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APC Gene

protein-coding   GIFtS: 71
GCID: GC05P112101

Adenomatous Polyposis Coli

(Previous name: adenomatosis polyposis coli)
  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)
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Aliases
Adenomatous Polyposis Coli1 2     DP22
Deleted In Polyposis 2.52 3     DP32
DP2.52 3     PPP1R462
BTPS22 5     Adenomatosis Polyposis Coli Tumor Suppressor2
GS2 5     Adenomatous Polyposis Coli Protein2
Adenomatosis Polyposis Coli1     Protein Phosphatase 1, Regulatory Subunit 462
Protein Phosphatase 11     Protein APC3
Regulatory Subunit 461     FPC5

External Ids:    HGNC: 5831   Entrez Gene: 3242   Ensembl: ENSG000001349827   OMIM: 6117315   UniProtKB: P250543   

Export aliases for APC gene to outside databases

Previous GC identifers: GC05P111687 GC05P112537 GC05P112074 GC05P112149 GC05P107222


(According to Entrez Gene, GeneCards, Tocris Bioscience, Wikipedia's Gene Wiki, PharmGKB,
UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL)
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Entrez Gene summary for APC Gene:
This gene encodes a tumor suppressor protein that acts as an antagonist of the Wnt signaling pathway. It is also
involved in other processes including cell migration and adhesion, transcriptional activation, and apoptosis.
Defects in this gene cause familial adenomatous polyposis (FAP), an autosomal dominant pre-malignant disease that
usually progresses to malignancy. Disease-associated mutations tend to be clustered in a small region designated
the mutation cluster region (MCR) and result in a truncated protein product. (provided by RefSeq, Jul 2008)

GeneCards Summary for APC Gene:
APC (adenomatous polyposis coli) is a protein-coding gene. Diseases associated with APC include fourth cranial nerve palsy, and gardner syndrome. GO annotations related to this gene include beta-catenin binding and protein kinase binding. An important paralog of this gene is APC2.

UniProtKB/Swiss-Prot: APC_HUMAN, P25054
Function: Tumor suppressor. Promotes rapid degradation of CTNNB1 and participates in Wnt signaling as a negative
regulator. APC activity is correlated with its phosphorylation state. Activates the GEF activity of SPATA13 and
ARHGEF4. Plays a role in hepatocyte growth factor (HGF)-induced cell migration. Required for MMP9 up-regulation
via the JNK signaling pathway in colorectal tumor cells. Acts as a mediator of ERBB2-dependent stabilization of
microtubules at the cell cortex. It is required for the localization of MACF1 to the cell membrane and this
localization of MACF1 is critical for its function in microtubule stabilization

Gene Wiki entry for APC (Adenomatous polyposis coli) 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 75), Regulatory elements and Epigenetics data according to QIAGEN, and/or SwitchGear Genomics)
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RefSeq DNA sequence:
NC_000005.10  NC_018916.2  NT_034772.7  
Regulatory elements:
   Regulatory transcription factor binding sites in the APC gene promoter:
         TBP   STAT5B   Spz1   NF-1   NF-1/L   C/EBPbeta   MyoD   TFIID   
         Other transcription factors

SwitchGear Promoter luciferase reporter plasmids (see all 4): APC promoter sequence
   Search Chromatin IP Primers for APC

Epigenetics:
DNA Methylation CpG Assay Predesigned for Pyrosequencing in human, mouse, rat APC


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

Entrez Gene cytogenetic band: 5q21-q22   Ensembl cytogenetic band:  5q22.2   HGNC cytogenetic band: 5q21-q22

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

GeneLoc information about chromosome 5         GeneLoc Exon Structure

GeneLoc location for GC05P112101:  view genomic region     (about GC identifiers)

Start:
112,043,195 bp from pter      End:
112,181,936 bp from pter
Size:
138,742 bases      Orientation:
plus strand

(According to 1UniProtKB, HORDE, 2neXtProt, Ensembl, and/or Reactome, Modification sites according to PhosphoSitePlus, Specific Peptides from DME, 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., Antibodies by EMD Millipore, R&D Systems, Cell Signaling Technology, OriGene, Novus Biologicals, Thermo Fisher Scientific, LSBio, Abcam, Cloud-Clone Corp, and/or others.)
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UniProtKB/Swiss-Prot: APC_HUMAN, P25054 (See protein sequence)
Recommended Name: Adenomatous polyposis coli protein  
Size: 2843 amino acids; 311646 Da
Subunit: Forms homooligomers and heterooligomers with APC2. Interacts with DIAPH1 and DIAPH2 (By similarity).
Interacts with PDZ domains of DLG1 and DLG3. Associates with catenins. Binds axin. Interacts with ARHGEF4 (via
N-terminus). Interacts with MAPRE1 (via C-terminus); probably required for APC targeting to the growing
microtubule plus ends. Interacts with MAPRE2 and MAPRE3 (via C-terminus). Found in a complex consisting of
ARHGEF4, APC and CTNNB1. Interacts with SCRIB; may mediate APC targeting to adherens junctions of epithelial
cells. Interacts with SPATA13 (via N-terminus and SH3 domain). Interacts with ASAP1 (via SH3 domain). Found in a
complex composed of MACF1, APC, AXIN1, CTNNB1 and GSK3B (By similarity). Interacts at the cell membrane with
AMER1 and AMER2 (via ARM repeats)
Miscellaneous: APC mutations have led to some interesting observations. (1) the great majority of the mutations
found to date would result in truncation of the APC product. (2) almost all the mutations have occurred within
the first half of the coding sequence, and somatic mutations in colorectal tumors are further clustered in a
particular region, called MCR (mutation cluster region). (3) most identified point mutations in the APC gene are
transitions from cytosine to other nucleotides. (4) the location of germline mutations tends to correlate with
the number of colorectal polyps in FAP patients. Inactivation of both alleles of the APC gene seems to be
required as an early event to develop most adenomas and carcinomas in the colon and rectum as well as some of
those in the stomach
Selected PDB 3D structures from and Proteopedia for APC (see all 17):
1DEB (3D)        1EMU (3D)        1JPP (3D)        1M5I (3D)        1T08 (3D)        1TH1 (3D)    
Secondary accessions: D3DT03 Q15162 Q15163 Q93042
Alternative splicing: 2 isoforms:  P25054-1   P25054-2   

Explore the universe of human proteins at neXtProt for APC: NX_P25054

Explore proteomics data for APC at MOPED

Post-translational modifications: 

  • Phosphorylated by GSK3B1
  • Ubiquitinated, leading to its degradation by the proteasome. Ubiquitination is facilitated by Axin.
    Deubiquitinated by ZRANB1/TRABID1
  • Modification sites at neXtProt
  • Modification sites at PhosphoSitePlus

  • See APC Protein Expression from SPIRE MOPED, PaxDB, and MaxQB

    REFSEQ proteins (3 alternative transcripts): 
    NP_000029.2  NP_001120982.1  NP_001120983.2  

    ENSEMBL proteins: 
     ENSP00000426541   ENSP00000423224   ENSP00000424265   ENSP00000257430   ENSP00000427089  
     ENSP00000423828   ENSP00000473355   ENSP00000413133  
    Reactome Protein details: P25054

    APC Human Recombinant Protein Products:

    Browse Purified and Recombinant Proteins at EMD Millipore
    Browse R&D Systems for human recombinant proteins
    Browse recombinant and purified proteins available from Enzo Life Sciences
    Browse OriGene full length recombinant human proteins expressed in human HEK293 cells
    OriGene Protein Over-expression Lysate for APC
    OriGene Custom MassSpec
    OriGene Custom Protein Services for APC
    GenScript Custom Purified and Recombinant Proteins Services for APC
    Novus Biologicals APC Protein
    Novus Biologicals APC Lysates
    Browse Sino Biological Recombinant Proteins
    Browse Sino Biological Cell Lysates
    Browse ProSpec Recombinant Proteins
    Cloud-Clone Corp. Proteins for APC

    APC Antibody Products:

    EMD Millipore Mono- and Polyclonal Antibodies for the study of APC
    R&D Systems Antibodies for APC
    Cell Signaling Technology (CST) Antibodies for APC 
    OriGene Antibodies for APC
    OriGene Custom Antibody Services for APC
    Novus Biologicals APC Antibodies
    Abcam antibodies for APC
    Cloud-Clone Corp. Antibodies for APC
    ThermoFisher Antibody for APC
    LSBio Antibodies in human, mouse, rat for APC

    APC Assay Products:

    Browse Kits and Assays available from EMD Millipore
    OriGene Custom Assay Services for APC
    Browse R&D Systems for biochemical assays
    GenScript Custom Assay Services for APC
    Browse Enzo Life Sciences for kits & assays
    Cloud-Clone Corp. ELISAs for APC
    Cloud-Clone Corp. CLIAs for APC


    (According to HGNC, IUPHAR, InterPro, ProtoNet, UniProtKB, and/or BLOCKS, Sets of similar genes according to GeneDecks)
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    HGNC Gene Families:
    ARMC: Armadillo repeat containing
    PPP1R: Serine/threonine phosphatases / Protein phosphatase 1, regulatory subunits

    Selected InterPro protein domains (see all 11):
     IPR011989 ARM-like
     IPR009224 SAMP
     IPR000225 Armadillo
     IPR009232 EB1-bd
     IPR026831 APC_dom

    Graphical View of Domain Structure for InterPro Entry P25054

    ProtoNet protein and cluster: P25054

    1 Blocks protein domain: IPB000225 Armadillo repeat

    UniProtKB/Swiss-Prot: APC_HUMAN, P25054
    Domain: The microtubule tip localization signal (MtLS) motif; mediates interaction with MAPRE1 and targeting to
    the growing microtubule plus ends (By similarity)
    Similarity: Belongs to the adenomatous polyposis coli (APC) family
    Similarity: Contains 7 ARM repeats


    APC 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,
    transcription factor targeting from QIAGEN and/or HOMER, miRNA Gene Targets from miRTarBase, shRNA from OriGene, siRNAs from OriGene, QIAGEN, microRNA from QIAGEN, SwitchGear Genomics, Gene Editing from DNA2.0, Clones from OriGene, GenScript, Sino Biological, DNA2.0, and Vector BioLabs, Cell Lines from GenScript, ESI BIO, In Situ Hybridization Assays from Advanced Cell Diagnostics, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene.)
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    Molecular Function:

         UniProtKB/Swiss-Prot Summary: APC_HUMAN, P25054
    Function: Tumor suppressor. Promotes rapid degradation of CTNNB1 and participates in Wnt signaling as a negative
    regulator. APC activity is correlated with its phosphorylation state. Activates the GEF activity of SPATA13 and
    ARHGEF4. Plays a role in hepatocyte growth factor (HGF)-induced cell migration. Required for MMP9 up-regulation
    via the JNK signaling pathway in colorectal tumor cells. Acts as a mediator of ERBB2-dependent stabilization of
    microtubules at the cell cortex. It is required for the localization of MACF1 to the cell membrane and this
    localization of MACF1 is critical for its function in microtubule stabilization

         Genatlas biochemistry entry for APC:
    multidomain protein,binding beta-catenin and regulating free beta-catenin level,involved in cell adhesion and
    active cell migration,mutated in adenomatous polyposis coli,colon and rectum carcinoma non polyposis,modulating
    the frequency and classes of mutation leading to colon polyps

         Gene Ontology (GO): Selected molecular function terms (see all 9):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0005488binding ----
    GO:0005515protein binding IPI10656683
    GO:0008013beta-catenin binding IPI10773885
    GO:0008017microtubule binding IDA11166179
    GO:0019887protein kinase regulator activity IDA11972058
         
    APC for ontologies           About GeneDecksing


    Phenotypes:
         3 GenomeRNAi human phenotypes for APC:
     Decreased POU5F1-GFP protein e  Decreased focal adhesion (FA)   Upregulation of Wnt/beta-caten 

         Selected MGI mutant phenotypes (inferred from 26 alleles(MGI details for Apc) (see all 27):
     adipose tissue  behavior/neurological  cardiovascular system  cellular  craniofacial 
     digestive/alimentary  embryogenesis  endocrine/exocrine gland  growth/size/body  hearing/vestibular/ear 
     hematopoietic system  homeostasis/metabolism  immune system  integument  limbs/digits/tail 

    APC for phenotypes           About GeneDecksing

    Animal Models:
         MGI mouse knock-outs for APC: Apctm1.1Tyj Apctm4Mmt Apctm1Cip Apctm1Rak Apctm1.1Tno Apctm1Mmt
                                                         Apctm1Hsa Apctm1.1Ecrm Apctm2.1Rak

       inGenious Targeting Laboratory: Let us create your new Knockout/Knockin mouse model for APC
       inGenious Targeting Laboratory: Contact us about creating complex and humanized mouse models for APC

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

    miRNA
    Products:
        
    miRTarBase miRNAs that target APC:
    hsa-mir-215-5p (MIRT024577), hsa-mir-21-5p (MIRT031054), hsa-mir-148a-3p (MIRT048033), hsa-mir-186-5p (MIRT045069), hsa-mir-210-3p (MIRT003183), hsa-mir-155-5p (MIRT001207), hsa-mir-192-5p (MIRT026886), hsa-mir-27a-3p (MIRT006221), hsa-mir-106b-5p (MIRT007071)

    Block miRNA regulation of human, mouse, rat APC using miScript Target Protectors
    112 qRT-PCR Assays for microRNAs that regulate APC (see first 8):
    hsa-miR-579 hsa-miR-520e hsa-miR-300 hsa-miR-374a hsa-miR-519a hsa-miR-3916 hsa-miR-502-3p hsa-miR-3161
    hsa-miR-890 hsa-miR-208b hsa-miR-4274 hsa-miR-3148 hsa-miR-556-3p hsa-miR-520b hsa-miR-1298 hsa-miR-1206
    hsa-miR-186* hsa-miR-27a hsa-miR-1267 hsa-miR-519e hsa-miR-373 hsa-miR-873 hsa-miR-520c-3p hsa-miR-466
    hsa-miR-3607-5p hsa-miR-448 hsa-miR-4318 hsa-miR-555 hsa-miR-501-3p hsa-miR-944 hsa-miR-1257 hsa-miR-20b*
    hsa-miR-520a-3p hsa-miR-499-5p hsa-miR-125b hsa-miR-2115 hsa-miR-1909* hsa-miR-3119 hsa-miR-515-3p hsa-miR-569
    hsa-miR-548p hsa-miR-302a hsa-miR-3617 hsa-miR-3137 hsa-miR-582-5p hsa-miR-802 hsa-miR-524-5p hsa-miR-32*
    hsa-miR-302d hsa-miR-4307 hsa-miR-4328 hsa-miR-513a-5p hsa-miR-507 hsa-miR-548l hsa-miR-3171 hsa-miR-374c
    hsa-miR-223 hsa-miR-372 hsa-miR-1276 hsa-miR-208a hsa-miR-3658 hsa-miR-155 hsa-miR-1183 hsa-miR-330-3p
    hsa-miR-302b hsa-miR-203 hsa-miR-3163 hsa-miR-222* hsa-miR-561 hsa-miR-374b hsa-miR-381 hsa-miR-3120-3p
    hsa-miR-519c-3p hsa-miR-4282 hsa-miR-519b-3p hsa-miR-33a* hsa-miR-302c hsa-miR-655 hsa-miR-670 hsa-miR-129-5p
    hsa-miR-590-3p hsa-miR-150 hsa-miR-4319 hsa-miR-142-3p hsa-miR-125a-5p hsa-miR-520d-5p hsa-miR-3942-5p hsa-miR-302e
    hsa-miR-520a-5p hsa-miR-3125 hsa-miR-583 hsa-miR-641 hsa-miR-7-1* hsa-miR-205* hsa-miR-520d-3p hsa-miR-450b-5p
    hsa-miR-892a hsa-miR-3941 hsa-miR-3671 hsa-miR-577 hsa-miR-7-2* hsa-miR-589* hsa-miR-2278 hsa-miR-3672
    hsa-miR-153 hsa-miR-135b hsa-miR-935 hsa-miR-525-5p hsa-miR-3185 hsa-miR-494 hsa-miR-27b hsa-miR-135a
    SwitchGear 3'UTR luciferase reporter plasmidAPC 3' UTR sequence
    Inhib. RNA
    Products:
        
    OriGene RNAi products in human, mouse, rat for APC
    Predesigned siRNA for gene silencing in human, mouse, rat APC

    Gene Editing
    Products:
    DNA2.0 Custom Protein Engineering Service for APC

    Clone
    Products:
         
    OriGene clones in human, mouse for APC (see all 13)
    OriGene ORF clones in mouse, rat for APC
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    GenScript: all cDNA clones in your preferred vector (see all 3): APC (NM_001127510)
    Browse Sino Biological Human cDNA Clones
    DNA2.0 Custom Codon Optimized Gene Synthesis Service for APC
    Vector BioLabs ready-to-use adenovirus/AAV for human, mouse, rat APC

    Cell Line
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    Browse ESI BIO Cell Lines and PureStem Progenitors for APC 
    In Situ Assay
    Products:
       

     
    Advanced Cell Diagnostics RNAscope RNA in situ hybridization assays for APC


    (According to UniProtKB, COMPARTMENTS Subcellular localization database, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene.)
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    Subcellular locations from UniProtKB/Swiss-Prot
    APC_HUMAN, P25054: Cell junction, adherens junction. Cytoplasm, cytoskeleton. Cell projection, lamellipodium.
    Cell projection, ruffle membrane. Cytoplasm. Cell membrane. Note=Associated with the microtubule network at the
    growing distal tip of microtubules. Accumulates in the lamellipodium and ruffle membrane in response to
    hepatocyte growth factor (HGF) treatment. The MEMO1-RHOA-DIAPH1 signaling pathway controls localization of the
    phosophorylated form to the cell membrane
    Subcellular locations from COMPARTMENTS: 

    CompartmentConfidence
    cytoskeleton5
    nucleus5
    plasma membrane5
    cytosol4

    Gene Ontology (GO): Selected cellular component terms (see all 19):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0000776kinetochore IDA11283619
    GO:0005634nucleus IDA11035805
    GO:0005737cytoplasm IDA11035805
    GO:0005813centrosome IDA11283619
    GO:0005829cytosol TAS--

    APC for ontologies           About GeneDecksing


    (SuperPaths according to PathCards, Pathways according to 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 QIAGEN, 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 Apr 2014 via Entrez Gene).
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    SuperPaths for APC About   (see all 36)  
    See pathways by source

    SuperPathContained pathways About
    1Wnt signaling pathway (KEGG)
    Wnt signaling pathway0.40
    Wnt Signaling Pathway NetPath0.37
    Wnt Signaling Pathways0.40
    2Regulation of actin cytoskeleton
    Regulation of actin cytoskeleton0.57
    Regulation of Actin Cytoskeleton0.57
    3CDK-mediated phosphorylation and removal of Cdc6
    Degradation of beta-catenin by the destruction complex0.73
    Beta-catenin phosphorylation cascade0.00
    Apoptosis0.38
    4Wnt Signaling Pathway (WikiPathways)
    Wnt Signaling Pathway0.55
    DNA damage response (only ATM dependent)0.32
    Wnt Signaling Pathway and Pluripotency0.55
    5Apoptotic cleavage of cellular proteins
    Apoptotic cleavage of cellular proteins0.74
    Apoptotic execution phase0.74

    Pathways by source                                                                                                                                                                 See SuperPaths
    Show all pathways

    1 R&D Systems Pathway for APC
        Wnt Signaling Pathways

    Selected Downloadable PowerPoint Slides of GeneGlobe Pathway Central Maps for APC (see all 11)
        Factors Promoting Cardiogenesis in Vertebrates
    Molecular Mechanisms of Cancer
    G12-G13 in Cellular Signaling
    Colorectal Cancer Metastasis
    Glioblastoma Multiforme

    1 Cell Signaling Technology (CST) Pathway for APC
        Wnt / Hedgehog / Notch

    Selected BioSystems Pathways for APC (see all 17)
        Wnt Signaling Pathway
    Wnt Signaling Pathway and Pluripotency
    DNA damage response (only ATM dependent)
    Irinotecan Pathway
    Gastric cancer network 1

    5 Reactome Pathways for APC
        deactivation of the beta-catenin transactivating complex
    disassembly of the destruction complex and recruitment of AXIN to the membrane
    Apoptotic cleavage of cellular proteins
    Degradation of beta-catenin by the destruction complex
    Beta-catenin phosphorylation cascade


    Selected Kegg Pathways  (Kegg details for APC) (see all 9):
        Wnt signaling pathway
    Hippo signaling pathway
    Regulation of actin cytoskeleton
    HTLV-I infection
    Pathways in cancer


    APC for pathways           About GeneDecksing

        Pathway & Disease-focused RT2 Profiler PCR Arrays including APC (see all 15): 
              Parkinson's Disease in human mouse rat
              Oncogenes & Tumor Suppressor Genes in human mouse rat
              Lung Cancer in human mouse rat
              Multiple Sclerosis in human mouse rat
              WNT Signaling Pathway in human mouse rat

    Interactions:

        GeneGlobe Interaction Network for APC

    STRING Interaction Network Preview (showing 5 interactants - click image to see 25)

    Selected Interacting proteins for APC (P250541, 2, 3 ENSP000002574304) via UniProtKB, MINT, STRING, and/or I2D (see all 530)
    InteractantInteraction Details
    GeneCardExternal ID(s)
    DVL1O146401, 2, 3, ENSP000003681694EBI-727707,EBI-723489 MINT-7897032 MINT-7897055 MINT-7897075 MINT-7897100 I2D: score=1 STRING: ENSP00000368169
    CTNNB1P352221, 2, 3, ENSP000003444564EBI-727707,EBI-491549 MINT-4508229 I2D: score=8 STRING: ENSP00000344456
    DVL1P1P547921, 2, 3EBI-727707,EBI-7848109 MINT-7891084 MINT-7891069 I2D: score=1 
    DVL2O146412, 3, ENSP000000053404MINT-7890898 MINT-7897032 MINT-7897075 I2D: score=2 STRING: ENSP00000005340
    PXNP490232, 3, ENSP000002283074MINT-7891130 MINT-7897100 I2D: score=2 STRING: ENSP00000228307
    About this table

    Gene Ontology (GO): Selected biological process terms (see all 60):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0000281mitotic cytokinesis IMP17570218
    GO:0001822kidney development IEA--
    GO:0001942hair follicle development IEA--
    GO:0006461protein complex assembly IDA16188939
    GO:0006915apoptotic process TAS--

    APC for ontologies           About GeneDecksing



    (Chemical Compounds according to UniProtKB, Enzo Life Sciences, EMD Millipore, Tocris Bioscience, ApexBio, HMDB, BitterDB, and/or Novoseek, Ligands according to IUPHAR, and Drugs according to DrugBank, Enzo Life Sciences, and/or PharmGKB)
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    Browse Small Molecules at EMD Millipore
       Browse drugs & compounds from Enzo Life Sciences
      Browse compounds at ApexBio 

    Browse Tocris compounds for APC

    Selected Novoseek inferred chemical compound relationships for APC gene (see all 88)    About this table
    Compound   -log (P-Val)   Hits   PubMed IDs for Articles with Shared Sentences (# sentences)
    af/ap 80.5 4 10494086 (2), 11786778 (1), 15623495 (1)
    crcs 74.3 10 11270422 (1), 17704924 (1), 11751382 (1), 14578138 (1) (see all 8)
    sulindac 60.9 8 11535846 (3), 12663524 (2), 19755659 (1), 8707116 (1)
    phip 60.7 17 19628463 (2), 9202752 (2), 11181456 (2), 9202738 (1) (see all 11)
    glycogen 59.9 144 19339242 (9), 9003374 (5), 10233043 (5), 12829248 (5) (see all 55)
    pphp 48.9 2 1621772 (1)
    1-hydroxyanthraquinone 48 3 9433483 (2), 10204808 (1)
    samp 47.7 3 10346819 (1), 10021369 (1), 10966653 (1)
    5-aza-2'deoxycytidine 46.1 5 17065059 (1), 15087381 (1), 15225415 (1), 18058533 (1) (see all 5)
    adenylate 38.1 15 2167212 (1), 10421220 (1), 1637317 (1), 8131796 (1) (see all 15)



    APC for compounds           About GeneDecksing



    (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,
    exon structure from GeneLoc, alternative splicing isoforms according to ASD and/or ECgene,
    siRNAs from OriGene, QIAGEN, shRNA from OriGene, microRNA from QIAGEN, SwitchGear Genomics,
    Tagged/untagged cDNA clones from OriGene, GenScript, DNA2.0, Vector BioLabs, Primers from OriGene, and/or QIAGEN )
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    REFSEQ mRNAs for APC gene (3 alternative transcripts): 
    NM_000038.5  NM_001127510.2  NM_001127511.2  

    Unigene Cluster for APC:

    Adenomatous polyposis coli
    Hs.158932  [show with all ESTs]
    Unigene Representative Sequence: NM_001127510
    13 Ensembl transcripts including schematic representations, and UCSC links where relevant:
    ENST00000509732 ENST00000505350 ENST00000507379 ENST00000508624 ENST00000257430(uc003kpz.4 uc003kpy.4 uc010jbz.3 uc010jca.3)
    ENST00000508376 ENST00000512211 ENST00000506342 ENST00000502371 ENST00000504915
    ENST00000505084 ENST00000514164 ENST00000457016(uc011cvt.2)
    miRNA
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    Block miRNA regulation of human, mouse, rat APC using miScript Target Protectors
    Selected qRT-PCR Assays for microRNAs that regulate APC (see all 112):
    hsa-miR-579 hsa-miR-520e hsa-miR-300 hsa-miR-374a hsa-miR-519a hsa-miR-3916 hsa-miR-502-3p hsa-miR-3161
    SwitchGear 3'UTR luciferase reporter plasmidAPC 3' UTR sequence
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    Predesigned siRNA for gene silencing in human, mouse, rat APC
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    OriGene custom cloning services - gene synthesis, subcloning, mutagenesis, variant library, vector shuttling
    GenScript: all cDNA clones in your preferred vector (see all 3): APC (NM_001127510)
    DNA2.0 Custom Codon Optimized Gene Synthesis Service for APC
    Vector BioLabs ready-to-use adenovirus/AAV for human, mouse, rat APC
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    Additional mRNA sequence: 

    AB210001.1 AF038181.1 AK289567.1 AK294544.1 AK309033.1 BC034955.1 BC056268.1 M73548.1 
    M74088.1 S56365.1 S67787.1 S67788.1 S67789.1 

    15 DOTS entries:

    DT.99981468  DT.120809542  DT.40310104  DT.95121675  DT.99962531  DT.119384  DT.95374795  DT.120809704 
    DT.120809770  DT.452608  DT.449103  DT.91757887  DT.100721411  DT.432665  DT.91950191 

    Selected AceView cDNA sequences (see all 445):

    BQ549628 BE256854 AL706482 BM791285 CA313732 BM723345 AI566022 BM930344 
    AL535988 AA421913 F01948 BX100792 F05691 BQ182033 AA033768 AA376964 
    F12582 BM977243 BG985951 BM987992 NM_005083 F09958 BF001542 BI333071 

    GeneLoc Exon Structure

    3 Alternative Splicing Database (ASD) splice patterns (SP) for APC    About this scheme

    ExUns: 1a · 1b ^ 2 ^ 3 ^ 4 ^ 5 ^ 6a · 6b ^ 7 ^ 8 ^ 9 ^ 10 ^ 11 ^ 12 ^ 13a · 13b ^ 14 ^ 15a · 15b ^ 16 ^ 17
    SP1:                                                                                                              -               
    SP2:              -                                                                                                               
    SP3:                                                                                                                              


    ECgene alternative splicing isoforms for APC

    (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™, Protein expression images according to data from SPIRE 1MOPED, 2PaxDb, and 3MaxQB, plus additional links to SOURCE, and/or BioGPS, and/or UniProtKB,
    PCR Arrays from QIAGEN, Primers from OriGene, and/or QIAGEN, In Situ Hybridization Assays from Advanced Cell Diagnostics)
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    APC expression in normal human tissues (normalized intensities)
    See probesets specificity/sensitivity at GeneAnnot
    About this imageBioGPS <intensity>2/3
    CGAP TAG: --
    APC Expression
    About this image


    APC expression in embryonic tissues and stem cells    About this table
    Data from LifeMap, the Embryonic Development and Stem Cells Database
     selected tissues (see all 11) fully expand
     
     Brain (Nervous System)    fully expand to see all 6 entries
             Myelinating Oligodendrocyte Cells Forebrain White Matter
             Cerebral Cortex
     
     Spinal Cord (Nervous System)
             Myelinating Oligodendrocyte Cells Spinal Cord White Matter
     
     Eye (Sensory Organs)    fully expand to see all 2 entries
             Mature Retinal Pigmented Epithelium Cells Retinal Pigmented Epithelium
             Retina
     
     Epithelial Cells
             Mature Retinal Pigmented Epithelium Cells Retinal Pigmented Epithelium
     
     Primitive Streak (Early Embryonic Tissues)
             Primitive Streak Cells Anterior Primitive Streak
    APC Protein expression data from MOPED1, PaxDb2 and MaxQB3    About this image

    APC Protein Expression

    SOURCE GeneReport for Unigene cluster: Hs.158932

    UniProtKB/Swiss-Prot: APC_HUMAN, P25054
    Tissue specificity: Expressed in a variety of tissues

        Pathway & Disease-focused RT2 Profiler PCR Arrays including APC (see all 15): 
              Parkinson's Disease in human mouse rat
              Oncogenes & Tumor Suppressor Genes in human mouse rat
              Lung Cancer in human mouse rat
              Multiple Sclerosis in human mouse rat
              WNT Signaling Pathway in human mouse rat

    Primer
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    In Situ
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    Advanced Cell Diagnostics RNAscope RNA in situ hybridization assays for APC

    (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)
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    This gene was present in the common ancestor of animals.

    Orthologs for APC gene from Selected species (see all 14)    About this table
    Organism Taxonomic
    classification
    Gene Description Human
    Similarity
    Orthology
    Type
    Details
    mouse
    (Mus musculus)
    Mammalia Apc1 , 5 adenomatosis polyposis coli1, 5 87.53(n)1
    90.77(a)1
      18 (18.53 cM)5
    117891  NM_007462.31  NP_031488.21 
     342209245 
    chicken
    (Gallus gallus)
    Aves APC1 adenomatous polyposis coli 80.62(n)
    85.48(a)
      415607  XM_004949283.1  XP_004949340.1 
    lizard
    (Anolis carolinensis)
    Reptilia --
    --
    Uncharacterized protein
    97(a)
    82(a)
    many ↔ many
    many ↔ many
    GL343193.1(6920773-6928072)
    GL343193.1(6928765-6980589)
    African clawed frog
    (Xenopus laevis)
    Amphibia Xl.84362 Xenopus laevis adenomatous polyposis coli mRNA, complete more 78.78(n)    U64442.1 
    zebrafish
    (Danio rerio)
    Actinopterygii apc1 adenomatosis polyposis coli 66.85(n)
    70.8(a)
      386762  NM_001143840.1  NP_001137312.1 
    fruit fly
    (Drosophila melanogaster)
    Insecta Apc3 frizzled-2 receptor signaling pathway
    microtubule more
    54(a)
    (best of 2)
        --
    worm
    (Caenorhabditis elegans)
    Secernentea apr-16
    Protein APR-1, isoform b (apr-1) mRNA, complete cd...
    22(a)
    1 → many
    I(8050043-8055474) WBGene00000156


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

    (Paralogs according to 1HomoloGene,
    2Ensembl, and 3SIMAP, Pseudogenes according to 4Pseudogene.org Build 68)
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    Paralogs for APC gene
    APC22  ENSG000002588642  
    2 SIMAP similar genes for APC using alignment to 26 protein entries:     APC_HUMAN (see all proteins):
    APC variant protein    APC2

    APC 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), the Human Cytochrome P450 Allele Nomenclature Database, and the Locus Specific Mutation Databases (LSDB), Blood group antigen gene mutations by BGMUT, Resequencing Primers, Cancer Mutation PCR Arrays and Assays, and Copy Number PCR Arrays from QIAGEN)
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    Selected SNPs for APC (see all 4088)    About this table    
    Genomic DataTranscription Related DataAllele Frequencies
    SNP IDValidClinical
    significance
    Chr 5 posSequence#AA
    Chg
    TypeMore#Allele
    freq
    PopTotal
    sample
    More
    ----------
    rs1378545671,2,,4
    C,FFamilial adenomatous polyposis (FAP)4 pathogenic1112435736(+) AGATAC/TGCGCT 6 R C mis12Minor allele frequency- T:0.00NA EU 5871
    rs725418161,2,,4
    C,FFamilial adenomatous polyposis (FAP)4 --112460025(+) ATTTTC/GTCCCA 6 S C mis17Minor allele frequency- G:0.30EU NA 7221
    VAR_0096144
    Familial adenomatous polyposis (FAP)4--see VAR_0096142 S G mis40--------
    VAR_0096164
    Familial adenomatous polyposis (FAP)4--see VAR_0096162 A P mis40--------
    VAR_0050454
    Gastric cancer (GASC)4--see VAR_0050452 F S mis40--------
    VAR_0050504
    Gastric cancer (GASC)4--see VAR_0050502 G E mis40--------
    VAR_0050514
    Familial adenomatous polyposis (FAP)4--see VAR_0050512 T A mis40--------
    VAR_0050354
    Gastric cancer (GASC)4--see VAR_0050352 G C mis40--------
    VAR_0176554
    Medulloblastoma (MDB)4--see VAR_0176552 S G mis40--------
    VAR_0050524
    Gastric cancer (GASC)4--see VAR_0050522 V A mis40--------

    HapMap Linkage Disequilibrium report for APC (112043195 - 112181936 bp)

    Structural Variations
         Database of Genomic Variants (DGV) 3 variations for APC:    About this table    
    Variant IDTypeSubtypePubMed ID
    nsv4959CNV Insertion18451855
    nsv462387CNV Loss19166990
    nsv830450CNV Gain17160897

    Human Gene Mutation Database (HGMD): APC
    Locus Specific Mutation Databases (LSDB): APC

    Selected Site Specific Mutation Identification with PCR Assays for APC (see all 63):
    Cosmic IdAA Change
    19033p.P1372fs*2
    18999p.L1488fs*19
    41618p.L1488fs*18
    25826p.S1346*
    18822p.E1408*
    Selected Site Specific Cancer Mutation PCR Panels containing APC (see all 10):
    Breast Cancer
    Cancer Comprehensive Panel 384HT
    APC/CTNNB1 Pathway
    Soft Tissue Tumors
    Tumor Suppressor Panel 384HT
    2 Copy Number PCR Panels containing APC:
    Oncogenes & Tumor Suppressor Genes 384HC
    WNT Signaling
    SeqTarget long-range PCR primers for resequencing APC
    DNA2.0 Custom Variant and Variant Library Synthesis for APC

    (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.)
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    OMIM gene information: 611731   
    OMIM disorders: 175100  613659  114550  135290  114500  
    UniProtKB/Swiss-Prot: APC_HUMAN, P25054
  • Familial adenomatous polyposis (FAP) [MIM:175100]: A cancer predisposition syndrome characterized by
    adenomatous polyps of the colon and rectum, but also of upper gastrointestinal tract (ampullary, duodenal and
    gastric adenomas). This is a viciously premalignant disease with one or more polyps progressing through dysplasia
    to malignancy in untreated gene carriers with a median age at diagnosis of 40 years. Note=The disease is caused
    by mutations affecting the gene represented in this entry
  • Hereditary desmoid disease (HDD) [MIM:135290]: Autosomal dominant trait with 100% penetrance and possible
    variable expression among affected relatives. HDD patients show multifocal fibromatosis of the paraspinal
    muscles, breast, occiput, arms, lower ribs, abdominal wall, and mesentery. Desmoid tumors appears also as a
    complication of familial adenomatous polyposis. Note=The disease is caused by mutations affecting the gene
    represented in this entry
  • Medulloblastoma (MDB) [MIM:155255]: Malignant, invasive embryonal tumor of the cerebellum with a
    preferential manifestation in children. Note=The gene represented in this entry may be involved in disease
    pathogenesis
  • Mismatch repair cancer syndrome (MMRCS) [MIM:276300]: Autosomal dominant disorder characterized by
    malignant tumors of the brain associated with multiple colorectal adenomas. Skin features include sebaceous
    cysts, hyperpigmented and cafe au lait spots. Note=The disease is caused by mutations affecting the gene
    represented in this entry
  • Gastric cancer (GASC) [MIM:613659]: A malignant disease which starts in the stomach, can spread to the
    esophagus or the small intestine, and can extend through the stomach wall to nearby lymph nodes and organs. It
    also can metastasize to other parts of the body. The term gastric cancer or gastric carcinoma refers to
    adenocarcinoma of the stomach that accounts for most of all gastric malignant tumors. Two main histologic types
    are recognized, diffuse type and intestinal type carcinomas. Diffuse tumors are poorly differentiated
    infiltrating lesions, resulting in thickening of the stomach. In contrast, intestinal tumors are usually
    exophytic, often ulcerating, and associated with intestinal metaplasia of the stomach, most often observed in
    sporadic disease. Note=The gene represented in this entry may be involved in disease pathogenesis
  • Hepatocellular carcinoma (HCC) [MIM:114550]: A primary malignant neoplasm of epithelial liver cells. The
    major risk factors for HCC are chronic hepatitis B virus (HBV) infection, chronic hepatitis C virus (HCV)
    infection, prolonged dietary aflatoxin exposure, alcoholic cirrhosis, and cirrhosis due to other causes. Note=The
    gene represented in this entry may be involved in disease pathogenesis

  • Selected diseases for APC (see all 156):    
    About MalaCards
    fourth cranial nerve palsy    gardner syndrome    familial adenomatous polyposis due to 5q22.2 microdeletion    brain tumor-polyposis syndrome 2
    desmoid tumor    desmoid disease, hereditary    familial adenomatous polyposis    hepatoblastoma, somatic
    adenoma, periampullary, somatic    apc-associated polyposis conditions    intestinal neoplasm    hepatoblastoma
    cranial nerve palsy    attenuated familial adenomatous polyposis    fibrous dysplasia    medulloblastoma
    brachydactyly type e    nonpapillary renal cell carcinoma    mutyh-associated polyposis    turcot syndrome

    5 diseases from the University of Copenhagen DISEASES database for APC:
    Familial adenomatous polyposis     Colorectal cancer     Adenoma     Intestinal neoplasm
    Carcinoma

    APC for disorders           About GeneDecksing

    Selected Novoseek inferred disease relationships for APC gene (see all 95)    About this table

    Disease   -log (P-Val)   Hits   PubMed IDs for Articles with Shared Sentences (# sentences)
    familial adenomatous polyposis 96.7 454 15793634 (4), 8835324 (4), 15540296 (4), 11786778 (3) (see all 99)
    polyposis 89.7 92 17568392 (6), 11867715 (4), 15761860 (3), 11868006 (2) (see all 58)
    colorectal cancer 85.6 236 8835324 (6), 15375009 (5), 11211307 (4), 11135372 (4) (see all 99)
    adenoma 85.1 218 8012980 (6), 12673484 (6), 12163385 (6), 10440612 (5) (see all 99)
    colorectal tumors 83.1 44 10737795 (3), 10921028 (3), 10493496 (2), 9724771 (2) (see all 35)
    microsatellite instability 83.1 54 9924427 (2), 11819821 (2), 12378616 (2), 11107173 (2) (see all 47)
    desmoid tumor 81.7 59 15793634 (6), 18646694 (3), 18854359 (3), 10782927 (3) (see all 24)
    turcot syndrome 81.1 14 7515658 (2), 7662026 (1), 9641305 (1), 11005140 (1) (see all 10)
    adenomatous polyps 79.4 11 14502807 (2), 7559732 (1), 12833148 (1), 14578138 (1) (see all 10)
    germ-line mutation 78.5 41 11867715 (3), 1316610 (2), 15857185 (2), 11754114 (2) (see all 32)

    GeneTests: APC
    GeneReviews: APC
    Genetic Association Database (GAD): APC
    Human Genome Epidemiology (HuGE) Navigator: APC (236 documents)
    Tumor Gene Database (TGDB): APC

    Export disorders for APC 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)
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    PubMed articles for APC gene, integrated from 10 sources (see all 1628):
    (articles sorted by number of sources associating them with APC)
        Utopia: connect your pdf to the dynamic
    world of online information

    1. The APC variants I1307K and E1317Q are associated with colorectal tumors, but not always with a family history. (PubMed id 9724771)1, 2, 4, 9 Frayling I.M.... Tomlinson I.P.M. (Proc. Natl. Acad. Sci. U.S.A. 1998)
    2. A germline mutation at the extreme 3' end of the APC gene results in a severe desmoid phenotype and is associated with overexpression of beta-catenin in the desmoid tumor. (PubMed id 10782927)1, 2, 4, 9 Couture J.... Bapat B. (Clin. Genet. 2000)
    3. Mutations of chromosome 5q21 genes in FAP and colorectal cancer patients. (PubMed id 1651563)1, 2, 3, 9 Nishisho I.... Vogelstein B. (Science 1991)
    4. Relative role of APC and MUTYH mutations in the pathogenesis of familial adenomatous polyposis. (PubMed id 19593690)1, 4, 9 Pezzi A....Ponz De Leon M. (Scand. J. Gastroenterol. 2009)
    5. APC and CTNNB1 mutations are rare in sporadic ependymomas. (PubMed id 16843107)1, 4, 9 Onilude O.E....Clifford S.C. (Cancer Genet. Cytogenet. 2006)
    6. [The I1307K mutation and protein expression of APC gene in gastric cancer]. (PubMed id 15639864)1, 4, 9 Sun X.J....Sun K.L. (Yi Chuan 2003)
    7. Molecular analysis of the APC and MUTYH genes in Galician and Catalonian FAP families: a different spectrum of mutations? (PubMed id 19531215)1, 4, 9 GA^mez-FernA!ndez N....Ruiz-Ponte C. (BMC Med. Genet. 2009)
    8. [Polymorphism/loss of heterozygosity of APC gene in GERD-Barrett's metaplasia-dysplasia-adenocarcinoma sequence]. (PubMed id 19606680)1, 4, 9 Mokrowiecka A....Malecka-Panas E. (Pol. Merkur. Lekarski 2009)
    9. Prevalence of mutations in APC, CTNNB1, and BRAF in Tunisian patients with sporadic colorectal cancer. (PubMed id 18992635)1, 4, 9 Bougatef K....Marrakchi R. (Cancer Genet. Cytogenet. 2008)
    10. APC gene loss of heterozygosity, mutations, E1317Q, and I1307K germ-line variants in sporadic colon cancer in Croatia. (PubMed id 15507235)1, 4, 9 KapitanoviA8 S....PaveliA8 K. (Exp. Mol. Pathol. 2004)

    (in PubMed, OMIM, and NCBI Bookshelf)
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     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)
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    Entrez Gene: 324 HGNC: 583 AceView: APCandSRP19andU2AF1L1 Ensembl:ENSG00000134982 euGenes: HUgn324
    ECgene: APC Kegg: 324 H-InvDB: APC

    (According to HUGE)
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      --

    (According to PharmGKB, ATLAS, HORDE, IMGT, LEIDEN, UniProtKB/Swiss-Prot, UniProtKB/TrEMBL, and/or others, e.g. Wikipedia and GeneReviews, via UniProtKB/Swiss-Prot)
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    NameDescription
    PharmGKB entry for APC Pharmacogenomics, SNPs, Pathways
    ATLAS Chromosomes in Cancer entry for APC Genetics and Cytogenetics in Oncology and Haematology
    GeneReviewshttp://www.ncbi.nlm.nih.gov/books/NBK1116/?term=APC[genesymbol]
    SHMPDhttp://shmpd.bii.a-star.edu.sg/gene.php?genestart=A&genename=APC
    Wikipedia http://en.wikipedia.org/wiki/APC_%28gene%29

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

    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, Novus Biologicals, Sino Biological, Enzo Life Sciences, Abcam, ProSpec, Cloud-Clone Corp., Thermo Fisher Scientific, LSBio, Gene Editing from DNA2.0. Clones from OriGene, GenScript, Sino Biological, DNA2.0, SwitchGear Genomics, Vector BioLabs, Cell lines from GenScript, and ESI BIO, PCR Arrays from QIAGEN, Drugs and/or compounds from EMD Millipore, Tocris Bioscience, Enzo Life Sciences, and/or ApexBio, In Situ Hybridization Assays from
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    GeneCards Homepage - Last full update: 7 May 2014 - Incrementals: 9 May 2014 , 2 Jun 2014 , 26 Jun 2014 , 30 Jun 2014

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