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    CXXC4 CXXC finger protein 4 [ Homo sapiens (human) ]

    Gene ID: 80319, updated on 9-Dec-2024

    Summary

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    Official Symbol
    CXXC4provided by HGNC
    Official Full Name
    CXXC finger protein 4provided by HGNC
    Primary source
    HGNC:HGNC:24593
    See related
    Ensembl:ENSG00000168772 MIM:611645; AllianceGenome:HGNC:24593
    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
    IDAX
    Summary
    This gene encodes a CXXC-type zinc finger domain-containing protein that functions as an antagonist of the canonical wingless/integrated signaling pathway. The encoded protein negatively regulates wingless/integrated signaling through interaction with the post synaptic density protein/ Drosophila disc large tumor suppressor/ zonula occludens-1 protein domain of Dishevelled, a scaffolding protein required for the stabilization of the transcriptional co-activator beta-catenin. In addition, the CXXC domain of this protein has been shown to bind unmethylated CpG dinucleotides, localize to promoters and CpG islands, and interact with the catalytic domain of methylcytosine dioxygenase ten-eleven-translocation 2, an iron and alpha-ketoglutarate-dependent dioxygenase that modifies the methylation status of DNA. In humans, a mutation in this gene has been associated with development of malignant renal cell carcinoma. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Sep 2015]
    Expression
    Broad expression in brain (RPKM 4.6), thyroid (RPKM 1.9) and 20 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    See CXXC4 in Genome Data Viewer
    Location:
    4q24
    Exon count:
    4
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 4 NC_000004.12 (104468308..104494894, complement)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 4 NC_060928.1 (107779515..107806100, complement)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 4 NC_000004.11 (105389465..105416051, complement)

    Chromosome 4 - NC_000004.12Genomic Context describing neighboring genes Neighboring gene uncharacterized LOC105377350 Neighboring gene uncharacterized LOC124900744 Neighboring gene VISTA enhancer hs260 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 21764 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 21765 Neighboring gene CXXC4 antisense RNA 1 Neighboring gene uncharacterized LOC124900745 Neighboring gene OCT4-NANOG hESC enhancer GRCh37_chr4:105512595-105513176 Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr4:105613262-105613822 Neighboring gene uncharacterized LOC124900746 Neighboring gene Sharpr-MPRA regulatory region 3032

    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. Malignant Transformation Involving CXXC4 Mutations Identified in a Leukemic Progression Model of Severe Congenital Neutropenia. Olofsen PA, et al. Cell Rep Med, 2020 Aug 25. PMID 33205068, Free PMC Article
    2. Decreased expression of CXXC4 promotes a malignant phenotype in renal cell carcinoma by activating Wnt signaling. Kojima T, et al. Oncogene, 2009 Jan 15. PMID 18931698
    3. Differentiation of tubular and villous adenomas based on Wnt pathway-related gene expression profiles. Nguyen AV, et al. Int J Mol Med, 2010 Jul. PMID 20514431
    4. CXXC4 mRNA levels are associated with clinicopathological parameters and survival of myelodysplastic syndrome patients. Li S, et al. Leuk Res, 2014 Sep. PMID 25085016
    5. SPZ1 promotes glioma aggravation via targeting CXXC4. Di C, et al. J BUON, 2021 Mar-Apr. PMID 34076982

    See all (27) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. Malignant Transformation Involving CXXC4 Mutations Identified in a Leukemic Progression Model of Severe Congenital Neutropenia.
      Title: Malignant Transformation Involving CXXC4 Mutations Identified in a Leukemic Progression Model of Severe Congenital Neutropenia.
    2. SPZ1 promotes glioma aggravation via targeting CXXC4.
      Title: SPZ1 promotes glioma aggravation via targeting CXXC4.
    3. CXXC finger protein 4 inhibits the CDK18-ERK1/2 axis to suppress the immune escape of gastric cancer cells with involvement of ELK1/MIR100HG pathway.
      Title: CXXC finger protein 4 inhibits the CDK18-ERK1/2 axis to suppress the immune escape of gastric cancer cells with involvement of ELK1/MIR100HG pathway.
    4. LUCAT1 Epigenetically Downregulates the Tumor Suppressor Genes CXXC4 and SFRP2 in Gastric Cancer.
      Title: LUCAT1 Epigenetically Downregulates the Tumor Suppressor Genes CXXC4 and SFRP2 in Gastric Cancer.
    5. The results presented here suggest that miR-629-5p functions as a tumor promoter by improving proliferation and migration and repressing apoptosis and 5-FU sensitivity in colorectal cancer progression by directly down-regulating CXXC4.
      Title: MiR-629-5p promotes colorectal cancer progression through targetting CXXC finger protein 4.
    6. The findings indicate that BMI1-mediated IDAX epigenetic suppression is crucial for enhancement of colon carcinogenesis.
      Title: BMI1 activates WNT signaling in colon cancer by negatively regulating the WNT antagonist IDAX.
    7. Age of patients and levels of CXXC4 mRNA, hemoglobin, and marrow blast associated with survival of Myelodysplastic syndrome patients.
      Title: CXXC4 mRNA levels are associated with clinicopathological parameters and survival of myelodysplastic syndrome patients.
    8. EZH2 can activate MAPK signaling by inhibiting CXXC4 expression.
      Title: New tumor suppressor CXXC finger protein 4 inactivates mitogen activated protein kinase signaling.
    9. CXXC4 is a novel potential tumor suppressor directly regulated by EZH2, and its expression is a significant prognosis factor for patients with early stages of gastric cancer.
      Title: Enhancer of zeste homolog 2 activates wnt signaling through downregulating CXXC finger protein 4.
    10. IDAX expression results in caspase activation and TET2 protein downregulation, in a manner that depends on DNA binding through the IDAX CXXC domain, suggesting that IDAX recruits TET2 to DNA before degradation
      Title: Modulation of TET2 expression and 5-methylcytosine oxidation by the CXXC domain protein IDAX.
    Submit: New GeneRIF Correction See all GeneRIFs (12)

    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)

    HIV-1 interactions

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    Replication interactions

    Interaction Pubs
    Knockdown of CXXC finger protein 4 (CXXC4; IDAX) by shRNA library screening inhibits HIV-1 replication in cultured Jurkat T-cells PubMed

    Go to the HIV-1, Human Interaction Database

    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

    • MGC149872

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables PDZ domain binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables methyl-CpG binding IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables methyl-CpG binding IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables zinc ion binding IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    Process Evidence Code Pubs
    involved_in Wnt signaling pathway IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in negative regulation of Wnt signaling pathway IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in zygotic specification of dorsal/ventral axis ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    Component Evidence Code Pubs
    located_in cytoplasm IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in cytoplasmic vesicle IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    is_active_in nucleus IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  

    General protein information

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    Preferred Names
    CXXC-type zinc finger protein 4
    Names
    CXXC finger 4
    Dvl-binding protein IDAX (inhibition of the Dvl and Axin complex)
    inhibition of the Dvl and axin complex protein

    NCBI Reference Sequences (RefSeq)

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    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_025212.4 → NP_079488.2  CXXC-type zinc finger protein 4

      See identical proteins and their annotated locations for NP_079488.2

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) represents the longer transcript and encodes the protein.
      Source sequence(s)
      AA708035, AC093628, AK125395, CB068467, DA804531
      Consensus CDS
      CCDS3665.2
      UniProtKB/TrEMBL
      J9JIF5
      Related
      ENSP00000378248.2, ENST00000394767.3
      Conserved Domains (1) summary
      pfam02008
      Location:301 → 341
      zf-CXXC; CXXC zinc finger domain

    RNA

    1. NR_132741.2 RNA Sequence

      Status: REVIEWED

      Description
      Transcript Variant: This variant (2) contains an alternate internal exon and lacks another alternate internal exon compared to variant 1. This variant is represented as non-coding because it lacks a large portion of the coding region, including the translational start codon, found in variant 1.
      Source sequence(s)
      AA708035, AC093628, AK125395, CB068467, CR627201, DA397981

    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_000004.12 Reference GRCh38.p14 Primary Assembly

      Range
      104468308..104494894 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_011532284.3 → XP_011530586.1  CXXC-type zinc finger protein 4 isoform X1

      See identical proteins and their annotated locations for XP_011530586.1

      UniProtKB/TrEMBL
      J9JIF5
      Conserved Domains (1) summary
      pfam02008
      Location:301 → 341
      zf-CXXC; CXXC zinc finger domain

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060928.1 Alternate T2T-CHM13v2.0

      Range
      107779515..107806100 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_054350899.1 → XP_054206874.1  CXXC-type zinc finger protein 4 isoform X1

      UniProtKB/TrEMBL
      J9JIF5

    2. XM_054350898.1 → XP_054206873.1  CXXC-type zinc finger protein 4 isoform X2

      UniProtKB/TrEMBL
      A0A8V8TLX0

    3. XM_054350896.1 → XP_054206871.1  CXXC-type zinc finger protein 4 isoform X2

      UniProtKB/TrEMBL
      A0A8V8TLX0

    4. XM_054350897.1 → XP_054206872.1  CXXC-type zinc finger protein 4 isoform X2

      UniProtKB/TrEMBL
      A0A8V8TLX0
    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    Q9H2H0.1 GenPept UniProtKB/Swiss-Prot:Q9H2H0

    Gene LinkOut

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