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    ZNRF3 zinc and ring finger 3 [ Homo sapiens (human) ]

    Gene ID: 84133, updated on 10-Dec-2024

    Summary

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    Official Symbol
    ZNRF3provided by HGNC
    Official Full Name
    zinc and ring finger 3provided by HGNC
    Primary source
    HGNC:HGNC:18126
    See related
    Ensembl:ENSG00000183579 MIM:612062; AllianceGenome:HGNC:18126
    Gene type
    protein coding
    RefSeq status
    VALIDATED
    Organism
    Homo sapiens
    Lineage
    Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
    Also known as
    RNF203; BK747E2.3
    Summary
    Enables frizzled binding activity and ubiquitin-protein transferase activity. Involved in negative regulation of Wnt signaling pathway; protein ubiquitination; and ubiquitin-dependent protein catabolic process. Located in plasma membrane. [provided by Alliance of Genome Resources, Dec 2024]
    Expression
    Ubiquitous expression in kidney (RPKM 4.8), brain (RPKM 4.7) and 24 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    See ZNRF3 in Genome Data Viewer
    Location:
    22q12.1
    Exon count:
    10
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 22 NC_000022.11 (28883572..29057488)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 22 NC_060946.1 (29344932..29518764)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 22 NC_000022.10 (29279560..29453476)

    Chromosome 22 - NC_000022.11Genomic Context describing neighboring genes Neighboring gene H3K4me1 hESC enhancer GRCh37_chr22:29231311-29231812 Neighboring gene uncharacterized LOC107985549 Neighboring gene BBLN pseudogene 2 Neighboring gene Sharpr-MPRA regulatory region 13625 Neighboring gene ReSE screen-validated silencer GRCh37_chr22:29275395-29275496 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 13582 Neighboring gene Sharpr-MPRA regulatory region 4838 Neighboring gene Sharpr-MPRA regulatory region 5766 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr22:29298674-29299487 Neighboring gene CDK7 strongly-dependent group 2 enhancer GRCh37_chr22:29299851-29301050 Neighboring gene NANOG hESC enhancer GRCh37_chr22:29335494-29335995 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr22:29371305-29371805 Neighboring gene BRD4-independent group 4 enhancer GRCh37_chr22:29378648-29379847 Neighboring gene OCT4-NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr22:29384398-29385198 Neighboring gene NANOG-H3K27ac hESC enhancer GRCh37_chr22:29396251-29396817 Neighboring gene H3K27ac hESC enhancer GRCh37_chr22:29396818-29397383 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr22:29399041-29399852 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr22:29399853-29400662 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr22:29400663-29401473 Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr22:29406873-29407710 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_63211 Neighboring gene ZNRF3 antisense RNA 1 Neighboring gene Sharpr-MPRA regulatory region 3696 Neighboring gene Sharpr-MPRA regulatory region 8961 Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr22:29458189-29458956 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 13583 Neighboring gene chromosome 22 open reading frame 31 Neighboring gene kringle containing transmembrane protein 1 Neighboring gene ReSE screen-validated silencer GRCh37_chr22:29524988-29525196 Neighboring gene RNA, U6 small nuclear 810, pseudogene

    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. Comprehensive analysis of zinc and ring finger 3 in prognostic value and pan-cancer immunity. Liu M, et al. FASEB J, 2024 Mar 15. PMID 38457275
    2. Potent and selective binders of the E3 ubiquitin ligase ZNRF3 stimulate Wnt signaling and intestinal organoid growth. Kschonsak YT, et al. Cell Chem Biol, 2024 Jun 20. PMID 38056465
    3. Single-Exon Deletions of ZNRF3 Exon 2 Cause Congenital Adrenal Hypoplasia. Amano N, et al. J Clin Endocrinol Metab, 2024 Feb 20. PMID 37878959
    4. Association of Genes implicated in primary angle-closure Glaucoma and the ocular biometric parameters of anterior chamber depth and axial length in a northern Chinese population. Wang S, et al. BMC Ophthalmol, 2018 Oct 22. PMID 30348125, Free PMC Article
    5. ZnRF3 induces apoptosis of gastric cancer cells by antagonizing Wnt and Hedgehog signaling. Qin H, et al. Panminerva Med, 2015 Dec. PMID 25923840

    See all (70) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. Deleterious ZNRF3 germline variants cause neurodevelopmental disorders with mirror brain phenotypes via domain-specific effects on Wnt/beta-catenin signaling.
      Title: Deleterious ZNRF3 germline variants cause neurodevelopmental disorders with mirror brain phenotypes via domain-specific effects on Wnt/β-catenin signaling.
    2. E3 ligases RNF43 and ZNRF3 display differential specificity for endocytosis of Frizzled receptors.
      Title: E3 ligases RNF43 and ZNRF3 display differential specificity for endocytosis of Frizzled receptors.
    3. Potent and selective binders of the E3 ubiquitin ligase ZNRF3 stimulate Wnt signaling and intestinal organoid growth.
      Title: Potent and selective binders of the E3 ubiquitin ligase ZNRF3 stimulate Wnt signaling and intestinal organoid growth.
    4. Comprehensive analysis of zinc and ring finger 3 in prognostic value and pan-cancer immunity.
      Title: Comprehensive analysis of zinc and ring finger 3 in prognostic value and pan-cancer immunity.
    5. Single-Exon Deletions of ZNRF3 Exon 2 Cause Congenital Adrenal Hypoplasia.
      Title: Single-Exon Deletions of ZNRF3 Exon 2 Cause Congenital Adrenal Hypoplasia.
    6. Additional evidence for the role of chromosomal imbalances and SOX8, ZNRF3 and HHAT gene variants in early human testis development.
      Title: Additional evidence for the role of chromosomal imbalances and SOX8, ZNRF3 and HHAT gene variants in early human testis development.
    7. RNF43/ZNRF3 loss predisposes to hepatocellular-carcinoma by impairing liver regeneration and altering the liver lipid metabolic ground-state.
      Title: RNF43/ZNRF3 loss predisposes to hepatocellular-carcinoma by impairing liver regeneration and altering the liver lipid metabolic ground-state.
    8. A positive feedback loop of lncRNA-RMRP/ZNRF3 axis and Wnt/beta-catenin signaling regulates the progression and temozolomide resistance in glioma.
      Title: A positive feedback loop of lncRNA-RMRP/ZNRF3 axis and Wnt/β-catenin signaling regulates the progression and temozolomide resistance in glioma.
    9. Somatic driver mutation prevalence in 1844 prostate cancers identifies ZNRF3 loss as a predictor of metastatic relapse.
      Title: Somatic driver mutation prevalence in 1844 prostate cancers identifies ZNRF3 loss as a predictor of metastatic relapse.
    10. MicroRNA301a/ZNRF3/wnt/betacatenin signal regulatory crosstalk mediates glioma progression.
      Title: MicroRNA‑301a/ZNRF3/wnt/β‑catenin signal regulatory crosstalk mediates glioma progression.
    Submit: New GeneRIF Correction See all GeneRIFs (35)

    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
    Genome-wide association study identifies multiple susceptibility loci for pancreatic cancer.
    EBI GWAS Catalog
    Meta-analysis identifies 13 new loci associated with waist-hip ratio and reveals sexual dimorphism in the genetic basis of fat distribution.
    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

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables frizzled binding IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables frizzled 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 ubiquitin protein ligase activity IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables ubiquitin protein ligase activity TAS
    Traceable Author Statement
    more info
    		 PubMed 
    enables ubiquitin-protein transferase activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    Process Evidence Code Pubs
    involved_in Wnt receptor catabolic process IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in Wnt receptor catabolic process IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in Wnt receptor catabolic process TAS
    Traceable Author Statement
    more info
    		 PubMed 
    involved_in Wnt signaling pathway IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in limb development ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    involved_in negative regulation of canonical Wnt signaling pathway IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in negative regulation of canonical Wnt signaling pathway IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in negative regulation of non-canonical Wnt signaling pathway IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in protein ubiquitination IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in protein ubiquitination IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in regulation of Wnt signaling pathway, planar cell polarity pathway IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in stem cell proliferation ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    involved_in ubiquitin-dependent protein catabolic process IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in ubiquitin-dependent protein catabolic process IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    Component Evidence Code Pubs
    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
    		  

    General protein information

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    Preferred Names
    E3 ubiquitin-protein ligase ZNRF3
    Names
    CTA-292E10.6
    RING finger protein 203
    RING-type E3 ubiquitin transferase ZNRF3
    novel C3HC4 type Zinc finger (ring finger)
    zinc/RING finger protein 3
    NP_001193927.1
    NP_115549.2

    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.

    mRNA and Protein(s)

    1. NM_001206998.2 → NP_001193927.1  E3 ubiquitin-protein ligase ZNRF3 isoform 1 precursor

      See identical proteins and their annotated locations for NP_001193927.1

      Status: VALIDATED

      Description
      Transcript Variant: This variant (1) represents the longer transcript and encodes the longer isoform (1).
      Source sequence(s)
      AB051436, AI244417, AL021393, AL031596
      Consensus CDS
      CCDS56225.1
      UniProtKB/Swiss-Prot
      B3KU18, Q6ICH1, Q6NTF8, Q8WU18, Q9ULT6
      Related
      ENSP00000443824.2, ENST00000544604.7
      Conserved Domains (1) summary
      pfam13639
      Location:293 → 334
      zf-RING_2; Ring finger domain

    2. NM_032173.4 → NP_115549.2  E3 ubiquitin-protein ligase ZNRF3 isoform 2

      See identical proteins and their annotated locations for NP_115549.2

      Status: VALIDATED

      Description
      Transcript Variant: This variant (2) differs in the 5' UTR, lacks a portion of the 5' coding region, and initiates translation at a downstream start codon, compared to variant 1. The encoded isoform (2) has a shorter N-terminus, compared to isoform 1.
      Source sequence(s)
      AB051436, AI244417, AK096397, AL021393
      Consensus CDS
      CCDS42999.1
      UniProtKB/Swiss-Prot
      Q9ULT6
      Related
      ENSP00000384456.1, ENST00000402174.5
      Conserved Domains (1) summary
      pfam13639
      Location:193 → 234
      zf-RING_2; Ring finger domain

    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_000022.11 Reference GRCh38.p14 Primary Assembly

      Range
      28883572..29057488
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060946.1 Alternate T2T-CHM13v2.0

      Range
      29344932..29518764
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)
    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    Q9ULT6.3 GenPept UniProtKB/Swiss-Prot:Q9ULT6

    Gene LinkOut

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

    Chemical Information
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