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

FOXN4 Gene

protein-coding   GIFtS: 43
GCID: GC12M109715

Forkhead Box N4

  See related diseases
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
Forkhead Box N41 2
Forkhead Box Protein N42
Forkhead/Winged Helix Transcription Factor FOXN42

External Ids:    HGNC: 213991   Entrez Gene: 1216432   Ensembl: ENSG000001394457   OMIM: 6094295   UniProtKB: Q96NZ13   

Export aliases for FOXN4 gene to outside databases

Previous GC identifers: GC12M108775 GC12M109554 GC12M108180 GC12M108178 GC12M106733


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

Entrez Gene summary for FOXN4 Gene:
Members of the winged-helix/forkhead family of transcription factors, such as FOXN4, are characterized by a
110-amino acid DNA-binding domain that can fold into a variant of the helix-turn-helix motif consisting of 3
alpha helices flanked by 2 large loops or wings. These transcription factors are involved in a variety of
biologic processes as key regulators in development and metabolism (Li et al., 2004 (PubMed 15363391)).(supplied
by OMIM, Mar 2008)

GeneCards Summary for FOXN4 Gene: 
FOXN4 (forkhead box N4) is a protein-coding gene. Diseases associated with FOXN4 include hallervorden-spatz syndrome, and retinitis. GO annotations related to this gene include double-stranded DNA binding and sequence-specific DNA binding. An important paralog of this gene is FOXN3.




(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_000012.11  NT_009775.17  NC_018923.2  
Regulatory elements:
   SABiosciences Regulatory transcription factor binding sites in the FOXN4 gene promoter:
         AML1a   FOXO4   FOXO1a   Ik-3   FOXO1   
         Other transcription factors

SwitchGear Promoter luciferase reporter plasmidFOXN4 promoter sequence
   Search SABiosciences Chromatin IP Primers for FOXN4

Epigenetics:
QIAGEN PyroMark CpG Assay predesigned Pyrosequencing DNA Methylation assays in human, mouse, rat FOXN4


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

Entrez Gene cytogenetic band: 12q24.11   Ensembl cytogenetic band:  12q24.11   HGNC cytogenetic band: 12q24.12

FOXN4 Gene in genomic location: bands according to Ensembl, locations according to (and/or Entrez Gene and/or Ensembl if different)
FOXN4 gene location

GeneLoc information about chromosome 12         GeneLoc Exon Structure

GeneLoc location for GC12M109715:  view genomic region     (about GC identifiers)

Start:
109,715,783 bp from pter      End:
109,747,025 bp from pter
Size:
31,243 bases      Orientation:
minus strand

(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: FOXN4_HUMAN, Q96NZ1 (See protein sequence)
Recommended Name: Forkhead box protein N4  
Size: 517 amino acids; 55215 Da
Subcellular location: Nucleus (Potential)
Sequence caution: Sequence=BAD18661.1; Type=Erroneous initiation;
Secondary accessions: Q6ZMR4 Q96NZ0
Alternative splicing: 2 isoforms:  Q96NZ1-1   Q96NZ1-2   (No experimental confirmation available)

Explore the universe of human proteins at neXtProt for FOXN4: NX_Q96NZ1

Explore proteomics data for FOXN4 at MOPED 

Post-translational modifications:

  • View modification sites using PhosphoSitePlus
  • View neXtProt modification sites for NX_Q96NZ1

  • FOXN4 Protein expression data from MOPED1, PaxDb2 and MAXQB3 :    About this image 

    FOXN4 Protein Expression
    REFSEQ proteins: NP_998761.2  
    ENSEMBL proteins: 
     ENSP00000474754   ENSP00000347354   ENSP00000299162   ENSP00000408085  

    Human Recombinant Protein Products for FOXN4: 
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    Cloud-Clone Corp. Proteins for FOXN4 

    Gene Ontology (GO): 2 cellular component terms (GO ID links to tree view):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0005634nucleus IEA--
    GO:0005667transcription factor complex ----

    FOXN4 for ontologies           About GeneDecksing



    FOXN4 Antibody Products: 
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    Cloud-Clone Corp. ELISAs for FOXN4 
    Cloud-Clone Corp. CLIAs for FOXN4


    (According to HGNC, IUPHAR, InterPro, ProtoNet, UniProtKB, and/or BLOCKS, Sets of similar genes according to GeneDecks)
    About This Section
    HGNC Gene Families: 
    FOX: Forkhead boxes

    3 InterPro protein domains:
     IPR011991 WHTH_DNA-bd_dom
     IPR018122 TF_fork_head_CS
     IPR001766 TF_fork_head

    Graphical View of Domain Structure for InterPro Entry Q96NZ1

    ProtoNet protein and cluster: Q96NZ1

    UniProtKB/Swiss-Prot: FOXN4_HUMAN, Q96NZ1
    Similarity: Contains 1 fork-head DNA-binding domain


    FOXN4 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

         Gene Ontology (GO): 5/6 molecular function terms (GO ID links to tree view) (see all 6):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0003690double-stranded DNA binding ----
    GO:0003700sequence-specific DNA binding transcription factor activity IEA--
    GO:0003705RNA polymerase II distal enhancer sequence-specific DNA binding transcription factor activity ----
    GO:0008134transcription factor binding ----
    GO:0008301DNA binding, bending ----
         
    FOXN4 for ontologies           About GeneDecksing


    Phenotypes:
         1 GenomeRNAi human phenotype for FOXN4:
     Decreased viability with pacli 

         4 MGI mutant phenotypes (inferred from 1 allele(MGI details for Foxn4):
     cellular  mortality/aging  nervous system  vision/eye 

    FOXN4 for phenotypes           About GeneDecksing

    Animal Models:
         MGI mouse knock-out Foxn4tm1Xia for FOXN4

       inGenious Targeting Laboratory - Custom generated mouse model solutions for FOXN4 
       inGenious Targeting Laboratory - Custom generated inducible mouse model solutions for FOXN4

       genOway customized KO model: permanent, tissue-specific or time-controlled inactivation for FOXN4 
       genOway customized Knockin model: humanization, point mutation, expression monitoring, etc. for FOXN4 

    miRNA
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    8/10 QIAGEN miScript miRNA Assays for microRNAs that regulate FOXN4 (see all 10):
    hsa-miR-520f hsa-miR-513a-5p hsa-miR-27a hsa-miR-513a-3p hsa-miR-128 hsa-miR-3681* hsa-miR-144 hsa-miR-149
    SwitchGear 3'UTR luciferase reporter plasmidFOXN4 3' UTR sequence
    Inhib. RNA
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    Gene Editing
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    Advanced Cell Diagnostics RNAscope RNA in situ hybridization assays for FOXN4


    (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



    Interactions:

        Search SABiosciences Gene Network CentralTM Interacting Genes and Proteins Networks for FOXN4

    Gene Ontology (GO): 5/11 biological process terms (GO ID links to tree view) (see all 11):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0006351transcription, DNA-dependent IEA--
    GO:0006355regulation of transcription, DNA-dependent ----
    GO:0007389pattern specification process ----
    GO:0008016regulation of heart contraction ----
    GO:0009790embryo development ----

    FOXN4 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 FOXN4

    Search CenterWatch for drugs/clinical trials and news about FOXN4

    (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 FOXN4 gene: 
    NM_213596.2  

    Unigene Cluster for FOXN4:

    Forkhead box N4
    Hs.528316  [show with all ESTs]
    Unigene Representative Sequence: BC146825
    4 Ensembl transcripts including schematic representations, and UCSC links where relevant:
    ENST00000468516 ENST00000355216(uc001tof.4) ENST00000299162(uc009zvg.3 uc001toe.4)
    ENST00000423960
    miRNA
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    8/10 QIAGEN miScript miRNA Assays for microRNAs that regulate FOXN4 (see all 10):
    hsa-miR-520f hsa-miR-513a-5p hsa-miR-27a hsa-miR-513a-3p hsa-miR-128 hsa-miR-3681* hsa-miR-144 hsa-miR-149
    SwitchGear 3'UTR luciferase reporter plasmidFOXN4 3' UTR sequence
    Inhib. RNA
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    Vector BioLabs ready-to-use adenovirus/AAV for human, mouse, rat FOXN4
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      QIAGEN QuantiTect SYBR Green Assays in human, mouse, rat FOXN4
      QIAGEN QuantiFast Probe-based Assays in human, mouse, rat FOXN4

    Additional mRNA sequence: 

    AF425596.1 AF425597.1 AK093286.1 AK131519.1 BC113073.1 BC146825.1 

    2 DOTS entries:

    DT.99974511  DT.95259358 

    14 AceView cDNA sequences:

    AI805494 AK093286 BU156681 AF425596 AF425597 AA421371 NM_213596 AK131519 
    AI221704 AW117425 AI243313 AA421288 AI187920 BX096551 

    GeneLoc Exon Structure

    4 Alternative Splicing Database (ASD) splice patterns (SP) for FOXN4    About this scheme

    ExUns: 1 ^ 2 ^ 3a · 3b ^ 4 ^ 5a · 5b ^ 6 ^ 7a · 7b ^ 8a · 8b ^ 9 ^ 10 ^ 11
    SP1:                                      -                                                   
    SP2:                                      -     -                                             
    SP3:                                                                                          
    SP4:                                                                    -     -     -         


    ECgene alternative splicing isoforms for FOXN4

    (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

    FOXN4 expression in normal human tissues (normalized intensities)      FOXN4 embryonic expression: see
    See probesets specificity/sensitivity at GeneAnnot
    About this imageBioGPS <intensity>2/3
    CGAP TAG: ACCCCTGATA
    FOXN4 Expression
    About this image


    FOXN4 expression in embryonic tissues and stem cells    About this table
    Data from LifeMap, the Embryonic Development and Stem Cells Database 
     5/1 selected tissues (see all 1) fully expand
     
     Eye (Sensory Organs)    fully expand to see all 4 entries
             Late Amacrine Horizontal Precursor Cells Retinal Neuroblastic Layer
             Retina
             retinal progenitor cell e12.5   

    See FOXN4 Protein Expression from SPIRE MOPED and PaxDB
    Genevestigator expression for FOXN4

    SOURCE GeneReport for Unigene cluster: Hs.528316
        SABiosciences Custom PCR Arrays for FOXN4
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    In Situ
    Assay Products:
     

     
    Advanced Cell Diagnostics RNAscope RNA in situ hybridization assays for FOXN4

    (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 and fungi.

    Orthologs for FOXN4 gene from 6/12 species (see all 12)    About this table
    Organism Taxonomic
    classification
    Gene Description Human
    Similarity
    Orthology
    Type
    Details
    mouse
    (Mus musculus)
    Mammalia Foxn41 , 5 forkhead box N41, 5 81.3(n)1
    80.85(a)1
      5 (55.99 cM)5
    1168101  NM_148935.21  NP_683737.21 
     1142541645 
    chicken
    (Gallus gallus)
    Aves FOXN41 forkhead box N4 71.36(n)
    70.24(a)
      416898  NM_001083359.1  NP_001076828.1 
    lizard
    (Anolis carolinensis)
    Reptilia FOXN46
    Uncharacterized protein
    64(a)
    1 ↔ 1
    AAWZ02041607(425-5471)
    zebrafish
    (Danio rerio)
    Actinopterygii foxn42 forkhead box N4 75.58(n)   30315  AF198446.2 
    fruit fly
    (Drosophila melanogaster)
    Insecta jumu6
    jumeau
    18(a)
    1 → many
    3R(6175906-6187343)
    baker's yeast
    (Saccharomyces cerevisiae)
    Saccharomycetes FHL16
    Regulator of ribosomal protein transcription; has ...
    8(a)
    1 → many
    XVI(733623-736433)


    ENSEMBL Gene Tree for FOXN4 (if available)
    TreeFam Gene Tree for FOXN4 (if available)

    (Paralogs according to 1HomoloGene,
    2Ensembl, and 3SIMAP, Pseudogenes according to 4Pseudogene.org Build 68)
    About This Section
    Paralogs for FOXN4 gene
    FOXN32  FOXJ12  FOXK12  FOXK22  FOXP42  FOXN12  FOXG12  FOXJ32  
    FOXP22  FOXJ22  FOXN22  FOXP32  FOXP12  

    FOXN4 for paralogs           About GeneDecksing



    (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

    10/660 SNPs in FOXN4 are shown (see all 660)    About this table     
    Genomic DataTranscription Related DataAllele Frequencies
    SNP IDValidClinical
    significance
    Chr 12 posSequence#AA
    Chg
    TypeMore#Allele
    freq
    PopTotal
    sample
    More
    ----------
    rs1431480011,2
    C--109715321(+) CTGTT-/AATGAG 1 -- int10--------
    rs342906291,2
    C,F--109715441(+) CCTGAG/TCTGTG 1 -- int13Minor allele frequency- T:0.20NA 10
    rs1811159711,2
    --109715801(+) TTATTA/GATAGA 1 -- ut310--------
    rs1468536311,2
    C--109715868(+) TGTGAA/GTAACA 1 -- ut310--------
    rs592264971,2
    C,F--109715932(+) TCAGAC/AGGGTA 1 -- ut311Minor allele frequency- A:0.50WA 2
    rs1503318601,2
    --109716104(+) CTCCCA/GGACAC 1 -- ut310--------
    rs776631971,2
    C--109716292(+) GAGAGA/GAAAAG 1 -- ut313Minor allele frequency- G:0.07CSA WA EA 240
    rs110660731,2
    C,F,A,H--109716331(+) GAGGTG/AAGGAA 1 -- ut31 ese38Minor allele frequency- A:0.33NA WA EA 370
    rs1378930731,2
    C--109716390(+) GGTTCA/GAGCTT 1 -- ut310--------
    rs606899981,2
    C--109716455(+) AAGCA-/CCCCCC 1 -- ut310--------

    HapMap Linkage Disequilibrium report for FOXN4 (109715783 - 109747025 bp)

    Structural Variations
          Database of Genomic Variants (DGV) variations for FOXN4: --
    SABiosciences Cancer Mutation PCR Assays
    SeqTarget long-range PCR primers for resequencing FOXN4
    DNA2.0 Custom Variant and Variant Library Synthesis for FOXN4

    (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: 609429    OMIM disorders: --

    3 diseases for FOXN4:    About MalaCards
    hallervorden-spatz syndrome    retinitis    neuronitis


    FOXN4 for disorders           About GeneDecksing


    Export disorders for FOXN4 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 FOXN4 gene integrated from 9 sources:
    (articles sorted by number of sources associating them with FOXN4)
        Utopia: connect your pdf to the dynamic
    world of online information

    1. The finished DNA sequence of human chromosome 12. (PubMed id 16541075)1, 2 Scherer S.E.... Gibbs R.A. (2006)
    2. Expression of the winged helix/forkhead gene, foxn4, during zebrafish development. (PubMed id 15464224)1, 2 Danilova N.... Steiner L.A. (2004)
    3. Complete sequencing and characterization of 21,243 full-length human cDNAs. (PubMed id 14702039)1, 2 Ota T.... Sugano S. (2004)
    4. Characterization of human FOXN4 gene in silico. (PubMed id 15492871)1 Katoh M. and Katoh M. (2004)
    5. Foxn4 controls the genesis of amacrine and horizontal cells by retinal progenitors. (PubMed id 15363391)1 Li S....Xiang M. (2004)
    6. Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. (PubMed id 12477932)1 Strausberg R.L....Marra M.A. (2002)

    (in PubMed, OMIM, and NCBI Bookshelf)
    About This Section
     ANDOR
    Aliases
    Free Text  

      Query String
    PubMed
    OMIM
    NCBI Bookshelf
      (Note: In FireFox, select the above section and copy using Ctrl-C)

    (According to Entrez Gene, HGNC, AceView, euGenes, Ensembl, miRBase, ECgene, Kegg, and/or H-InvDB)
    About This Section
    Entrez Gene: 121643 HGNC: 21399 AceView: FOXN4 Ensembl:ENSG00000139445 euGenes: HUgn121643
    ECgene: FOXN4 H-InvDB: FOXN4

    (According to HUGE)
    About This Section
      --

    (According to PharmGKB, ATLAS, HORDE, IMGT, LEIDEN, UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL,
    Wikipedia and/or GeneReviews via UniProtKB/Swiss-Prot)
    About This Section
    NameDescription
    PharmGKB entry for FOXN4 Pharmacogenomics, SNPs, Pathways

    (Patent information from GeneIP,
    Licensable technologies from WIS Yeda, Salk, Tufts,
    IP news from LifeMap Sciences, Inc.)
    About This Section
    Patent Information for FOXN4 gene:
    Search GeneIP for patents involving FOXN4

    GeneCards and IP:
    Japan Patent Office Licenses GeneCards     European Patent Office Licenses GeneCards     Improving the IP Search



    (Antibodies, recombinant proteins, and assays from EMD Millipore, R&D Systems, OriGene, QIAGEN, GenScript, Cell Signaling Technology, SABiosciences, Novus Biologicals, Sino Biological, Enzo Life Sciences, Abcam, ProSpec, Cloud-Clone Corp., Thermo Fisher Scientific, LSBio, Gene Editing from DNA2.0 and Sirion Biotech, Clones from EMD Millipore, OriGene, GenScript, Sino Biological, DNA2.0, SwitchGear Genomics, Vector BioLabs, Sirion Biotech, Cell lines from GenScript, and LifeMap BioReagents, PCR Arrays from SABiosciences, Drugs and/or compounds from EMD Millipore, Tocris Bioscience, and/or Enzo Life Sciences, In Situ Hybridization Assays from
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    About This Section

     
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    GeneCards Homepage - Last full update: 23 Oct 2013 - Incrementals: 4 Nov 2013 , 7 Nov 2013 , 23 Jan 2014

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