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Category   Symbol Source: HGNC EntrezGene Ensembl GeneCards RNA genes CroW21
GIFtS

ZNRF2 Gene

protein-coding   GIFtS: 49
GCID: GC07P030290

Zinc And Ring Finger 2

  See related disease
at  

(According to 1HGNC, 2Entrez Gene,
3UniProtKB/Swiss-Prot, 4UniProtKB/TrEMBL, 5OMIM, 6GeneLoc, 7Ensembl, 8DME, 9miRBase, 10fRNAdb, 12H-InvDB, 13NCBI, 14NONCODE, and/or 15RNAdb)
About This Section

Aliases
Zinc And Ring Finger 21 2     RING Finger Protein 2022 3
Protein Ells22 3     E3 Ubiquitin-Protein Ligase ZNRF22
Zinc/RING Finger Protein 22 3     Zinc Finger/RING Finger 22
RNF2022 3     EC 6.3.2.-3

External Ids:    HGNC: 223161   Entrez Gene: 2230822   Ensembl: ENSG000001802337   OMIM: 6120615   UniProtKB: Q8NHG83   

Export aliases for ZNRF2 gene to outside databases

Previous GC identifers: GC07P030068 GC07P030097


(According to Entrez Gene, Tocris Bioscience, Wikipedia's Gene Wiki, PharmGKB,
UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL)
About This Section

GeneCards Summary for ZNRF2 Gene: 
ZNRF2 (zinc and ring finger 2) is a protein-coding gene. Diseases associated with ZNRF2 include neuronitis. GO annotations related to this gene include zinc ion binding and ligase activity. An important paralog of this gene is ZNRF1.

UniProtKB/Swiss-Prot: ZNRF2_HUMAN, Q8NHG8
Function: May play a role in the establishment and maintenance of neuronal transmission and plasticity via its
ubiquitin ligase activity. E3 ubiquitin ligases accept ubiquitin from an E2 ubiquitin-conjugating enzyme in the
form of a thioester and then directly transfer the ubiquitin to targeted substrates




(According to GeneLoc and/or HGNC, and/or
Entrez Gene (NCBI build 37),
and/or miRBase,
Genomic Views according to UCSC (hg19) and Ensembl (release 73), Regulatory elements and Epigenetics data according to QIAGEN, SABiosciences, and/or SwitchGear Genomics)
About This Section
RefSeq DNA sequence:
NC_000007.13  NC_018918.2  NT_007819.17  NT_079592.2  
Regulatory elements:
   SABiosciences Regulatory transcription factor binding sites in the ZNRF2 gene promoter:
         GR   Pax-5   HSF1 (long)   RORalpha1   PPAR-gamma1   USF-1   HSF1short   PPAR-gamma2   GR-alpha   LyF-1   
         Other transcription factors

SwitchGear Promoter luciferase reporter plasmids (see all 2): ZNRF2 promoter sequence
   Search SABiosciences Chromatin IP Primers for ZNRF2

Epigenetics:
QIAGEN PyroMark CpG Assay predesigned Pyrosequencing DNA Methylation assays in human, mouse, rat ZNRF2


Genomic Location:
Genomic View: UCSC Golden Path with GeneCards custom track

Entrez Gene cytogenetic band: 7p14.3   Ensembl cytogenetic band:  7p14.3   HGNC cytogenetic band: 7p15.1

ZNRF2 Gene in genomic location: bands according to Ensembl, locations according to (and/or Entrez Gene and/or Ensembl if different)
ZNRF2 gene location

GeneLoc information about chromosome 7         GeneLoc Exon Structure

GeneLoc location for GC07P030290:  view genomic region     (about GC identifiers)

Start:
30,323,923 bp from pter      End:
30,452,118 bp from pter
Size:
128,196 bases      Orientation:
plus strand

1 alternative location:
Chr7+,CRA_TCAG 30,373,689-30,457,078     

(According to UniProtKB, HORDE, neXtProt, Ensembl, and/or Reactome, Modification sites according to PhosphoSitePlus, Specific Peptides from DME, Protein expression images according to data from SPIRE 1MOPED, 2PaxDb, and 3MAXQB RefSeq according to NCBI, PDB rendering according to OCA and/or Proteopedia, Recombinant Proteins from EMD Millipore, R&D Systems, GenScript, Enzo Life Sciences, OriGene, Novus Biologicals, Sino Biological, ProSpec, and/or Cloud-Clone Corp.,
Biochemical Assays by EMD Millipore, R&D Systems, OriGene, GenScript, Cell Signaling Technology, Enzo Life Sciences, and/or Cloud-Clone Corp., Ontologies according to Gene Ontology Consortium 01 Oct 2013 and Entrez Gene, Antibodies by EMD Millipore, R&D Systems, GenScript, Cell Signaling Technology, OriGene, Novus Biologicals, Thermo Fisher Scientific, LSBio, Abcam, and/or Cloud-Clone Corp.)
About This Section

UniProtKB/Swiss-Prot: ZNRF2_HUMAN, Q8NHG8 (See protein sequence)
Recommended Name: E3 ubiquitin-protein ligase ZNRF2  
Size: 242 amino acids; 24115 Da
Subunit: Interacts with UBE2N
Subcellular location: Endosome membrane; Peripheral membrane protein. Lysosome membrane; Peripheral membrane
protein. Cell junction, synapse, presynaptic cell membrane; Peripheral membrane protein. Note=Present in
presynaptic plasma membranes in neurons

Explore the universe of human proteins at neXtProt for ZNRF2: NX_Q8NHG8

Explore proteomics data for ZNRF2 at MOPED 

Post-translational modifications:

  • View modification sites using PhosphoSitePlus
  • View neXtProt modification sites for NX_Q8NHG8

  • ZNRF2 Protein expression data from MOPED1, PaxDb2 and MAXQB3 :    About this image 

    ZNRF2 Protein Expression
    REFSEQ proteins: NP_667339.1  
    ENSEMBL proteins: 
     ENSP00000323879   ENSP00000456371  

    Human Recombinant Protein Products for ZNRF2: 
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    Cloud-Clone Corp. Proteins for ZNRF2 

    Gene Ontology (GO): 5 cellular component terms (GO ID links to tree view):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0005765lysosomal membrane IEA--
    GO:0005886plasma membrane IEA--
    GO:0010008endosome membrane IEA--
    GO:0030054cell junction IEA--
    GO:0042734presynaptic membrane IEA--

    ZNRF2 for ontologies           About GeneDecksing



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    (According to HGNC, IUPHAR, InterPro, ProtoNet, UniProtKB, and/or BLOCKS, Sets of similar genes according to GeneDecks)
    About This Section
    HGNC Gene Families: 
    RNF: RING-type (C3HC4) zinc fingers

    2 InterPro protein domains:
     IPR001841 Znf_RING
     IPR013083 Znf_RING/FYVE/PHD

    Graphical View of Domain Structure for InterPro Entry Q8NHG8

    ProtoNet protein and cluster: Q8NHG8

    1 Blocks protein domain: IPB001841 Zn-finger

    UniProtKB/Swiss-Prot: ZNRF2_HUMAN, Q8NHG8
    Domain: The RING-type zinc finger domain is required for E3 ligase activity (By similarity)
    Similarity: Contains 1 RING-type zinc finger


    ZNRF2 for domains           About GeneDecksing


    (According to 1UniProtKB, Genatlas, LifeMap Discovery™, IUBMB, and/or 2DME, Human phenotypes from GenomeRNAi, Animal models from MGI Mar 06 2013, inGenious Targeting Laboratory, genOway,
    bound targets from SABiosciences, miRNA Gene Targets from miRTarBase, shRNA from OriGene, RNAi from EMD Millipore, siRNAs from OriGene, QIAGEN, microRNA from QIAGEN, Gene Editing from DNA2.0, Sirion Biotech, Clones from EMD Millipore, OriGene, SwitchGear Genomics, GenScript, Sino Biological, DNA2.0, Vector BioLabs, and Sirion Biotech, Cell Lines from GenScript, LifeMap BioReagents, In Situ Hybridization Assays from Advanced Cell Diagnostics, Ontologies according to Gene Ontology Consortium 01 Oct 2013 via Entrez Gene.)
    About This Section

    Molecular Function:

         UniProtKB/Swiss-Prot Summary: ZNRF2_HUMAN, Q8NHG8
    Function: May play a role in the establishment and maintenance of neuronal transmission and plasticity via its
    ubiquitin ligase activity. E3 ubiquitin ligases accept ubiquitin from an E2 ubiquitin-conjugating enzyme in the
    form of a thioester and then directly transfer the ubiquitin to targeted substrates

         Enzyme Number (IUBMB): EC 6.3.2.-1

         Gene Ontology (GO): 4 molecular function terms (GO ID links to tree view):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0005515protein binding ----
    GO:0008270zinc ion binding IEA--
    GO:0016874ligase activity IEA--
    GO:0046872metal ion binding ----
         
    ZNRF2 for ontologies           About GeneDecksing


    Phenotypes:
         2 GenomeRNAi human phenotypes for ZNRF2:
     Decreased viability  Synthetic lethal with Ras 

    Animal Models:
       inGenious Targeting Laboratory - Custom generated mouse model solutions for ZNRF2 
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    SwitchGear 3'UTR luciferase reporter plasmidZNRF2 3' UTR sequence
    Inhib. RNA
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    (Pathways according to EMD Millipore, R&D Systems, Cell Signaling Technology, KEGG, PharmGKB, BioSystems, Sino Biological, Reactome, Tocris Bioscience, GeneGo (Thomson Reuters), QIAGEN, and/or UniProtKB, Sets of similar genes according to GeneDecks, Interaction Networks according to SABiosciences, and/or STRING, Interactions according to 1UniProtKB, 2MINT, 3I2D, and/or 4STRING, with links to IntAct and Ensembl, Ontologies according to Gene Ontology Consortium 01 Oct 2013 via Entrez Gene).
    About This Section



    UniProtKB/Swiss-Prot: ZNRF2_HUMAN, Q8NHG8
    Pathway: Protein modification; protein ubiquitination

    Interactions:

        Search SABiosciences Gene Network CentralTM Interacting Genes and Proteins Networks for ZNRF2

    STRING Interaction Network Preview (showing 5 interactants - click image to see 6)

    5/7 Interacting proteins for ZNRF2 (Q8NHG82, 3 ENSP000003238794) via UniProtKB, MINT, STRING, and/or I2D (see all 7)

    InteractantInteraction Details
    GeneCardExternal ID(s)
    UBE2D2P628373, ENSP000003817174I2D: score=1 STRING: ENSP00000381717
    UBE2D3P610773, ENSP000003497224I2D: score=1 STRING: ENSP00000349722
    UBE2NP610883, ENSP000003161764I2D: score=1 STRING: ENSP00000316176
    UBE2D1P516683, ENSP000003630194I2D: score=1 STRING: ENSP00000363019
    UBE2D4Q9Y2X83, ENSP000002224024I2D: score=1 STRING: ENSP00000222402
    About this table

    Gene Ontology (GO): 1 biological process term (GO ID links to tree view):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0016567protein ubiquitination IEA--

    ZNRF2 for ontologies           About GeneDecksing



    (Chemical Compounds according to UniProtKB, Enzo Life Sciences, EMD Millipore, Tocris Bioscience HMDB, BitterDB, and/or Novoseek, Ligands according to IUPHAR, and Drugs according to DrugBank, Enzo Life Sciences, and/or PharmGKB, with drugs/clinical trials/news search links to CenterWatch)
    About This Section
    Browse Small Molecules at EMD Millipore
    Browse drugs & compounds from Enzo Life Sciences

    Browse Tocris compounds for ZNRF2

    4 HMDB Compounds for ZNRF2    About this table
    CompoundSynonyms CAS #PubMed Ids
    Adenosine monophosphate5'-AMP (see all 28)61-19-8--
    Adenosine triphosphate5'-(tetrahydrogen triphosphate) Adenosine (see all 24)56-65-5--
    Phosphoric acidacide phosphorique (FRENCH) (see all 20)7664-38-2--
    Pyrophosphate(4-)Diphosphoric acid ion (see all 10)14000-31-8--

    Search CenterWatch for drugs/clinical trials and news about ZNRF2

    (Secondary structures according to fRNAdb,
    GenBank/EMBL/DDBJ Accessions according to
    Unigene (Build 236 Homo sapiens; Apr 25 2013) or GenBank,
    RefSeq according to Entrez Gene,
    DOTS (version 10), and/or AceView, transcript ids from Ensembl with links to UCSC,
    Conferences by KenesGroup, exon structure from GeneLoc, alternative splicing isoforms according to ASD and/or ECgene,
    RNAi Products from EMD Millipore,
    siRNAs from OriGene, QIAGEN, shRNA from OriGene, microRNA from QIAGEN,
    Tagged/untagged cDNA clones from OriGene, SwitchGear Genomics, GenScript, DNA2.0, Vector BioLabs, Sirion Biotech, Primers from OriGene, SABiosciences, and/or QIAGEN )
    About This Section

    REFSEQ mRNAs for ZNRF2 gene: 
    NM_147128.3  

    Unigene Cluster for ZNRF2:

    Zinc and ring finger 2
    Hs.263912  [show with all ESTs]
    Unigene Representative Sequence: AF513707
    4 Ensembl transcripts including schematic representations, and UCSC links where relevant:
    ENST00000323037(uc003tat.3) ENST00000459998 ENST00000442800 ENST00000414621

    miRNA
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    Inhib. RNA
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      QIAGEN QuantiTect SYBR Green Assays in human, mouse, rat ZNRF2
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    Additional mRNA sequence: 

    AF513707.1 AF527533.1 AK025240.1 AY054122.1 

    7 DOTS entries:

    DT.445901  DT.310584  DT.121108459  DT.91726658  DT.75128085  DT.121108533  DT.432266 

    24/190 AceView cDNA sequences (see all 190):

    BG427982 AW118226 BM797760 AI223439 AA453611 AL700627 AW473535 BP429644 
    AI902198 BQ014946 BI966092 NM_147128 BM787187 NM_152747 AL050378 CK904110 
    BX485301 BM468619 AI418204 AF527533 AW166368 AI801498 AA412204 AA907191 

    GeneLoc Exon Structure


    (RNA expression data according to H-InvDB, NONCODE, miRBase, and RNAdb, Expression images according to data from BioGPS, Illumina Human BodyMap, and CGAP SAGE, Sets of similar genes according to GeneDecks, in vivo and in vitro expression data from LifeMap Discovery™, plus additional links to Genevestigator, and/or SOURCE, and/or BioGPS, and/or UniProtKB,
    PCR Arrays from SABiosciences, Primers from OriGene, SABiosciences, and/or QIAGEN, In Situ Hybridization Assays from Advanced Cell Diagnostics)
    About This Section

    ZNRF2 expression in normal human tissues (normalized intensities)
    See probesets specificity/sensitivity at GeneAnnot
    About this imageBioGPS <intensity>2/3
    CGAP TAG: TGTTATTACT
    ZNRF2 Expression
    About this image


    See ZNRF2 Protein Expression from SPIRE MOPED and PaxDB
    Genevestigator expression for ZNRF2

    SOURCE GeneReport for Unigene cluster: Hs.263912

    UniProtKB/Swiss-Prot: ZNRF2_HUMAN, Q8NHG8
    Tissue specificity: Highly expressed in the brain, with higher expression during development than in adult.
    Expressed also in mammary glands, testis, colon and kidney

        SABiosciences Expression via Pathway-Focused PCR Array including ZNRF2: 
              Ubiquitin Ligases in human mouse rat

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    (Orthologs according to 1,2HomoloGene (2older version, for species not in 1newer version), 3euGenes, 4SGD , 5MGI Mar 06 2013, with possible further links to Flybase and/or WormBase, and/or 6Ensembl pan taxonomic compara , Gene Trees according to Ensembl and TreeFam)
    About This Section

    This gene was present in the common ancestor of animals.

    Orthologs for ZNRF2 gene from 7/14 species (see all 14)    About this table
    Organism Taxonomic
    classification
    Gene Description Human
    Similarity
    Orthology
    Type
    Details
    mouse
    (Mus musculus)
    Mammalia Znrf21 , 5 zinc and ring finger 21, 5 85.98(n)1
    88.41(a)1
      6 (27.15 cM)5
    3875241  NM_199143.21  NP_954594.11 
     548169165 
    chicken
    (Gallus gallus)
    Aves ZNRF21 zinc and ring finger 2 87.97(n)
    94.74(a)
      420678  XM_418778.3  XP_418778.3 
    lizard
    (Anolis carolinensis)
    Reptilia ZNRF26
    Uncharacterized protein
    73(a)
    1 ↔ 1
    6(36269665-36329256)
    African clawed frog
    (Xenopus laevis)
    Amphibia Xl.124752 Xenopus laevis transcribed sequence with weak similarity more 84.97(n)    BJ086886.1 
    zebrafish
    (Danio rerio)
    Actinopterygii znrf2b1 zinc and ring finger 2b 68.36(n)
    73.73(a)
      767761  NM_001076728.1  NP_001070196.1 
    fruit fly
    (Drosophila melanogaster)
    Insecta CG144351 CG14435 52.92(n)
    48.33(a)
      31628  NM_132131.3  NP_572359.2 
    worm
    (Caenorhabditis elegans)
    Secernentea Y71F9AL.101 Protein Y71F9AL.10 52.59(n)
    52.59(a)
      171852  NM_058658.4  NP_491059.2 


    ENSEMBL Gene Tree for ZNRF2 (if available)
    TreeFam Gene Tree for ZNRF2 (if available)

    (Paralogs according to 1HomoloGene,
    2Ensembl, and 3SIMAP, Pseudogenes according to 4Pseudogene.org Build 68)
    About This Section
    Paralogs for ZNRF2 gene
    ZNRF12  
    1 SIMAP similar gene for ZNRF2 using alignment to 2 protein entries:     ZNRF2_HUMAN (see all proteins):
    ZNRF1

    ZNRF2 for paralogs           About GeneDecksing


    1 Pseudogenes.org Pseudogene for ZNRF2
    PGOHUM00000232633


    (SNPs/Variants according to the 1NCBI SNP Database, 2Ensembl, 3PupaSUITE, 4UniProtKB, and DNA2.0, Linkage Disequilibrium by HapMap, Structural Variations(CNVs/InDels/Inversions) from the Database of Genomic Variants, Mutations from the Human Gene Mutation Database (HGMD) and the Locus Specific Mutation Databases (LSDB), Blood group antigen gene mutations by BGMUT, Resequencing Primers from QIAGEN, Cancer Mutation PCR Arrays and Assays and Copy Number PCR Arrays from SABiosciences)
    About This Section

    10/1630 SNPs in ZNRF2 are shown (see all 1630)    About this table     
    Genomic DataTranscription Related DataAllele Frequencies
    SNP IDValidClinical
    significance
    Chr 7 posSequence#AA
    Chg
    TypeMore#Allele
    freq
    PopTotal
    sample
    More
    ----------
    rs2007995451,2
    C--30322210(+) GTCTC-/AAAT  
            
    AAATA
    1 -- us2k10--------
    rs69780121,2
    C,F,A,H--30322341(+) AAAGAA/GGGCCA 1 -- us2k1 trp317Minor allele frequency- G:0.26NS EA NA WA CSA 2101
    rs796995981,2
    C,F--30322482(+) GTTAAT/AGAGTG 1 -- us2k11Minor allele frequency- A:0.07WA 118
    rs1861237611,2
    --30322547(+) ACTCAC/TTCATT 1 -- us2k10--------
    rs1894156511,2
    --30322645(+) GCCAAC/TTGAGT 1 -- us2k10--------
    rs1814656611,2
    --30322681(+) AATAAC/TAACAT 1 -- us2k10--------
    rs3753500841,2
    C--30322758(+) GGGATA/C/GGGGAG 1 -- us2k10--------
    rs1869375521,2
    --30322880(+) ATGTGA/TGTTTG 1 -- us2k10--------
    rs69446721,2
    C,F,A,H--30322890(+) GTGTAC/TACAGA 1 -- us2k111Minor allele frequency- T:0.15NS NA CSA WA 1401
    rs1914048821,2
    --30322999(+) CAAATA/TGTGAA 1 -- us2k10--------

    HapMap Linkage Disequilibrium report for ZNRF2 (30323923 - 30452118 bp)

    Structural Variations
         Database of Genomic Variants (DGV) 3 variations for ZNRF2:    About this table     
    Variant IDTypeSubtypePubMed ID
    nsv436557CNV Deletion17901297
    nsv525379CNV Loss19592680
    nsv523514CNV Gain19592680

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    (in which this Gene is Involved, According to MalaCards, OMIM, UniProtKB, the University of Copenhagen DISEASES database, Conferences by KenesGroup, Genatlas, GeneTests, GAD, HuGE Navigator, and/or TGDB.)
    About This Section
    OMIM gene information: 612061    OMIM disorders: --

    2 diseases for ZNRF2:    About MalaCards
    neuronitis    


    ZNRF2 for disorders           About GeneDecksing


    Export disorders for ZNRF2 gene to outside databases

    (in PubMed. Associations of this gene to articles via 1Entrez Gene, 2UniProtKB/Swiss-Prot, 3HGNC, 4GAD, 5PharmGKB, 6HMDB, 7DrugBank, 8UniProtKB/TrEMBL, 9 Novoseek, and/or 10fRNAdb)
    About This Section

    PubMed articles for ZNRF2 gene, integrated from 9 sources (see all 16):
    (articles sorted by number of sources associating them with ZNRF2)
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    1. ZNRF proteins constitute a family of presynaptic E3 ubiquitin ligases. (PubMed id 14561866)1, 2, 9 Araki T. and Milbrandt J. (2003)
    2. The RING finger protein RNF8 recruits UBC13 for lysine 63-based self polyubiquitylation. (PubMed id 16215985)1, 2 Plans V.... Thomson T.M. (2006)
    3. Global, in vivo, and site-specific phosphorylation dynamics in signaling networks. (PubMed id 17081983)1, 2 Olsen J.V....Mann M. (2006)
    4. 14-3-3 proteins sequester a pool of soluble TRIM32 ubi quitin ligase to repress autoubiquitylation and cytoplasmic body formation. (PubMed id 23444366)1 Ichimura T....Hachiya N. (2013)
    5. ZNRF2 is released from membranes by growth factors and , together with ZNRF1, regulates the Na+/K+ATPase. (PubMed id 22797923)1 Hoxhaj G....MacKintosh C. (2012)
    6. System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation. (PubMed id 21406692)2 Rigbolt K.T....Blagoev B. (2011)
    7. Mass spectrometric analysis of lysine ubiquitylation r eveals promiscuity at site level. (PubMed id 21139048)1 Danielsen J.M....Nielsen M.L. (2011)
    8. Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis. (PubMed id 20068231)2 Olsen J.V....Mann M. (2010)
    9. Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach. (PubMed id 19413330)2 Gauci S....Mohammed S. (2009)
    10. Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions. (PubMed id 19690332)2 Mayya V.... Han D.K. (2009)

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    (According to Entrez Gene, HGNC, AceView, euGenes, Ensembl, miRBase, ECgene, Kegg, and/or H-InvDB)
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    Entrez Gene: 223082 HGNC: 22316 AceView: ZNRF2andDKFZp586I1420 Ensembl:ENSG00000180233 euGenes: HUgn223082
    ECgene: ZNRF2 H-InvDB: ZNRF2

    (According to HUGE)
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    NameDescription
    PharmGKB entry for ZNRF2 Pharmacogenomics, SNPs, Pathways

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