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

FNDC5 Gene

protein-coding   GIFtS: 46
GCID: GC01M033327

fibronectin type III domain containing 5

  Search for FNDC5
in our new
 Human Malady Compendium 
Biological research products
for FNDC5
    

(According to 1HGNC, 2Entrez Gene,
3UniProtKB/Swiss-Prot, 4UniProtKB/TrEMBL, 5OMIM, 6GeneLoc, 7Ensembl, 8DME, 9miRBase, and/or 10fRNAdb)
About This Section

Aliases
Fibronectin Type III Domain Containing 51 2
FRCP21 2 3 5
Fibronectin Type III Repeat-Containing Protein 22 3
Fibronectin Type III Domain-Containing Protein 52
Irisin1

External Ids:    HGNC: 202401   Entrez Gene: 2529952   Ensembl: ENSG000001600977   OMIM: 6119065   UniProtKB: Q8NAU13   

Export aliases for FNDC5 gene to outside databases

Previous GC identifers: GC01M032830 GC01M032996 GC01M033100 GC01M031443


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

UniProtKB/Swiss-Prot: FNDC5_HUMAN, Q8NAU1
Function: Irisin: mediates beneficial effects of muscular exercise. Induces browning of white adipose tissue by
stimulating UCP1 expression, at least in part, via the nuclear receptor PPARA (By similarity)




(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 69), Regulatory elements and Epigenetics data according to QIAGEN, SABiosciences, and/or SwitchGear Genomics)
About This Section
RefSeq DNA sequence:
NC_000001.10  NC_018912.1  NT_032977.9  
Regulatory elements:
   SABiosciences Regulatory transcription factor binding sites in the FNDC5 gene promoter:
         Nkx3-1   CREB   deltaCREB   NRSF form 1   Nkx3-1 v1   NRSF form 2   GATA-2   
         Other transcription factors

SwitchGear Promoter luciferase reporter plasmidFNDC5 promoter sequence
   Search SABiosciences Chromatin IP Primers for FNDC5

Epigenetics:
QIAGEN PyroMark CpG Assay predesigned Pyrosequencing DNA Methylation assays in human, mouse, rat FNDC5


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

Entrez Gene cytogenetic band: 1p35.1   Ensembl cytogenetic band:  1p35.1   HGNC cytogenetic band: 1p34.3

FNDC5 Gene in genomic location: bands according to Ensembl, locations according to (and/or Entrez Gene and/or Ensembl if different)
FNDC5 gene location

GeneLoc information about chromosome 1         GeneLoc Exon Structure

GeneLoc location for GC01M033327:  view genomic region     (about GC identifiers)

Start:
33,327,869 bp from pter      End:
33,338,083 bp from pter
Size:
10,215 bases      Orientation:
minus strand

(According to 1UniProtKB, HORDE, neXtProt, Ensembl, and/or Reactome, Modification sites according to 2PhosphoSitePlus, Specific Peptides from DME, Protein expression images according to data from SPIRE MOPED and PaxDb, 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 Uscn,
Biochemical Assays by EMD Millipore, R&D Systems, OriGene, GenScript, Cell Signaling Technology, Enzo Life Sciences, and/or Uscn, Ontologies according to Gene Ontology Consortium 01 Mar 2013 and Entrez Gene, Antibodies by EMD Millipore, R&D Systems, GenScript, Cell Signaling Technology, OriGene, Novus Biologicals, Thermo Fisher Scientific, Abcam, and/or Uscn)
About This Section

UniProtKB/Swiss-Prot: FNDC5_HUMAN, Q8NAU1 (See protein sequence)
Recommended Name: Fibronectin type III domain-containing protein 5 precursor  
Size: 212 amino acids; 23659 Da
Subcellular location: Cell membrane; Single-pass type I membrane protein. Peroxisome membrane; Single-pass type I
membrane protein (By similarity). Note=Imported in peroxisomes through the PEX5 receptor pathway (By similarity)
Subcellular location: Irisin: Secreted. Note=Detected in the blood of individuals subjected to endurance exercise
Caution: It is uncertain whether Met-1 or Met-76 is the initiator. Transcript evidence available at present time points
at Met-76. In this short version of the protein, the signal peptide cannot be predicted and the irisin peptide is
severely truncated. The first initiation codon corresponds to a non-AUG site, an N-terminal ATA codon, and has been
annotated as it is in good Kozak context. Although the existence of such a form has not been demonstrated western blot
analysis following endurance exercise shows the presence of an irisin peptide of similar size in human and mouse
plasma (PubMed:22237023), strongly suggesting the existence of full length irisin in human, at least in some tissues
Secondary accessions: A6NMC9 D3DPQ6 Q6P6D9 Q7Z676
Alternative splicing: 4 isoforms:  Q8NAU1-1   Q8NAU1-2   Q8NAU1-3   Q8NAU1-4   (No experimental confirmation available)

Explore the universe of human proteins at neXtProt for FNDC5: NX_Q8NAU1

Post-translational modifications:

  • The extracellular domain is cleaved and released from the cell membrane1
  • N-Glycosylated (By similarity)1
  • View modification sites using PhosphoSitePlus2
  • View neXtProt modification sites for NX_Q8NAU1

  • FNDC5 Protein expression data from MOPED and PaxDb:    About this image 
    Estimated protein expression log10 (pmol).

    REFSEQ proteins (3 alternative transcripts): 
    NP_001165411.1  NP_001165412.1  NP_715637.1  

    ENSEMBL proteins: 
     ENSP00000362569   ENSP00000362570  

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    Uscn Proteins for FNDC5

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

    GO IDQualified GO termEvidencePubMed IDs
    GO:0005576extracellular region ISS--
    GO:0005778peroxisomal membrane IEA--
    GO:0005783endoplasmic reticulum ISS--
    GO:0005886plasma membrane ISS--
    GO:0016021integral to membrane IEA--


    FNDC5 for ontologies           About GeneDecksing



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    (According to InterPro, ProtoNet, UniProtKB, and/or BLOCKS, Sets of similar genes according to GeneDecks)
    About This Section

    FNDC5 for domains           About GeneDecksing

    2 InterPro domains/families:
     IPR003961 Fibronectin_type3
     IPR013783 Ig-like_fold

    Graphical View of Domain Structure for InterPro Entry Q8NAU1

    ProtoNet protein and cluster: Q8NAU1

    UniProtKB/Swiss-Prot: FNDC5_HUMAN, Q8NAU1
    Similarity: Contains 1 fibronectin type-III domain


    (According to 1UniProtKB, Genatlas, LifeMap Discovery™, IUBMB, and/or 2DME, Human phenotypes from GenomeRNAi, Animal models from MGI Mar 06 2013,
    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, Clones from EMD Millipore, OriGene, SwitchGear Genomics, GenScript, Sino Biological, DNA2.0, and Vector BioLabs, Cell Lines from GenScript, LifeMap BioReagents, In Situ Hybridization Assays from Advanced Cell Diagnostics, Ontologies according to Gene Ontology Consortium 01 Mar 2013 via Entrez Gene.)
    About This Section

    Function Summary:

         UniProtKB/Swiss-Prot: FNDC5_HUMAN, Q8NAU1
    Function: Irisin: mediates beneficial effects of muscular exercise. Induces browning of white adipose tissue by
    stimulating UCP1 expression, at least in part, via the nuclear receptor PPARA (By similarity)
    Induction: Up-regulated by muscular exercise. This effect is probably mediated by PPARGC1A

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    hsa-miR-579 hsa-miR-140-5p hsa-miR-3678-3p hsa-miR-938 hsa-miR-3921 hsa-miR-3916 hsa-miR-3142 hsa-miR-629*
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    Gene Ontology (GO): 3 molecular function terms (GO ID links to tree view):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0003674molecular_function ND--
    GO:0005179hormone activity IEA--
    GO:0005515protein binding ----


    FNDC5 for ontologies           About GeneDecksing


    1 GenomeRNAi human phenotype for FNDC5:
     Increased S DNA content 


    (Pathways according to EMD Millipore, R&D Systems, Cell Signaling Technology, KEGG, PharmGKB, BioSystems, 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 Mar 2013 via Entrez Gene).
    About This Section



    Interactions:

        Search SABiosciences Gene Network CentralTM Interacting Genes and Proteins Networks for FNDC5

    STRING Interaction Network Preview (showing 4 interactants - click image to see more details)

    4 Interacting proteins for FNDC5 (Q8NAU13 ENSP000003625704) via UniProtKB, MINT, STRING, and/or I2D
    InteractantInteraction Details
    GeneCardExternal ID(s)
    PTSQ033933, ENSP000002803624I2D: score=4 STRING: ENSP00000280362
    C1orf105ENSP000003567004STRING: ENSP00000356700
    CRYZENSP000003393994STRING: ENSP00000339399
    ENSG00000228284ENSP000004143604STRING: ENSP00000414360
    About this table

    Gene Ontology (GO): 3 biological process terms (GO ID links to tree view):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0008150biological_process ND--
    GO:0014850response to muscle activity ISS--
    GO:0090336positive regulation of brown fat cell differentiation ISS--


    FNDC5 for ontologies           About GeneDecksing



    (Chemical Compounds according to UniProtKB, Enzo Life Sciences, EMD Millipore, Tocris Bioscience HMDB, BitterDB, and/or Novoseek, 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 FNDC5
    Search CenterWatch for drugs/clinical trials and news about FNDC5 

    (Secondary structures according to fRNAdb,
    GenBank/EMBL/DDBJ Accessions according to
    Unigene (Build 235 Homo sapiens; Mar 10 2013) or GenBank,
    RefSeq according to Entrez Gene,
    DOTS (version 10), and/or AceView, transcript ids from Ensembl with links to UCSC,
    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, Primers from OriGene, SABiosciences, and/or QIAGEN )
    About This Section

    REFSEQ mRNAs for FNDC5 gene (3 alternative transcripts): 
    NM_001171940.1  NM_001171941.1  NM_153756.2  

    Unigene Cluster for FNDC5:

    Fibronectin type III domain containing 5
    Hs.524234  [show with all ESTs]
    Unigene Representative Sequence: NM_001171941
    7 Ensembl transcripts including schematic representations, and UCSC links where relevant:
    ENST00000483143 ENST00000481487 ENST00000373470 ENST00000373471(uc001bwe.3 uc021okv.1 uc001bwf.2 uc001bwg.3)
    ENST00000497068 ENST00000496770 ENST00000465346

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    8/81 QIAGEN miScript miRNA Assays for microRNAs that regulate FNDC5 (see all 81):
    hsa-miR-579 hsa-miR-140-5p hsa-miR-3678-3p hsa-miR-938 hsa-miR-3921 hsa-miR-3916 hsa-miR-3142 hsa-miR-629*
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    Additional cDNA sequence: 

    AK092102.1 BC007548.1 BC033123.1 BC062297.1 BX537781.1 

    5 DOTS entries:

    DT.106354  DT.75152000  DT.100752500  DT.100752501  DT.92420744 

    24/135 AceView cDNA sequences (see all 135):

    AX747354 BE551417 BE218308 AA987622 T16538 BM714183 BF221649 BE467868 
    BE779112 AI680619 Z40909 T31185 BF445493 BE467031 BE549729 BF447318 
    AI468318 AW612671 BC033123 AI391724 BI757899 NM_153756 AA570017 AI694150 

    GeneLoc Exon Structure

    4 Alternative Splicing Database (ASD) splice patterns (SP) for FNDC5    About this scheme

    ExUns: 1 ^ 2a · 2b ^ 3 ^ 4 ^ 5 ^ 6a · 6b · 6c ^ 7a · 7b · 7c
    SP1:                                                  -                     
    SP2:                                            -     -     -     -         
    SP3:        -     -                                                         
    SP4:                                                  -     -               


    ECgene alternative splicing isoforms for FNDC5

    (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

    FNDC5 expression in normal human tissues (normalized intensities)
    See probesets specificity/sensitivity at GeneAnnot
    About this imageBioGPS
    CGAP TAG: AGGCTCCACT

    Microarray
    RNAseq (Illumina Body Map)
    (100×FPKM)½
    SAGE (Serial Analysis of Gene Expression)

    About this image

    FNDC5 expression in embryonic tissues and stem cells
    Expression by the Database of Embryonic development, Stem cell research, and Regenerative medicine    About this table
    2 LifeMap In Vivo Development Anatomical Compartments/Cells 
    Tissue Anatomical Compartment CellCategory (developmental path)
    OvaryPrimary FollicleGranulosa CellsOvary
    OvaryPrimordial FolliclePre-Granulosa CellsOvary
    Expression: Positive    Negative     Selective marker
    Experimental details: Curated     Microarrays     In-situ hybridization
    Stem Cell Differentiation: 3 LifeMap Cells 
    NameCategory
    PureStem™ mesenchymal progenitor SM30 (Embryonic Progenitor Cell)Adipose, Bone, Cartilage
    PureStem™ progenitor RASMO12 (Embryonic Progenitor Cell)
    PureStem™ progenitor Z1 (Embryonic Progenitor Cell)

    See FNDC5 Protein Expression from SPIRE MOPED and PaxDB
    Genevestigator expression for FNDC5

    SOURCE GeneReport for Unigene cluster: Hs.524234
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    In Situ
    Assay Products:
     

     
    Advanced Cell Diagnostics RNAscope RNA in situ hybridization assays for FNDC5

    (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 chordates.

    Orthologs for FNDC5 gene from 4/9 species (see all 9)    About this table
    Organism Taxonomic
    classification
    Gene Description Human
    Similarity
    Orthology
    Type
    Details
    mouse
    (Mus musculus)
    Mammalia Fndc51 , 5 fibronectin type III domain containing 51, 5 89.29(n)1
    99.27(a)1
      4 (62.93 cM)5
    3840611  NM_027402.31  NP_081678.11 
     1291369995 
    chicken
    (Gallus gallus)
    Aves FNDC51 fibronectin type III domain containing 5 83.58(n)
    94.12(a)
      419667  XM_417814.3  XP_417814.3 
    lizard
    (Anolis carolinensis)
    Reptilia FNDC56
    --
    30(a)
    1 ↔ 1
    GL343711.1(154096-160077)
    zebrafish
    (Danio rerio)
    Actinopterygii LOC7952651 novel protein similar to rodent fibronectin type III more 73.97(n)
    80.29(a)
      795265  XM_001335368.1  XP_001335404.1 


    ENSEMBL Gene Tree for FNDC5 (if available)
    TreeFam Gene Tree for FNDC5 (if available) 

    (Paralogs according to 1HomoloGene,
    2Ensembl, and 3SIMAP, Pseudogenes according to 4Pseudogene.org Build 68)
    About This Section
    Paralogs for FNDC5 gene
    FNDC42  
    1 SIMAP similar gene for FNDC5 using alignment to 1 protein entry:     FNDC5_HUMAN:
    FNDC4

    FNDC5 for paralogs           About GeneDecksing



    (SNPs/Variants according to the 1NCBI SNP Database, 2Ensembl, 3PupaSUITE, UniProtKB, 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

    10/173 NCBI SNPs in FNDC5 are shown (see all 173    About this table
    Genomic DataTranscription Related DataAllele Frequencies
    SNP IDValidClinical
    significance
    Chr 1 posSequence#AA
    Chg
    TypeMore#Allele
    freq
    PopTotal
    sample
    More
    ----------
    rs120860091,2
    C,--31452646(+) AGTCTG/ACAGCA 1 -- int12Minor allele frequency- A:0.15WA 120
    rs756682531,2
    F,--31453642(+) ACCTTG/AGCGCC 1 -- int11Minor allele frequency- A:0.02WA 118
    rs745978051,2
    F,--31453699(+) GGAGGG/TAGGAG 1 -- int11Minor allele frequency- T:0.08WA 118
    rs115882431,2
    C,H--31455114(+) TCTTAA/GGCTgg 1 -- int11Minor allele frequency- G:0.00NA 2
    rs572194181,2
    C,F,--31455178(+) GGGGAC/TTTGCC 1 -- int14Minor allele frequency- T:0.14WA NA 242
    rs1437936591,2
    --33327409(+) TTGGGA/CTCATA 3 -- int10--------
    rs1481527481,2
    --33327452(+) CTGTGA/GATACT 3 -- int10--------
    rs728823131,2
    C,--33327780(+) AGAGAA/CACTGA 3 -- int12Minor allele frequency- C:0.02WA 120
    rs1419408061,2
    --33328158(+) GGGGCA/GGTCAT 3 -- ut310--------
    rs34801,2
    C,F,A,H,--33328165(+) TCATTA/GGGTGA 3 -- ut31 ese326Minor allele frequency- G:0.44MN NS EA NA WA CSA 2720

    HapMap Linkage Disequilibrium report for FNDC5 (33327869 - 33338083 bp)
    Structural Variations (Copy Number Variations, Insertions/Deletions, Inversions)
    Database of Genomic Variants (DGV): 1 variation for FNDC5
         1 CNV: 48310

    SABiosciences Cancer Mutation PCR Assays
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    (in which this Gene is Involved, According to MalaCards, OMIM, UniProtKB, the University of Copenhagen DISEASES database, Genatlas, GeneTests, GAD, HuGE Navigator, and/or TGDB.)
    About This Section

    FNDC5 for disorders           About MalaCards

    FNDC5 for disorders           About GeneDecksing

    OMIM gene information: 611906    OMIM disorders: --


    Export disorders for FNDC5 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 FNDC5 gene integrated from 9 sources:
    (articles sorted by number of sources associating them with FNDC5)
        Utopia: connect your pdf to the dynamic
    world of online information

    1. A PGC1-alpha-dependent myokine that drives brown-fat-like development of white fat and thermogenesis. (PubMed id 22237023)1, 2, 3 Bostrom P....Spiegelman B.M. (2012)
    2. Complete sequencing and characterization of 21,243 full-length human cDNAs. (PubMed id 14702039)1, 2 Ota T.... Sugano S. (2004)
    3. Frcp1 and Frcp2, two novel fibronectin type III repeat containing genes. (PubMed id 12384288)1, 3 Teufel A....Westphal H. (2002)
    4. FNDC5 and irisin in humans: I. Predictors of circulati ng concentrations in serum and plasma and II. mRNA expression and circulating co ncentrations in response to weight loss and exercise. (PubMed id 23018146)1 Huh J.Y....Mantzoros C.S. (2012)
    5. The full-ORF clone resource of the German cDNA consortium. (PubMed id 17974005)2 Bechtel S.... Schupp I. (2007)
    6. Diversification of transcriptional modulation: large-scale identification and characterization of putative alternative promoters of human genes. (PubMed id 16344560)1 Kimura K.... Sugano S. (2006)
    7. The DNA sequence and biological annotation of human chromosome 1. (PubMed id 16710414)2 Gregory S.G.... Bentley D.R. (2006)
    8. The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). (PubMed id 15489334)2 Gerhard D.S....Malek J. (2004)
    9. 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)
    10. Protein-protein interaction panel using mouse full-length cDNAs. (PubMed id 11591653)1 Suzuki H....Hayashizaki Y. (2001)

    (in PubMed, OMIM, and NCBI Bookshelf)
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    (According to Entrez Gene, HGNC, AceView, euGenes, Ensembl, miRBase, ECgene, Kegg, and/or H-InvDB)
    About This Section
    Entrez Gene: 252995 HGNC: 20240 AceView: FNDC5 Ensembl:ENSG00000160097 euGenes: HUgn252995
    ECgene: FNDC5 H-InvDB: FNDC5

    (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 FNDC5 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 FNDC5 gene:
    Search GeneIP for patents involving FNDC5

    GeneCards and IP:
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