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    ZHX2 zinc fingers and homeoboxes 2 [ Homo sapiens (human) ]

    Gene ID: 22882, updated on 10-Dec-2024

    Summary

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    Official Symbol
    ZHX2provided by HGNC
    Official Full Name
    zinc fingers and homeoboxes 2provided by HGNC
    Primary source
    HGNC:HGNC:18513
    See related
    Ensembl:ENSG00000178764 MIM:609185; AllianceGenome:HGNC:18513
    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
    RAF; AFR1
    Summary
    The members of the zinc fingers and homeoboxes gene family are nuclear homodimeric transcriptional repressors that interact with the A subunit of nuclear factor-Y (NF-YA) and contain two C2H2-type zinc fingers and five homeobox DNA-binding domains. This gene encodes member 2 of this gene family. In addition to forming homodimers, this protein heterodimerizes with member 1 of the zinc fingers and homeoboxes family. [provided by RefSeq, Jul 2008]
    Expression
    Ubiquitous expression in ovary (RPKM 12.8), lymph node (RPKM 11.9) and 25 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    See ZHX2 in Genome Data Viewer
    Location:
    8q24.13
    Exon count:
    16
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 8 NC_000008.11 (122780379..122974510)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 8 NC_060932.1 (123911550..124105660)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 8 NC_000008.10 (123792618..123986750)

    Chromosome 8 - NC_000008.11Genomic Context describing neighboring genes Neighboring gene uncharacterized LOC107986904 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 27852 Neighboring gene Sharpr-MPRA regulatory region 2746 Neighboring gene hESC enhancers GRCh37_chr8:123770608-123771162 and GRCh37_chr8:123771163-123771718 Neighboring gene H3K27ac hESC enhancer GRCh37_chr8:123792337-123792838 Neighboring gene H3K27ac hESC enhancer GRCh37_chr8:123792839-123793338 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 19487 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 19486 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 27853 Neighboring gene NANOG hESC enhancer GRCh37_chr8:123795211-123795745 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 19488 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 27854 Neighboring gene OCT4-NANOG-H3K27ac hESC enhancer GRCh37_chr8:123799669-123800426 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 27856 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 19489 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 27857 Neighboring gene ZHX2 antisense RNA 2 Neighboring gene BRD4-independent group 4 enhancer GRCh37_chr8:123809400-123810599 Neighboring gene cyclin dependent kinase 5 pseudogene 1 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 19490 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr8:123814233-123815192 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr8:123815193-123816150 Neighboring gene P300/CBP strongly-dependent group 1 enhancer GRCh37_chr8:123817802-123819001 Neighboring gene CDK7 strongly-dependent group 2 enhancer GRCh37_chr8:123848010-123849209 Neighboring gene OCT4-NANOG-H3K27ac hESC enhancer GRCh37_chr8:123849857-123850688 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 27859 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr8:123869217-123869717 Neighboring gene CDK7 strongly-dependent group 2 enhancer GRCh37_chr8:123874507-123875706 Neighboring gene uncharacterized LOC124902011 Neighboring gene OCT4-NANOG-H3K4me1 hESC enhancer GRCh37_chr8:123927788-123928344 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 27860 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 27862 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 27863 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 27861 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr8:123960147-123960646 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 19491 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 27864 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 19492 Neighboring gene P300/CBP strongly-dependent group 1 enhancer GRCh37_chr8:124000413-124001612 Neighboring gene uncharacterized LOC124902013 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 27865 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 27866 Neighboring gene derlin 1 Neighboring gene RNY4 pseudogene 5

    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
    • 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. Proliferation and osteo/odontogenic differentiation of stem cells from apical papilla regulated by Zinc fingers and homeoboxes 2: An in vitro study. Wan F, et al. Biochem Biophys Res Commun, 2016 Jan 15. PMID 26679602
    2. Transcriptional deregulation of homeobox gene ZHX2 in Hodgkin lymphoma. Nagel S, et al. Leuk Res, 2012 May. PMID 22078940
    3. ZHX2 restricts hepatocellular carcinoma by suppressing stem cell-like traits through KDM2A-mediated H3K36 demethylation. Lin Q, et al. EBioMedicine, 2020 Mar. PMID 32114388, Free PMC Article
    4. Zinc fingers and homeoboxes 2 inhibition could suppress the proliferation of ovarian cancer cells by apoptosis pathway. Ding R, et al. Clin Transl Oncol, 2023 Jul. PMID 36746874
    5. ZHX2 drives cell growth and migration via activating MEK/ERK signal and induces Sunitinib resistance by regulating the autophagy in clear cell Renal Cell Carcinoma. Zhu L, et al. Cell Death Dis, 2020 May 7. PMID 32382017, Free PMC Article

    See all (73) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. METTL3 and IGF2BP1-Mediated m6A Modification of ZHX2 Promotes Tumor Property of Renal Cell Carcinoma.
      Title: METTL3 and IGF2BP1-Mediated m6A Modification of ZHX2 Promotes Tumor Property of Renal Cell Carcinoma.
    2. Elongation of very long chain fatty acids-3 (Elovl3) is activated by ZHX2 and is a regulator of cell cycle progression.
      Title: Elongation of very long chain fatty acids-3 (Elovl3) is activated by ZHX2 and is a regulator of cell cycle progression.
    3. Transcription factor Zhx2 is a checkpoint that programs macrophage polarization and antitumor response.
      Title: Transcription factor Zhx2 is a checkpoint that programs macrophage polarization and antitumor response.
    4. Zinc fingers and homeoboxes 2 inhibition could suppress the proliferation of ovarian cancer cells by apoptosis pathway.
      Title: Zinc fingers and homeoboxes 2 inhibition could suppress the proliferation of ovarian cancer cells by apoptosis pathway.
    5. USP13 promotes deubiquitination of ZHX2 and tumorigenesis in kidney cancer.
      Title: USP13 promotes deubiquitination of ZHX2 and tumorigenesis in kidney cancer.
    6. Upregulation of ZHX2 predicts poor prognosis and is correlated with immune infiltration in gastric cancer.
      Title: Upregulation of ZHX2 predicts poor prognosis and is correlated with immune infiltration in gastric cancer.
    7. Transcription factor Zhx2 restricts NK cell maturation and suppresses their antitumor immunity.
      Title: Transcription factor Zhx2 restricts NK cell maturation and suppresses their antitumor immunity.
    8. HNRNPD interacts with ZHX2 regulating the vasculogenic mimicry formation of glioma cells via linc00707/miR-651-3p/SP2 axis.
      Title: HNRNPD interacts with ZHX2 regulating the vasculogenic mimicry formation of glioma cells via linc00707/miR-651-3p/SP2 axis.
    9. The zinc fingers and homeoboxes 2 protein ZHX2 and its interacting proteins regulate upstream pathways in podocyte diseases.
      Title: The zinc fingers and homeoboxes 2 protein ZHX2 and its interacting proteins regulate upstream pathways in podocyte diseases.
    10. Tumor suppressor ZHX2 inhibits NAFLD-HCC progression via blocking LPL-mediated lipid uptake.
      Title: Tumor suppressor ZHX2 inhibits NAFLD-HCC progression via blocking LPL-mediated lipid uptake.
    Submit: New GeneRIF Correction See all GeneRIFs (36)

    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

    EBI GWAS Catalog

    Description
    A genome-wide association study of behavioral disinhibition.
    EBI GWAS Catalog
    Genome-wide association study of antibody response to smallpox vaccine.
    EBI GWAS Catalog
    Meta-analysis of genome-wide association studies from the CHARGE consortium identifies common variants associated with carotid intima media thickness and plaque.
    EBI GWAS Catalog

    Variation

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    See variants in ClinVar

    See studies and variants in dbVar

    See Variation Viewer (GRCh37.p13)

    See Variation Viewer (GRCh38)

    Interactions

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    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

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    Markers

    Homology

    Clone Names

    • KIAA0854

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables DNA binding IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables DNA-binding transcription factor activity, RNA polymerase II-specific IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables DNA-binding transcription factor activity, RNA polymerase II-specific ISA
    Inferred from Sequence Alignment
    more info
    		  
    enables identical protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables metal ion binding IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables protein heterodimerization activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables protein homodimerization activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    Process Evidence Code Pubs
    involved_in mRNA catabolic process IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in negative regulation of DNA-templated transcription IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in negative regulation of neuron differentiation IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in negative regulation of transcription by RNA polymerase II IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in regulation of transcription by RNA polymerase II IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in retinal bipolar neuron differentiation IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in somatic stem cell population maintenance IEA
    Inferred from Electronic Annotation
    more info
    		  
    Component Evidence Code Pubs
    located_in chromatin ISA
    Inferred from Sequence Alignment
    more info
    		  
    located_in cytosol IDA
    Inferred from Direct Assay
    more info
    		  
    located_in nucleoplasm IDA
    Inferred from Direct Assay
    more info
    		  
    is_active_in nucleus IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    is_active_in nucleus IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in nucleus IDA
    Inferred from Direct Assay
    more info
    		 PubMed 

    General protein information

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    Preferred Names
    zinc fingers and homeoboxes protein 2
    Names
    AFP regulator 1
    alpha-fetoprotein regulator 1
    regulator of AFP
    transcription factor ZHX2
    zinc finger and homeodomain protein 2

    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_046951.1 RefSeqGene

      Range
      5307..198162
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. NM_001362797.2 → NP_001349726.1  zinc fingers and homeoboxes protein 2 isoform 1

      Status: REVIEWED

      Source sequence(s)
      AC016405, AC104316, BC042145, BM148156, HY099683
      Consensus CDS
      CCDS6336.1
      UniProtKB/Swiss-Prot
      Q9Y6X8
      Conserved Domains (2) summary
      smart00389
      Location:537 → 582
      HOX; Homeodomain
      cd00086
      Location:444 → 496
      homeodomain; Homeodomain; DNA binding domains involved in the transcriptional regulation of key eukaryotic developmental processes; may bind to DNA as monomers or as homo- and/or heterodimers, in a sequence-specific manner.

    2. NM_001412796.1 → NP_001399725.1  zinc fingers and homeoboxes protein 2 isoform 1

      Status: REVIEWED

      Source sequence(s)
      AC016405, AC104316
      UniProtKB/Swiss-Prot
      Q9Y6X8

    3. NM_001412797.1 → NP_001399726.1  zinc fingers and homeoboxes protein 2 isoform 1

      Status: REVIEWED

      Source sequence(s)
      AC016405, AC104316
      UniProtKB/Swiss-Prot
      Q9Y6X8

    4. NM_001412798.1 → NP_001399727.1  zinc fingers and homeoboxes protein 2 isoform 1

      Status: REVIEWED

      Source sequence(s)
      AC016405, AC104316
      UniProtKB/Swiss-Prot
      Q9Y6X8

    5. NM_001412799.1 → NP_001399728.1  zinc fingers and homeoboxes protein 2 isoform 1

      Status: REVIEWED

      Source sequence(s)
      AC016405, AC104316
      UniProtKB/Swiss-Prot
      Q9Y6X8

    6. NM_001412800.1 → NP_001399729.1  zinc fingers and homeoboxes protein 2 isoform 1

      Status: REVIEWED

      Source sequence(s)
      AC016405, AC104316
      UniProtKB/Swiss-Prot
      Q9Y6X8

    7. NM_001412801.1 → NP_001399730.1  zinc fingers and homeoboxes protein 2 isoform 1

      Status: REVIEWED

      Source sequence(s)
      AC016405, AC104316
      UniProtKB/Swiss-Prot
      Q9Y6X8

    8. NM_001412802.1 → NP_001399731.1  zinc fingers and homeoboxes protein 2 isoform 1

      Status: REVIEWED

      Source sequence(s)
      AC016405, AC104316
      UniProtKB/Swiss-Prot
      Q9Y6X8

    9. NM_001412803.1 → NP_001399732.1  zinc fingers and homeoboxes protein 2 isoform 1

      Status: REVIEWED

      Source sequence(s)
      AC016405, AC104316
      UniProtKB/Swiss-Prot
      Q9Y6X8

    10. NM_001412804.1 → NP_001399733.1  zinc fingers and homeoboxes protein 2 isoform 1

      Status: REVIEWED

      Source sequence(s)
      AC016405, AC104316
      UniProtKB/Swiss-Prot
      Q9Y6X8

    11. NM_001412805.1 → NP_001399734.1  zinc fingers and homeoboxes protein 2 isoform 1

      Status: REVIEWED

      Source sequence(s)
      AC016405, AC104316
      UniProtKB/Swiss-Prot
      Q9Y6X8

    12. NM_001412806.1 → NP_001399735.1  zinc fingers and homeoboxes protein 2 isoform 1

      Status: REVIEWED

      Source sequence(s)
      AC016405, AC104316
      UniProtKB/Swiss-Prot
      Q9Y6X8

    13. NM_001412807.1 → NP_001399736.1  zinc fingers and homeoboxes protein 2 isoform 1

      Status: REVIEWED

      Source sequence(s)
      AC016405, AC104316
      UniProtKB/Swiss-Prot
      Q9Y6X8

    14. NM_001412808.1 → NP_001399737.1  zinc fingers and homeoboxes protein 2 isoform 1

      Status: REVIEWED

      Source sequence(s)
      AC016405, AC104316
      UniProtKB/Swiss-Prot
      Q9Y6X8

    15. NM_001412809.1 → NP_001399738.1  zinc fingers and homeoboxes protein 2 isoform 1

      Status: REVIEWED

      Source sequence(s)
      AC016405, AC104316
      UniProtKB/Swiss-Prot
      Q9Y6X8

    16. NM_001412810.1 → NP_001399739.1  zinc fingers and homeoboxes protein 2 isoform 1

      Status: REVIEWED

      Source sequence(s)
      AC016405, AC104316
      UniProtKB/Swiss-Prot
      Q9Y6X8

    17. NM_001412811.1 → NP_001399740.1  zinc fingers and homeoboxes protein 2 isoform 1

      Status: REVIEWED

      Source sequence(s)
      AC016405, AC104316
      UniProtKB/Swiss-Prot
      Q9Y6X8

    18. NM_001412812.1 → NP_001399741.1  zinc fingers and homeoboxes protein 2 isoform 1

      Status: REVIEWED

      Source sequence(s)
      AC016405, AC104316
      UniProtKB/Swiss-Prot
      Q9Y6X8

    19. NM_001412813.1 → NP_001399742.1  zinc fingers and homeoboxes protein 2 isoform 2

      Status: REVIEWED

      Source sequence(s)
      AC016405, AC104316

    20. NM_014943.5 → NP_055758.1  zinc fingers and homeoboxes protein 2 isoform 1

      See identical proteins and their annotated locations for NP_055758.1

      Status: REVIEWED

      Source sequence(s)
      AC104316, BC042145, BM148156, HY099683
      Consensus CDS
      CCDS6336.1
      UniProtKB/Swiss-Prot
      Q9Y6X8
      Related
      ENSP00000314709.4, ENST00000314393.6
      Conserved Domains (2) summary
      smart00389
      Location:537 → 582
      HOX; Homeodomain
      cd00086
      Location:444 → 496
      homeodomain; Homeodomain; DNA binding domains involved in the transcriptional regulation of key eukaryotic developmental processes; may bind to DNA as monomers or as homo- and/or heterodimers, in a sequence-specific manner.

    RNA

    1. NR_182048.1 RNA Sequence

      Status: REVIEWED

      Source sequence(s)
      AC016405, AC104316

    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_000008.11 Reference GRCh38.p14 Primary Assembly

      Range
      122780379..122974510
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_047421590.1 → XP_047277546.1  zinc fingers and homeoboxes protein 2 isoform X1

      UniProtKB/Swiss-Prot
      Q9Y6X8

    2. XM_011516932.4 → XP_011515234.1  zinc fingers and homeoboxes protein 2 isoform X1

      See identical proteins and their annotated locations for XP_011515234.1

      UniProtKB/Swiss-Prot
      Q9Y6X8
      Conserved Domains (2) summary
      smart00389
      Location:537 → 582
      HOX; Homeodomain
      cd00086
      Location:444 → 496
      homeodomain; Homeodomain; DNA binding domains involved in the transcriptional regulation of key eukaryotic developmental processes; may bind to DNA as monomers or as homo- and/or heterodimers, in a sequence-specific manner.

    3. XM_005250836.6 → XP_005250893.1  zinc fingers and homeoboxes protein 2 isoform X1

      See identical proteins and their annotated locations for XP_005250893.1

      UniProtKB/Swiss-Prot
      Q9Y6X8
      Conserved Domains (2) summary
      smart00389
      Location:537 → 582
      HOX; Homeodomain
      cd00086
      Location:444 → 496
      homeodomain; Homeodomain; DNA binding domains involved in the transcriptional regulation of key eukaryotic developmental processes; may bind to DNA as monomers or as homo- and/or heterodimers, in a sequence-specific manner.

    4. XM_047421589.1 → XP_047277545.1  zinc fingers and homeoboxes protein 2 isoform X1

      UniProtKB/Swiss-Prot
      Q9Y6X8

    5. XM_047421588.1 → XP_047277544.1  zinc fingers and homeoboxes protein 2 isoform X1

      UniProtKB/Swiss-Prot
      Q9Y6X8

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060932.1 Alternate T2T-CHM13v2.0

      Range
      123911550..124105660
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_054360145.1 → XP_054216120.1  zinc fingers and homeoboxes protein 2 isoform X1

      UniProtKB/Swiss-Prot
      Q9Y6X8

    2. XM_054360144.1 → XP_054216119.1  zinc fingers and homeoboxes protein 2 isoform X1

      UniProtKB/Swiss-Prot
      Q9Y6X8

    3. XM_054360142.1 → XP_054216117.1  zinc fingers and homeoboxes protein 2 isoform X1

      UniProtKB/Swiss-Prot
      Q9Y6X8

    4. XM_054360141.1 → XP_054216116.1  zinc fingers and homeoboxes protein 2 isoform X1

      UniProtKB/Swiss-Prot
      Q9Y6X8

    5. XM_054360143.1 → XP_054216118.1  zinc fingers and homeoboxes protein 2 isoform X1

      UniProtKB/Swiss-Prot
      Q9Y6X8
    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    Q9Y6X8.1 GenPept UniProtKB/Swiss-Prot:Q9Y6X8

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