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VHL Gene

protein-coding   GIFtS: 68
GCID: GC03P010200

Von Hippel-Lindau Tumor Suppressor, E3 Ubiquitin Protein...

(Previous names: von Hippel-Lindau syndrome, von Hippel-Lindau tumor suppressor)
  See VHL-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
Von Hippel-Lindau Tumor Suppressor, E3 Ubiquitin Protein Ligase1 2     HRCA12
Protein G72 3     RCA12
pVHL2 3     VHL12
Von Hippel-Lindau Syndrome1     Elongin Binding Protein2
Von Hippel-Lindau Tumor Suppressor1     Von Hippel-Lindau Disease Tumor Suppressor2

External Ids:    HGNC: 126871   Entrez Gene: 74282   Ensembl: ENSG000001340867   OMIM: 6085375   UniProtKB: P403373   

Export aliases for VHL gene to outside databases

Previous GC identifers: GC03P010112 GC03P010175 GC03P010158 GC03P010183 GC03P010119 GC03P010185


(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 VHL Gene:
Von Hippel-Lindau syndrome (VHL) is a dominantly inherited familial cancer syndrome predisposing to a variety of
malignant and benign tumors. A germline mutation of this gene is the basis of familial inheritance of VHL
syndrome. The protein encoded by this gene is a component of the protein complex that includes elongin B, elongin
C, and cullin-2, and possesses ubiquitin ligase E3 activity. This protein is involved in the ubiquitination and
degradation of hypoxia-inducible-factor (HIF), which is a transcription factor that plays a central role in the
regulation of gene expression by oxygen. RNA polymerase II subunit POLR2G/RPB7 is also reported to be a target of
this protein. Alternatively spliced transcript variants encoding distinct isoforms have been observed. (provided
by RefSeq, Jul 2008)

GeneCards Summary for VHL Gene:
VHL (von Hippel-Lindau tumor suppressor, E3 ubiquitin protein ligase) is a protein-coding gene. Diseases associated with VHL include vhl-related pheochromocytoma, and renal cell carcinoma, somatic. GO annotations related to this gene include enzyme binding and transcription factor binding. An important paralog of this gene is VHLL.

UniProtKB/Swiss-Prot: VHL_HUMAN, P40337
Function: Involved in the ubiquitination and subsequent proteasomal degradation via the von Hippel-Lindau
ubiquitination complex. Seems to act as target recruitment subunit in the E3 ubiquitin ligase complex and
recruits hydroxylated hypoxia-inducible factor (HIF) under normoxic conditions. Involved in transcriptional
repression through interaction with HIF1A, HIF1AN and histone deacetylases. Ubiquitinates, in an
oxygen-responsive manner, ADRB2

Gene Wiki entry for VHL (Von Hippel-Lindau tumor suppressor) 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_000003.11  NC_018914.2  NT_022517.19  
Regulatory elements:
   Regulatory transcription factor binding sites in the VHL gene promoter:
         HOXA9   HOXA9B   FAC1   p53   MIF-1   Ik-1   C/EBPalpha   
         Other transcription factors

SwitchGear Promoter luciferase reporter plasmidVHL promoter sequence
   Search Chromatin IP Primers for VHL

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


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

Entrez Gene cytogenetic band: 3p25.3   Ensembl cytogenetic band:  3p25.3   HGNC cytogenetic band: 3p25.3

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

GeneLoc information about chromosome 3         GeneLoc Exon Structure

GeneLoc location for GC03P010200:  view genomic region     (about GC identifiers)

Start:
10,182,692 bp from pter      End:
10,195,354 bp from pter
Size:
12,663 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: VHL_HUMAN, P40337 (See protein sequence)
Recommended Name: Von Hippel-Lindau disease tumor suppressor  
Size: 213 amino acids; 24153 Da
Subunit: Component of the VCB (VHL-Elongin BC-CUL2) complex; this complex acts as a ubiquitin-ligase E3 and
directs proteasome-dependent degradation of targeted proteins. Interacts with CUL2; this interaction is dependent
on the integrity of the trimeric VBC complex. Interacts (via the beta domain) with HIF1A (via the NTAD domain);
this interaction mediates degradation of HIF1A in normoxia and, in hypoxia, prevents ubiqitination and
degradation of HIF1A by mediating hypoxia-induced translocation to the nucleus, a process which requires a
hypoxia-dependent regulatory signal. Interacts with ADRB2; the interaction, in normoxia, is dependent on
hydroxylation of ADRB2 and the subsequent VCB-mediated ubiquitination and degradation of ADRB2. Under hypoxia,
hydroxylation, interaction with VHL, ubiquitination and subsequent degradation of ADRB2 are dramatically
decreased. Interacts with RNF139, USP33 and JADE1. Found in a complex composed of LIMD1, VHL, EGLN1/PHD2, TCEB2
AND CUL2. Isoform 1 and isoform 3 interact with LIMD1 (via LIM zinc-binding 2), AJUBA (via LIM domains) and WTIP
(via LIM domains). Interacts with EPAS1
Developmental stage: At 4-10 weeks pc, strong expression in the developing central nervous system, kidneys, testis
and lung. Differentially expressed within renal tubules
Selected PDB 3D structures from and Proteopedia for VHL (see all 14):
1LM8 (3D)        1LQB (3D)        1VCB (3D)        3ZRC (3D)        3ZRF (3D)        3ZTC (3D)    
Secondary accessions: B2RE45 Q13599 Q6PDA9
Alternative splicing, Alternative initiation: 3 isoforms:  P40337-1   P40337-2   P40337-3   (Produced by alternative initiation at Met-54 of isoform 1)

Explore the universe of human proteins at neXtProt for VHL: NX_P40337

Explore proteomics data for VHL at MOPED

Post-translational modifications: 

  • Ubiquitination2 at Lys196
  • Modification sites at PhosphoSitePlus

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

    REFSEQ proteins (2 alternative transcripts): 
    NP_000542.1  NP_937799.1  

    ENSEMBL proteins: 
     ENSP00000256474   ENSP00000344757  
    Reactome Protein details: P40337

    VHL Human Recombinant Protein Products:

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    Novus Biologicals VHL Proteins
    Novus Biologicals VHL Lysates
    Browse Sino Biological Recombinant Proteins
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    ProSpec Recombinant Protein for VHL
    Browse Proteins at Cloud-Clone Corp.

     
    Search eBioscience for Proteins for VHL 

     
    antibodies-online proteins for VHL (7 products) 

     
    antibodies-online peptides for VHL

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    antibodies-online antibodies for VHL (86 products) 

    VHL Assay Products:

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    antibodies-online kits for VHL (3 products) 


    (According to HGNC, IUPHAR, InterPro, ProtoNet, UniProtKB, and/or BLOCKS, Sets of similar genes according to GeneDecks)
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    4 InterPro protein domains:
     IPR022772 VHL_tumour_suppress_b/a_dom
     IPR024053 VHL_beta_dom
     IPR002714 Tumour_suppress_VHL-disease
     IPR024048 VHL_alpha_dom

    Graphical View of Domain Structure for InterPro Entry P40337

    ProtoNet protein and cluster: P40337

    UniProtKB/Swiss-Prot: VHL_HUMAN, P40337
    Domain: The Elongin BC complex binding domain is also known as BC-box with the consensus
    [APST]-L-x(3)-C-x(3)-[AILV]


    Find genes that share domains with VHL           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: VHL_HUMAN, P40337
    Function: Involved in the ubiquitination and subsequent proteasomal degradation via the von Hippel-Lindau
    ubiquitination complex. Seems to act as target recruitment subunit in the E3 ubiquitin ligase complex and
    recruits hydroxylated hypoxia-inducible factor (HIF) under normoxic conditions. Involved in transcriptional
    repression through interaction with HIF1A, HIF1AN and histone deacetylases. Ubiquitinates, in an
    oxygen-responsive manner, ADRB2

         Genatlas biochemistry entry for VHL:
    Tumor suppressor protein,complexing with CUL2,elongin B,elongin C Rbx/ROC1 and an ubiquitin conjugating enzyme
    other than CDC34,either UBE2B,2D1,L6 or others to form an active E3 ubiquitin ligase complex named the VCB-CUL2
    complex,targetting and regulating the hypoxia inducible protein HIF in normoxic conditions,also involved in cell
    cycle regulation exit of cell cycle upon serum withdrawal and in extracellular matrix formation through
    interaction with fibronectin may be an inhibitor of the transcriptor elongation factor B (SIII) through
    competition to binding TCEB1 and TCEBD

         Gene Ontology (GO): 4 molecular function terms:    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0004842ubiquitin-protein ligase activity TAS--
    GO:0005515protein binding IPI11641274
    GO:0008134transcription factor binding IPI11641274
    GO:0019899enzyme binding IPI11641274
         
    Find genes that share ontologies with VHL           About GenesLikeMe


    Phenotypes:
         4 GenomeRNAi human phenotypes for VHL:
     Decreased cilium length after   Increased gamma-H2AX phosphory  Increased sensitivity to pacli  Synthetic lethal with Ras 

         Selected MGI mutant phenotypes (inferred from 9 alleles(MGI details for Vhl) (see all 20):
     cardiovascular system  cellular  craniofacial  digestive/alimentary  embryogenesis 
     endocrine/exocrine gland  growth/size/body  hematopoietic system  homeostasis/metabolism  immune system 
     integument  limbs/digits/tail  liver/biliary system  mortality/aging  muscle 

    Find genes that share phenotypes with VHL           About GenesLikeMe

    Animal Models:
         MGI mouse knock-outs for VHL: Vhltm1.1Lss Vhltm1.1Jae Vhltm1Wml Vhltm1Bjg

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

    miRNA
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    miRTarBase miRNAs that target VHL:
    hsa-mir-24-3p (MIRT030519), hsa-mir-122-5p (MIRT023372), hsa-mir-23b-3p (MIRT007006)

    Block miRNA regulation of human, mouse, rat VHL using miScript Target Protectors
    Selected qRT-PCR Assays for microRNAs that regulate VHL (see all 31):
    hsa-miR-3938 hsa-miR-181c hsa-miR-29c hsa-miR-29a hsa-miR-767-5p hsa-miR-548v hsa-miR-371-5p hsa-miR-29b-1*
    SwitchGear 3'UTR luciferase reporter plasmidVHL 3' UTR sequence
    Inhib. RNA
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    Predesigned siRNA for gene silencing in human, mouse, rat VHL

    Gene Editing
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    Clone
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    GenScript: all cDNA clones in your preferred vector (see all 2): VHL (NM_000551)
    Sino Biological Human cDNA Clone for VHL
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    Vector BioLabs ready-to-use adenovirus/AAV for human, mouse, rat VHL
    Addgene plasmids for VHL 

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    (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
    VHL_HUMAN, P40337: Isoform 1: Cytoplasm. Membrane; Peripheral membrane protein. Nucleus. Note=Found
    predominantly in the cytoplasm and with less amounts nuclear or membrane-associated. Colocalizes with ADRB2 at
    the cell membrane
    VHL_HUMAN, P40337: Isoform 3: Cytoplasm. Nucleus. Note=Equally distributed between the nucleus and the
    cytoplasm but not membrane-associated
    Subcellular locations from COMPARTMENTS: 

    CompartmentConfidence
    endoplasmic reticulum5
    mitochondrion5
    nucleus5
    cytosol4
    cytoskeleton1
    extracellular1

    Gene Ontology (GO): Selected cellular component terms (see all 8):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0005634nucleus IDA--
    GO:0005654nucleoplasm TAS--
    GO:0005730NOT nucleolus IDA--
    GO:0005739mitochondrion NAS12169691
    GO:0005783endoplasmic reticulum NAS12169691

    Find genes that share ontologies with VHL           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 VHL About   (see all 14)  
    See pathways by source

    SuperPathContained pathways About
    1Class I MHC mediated antigen processing and presentation
    Class I MHC mediated antigen processing and presentation0.84
    Adaptive Immune System0.41
    Antigen processing- Ubiquitination and Proteasome degradation0.84
    Ubiquitin mediated proteolysis0.35
    2Regulation of Hypoxia-inducible Factor (HIF) by Oxygen
    Regulation of Hypoxia-inducible Factor (HIF) by Oxygen1.00
    Oxygen-dependent Proline Hydroxylation of Hypoxia-inducible Factor Alpha0.00
    Cellular response to hypoxia1.00
    3Cellular Senescence
    Cellular responses to stress0.81
    4ERK Signaling
    Molecular Mechanisms of Cancer0.51
    5Signaling events mediated by VEGFR1 and VEGFR2
    Signaling events mediated by VEGFR1 and VEGFR20.37


    Find genes that share SuperPaths with VHL           About GenesLikeMe

    Pathways by source                                                                                                                                                                 See SuperPaths
    Show all pathways

    2 Downloadable PowerPoint Slides of GeneGlobe Pathway Central Maps for VHL
        Molecular Mechanisms of Cancer
    HIF1Alpha Pathway

    3 Cell Signaling Technology (CST) Pathways for VHL
        Angiogenesis
    Neuroscience
    Protein Stability

    3 BioSystems Pathways for VHL
        Signaling events mediated by VEGFR1 and VEGFR2
    HIF-2-alpha transcription factor network
    Hypoxic and oxygen homeostasis regulation of HIF-1-alpha


    2 Reactome Pathways for VHL
        Oxygen-dependent proline hydroxylation of Hypoxia-inducible Factor Alpha
    Antigen processing: Ubiquitination & Proteasome degradation


    4 Kegg Pathways  (Kegg details for VHL):
        HIF-1 signaling pathway
    Ubiquitin mediated proteolysis
    Pathways in cancer
    Renal cell carcinoma

    UniProtKB/Swiss-Prot: VHL_HUMAN, P40337
    Pathway: Protein modification; protein ubiquitination

        Pathway & Disease-focused RT2 Profiler PCR Arrays including VHL: 

              Ubiquitination (Ubiquitylation) Pathway in human mouse rat
              Oncogenes & Tumor Suppressor Genes in human mouse rat
              Apoptosis 384HT in human mouse rat
              Ubiquitin Ligases in human mouse rat

    Interactions:

        GeneGlobe Interaction Network for VHL

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

    Selected Interacting proteins for VHL (P403371, 2, 3 ENSP000002564744) via UniProtKB, MINT, STRING, and/or I2D (see all 356)
    InteractantInteraction Details
    GeneCardExternal ID(s)
    HIF1AQ166651, 2, 3, ENSP000003380184EBI-301246,EBI-447269 MINT-6543069 MINT-1957453 MINT-1957650 I2D: score=9 STRING: ENSP00000338018
    FN1P027511, 2, 3, ENSP000003468394EBI-301246,EBI-1220319 MINT-6543105 MINT-6542668 I2D: score=5 STRING: ENSP00000346839
    GLI1P081511, 2EBI-3504450,EBI-308084 MINT-8412108 MINT-8412126
    ZNF512BQ96KM62, 3MINT-60810 I2D: score=2 
    CUL2Q136171, 2, 3, ENSP000003638804EBI-301246,EBI-456179 MINT-6543069 MINT-6543008 MINT-6543087 MINT-6542668 MINT-6543038 MINT-6543051 I2D: score=9 STRING: ENSP00000363880
    About this table

    Gene Ontology (GO): Selected biological process terms (see all 14):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0000122negative regulation of transcription from RNA polymerase II promoter TAS7660122
    GO:0000902cell morphogenesis NAS12169691
    GO:0006355regulation of transcription, DNA-templated IMP15824735
    GO:0006508proteolysis TAS10353251
    GO:0006950response to stress NAS12169691

    Find genes that share ontologies with VHL           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 VHL

    Selected Novoseek inferred chemical compound relationships for VHL gene (see all 35)    About this table
    Compound   -log (P-Val)   Hits   PubMed IDs for Articles with Shared Sentences (# sentences)
    vegf 68.8 129 19755989 (7), 10475065 (5), 9271438 (5), 8625303 (4) (see all 54)
    succinate 58.1 8 18334619 (1), 15988378 (1), 20130071 (1), 18001193 (1) (see all 7)
    ehen 54.8 1 9290699 (1)
    fumarate 54.5 7 17255292 (2), 17699843 (1), 19285230 (1)
    oxygen 50.3 67 11336512 (3), 11175344 (2), 12507560 (2), 15181450 (2) (see all 46)
    proline 49 11 11504942 (2), 19584355 (1), 19470762 (1), 11823643 (1) (see all 10)
    cobalt chloride 38.7 1 18305400 (1)
    sunitinib 33.1 1 19402069 (1)
    trichloroethylene 28.3 10 15177666 (3), 19473641 (2), 10852497 (2), 10714214 (1) (see all 5)
    deferoxamine 28.1 2 15878351 (1)



    Find genes that share compounds with VHL           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 VHL gene (2 alternative transcripts): 
    NM_000551.3  NM_198156.2  

    Unigene Cluster for VHL:

    Von Hippel-Lindau tumor suppressor, E3 ubiquitin protein ligase
    Hs.517792  [show with all ESTs]
    Unigene Representative Sequence: NM_000551
    3 Ensembl transcripts including schematic representations, and UCSC links where relevant:
    ENST00000256474(uc003bvc.3 uc003bvd.3) ENST00000345392 ENST00000477538

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    hsa-miR-3938 hsa-miR-181c hsa-miR-29c hsa-miR-29a hsa-miR-767-5p hsa-miR-548v hsa-miR-371-5p hsa-miR-29b-1*
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    Additional mRNA sequence: 

    AF088066.1 AK304002.1 AK309560.1 AK315799.1 BC027957.1 BC058831.1 L15409.1 

    13 DOTS entries:

    DT.101982322  DT.87016137  DT.120922749  DT.95353470  DT.120922689  DT.100749785  DT.452953  DT.87015079 
    DT.92046146  DT.97778760  DT.100707708  DT.120922748  DT.92439090 

    Selected AceView cDNA sequences (see all 115):

    BC027957 R26242 NM_000551 NM_198156 BQ893536 BG288777 BM975139 AA302681 
    AI254340 BX956555 AA807967 BG753018 CA433522 BC058831 BF305686 BX956514 
    BG548629 AI417227 BE786327 BI767841 BG914051 CA414706 R79504 BM564781 

    GeneLoc Exon Structure

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

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


    ECgene alternative splicing isoforms for VHL

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

    VHL Protein expression data from MOPED1, PaxDb2 and MaxQB3    About this image

    VHL Protein Expression

    SOURCE GeneReport for Unigene cluster: Hs.517792

    UniProtKB/Swiss-Prot: VHL_HUMAN, P40337
    Tissue specificity: Expressed in the adult and fetal brain and kidney

        Pathway & Disease-focused RT2 Profiler PCR Arrays including VHL: 
              Ubiquitination (Ubiquitylation) Pathway in human mouse rat
              Oncogenes & Tumor Suppressor Genes in human mouse rat
              Apoptosis 384HT in human mouse rat
              Ubiquitin Ligases 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 VHL gene from Selected species (see all 10)    About this table
    Organism Taxonomic
    classification
    Gene Description Human
    Similarity
    Orthology
    Type
    Details
    mouse
    (Mus musculus)
    Mammalia Vhl1 , 5 von Hippel-Lindau tumor suppressor1, 5 83.33(n)1
    86.36(a)1
      6 (52.81 cM)5
    223461  NM_009507.31  NP_033533.11 
     1136239595 
    chicken
    (Gallus gallus)
    Aves VHL1 von Hippel-Lindau tumor suppressor, E3 ubiquitin protein more 71.39(n)
    71.63(a)
      416117  XM_414447.3  XP_414447.3 
    lizard
    (Anolis carolinensis)
    Reptilia --
    Uncharacterized protein
    68(a)
    1 → many
    GL343273.1(939833-946315)
    tropical clawed frog
    (Xenopus tropicalis)
    Amphibia Str.173852 Transcribed sequence with weak similarity to protein more 70.98(n)    AL869123.2 
    zebrafish
    (Danio rerio)
    Actinopterygii vhl1 von Hippel-Lindau tumor suppressor 55.94(n)
    54.11(a)
      791202  NM_001080684.1  NP_001074153.1 


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

    (Paralogs according to 1HomoloGene,
    2Ensembl, and 3SIMAP, Pseudogenes according to 4Pseudogene.org Build 68)
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    Paralogs for VHL gene
    VHLL2  
    1 SIMAP similar gene for VHL using alignment to 5 protein entries:     VHL_HUMAN (see all proteins):
    VHLL

    Find genes that share paralogs with VHL           About GenesLikeMe



    (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 VHL (see all 637)    About this table                                 

    Genomic DataTranscription Related DataAllele Frequencies
    SNP IDValidClinical
    significance
    Chr 3 posSequence#AA
    Chg
    TypeMore#Allele
    freq
    PopTotal
    sample
    More
    ----------
    rs354607681,2,,4
    C,FPheochromocytoma (PCC)4 --10118612(+) CGGCCC/TTGAAG 4 P L mis12Minor allele frequency- T:0.03NA 76
    rs50308271,2,,4
    CVon Hippel-Lindau disease (VHLD)4 pathogenic110118788(+) GCGTCG/TTGCTG 4 V L mis12Minor allele frequency- T:0.00NA 4
    rs50308071,2,,4
    CVon Hippel-Lindau disease (VHLD)4 untested110118804(+) ATGGCA/C/TCAACT 4 H L mis12NA 4
    rs50308081,2,,4
    CVon Hippel-Lindau disease (VHLD)4 pathogenic110118815(+) TCGACA/C/GGCGAG 4 S G mis12NA 4
    rs50308091,2,,4
    CVon Hippel-Lindau disease (VHLD)4 pathogenic110118830(+) AGCCCT/CACCCA 4 /H /Y mis12Minor allele frequency- C:0.00NA 4
    rs50308111,2,,4
    CVon Hippel-Lindau disease (VHLD)4 --10123215(+) TAGGTC/TRCCTT 3 H Y mis1 int17Minor allele frequency- T:0.00MN NA 368
    rs50308121,2,,4
    CVon Hippel-Lindau disease (VHLD)4 --10123215(+) AGGTYA/GCCTTT 4 T H A fra1 int17Minor allele frequency- G:0.00MN NA 368
    rs50308301,2,,4
    CVon Hippel-Lindau disease (VHLD)4 --10123225(+) TTGGCT/CCTTCA 3 /P /L mis1 int17Minor allele frequency- C:0.00MN NA 368
    rs50308321,2,,4
    CVon Hippel-Lindau disease (VHLD)4 --10123234(+) CAGAGA/GTGCAG 3 D G mis1 int17Minor allele frequency- G:0.00MN NA 368
    rs50308331,2,,4
    CVon Hippel-Lindau disease (VHLD)4 --10123279(+) ATTATT/GTGTGC 3 /C /F mis1 int17Minor allele frequency- G:0.00MN NA 392

    HapMap Linkage Disequilibrium report for VHL (10182692 - 10195354 bp)

    Structural Variations
         Database of Genomic Variants (DGV) 6 variations for VHL:    About this table    
    Variant IDTypeSubtypePubMed ID
    dgv809e201CNV Deletion23290073
    nsv436362CNV Deletion17901297
    esv2662777CNV Deletion23128226
    nsv3693CNV Insertion18451855
    nsv436869CNV Insertion17901297
    esv4117CNV Complex18987735

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

    Selected Site Specific Mutation Identification with PCR Assays for VHL (see all 19):
    Cosmic IdAA Change
    14305p.L89H
    17642p.G114C
    14380p.S183*
    17859p.L85P
    17735p.F148fs*11
    4 Site Specific Cancer Mutation PCR Panels containing VHL:
    Oncogene and Tumor Suppressor Panel 384HT
    c-MET
    Cancer Comprehensive Panel 384HT
    Tumor Suppressor Panel 384HT
    SeqTarget long-range PCR primers for resequencing VHL
    DNA2.0 Custom Variant and Variant Library Synthesis for VHL

    (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: 608537   
    OMIM disorders: 193300  144700  171300  263400  
    UniProtKB/Swiss-Prot: VHL_HUMAN, P40337
  • Pheochromocytoma (PCC) [MIM:171300]: A catecholamine-producing tumor of chromaffin tissue of the adrenal
    medulla or sympathetic paraganglia. The cardinal symptom, reflecting the increased secretion of epinephrine and
    norepinephrine, is hypertension, which may be persistent or intermittent. Note=Disease susceptibility is
    associated with variations affecting the gene represented in this entry
  • von Hippel-Lindau disease (VHLD) [MIM:193300]: VHLD is a dominantly inherited familial cancer syndrome
    predisposing to a variety of malignant and benign neoplasms, most frequently retinal, cerebellar and spinal
    hemangioblastoma, renal cell carcinoma (RCC), pheochromocytoma, and pancreatic tumors. VHL type 1 is without
    pheochromocytoma, type 2 is with pheochromocytoma. VHL type 2 is further subdivided into types 2A
    (pheochromocytoma, retinal angioma, and hemangioblastomas without renal cell carcinoma and pancreatic cyst) and
    2B (pheochromocytoma, retinal angioma, and hemangioblastomas with renal cell carcinoma and pancreatic cyst).
    Note=The disease is caused by mutations affecting the gene represented in this entry
  • Erythrocytosis, familial, 2 (ECYT2) [MIM:263400]: An autosomal recessive disorder characterized by an
    increase in serum red blood cell mass, hypersensitivity of erythroid progenitors to erythropoietin, increased
    erythropoietin serum levels, and normal oxygen affinity. Patients with ECYT2 carry a high risk for peripheral
    thrombosis and cerebrovascular events. Note=The disease is caused by mutations affecting the gene represented in
    this entry
  • Renal cell carcinoma (RCC) [MIM:144700]: Renal cell carcinoma is a heterogeneous group of sporadic or
    hereditary carcinoma derived from cells of the proximal renal tubular epithelium. It is subclassified into clear
    cell renal carcinoma (non-papillary carcinoma), papillary renal cell carcinoma, chromophobe renal cell carcinoma,
    collecting duct carcinoma with medullary carcinoma of the kidney, and unclassified renal cell carcinoma. Clear
    cell renal cell carcinoma is the most common subtype. Note=The disease is caused by mutations affecting the gene
    represented in this entry

  • Selected diseases for VHL (see all 40):    
    About MalaCards
    vhl-related pheochromocytoma    renal cell carcinoma, somatic    familial erythrocytosis 2    clear cell papillary renal cell carcinoma
    cerebellar astrocytoma    microcystic adenoma    nonpapillary renal cell carcinoma    angiomatosis
    von hippel-lindau disease    hemangioblastoma    hemangioblastoma, cerebellar, somatic    vascular cancer
    clear cell renal cell carcinoma    von hippel-lindau syndrome, modifier of    fumarate hydratase deficiency    neuroma
    multilocular cystic renal cell carcinoma    renal cell carcinoma, clear cell, somatic    keratomalacia    hereditary renal cell carcinoma

    4 diseases from the University of Copenhagen DISEASES database for VHL:
    Renal cell carcinoma     Hemangioma     Vascular cancer     Polycythemia

    Find genes that share disorders with VHL           About GenesLikeMe

    Selected Novoseek inferred disease relationships for VHL gene (see all 82)    About this table

    Disease   -log (P-Val)   Hits   PubMed IDs for Articles with Shared Sentences (# sentences)
    renal clear cell carcinoma 93.2 86 18660794 (5), 15062033 (3), 17255293 (3), 18464292 (2) (see all 52)
    von hippel-lindau disease 93 82 11309459 (3), 9156047 (2), 10567493 (2), 12584999 (2) (see all 61)
    carcinoma renal cell 89.9 239 11792959 (7), 19933033 (3), 10475065 (3), 15386385 (3) (see all 99)
    hemangioblastoma 88.1 45 9458097 (4), 9787178 (3), 9370235 (3), 16869749 (2) (see all 23)
    renal cancer 85.1 46 12169691 (2), 18389622 (2), 9820032 (1), 15180922 (1) (see all 33)
    pheochromocytoma 83.8 142 12673678 (7), 19215943 (5), 15883705 (4), 17102081 (4) (see all 67)
    cancer syndromes hereditary 83 13 11331612 (1), 10823831 (1), 12209156 (1), 16585181 (1) (see all 9)
    paraganglioma 79.8 27 16001332 (1), 16098460 (1), 15988378 (1), 19825962 (1) (see all 17)
    erythrocytosis, familial 74 1 19494350 (1)
    tumors 72.9 633 12359370 (5), 15771820 (5), 10852497 (5), 12937142 (4) (see all 99)

    GeneTests: VHL
    GeneReviews: VHL
    Genetic Association Database (GAD): VHL
    Human Genome Epidemiology (HuGE) Navigator: VHL (50 documents)
    Tumor Gene Database (TGDB): VHL

    Export disorders for VHL 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 VHL gene, integrated from 10 sources (see all 1010):
    (articles sorted by number of sources associating them with VHL)
        Utopia: connect your pdf to the dynamic
    world of online information

    1. Mutations of von Hippel-Lindau tumor-suppressor gene and congenital polycythemia. (PubMed id 12844285)1, 2, 4, 9 Pastore Y.D.... Prchal J.T. (Am. J. Hum. Genet. 2003)
    2. Germ-line mutations in nonsyndromic pheochromocytoma. (PubMed id 12000816)1, 2, 4, 9 Neumann H.P.H.... Eng C. (N. Engl. J. Med. 2002)
    3. A second major native von Hippel-Lindau gene product, initiated from an internal translation start site, functions as a tumor suppressor. (PubMed id 9671762)1, 2, 3, 9 Schoenfeld A.... Burk R.D. (Proc. Natl. Acad. Sci. U.S.A. 1998)
    4. Phenotypic expression in von Hippel-Lindau disease: correlations with germline VHL gene mutations. (PubMed id 8730290)1, 2, 9 Maher E.R.... Moore A.T. (J. Med. Genet. 1996)
    5. Denaturing high performance liquid chromatography detection of SDHB, SDHD, and VHL germline mutations in pheochromocytoma. (PubMed id 19215943)1, 4, 9 Meyer-Rochow G.Y....Benn D.E. (J. Surg. Res. 2009)
    6. Head and neck paragangliomas in von Hippel-Lindau disease and multiple endocrine neoplasia type 2. (PubMed id 19336503)1, 4, 9 Boedeker C.C....Neumann H.P. (J. Clin. Endocrinol. Metab. 2009)
    7. The von Hippel-Lindau tumor suppressor stabilizes novel plant homeodomain protein Jade-1. (PubMed id 12169691)1, 2, 9 Zhou M.I.... Cohen H.T. (J. Biol. Chem. 2002)
    8. TP53, EGFR, and KRAS mutations in relation to VHL inactivation and lifestyle risk factors in renal-cell carcinoma from central and eastern Europe. (PubMed id 20137853)1, 4, 9 SzymaA8ska K....Brennan P. (Cancer Lett. 2010)
    9. Two hypoxia sensor genes and their association with symptoms of acute mountain sickness in Sherpas. (PubMed id 18998488)1, 4, 9 Droma Y....Kubo K. (Aviat Space Environ Med 2008)
    10. Hypertension, antihypertensives and mutations in the Von Hippel-Lindau gene in renal cell carcinoma: results from the Netherlands Cohort Study. (PubMed id 16208141)1, 4, 9 Schouten L.J....van den Brandt P.A. (J. Hypertens. 2005)

    (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: 7428 HGNC: 12687 AceView: VHL Ensembl:ENSG00000134086 euGenes: HUgn7428
    ECgene: VHL Kegg: 7428 H-InvDB: VHL

    (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 VHL Pharmacogenomics, SNPs, Pathways
    ATLAS Chromosomes in Cancer entry for VHL Genetics and Cytogenetics in Oncology and Haematology
    GeneReviewshttp://www.ncbi.nlm.nih.gov/books/NBK1116/?term=VHL[genesymbol]

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

    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, eBioscience, antibodies-online, and/or others, Gene Editing from DNA2.0. Clones from OriGene, GenScript, Sino Biological, DNA2.0, SwitchGear Genomics, Vector BioLabs, Addgene, Cell lines from GenScript, and ESI BIO, Flow cytometery from eBioscience, 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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