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APOE Gene

protein-coding   GIFtS: 71
GCID: GC19P045408

Apolipoprotein E

(Previous names: Alzheimer disease 2 (APOE*E4-associated, late onset))
(Previous symbol: AD2)
  See APOE-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
Apolipoprotein E1 2     Alzheimer Disease 2 (APOE*E4-Associated, Late Onset)1
AD21 2 5     apo-E2
LDLCQ52 5     Apolipoprotein E32
LPG2 5     Apo-E3

External Ids:    HGNC: 6131   Entrez Gene: 3482   Ensembl: ENSG000001302037   OMIM: 1077415   UniProtKB: P026493   

Export aliases for APOE gene to outside databases

Previous GC identifers: GC19P046053 GC19P045799 GC19P050085 GC19P050100 GC19P041839


(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 APOE Gene:
Chylomicron remnants and very low density lipoprotein (VLDL) remnants are rapidly removed from the circulation by
receptor-mediated endocytosis in the liver. Apolipoprotein E, a main apoprotein of the chylomicron, binds to a
specific receptor on liver cells and peripheral cells. ApoE is essential for the normal catabolism of
triglyceride-rich lipoprotein constituents. The APOE gene is mapped to chromosome 19 in a cluster with APOC1 and
APOC2. Defects in apolipoprotein E result in familial dysbetalipoproteinemia, or type III hyperlipoproteinemia
(HLP III), in which increased plasma cholesterol and triglycerides are the consequence of impaired clearance of
chylomicron and VLDL remnants. (provided by RefSeq, Jul 2008)

GeneCards Summary for APOE Gene:
APOE (apolipoprotein E) is a protein-coding gene. Diseases associated with APOE include age related macular degeneration, and mesial temporal lobe epilepsy with hippocampal sclerosis. GO annotations related to this gene include protein heterodimerization activity and protein homodimerization activity.

UniProtKB/Swiss-Prot: APOE_HUMAN, P02649
Function: Mediates the binding, internalization, and catabolism of lipoprotein particles. It can serve as a ligand
for the LDL (apo B/E) receptor and for the specific apo-E receptor (chylomicron remnant) of hepatic tissues

Gene Wiki entry for APOE (Apolipoprotein E) 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 at NCBI GenBank:
NC_000019.9  NT_011109.17  NC_018930.2  
Regulatory elements:
   Regulatory transcription factor binding sites in the APOE gene promoter:
         c-Fos   Sp1   AP-1   ATF-2   c-Jun   
         Other transcription factors

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

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


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

Entrez Gene cytogenetic band: 19q13.2   Ensembl cytogenetic band:  19q13.32   HGNC cytogenetic band: 19q13.31

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

GeneLoc information about chromosome 19         GeneLoc Exon Structure

GeneLoc location for GC19P045408:  view genomic region     (about GC identifiers)

Start:
45,409,011 bp from pter      End:
45,412,650 bp from pter
Size:
3,640 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, Cloud-Clone Corp., eBioscience, and/or antibodies-online,
Biochemical Assays by EMD Millipore, R&D Systems, OriGene, GenScript, Cell Signaling Technology, Enzo Life Sciences, Cloud-Clone Corp., eBioscience, and/or antibodies-online, Antibodies by EMD Millipore, R&D Systems, Cell Signaling Technology, OriGene, Novus Biologicals, Thermo Fisher Scientific, Abcam, Cloud-Clone Corp, antibodies-online, and/or others.)
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UniProtKB/Swiss-Prot: APOE_HUMAN, P02649 (See protein sequence)
Recommended Name: Apolipoprotein E precursor  
Size: 317 amino acids; 36154 Da
Selected PDB 3D structures from and Proteopedia for APOE (see all 17):
1B68 (3D)        1BZ4 (3D)        1EA8 (3D)        1GS9 (3D)        1H7I (3D)        1LE2 (3D)    
Secondary accessions: B2RC15 C0JYY5 Q9P2S4

Explore the universe of human proteins at neXtProt for APOE: NX_P02649

Explore proteomics data for APOE at MOPED

Post-translational modifications: 

  • Synthesized with the sialic acid attached by O-glycosidic linkage and is subsequently desialylated in plasma.
    O-glycosylated with core 1 or possibly core 8 glycans. Thr-307 and Thr-314 are minor glycosylation siteS compared
    to Ser-3081
  • Glycated in plasma VLDL of normal subjects, and of hyperglycemic diabetic patients at a higher level (2-3 fold)1
  • Phosphorylation sites are present in the extracellular medium1
  • Glycosylation2 at Thr26, Thr36, Lys93, Thr212, Ser215, Thr307, Ser308, Ser314
  • Modification sites at PhosphoSitePlus

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

    REFSEQ proteins: NP_000032.1  
    ENSEMBL proteins: 
     ENSP00000252486   ENSP00000413135   ENSP00000413653   ENSP00000410423  
    Reactome Protein details: P02649

    APOE Human Recombinant Protein Products:

    EMD Millipore Purified and/or Recombinant APOE Protein
    R&D Systems Recombinant & Natural Proteins for APOE (Apolipoprotein E3/ApoE3)
    Browse recombinant and purified proteins available from Enzo Life Sciences
    OriGene Purified Protein for APOE
    OriGene Protein Over-expression Lysate for APOE
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    OriGene Custom Protein Services for APOE
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    Novus Biologicals APOE Proteins
    Novus Biologicals APOE Lysate
    Browse Sino Biological Recombinant Proteins
    Browse Sino Biological Cell Lysates
    Browse ProSpec Recombinant Proteins
    Cloud-Clone Corp. Proteins for APOE

     
    Search eBioscience for Proteins for APOE 

     
    antibodies-online proteins for APOE (21 products) 

     
    antibodies-online peptides for APOE

    APOE Antibody Products:

    EMD Millipore Mono- and Polyclonal Antibodies for the study of APOE
    R&D Systems Antibodies for APOE (Apolipoprotein E/ApoE, Apolipoprotein E3/ApoE3)
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    OriGene Antibodies for APOE
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    antibodies-online antibodies for APOE (216 products) 

    APOE Assay Products:

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    GenScript Custom Assay Services for APOE
    Browse Enzo Life Sciences for kits & assays
    Cloud-Clone Corp. ELISAs for APOE
    Cloud-Clone Corp. CLIAs for APOE
    Search eBioscience for ELISAs for APOE 
    antibodies-online kits for APOE (55 products) 


    (According to HGNC, IUPHAR, InterPro, ProtoNet, UniProtKB, and/or BLOCKS, Sets of similar genes according to GeneDecks)
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    HGNC Gene Families:
    APOLIPO: Apolipoproteins

    1 InterPro protein domain:
     IPR000074 ApoA1_A4_E

    Graphical View of Domain Structure for InterPro Entry P02649

    ProtoNet protein and cluster: P02649

    1 Blocks protein domain: IPB000074 Apolipoprotein A1/A4/E

    UniProtKB/Swiss-Prot: APOE_HUMAN, P02649
    Similarity: Belongs to the apolipoprotein A1/A4/E family


    Find genes that share domains with APOE           About GenesLikeMe


    (According to 1UniProtKB, Genatlas, LifeMap Discovery™, IUBMB, and/or 2DME, Human phenotypes from GenomeRNAi, Animal models from MGI Mar 06 2013, 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, Vector BioLabs and/or Addgene, Cell Lines from GenScript, ESI BIO, In Situ Hybridization Assays from Advanced Cell Diagnostics, Flow cytometry from eBioscience, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene.)
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    Molecular Function:

         UniProtKB/Swiss-Prot Summary: APOE_HUMAN, P02649
    Function: Mediates the binding, internalization, and catabolism of lipoprotein particles. It can serve as a ligand
    for the LDL (apo B/E) receptor and for the specific apo-E receptor (chylomicron remnant) of hepatic tissues

         Genatlas biochemistry entry for APOE:
    apolipoprotein E,component of VLDL and ApoE receptors,putative susceptibility factor (epsilon 4 allele) for
    agressive multiple sclerosis and for early-onset coronary heart disease

         Gene Ontology (GO): Selected molecular function terms (see all 18):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0001540beta-amyloid binding IDA11305869
    GO:0005319lipid transporter activity IDA17305370
    GO:0005515protein binding IPI12950167
    GO:0005543phospholipid binding IDA4066713
    GO:0008201heparin binding IDA2745454
         
    Find genes that share ontologies with APOE           About GenesLikeMe


    Phenotypes:
         1 GenomeRNAi human phenotype for APOE:
     Decreased G3BP1 protein expres 

         Selected MGI mutant phenotypes (inferred from 17 alleles(MGI details for Apoe) (see all 26):
     adipose tissue  behavior/neurological  cardiovascular system  cellular  digestive/alimentary 
     endocrine/exocrine gland  growth/size/body  hearing/vestibular/ear  hematopoietic system  homeostasis/metabolism 
     immune system  integument  limbs/digits/tail  liver/biliary system  mortality/aging 

    Find genes that share phenotypes with APOE           About GenesLikeMe

    Animal Models:
         MGI mouse knock-outs for APOE: Apoetm4Mae Apoetm1Lmh Apoetm1Bres Apoetm1Unc

       genOway: Develop your customized and physiologically relevant rodent model for APOE

    miRNA
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    Search for qRT-PCR Assays for microRNAs that regulate APOE
    Browse SwitchGear 3'UTR luciferase reporter plasmids
    Inhib. RNA
    Products:
        
    OriGene RNAi products in human, mouse, rat for APOE
    Predesigned siRNA for gene silencing in human, mouse, rat APOE

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

    Clone
    Products:
         
    OriGene clones in human, mouse for APOE (see all 6)
    OriGene ORF clones in mouse, rat for APOE
    OriGene custom cloning services - gene synthesis, subcloning, mutagenesis, variant library, vector shuttling
    GenScript: all cDNA clones in your preferred vector: APOE (NM_000041)
    Sino Biological Human cDNA Clone for APOE
    DNA2.0 Custom Codon Optimized Gene Synthesis Service for APOE
    Vector BioLabs ready-to-use adenovirus/AAV for human, mouse, rat APOE
    Addgene plasmids for APOE 

    Cell Line
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    ESI BIO PureStem Progenitor for APOE: 
    PureStem ES-210, Ecto-ntu Progenitor
    In Situ Assay
    Products:
       

     
    Advanced Cell Diagnostics RNAscope RNA in situ hybridization assays for APOE


    (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
    APOE_HUMAN, P02649: Secreted
    Subcellular locations from COMPARTMENTS: 

    CompartmentConfidence
    extracellular5
    endosome4
    plasma membrane4
    cytoskeleton2
    endoplasmic reticulum2
    golgi apparatus2
    lysosome2
    mitochondrion2
    nucleus2
    peroxisome2
    vacuole2
    cytosol1

    Gene Ontology (GO): Selected cellular component terms (see all 18):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0005576extracellular region TAS--
    GO:0005615extracellular space IDA--
    GO:0005737cytoplasm TAS9622609
    GO:0005769early endosome TAS--
    GO:0005770late endosome IEA--

    Find genes that share ontologies with APOE           About GenesLikeMe


    (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 APOE About   (see all 15)  
    See pathways by source

    SuperPathContained pathways About
    1Statin Pathway
    Statin Pathway0.73
    Statin Pathway, Pharmacodynamics0.73
    2Alzheimer's disease
    Alzheimers Disease0.44
    Alzheimer's disease0.44
    3Lipoprotein metabolism
    Lipoprotein metabolism0.59
    Chylomicron-mediated lipid transport0.00
    Lipid digestion, mobilization, and transport0.59
    HDL-mediated lipid transport0.00
    4Diseases associated with visual transduction
    Visual phototransduction0.44
    Diseases associated with visual transduction0.43
    Retinoid metabolism and transport0.44
    5Binding and Uptake of Ligands by Scavenger Receptors
    Binding and Uptake of Ligands by Scavenger Receptors0.53
    Scavenging by Class A Receptors0.00


    Find genes that share SuperPaths with APOE           About GenesLikeMe

    Pathways by source                                                                                                                                                                 See SuperPaths
    Show all pathways

    1 R&D Systems Pathway for APOE
        A-beta Uptake & Degradation

    2 Downloadable PowerPoint Slides of GeneGlobe Pathway Central Maps for APOE
        Reelin Pathway (Cajal-Retzius cells)
    Alzheimers Disease Pathway

    2 Cell Signaling Technology (CST) Pathways for APOE
        Neuroscience
    Glucose / Energy Metabolism

    1 GeneGo (Thomson Reuters) Pathway for APOE
        Transcription Role of VDR in regulation of genes involved in osteoporosis

    3 BioSystems Pathways for APOE
        Statin Pathway
    Vitamin B12 Metabolism
    Alzheimers Disease


    4 Reactome Pathways for APOE
        Retinoid metabolism and transport
    Scavenging by Class A Receptors
    HDL-mediated lipid transport
    Chylomicron-mediated lipid transport

    1 PharmGKB Pathway for APOE
        Statin Pathway, Pharmacodynamics

    1 Kegg Pathway  (Kegg details for APOE):
        Alzheimer's disease

        Pathway & Disease-focused RT2 Profiler PCR Arrays including APOE (see all 14): 
              Neurogenesis in human mouse rat
              Oxidative Stress in human mouse rat
              Nitric Oxide Signaling Pathway in human mouse rat
              Alzheimer's Disease in human mouse rat
              Drug Metabolism in human mouse rat

    Interactions:

        GeneGlobe Interaction Network for APOE

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

    Selected Interacting proteins for APOE (P026491, 2, 3 ENSP000002524864) via UniProtKB, MINT, STRING, and/or I2D (see all 54)
    InteractantInteraction Details
    GeneCardExternal ID(s)
    HPP007381, 2, 3, ENSP000003481704EBI-1222467,EBI-1220767 MINT-7258801 MINT-7258760 MINT-7258778 MINT-7258819 MINT-7258848 MINT-7258877 MINT-7258791 I2D: score=2 STRING: ENSP00000348170
    CDC37Q165431, 3EBI-1222467,EBI-295634 I2D: score=1 
    ECSITQ9BQ951, 3EBI-1222467,EBI-712452 I2D: score=1 
    ST13P505021, 3EBI-1222467,EBI-357285 I2D: score=1 
    PDCD4Q53EL61, 3, ENSP000002801544EBI-1222467,EBI-935824 I2D: score=1 STRING: ENSP00000280154
    About this table

    Gene Ontology (GO): Selected biological process terms (see all 67):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0000302response to reactive oxygen species NAS11743999
    GO:0001523retinoid metabolic process TAS--
    GO:0001937negative regulation of endothelial cell proliferation IDA9685360
    GO:0002021response to dietary excess IEA--
    GO:0006629lipid metabolic process ----

    Find genes that share ontologies with APOE           About GenesLikeMe



    (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 APOE

    1 HMDB Compound for APOE    About this table
    CompoundSynonyms CAS #PubMed Ids
    HeparinArteven (see all 17)9005-49-6--

    2 DrugBank Compounds for APOE    About this table
    CompoundSynonyms CAS #TypeActionsPubMed Ids
    Human Serum Albumin-- 9048-49-1target--12887764 12860569 17553935 17141733 16554356
    Serum albumin iodonated-- 9048-49-1target--17016423 17378158 17139284 16441928

    Selected Novoseek inferred chemical compound relationships for APOE gene (see all 119)    About this table
    Compound   -log (P-Val)   Hits   PubMed IDs for Articles with Shared Sentences (# sentences)
    cholesterol 88.7 2199 9541497 (7), 11369802 (7), 16185081 (7), 10484608 (7) (see all 99)
    lipid 82.2 1527 15264189 (6), 16295048 (5), 10693931 (5), 15487712 (5) (see all 99)
    24s-hydroxy-cholesterol 67.6 24 15975088 (4), 17822846 (4), 16524875 (3), 12707064 (2) (see all 10)
    xbai 59.1 34 9298741 (2), 16699281 (2), 15543563 (2), 8013886 (2) (see all 23)
    cholesterol ester 58.9 32 8420942 (3), 10870678 (3), 15955471 (2), 12919138 (2) (see all 16)
    lathosterol 53.7 5 8548414 (1), 11726725 (1), 15331430 (1), 1865824 (1)
    phospholipid 52.9 140 1730636 (4), 8908157 (4), 19159618 (3), 1540589 (3) (see all 73)
    homocysteine 52.4 98 17764386 (6), 17243563 (3), 18023533 (2), 17420762 (2) (see all 43)
    dimyristoylphosphatidylcholine 50.5 33 12633731 (3), 10751422 (2), 12364553 (2), 2026270 (1) (see all 11)
    sterol 49 77 10760464 (5), 16254198 (5), 11893773 (5), 11742879 (5) (see all 27)

    8 PharmGKB related drug/compound annotations for APOE gene    About this table
    Drug/compound PharmGKB Annotation
    Antivirals for treatment of HIV infections, combinationsCA  
    atorvastatinCA  
    fenofibrateCA  
    fluvastatinCA  
    pravastatin  CA  
    ritonavirCA  
    rosuvastatinCA  
    simvastatinCA  



    Find genes that share compounds with APOE           About GenesLikeMe



    (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, and/or Addgene, Primers from OriGene, and/or QIAGEN, Flow cytometry from eBioscience )
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    REFSEQ mRNAs for APOE gene: 
    NM_000041.2  

    Unigene Cluster for APOE:

    Apolipoprotein E
    Hs.654439  [show with all ESTs]
    Unigene Representative Sequence: BQ683419
    5 Ensembl transcripts including schematic representations, and UCSC links where relevant:
    ENST00000252486(uc002pab.3) ENST00000446996 ENST00000485628 ENST00000434152
    ENST00000425718
    miRNA
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    Vector BioLabs ready-to-use adenovirus/AAV for human, mouse, rat APOE
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    Primer
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    OriGene qSTAR qPCR primer pairs in human, mouse for APOE
    Pre-validated RT2 qPCR Primer Assay in human, mouse, rat APOE
      QuantiTect SYBR Green Assays in human, mouse, rat APOE
      QuantiFast Probe-based Assays in human, mouse, rat APOE

    Additional mRNA sequence: 

    AK308546.1 AK314898.1 BC003557.1 K00396.1 M12529.1 X00199.1 Z70760.1 

    23 DOTS entries:

    DT.100888329  DT.451248  DT.40133697  DT.97779727  DT.100888334  DT.100888336  DT.97792321  DT.91981242 
    DT.92463553  DT.100888335  DT.92463568  DT.92463567  DT.100045379  DT.100888330  DT.100888341  DT.121427095 
    DT.92015941  DT.92463546  DT.95136088  DT.95136093  DT.95136111  DT.100879799  DT.121121638 

    Selected AceView cDNA sequences (see all 1484):

    BE327636 AI697758 BF940777 AI364378 AI422116 AI347700 AI817710 AI479896 
    BI764894 BC009698 AI824153 BE857311 AW183183 BI822926 BU733040 CB162526 
    AW028061 BI759112 AI423094 AI363024 BE672837 BM992903 AW963768 BE858681 

    GeneLoc Exon Structure

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

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


    ECgene alternative splicing isoforms for APOE

    (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)
    About This Section

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


    APOE expression in embryonic tissues and stem cells    About this table
    Data from LifeMap, the Embryonic Development and Stem Cells Database
     selected tissues (see all 25) fully expand
     
     Brain (Nervous System)    fully expand to see all 7 entries
             Cerebral Cortex
     
     Liver (Hepatobiliary System)    fully expand to see all 2 entries
             Hepatocytes Liver Lobule
             Liver Lobule
     
     Adipose (Muscoskeletal System)    fully expand to see all 2 entries
             Visceral White Adipose
             HyStem+BMP4-induced E15 cells
     
     Bone (Muscoskeletal System)    fully expand to see all 2 entries
             Bone Marrow
             HyStem+BMP4-induced E15 cells
     
     Neural Tube (Nervous System)    fully expand to see all 2 entries
             Metencephalon
    APOE Protein expression data from MOPED1, PaxDb2 and MaxQB3    About this image

    APOE Protein Expression

    SOURCE GeneReport for Unigene cluster: Hs.654439

    UniProtKB/Swiss-Prot: APOE_HUMAN, P02649
    Tissue specificity: Occurs in all lipoprotein fractions in plasma. It constitutes 10-20% of very low density
    lipoproteins (VLDL) and 1-2% of high density lipoproteins (HDL). APOE is produced in most organs. Significant
    quantities are produced in liver, brain, spleen, lung, adrenal, ovary, kidney and muscle

        Pathway & Disease-focused RT2 Profiler PCR Arrays including APOE (see all 14): 
              Neurogenesis in human mouse rat
              Oxidative Stress in human mouse rat
              Nitric Oxide Signaling Pathway in human mouse rat
              Alzheimer's Disease in human mouse rat
              Drug Metabolism in human mouse rat

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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)
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    This gene was present in the common ancestor of chordates.

    Orthologs for APOE gene from Selected species (see all 9)    About this table
    Organism Taxonomic
    classification
    Gene Description Human
    Similarity
    Orthology
    Type
    Details
    mouse
    (Mus musculus)
    Mammalia Apoe1 , 5 apolipoprotein E1, 5 78.68(n)1
    73.38(a)1
      7 (9.94 cM)5
    118161  NM_009696.31  NP_033826.21 
     196961095 
    tropical clawed frog
    (Xenopus tropicalis)
    Amphibia apoe1 apolipoprotein E 43.67(n)
    27.01(a)
      394678  XM_004912006.1  XP_004912063.1 
    zebrafish
    (Danio rerio)
    Actinopterygii apoeb6
    apoea6
    apolipoprotein Ea
    28(a)
    25(a)
    many → 1
    many → 1
    16(26200037-26202754) ENSDARG00000040295
    19(11954418-11958954) ENSDARG00000086370


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

    (Paralogs according to 1HomoloGene,
    2Ensembl, and 3SIMAP, Pseudogenes according to 4Pseudogene.org Build 68)
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    (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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    Polymorphic Variants from UniProtKB/Swiss-Prot
    APOE_HUMAN, P02649: Three common APOE alleles have been identified: APOE*2, APOE*3, and APOE*4. The corresponding three
    major isoforms, E2, E3, and E4, are recognized according to their relative position after isoelectric focusing.
    Different mutations causing the same migration pattern after isoelectric focusing define different isoform
    subtypes. The most common isoform is E3 and is present in 40-90% of the population. Common APOE variants
    influence lipoprotein metabolism in healthy individuals


    Selected SNPs for APOE (see all 195)    About this table                                 

    Genomic DataTranscription Related DataAllele Frequencies
    SNP IDValidClinical
    significance
    Chr 19 posSequence#AA
    Chg
    TypeMore#Allele
    freq
    PopTotal
    sample
    More
    ----------
    rs2016720111,2,,4
    CHyperlipoproteinemia 3 (HLPP3)4 pathogenic145601196(+) AGCCCA/GAGCTG 2 K E mis10--------
    rs4293581,2,,4
    C,F,A,HHyperlipoproteinemia 3 (HLPP3)4 pathogenic145602073(+) ACGTGT/CGCGGC 2 /R /C mis1 ese317Minor allele frequency- C:0.13NA EU CSAM EA NS WA 5820
    rs7694551,2,,4
    C,F,HHyperlipoproteinemia 3 (HLPP3)4 pathogenic145602172(+) AGCTGC/TGTAAG 2 R C mis1 ese311Minor allele frequency- T:0.01NA EU CSAM MN NS WA 1524
    rs74121,2,,4
    C,F,A,HHyperlipoproteinemia 3 (HLPP3)4 pathogenic145602211(+) AGAAGC/TGCCTG 2 R C mis124Minor allele frequency- T:0.08NA EU CSAM MN EA NS WA 6867
    VAR_0427354
    Lipoprotein glomerulopathy (LPG)4--see VAR_0427352 R P mis40--------
    VAR_0006624
    Hyperlipoproteinemia 3 (HLPP3)4--see VAR_0006622 K E mis40--------
    VAR_0427344
    Lipoprotein glomerulopathy (LPG)4--see VAR_0427342 R C mis40--------
    VAR_0006574
    Hyperlipoproteinemia 3 (HLPP3)4--see VAR_0006572 R C mis40--------
    VAR_0006614
    Hyperlipoproteinemia 3 (HLPP3)4--see VAR_0006612 K Q mis40--------
    VAR_0006564
    Hyperlipoproteinemia 3 (HLPP3)4--see VAR_0006562 R S mis40--------

    HapMap Linkage Disequilibrium report for APOE (45409011 - 45412650 bp)

    Structural Variations
         Database of Genomic Variants (DGV) 7 variations for APOE:    About this table    
    Variant IDTypeSubtypePubMed ID
    nsv509747CNV Insertion20534489
    nsv912136CNV Loss21882294
    dgv3950n71CNV Loss21882294
    nsv912134CNV Loss21882294
    nsv912133CNV Loss21882294
    dgv3949n71CNV Loss21882294
    dgv3948n71CNV Loss21882294

    Human Gene Mutation Database (HGMD): APOE
    Site Specific Mutation Identification with PCR Assays
    SeqTarget long-range PCR primers for resequencing APOE
    DNA2.0 Custom Variant and Variant Library Synthesis for APOE

    (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: 107741   
    OMIM disorders: 269600  104310  603075  611771  
    UniProtKB/Swiss-Prot: APOE_HUMAN, P02649
  • Hyperlipoproteinemia 3 (HLPP3) [MIM:107741]: A disorder characterized by the accumulation of
    intermediate-density lipoprotein particles (IDL or broad-beta-lipoprotein) rich in cholesterol. Clinical features
    include xanthomas, yellowish lipid deposits in the palmar crease, or less specific on tendons and on elbows. The
    disorder rarely manifests before the third decade in men. In women, it is usually expressed only after the
    menopause. Note=The disease is caused by mutations affecting the gene represented in this entry. The vast
    majority of the patients are homozygous for APOE*2 alleles. More severe cases of HLPP3 have also been observed in
    individuals heterozygous for rare APOE variants. The influence of APOE on lipid levels is often suggested to have
    major implications for the risk of coronary artery disease (CAD). Individuals carrying the common APOE*4 variant
    are at higher risk of CAD
  • Alzheimer disease 2 (AD2) [MIM:104310]: A late-onset neurodegenerative disorder characterized by
    progressive dementia, loss of cognitive abilities, and deposition of fibrillar amyloid proteins as intraneuronal
    neurofibrillary tangles, extracellular amyloid plaques and vascular amyloid deposits. The major constituent of
    these plaques is the neurotoxic amyloid-beta-APP 40-42 peptide (s), derived proteolytically from the
    transmembrane precursor protein APP by sequential secretase processing. The cytotoxic C-terminal fragments (CTFs)
    and the caspase-cleaved products such as C31 derived from APP, are also implicated in neuronal death.
    Note=Disease susceptibility is associated with variations affecting the gene represented in this entry. The
    APOE*4 allele is genetically associated with the common late onset familial and sporadic forms of Alzheimer
    disease. Risk for AD increased from 20% to 90% and mean age at onset decreased from 84 to 68 years with
    increasing number of APOE*4 alleles in 42 families with late onset AD. Thus APOE*4 gene dose is a major risk
    factor for late onset AD and, in these families, homozygosity for APOE*4 was virtually sufficient to cause AD by
    age 80. The mechanism by which APOE*4 participates in pathogenesis is not known
  • Sea-blue histiocyte disease (SBHD) [MIM:269600]: Characterized by splenomegaly, mild thrombocytopenia
    and, in the bone marrow, numerous histiocytes containing cytoplasmic granules which stain bright blue with the
    usual hematologic stains. The syndrome is the consequence of an inherited metabolic defect analogous to Gaucher
    disease and other sphingolipidoses. Note=The disease is caused by mutations affecting the gene represented in
    this entry
  • Lipoprotein glomerulopathy (LPG) [MIM:611771]: Uncommon kidney disease characterized by proteinuria,
    progressive kidney failure, and distinctive lipoprotein thrombi in glomerular capillaries. Note=The disease is
    caused by mutations affecting the gene represented in this entry
  • Familial hypercholesterolemia (FH) [MIM:143890]: Common autosomal semi-dominant disease that affects
    about 1 in 500 individuals. The receptor defect impairs the catabolism of LDL, and the resultant elevation in
    plasma LDL-cholesterol promotes deposition of cholesterol in the skin (xanthelasma), tendons (xanthomas), and
    coronary arteries (atherosclerosis). Note=The disease is caused by mutations affecting the gene represented in
    this entry

  • Selected diseases for APOE (see all 67):    
    About MalaCards
    age related macular degeneration    mesial temporal lobe epilepsy with hippocampal sclerosis    sea-blue histiocyte syndrome    lipoprotein glomerulopathy
    hyperlipidemia type 3    alzheimer disease risk factor    moderate and severe traumatic brain injury    myocardial infarction susceptibility
    persistent vegetative state    hereditary cerebral amyloid angiopathy    posterior cortical atrophy    lung sarcoma
    temporal lobe epilepsy    creutzfeldt-jakob disease    finnish type amyloidosis    cerebral amyloid angiopathy
    schizophreniform disorder    genetic prion diseases    vascular dementia    wernicke-korsakoff syndrome

    19 diseases from the University of Copenhagen DISEASES database for APOE:
    Alzheimer's disease     Atherosclerosis     Vascular dementia     Coronary heart disease
    Amyloidosis     Cerebrovascular accident     Diabetes mellitus     Familial hyperlipidemia
    Aortic disease     Lewy body dementia     Hypertension     Myocardial infarction
    Down syndrome     Frontotemporal dementia     Abdominal aortic aneurysm     Kidney disease
    Parkinson's disease     Age related macular degeneration     Progressive supranuclear palsy

    Find genes that share disorders with APOE           About GenesLikeMe

    Selected Novoseek inferred disease relationships for APOE gene (see all 94)    About this table

    Disease   -log (P-Val)   Hits   PubMed IDs for Articles with Shared Sentences (# sentences)
    alzheimers disease 95 2575 14757857 (6), 9831633 (5), 11071064 (5), 9468467 (5) (see all 99)
    hyperlipoproteinemia type iii 89.8 89 8175773 (4), 1730728 (3), 8185134 (3), 7772063 (3) (see all 55)
    late onset alzheimer disease 88.1 55 8971103 (4), 7970184 (2), 8840393 (1), 11283204 (1) (see all 35)
    dementia 86.6 681 9678314 (6), 12634288 (5), 9074395 (5), 19720080 (4) (see all 99)
    senile plaques 85.4 257 9100668 (4), 11325345 (4), 7615568 (3), 10487843 (3) (see all 99)
    cerebral amyloid angiopathy 82.6 68 8571412 (2), 15654038 (2), 18755411 (2), 17322072 (2) (see all 43)
    neurofibrillary tangles 82.4 131 10487843 (3), 9018389 (3), 9258912 (2), 2029618 (2) (see all 86)
    atherosclerosis 80.6 547 11369802 (5), 11007687 (5), 7593602 (5), 10933930 (5) (see all 99)
    dementia vascular 77.9 92 8848934 (3), 8786847 (3), 9147873 (3), 15084782 (2) (see all 54)
    hypertriglyceridemia 70.7 101 11337906 (4), 17919884 (3), 11163021 (3), 15576362 (3) (see all 53)

    Genetic Association Database (GAD): APOE
    Human Genome Epidemiology (HuGE) Navigator: APOE (2777 documents)

    Export disorders for APOE 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 APOE gene, integrated from 10 sources (see all 5633):
    (articles sorted by number of sources associating them with APOE)
        Utopia: connect your pdf to the dynamic
    world of online information

    1. Familial splenomegaly: macrophage hypercatabolism of lipoproteins associated with apolipoprotein E mutation [apolipoprotein E (delta149 Leu)]. (PubMed id 11095479)1, 2, 4, 9 Nguyen T.T.... O'Brien T. (J. Clin. Endocrinol. Metab. 2000)
    2. Analysis of association at single nucleotide polymorphisms in the APOE region. (PubMed id 10662539)1, 3, 4 Martin E.R....Vance J.M. (Genomics 2000)
    3. Apolipoprotein E (APOE) polymorphism influences serum APOE levels in Alzheimer's disease patients and centenarians. (PubMed id 12657895)1, 4, 9 Panza F....Capurso A. (Neuroreport 2003)
    4. Effect of apolipoprotein E (apoE) phenotype on the apoE content of CSF-HDL in children. (PubMed id 15936307)1, 4, 9 Hirayama S....Aizawa Y. ( international journal of clinical chemistry 2005)
    5. The influence of serum apolipoprotein E concentration and polymorphism on serum lipid parameters in hemodialysis patients. (PubMed id 15264189)1, 4, 9 Liberopoulos E.N....Elisaf M.S. (Am. J. Kidney Dis. 2004)
    6. The effect of apoE genotype and sex on ApoE plasma concentration is determined by dietary fat in healthy subjects. (PubMed id 19025720)1, 4, 9 Moreno J.A....LA^pez-Miranda J. (Br. J. Nutr. 2009)
    7. Apolipoprotein E in temporal lobe epilepsy: a case-control study. (PubMed id 17264404)1, 4, 9 Kumar A....Luthra K. (Dis. Markers 2006)
    8. Obesity modulates the association among APOE genotype, insulin, and glucose in men. (PubMed id 14694215)1, 4, 9 Elosua R....Ordovas J.M. (Obes. Res. 2003)
    9. Influence of apolipoprotein E, smoking, and alcohol intake on carotid atherosclerosis: National Heart, Lung, and Blood Institute Family Heart Study. (PubMed id 11988615)1, 4, 9 DjoussAc L....Ellison R.C. ( a journal of cerebral circulation 2002)
    10. Variation at the APOE -491 promoter locus is associated with altered brain levels of apolipoprotein E. (PubMed id 12232782)1, 4, 9 Laws S.M....Martins R.N. (Mol. Psychiatry 2002)

    (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: 348 HGNC: 613 AceView: APOEandAPOC1 Ensembl:ENSG00000130203 euGenes: HUgn348
    ECgene: APOE Kegg: 348 H-InvDB: APOE

    (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 APOE Pharmacogenomics, SNPs, Pathways
    ATLAS Chromosomes in Cancer entry for APOE Genetics and Cytogenetics in Oncology and Haematology
    GeneReviewshttp://www.ncbi.nlm.nih.gov/books/NBK1116/?term=APOE[genesymbol]
    SHMPDhttp://shmpd.bii.a-star.edu.sg/gene.php?genestart=A&genename=APOE
    Wikipedia http://en.wikipedia.org/wiki/Apolipoprotein_E
    Protein Spotlighthttp://web.expasy.org/spotlight/back_issues/083

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    Patent Information for APOE gene:
    Search GeneIP for patents involving APOE

    GeneCards and IP:
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