11 (121647932..121671909)

    Chromosome 12 - NC_000012.12Genomic Context describing neighboring genes Neighboring gene uncharacterized LOC105370030 Neighboring gene uncharacterized LOC105370032 Neighboring gene Sharpr-MPRA regulatory region 4268 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 7157 Neighboring gene NANOG hESC enhancer GRCh37_chr12:121593595-121594096 Neighboring gene purinergic receptor P2X 7 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr12:121627731-121628231 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 4970 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 7158 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr12:121661200-121661700 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 7159 Neighboring gene Sharpr-MPRA regulatory region 10951 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr12:121671545-121672172 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 4971 Neighboring gene ReSE screen-validated silencer GRCh37_chr12:121683587-121683800 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 7161 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr12:121693396-121693896 Neighboring gene calcium/calmodulin dependent protein kinase kinase 2 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr12:121720271-121720878 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr12:121720879-121721486 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 4972 Neighboring gene anaphase promoting complex subunit 5 Neighboring gene ReSE screen-validated silencer GRCh37_chr12:121773208-121773399 Neighboring gene H3K27ac hESC enhancer GRCh37_chr12:121789289-121789964 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 7162 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr12:121790641-121791316 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr12:121791317-121791990

    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. Non-synonymous polymorphisms in the P2RX ( 4 ) are related to bone mineral density and osteoporosis risk in a cohort of Dutch fracture patients. Wesselius A, et al. Purinergic Signal, 2013 Mar. PMID 23138503, Free PMC Article
    2. Endogenously released ATP mediates shear stress-induced Ca2+ influx into pulmonary artery endothelial cells. Yamamoto K, et al. Am J Physiol Heart Circ Physiol, 2003 Aug. PMID 12714321
    3. ATP Evokes Ca(2+) Responses and CXCL5 Secretion via P2X(4) Receptor Activation in Human Monocyte-Derived Macrophages. Layhadi JA, et al. J Immunol, 2018 Feb 1. PMID 29255078, Free PMC Article
    4. P2X4 Receptor-Dependent Ca(2+) Influx in Model Human Monocytes and Macrophages. Layhadi JA, et al. Int J Mol Sci, 2017 Oct 27. PMID 29077063, Free PMC Article
    5. [Neuropharmacological Study of ATP Receptors, Especially in the Relationship between Glia and Pain]. Inoue K. Yakugaku Zasshi, 2017. PMID 28458288

    See all (100) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. P2X7R and P2X4R expression of mice submandibular gland in high-fat diet/streptozotocin-induced type 2 diabetes.
      Title: P2X7R and P2X4R expression of mice submandibular gland in high-fat diet/streptozotocin-induced type 2 diabetes.
    2. Expression in skin biopsies supports genetic evidence linking CAMKK2, P2X7R and P2X4R with HIV-associated sensory neuropathy.
      Title: Expression in skin biopsies supports genetic evidence linking CAMKK2, P2X7R and P2X4R with HIV-associated sensory neuropathy.
    3. Colon tumour cell death causes mTOR dependence by paracrine P2X4 stimulation.
      Title: Colon tumour cell death causes mTOR dependence by paracrine P2X4 stimulation.
    4. Blocking P2X purinoceptor 4 signalling alleviates cigarette smoke induced pulmonary inflammation.
      Title: Blocking P2X purinoceptor 4 signalling alleviates cigarette smoke induced pulmonary inflammation.
    5. Activation of P2X4 receptor exacerbates acute brain injury after intracerebral hemorrhage.
      Title: Activation of P2X4 receptor exacerbates acute brain injury after intracerebral hemorrhage.
    6. Lysosome purinergic receptor P2X4 regulates neoangiogenesis induced by microvesicles from sarcoma patients.
      Title: Lysosome purinergic receptor P2X4 regulates neoangiogenesis induced by microvesicles from sarcoma patients.
    7. [Elucidation of Mast Cell Activation Mechanism Mediated by Purinergic Signaling].
      Title: [Elucidation of Mast Cell Activation Mechanism Mediated by Purinergic Signaling].
    8. P2X4 Receptors Mediate Ca(2+) Release from Lysosomes in Response to Stimulation of P2X7 and H1 Histamine Receptors.
      Title: P2X4 Receptors Mediate Ca(2+) Release from Lysosomes in Response to Stimulation of P2X7 and H(1) Histamine Receptors.
    9. Immunohistochemical evidence of P2X7R, P2X4R and CaMKK2 in pyramidal neurons of frontal cortex does not align with Alzheimer's disease.
      Title: Immunohistochemical evidence of P2X7R, P2X4R and CaMKK2 in pyramidal neurons of frontal cortex does not align with Alzheimer's disease.
    10. Functional expression of P2X1, P2X4 and P2X7 purinergic receptors in human monocyte-derived macrophages.
      Title: Functional expression of P2X1, P2X4 and P2X7 purinergic receptors in human monocyte-derived macrophages.
    Submit: New GeneRIF Correction See all GeneRIFs (70)

    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

    Variation

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    See variants in ClinVar

    See studies and variants in dbVar

    See Variation Viewer (GRCh37.p13)

    See Variation Viewer (GRCh38)

    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

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables ATP binding IC
    Inferred by Curator
    more info
    		 PubMed 
    enables cadherin binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables copper ion binding ISS
    Inferred from Sequence or Structural Similarity
    more info
    		 PubMed 
    enables extracellularly ATP-gated monoatomic cation channel activity IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables extracellularly ATP-gated monoatomic cation channel activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables identical protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables ligand-gated calcium channel activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables ligand-gated calcium channel activity ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables purinergic nucleotide receptor activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables purinergic nucleotide receptor activity IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    enables signaling receptor binding ISS
    Inferred from Sequence or Structural Similarity
    more info
    		 PubMed 
    enables zinc ion binding ISS
    Inferred from Sequence or Structural Similarity
    more info
    		 PubMed 
    Process Evidence Code Pubs
    involved_in apoptotic signaling pathway IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in behavioral response to pain ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    involved_in calcium ion transmembrane transport IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in calcium ion transmembrane transport IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in calcium-mediated signaling TAS
    Traceable Author Statement
    more info
    		 PubMed 
    involved_in cellular response to ATP IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in cellular response to zinc ion ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    involved_in endothelial cell activation TAS
    Traceable Author Statement
    more info
    		 PubMed 
    involved_in excitatory postsynaptic potential IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in membrane depolarization IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in monoatomic ion transmembrane transport IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in negative regulation of cardiac muscle hypertrophy IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in neuronal action potential IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in positive regulation of blood vessel endothelial cell migration IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in positive regulation of calcium ion transport NAS
    Non-traceable Author Statement
    more info
    		 PubMed 
    involved_in positive regulation of calcium ion transport into cytosol IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in positive regulation of calcium ion transport into cytosol IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in positive regulation of calcium-mediated signaling IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in positive regulation of calcium-mediated signaling IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in positive regulation of endothelial cell chemotaxis IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in positive regulation of microglial cell migration ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    involved_in positive regulation of microglial cell migration TAS
    Traceable Author Statement
    more info
    		 PubMed 
    involved_in positive regulation of nitric oxide biosynthetic process NAS
    Non-traceable Author Statement
    more info
    		 PubMed 
    involved_in positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    involved_in positive regulation of prostaglandin secretion NAS
    Non-traceable Author Statement
    more info
    		 PubMed 
    involved_in purinergic nucleotide receptor signaling pathway IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in regulation of blood pressure IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in regulation of cardiac muscle contraction IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in regulation of chemotaxis ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    NOT involved_in regulation of ruffle assembly ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    involved_in regulation of sodium ion transport ISS
    Inferred from Sequence or Structural Similarity
    more info
    		 PubMed 
    involved_in relaxation of cardiac muscle IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in response to ATP IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in response to axon injury ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    involved_in response to fluid shear stress IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in response to ischemia ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    involved_in sensory perception of pain ISS
    Inferred from Sequence or Structural Similarity
    more info
    		 PubMed 
    involved_in sensory perception of touch ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    involved_in signal transduction IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in tissue homeostasis NAS
    Non-traceable Author Statement
    more info
    		 PubMed 
    Component Evidence Code Pubs
    located_in cell body ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    located_in cell junction IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in dendritic spine IEA
    Inferred from Electronic Annotation
    more info
    		  
    located_in extracellular exosome HDA PubMed 
    located_in glutamatergic synapse IEA
    Inferred from Electronic Annotation
    more info
    		  
    located_in lysosomal membrane HDA PubMed 
    located_in lysosomal membrane IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in membrane HDA PubMed 
    located_in membrane IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in neuronal cell body IEA
    Inferred from Electronic Annotation
    more info
    		  
    located_in parallel fiber to Purkinje cell synapse IEA
    Inferred from Electronic Annotation
    more info
    		  
    located_in perinuclear region of cytoplasm IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    is_active_in plasma membrane IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    located_in plasma membrane IC
    Inferred by Curator
    more info
    		 PubMed 
    located_in plasma membrane IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in plasma membrane IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    located_in plasma membrane ISS
    Inferred from Sequence or Structural Similarity
    more info
    		 PubMed 
    located_in plasma membrane TAS
    Traceable Author Statement
    more info
    		 PubMed 
    located_in postsynaptic density membrane IEA
    Inferred from Electronic Annotation
    more info
    		  
    located_in terminal bouton IEA
    Inferred from Electronic Annotation
    more info
    		  

    General protein information

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    Preferred Names
    P2X purinoceptor 4
    Names
    ATP receptor
    ATP-gated cation channel protein
    P2X receptor, subunit 4
    purinergic receptor P2X, ligand gated ion channel, 4
    purinergic receptor P2X4
    purinoceptor P2X4

    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.

    mRNA and Protein(s)

    1. NM_001256796.2 → NP_001243725.1  P2X purinoceptor 4 isoform 1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) represents the longest transcript and encodes the longest isoform (1).
      Source sequence(s)
      AC069209, BX402887, U83993
      Consensus CDS
      CCDS58282.1
      UniProtKB/TrEMBL
      B7Z6W8
      Related
      ENSP00000353032.7, ENST00000359949.11
      Conserved Domains (1) summary
      pfam00864
      Location:13 → 397
      P2X_receptor; ATP P2X receptor

    2. NM_001261397.2 → NP_001248326.1  P2X purinoceptor 4 isoform 3

      Status: REVIEWED

      Description
      Transcript Variant: This variant (5) lacks an in-frame exon in the 5' coding region and an in-frame segment in the central coding region, compared to variant 1. The resulting isoform (3) lacks two internal segments, compared to isoform 1.
      Source sequence(s)
      AC069209, BC033826, BT019739
      UniProtKB/TrEMBL
      B7Z6W8
      Related
      ENSP00000438329.1, ENST00000542067.5
      Conserved Domains (1) summary
      pfam00864
      Location:13 → 354
      P2X_receptor; ATP P2X receptor

    3. NM_001261398.2 → NP_001248327.1  P2X purinoceptor 4 isoform 4

      See identical proteins and their annotated locations for NP_001248327.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (6) lacks an in-frame exon in the 5' coding region and a segment in the 3' region, compared to variant 1. The resulting isoform (4) lacks an internal segment and has a shorter and distinct C-terminus, compared to isoform 1.
      Source sequence(s)
      AC069209, AK225604
      UniProtKB/TrEMBL
      B7Z6W8
      Conserved Domains (1) summary
      pfam00864
      Location:13 → 334
      P2X_receptor; ATP P2X receptor

    4. NM_002560.3 → NP_002551.2  P2X purinoceptor 4 isoform 2

      See identical proteins and their annotated locations for NP_002551.2

      Status: REVIEWED

      Description
      Transcript Variant: This variant (2) lacks an in-frame exon in the 5' coding region, compared to variant 1. The resulting isoform (2) lacks an internal segment, compared to isoform 1.
      Source sequence(s)
      AC069209
      Consensus CDS
      CCDS9214.1
      UniProtKB/Swiss-Prot
      E7EPF7, F6RU17, O00450, O14722, Q5U089, Q5U090, Q8N4N1, Q99571, Q9UBG9
      UniProtKB/TrEMBL
      B7Z6W8
      Related
      ENSP00000336607.4, ENST00000337233.9
      Conserved Domains (1) summary
      pfam00864
      Location:13 → 381
      P2X_receptor; ATP P2X receptor

    RNA

    1. NR_046372.2 RNA Sequence

      Status: REVIEWED

      Description
      Transcript Variant: This variant (3) lacks an exon in the 5' region and contains an additional exon in the central region, compared to variant 1. This variant is represented as non-coding because the use of the 5'-most expected translational start codon, as used in variant 1, renders the transcript a candidate for nonsense-mediated mRNA decay (NMD).
      Source sequence(s)
      AK308549, U83993

    2. NR_046373.2 RNA Sequence

      Status: REVIEWED

      Description
      Transcript Variant: This variant (4) lacks two internal exons, compared to variant 1. This variant is represented as non-coding because the use of the 5'-most expected translational start codon, as used in variant 1, renders the transcript a candidate for nonsense-mediated mRNA decay (NMD).
      Source sequence(s)
      AK297704, U83993
      Related
      ENST00000543984.5

    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_000012.12 Reference GRCh38.p14 Primary Assembly

      Range
      121210129..121234106
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_011538416.3 → XP_011536718.1  P2X purinoceptor 4 isoform X2

      Conserved Domains (1) summary
      pfam00864
      Location:13 → 251
      P2X_receptor; ATP P2X receptor

    2. XM_047428910.1 → XP_047284866.1  P2X purinoceptor 4 isoform X1

    3. XM_047428911.1 → XP_047284867.1  P2X purinoceptor 4 isoform X3

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060936.1 Alternate T2T-CHM13v2.0

      Range
      121200899..121224872
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_054372138.1 → XP_054228113.1  P2X purinoceptor 4 isoform X2

    2. XM_054372137.1 → XP_054228112.1  P2X purinoceptor 4 isoform X1

    3. XM_054372139.1 → XP_054228114.1  P2X purinoceptor 4 isoform X3

    Suppressed Reference Sequence(s)

    The following Reference Sequences have been suppressed. Explain

    1. NM_175567.1: Suppressed sequence

      Description
      NM_175567.1: This RefSeq was permanently suppressed because it is a nonsense-mediated mRNA decay (NMD) candidate.

    2. NM_175568.1: Suppressed sequence

      Description
      NM_175568.1: This RefSeq was permanently suppressed because it is a nonsense-mediated mRNA decay (NMD) candidate.
    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    Q99571.2 GenPept UniProtKB/Swiss-Prot:Q99571

    Gene LinkOut

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

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