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

FRS3 Gene

protein-coding   GIFtS: 52
GCID: GC06M041737

fibroblast growth factor receptor substrate 3

 Explore 5 diseases affiliated with
FRS3 via our new
 Human Malady Compendium 
Biological research products
for FRS3
    

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

Aliases
Fibroblast Growth Factor Receptor Substrate 31 2     FGFR-Signaling Adaptor SNT22 3
SNT-21 2 3     FRS2-Beta1
FRS2B1 2     SNT22
FRS2beta1 2     Suc1-Associated Neurotrophic Factor Target 2 (FGFR Signalling Adaptor)2
FGFR Substrate 32 3     Suc1-Associated Neurotrophic Factor Target 23

External Ids:    HGNC: 169701   Entrez Gene: 108172   Ensembl: ENSG000001372187   OMIM: 6077445   UniProtKB: O435593   

Export aliases for FRS3 gene to outside databases

Previous GC identifers: GC06M041740 GC06M041784 GC06M041845 GC06M041456


(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 FRS3:
The protein encoded by this gene is a substrate for the fibroblast growth factor receptor. It is found in peripheral
plasma membrane and functions in linking FGF receptor stimulation to activators of Ras. (provided by RefSeq, Jul 2008)

UniProtKB/Swiss-Prot: FRS3_HUMAN, O43559
Function: Adapter protein that links FGF and NGF receptors to downstream signaling pathways. Involved in the activation
of MAP kinases. Down-regulates ERK2 signaling by interfering with the phosphorylation and nuclear translocation of
ERK2

Gene Wiki entry for FRS3


(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_000006.11  NC_018917.1  NT_007592.15  
Regulatory elements:
   SABiosciences Regulatory transcription factor binding sites in the FRS3 gene promoter:
         E2F-3a   E2F-4   E2F-5   C/EBPbeta   Lmo2   E2F-2   Evi-1   MZF-1   E2F   E2F-1   
         Other transcription factors

SwitchGear Promoter luciferase reporter plasmidFRS3 promoter sequence
   Search SABiosciences Chromatin IP Primers for FRS3

Epigenetics:
QIAGEN PyroMark CpG Assay predesigned Pyrosequencing DNA Methylation assays in human, mouse, rat FRS3


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

Entrez Gene cytogenetic band: 6p21.1   Ensembl cytogenetic band:  6p21.1   HGNC cytogenetic band: 6p21.1

FRS3 Gene in genomic location: bands according to Ensembl, locations according to (and/or Entrez Gene and/or Ensembl if different)
FRS3 gene location

GeneLoc information about chromosome 6         GeneLoc Exon Structure

GeneLoc location for GC06M041737:  view genomic region     (about GC identifiers)

Start:
41,737,914 bp from pter      End:
41,754,280 bp from pter
Size:
16,367 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: FRS3_HUMAN, O43559 (See protein sequence)
Recommended Name: Fibroblast growth factor receptor substrate 3  
Size: 492 amino acids; 54462 Da
Subunit: Binds NTRK1 (By similarity). Binds FGFR1, NGFR, GRB2, PTPN11 and ERK2
Subcellular location: Membrane; Lipid-anchor
Sequence caution: Sequence=CAI13184.2; Type=Erroneous gene model prediction;
4 PDB 3D structures from and Proteopedia for FRS3:
2KUP (3D)        2KUQ (3D)        2YS5 (3D)        2YT2 (3D)    
Secondary accessions: Q5T3D5

Explore the universe of human proteins at neXtProt for FRS3: NX_O43559

Post-translational modifications:

  • Phosphorylated by ULK2 in vitro (By similarity). Phosphorylated on tyrosine residues upon stimulation by BFGF or NGFB1
  • View modification sites using PhosphoSitePlus2
  • View neXtProt modification sites for NX_O43559

  • FRS3 Protein expression data from MOPED and PaxDb:    About this image 
    Estimated protein expression log10 (pmol).

    REFSEQ proteins: NP_006644.1  
    ENSEMBL proteins: 
     ENSP00000362109   ENSP00000396715   ENSP00000413214   ENSP00000259748  
    Reactome Protein details: O43559
    Human Recombinant Protein Products: 
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    Browse ProSpec Recombinant Proteins
    Uscn Proteins for FRS3

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

    GO IDQualified GO termEvidencePubMed IDs
    GO:0005886plasma membrane TAS--


    FRS3 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

    FRS3 for domains           About GeneDecksing

    2 InterPro domains/families:
     IPR002404 Insln_rcpt_S1
     IPR011993 PH_like_dom

    Graphical View of Domain Structure for InterPro Entry O43559

    ProtoNet protein and cluster: O43559

    UniProtKB/Swiss-Prot: FRS3_HUMAN, O43559
    Similarity: Contains 1 IRS-type PTB 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: FRS3_HUMAN, O43559
    Function: Adapter protein that links FGF and NGF receptors to downstream signaling pathways. Involved in the activation
    of MAP kinases. Down-regulates ERK2 signaling by interfering with the phosphorylation and nuclear translocation of
    ERK2

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    hsa-miR-3163 hsa-miR-513a-5p hsa-miR-27a hsa-miR-128 hsa-miR-3681* hsa-miR-944 hsa-miR-551b* hsa-miR-421
    SwitchGear 3'UTR luciferase reporter plasmidFRS3 3' UTR sequence
    Inhib. RNA
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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:0004872receptor activity ----
    GO:0005104fibroblast growth factor receptor binding IPI9660748
    GO:0005158insulin receptor binding IEA--


    FRS3 for ontologies           About GeneDecksing



    (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

    Unified GeneCards pathways  About this table 
    See pathways by source

    Super-pathwaycontained gene-specific pathways
    1Signaling by FGFR
    Signaling by FGFR1.00
    Signaling by FGFR in disease0.91
    Downstream signaling of activated FGFR0.92
    2Disease
    Disease1.00
    3Neurotrophic factor-mediated Trk receptor signaling
    Neurotrophic factor-mediated Trk receptor signaling1.00
    4Signaling by GPCR
    Signal Transduction0.56
    5FGFR2c binds to FGF
    FRS2-mediated cascade0.34

    Pathway sources
    See GeneCards unified pathways
    Show all pathways


    1 BioSystems Pathway for FRS3 
        Neurotrophic factor-mediated Trk receptor signaling

    5/6        Reactome Pathways for FRS3 (see all 6)
        Signaling by FGFR
    Downstream signaling of activated FGFR
    Signal Transduction
    FRS2-mediated cascade
    Signaling by FGFR in disease



    FRS3 for pathways           About GeneDecksing

    Interactions:

        SABiosciences Gene Network CentralTM Interacting Genes and Proteins Network for FRS3

    STRING Interaction Network Preview (showing 5 interactants - click image to see 23)

    5/25 Interacting proteins for FRS3 (O435592, 3 ENSP000002597484) via UniProtKB, MINT, STRING, and/or I2D (see all 25)
    InteractantInteraction Details
    GeneCardExternal ID(s)
    PTPN11Q061242, 3, ENSP000003409444MINT-8035512 MINT-8026161 I2D: score=2 STRING: ENSP00000340944
    KARSQ150462, 3, ENSP000003254484MINT-65540 I2D: score=4 STRING: ENSP00000325448
    MAPK1P284823, ENSP000002158324I2D: score=1 STRING: ENSP00000215832
    RND1Q927303, ENSP000003084614I2D: score=1 STRING: ENSP00000308461
    FGFR1P113623, ENSP000003802804I2D: score=3 STRING: ENSP00000380280
    About this table

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

    GO IDQualified GO termEvidencePubMed IDs
    GO:0007165signal transduction TAS8761293
    GO:0008543fibroblast growth factor receptor signaling pathway TAS--


    FRS3 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

    FRS3 for compounds           About GeneDecksing

    Browse Small Molecules at EMD Millipore
    Browse drugs & compounds from Enzo Life Sciences

    Browse Tocris compounds for FRS3
    1 Novoseek chemical compound relationship for FRS3 gene    About this table
    Compound   -log (P-Val)   Hits   PubMed IDs for Articles with Shared Sentences (# sentences)
    tyrosine 52.9 9 16697063 (2), 16702953 (2), 15738000 (1), 15485655 (1) (see all 6)

    Search CenterWatch for drugs/clinical trials and news about FRS3 

    (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,
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    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 FRS3 gene: 
    NM_006653.3  

    Unigene Cluster for FRS3:

    Fibroblast growth factor receptor substrate 3
    Hs.194208  [show with all ESTs]
    Unigene Representative Sequence: NM_006653
    5 Ensembl transcripts including schematic representations, and UCSC links where relevant:
    ENST00000373018(uc003orc.1) ENST00000426290 ENST00000422888 ENST00000466420
    ENST00000259748

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    hsa-miR-3163 hsa-miR-513a-5p hsa-miR-27a hsa-miR-128 hsa-miR-3681* hsa-miR-944 hsa-miR-551b* hsa-miR-421
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    Additional cDNA sequence: 

    AF036718.1 BC010611.1 CR457026.1 

    2 DOTS entries:

    DT.202700  DT.92388410 

    24/52 AceView cDNA sequences (see all 52):

    BM756817 BC010611 BM757060 NM_006653 BM766335 BM741226 BM771050 BX098956 
    BM764849 CR598942 CD557174 BM680142 CR457026 CD109594 AF036718 AI879970 
    CB960314 BF512369 AI216717 BM922247 BI757794 BF338354 BM741175 BQ774604 

    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

    FRS3 expression in normal human tissues (normalized intensities)
    See probesets specificity/sensitivity at GeneAnnot
    About this imageBioGPS
    CGAP TAG: GAGGTGGGAC

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

    About this image
    See FRS3 Protein Expression from SPIRE MOPED and PaxDB
    Genevestigator expression for FRS3

    SOURCE GeneReport for Unigene cluster: Hs.194208
        SABiosciences Expression via Pathway-Focused PCR Arrays including FRS3: 
              Insulin Signaling Pathway in human mouse rat
              Neurotrophins & Receptors in human mouse rat

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    In Situ
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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 FRS3 gene from 5/16 species (see all 16)    About this table
    Organism Taxonomic
    classification
    Gene Description Human
    Similarity
    Orthology
    Type
    Details
    chicken
    (Gallus gallus)
    Aves FRS31 fibroblast growth factor receptor substrate 3 69.32(n)
    65.06(a)
      419923  XM_418044.3  XP_418044.3 
    lizard
    (Anolis carolinensis)
    Reptilia FRS36
    --
    61(a)
    1 ↔ 1
    4(119494295-119504888)
    zebrafish
    (Danio rerio)
    Actinopterygii LOC1003301471 fibroblast growth factor receptor substrate 2-like 62.3(n)
    59.2(a)
      100330147  XM_002662499.2  XP_002662545.2 
    fruit fly
    (Drosophila melanogaster)
    Insecta CG133986
    --
    19(a)
    1 → many
    2L(8412144-8415256)
    worm
    (Caenorhabditis elegans)
    Secernentea rog-16
    --
    15(a)
    1 → many
    II(1369053-1374992)


    ENSEMBL Gene Tree for FRS3 (if available)
    TreeFam Gene Tree for FRS3 (if available) 

    (Paralogs according to 1HomoloGene,
    2Ensembl, and 3SIMAP, Pseudogenes according to 4Pseudogene.org Build 68)
    About This Section
    Paralogs for FRS3 gene
    FRS22  
    1 SIMAP similar gene for FRS3 using alignment to 2 protein entries:     FRS3_HUMAN (see all proteins):
    FRS2

    FRS3 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

    10/239 NCBI SNPs in FRS3 are shown (see all 239    About this table
    Genomic DataTranscription Related DataAllele Frequencies
    SNP IDValidClinical
    significance
    Chr 6 posSequence#AA
    Chg
    TypeMore#Allele
    freq
    PopTotal
    sample
    More
    ----------
    rs1452068161,2
    --41737447(+) GTTCAC/TGACCA 1 -- ds50010--------
    rs1835107131,2
    --41737470(+) GGAGAA/CAAATA 1 -- ds50010--------
    rs47145121,2
    C,A,--41737562(+) GAGTTC/TGAGAC 1 -- ds50018Minor allele frequency- T:0.00NA WA CSA 14
    rs1413799151,2
    --41737656(+) GCTACC/TTGGGA 1 -- ds50010--------
    rs557712161,2
    C--41737766(+) AAAAAA/-TCATG 1 -- ds50011Minor allele frequency- -:0.00NA 2
    rs1894157901,2
    --41737962(+) ACATTG/TAAAAC 1 -- ut310--------
    rs1433936871,2
    --41738123(+) TTGACA/GTCTCG 1 -- ut310--------
    rs10572271,2
    C,F,H,--41738158(-) CTGGGG/AAGAGA 1 -- ut31 trp318Minor allele frequency- A:0.13EA MN NS NA WA 4010
    rs1923184001,2
    --41738159(+) CTCTCC/TCCAGC 1 -- ut310--------
    rs759345251,2
    C--41738230(+) AAGCA-/TCTGGT 1 -- ut310--------

    HapMap Linkage Disequilibrium report for FRS3 (41737914 - 41754280 bp)
    Structural Variations (Copy Number Variations, Insertions/Deletions, Inversions)
          Database of Genomic Variants (DGV) variations for FRS3: --

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

    FRS3 for disorders           About GeneDecksing

    OMIM gene information: 607744    OMIM disorders: --

    5 diseases for FRS3:    About MalaCards
    hemorrhagic fever with renal syndrome    hemorrhagic fever    hermaphroditism    lung cancer
    thyroiditis

    1 disease from the University of Copenhagen DISEASES database for FRS3:
    Hemorrhagic fever with renal syndrome

    1 Novoseek disease relationship for FRS3 gene    About this table

    Disease   -log (P-Val)   Hits   PubMed IDs for Articles with Shared Sentences (# sentences)
    cancer 0 2 16702953 (1)

    Human Genome Epidemiology (HuGE) Navigator: FRS3 (2 documents)

    Export disorders for FRS3 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 FRS3 gene, integrated from 9 sources (see all 25):
    (articles sorted by number of sources associating them with FRS3)
        Utopia: connect your pdf to the dynamic
    world of online information

    1. Novel recognition motif on fibroblast growth factor receptor mediates direct association and activation of SNT adapter proteins. (PubMed id 9660748)1, 2, 3 Xu H.... Goldfarb M.P. (1998)
    2. SNT-2 interacts with ERK2 and negatively regulates ERK2 signaling in response to EGF stimulation. (PubMed id 15485655)1, 2, 9 Huang L.... Tsuchida N. (2004)
    3. The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). (PubMed id 15489334)1, 2 Gerhard D.S....Malek J. (2004)
    4. FRS2 family docking proteins with overlapping roles in activation of MAP kinase have distinct spatial-temporal patterns of expression of their transcripts. (PubMed id 15094036)1, 2 Gotoh N.... Schlessinger J. (2004)
    5. The DNA sequence and analysis of human chromosome 6. (PubMed id 14574404)1, 2 Mungall A.J.... Beck S. (2003)
    6. Broadly expressed SNT-like proteins link FGF receptor stimulation to activators of Ras. (PubMed id 8761293)1, 3 Wang J.K....Goldfarb M. (1996)
    7. Unique role of SNT-2/FRS2beta/FRS3 docking/adaptor protein for negative regulation in EGF receptor tyrosine kinase signaling pathways. (PubMed id 16702953)1, 9 Huang L....Tsuchida N. (2006)
    8. Direct interaction of Rnd1 with FRS2 beta regulates Rnd1-induced down-regulation of RhoA activity and is involved in fibroblast growth factor-induced neurite outgrowth in PC12 cells. (PubMed id 15738000)1, 9 Harada A....Negishi M. (2005)
    9. The signaling adapters fibroblast growth factor receptor substrate 2 and 3 are activated by the thyroid TRK oncoproteins. (PubMed id 12586769)1, 9 Ranzi V....Greco A. (2003)
    10. Analysis of tyrosine phosphorylation-dependent protein-protein interactions in TrkB-mediated intracellular signaling using modified yeast two-hybrid system. (PubMed id 11432792)1, 9 Yamada M....Hatanaka H. (2001)

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    (According to Entrez Gene, HGNC, AceView, euGenes, Ensembl, miRBase, ECgene, Kegg, and/or H-InvDB)
    About This Section
    Entrez Gene: 10817 HGNC: 16970 AceView: FRS3 Ensembl:ENSG00000137218 euGenes: HUgn10817
    ECgene: FRS3 H-InvDB: FRS3

    (According to HUGE)
    About This Section
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    (According to PharmGKB, ATLAS, HORDE, IMGT, LEIDEN, UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL,
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    About This Section
    NameDescription
    PharmGKB entry for FRS3 Pharmacogenomics, SNPs, Pathways

    (Patent information from GeneIP,
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    Patent Information for FRS3 gene:
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