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

FPGS Gene

protein-coding   GIFtS: 64
GCID: GC09P130556

Folylpolyglutamate Synthase

Microbiology & Infectious Diseases Congress
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(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
Folylpolyglutamate Synthase1 2
Folylpoly-Gamma-Glutamate Synthetase2 3
Tetrahydrofolate Synthase2 3
Tetrahydrofolylpolyglutamate Synthase2 3
EC 6.3.2.173 8
Folylpolyglutamate Synthase, Mitochondrial2

External Ids:    HGNC: 38241   Entrez Gene: 23562   Ensembl: ENSG000001368777   OMIM: 1365105   UniProtKB: Q059323   

Export aliases for FPGS gene to outside databases

Previous GC identifers: GC09P121679 GC09P122211 GC09P124018 GC09P125941 GC09P127644 GC09P129604 GC09P100181


(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 FPGS Gene:
This gene encodes the folylpolyglutamate synthetase enzyme. This enzyme has a central role in establishing and
maintaining both cytosolic and mitochondrial folylpolyglutamate concentrations and, therefore, is essential for
folate homeostasis and the survival of proliferating cells. This enzyme catalyzes the ATP-dependent addition of
glutamate moieties to folate and folate derivatives. While several transcript variants may exist for this gene,
the full-length natures of only two have been biologically validated to date. These two variants encode distinct
isoforms. (provided by RefSeq, Jul 2008)

GeneCards Summary for FPGS Gene: 
FPGS (folylpolyglutamate synthase) is a protein-coding gene. Diseases associated with FPGS include childhood leukemia, and malignant pleural mesothelioma, and among its related super-pathways are glycine biosynthesis I and Metabolic pathways. GO annotations related to this gene include tetrahydrofolylpolyglutamate synthase activity and ATP binding.

UniProtKB/Swiss-Prot: FOLC_HUMAN, Q05932
Function: Catalyzes conversion of folates to polyglutamate derivatives allowing concentration of folate compounds
in the cell and the intracellular retention of these cofactors, which are important substrates for most of the
folate-dependent enzymes that are involved in one-carbon transfer reactions involved in purine, pyrimidine and
amino acid synthesis. Unsubstitued reduced folates are the preferred substrates. Metabolizes methotrexate (MTX)
to polyglutamates

Gene Wiki entry for FPGS Gene


(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_000009.11  NT_008470.19  NC_018920.2  
Regulatory elements:
   SABiosciences Regulatory transcription factor binding sites in the FPGS gene promoter:
         p53   p300   ATF   
         Other transcription factors

SwitchGear Promoter luciferase reporter plasmidFPGS promoter sequence
   Search SABiosciences Chromatin IP Primers for FPGS

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


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

Entrez Gene cytogenetic band: 9q34.1   Ensembl cytogenetic band:  9q34.11   HGNC cytogenetic band: 9q34.11

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

GeneLoc information about chromosome 9         GeneLoc Exon Structure

GeneLoc location for GC09P130556:  view genomic region     (about GC identifiers)

Start:
130,556,876 bp from pter      End:
130,576,606 bp from pter
Size:
19,731 bases      Orientation:
plus 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: FOLC_HUMAN, Q05932 (See protein sequence)
Recommended Name: Folylpolyglutamate synthase, mitochondrial precursor  
Size: 587 amino acids; 64609 Da
Cofactor: A monovalent cation. K(+) is most effective, followed by NH4(+) and Rb(+). Na(+), Li(+) and Cs(+) are
ineffective
Subunit: Monomer
Subcellular location: Isoform 1: Mitochondrion inner membrane. Mitochondrion matrix
Subcellular location: Isoform 2: Cytoplasm
Sequence caution: Sequence=AAA35852.1; Type=Erroneous initiation; Note=Translation N-terminally extended;
Secondary accessions: B3KPW4 B7Z2Z3 F5H0K6 Q5JU19 Q5JU22 Q6P2P6
Alternative splicing, Alternative initiation: 4 isoforms:  Q05932-1   Q05932-2   Q05932-3   Q05932-4   (Produced by alternative splicing of isoform 1)

Explore the universe of human proteins at neXtProt for FPGS: NX_Q05932

Explore proteomics data for FPGS at MOPED 

Post-translational modifications:

  • View modification sites using PhosphoSitePlus
  • View neXtProt modification sites for NX_Q05932

  • 4/5 DME Specific Peptides for FPGS (Q05932) (see all 5)
     DHTSLLG  YFRFLTLMA  EKIAWQKGGIFK  VLVTGSLHLVGGVL 

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

    FPGS Protein Expression
    REFSEQ proteins (2 alternative transcripts): 
    NP_001018088.1  NP_004948.4  

    ENSEMBL proteins: 
     ENSP00000362344   ENSP00000362325   ENSP00000362322   ENSP00000400007   ENSP00000406328  
     ENSP00000377309   ENSP00000362342  
    Reactome Protein details: Q05932
    Human Recombinant Protein Products for FPGS: 
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    GenScript Custom Purified and Recombinant Proteins Services for FPGS
    Novus Biologicals FPGS Protein
    Browse Sino Biological Recombinant Proteins
    Browse Sino Biological Cell Lysates 
    Browse ProSpec Recombinant Proteins
    Cloud-Clone Corp. Proteins for FPGS 

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

    GO IDQualified GO termEvidencePubMed IDs
    GO:0005737cytoplasm TAS1409616
    GO:0005739mitochondrion TAS7721888
    GO:0005743mitochondrial inner membrane IEA--
    GO:0005759mitochondrial matrix TAS--
    GO:0005829cytosol TAS--

    FPGS for ontologies           About GeneDecksing



    FPGS Antibody Products: 
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    LSBio Antibodies in human, mouse, rat for FPGS 

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    (According to HGNC, IUPHAR, InterPro, ProtoNet, UniProtKB, and/or BLOCKS, Sets of similar genes according to GeneDecks)
    About This Section
    5 InterPro protein domains:
     IPR004101 Mur_ligase_C
     IPR023600 Folylpolyglutamate_synth_euk
     IPR013221 Mur_ligase_cen
     IPR001645 Folylpolyglutamate_synth
     IPR018109 Folylpolyglutamate_synth_CS

    Graphical View of Domain Structure for InterPro Entry Q05932

    ProtoNet protein and cluster: Q05932

    1 Blocks protein domain: IPB001645 Folylpolyglutamate synthetase

    UniProtKB/Swiss-Prot: FOLC_HUMAN, Q05932
    Similarity: Belongs to the folylpolyglutamate synthase family


    FPGS 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: FOLC_HUMAN, Q05932
    Function: Catalyzes conversion of folates to polyglutamate derivatives allowing concentration of folate compounds
    in the cell and the intracellular retention of these cofactors, which are important substrates for most of the
    folate-dependent enzymes that are involved in one-carbon transfer reactions involved in purine, pyrimidine and
    amino acid synthesis. Unsubstitued reduced folates are the preferred substrates. Metabolizes methotrexate (MTX)
    to polyglutamates
    Catalytic activity: ATP + tetrahydropteroyl-(gamma-Glu)(n) + L-glutamate = ADP + phosphate +
    tetrahydropteroyl-(gamma-Glu)(n+1)
    Enzyme regulation: Activated by 10 mM sodium bicarbonate
    Biophysicochemical properties: Kinetic parameters: KM=201 uM for L-glutamate (isoform 2 at 37 degrees Celsius in
    the presence of 1 mM ATP and 2 mM L-glutamate); KM=200 uM for MgATP (isoform 2 at 37 degrees Celsius in the
    presence of 1 mM ATP and 2 mM L-glutamate); KM=59 uM for pteroylglutamic acid (PteGlu) (isoform 2 at 37 degrees
    Celsius in the presence of 1 mM ATP and 2 mM L- glutamate); KM=16 uM for PteGlu(2) (isoform 2 at 37 degrees
    Celsius in the presence of 1 mM ATP and 2 mM L-glutamate); KM=20 uM for PteGlu(3) (isoform 2 at 37 degrees
    Celsius in the presence of 1 mM ATP and 2 mM L-glutamate); KM=12 uM for PteGlu(4) (isoform 2 at 37 degrees
    Celsius in the presence of 1 mM ATP and 2 mM L-glutamate); KM=64 uM for PteGlu(5) (isoform 2 at 37 degrees
    Celsius in the presence of 1 mM ATP and 2 mM L-glutamate); KM=0.81 uM for H(2)PteGlu (isoform 2 at 37 degrees
    Celsius in the presence of 1 mM ATP and 2 mM L-glutamate); KM=47 uM for H(2)PteGlu(2) (isoform 2 at 37 degrees
    Celsius in the presence of 1 mM ATP and 2 mM L-glutamate); KM=1.6 uM for
    (6ambo)-tetrahydropteroylpoly-gamma-glutamate (H(4)PteGlu) (isoform 2 at 37 degrees Celsius in the presence of 1
    mM ATP and 2 mM L-glutamate); KM=4.4 uM for (6S)-H(4)PteGlu (isoform 2 at 37 degrees Celsius in the presence of 1
    mM ATP and 2 mM L-glutamate); KM=3.3 uM for (6S)-H(4)PteGlu(2) (isoform 2 at 37 degrees Celsius in the presence
    of 1 mM ATP and 2 mM L-glutamate); KM=1.4 uM for (6S)-H(4)PteGlu(3) (isoform 2 at 37 degrees Celsius in the
    presence of 1 mM ATP and 2 mM L-glutamate); KM=1.6 uM for (6S)-H(4)PteGlu(4) (isoform 2 at 37 degrees Celsius in
    the presence of 1 mM ATP and 2 mM L-glutamate); KM=1.4 uM for (6S)-H(4)PteGlu(5) (isoform 2 at 37 degrees Celsius
    in the presence of 1 mM ATP and 2 mM L-glutamate); KM=3.7 uM for (6R)-10-formyl-H(4)PteGlu (isoform 2 at 37
    degrees Celsius in the presence of 1 mM ATP and 2 mM L-glutamate); KM=2.7 uM for (6R)-10-formyl-H(4)PteGlu(2)
    (isoform 2 at 37 degrees Celsius in the presence of 1 mM ATP and 2 mM L- glutamate); KM=105 uM for
    (6S)-5-formyl-H(4)PteGlu (isoform 2 at 37 degrees Celsius in the presence of 1 mM ATP and 2 mM L-glutamate);
    KM=13 uM for (6S)-5-formyl-H(4)PteGlu(2) (isoform 2 at 37 degrees Celsius in the presence of 1 mM ATP and 2 mM L-
    glutamate); KM=48 uM for (6S)-5-methyl-H(4)PteGlu (isoform 2 at 37 degrees Celsius in the presence of 1 mM ATP
    and 2 mM L-glutamate); KM=4.4 uM for aminopterin (isoform 2 at 37 degrees Celsius in the presence of 1 mM ATP and
    2 mM L-glutamate); KM=55.5 uM for methotrexate (isoform 2, PubMed:17875718, at 37 degrees Celsius in the presence
    of 10 mM ATP and pH 8.5); KM=52.6 uM for methotrexate (isoform 1, PubMed:17875718, at 37 degrees Celsius in the
    presence of 10 mM ATP and pH 8.5); KM=71 uM for methotrexate (Glu-1) (isoform 2, PubMed:8662720, at 37 degrees
    Celsius in the presence of 1 mM ATP and 2 mM L- glutamate); KM=50 uM for methotrexate (Glu-2) (isoform 2,
    PubMed:8662720, at 37 degrees Celsius in the presence of 1 mM ATP and 2 mM L- glutamate); KM=148 uM for
    methotrexate (Glu-3) (isoform 2, PubMed:8662720, at 37 degrees Celsius in the presence of 1 mM ATP and 2 mM L-
    glutamate); KM=5.3 uM for 5-deazaacyclotetrahydrofolate (isoform 2, at 37 degrees Celsius in the presence of 1 mM
    ATP and 2 mM L- glutamate); KM=2.8 uM for 2-methyl-5,8-dideazaisofolate (isoform 2, at 37 degrees Celsius in the
    presence of 1 mM ATP and 2 mM L- glutamate); KM=1702 uM for glutamic acid (isoform 2, PubMed:17875718, at 37
    degrees Celsius in the presence of 10 mM ATP and pH 8.5); KM=2068 uM for glutamic acid (isoform 1,
    PubMed:17875718, at 37 degrees Celsius in the presence of 10 mM ATP and pH 8.5); Vmax=0.34 umol/h/mg enzyme with
    methotrexate as substrate (isoform 2, PubMed:17875718, at 37 degrees Celsius in the presence of 10 mM ATP and pH
    8.5); Vmax=0.05 umol/h/mg enzyme with methotrexate as substrate (isoform 1, PubMed:17875718, at 37 degrees
    Celsius in the presence of 10 mM ATP and pH 8.5); Vmax=1.26 umol/h/mg enzyme with glutamic acid as substrate
    (isoform 2, PubMed:17875718, at 37 degrees Celsius in the presence of 10 mM ATP and pH 8.5); Vmax=0.25 umol/h/mg
    enzyme with glutamic acid as substrate (isoform 1, PubMed:17875718, at 37 degrees Celsius in the presence of 10
    mM ATP and pH 8.5); pH dependence: Optimum pH is 9.6 (isoform 2);

         Genatlas biochemistry entry for FPGS:
    folylpoly-gamma-glutamate synthase

         Enzyme Number (IUBMB): EC 6.3.2.171 2

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

    GO IDQualified GO termEvidencePubMed IDs
    GO:0004326tetrahydrofolylpolyglutamate synthase activity IEA--
    GO:0005524ATP binding IEA--
    GO:0016874ligase activity ----
         
    FPGS for ontologies           About GeneDecksing


    Phenotypes:
         1 GenomeRNAi human phenotype for FPGS:
     Increased viability after born 

         1 MGI mutant phenotype (inferred from 1 allele(MGI details for Fpgs):
     homeostasis/metabolism 

    FPGS for phenotypes           About GeneDecksing

    Animal Models:
       inGenious Targeting Laboratory - Custom generated mouse model solutions for FPGS 
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       genOway customized KO model: permanent, tissue-specific or time-controlled inactivation for FPGS 
       genOway customized Knockin model: humanization, point mutation, expression monitoring, etc. for FPGS 

    miRNA
    Products:
        
    QIAGEN Custom miScript Target Protector blocks miRNA-binding site of human, mouse, rat FPGS
    5 QIAGEN miScript miRNA Assays for microRNAs that regulate FPGS:
    hsa-miR-124 hsa-miR-320e hsa-miR-765 hsa-miR-506 hsa-miR-30b*
    SwitchGear 3'UTR luciferase reporter plasmidFPGS 3' UTR sequence
    Inhib. RNA
    Products:
        
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    Gene Editing
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    Clone
    Products:
         
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    GenScript: all cDNA clones in your preferred vector (see all 2): FPGS (NM_004957)
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    Advanced Cell Diagnostics RNAscope RNA in situ hybridization assays for FPGS


    (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

    SuperPaths for FPGS About   (see all 7)                                                                                              See pathways by source

    SuperPathContained pathways About
    1glycine biosynthesis I
    folate polyglutamylation0.50
    Metabolism of folate and pterines0.30
    2Metabolism
    Metabolism0.40
    Metabolic pathways0.40
    3Metabolism of vitamins and cofactors
    Metabolism of water-soluble vitamins and cofactors1.00
    Metabolism of vitamins and cofactors1.00
    4Antimetabolite Pathway - Folate Cycle, Pharmacodynamics
    Methotrexate Pathway (Cancer Cell), Pharmacodynamics0.87
    5Fluoropyrimidine Activity
    Fluoropyrimidine Activity0.69

    Pathways by source                                                                                                                                                                 See SuperPaths
    Show all pathways


    2 BioSystems Pathways for FPGS
        Fluoropyrimidine Activity
    folate polyglutamylation

    4        Reactome Pathways for FPGS
        Metabolism of folate and pterines
    Metabolism
    Metabolism of vitamins and cofactors
    Metabolism of water-soluble vitamins and cofactors

    2 PharmGKB Pathways for FPGS
        Fluoropyrimidine Pathway, Pharmacodynamics
    Methotrexate Pathway (Cancer Cell), Pharmacodynamics

    2         Kegg Pathways  (Kegg details for FPGS):
        Folate biosynthesis
    Metabolic pathways

    UniProtKB/Swiss-Prot: FOLC_HUMAN, Q05932
    Pathway: Cofactor biosynthesis; tetrahydrofolylpolyglutamate biosynthesis


    FPGS for pathways           About GeneDecksing

    Interactions:

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

    STRING Interaction Network Preview (showing 5 interactants - click image to see 13)

    5/57 Interacting proteins for FPGS (Q059323 ENSP000003623444) via UniProtKB, MINT, STRING, and/or I2D (see all 57)

    InteractantInteraction Details
    GeneCardExternal ID(s)
    ENSG00000096171P266403I2D: score=1 
    ENSG00000226589P266403I2D: score=1 
    VARSP266403I2D: score=1 
    ENSG00000258947Q135093I2D: score=1 
    FEN1P397483, ENSP000003054804I2D: score=1 STRING: ENSP00000305480
    About this table

    Gene Ontology (GO): 5/13 biological process terms (GO ID links to tree view) (see all 13):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0001889liver development IEA--
    GO:0006139nucleobase-containing compound metabolic process TAS7721888
    GO:0006730one-carbon metabolic process IEA--
    GO:0006766vitamin metabolic process TAS--
    GO:0006767water-soluble vitamin metabolic process TAS--

    FPGS 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

    FPGS for compounds           About GeneDecksing

    Browse Small Molecules at EMD Millipore
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    Browse Tocris compounds for FPGS (FOLC)

    10 HMDB Compounds for FPGS    About this table
    CompoundSynonyms CAS #PubMed Ids
    7,8-Dihydropteroic acid4-[[(2-amino-1,4,7,8-tetrahydro-4-oxo-6-pteridinyl)methyl]amino]-Benzoic acid (see all 12)2134-76-1--
    ADPadenosindiphosphorsaeure (see all 8)58-64-0--
    Adenosine triphosphate5'-(tetrahydrogen triphosphate) Adenosine (see all 24)56-65-5--
    Dihydrofolic acid7,8-Dihydro-L-folic acid (see all 13)4033-27-6--
    FamotidineAmfamox (see all 83)76824-35-6--
    L-Glutamic acid(2S)-2-Aminopentanedioate (see all 49)56-86-0--
    PhosphateNFB Orthophosphate (see all 13)14265-44-2--
    Tetrahydrofolic acid(6S)-Tetrahydrofolate (see all 10)135-16-0--
    Tetrahydrofolyl-[Glu](2)THF-L-glutamate (see all 7)----
    Tetrahydrofolyl-[Glu](n)Tetrahydrofolyl-[Glu](n+1) (see all 5)----

    4 DrugBank Compounds for FPGS    About this table
    CompoundSynonyms CAS #TypeActionsPubMed Ids
    L-Glutamic Acid(2S)-2-Aminopentanedioic acid (see all 15)56-86-0target--16686541 16990006
    MethotrexateAmethopterin (see all 12)59-05-2enzymesubstrate17586865
    Pralatrexate-- 146464-95-1enzymesubstrate23409799
    RaltitrexedZD-1694 (see all 2)112887-68-0targetantagonist11916544

    10/47 Novoseek inferred chemical compound relationships for FPGS gene (see all 47)    About this table
    Compound   -log (P-Val)   Hits   PubMed IDs for Articles with Shared Sentences (# sentences)
    lometrexol 93.5 12 8869756 (2), 8937460 (1), 7565626 (1), 10598554 (1) (see all 8)
    glycinamide ribonucleotide 93.2 8 7565626 (1), 8027993 (1), 10598551 (1), 11469716 (1) (see all 7)
    tomudex 93.2 30 10477170 (5), 7646540 (3), 7513935 (2), 8255099 (1) (see all 14)
    1843u89 93.1 6 8764125 (4), 9816025 (1), 9242558 (1)
    thymidylate 92.2 52 10598551 (2), 9825730 (1), 10699949 (1), 16078850 (1) (see all 32)
    zd9331 91.7 5 9654109 (1), 8624289 (1), 12721264 (1), 9815766 (1)
    5-deazafolate 90.2 9 1578484 (2), 7565626 (1), 12408727 (1), 10479284 (1)
    dihydrofolate 89 32 1835598 (1), 8568827 (1), 9778690 (1), 10699949 (1) (see all 22)
    folate 89 283 8937460 (6), 8408018 (6), 8408019 (6), 18025275 (4) (see all 95)
    aminopterin 86.4 10 2007575 (1), 7506026 (1), 7565626 (1), 9744777 (1) (see all 6)

    1 PharmGKB related drug/compound annotation for FPGS gene    About this table
    Drug/compound PharmGKB Annotation
    methotrexateCA  

    Search CenterWatch for drugs/clinical trials and news about FPGS / FOLC

    (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 FPGS gene (2 alternative transcripts): 
    NM_001018078.1  NM_004957.4  

    Unigene Cluster for FPGS:

    Folylpolyglutamate synthase
    Hs.335084  [show with all ESTs]
    Unigene Representative Sequence: NM_004957
    18/21 Ensembl transcripts including schematic representations, and UCSC links where relevant (see all 21):
    ENST00000479147(uc004bsf.1) ENST00000479375 ENST00000373247 ENST00000488307
    ENST00000373228 ENST00000481552 ENST00000460181 ENST00000475765 ENST00000496586
    ENST00000373225(uc004bsi.1) ENST00000431857 ENST00000423577 ENST00000469310
    ENST00000497386 ENST00000488506 ENST00000489522 ENST00000467826 ENST00000473536

    Congresses - knowledge worth sharing:  
    European Congress of Clinical Microbiology and Infectious Diseases (ECCMID) 10 - 13 May 2014

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    Additional mRNA sequence: 

    AK056920.1 AK295309.1 AK315523.1 AY007210.1 AY007211.1 AY007212.1 BC007121.1 BC009901.2 
    BC064393.1 BT006639.1 M98045.1 

    18 DOTS entries:

    DT.100852186  DT.100030070  DT.92449883  DT.100640867  DT.100871571  DT.121190252  DT.95361622  DT.95361621 
    DT.40105946  DT.95361628  DT.95361629  DT.100659299  DT.121617824  DT.92449874  DT.92449886  DT.97764328 
    DT.97796004  DT.97854091 

    24/407 AceView cDNA sequences (see all 407):

    BF589704 BQ232229 BM818657 BM984246 BC007121 T25116 AY007210 BQ955185 
    BI836452 AI351075 BE378662 BG257628 AW301211 BX436442 AI687246 BM796579 
    BG014232 BM468258 BG014233 BI837967 AI082295 BF514175 BF916661 M98045 

    GeneLoc Exon Structure

    5/15 Alternative Splicing Database (ASD) splice patterns (SP) for FPGS (see all 15)    About this scheme

    ExUns: 1a · 1b · 1c ^ 2 ^ 3a · 3b ^ 4 ^ 5a · 5b ^ 6a · 6b · 6c · 6d ^ 7 ^ 8 ^ 9a · 9b ^ 10a · 10b ^ 11a · 11b ^ 12a · 12b · 12c ^ 13 ^ 14 ^
    SP1:                    -     -                       -     -                                         -     -                       -                           
    SP2:                    -     -                       -     -     -                                   -     -                       -                           
    SP3:                          -                       -     -                                         -     -                       -                           
    SP4:                                                  -     -     -                                   -     -           -     -     -                           
    SP5:                                                  -     -                                         -     -           -     -     -                           

    ExUns: 15 ^ 16a · 16b ^ 17
    SP1:                        
    SP2:                        
    SP3:                        
    SP4:                        
    SP5:                        


    ECgene alternative splicing isoforms for FPGS

    (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

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


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

    SOURCE GeneReport for Unigene cluster: Hs.335084
        SABiosciences Custom PCR Arrays for FPGS
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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 eukaryotes.

    Orthologs for FPGS gene from 9/20 species (see all 20)    About this table
    Organism Taxonomic
    classification
    Gene Description Human
    Similarity
    Orthology
    Type
    Details
    mouse
    (Mus musculus)
    Mammalia Fpgs1 , 5 folylpolyglutamyl synthetase1, 5 82.51(n)1
    82.11(a)1
      2 (22.09 cM)5
    142871  NM_010236.21  NP_034366.21 
     326826095 
    chicken
    (Gallus gallus)
    Aves FPGS1 folylpolyglutamate synthase 72.25(n)
    70.31(a)
      417227  XM_003642277.1  XP_003642325.1 
    lizard
    (Anolis carolinensis)
    Reptilia FPGS6
    Folylpolyglutamate synthase
    63(a)
    1 ↔ 1
    GL345096.1(3019-11417)
    zebrafish
    (Danio rerio)
    Actinopterygii wufk51d092 Danio rerio cDNA clone MGC63807 IMAGE3815522, complete more 74.99(n)    BC058343.1 
    fruit fly
    (Drosophila melanogaster)
    Insecta CG25431 , 3 folylpolyglutamate synthase3
    CG25431
    40(a)3
    53.8(n)1
    45.85(a)1
      322121  NM_132586.11  NP_572814.11 
    worm
    (Caenorhabditis elegans)
    Secernentea F25B5.6a3
    F25B5.61
    tetrahydrofolylpolyglutamate synthase3
    Protein F25B5.61
    36(a)
    (best of 2)3
    47.35(n)1
    43.57(a)1
      III(6018152-6019942)3
    1758421  NM_065891.31  NP_498292.11 
    baker's yeast
    (Saccharomyces cerevisiae)
    Saccharomycetes MET7(YOR241W)4
    MET71
    Folylpolyglutamate synthetase, catalyzes extension more4
    Met7p1
    47.02(n)1
    45.17(a)1
      15(786995-788641)4
    8544151, 4  NP_014884.11, 4 
    thale cress
    (Arabidopsis thaliana)
    eudicotyledons DFB1 DHFS-FPGS homolog B 48.89(n)
    44.97(a)
      830484  NM_120680.3  NP_196217.2 
    rice
    (Oryza sativa)
    Liliopsida Os03g01111001 hypothetical protein 49.78(n)
    44.54(a)
      4331360  NM_001055256.1  NP_001048721.1 


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

    (Paralogs according to 1HomoloGene,
    2Ensembl, and 3SIMAP, Pseudogenes according to 4Pseudogene.org Build 68)
    About This Section
      --

    (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

    10/390 SNPs in FPGS are shown (see all 390)    About this table     
    Genomic DataTranscription Related DataAllele Frequencies
    SNP IDValidClinical
    significance
    Chr 9 posSequence#AA
    Chg
    TypeMore#Allele
    freq
    PopTotal
    sample
    More
    ----------
    rs109877411,2
    C--100179697(+) AACCCC/TGTCTC 1 -- us2k12Minor allele frequency- T:0.25NA 4
    rs1466727351,2
    --100179728(+) GCCGGC/GTGTGA 1 -- us2k10--------
    rs117900751,2
    C,F,A,H--100179833(+) CACTGT/CACTCC 1 -- us2k14Minor allele frequency- C:0.42NA 12
    rs285702991,2
    C,F--100180127(+) CTAAGA/TTGCAA 2 -- us2k15Minor allele frequency- T:0.21NA WA 126
    rs362047091,2
    C,F--100180208(+) CTATGG/TGACAC 2 -- us2k11Minor allele frequency- T:0.07EA 120
    rs1457697811,2
    C--100180317(+) TCATG-/ATTATTAT 2 -- us2k10--------
    rs1881751451,2
    --100180366(+) TGTCAA/CCCAGG 2 -- us2k10--------
    rs589962981,2
    C--100180472(+) AGGCGC/TCTGCT 2 -- us2k10--------
    rs597494071,2
    C--100180618(+) CACACC/TGGCTA 2 -- us2k10--------
    rs1144136261,2
    F--100180749(+) ACTGCG/ATCCAG 2 -- us2k11Minor allele frequency- A:0.09WA 118

    HapMap Linkage Disequilibrium report for FPGS (130556876 - 130576606 bp)

    Structural Variations
         Database of Genomic Variants (DGV) 10 variations for FPGS:    About this table     
    Variant IDTypeSubtypePubMed ID
    nsv466576CNV Loss19166990
    dgv8288n71CNV Loss21882294
    nsv893868CNV Loss21882294
    nsv893865CNV Loss21882294
    nsv471323CNV Loss18288195
    dgv8287n71CNV Loss21882294
    nsv466575CNV Loss19166990
    nsv893874CNV Loss21882294
    nsv893859CNV Loss21882294
    nsv893860CNV Gain21882294


    Human Gene Mutation Database (HGMD): FPGS
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    (in which this Gene is Involved, According to MalaCards, OMIM, UniProtKB, the University of Copenhagen DISEASES database, Conferences by KenesGroup, Novoseek, Genatlas, GeneTests, GAD, HuGE Navigator, and/or TGDB.)
    About This Section
    OMIM gene information: 136510    OMIM disorders: --

    20/32 diseases for FPGS (see all 32):    About MalaCards
    childhood leukemia    malignant pleural mesothelioma    soft tissue sarcoma    acute leukemia
    lymphoblastic leukemia    follicular lymphoma    spina bifida    diffuse large b-cell lymphoma
    colorectal cancer    acute lymphoblastic leukemia    b-cell lymphomas    esophageal adenocarcinoma
    colon cancer    non-hodgkin lymphoma    cleft lip    rheumatoid arthritis
    hodgkin's lymphoma    sarcoma    blindness    psoriasis


    FPGS for disorders           About GeneDecksing

    10/26 Novoseek inferred disease relationships for FPGS gene (see all 26)    About this table

    Disease   -log (P-Val)   Hits   PubMed IDs for Articles with Shared Sentences (# sentences)
    leukemia 58.3 32 19131550 (3), 8255099 (2), 11309345 (2), 2007575 (1) (see all 21)
    folate deficiency 50.9 4 15047700 (1), 18499665 (1), 8869756 (1), 18804693 (1)
    lymphoblastic leukemia acute 48.4 8 1435744 (2), 9654109 (1), 19131550 (1), 9242558 (1) (see all 6)
    t-all 47.6 9 16707018 (4), 10029597 (3), 11187907 (1)
    colorectal cancer 46.9 7 20037791 (2), 18418463 (1), 14676127 (1)
    tumors 43.1 78 8937460 (4), 14676127 (4), 1450491 (3), 18039426 (3) (see all 39)
    leukemia l1210 42.7 1 8605241 (1)
    leukemia nonlymphocytic acute 36.8 1 10777604 (1)
    colon cancer 34.4 10 15542523 (4), 20037791 (1), 12907242 (1), 14676127 (1)
    lymphoblastic leukemia acute childhood 31 1 20072153 (1)

    Genetic Association Database (GAD): FPGS
    Human Genome Epidemiology (HuGE) Navigator: FPGS (17 documents)

    Export disorders for FPGS 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 FPGS gene, integrated from 9 sources (see all 237):
    (articles sorted by number of sources associating them with FPGS)
        Utopia: connect your pdf to the dynamic
    world of online information

    1. Identification and characterization of genetic variation in the folylpolyglutamate synthase gene. (PubMed id 17875718)1, 2, 9 Leil T.A....Adjei A.A. (2007)
    2. Purification and properties of human cytosolic folylpoly-gamma-glutamate synthetase and organization, localization, and differential splicing of its gene. (PubMed id 8662720)1, 2, 9 Chen L....Shane B. (1996)
    3. Upstream organization of and multiple transcripts from the human folylpoly-gamma-glutamate synthetase gene. (PubMed id 7721888)1, 2, 9 Freemantle S.J.... Moran R.G. (1995)
    4. Concentration-dependent processivity of multiple glutamate ligations catalyzed by folylpoly-gamma-glutamate synthetase. (PubMed id 18672898)1, 2, 9 Tomsho J.W....Coward J.K. (2008)
    5. Exploratory analysis of four polymorphisms in human GGH and FPGS genes and their effect in methotrexate-treated rheumatoid arthritis patients. (PubMed id 17286537)1, 4, 9 van der Straaten R.J....Guchelaar H.J. (2007)
    6. Submitochondrial localization of the mitochondrial isoform of folylpolyglutamate synthetase in CCRF-CEM human T-lymphoblastic leukemia cells. (PubMed id 16169100)1, 2, 9 Nair J.R. and McGuire J.J. (2005)
    7. Expression cloning of a human cDNA encoding folylpoly(gamma- glutamate) synthetase and determination of its primary structure. (PubMed id 1409616)1, 2, 9 Garrow T.A.... Shane B. (1992)
    8. Phase II trial of pemetrexed plus bevacizumab for sec ond-line therapy of patients with advanced non-small-cell lung cancer: NCCTG an d SWOG study N0426. (PubMed id 19841321)1, 4, 9 Adjei A.A....Zinner R.G. (2010)
    9. Genes involved with folate uptake and distribution an d their association with colorectal cancer risk. (PubMed id 20037791)1, 4, 9 Figueiredo J.C....Haile R.W. (2010)
    10. Outcomes of methotrexate therapy for psoriasis and relationship to genetic polymorphisms. (PubMed id 19016697)1, 4, 9 Warren R.B....Griffiths C.E. (2008)

    (in PubMed, OMIM, and NCBI Bookshelf)
    About This Section
     ANDOR
    Aliases
    Disorders
    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: 2356 HGNC: 3824 AceView: CDK9andFPGS Ensembl:ENSG00000136877 euGenes: HUgn2356
    ECgene: FPGS Kegg: 2356 H-InvDB: FPGS

    (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 FPGS 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 FPGS gene:
    Search GeneIP for patents involving FPGS

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



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    About This Section

     
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