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Category   Symbol Source: HGNC EntrezGene Ensembl GeneCards RNA genes CroW21
GIFtS

SHH Gene

protein-coding   GIFtS: 71
GCID: GC07M155592

Sonic Hedgehog

(Previous names: sonic hedgehog (Drosophila) homolog, sonic hedgehog homolog...)
(Previous symbols: HPE3, HLP3)
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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)
About This Section

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, Tocris Bioscience, Wikipedia's Gene Wiki, PharmGKB,
UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL)
About This Section

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 tracheoesophageal fistula, and pancreatic gastrinoma, and among its related super-pathways are Hedgehog Pathway and Hedgehog signaling pathway. 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 73), Regulatory elements and Epigenetics data according to QIAGEN, SABiosciences, and/or SwitchGear Genomics)
About This Section
RefSeq DNA sequence:
NC_000007.13  NC_018918.2  NT_007741.14  NT_079596.2  
Regulatory elements:
   SABiosciences 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 SABiosciences Chromatin IP Primers for SHH

Epigenetics:
QIAGEN PyroMark CpG Assay predesigned Pyrosequencing DNA Methylation assays 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 UniProtKB, HORDE, neXtProt, Ensembl, and/or Reactome, Modification sites according to PhosphoSitePlus, Specific Peptides from DME, Protein expression images according to data from SPIRE 1MOPED, 2PaxDb, and 3MAXQB 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., Ontologies according to Gene Ontology Consortium 01 Oct 2013 and Entrez Gene, Antibodies by EMD Millipore, R&D Systems, GenScript, Cell Signaling Technology, OriGene, Novus Biologicals, Thermo Fisher Scientific, LSBio, Abcam, and/or Cloud-Clone Corp.)
About This Section

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 (By similarity)
Subcellular location: Sonic hedgehog protein C-product: Secreted, extracellular space (By similarity). Note=The
C-terminal peptide diffuses from the cell (By similarity)
Subcellular location: Sonic hedgehog protein N-product: Cell membrane; Lipid-anchor (By similarity). 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)
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:

  • UniProtKB: 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 activity
  • UniProtKB: Cholesterylation is required for N-product targeting to lipid rafts and multimerization (By similarity)
  • UniProtKB: N-palmitoylation of Cys-24 by HHAT is required for N-product multimerization and full activity (By similarity)
  • View modification sites using PhosphoSitePlus
  • View neXtProt modification sites for NX_Q15465

  • SHH Protein expression data from MOPED1, PaxDb2 and MAXQB3 :    About this image 

    SHH Protein Expression
    REFSEQ proteins: NP_000184.1  
    ENSEMBL proteins: 
     ENSP00000297261   ENSP00000410546   ENSP00000396621   ENSP00000413871  

    Human Recombinant Protein Products for SHH: 
    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 

    Gene Ontology (GO): 5/8 cellular component terms (GO ID links to tree view) (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--

    SHH for ontologies           About GeneDecksing



    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
    GenScript Custom Superior Antibodies 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 

    Assay Products for SHH: 
    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


    (According to HGNC, IUPHAR, InterPro, ProtoNet, UniProtKB, and/or BLOCKS, Sets of similar genes according to GeneDecks)
    About This Section
    5/7 InterPro protein domains (see all 7):
     IPR009045 Hedgehog_sig/DD-Pept_Zn-bd_dom
     IPR001657 Hedgehog
     IPR003586 Hint_dom_C
     IPR000320 Hedgehog_signaling_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
    Similarity: Belongs to the hedgehog family


    SHH 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,
    bound targets from SABiosciences, miRNA Gene Targets from miRTarBase, shRNA from OriGene, RNAi from EMD Millipore, siRNAs from OriGene, QIAGEN, microRNA from QIAGEN, Gene Editing from DNA2.0, Sirion Biotech, Clones from EMD Millipore, OriGene, SwitchGear Genomics, GenScript, Sino Biological, DNA2.0, Vector BioLabs, and Sirion Biotech, Cell Lines from GenScript, LifeMap BioReagents, In Situ Hybridization Assays from Advanced Cell Diagnostics, Ontologies according to Gene Ontology Consortium 01 Oct 2013 via Entrez Gene.)
    About This Section

    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: Anterior Entopeduncular Progenitor Cells in Anterior Entopeduncular Area, Caudal Pharynx Cells in Pharynx (see all 25).

    It affects the following cells: Airway Smooth Muscle Progenitor Cells in Trachea, Anterior Entopeduncular Progenitor Cells in Anterior Entopeduncular Area (see all 113).

    SHH as growth factor is involved in stem cell differentiation protocols towards the derivation of the following cells: Midbrain neural progenitor-like cells from Neural Tube, Ventral midbrain dopaminergic-like neurons from Brain (see all).

         Gene Ontology (GO): 5/10 molecular function terms (GO ID links to tree view) (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
         
    SHH for ontologies           About GeneDecksing


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

         15/26 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  hearing/vestibular/ear  hematopoietic system 
     homeostasis/metabolism  immune system  integument  limbs/digits/tail  mortality/aging 

    SHH for phenotypes           About GeneDecksing

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

       inGenious Targeting Laboratory - Custom generated mouse model solutions for SHH 
       inGenious Targeting Laboratory - Custom generated inducible mouse model solutions 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:
        
    QIAGEN Custom miScript Target Protector blocks miRNA-binding site of human, mouse, rat SHH
    Search QIAGEN for miScript miRNA Assays for microRNAs that regulate SHH
    Browse SwitchGear 3'UTR luciferase reporter plasmids
    Inhib. RNA
    Products:
        
    Browse for Gene Knock-down Tools from EMD Millipore
    OriGene RNAi products in human, mouse, rat for SHH
    QIAGEN FlexiTube/FlexiPlate siRNA for gene silencing in human, mouse, rat SHH

    Gene Editing
    Products:
    DNA2.0 Custom Protein Engineering Service for SHH
    Sirion Biotech Customized adenovirus for overexpression of SHH

    Clone
    Products:
         
    Browse Clones for the Expression of Recombinant Proteins Available from EMD Millipore
    OriGene clones in human, mouse for SHH (see all 6)
    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
    Sirion Biotech Customized lentivirus for stable overexpression of SHH 
                         Customized lentivirus expression plasmids for stable overexpression of SHH 

    Cell Line
    Products:
         
    GenScript Custom overexpressing Cell Line Services for SHH
    Search LifeMap BioReagents cell lines for SHH
    In Situ Assay
    Products:
       

     
    Advanced Cell Diagnostics RNAscope RNA in situ hybridization assays for SHH


    (Pathways according to EMD Millipore, 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 SABiosciences, 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 Oct 2013 via Entrez Gene).
    About This Section

    SuperPaths for SHH About   (see all 12)                                                                                              See pathways by source

    SuperPathContained pathways About
    1Hedgehog Signaling Pathway
    Hedgehog Signaling Pathway0.32
    Hedgehog Pathway0.32
    2Basal cell carcinoma
    Hedgehog signaling pathway0.43
    Basal cell carcinoma0.43
    3Development Hedgehog and PTH signaling pathways in bone and cartilage development
    Development Hedgehog and PTH signaling pathways in bone and cartilage development0.97
    4TWEAK Pathway
    TWEAK Signaling Pathway0.31
    5Wnt / Hedgehog / Notch
    Wnt / Hedgehog / Notch

    Pathways by source                                                                                                                                                                 See SuperPaths
    Show all pathways

    1 EMD Millipore Pathway for SHH
        Development Hedgehog and PTH signaling pathways in bone and cartilage development


    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

    5/8 BioSystems Pathways for SHH (see all 8)
        Heart Development
    Hedgehog Signaling Pathway
    TWEAK Signaling Pathway
    Integrated Pancreatic Cancer Pathway
    Glypican 3 network



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


    SHH for pathways           About GeneDecksing

    Interactions:

        SABiosciences Gene Network CentralTM Interacting Genes and Proteins Network for SHH

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

    5/27 Interacting proteins for SHH (Q154653 ENSP000002972614) via UniProtKB, MINT, STRING, and/or I2D (see all 27)
    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
    SUFUQ9UMX13, ENSP000003589184I2D: score=1 STRING: ENSP00000358918
    About this table

    Gene Ontology (GO): 5/176 biological process terms (GO ID links to tree view) (see all 176):    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--

    SHH for ontologies           About GeneDecksing



    (Chemical Compounds according to UniProtKB, Enzo Life Sciences, EMD Millipore, Tocris Bioscience HMDB, BitterDB, and/or Novoseek, Ligands according to IUPHAR, and Drugs according to DrugBank, Enzo Life Sciences, and/or PharmGKB, with drugs/clinical trials/news search links to CenterWatch)
    About This Section

    SHH for compounds           About GeneDecksing

    EMD Millipore small molecules for SHH:
    Small Molecule - inhibitor
    Browse drugs & compounds from Enzo Life Sciences

    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)

    Search CenterWatch for drugs/clinical trials and news about SHH

    (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,
    RNAi Products from EMD Millipore,
    siRNAs from OriGene, QIAGEN, shRNA from OriGene, microRNA from QIAGEN,
    Tagged/untagged cDNA clones from OriGene, SwitchGear Genomics, GenScript, DNA2.0, Vector BioLabs, Sirion Biotech, Primers from OriGene, SABiosciences, and/or QIAGEN )
    About This Section

    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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    QIAGEN Custom miScript Target Protector blocks miRNA-binding site of human, mouse, rat SHH
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    Browse SwitchGear 3'UTR luciferase reporter plasmids
    Inhib. RNA
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    Browse for Gene Knock-down Tools from EMD Millipore
    OriGene RNAi products in human, mouse, rat for SHH
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    OriGene custom cloning services - gene synthesis, subcloning, mutagenesis, variant library, vector shuttling
    GenScript: all cDNA clones in your preferred vector: SHH (NM_000193)
    DNA2.0 Custom Codon Optimized Gene Synthesis Service for SHH
    Vector BioLabs ready-to-use adenovirus/AAV for human, mouse, rat SHH
    Sirion Biotech Customized lentivirus for stable overexpression of SHH 
                         Customized lentivirus expression plasmids for stable overexpression of SHH 
    Primer
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    OriGene qPCR primer pairs and template standards for SHH
    OriGene qSTAR qPCR primer pairs in human, mouse for SHH
    SABiosciences RT2 qPCR Primer Assay in human, mouse, rat SHH
      QIAGEN QuantiTect SYBR Green Assays in human, mouse, rat SHH
      QIAGEN QuantiFast Probe-based Assays in human, mouse, rat SHH

    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 L38518 AA076750 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™, plus additional links to Genevestigator, and/or SOURCE, and/or BioGPS, and/or UniProtKB,
    PCR Arrays from SABiosciences, Primers from OriGene, SABiosciences, and/or QIAGEN, In Situ Hybridization Assays from Advanced Cell Diagnostics)
    About This Section

    SHH expression in normal human tissues (normalized intensities)      SHH embryonic expression: see
    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 
     5/32 selected tissues (see all 32) fully expand
     
     Brain (Nervous System)    fully expand to see all 34 entries
             Early Floor Plate Cells Mesencephalic Floor Plate
             Thalamus
             Substantia Nigra   
     
     Neural Tube (Nervous System)    fully expand to see all 32 entries
             Early Floor Plate Cells Mesencephalic Floor Plate
             Mesencephalic Floor Plate
     
     Cartilage (Muscoskeletal System)    fully expand to see all 10 entries
             Intervertebral Disc Nucleus Pulposus Cells Sacral Intervertebral Disc
     
     Limb (Muscoskeletal System)    fully expand to see all 8 entries
             Mesenchymal Condensate Cells Zeugopod
             Limb Bud
             limb/hindlimb   
     
     Tooth (Integumentary System)    fully expand to see all 8 entries
             Primary Enamel Knot Cells Enamel Knot
             visceral organ/oral region/upper jaw   

    See SHH Protein Expression from SPIRE MOPED and PaxDB
    Genevestigator expression for SHH

    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

        SABiosciences Expression via Pathway-Focused 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)
    About This Section

    This gene was present in the common ancestor of animals.

    Orthologs for SHH gene from 6/13 species (see all 13)    About this table
    Organism Taxonomic
    classification
    Gene Description Human
    Similarity
    Orthology
    Type
    Details
    mouse
    (Mus musculus)
    Mammalia Shh1 , 5 sonic hedgehog1, 5 87.84(n)1
    92.66(a)1
      5 (14.39 cM)5
    204231  NM_009170.31  NP_033196.11 
     284568155 
    chicken
    (Gallus gallus)
    Aves SHH1 sonic hedgehog 80.81(n)
    84.36(a)
      395615  NM_204821.1  NP_990152.1 
    lizard
    (Anolis carolinensis)
    Reptilia SHH6
    Hedgehog protein
    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
    56.77(n)1
    49.63(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)
    About This Section
    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

    SHH for paralogs           About GeneDecksing


    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) and the Locus Specific Mutation Databases (LSDB), Blood group antigen gene mutations by BGMUT, Resequencing Primers from QIAGEN, Cancer Mutation PCR Arrays and Assays and Copy Number PCR Arrays from SABiosciences)
    About This Section

    10/343 SNPs in SHH are shown (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
    ----------
    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_0626424
    Holoprosencephaly 3 (HPE3)4--see VAR_0626422 A T 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--------
    VAR_0626404
    Holoprosencephaly 3 (HPE3)4--see VAR_0626402 F S 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
    SABiosciences Cancer Mutation 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, Conferences by KenesGroup, Novoseek, Genatlas, GeneTests, GAD, HuGE Navigator, and/or TGDB.)
    About This Section
    OMIM gene information: 600725   
    OMIM disorders: 142945  147250  120200  611638  
    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
    characterized by a wide spectrum of pre- and post-axial abnormalities due to altered SHH expression pattern
    during limb development. TPTPS mutations have been mapped to the 7q36 locus in the LMBR1 gene which contains in
    its intron 5 a long-range cis-regulatory element of SHH expression. 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)

  • 20/121 diseases for SHH (see all 121):    About MalaCards
    tracheoesophageal fistula    pancreatic gastrinoma    radial hemimelia, bilateral    polydactyly of a triphalangeal thumb, bilateral
    polydactyly of a triphalangeal thumb, unilateral    shh-related holoprosencephaly    schizencephaly    esophageal atresia
    hypoplastic tibiae - postaxial polydactyly    microphthalmia with coloboma 5    radial hemimelia, unilateral    holoprosencephaly
    triphalangeal thumb    triphalangeal thumb polysyndactyly syndrome    semilobar holoprosencephaly    splenic marginal zone lymphoma
    renal hypoplasia    smith-lemli-opitz syndrome    alobar holoprosencephaly    nervous system cancer

    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

    SHH for disorders           About GeneDecksing


    Congresses - knowledge worth sharing:  
    Alzheimer's & Parkinson's Diseases Congress (ADPD) 18 - 22 March 2015

    10/15 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)
    About This Section

    PubMed articles for SHH gene, integrated from 9 sources (see all 407):
    (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. (1995)
    2. SONIC HEDGEHOG mutations causing human holoprosencephaly impair neural patterning activity. (PubMed id 12709790)1, 4, 9 Schell-Apacik C....Ming J.E. (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. (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. (1999)
    5. The mutational spectrum of holoprosencephaly-associat ed changes within the SHH gene in humans predicts loss-of-function through eith er key structural alterations of the ligand or its altered synthesis. (PubMed id 19603532)1, 2, 9 Roessler E....Muenke M. (2009)
    6. Molecular mechanisms of Sonic hedgehog mutant effects in holoprosencephaly. (PubMed id 16282375)1, 2, 9 Maity T.... Beachy P.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. (2004)
    8. Genome-wide meta-analyses identifies seven loci assoc iated with platelet aggregation in response to agonists. (PubMed id 20526338)1, 4 Johnson A.D....Becker L.C. (2010)
    9. Maternal genes and facial clefts in offspring: a comp rehensive search for genetic associations in two population-based cleft studies from Scandinavia. (PubMed id 20634891)1, 4 Jugessur A....Murray J.C. (2010)
    10. A candidate gene study of obstructive sleep apnea in European Americans and African Americans. (PubMed id 20538960)1, 4 Larkin E.K....Redline S. (2010)

    (in PubMed, OMIM, and NCBI Bookshelf)
    About This Section
     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
    Entrez Gene: 6469 HGNC: 10848 AceView: SHH Ensembl:ENSG00000164690 euGenes: HUgn6469
    ECgene: SHH Kegg: 6469 H-InvDB: SHH

    (According to HUGE)
    About This Section
      --

    (According to PharmGKB, ATLAS, HORDE, IMGT, LEIDEN, UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL,
    Wikipedia and/or GeneReviews via UniProtKB/Swiss-Prot)
    About This Section
    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/sites/GeneTests/lab/gene/SHH
    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.)
    About This Section
    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, SABiosciences, Novus Biologicals, Sino Biological, Enzo Life Sciences, Abcam, ProSpec, Cloud-Clone Corp., Thermo Fisher Scientific, LSBio, Gene Editing from DNA2.0 and Sirion Biotech, Clones from EMD Millipore, OriGene, GenScript, Sino Biological, DNA2.0, SwitchGear Genomics, Vector BioLabs, Sirion Biotech, Cell lines from GenScript, and LifeMap BioReagents, PCR Arrays from SABiosciences, Drugs and/or compounds from EMD Millipore, Tocris Bioscience, and/or Enzo Life Sciences, In Situ Hybridization Assays from
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    About This Section

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