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SHH Gene

protein-coding   GIFtS: 73
GCID: GC07M155592

Sonic Hedgehog

(Previous names: sonic hedgehog (Drosophila) homolog, sonic hedgehog homolog...)
(Previous symbols: HPE3, HLP3)
  See SHH-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
Sonic Hedgehog1 2     HHG12
HLP31 2 5     TPT2
HPE31 2 5     TPTPS2
MCOPCB52 5     Sonic Hedgehog Homolog2
SMMCI2 5     Sonic Hedgehog Protein2
Sonic Hedgehog (Drosophila) Homolog1     HHG-13
Sonic Hedgehog Homolog (Drosophila)1     

External Ids:    HGNC: 108481   Entrez Gene: 64692   Ensembl: ENSG000001646907   OMIM: 6007255   UniProtKB: Q154653   

Export aliases for SHH gene to outside databases

Previous GC identifers: GC07M153825 GC07M154898 GC07M155013 GC07M155014 GC07M155095 GC07M155288 GC07M149327


(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 SHH Gene:
This gene encodes a protein that is instrumental in patterning the early embryo. It has been implicated as the key
inductive signal in patterning of the ventral neural tube, the anterior-posterior limb axis, and the ventral
somites. Of three human proteins showing sequence and functional similarity to the sonic hedgehog protein of
Drosophila, this protein is the most similar. The protein is made as a precursor that is autocatalytically
cleaved; the N-terminal portion is soluble and contains the signalling activity while the C-terminal portion is
involved in precursor processing. More importantly, the C-terminal product covalently attaches a cholesterol
moiety to the N-terminal product, restricting the N-terminal product to the cell surface and preventing it from
freely diffusing throughout the developing embryo. Defects in this protein or in its signalling pathway are a
cause of holoprosencephaly (HPE), a disorder in which the developing forebrain fails to correctly separate into
right and left hemispheres. HPE is manifested by facial deformities. It is also thought that mutations in this
gene or in its signalling pathway may be responsible for VACTERL syndrome, which is characterized by vertebral
defects, anal atresia, tracheoesophageal fistula with esophageal atresia, radial and renal dysplasia, cardiac
anomalies, and limb abnormalities. Additionally, mutations in a long range enhancer located approximately 1
megabase upstream of this gene disrupt limb patterning and can result in preaxial polydactyly. (provided by
RefSeq, Jul 2008)

GeneCards Summary for SHH Gene:
SHH (sonic hedgehog) is a protein-coding gene. Diseases associated with SHH include semilobar holoprosencephaly, and tracheoesophageal fistula. GO annotations related to this gene include peptidase activity and calcium ion binding. An important paralog of this gene is IHH.

UniProtKB/Swiss-Prot: SHH_HUMAN, Q15465
Function: Binds to the patched (PTC) receptor, which functions in association with smoothened (SMO), to activate
the transcription of target genes. In the absence of SHH, PTC represses the constitutive signaling activity of
SMO. Also regulates another target, the gli oncogene. Intercellular signal essential for a variety of patterning
events during development: signal produced by the notochord that induces ventral cell fate in the neural tube and
somites, and the polarizing signal for patterning of the anterior-posterior axis of the developing limb bud.
Displays both floor plate- and motor neuron-inducing activity. The threshold concentration of N-product required
for motor neuron induction is 5-fold lower than that required for floor plate induction (By similarity)

summary for SHH Gene:
The hedgehog (Hh) signaling pathway is crucial in the development of all known animals. In the embryo, it
regulates morphogenesis of a variety of tissues and organs, in the adult, it controls stem cell
proliferation. There are three human Hh proteins; Sonic hedgehog (Shh), Desert hedgehog (Dhh) and Indian
hedgehog (Ihh). Each is expressed at different times of development and in specific cell types and they are
tightly controlled by highly complex, yet divergent transcriptional enhancers. Hh protein release and
diffusion is controlled by various proteins including Skinny hedgehog (Sit), Dispatched (Disp), Tout-velu
(Ttv) and Hedgehog-interacting protein (Hip). Hh proteins bind to the twelve transmembrane domain protein,
Patched (Ptc). In the absence of Hh proteins, Ptc catalytically inhibits Smo. Hh-Ptc binding results in loss
of Ptc activity and activation of Smo, which transduces the Hh signal to the cytoplasm. This leads to the
activation of the Ci/GLI family of transcription factors, through complex interactions of Costal2 (Cos2),
Fused (Fu) and Suppressor of fu [Su(fu)]. Furthermore, PKA, CK1, GSK-3 and Slimb modulate this signal
transduction pathway. Abberant activation of the Hh pathway has been linked to multiple types of human
cancer, particularly basal cell carcinoma. Disruption of Hh signaling during embryonic development, either
through congenital mutation or maternal teratogen consumption, can lead to severe developmental disorders
such as holoprosencephaly.

Gene Wiki entry for SHH (Sonic hedgehog) 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_000007.14  NC_018918.2  NT_007933.16  
Regulatory elements:
   Regulatory transcription factor binding sites in the SHH gene promoter:
         POU2F2 (Oct-2.1)   Oct-B1   NF-1   oct-B3   POU3F2   POU2F2   POU2F1   POU2F1a   POU2F2B   NF-kappaB1   
         Other transcription factors

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

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


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

Entrez Gene cytogenetic band: 7q36   Ensembl cytogenetic band:  7q36.3   HGNC cytogenetic band: 7q36

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

GeneLoc information about chromosome 7         GeneLoc Exon Structure

GeneLoc location for GC07M155592:  view genomic region     (about GC identifiers)

Start:
155,592,680 bp from pter      End:
155,604,967 bp from pter
Size:
12,288 bases      Orientation:
minus strand

1 alternative location:
Chr7-,CRA_TCAG 154,827,119-154,836,528     

(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., and/or eBioscience,
Biochemical Assays by EMD Millipore, R&D Systems, OriGene, GenScript, Cell Signaling Technology, Enzo Life Sciences, Cloud-Clone Corp., and/or eBioscience, Antibodies by EMD Millipore, R&D Systems, Cell Signaling Technology, OriGene, Novus Biologicals, Thermo Fisher Scientific, LSBio, Abcam, Cloud-Clone Corp, and/or others.)
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UniProtKB/Swiss-Prot: SHH_HUMAN, Q15465 (See protein sequence)
Recommended Name: Sonic hedgehog protein precursor  
Size: 462 amino acids; 49607 Da
Subunit: Interacts with HHATL/GUP1 which negatively regulates HHAT-mediated palmitoylation of the SHH N-terminus.
N-product is active as a multimer. Interacts with BOC and CDON (By similarity). Interacts with HHIP
Mass spectrometry: Mass=19.560; Method=Electrospray; Range=24-197; Note=Soluble N-product, purified from insect
cells; Source=PubMed:9593755;
Mass spectrometry: Mass=20.167; Method=Electrospray; Range=24-197; Note=Membrane-bound N-product, purified from
insect cells; Source=PubMed:9593755;
3 PDB 3D structures from and Proteopedia for SHH:
3HO5 (3D)        3M1N (3D)        3MXW (3D)    
Secondary accessions: A4D247 Q75MC9

Explore the universe of human proteins at neXtProt for SHH: NX_Q15465

Explore proteomics data for SHH at MOPED

Post-translational modifications: 

  • The C-terminal domain displays an autoproteolysis activity and a cholesterol transferase activity. Both activities
    result in the cleavage of the full-length protein and covalent attachment of a cholesterol moiety to the
    C-terminal of the newly generated N-terminal fragment (N-product). The N-product is the active species in both
    local and long-range signaling, whereas the C-product has no signaling activity1
  • Cholesterylation is required for N-product targeting to lipid rafts and multimerization (By similarity)1
  • N-palmitoylation of Cys-24 by HHAT is required for N-product multimerization and full activity (By similarity)1
  • Glycosylation2 at Asn278
  • Modification sites at PhosphoSitePlus

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

    REFSEQ proteins: NP_000184.1  
    ENSEMBL proteins: 
     ENSP00000297261   ENSP00000410546   ENSP00000396621   ENSP00000413871  
    Reactome Protein details: Q15465

    SHH Human Recombinant Protein Products:

    EMD Millipore Purified and/or Recombinant SHH Protein
    R&D Systems Recombinant & Natural Proteins for SHH (Sonic Hedgehog/Shh)
    Browse recombinant and purified proteins available from Enzo Life Sciences
    OriGene Purified Protein for SHH
    OriGene Protein Over-expression Lysate for SHH
    OriGene MassSpec for SHH
    OriGene Custom Protein Services for SHH
    GenScript Purified and Recombinant Proteins for SHH
    Novus Biologicals SHH Proteins
    Novus Biologicals SHH Lysate
    Sino Biological Recombinant Protein for SHH
    Sino Biological Cell Lysate for SHH
    ProSpec Recombinant Protein for SHH
    Cloud-Clone Corp. Proteins for SHH

     
    eBioscience Proteins for SHH:  
                        Human Sonic Hedgehog (SHH) Recombinant Protein 5 ug

    SHH Antibody Products:

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

    SHH Assay Products:

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


    (According to HGNC, IUPHAR, InterPro, ProtoNet, UniProtKB, and/or BLOCKS, Sets of similar genes according to GeneDecks)
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    Selected InterPro protein domains (see all 7):
     IPR001657 Hedgehog
     IPR003586 Hint_dom_C
     IPR009045 Hedgehog_sig/DD-Pept_Zn-bd_dom
     IPR000320 Hedgehog_signalling_dom
     IPR006141 Intein_splice_site

    Graphical View of Domain Structure for InterPro Entry Q15465

    ProtoNet protein and cluster: Q15465

    5 Blocks protein domains:
    IPB000320 Hedgehog amino-terminal signaling domain
    IPB001657 Sonic hedgehog protein signature
    IPB001767 Hedgehog protein
    IPB003586 Hedgehog/Intein hint domain
    IPB009045 Hedgehog/DD-peptidase


    UniProtKB/Swiss-Prot: SHH_HUMAN, Q15465
    Domain: The sonic hedgehog protein N-product binds calcium and zinc ions; this stabilizes the protein fold and is
    essential for protein-protein interactions mediated by this domain
    Similarity: Belongs to the hedgehog family


    Find genes that share domains with SHH           About GenesLikeMe


    (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, 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: SHH_HUMAN, Q15465
    Function: Binds to the patched (PTC) receptor, which functions in association with smoothened (SMO), to activate
    the transcription of target genes. In the absence of SHH, PTC represses the constitutive signaling activity of
    SMO. Also regulates another target, the gli oncogene. Intercellular signal essential for a variety of patterning
    events during development: signal produced by the notochord that induces ventral cell fate in the neural tube and
    somites, and the polarizing signal for patterning of the anterior-posterior axis of the developing limb bud.
    Displays both floor plate- and motor neuron-inducing activity. The threshold concentration of N-product required
    for motor neuron induction is 5-fold lower than that required for floor plate induction (By similarity)

         Genatlas biochemistry entry for SHH:
    embryonic patterning gene,Drosophila segment polarity gene Sonic hedgehog homolog,general ventralizing
    signal,expressed in the notochord and floor plate cells,gut endoderm,posterior limb buds,inductive signal for
    somite differentiation and limb development at the anteroposterior axis,targetting BMP2 and HOXD genes through a
    FGF4 positive feedback loop,also expressed in fetal liver,lung and kidney and in hair follicle,involved in signal
    transduction,SHH pathway

         Summary: 
    During embryonic development, SHH as signaling molecule is secreted from the following cells:
          selected tissues (see all 14)      fully expand
    Neural Tube: Early Caudal Floor Plate Cells (Anterior Entopeduncular Area), Early Floor Plate Cells (Diencephalic Floor Plate)      fully expand to see all 6 cells
    Hair: Primary Hair Placode Cells (Hair Follicle), Fetal Hair Placode Cells (Hair Follicle)      fully expand to see all 3 cells

    It affects the following cells:
          selected tissues (see all 17)      fully expand
    Somite: Myoblasts (Cervical Mesenchymal Sclerotome), Cervical Sclerotome Cells (Cervical Mesenchymal Sclerotome)      fully expand to see all 21 cells
    Neural Tube: Medial Ganglionic Eminence Progenitor Cells (Anterior Entopeduncular Area), Meso-diencephalic Dopaminergic Precursor Cells (Diencephalic Floor Plate)      fully expand to see all 13 cells

    SHH as growth factor is involved in stem cell differentiation protocols towards the derivation of the following cells:
          selected tissues (see all 7)      fully expand
    Brain: Dopaminergic neuron precursors cells, Dopaminergic-like neurons      fully expand to see all 10 cells
    Spinal Cord: Motor neuron-like cells, Motor neurons progenitors      fully expand to see all 10 cells

         Gene Ontology (GO): Selected molecular function terms (see all 10):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0001948glycoprotein binding IEA--
    GO:0004871signal transducer activity IDA19561609
    GO:0005113patched binding IDA8906787
    GO:0005509calcium ion binding IDA19561609
    GO:0005515protein binding IPI19561609
         
    Find genes that share ontologies with SHH           About GenesLikeMe


    Phenotypes:
         1 GenomeRNAi human phenotype for SHH:
     Decreased Salmonella enterica  

         Selected MGI mutant phenotypes (inferred from 28 alleles(MGI details for Shh) (see all 26):
     behavior/neurological  cardiovascular system  cellular  craniofacial  digestive/alimentary 
     embryogenesis  endocrine/exocrine gland  growth/size/body  hearing/vestibular/ear  hematopoietic system 
     homeostasis/metabolism  immune system  integument  limbs/digits/tail  mortality/aging 

    Find genes that share phenotypes with SHH           About GenesLikeMe

    Animal Models:
         MGI mouse knock-outs for SHH: Shhtm3Amc Shhtm1Amc Shhtm1Chg Shhtm2.1Amc

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

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

    miRNA
    Products:
        
    miRTarBase miRNAs that target SHH:
    hsa-mir-335-5p (MIRT017061)

    Block miRNA regulation of human, mouse, rat SHH using miScript Target Protectors
    Search for qRT-PCR Assays for microRNAs that regulate SHH
    Browse SwitchGear 3'UTR luciferase reporter plasmids
    Inhib. RNA
    Products:
        
    OriGene RNAi products in human, mouse, rat for SHH
    Predesigned siRNA for gene silencing in human, mouse, rat SHH

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

    Clone
    Products:
         
    OriGene clones in human, mouse for SHH (see all 5)
    OriGene ORF clones in mouse, rat for SHH
    OriGene custom cloning services - gene synthesis, subcloning, mutagenesis, variant library, vector shuttling
    GenScript: all cDNA clones in your preferred vector: SHH (NM_000193)
    Sino Biological Human cDNA Clone for SHH
    DNA2.0 Custom Codon Optimized Gene Synthesis Service for SHH
    Vector BioLabs ready-to-use adenovirus/AAV for human, mouse, rat SHH
    Addgene plasmids for SHH 

    Cell Line
    Products:
         
    GenScript Custom overexpressing Cell Line Services for SHH
    Browse ESI BIO Cell Lines and PureStem Progenitors for SHH 
    In Situ Assay
    Products:
       

     
    Advanced Cell Diagnostics RNAscope RNA in situ hybridization assays for SHH


    (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
    SHH_HUMAN, Q15465: Sonic hedgehog protein C-product: Secreted, extracellular space (By similarity). Note=The
    C-terminal peptide diffuses from the cell (By similarity)
    SHH_HUMAN, Q15465: Sonic hedgehog protein N-product: Cell membrane; Lipid-anchor (By similarity). Cell
    membrane. Note=The N-product either remains associated with lipid rafts at the cell surface, or forms freely
    diffusible active multimers with its hydrophobic lipid-modified N- and C-termini buried inside (By similarity)
    Subcellular locations from COMPARTMENTS: 

    CompartmentConfidence
    extracellular5
    plasma membrane5
    cytoskeleton2
    nucleus2
    endoplasmic reticulum1
    golgi apparatus1
    lysosome1

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

    GO IDQualified GO termEvidencePubMed IDs
    GO:0005576extracellular region ----
    GO:0005615extracellular space ISS--
    GO:0005634nucleus IEA--
    GO:0005886plasma membrane IEA--
    GO:0009986cell surface ISS--

    Find genes that share ontologies with SHH           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 SHH About   (see all 15)  
    See pathways by source

    SuperPathContained pathways About
    1Hedgehog Signaling Pathway
    Hedgehog Pathway0.32
    Hedgehog Signaling Pathway0.32
    2Signaling by GPCR
    Signaling by GPCR0.90
    Signal Transduction0.58
    3Basal cell carcinoma
    Basal cell carcinoma0.43
    Hedgehog signaling pathway0.43
    4Peptide ligand-binding receptors
    GPCR ligand binding0.71
    5ADP signalling through P2Y purinoceptor 12
    Class B/2 (Secretin family receptors)0.36


    Find genes that share SuperPaths with SHH           About GenesLikeMe

    Pathways by source                                                                                                                                                                 See SuperPaths
    Show all pathways


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

    1 Tocris Bioscience Pathway for SHH
        Hedgehog Pathway

    1 GeneGo (Thomson Reuters) Pathway for SHH
        Development Hedgehog and PTH signaling pathways in bone and cartilage development

    Selected BioSystems Pathways for SHH (see all 8)
        Heart Development
    Hedgehog Signaling Pathway
    Integrated Pancreatic Cancer Pathway
    TWEAK Signaling Pathway
    FOXA1 transcription factor network


    1 Reactome Pathway for SHH
        Class B/2 (Secretin family receptors)


    3 Kegg Pathways  (Kegg details for SHH):
        Hedgehog signaling pathway
    Pathways in cancer
    Basal cell carcinoma

        Pathway & Disease-focused RT2 Profiler PCR Arrays including SHH (see all 8): 
              Neurogenesis in human mouse rat
              Hedgehog Signaling Pathway in human mouse rat
              Angiogenic Growth Factors in human mouse rat
              Primary Cilia in human mouse rat
              TGFB Signaling Targets in human mouse rat

    Interactions:

        GeneGlobe Interaction Network for SHH

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

    Selected Interacting proteins for SHH (Q154653 ENSP000002972614) via UniProtKB, MINT, STRING, and/or I2D (see all 149)
    InteractantInteraction Details
    GeneCardExternal ID(s)
    PTCH1Q136353, ENSP000003323534I2D: score=3 STRING: ENSP00000332353
    GAS1P548263, ENSP000002987434I2D: score=2 STRING: ENSP00000298743
    HHIPQ96QV13, ENSP000002965754I2D: score=2 STRING: ENSP00000296575
    PTCH2Q9Y6C53, ENSP000003612664I2D: score=1 STRING: ENSP00000361266
    SIN3AQ96ST33, ENSP000003536224I2D: score=1 STRING: ENSP00000353622
    About this table

    Gene Ontology (GO): Selected biological process terms (see all 177):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0000122negative regulation of transcription from RNA polymerase II promoter ISS--
    GO:0001525angiogenesis ----
    GO:0001569patterning of blood vessels ISS--
    GO:0001570vasculogenesis ISS--
    GO:0001656metanephros development ISS--

    Find genes that share ontologies with SHH           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
    Selected ApexBio Compounds for SHH (see all 14)     About this table
    CompoundAction CAS #
    AY 9944 dihydrochlorideInhibitor of hedgehog (Hh) signaling[366-93-8]
    AZ 12080282 dihydrochlorideInhibitor of Hedgehog (Hh) signaling--
    Ciliobrevin AHedgehog (Hh) pathway antagonist[302803-72-1]
    CyclopamineSmoothened inhibitor, directly binds to Smoothened and blocks Hedgehog pathway[4449-51-8]
    GANT 58novel and potent Gli antagonist[64048-12-0]
    GANT61GLI antagonist,inhibits GLI1 and GLI2-induced transcription[500579-04-4]
    GDC-0449 (Vismodegib)Hedgehog antagonist [879085-55-9]
    HPI 1Hedgehog (Hh) signaling inhibitor. [599150-20-6]
    JervineInhibitor of Hedgehog signaling[469-59-0]
    JK 184Potent downstream hedgehog (Hh) signaling inhibitor[315703-52-7]

    Compounds for SHH available from Tocris Bioscience    About this table
    CompoundAction CAS #
    CyclopamineInhibitor of Hedgehog (Hh) signaling[4449-51-8]
    AY 9944 dihydrochlorideInhibitor of Hedgehog (Hh) signaling. Inhibits delta7-dehydrocholesterol reductase[366-93-8]
    Ciliobrevin AHedgehog (Hh) pathway antagonist; inhibits ciliogenesis[302803-72-1]
    SANT-1Inhibitor of hedgehog (Hh) signaling; antagonizes smoothened activity[304909-07-7]
    20(S)-HydroxycholesterolAllosteric activator of Hedgehog (Hh) signaling; induces Smo accumulation[516-72-3]

    2 Novoseek inferred chemical compound relationships for SHH gene    About this table
    Compound   -log (P-Val)   Hits   PubMed IDs for Articles with Shared Sentences (# sentences)
    cyclopamine 89.5 8 17300775 (1), 19788370 (1), 20025076 (1), 20087349 (1)
    cholesterol 0 2 10799401 (1), 15539288 (1)



    Find genes that share compounds with SHH           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 )
    About This Section

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    REFSEQ mRNAs for SHH gene: 
    NM_000193.2  

    Unigene Cluster for SHH:

    Sonic hedgehog
    Hs.164537  [show with all ESTs]
    Unigene Representative Sequence: NM_000193
    5 Ensembl transcripts including schematic representations, and UCSC links where relevant:
    ENST00000297261(uc003wmj.1 uc003wmk.1) ENST00000441114(uc003wmh.1)
    ENST00000430104(uc003wmi.1) ENST00000435425 ENST00000472308
    miRNA
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    Additional mRNA sequence: 

    AY927450.1 AY927452.1 AY927453.1 AY927454.1 AY927455.1 L38518.1 

    3 DOTS entries:

    DT.121093532  DT.305318  DT.405095 

    4 AceView cDNA sequences:

    NM_000193 AA076750 L38518 BX452210 

    GeneLoc Exon Structure


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


    SHH 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
     
     Neural Tube (Nervous System)    fully expand to see all 33 entries
             Late Floor Plate Cells Mesencephalic Floor Plate
             Mesencephalic Floor Plate
             Floor plate-like cells
     
     Tooth (Integumentary System)    fully expand to see all 15 entries
             Odontoblasts Dentin
             Dentin
             visceral organ/oral region/upper jaw   
     
     Brain (Nervous System)    fully expand to see all 12 entries
             Early Floor Plate Cells Mesencephalic Floor Plate
             Midbrain tegmentum
     
     Epithelial Cells
             Fetal Inner Root Sheath Cells Inner Root Sheath
     
     Neural Ectoderm (Nervous System)    fully expand to see all 4 entries
             Zona Limitans Intrathalamica Cells Neural Plate
    SHH Protein expression data from MOPED1, PaxDb2 and MaxQB3    About this image

    SHH Protein Expression

    SOURCE GeneReport for Unigene cluster: Hs.164537

    UniProtKB/Swiss-Prot: SHH_HUMAN, Q15465
    Tissue specificity: Expressed in fetal intestine, liver, lung, and kidney. Not expressed in adult tissues

        Pathway & Disease-focused RT2 Profiler PCR Arrays including SHH (see all 8): 
              Neurogenesis in human mouse rat
              Hedgehog Signaling Pathway in human mouse rat
              Angiogenic Growth Factors in human mouse rat
              Primary Cilia in human mouse rat
              TGFB Signaling Targets 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 animals.

    Orthologs for SHH gene from Selected species (see all 15)    About this table
    Organism Taxonomic
    classification
    Gene Description Human
    Similarity
    Orthology
    Type
    Details
    mouse
    (Mus musculus)
    Mammalia Shh1 , 5 sonic hedgehog1, 5 87.9(n)1
    92.79(a)1
      5 (14.39 cM)5
    204231  NM_009170.31  NP_033196.11 
     284568155 
    chicken
    (Gallus gallus)
    Aves SHH1 sonic hedgehog 81.17(n)
    85.5(a)
      395615  NM_204821.1  NP_990152.1 
    lizard
    (Anolis carolinensis)
    Reptilia SHH6
    sonic hedgehog
    79(a)
    1 ↔ 1
    6(5935657-5968913)
    African clawed frog
    (Xenopus laevis)
    Amphibia LOC3980472 morphogen 76.82(n)    L39213.1 
    zebrafish
    (Danio rerio)
    Actinopterygii shh2 sonic hedgehog 75.88(n)   30269  L27585.1 
    fruit fly
    (Drosophila melanogaster)
    Insecta hh1 , 3 progression of morphogenetic furrow
    (sensu Drosophila) more3
    hedgehog1
    45(a)3
    58.71(n)1
    53.43(a)1
      3 94E13
    427371  NM_001038976.11  NP_001034065.11 


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

    (Paralogs according to 1HomoloGene,
    2Ensembl, and 3SIMAP, Pseudogenes according to 4Pseudogene.org Build 68)
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    Paralogs for SHH gene
    IHH2  DHH2  
    2 SIMAP similar genes for SHH using alignment to 5 protein entries:     SHH_HUMAN (see all proteins):
    IHH    DHH

    Find genes that share paralogs with SHH           About GenesLikeMe


    1 Pseudogenes.org Pseudogene for SHH
    PGOHUM00000250922


    (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 SHH (see all 343)    About this table                                 

    Genomic DataTranscription Related DataAllele Frequencies
    SNP IDValidClinical
    significance
    Chr 7 posSequence#AA
    Chg
    TypeMore#Allele
    freq
    PopTotal
    sample
    More
    ----------
    rs1048940471,2,,4
    C,FHoloprosencephaly 3 (HPE3)4 pathogenic1158944062(-) CTCGGG/ACTCGG 2 /D /G mis11Minor allele frequency- A:0.00NS 526
    rs289366751,2,,4
    CHoloprosencephaly 3 (HPE3)4 pathogenic1158952674(-) GGTTCA/GGGAAG 2 R G mis1 ese3 trp30--------
    VAR_0626234
    Holoprosencephaly 3 (HPE3)4--see VAR_0626232 S N mis40--------
    VAR_0626044
    Holoprosencephaly 3 (HPE3)4--see VAR_0626042 G D mis40--------
    VAR_0036204
    Holoprosencephaly 3 (HPE3)4--see VAR_0036202 W G mis40--------
    VAR_0626414
    Holoprosencephaly 3 (HPE3)4--see VAR_0626412 L P mis40--------
    VAR_0091764
    Holoprosencephaly 3 (HPE3)4--see VAR_0091762 P A mis40--------
    VAR_0626004
    Holoprosencephaly 3 (HPE3)4--see VAR_0626002 L F mis40--------
    VAR_0626314
    Holoprosencephaly 3 (HPE3)4--see VAR_0626312 R S mis40--------
    VAR_0626254
    Holoprosencephaly 3 (HPE3)4--see VAR_0626252 F V mis40--------

    HapMap Linkage Disequilibrium report for SHH (155592680 - 155604967 bp)

    Structural Variations
         Database of Genomic Variants (DGV) 4 variations for SHH:    About this table    
    Variant IDTypeSubtypePubMed ID
    esv2663062CNV Deletion23128226
    nsv509227CNV Insertion20534489
    dgv7559n71CNV Loss21882294
    nsv889560CNV Loss21882294

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

    (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: 600725   
    OMIM disorders: 142945  147250  611638  269160  
    UniProtKB/Swiss-Prot: SHH_HUMAN, Q15465
  • Microphthalmia, isolated, with coloboma, 5 (MCOPCB5) [MIM:611638]: A disorder of eye formation, ranging
    from small size of a single eye to complete bilateral absence of ocular tissues. Ocular abnormalities like
    opacities of the cornea and lens, scaring of the retina and choroid, and other abnormalities may also be present.
    Ocular colobomas are a set of malformations resulting from abnormal morphogenesis of the optic cup and stalk, and
    the fusion of the fetal fissure (optic fissure). Note=The disease is caused by mutations affecting the gene
    represented in this entry
  • Holoprosencephaly 3 (HPE3) [MIM:142945]: A structural anomaly of the brain, in which the developing
    forebrain fails to correctly separate into right and left hemispheres. Holoprosencephaly is genetically
    heterogeneous and associated with several distinct facies and phenotypic variability. The majority of
    holoprosencephaly type 3 cases are apparently sporadic, although clear examples of autosomal dominant inheritance
    have been described. Note=The disease is caused by mutations affecting the gene represented in this entry
  • Solitary median maxillary central incisor (SMMCI) [MIM:147250]: Rare dental anomaly characterized by the
    congenital absence of one maxillary central incisor. Note=The disease is caused by mutations affecting the gene
    represented in this entry
  • Triphalangeal thumb-polysyndactyly syndrome (TPTPS) [MIM:174500]: Autosomal dominant syndrome. It is
    characterized by a wide spectrum of pre- and post-axial abnormalities due to altered SHH expression pattern
    during limb development. Note=The gene represented in this entry is involved in disease pathogenesis. Mutations
    located in intron 5 of LMBR1 disrupt a long-range, cis-regulatory element of SHH expression
  • Preaxial polydactyly 2 (PPD2) [MIM:174500]: Polydactyly consists of duplication of the distal phalanx.
    The thumb in PPD2 is usually opposable and possesses a normal metacarpal. Note=The gene represented in this entry
    is involved in disease pathogenesis. Mutations located in intron 5 of LMBR1 disrupt a long-range, cis-regulatory
    element of SHH and result in abnormal, ectopic SHH expression with pathological consequences (PubMed:12837695)

  • Selected diseases for SHH (see all 39):    
    About MalaCards
    semilobar holoprosencephaly    tracheoesophageal fistula    microphthalmia with coloboma 5    shh-related holoprosencephaly
    holoprosencephaly-3    alobar holoprosencephaly    esophageal atresia    single median maxillary central incisor
    radial hemimelia, bilateral    triphalangeal thumb    polydactyly of a triphalangeal thumb, bilateral    polydactyly of a triphalangeal thumb, unilateral
    holoprosencephaly    syndactyly type 4    polydactyly, preaxial type ii    renal dysplasia
    smith-lemli-opitz syndrome    radial ray deficiency    hypoplastic tibiae - postaxial polydactyly    radial hemimelia, unilateral

    15 diseases from the University of Copenhagen DISEASES database for SHH:
    Holoprosencephaly     Polydactyly     Medulloblastoma     Basal cell carcinoma
    Nevoid basal cell carcinoma syndrome     VACTERL association     Smith-Lemli-Opitz syndrome     Esophageal atresia
    Pallister-Hall syndrome     Pancreatic cancer     Synostosis     Cleft palate
    Cleft lip     Parkinson's disease     Microcephaly

    Find genes that share disorders with SHH           About GenesLikeMe

    Selected Novoseek inferred disease relationships for SHH gene (see all 15)    About this table

    Disease   -log (P-Val)   Hits   PubMed IDs for Articles with Shared Sentences (# sentences)
    holoprosencephaly 94.3 16 10594002 (2), 11479728 (2), 10441331 (1), 15107988 (1) (see all 13)
    cyclopia 82.8 1 16282375 (1)
    semilobar holoprosencephaly 73.4 2 17556830 (2)
    polydactyly 70.7 4 17300775 (1), 9600232 (1), 18178536 (1)
    cleft lip 62.8 1 11112334 (1)
    smith-lemli-opitz syndrome 59.8 1 10799401 (1)
    microcephaly 55.9 1 15107988 (1)
    carcinoma basal cell 49.9 2 10504535 (1), 15547729 (1)
    craniofacial anomaly 47.9 1 11460262 (1)
    mental retardation 28.1 1 15107988 (1)

    GeneTests: SHH
    GeneReviews: SHH
    Genetic Association Database (GAD): SHH
    Human Genome Epidemiology (HuGE) Navigator: SHH (16 documents)

    Export disorders for SHH 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 SHH gene, integrated from 10 sources (see all 422):
    (articles sorted by number of sources associating them with SHH)
        Utopia: connect your pdf to the dynamic
    world of online information

    1. Cloning, expression, and chromosomal location of SHH and IHH: two human homologues of the Drosophila segment polarity gene hedgehog. (PubMed id 7590746)1, 2, 3, 9 Marigo V.... Tabin C. (Genomics 1995)
    2. SONIC HEDGEHOG mutations causing human holoprosencephaly impair neural patterning activity. (PubMed id 12709790)1, 4, 9 Schell-Apacik C....Ming J.E. (Hum. Genet. 2003)
    3. Expression of the Sonic hedgehog (SHH) gene during early human development and phenotypic expression of new mutations causing holoprosencephaly. (PubMed id 10441331)1, 2, 9 Odent S....Vekemans M. (Hum. Mol. Genet. 1999)
    4. The mutational spectrum of the sonic hedgehog gene in holoprosencephaly: SHH mutations cause a significant proportion of autosomal dominant holoprosencephaly. (PubMed id 10556296)1, 2, 9 Nanni L.... Muenke M. (Hum. Mol. Genet. 1999)
    5. The mutational spectrum of holoprosencephaly-associated changes within the SHH gene in humans predicts loss-of-function through either key structural alterations of the ligand or its altered synthesis. (PubMed id 19603532)1, 2, 9 Roessler E.... Muenke M. (Hum. Mutat. 2009)
    6. Molecular mechanisms of Sonic hedgehog mutant effects in holoprosencephaly. (PubMed id 16282375)1, 2, 9 Maity T.... Beachy P.A. (Proc. Natl. Acad. Sci. U.S.A. 2005)
    7. Molecular screening of SHH, ZIC2, SIX3, and TGIF genes in patients with features of holoprosencephaly spectrum: mutation review and genotype-phenotype correlations. (PubMed id 15221788)1, 2, 9 Dubourg C.... David V. (Hum. Mutat. 2004)
    8. Genome-wide meta-analyses identifies seven loci associated with platelet aggregation in response to agonists. (PubMed id 20526338)1, 4 Johnson A.D....Becker L.C. (Nat. Genet. 2010)
    9. Maternal genes and facial clefts in offspring: a comprehensive search for genetic associations in two population-based cleft studies from Scandinavia. (PubMed id 20634891)1, 4 Jugessur A....Murray J.C. (PLoS ONE 2010)
    10. Sonic hedgehog (SHH) mutation in patients within the spectrum of holoprosencephaly. (PubMed id 19398181)1, 4 Bertolacini C.D....Ribeiro-Bicudo L.A. (amp 2010)

    (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)
    About This Section

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    Entrez Gene: 6469 HGNC: 10848 AceView: SHH Ensembl:ENSG00000164690 euGenes: HUgn6469
    ECgene: SHH Kegg: 6469 H-InvDB: SHH

    (According to HUGE)
    About This Section

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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)
    About This Section

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    NameDescription
    PharmGKB entry for SHH Pharmacogenomics, SNPs, Pathways
    ATLAS Chromosomes in Cancer entry for SHH Genetics and Cytogenetics in Oncology and Haematology
    GeneReviewshttp://www.ncbi.nlm.nih.gov/books/NBK1116/?term=SHH[genesymbol]
    NIEHS-SNPshttp://egp.gs.washington.edu/data/shh/

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

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



    (Antibodies, recombinant proteins, and assays from EMD Millipore, R&D Systems, OriGene, QIAGEN, GenScript, Cell Signaling Technology, Novus Biologicals, Sino Biological, Enzo Life Sciences, Abcam, ProSpec, Cloud-Clone Corp., Thermo Fisher Scientific, LSBio, eBioscience, 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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