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PRNP Gene

protein-coding   GIFtS: 70
GCID: GC20P004615

Prion Protein

(Previous name: prion protein (p27-30))
(Previous symbols: PRIP, GSS, CJD)
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)
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Aliases
Prion Protein1 2     Creutzfeldt-Jakob Disease1
PRIP1 2 3 5     Fatal Familial Insomnia1
CJD1 2 5     Gerstmann-Strausler-Scheinker Syndrome1
GSS1 2     Prion Protein (P27-30)1
p27-301 2     AltPrP2
ASCR2 3     CD2302
PrP2 3     PrPc2
PrP27-302 3     Major Prion Protein2
PrP33-35C2 3     Prion-Related Protein2
CD230 Antigen2 3     PRP3
KURU2 5     

External Ids:    HGNC: 94491   Entrez Gene: 56212   Ensembl: ENSG000001718677   OMIM: 1766405   UniProtKB: P041563   

Export aliases for PRNP gene to outside databases

Previous GC identifers: GC20P004655 GC20P004662


(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 PRNP Gene:
The protein encoded by this gene is a membrane glycosylphosphatidylinositol-anchored glycoprotein that tends to
aggregate into rod-like structures. The encoded protein contains a highly unstable region of five tandem
octapeptide repeats. This gene is found on chromosome 20, approximately 20 kbp upstream of a gene which encodes a
biochemically and structurally similar protein to the one encoded by this gene. Mutations in the repeat region as
well as elsewhere in this gene have been associated with Creutzfeldt-Jakob disease, fatal familial insomnia,
Gerstmann-Straussler disease, Huntington disease-like 1, and kuru. An overlapping open reading frame has been
found for this gene that encodes a smaller, structurally unrelated protein, AltPrp. Alternative splicing results
in multiple transcript variants. (provided by RefSeq, Oct 2012)

GeneCards Summary for PRNP Gene:
PRNP (prion protein) is a protein-coding gene. Diseases associated with PRNP include prion disease with protracted course, and familial alzheimer-like prion disease. GO annotations related to this gene include copper ion binding and identical protein binding.

UniProtKB/Swiss-Prot: PRIO_HUMAN, P04156
Function: May play a role in neuronal development and synaptic plasticity. May be required for neuronal myelin
sheath maintenance. May play a role in iron uptake and iron homeostasis. Soluble oligomers are toxic to cultured
neuroblastoma cells and induce apoptosis (in vitro). Association with GPC1 (via its heparan sulfate chains)
targets PRNP to lipid rafts. Also provides Cu(2+) or ZN(2+) for the ascorbate-mediated GPC1 deaminase degradation
of its heparan sulfate side chains (By similarity)

Gene Wiki entry for PRNP 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_000020.11  NC_018931.2  NT_011387.9  
Regulatory elements:
   Regulatory transcription factor binding sites in the PRNP gene promoter:
         p53   AP-1   ATF-2   c-Jun   
         Other transcription factors

Browse SwitchGear Promoter luciferase reporter plasmids
   Search Chromatin IP Primers for PRNP

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


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

Entrez Gene cytogenetic band: 20p13   Ensembl cytogenetic band:  20p13   HGNC cytogenetic band: 20p13

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

GeneLoc information about chromosome 20         GeneLoc Exon Structure

GeneLoc location for GC20P004615:  view genomic region     (about GC identifiers)

Start:
4,666,797 bp from pter      End:
4,682,236 bp from pter
Size:
15,440 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, and/or Cloud-Clone Corp.)
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UniProtKB/Swiss-Prot: PRIO_HUMAN, P04156 (See protein sequence)
Recommended Name: Major prion protein precursor  
Size: 253 amino acids; 27661 Da
Subunit: Monomer and homodimer. Has a tendency to aggregate into amyloid fibrils containing a cross-beta spine,
formed by a steric zipper of superposed beta-strands. Soluble oligomers may represent an intermediate stage on
the path to fibril formation. Copper binding may promote oligomerization. Interacts with GRB2, APP, ERI3/PRNPIP
and SYN1. Mislocalized cytosolically exposed PrP interacts with MGRN1; this interaction alters MGRN1 subcellular
location and causes lysosomal enlargement (By similarity). Interacts with KIAA1191
Miscellaneous: This protein is produced by a bicistronic gene which also produces the The alternative prion
protein/AltPrP from an overlapping reading frame
Miscellaneous: The alternative prion protein/AltPrP (AC F7VJQ1) and PRNP have no apparent direct functional
relation since a mutation that removes the start codon of the AltPrP has no apparent effect on the biology of
PRNP. In mouse and hamster, the alternative initiation AUG codon is absent and is replaced by a GUG codon
Selected PDB 3D structures from and Proteopedia for PRNP (see all 49):
1E1G (3D)        1E1J (3D)        1E1P (3D)        1E1S (3D)        1E1U (3D)        1E1W (3D)    
Secondary accessions: O60489 P78446 Q15216 Q15221 Q27H91 Q5QPB4 Q8TBG0 Q96E70 Q9UP19
Alternative initiation: 2 isoforms:  P04156-1   P04156-2   

Explore the universe of human proteins at neXtProt for PRNP: NX_P04156

Explore proteomics data for PRNP at MOPED

Post-translational modifications: 

  • The glycosylation pattern (the amount of mono-, di- and non-glycosylated forms or glycoforms) seems to differ in
    normal and CJD prion1
  • Isoform 2 is sumoylated with SUMO1 (By similarity)1
  • Glycosylation2 at Thr95, Asn181, Thr193, Asn197
  • Modification sites at PhosphoSitePlus

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

    REFSEQ proteins (6 alternative transcripts): 
    NP_000302.1  NP_001073590.1  NP_001073591.1  NP_001073592.1  NP_001258490.1  NP_898902.1  

    ENSEMBL proteins: 
     ENSP00000368752   ENSP00000399376   ENSP00000411599   ENSP00000415284  
    Reactome Protein details: P04156

    PRNP Human Recombinant Protein Products:

    EMD Millipore Purified and/or Recombinant PRNP Protein
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    Browse recombinant and purified proteins available from Enzo Life Sciences
    OriGene Purified Protein for PRNP
    OriGene Protein Over-expression Lysate for PRNP
    OriGene Custom MassSpec
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    GenScript Custom Purified and Recombinant Proteins Services for PRNP
    Novus Biologicals PRNP Proteins
    Novus Biologicals PRNP Lysate
    Sino Biological Recombinant Protein for PRNP
    Sino Biological Cell Lysate for PRNP
    ProSpec Recombinant Protein for PRNP
    Cloud-Clone Corp. Proteins for PRNP

    PRNP Antibody Products:

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    OriGene Antibodies for PRNP
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    Novus Biologicals PRNP Antibodies
    Abcam antibodies for PRNP
    Cloud-Clone Corp. Antibodies for PRNP
    ThermoFisher Antibody for PRNP
    LSBio Antibodies in human, mouse, rat for PRNP

    PRNP Assay Products:

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


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

    3 InterPro protein domains:
     IPR025860 Prion_N_dom
     IPR022416 Prion/Doppel_prot_b-ribbon_dom
     IPR000817 Prion

    Graphical View of Domain Structure for InterPro Entry P04156

    ProtoNet protein and cluster: P04156

    1 Blocks protein domain: IPB000817 Prion protein

    UniProtKB/Swiss-Prot: PRIO_HUMAN, P04156
    Domain: The normal, monomeric form, PRPN(C), has a mainly alpha-helical structure. Misfolding of this form
    produces a disease-associated, protease-resistant form, PRPN (Sc), accompanied by a large increase of the
    beta-sheet content and formation of amyloid fibrils. These fibrils consist of a cross-beta spine, formed by a
    steric zipper of superposed beta-strands. Disease mutations may favor intermolecular contacts via short beta
    strands, and may thereby trigger oligomerization. In addition, the heparan-sulfate proteoglycan, GPC1, promotes
    the association of PRPN (C) to lipid rafts and appears to facilitate the conversion to PRPN (Sc)
    Domain: Contains an N-terminal region composed of octamer repeats. At low copper concentrations, the sidechains of
    His residues from three or four repeats contribute to the binding of a single copper ion. Alternatively, a copper
    ion can be bound by interaction with the sidechain and backbone amide nitrogen of a single His residue. The
    observed copper binding stoichiometry suggests that two repeat regions cooperate to stabilize the binding of a
    single copper ion. At higher copper concentrations, each octamer can bind one copper ion by interactions with the
    His sidechain and Gly backbone atoms. A mixture of binding types may occur, especially in the case of octamer
    repeat expansion. Copper binding may stabilize the conformation of this region and may promote oligomerization
    Similarity: Belongs to the prion family


    PRNP 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: PRIO_HUMAN, P04156
    Function: May play a role in neuronal development and synaptic plasticity. May be required for neuronal myelin
    sheath maintenance. May play a role in iron uptake and iron homeostasis. Soluble oligomers are toxic to cultured
    neuroblastoma cells and induce apoptosis (in vitro). Association with GPC1 (via its heparan sulfate chains)
    targets PRNP to lipid rafts. Also provides Cu(2+) or ZN(2+) for the ascorbate-mediated GPC1 deaminase degradation
    of its heparan sulfate side chains (By similarity)

         Genatlas biochemistry entry for PRNP:
    prion protein (p27-30)

         Gene Ontology (GO): Selected molecular function terms (see all 7):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0005507copper ion binding TAS16294306
    GO:0005515protein binding IPI16286452
    GO:0008017microtubule binding IDA16004966
    GO:0015631tubulin binding IDA16004966
    GO:0042802identical protein binding IPI16286452
         
    PRNP for ontologies           About GeneDecksing


    Phenotypes:
         Selected MGI mutant phenotypes (inferred from 28 alleles(MGI details for Prnp) (see all 16):
     behavior/neurological  cellular  growth/size/body  hematopoietic system  homeostasis/metabolism 
     immune system  limbs/digits/tail  mortality/aging  muscle  nervous system 
     no phenotypic analysis  normal  other  reproductive system  skeleton 

    PRNP for phenotypes           About GeneDecksing

    Animal Models:
         MGI mouse knock-outs for PRNP: Prnptm2Tuzi Prnptm1Cwe Prnptm1Tuzi Prnptm2Rcm Prnp/PrndPrnp/tm1Dwm Prnp/PrndPrnp/tm1Aag
                                                         Prnptm1Miy Prnptm2.1Cwe Prnptm2Edin Prnptm1Ito

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

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

    miRNA
    Products:
        
    miRTarBase miRNAs that target PRNP:
    hsa-mir-148b-3p (MIRT019398), hsa-mir-215-5p (MIRT024424), hsa-mir-193b-3p (MIRT016426), hsa-mir-130b-3p (MIRT020222), hsa-mir-192-5p (MIRT026442), hsa-mir-148a-3p (MIRT026010), hsa-mir-615-3p (MIRT040276), hsa-mir-16-5p (MIRT031685)

    Block miRNA regulation of human, mouse, rat PRNP using miScript Target Protectors
    Selected qRT-PCR Assays for microRNAs that regulate PRNP (see all 37):
    hsa-miR-142-5p hsa-miR-548j hsa-miR-607 hsa-miR-548k hsa-miR-301a hsa-miR-219-5p hsa-miR-548l hsa-miR-548a-5p
    SwitchGear 3'UTR luciferase reporter plasmidPRNP 3' UTR sequence
    Inhib. RNA
    Products:
        
    OriGene RNAi products in human, mouse, rat for PRNP
    Predesigned siRNA for gene silencing in human, mouse, rat PRNP

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

    Clone
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    OriGene ORF clones in mouse, rat for PRNP
    OriGene custom cloning services - gene synthesis, subcloning, mutagenesis, variant library, vector shuttling
    GenScript: all cDNA clones in your preferred vector (see all 5): PRNP (NM_000311)
    Sino Biological Human cDNA Clone for PRNP
    DNA2.0 Custom Codon Optimized Gene Synthesis Service for PRNP
    Vector BioLabs ready-to-use adenovirus/AAV for human, mouse, rat PRNP

    Cell Line
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    Browse ESI BIO Cell Lines and PureStem Progenitors for PRNP 
    In Situ Assay
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    Advanced Cell Diagnostics RNAscope RNA in situ hybridization assays for PRNP


    (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
    PRIO_HUMAN, P04156: Cell membrane; Lipid-anchor, GPI-anchor. Golgi apparatus. Note=Targeted to lipid rafts via
    association with the heparan sulfate chains of GPC1. Colocates, in the presence of CU(2+), to vesicles in para-
    and perinuclear regions, where both proteins undergo internalization. Heparin displaces PRNP from lipid rafts and
    promotes endocytosis
    PRIO_HUMAN, P04156: Isoform 2: Cytoplasm. Nucleus. Note=Accumulates outside the secretory route in the
    cytoplasm, from where it relocates to the nucleus
    Subcellular locations from COMPARTMENTS: 

    CompartmentConfidence
    golgi apparatus5
    nucleus5
    plasma membrane5
    endoplasmic reticulum4
    cytoskeleton2
    cytosol2
    endosome2
    extracellular2
    lysosome2
    mitochondrion2
    vacuole2
    peroxisome1

    Gene Ontology (GO): Selected cellular component terms (see all 14):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0005634nucleus IEA--
    GO:0005730nucleolus ----
    GO:0005737cytoplasm TAS16004966
    GO:0005741mitochondrial outer membrane IDA--
    GO:0005783endoplasmic reticulum ISS--

    PRNP 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 PRNP About                                                                                                See pathways by source

    SuperPathContained pathways About
    1L1CAM interactions
    Axon guidance0.63
    Developmental Biology0.63
    2NCAM signaling for neurite out-growth
    NCAM1 interactions0.59
    NCAM signaling for neurite out-growth0.59
    3Prion diseases
    Prion diseases
    4Glypican 1 network
    Glypican 1 network

    Pathways by source                                                                                                                                                                 See SuperPaths
    Show all pathways


    1 BioSystems Pathway for PRNP
        Glypican 1 network


    1 Reactome Pathway for PRNP
        NCAM1 interactions


    1 Kegg Pathway  (Kegg details for PRNP):
        Prion diseases


    PRNP for pathways           About GeneDecksing

        Pathway & Disease-focused RT2 Profiler PCR Arrays including PRNP: 
              Oxidative Stress in human mouse rat
              Nitric Oxide Signaling Pathway in human mouse rat
              Apoptosis 384HT in human mouse rat

    Interactions:

        GeneGlobe Interaction Network for PRNP

    Selected Interacting proteins for PRNP (P041561, 2, 3) via UniProtKB, MINT, STRING, and/or I2D (see all 123)
    InteractantInteraction Details
    GeneCardExternal ID(s)
    PRNPP239071, 2EBI-977302,EBI-7670302 MINT-8302730 MINT-8302705 MINT-8302718 EBI-977302,EBI-7430632 MINT-8302667 MINT-8204296 MINT-8302653 MINT-8302679 MINT-8204515
    BAG6P463792, 3MINT-63361 I2D: score=5 
    ENSG00000096155P463792, 3MINT-63361 I2D: score=5 
    ENSG00000227761P463792, 3MINT-63361 I2D: score=5 
    ENSG00000228760P463792, 3MINT-63361 I2D: score=5 
    About this table

    Gene Ontology (GO): Selected biological process terms (see all 18):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0001933negative regulation of protein phosphorylation ISS--
    GO:0006878cellular copper ion homeostasis NAS16004966
    GO:0006979response to oxidative stress ISS--
    GO:0007050cell cycle arrest IEA--
    GO:0007411axon guidance TAS--

    PRNP 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 

    Compounds for PRNP available from Tocris Bioscience    About this table
    CompoundAction CAS #
    PLP (139-151)Encephalitogenic myelin proteolipid fragment[122018-58-0]
    ONO 2506Inhibits S100B synthesis; neuroprotective[185517-21-9]
    C3bot (154-182)Neurotrophic fragment of clostridial C3 protein[1246280-79-4]
    MOG (35-55)Encephalitogenic myelin oligodendrocyte glycoprotein fragment[149635-73-4]
    Nogo-66 (1-40)Competitive antagonist for Nogo-66 receptor; promotes neuron regeneration[475221-20-6]

    1 DrugBank Compound for PRNP    About this table
    CompoundSynonyms CAS #TypeActionsPubMed Ids
    Tetracycline-- 60-54-8targetinhibitor11752352 18365024

    Selected Novoseek inferred chemical compound relationships for PRNP gene (see all 58)    About this table
    Compound   -log (P-Val)   Hits   PubMed IDs for Articles with Shared Sentences (# sentences)
    methionine 75.9 149 19416900 (2), 17709374 (2), 15542057 (2), 8618678 (2) (see all 93)
    valine 74.9 91 9748018 (3), 17709374 (2), 8461023 (2), 16606639 (2) (see all 55)
    copper 48.2 103 11677424 (4), 18280261 (3), 10708581 (3), 11900542 (3) (see all 39)
    clds 45.8 4 16953297 (2), 11781132 (2)
    guanidine thiocyanate 44.4 1 12817879 (1)
    quinacrine 34.2 1 12857915 (1)
    guanidine hydrochloride 29.8 12 12161431 (4), 7761460 (1), 16219367 (1), 10529232 (1)
    asparagine 21.5 8 9521257 (1), 7767490 (1), 19269662 (1), 1684756 (1) (see all 6)
    proline 20.2 7 11566872 (1), 18955686 (1), 20154442 (1), 8461023 (1) (see all 6)
    polysaccharide 20.2 18 8530433 (2), 7678300 (1), 19226372 (1), 17029785 (1) (see all 10)



    PRNP 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,
    Conferences by KenesGroup, 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 PRNP gene (6 alternative transcripts): 
    NM_000311.3  NM_001080121.1  NM_001080122.1  NM_001080123.1  NM_001271561.1  NM_183079.2  

    Unigene Cluster for PRNP:

    Prion protein
    Hs.472010  [show with all ESTs]
    Unigene Representative Sequence: NM_000311
    4 Ensembl transcripts including schematic representations, and UCSC links where relevant:
    ENST00000379440(uc002wkt.1 uc002wkv.3 uc002wkw.3 uc002wkx.3 uc002wky.3)
    ENST00000430350(uc002wku.3) ENST00000424424 ENST00000457586
    Congresses - knowledge worth sharing:
    European Congress of Clinical Microbiology and Infectious Diseases (ECCMID) 10 - 13 May 2014

    miRNA
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    Block miRNA regulation of human, mouse, rat PRNP using miScript Target Protectors
    Selected qRT-PCR Assays for microRNAs that regulate PRNP (see all 37):
    hsa-miR-142-5p hsa-miR-548j hsa-miR-607 hsa-miR-548k hsa-miR-301a hsa-miR-219-5p hsa-miR-548l hsa-miR-548a-5p
    SwitchGear 3'UTR luciferase reporter plasmidPRNP 3' UTR sequence
    Inhib. RNA
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    Predesigned siRNA for gene silencing in human, mouse, rat PRNP
    Clone
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    OriGene ORF clones in mouse, rat for PRNP
    OriGene custom cloning services - gene synthesis, subcloning, mutagenesis, variant library, vector shuttling
    GenScript: all cDNA clones in your preferred vector (see all 5): PRNP (NM_000311)
    DNA2.0 Custom Codon Optimized Gene Synthesis Service for PRNP
    Vector BioLabs ready-to-use adenovirus/AAV for human, mouse, rat PRNP
    Primer
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    OriGene qPCR primer pairs and template standards for PRNP
    OriGene qSTAR qPCR primer pairs in human, mouse for PRNP
    Pre-validated RT2 qPCR Primer Assay in human, mouse, rat PRNP
      QuantiTect SYBR Green Assays in human, mouse, rat PRNP
      QuantiFast Probe-based Assays in human, mouse, rat PRNP

    Additional mRNA sequence: 

    AB300823.1 AB300824.1 AK090575.1 AK293312.1 AK295415.1 AK295943.1 AK312276.1 AY008282.1 
    AY569456.1 BC012844.1 BC016809.1 BC022532.1 BT019496.1 CR542039.1 CR542072.1 M13899.1 
    X82545.1 

    Selected DOTS entries (see all 31):

    DT.92456884  DT.120809501  DT.91729019  DT.100882026  DT.100882036  DT.92456894  DT.100882031  DT.92456882 
    DT.95116132  DT.101976293  DT.100030812  DT.120809855  DT.92456889  DT.92456883  DT.100882034  DT.95116141 
    DT.120809636  DT.120809922  DT.120809461  DT.92456872  DT.100882029  DT.120809359  DT.120809384  DT.120809534 

    Selected AceView cDNA sequences (see all 508):

    AI350081 BM312237 BM999821 BQ893030 AL556513 CB106311 BC012844 BM311109 
    BP352202 BP348938 R96394 BQ447361 CA430705 BU627167 BX387765 BM352180 
    AI358979 CR613118 BP356247 BM992911 NM_000311 CA416614 BU683405 N48643 

    GeneLoc Exon Structure

    Selected Alternative Splicing Database (ASD) splice patterns (SP) for PRNP (see all 7)    About this scheme

    ExUns: 1a · 1b ^ 2a · 2b ^ 3a · 3b · 3c ^ 4
    SP1:              -     -           -     -         
    SP2:              -     -                           
    SP3:              -     -                           
    SP4:              -     -                           
    SP5:              -     -                           


    ECgene alternative splicing isoforms for PRNP

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


    PRNP expression in embryonic tissues and stem cells    About this table
    Data from LifeMap, the Embryonic Development and Stem Cells Database
     selected tissues (see all 23) fully expand
     
     Kidney (Urinary System)    fully expand to see all 10 entries
             Loop of Henle Cells Loop of Henle
             Metanephros
     
     Brain (Nervous System)    fully expand to see all 4 entries
             Mature Endothelial Cells Blood Brain Barrier
             Cerebellum
     
     Epithelial Cells
             Loop of Henle Cells Loop of Henle
     
     Endothelium (Cardiovascular System)    fully expand to see all 2 entries
             Extraembryonic Angioblasts Extraembryonic Capillary Plexus
     
     Testis (Reproductive System)
             Epididymis
    PRNP Protein expression data from MOPED1, PaxDb2 and MaxQB3    About this image

    PRNP Protein Expression

    SOURCE GeneReport for Unigene cluster: Hs.472010
        Pathway & Disease-focused RT2 Profiler PCR Arrays including PRNP: 
              Oxidative Stress in human mouse rat
              Nitric Oxide Signaling Pathway in human mouse rat
              Apoptosis 384HT in human mouse rat

    Primer
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    Advanced Cell Diagnostics RNAscope RNA in situ hybridization assays for PRNP

    (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 PRNP gene from Selected species (see all 9)    About this table
    Organism Taxonomic
    classification
    Gene Description Human
    Similarity
    Orthology
    Type
    Details
    mouse
    (Mus musculus)
    Mammalia Prnp1 , 5 prion protein1, 5 84.13(n)1
    87.7(a)1
      2 (64.07 cM)5
    191221  NM_001278256.11  NP_001265185.11 
     1319099285 
    chicken
    (Gallus gallus)
    Aves PRNP6
    Gallus gallus prion protein (PRNP), mRNA.
    36(a)
    1 ↔ 1
    22(431948-436437)
    lizard
    (Anolis carolinensis)
    Reptilia --
    --
    Major prion protein
    36(a)
    31(a)
    many → 1
    many → 1
    GL343406.1(899252-900013)
    GL343406.1(889243-890645)


    ENSEMBL Gene Tree for PRNP (if available)
    TreeFam Gene Tree for PRNP (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
    PRIO_HUMAN, P04156: The five tandem octapeptide repeats region is highly unstable. Insertions or deletions of
    octapeptide repeat units are associated to prion disease


    Selected SNPs for PRNP (see all 422)    About this table    
    Genomic DataTranscription Related DataAllele Frequencies
    SNP IDValidClinical
    significance
    Chr 20 posSequence#AA
    Chg
    TypeMore#Allele
    freq
    PopTotal
    sample
    More
    ----------
    VAR_0087514
    Creutzfeldt-Jakob disease (CJD)4--see VAR_0087512 V I mis40--------
    VAR_0064764
    Gerstmann-Straussler disease (GSD)4--see VAR_0064762 Q R mis40--------
    VAR_0087524
    Creutzfeldt-Jakob disease (CJD)4--see VAR_0087522 E Q mis40--------
    VAR_0064654
    Gerstmann-Straussler disease (GSD)4--see VAR_0064652 P L mis40--------
    VAR_0087494
    Creutzfeldt-Jakob disease (CJD)4--see VAR_0087492 E K mis40--------
    VAR_0064744
    Creutzfeldt-Jakob disease (CJD)4--see VAR_0064742 R H mis40--------
    VAR_0142644
    Gerstmann-Straussler disease (GSD)4--see VAR_0142642 G V mis40--------
    VAR_0064694
    Fatal familial insomnia (FFI)4--see VAR_0064692 D N mis40--------
    VAR_0064734
    Creutzfeldt-Jakob disease (CJD)4--see VAR_0064732 E K mis40--------
    VAR_0064704
    Creutzfeldt-Jakob disease (CJD)4--see VAR_0064702 V I mis40--------

    HapMap Linkage Disequilibrium report for PRNP (4666797 - 4682236 bp)

    Structural Variations
         Database of Genomic Variants (DGV) 1 variation for PRNP:    About this table    
    Variant IDTypeSubtypePubMed ID
    nsv912627CNV Gain21882294

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

    Site Specific Mutation Identification with PCR Assays
    SeqTarget long-range PCR primers for resequencing PRNP
    DNA2.0 Custom Variant and Variant Library Synthesis for PRNP

    (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.)
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    OMIM gene information: 176640   
    OMIM disorders: 123400  137440  600072  606688  603218  245300  
    UniProtKB/Swiss-Prot: PRIO_HUMAN, P04156
  • Note=PrP is found in high quantity in the brain of humans and animals infected with neurodegenerative
    diseases known as transmissible spongiform encephalopathies or prion diseases, like: Creutzfeldt-Jakob disease
    (CJD), fatal familial insomnia (FFI), Gerstmann-Straussler disease (GSD), Huntington disease-like type 1 (HDL1)
    and kuru in humans; scrapie in sheep and goat; bovine spongiform encephalopathy (BSE) in cattle; transmissible
    mink encephalopathy (TME); chronic wasting disease (CWD) of mule deer and elk; feline spongiform encephalopathy
    (FSE) in cats and exotic ungulate encephalopathy (EUE) in nyala and greater kudu. The prion diseases illustrate
    three manifestations of CNS degeneration: (1) infectious (2) sporadic and (3) dominantly inherited forms. TME,
    CWD, BSE, FSE, EUE are all thought to occur after consumption of prion-infected foodstuffs
  • Creutzfeldt-Jakob disease (CJD) [MIM:123400]: Occurs primarily as a sporadic disorder (1 per million),
    while 10-15% are familial. Accidental transmission of CJD to humans appears to be iatrogenic (contaminated human
    growth hormone (HGH), corneal transplantation, electroencephalographic electrode implantation, etc.).
    Epidemiologic studies have failed to implicate the ingestion of infected animal meat in the pathogenesis of CJD
    in human. The triad of microscopic features that characterize the prion diseases consists of (1) spongiform
    degeneration of neurons, (2) severe astrocytic gliosis that often appears to be out of proportion to the degree
    of nerve cell loss, and (3) amyloid plaque formation. CJD is characterized by progressive dementia and myoclonic
    seizures, affecting adults in mid-life. Some patients present sleep disorders, abnormalities of high cortical
    function, cerebellar and corticospinal disturbances. The disease ends in death after a 3-12 months illness.
    Note=The disease is caused by mutations affecting the gene represented in this entry
  • Fatal familial insomnia (FFI) [MIM:600072]: Autosomal dominant disorder and is characterized by neuronal
    degeneration limited to selected thalamic nuclei and progressive insomnia. Note=The disease is caused by
    mutations affecting the gene represented in this entry
  • Gerstmann-Straussler disease (GSD) [MIM:137440]: A rare inherited prion disease characterized by adult
    onset of memory loss, dementia, ataxia, and pathologic deposition of amyloid-like plaques in the brain. GSD
    presents with progressive limb and truncal ataxia, dysarthria, and cognitive decline in the thirties and forties,
    and the average disease duration is 7 years. Note=The disease is caused by mutations affecting the gene
    represented in this entry
  • Huntington disease-like 1 (HDL1) [MIM:603218]: Autosomal dominant, early-onset neurodegenerative disorder
    with prominent psychiatric features. Note=The disease is caused by mutations affecting the gene represented in
    this entry
  • Kuru (KURU) [MIM:245300]: Kuru is transmitted during ritualistic cannibalism, among natives of the New
    Guinea highlands. Patients exhibit various movement disorders like cerebellar abnormalities, rigidity of the
    limbs, and clonus. Emotional lability is present, and dementia is conspicuously absent. Death usually occurs from
    3 to 12 month after onset. Note=The disease is caused by mutations affecting the gene represented in this entry
  • Spongiform encephalopathy with neuropsychiatric features (SENF) [MIM:606688]: Autosomal dominant
    presenile dementia with a rapidly progressive and protracted clinical course. The dementia was characterized
    clinically by frontotemporal features, including early personality changes. Some patients had memory loss,
    several showed aggressiveness, hyperorality and verbal stereotypy, others had parkinsonian symptoms. Note=The
    disease is caused by mutations affecting the gene represented in this entry

  • Selected diseases for PRNP (see all 91):    About MalaCards
    prion disease with protracted course    familial alzheimer-like prion disease    huntington disease-like 1    scrapie
    cerebral amyloid angiopathy, prnp-related    fatal familial insomnia    creutzfeldt-jakob syndrome    familial creutzfeldt-jakob disease
    gerstmann-straussler-scheinker disease    genetic prion diseases    kuru encephalopathy    insomnia
    variant creutzfeldt-jakob disease    bovine spongiform encephalopathy    primary progressive aphasia    huntington's disease
    akinetic mutism    chronic wasting disease    mutism    prion disease

    11 diseases from the University of Copenhagen DISEASES database for PRNP:
    Scrapie     Bovine spongiform encephalopathy     Chronic wasting disease     Fatal familial insomnia
    Kuru encephalopathy     Creutzfeldt-Jakob syndrome     Gerstmann-Straussler-Scheinker disease     Toxic encephalopathy
    Akinetic mutism     Alzheimer's disease     Neuroblastoma

    PRNP for disorders           About GeneDecksing


    Congresses - knowledge worth sharing:
    The International Symposium on Pneumococci and Pneumococcal Diseases (ISPPD) 9 - 13 March 2014
    Alzheimer's & Parkinson's Diseases Congress (ADPD) 18 - 22 March 2015

    Selected Novoseek inferred disease relationships for PRNP gene (see all 84)    About this table

    Disease   -log (P-Val)   Hits   PubMed IDs for Articles with Shared Sentences (# sentences)
    prion diseases 98 690 7913756 (7), 7774117 (5), 17360589 (4), 18571782 (4) (see all 99)
    creutzfeldt-jakob disease 97.6 256 10762506 (3), 19092329 (2), 16217673 (2), 19703264 (2) (see all 99)
    gerstmann-straussler-scheinker disease 95.5 48 11087738 (3), 1677605 (1), 1686599 (1), 8097911 (1) (see all 41)
    insomnia fatal familial 94.6 36 1346338 (4), 19571725 (2), 8270114 (1), 9521257 (1) (see all 30)
    scrapie 94.4 246 7902565 (4), 11119579 (4), 1969126 (4), 1348570 (3) (see all 99)
    familial creutzfeldt-jakob disease 94.2 30 1351274 (1), 8270114 (1), 11568919 (1), 7767490 (1) (see all 28)
    kuru 94 39 8097911 (2), 19923577 (2), 9034563 (2), 18849292 (2) (see all 27)
    encephalopathy bovine spongiform 92.2 34 16141216 (2), 17947547 (1), 20429907 (1), 15107244 (1) (see all 27)
    neurodegenerative diseases 81.9 77 16055747 (3), 7913755 (1), 9003061 (1), 9276441 (1) (see all 64)
    new variant creutzfeldt-jakob disease 78 3 11833672 (1), 19495414 (1), 10878555 (1)

    GeneTests: PRNP
    GeneReviews: PRNP
    Genetic Association Database (GAD): PRNP
    Human Genome Epidemiology (HuGE) Navigator: PRNP (97 documents)

    Export disorders for PRNP 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 PRNP gene, integrated from 10 sources (see all 1296):
    (articles sorted by number of sources associating them with PRNP)
        Utopia: connect your pdf to the dynamic
    world of online information

    1. PRNP mutations in a series of apparently sporadic neurodegenerative dementias in China. (PubMed id 18425766)1, 4, 9 Zheng L....Jianping J. (Am. J. Med. Genet. B Neuropsychiatr. Genet. 2008)
    2. Sporadic--but not variant--Creutzfeldt-Jakob disease is associated with polymorphisms upstream of PRNP exon 1. (PubMed id 11704923)1, 4, 9 Mead S....Collinge J. (Am. J. Hum. Genet. 2001)
    3. Significant association of a M129V independent polymorphism in the 5' UTR of the PRNP gene with sporadic Creutzfeldt-Jakob disease in a large German case-control study. (PubMed id 17047093)1, 4, 9 Vollmert C....Kretzschmar H.A. (J. Med. Genet. 2006)
    4. Exclusion of mutations in the PRNP, JPH3, TBP, ATN1, CREBBP, POU3F2 and FTL genes as a cause of disease in Portuguese patients with a Huntington-like phenotype. (PubMed id 16858508)1, 4, 9 Costa M.d.o. .C....Maciel P. (J. Hum. Genet. 2006)
    5. Molecular features of the copper binding sites in the octarepeat domain of the prion protein. (PubMed id 11900542)1, 2, 9 Burns C.S.... Millhauser G.L. (Biochemistry 2002)
    6. Identification of three novel mutations (E196K, V203I, E211Q) in the prion protein gene (PRNP) in inherited prion diseases with Creutzfeldt-Jakob disease phenotype. (PubMed id 10790216)1, 2, 9 Peoc'h K.... Laplanche J.-L. (Hum. Mutat. 2000)
    7. Molecular genetics of human prion diseases in Germany. (PubMed id 10987652)1, 2, 9 Windl O.... Kretzschmar H.A. (Hum. Genet. 1999)
    8. Genetic risk factors for variant Creutzfeldt-Jakob disease: a genome-wide association study. (PubMed id 19081515)1, 4, 9 Mead S....Collinge J. (Lancet Neurol 2009)
    9. Earlier onset of Alzheimer's disease: risk polymorphisms within PRNP, PRND, CYP46, and APOE genes. (PubMed id 19363267)1, 4, 9 Golanska E....Corder E.H. (J. Alzheimers Dis. 2009)
    10. Influence of homozygosity for methionine at codon 129 of the human prion gene on the onset of neurological and hepatic symptoms in Wilson disease. (PubMed id 16831968)1, 4, 9 Merle U....Gessner R. (Arch. Neurol. 2006)

    (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: 5621 HGNC: 9449 AceView: PRNP Ensembl:ENSG00000171867 euGenes: HUgn5621
    ECgene: PRNP Kegg: 5621 H-InvDB: PRNP

    (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 PRNP Pharmacogenomics, SNPs, Pathways
    The Official Mad Cow Disease Home Pagehttp://www.mad-cow.org/
    GeneReviewshttp://www.ncbi.nlm.nih.gov/books/NBK1116/?term=PRNP[genesymbol]
    Wikipedia http://en.wikipedia.org/wiki/PRNP

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

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



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