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

SHH Gene

protein-coding   GIFtS: 70
GCID: GC07M155592

sonic hedgehog

(Previous names: sonic hedgehog (Drosophila) homolog, sonic hedgehog homolog...)
(Previous symbols: HPE3, HLP3)
 Explore 103 diseases affiliated with
SHH via
MalaCards
our new
 Human Malady Compendium 
Biological research products
for SHH    

Aliases
for SHH gene

(According to 1HGNC, 2Entrez Gene,
3UniProtKB/Swiss-Prot, 4UniProtKB/TrEMBL, 5OMIM, 6GeneLoc, 7Ensembl, 8DME, 9miRBase, and/or 10fRNAdb)
About This Section
Aliases
Sonic Hedgehog1 2     TPTPS1 2
HLP31 2 5     Sonic Hedgehog (Drosophila) Homolog1
HPE31 2 5     Sonic Hedgehog Homolog (Drosophila)1
MCOPCB51 2 5     Sonic Hedgehog Homolog2
SMMCI1 2 5     Sonic Hedgehog Protein2
HHG11 2     HHG-13
TPT1 2     

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


Summaries
for SHH gene

(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:
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)

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:
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)


Genomic Views
for SHH 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 69), Regulatory elements and Epigenetics data according to QIAGEN, SABiosciences, and/or SwitchGear Genomics)
About This Section
RefSeq DNA sequence:
NC_000007.13  NC_018918.1  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     

Proteins
for SHH gene

(According to 1UniProtKB, HORDE, neXtProt, Ensembl, and/or Reactome, Modification sites according to 2PhosphoSitePlus, Specific Peptides from DME, Protein expression images according to data from SPIRE MOPED and PaxDb, 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 Uscn,
Biochemical Assays by EMD Millipore, R&D Systems, OriGene, GenScript, Cell Signaling Technology, Enzo Life Sciences, and/or Uscn, Ontologies according to Gene Ontology Consortium 01 Mar 2013 and Entrez Gene, Antibodies by EMD Millipore, R&D Systems, GenScript, Cell Signaling Technology, OriGene, Novus Biologicals, Thermo Fisher Scientific, Abcam, and/or Uscn)
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

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
  • View modification sites using PhosphoSitePlus2
  • View neXtProt modification sites for NX_Q15465

    • SHH Protein expression data from MOPED and PaxDb:    About this image 
    Estimated protein expression log10 (pmol).

    REFSEQ proteins: NP_000184.1  
    ENSEMBL proteins: 
     ENSP00000297261   ENSP00000410546   ENSP00000396621   ENSP00000413871  

    Human Recombinant Protein Products: 
    EMD Millipore Purified and/or Recombinant SHH Protein
    R&D Systems Recombinant & Natural Proteins for SHH (Sonic Hedgehog/Shh)
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    OriGene Purified Protein: SHH
    OriGene Protein Over-expression Lysate: SHH
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    GenScript Purified and Recombinant Proteins for SHH
    Novus Biologicals SHH Proteins
    Novus Biologicals SHH Lysate
    Browse Sino Biological Recombinant Proteins
    ProSpec Recombinant Protein for SHH
    Uscn Proteins for SHH

    Gene Ontology (GO): 5/11 cellular component terms (GO ID links to tree view) (see all 11):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0005576extracellular region ----
    GO:0005615extracellular space ISS--
    GO:0005624membrane fraction ----
    GO:0005634nucleus IEA--
    GO:0005783endoplasmic reticulum ----


    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 (see all 3): SHH
    OriGene Custom Antibody Services for SHH 
    GenScript Custom Superior Antibodies Services for SHH
    Novus Biologicals SHH Antibodies
    Abcam antibodies for SHH 
    Uscn Antibodies for SHH
    ThermoFisher Antibodies for SHH

    Assay Products for SHH: 
    Browse Kits and Assays available from EMD Millipore
    OriGene Custom Immunoassay Development
    Browse OriGene Fluorogenic Cell Assay Kits
    Browse R&D Systems for biochemical assays
    GenScript Custom Assay Services for SHH
    Browse Enzo Life Sciences for kits & assays
    Uscn ELISAs and CLIAs for SHH

    Protein Domains /
    Families
    for SHH gene

    (According to InterPro, ProtoNet, UniProtKB, and/or BLOCKS, Sets of similar genes according to GeneDecks)
    About This Section
    SHH for domains           About GeneDecksing

    5/7 InterPro domains/families (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 families:
    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


    Function
    for SHH gene

    (According to 1UniProtKB, Genatlas, LifeMap Discovery™, IUBMB, and/or 2DME, Human phenotypes from GenomeRNAi, Animal models from MGI Mar 06 2013,
    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, Clones from EMD Millipore, OriGene, SwitchGear Genomics, GenScript, Sino Biological, DNA2.0, and Vector BioLabs, Cell Lines from GenScript, LifeMap BioReagents, In Situ Hybridization Assays from Advanced Cell Diagnostics, Ontologies according to Gene Ontology Consortium 01 Mar 2013 via Entrez Gene.)
    About This Section
    Function Summary:

         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)

         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: Branchial Arch 1 Ectoderm Cells in Branchial Arch 1, Branchial Arch 2 Ectoderm Cells in Branchial Arch 2 (see all 21).

    It affects the following cells: Airway Smooth Muscle Progenitor Cells in Trachea, Apical Ectodermal Ridge Cells in Limb Ectoderm (see all 96).

    SHH as growth factor is involved in stem cell differentiation protocols towards the derivation of the following cells: Primitive neural rosettes, Retina-like cells (see all 20).

    miRNA
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    Browse MicroRNA Expression Plasmids
    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 29mer shRNA kits in GFP-retroviral vector in human, mouse, rat for SHH (see all 7)
    OriGene shRNA RFP: SHH
    OriGene siRNA: SHH
    QIAGEN FlexiTube/FlexiPlate siRNA for gene silencing in human, mouse, rat SHH

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

    Clone
    Products:             		Browse Clones for the Expression of Recombinant Proteins Available from EMD Millipore
    OriGene Myc/DDK tagged cDNA clones in CMV expression vector in human, mouse, rat for SHH (see all 3)
    OriGene untagged cDNA clones in CMV expression vector in human, 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 

    Cell Line
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    Search LifeMap BioReagents cell lines for SHH

    In Situ Assay
    Products:       
         		Advanced Cell Diagnostics RNAscope RNA in situ hybridization assays for SHH

    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


    1 GenomeRNAi human phenotype for SHH:
     Decreased Salmonella enterica  

    Animal Models:
         Mouse knock-outs for SHH: Shhtm3Amc Shhtm1Amc Shhtm1Chg
         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


    Pathways & Interactions
    for SHH gene

    (Pathways according to EMD Millipore, R&D Systems, Cell Signaling Technology, KEGG, PharmGKB, BioSystems, 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 Mar 2013 via Entrez Gene).
    About This Section

    Unified GeneCards pathways - 5/12 super-pathways (see all 12) About this table 
    See pathways by source

    Super-pathwaycontained gene-specific pathways
    1Development_Hedgehog and PTH signaling pathways in bone and cartilage development
    		Development_Hedgehog and PTH signaling pathways in bone and cartilage development1.00
    		Development Hedgehog and PTH signaling pathways in bone and cartilage development0.97
    2Hedgehog Signaling Pathway
    		Hedgehog Signaling Pathway1.00
    		Hedgehog Pathway0.32
    3Basal cell carcinoma
    		Basal cell carcinoma1.00
    		Hedgehog signaling pathway0.41
    4Integrated Pancreatic Cancer Pathway
    		Integrated Pancreatic Cancer Pathway1.00
    		Integrated Pancreatic Cancer Pathway0.99
    5Wnt / Hedgehog / Notch
    		Wnt / Hedgehog / Notch1.00

    Pathway sources
    See GeneCards unified pathways
    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

    5/9 BioSystems Pathways for SHH (see all 9) 
        Heart Development
    Hedgehog Signaling Pathway
    Integrated Pancreatic Cancer Pathway
    Integrated Pancreatic Cancer Pathway
    TWEAK Signaling Pathway


    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): 5/191 biological process terms (GO ID links to tree view) (see all 191):    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



    Drugs & Compounds
    for SHH gene

    (Chemical Compounds according to UniProtKB, Enzo Life Sciences, EMD Millipore, Tocris Bioscience HMDB, BitterDB, and/or Novoseek, 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 #
    SANT-2Inhibitor of Hedgehog (Hh) signaling; antagonizes smoothened activity[329196-48-7]
    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 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 

    Transcripts
    for SHH gene

    (Secondary structures according to fRNAdb,
    GenBank/EMBL/DDBJ Accessions according to
    Unigene (Build 235 Homo sapiens; Mar 10 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,
    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, 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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    Clone
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    Primer
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      QIAGEN QuantiTect SYBR Green Assays in human, mouse, rat SHH
      QIAGEN QuantiFast Probe-based Assays in human, mouse, rat SHH

    Additional cDNA 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


    Expression
    for SHH gene

    (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)
    See probesets specificity/sensitivity at GeneAnnot
    About this imageBioGPS
    CGAP TAG: GCGGTCAAGT

    Microarray
    RNAseq (Illumina Body Map)
    (100×FPKM)½
    SAGE (Serial Analysis of Gene Expression)
    About this image

    SHH expression in embryonic tissues and stem cells
    Expression by the Database of Embryonic development, Stem cell research, and Regenerative medicine    About this table
    10/55 LifeMap In Vivo Development Anatomical Compartments/Cells (see all 55) 
    Tissue Anatomical Compartment CellCategory (developmental path)
    EyeGanglion Cell LayerMature Ganglion CellsGanglion, Retina
    Neural TubeDiencephalic Floor PlateEarly Caudal Floor Plate CellsNeural Ectoderm
    Neural TubeDiencephalic Floor PlateLate Caudal Floor Plate CellsNeural Ectoderm
    Neural TubeMesencephalic Floor PlateEarly Floor Plate CellsNeural Ectoderm
    Neural TubeMesencephalic Floor PlateLate Floor Plate CellsNeural Ectoderm
    Neural TubeRhombencephalonFloor Plate Cells Neural Ectoderm
    Primitive StreakNotochordNotochord CellsCartilage
    Gut TubeVentral Foregut EndodermVentral Foregut Endoderm CellsEndoderm
    PancreasPrepancreatic Dorsal Foregut EndodermPre-Pancreatic Foregut Endoderm CellsPancreas
    PancreasPrepancreatic Ventral Foregut EndodermPre-Pancreatic Foregut Endoderm CellsPancreas
    Expression: Positive    Negative     Selective marker
    Experimental details: Curated     Microarrays     In-situ hybridization
    Stem Cell Differentiation: 3 LifeMap Cells 
    NameCategory
    Anterior neural specified EBs (Differentiation of h...)
    Photoreceptor-like cells (Differentiation of h...)
    Posterior foregut-like cells (A scalable, suspensi...)

    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

    Primer
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    Orthologs
    for SHH gene

    (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 5/17 species (see all 17)    About this table
    Organism Taxonomic
    classification    		 Gene Description Human
    Similarity    		 Orthology
    Type    		 Details
    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
    		 --
    		 80(a)
    		 1 ↔ 1
    		 6(5937141-5968324)
    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
    for SHH gene

    (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


    Genomic Variants
    for SHH gene

    (SNPs/Variants according to the 1NCBI SNP Database, 2Ensembl, 3PupaSUITE, UniProtKB, 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

    10/215 NCBI SNPs in SHH are shown (see all 215)     About this table
    Genomic DataTranscription Related DataAllele Frequencies
    SNP IDValidClinical
    significance    		Chr 7 posSequence#AA
    Chg    		TypeMore#Allele
    freq    		PopTotal
    sample    		More
    ----------
    rs1048940481,2
    		Cpathogenic154827275(-) ACGCTC/GCGGGT 2 P A mis10--------
    rs1048940521,2
    		Cpathogenic154827550(-) CGCTGC/TGCACA 2 A V mis10--------
    rs1048940461,2
    		Cpathogenic154827695(-) CCGGGG/TAGCCC 2 E * stg10--------
    rs1048940511,2
    		Cpathogenic154827779(-) TGATCG/TAGACG 2 E * stg10--------
    rs1048940431,2
    		Cpathogenic154827869(-) TGCTGA/GCGGCG 2 T A mis10--------
    rs1048940421,2
    		Cpathogenic154827874(-) CCGCGA/TGCTGG 2 E V mis10--------
    rs1048940531,2
    		Cpathogenic154830731(-) GGGCTA/GGGACG 2 * W stg10--------
    rs1048940401,2
    		Cpathogenic154830765(-) ACCAGC/G/TGGCCA 3 R G W mis10--------
    rs1048940491,2
    		Cpathogenic154830783(-) TGGCCA/TTCTCG 2 I F mis10--------
    rs1048940451,2
    		Cpathogenic154830801(-) AGGACA/TAGTTG 2 K * stg10--------

    HapMap Linkage Disequilibrium report for SHH (155592680 - 155604967 bp)
    Structural Variations (Copy Number Variations, Insertions/Deletions, Inversions)
          Database of Genomic Variants (DGV) variations for SHH: --
    Human Gene Mutation Database (HGMD): SHH

    SABiosciences Cancer Mutation PCR Assays
    QIAGEN SeqTarget long-range PCR primers in human, mouse, rat for resequencing SHH
    DNA2.0 Custom Variant and Variant Library Synthesis for SHH

    Disorders / Diseases
    for SHH gene

    (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.)
    About This Section
    SHH for disorders           About GeneDecksing

    OMIM gene information: 600725   
    OMIM disorders: 142945  147250  120200  611638  
    UniProtKB/Swiss-Prot: SHH_HUMAN, Q15465
  • Defects in SHH are the cause of microphthalmia isolated with coloboma type 5 (MCOPCB5) [MIM:611638].
    • Microphthalmia is a clinically heterogeneous 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, cataract and other abnormalities like cataract 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)
  • Defects in SHH are the cause of holoprosencephaly type 3 (HPE3) [MIM:142945]. Holoprosencephaly (HPE)
    • [MIM:236100] is the most common 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 HPE3 cases are apparently sporadic, although clear
    examples of autosomal dominant inheritance have been described. Interestingly, up to 30% of obligate carriers of HPE3
    gene in autosomal dominant pedigrees are clinically unaffected
  • Defects in SHH are a cause of solitary median maxillary central incisor (SMMCI) [MIM:147250]. SMMCI is a rare
    • dental anomaly characterized by the congenital absence of one maxillary central incisor
  • Defects in SHH are the cause of triphalangeal thumb-polysyndactyly syndrome (TPTPS) [MIM:174500]. TPTPS is an
    • 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

    20/103 diseases for SHH (see all 103):    About MalaCards
    tracheoesophageal fistula    smith-lemli-opitz syndrome    solitary median maxillary central incisor    holoprosencephaly
    esophageal atresia    triphalangeal thumb-polysyndactyly syndrome    basal cell carcinoma    triphalangeal thumb
    polydactyly    splenic marginal zone lymphoma    pallister-hall syndrome    spinal cord injury
    esophagitis    craniofacial anomalies    brachydactyly type a1    diffuse large b-cell lymphoma
    carcinoma    sacral agenesis    situs ambiguus    hidradenitis suppurativa

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

    10/15 Novoseek 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
    Holoprosencephaly

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

    Export disorders for SHH gene to outside databases

    Publications
    for SHH gene

    (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 387):
    (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. Triphalangeal thumb-polysyndactyly syndrome and syndactyly type IV are caused by genomic duplications involving the long range, limb- specific SHH enhancer. (PubMed id 18417549)1, 2 Sun M.... Zhang X. (2008)
    9. Human plasma N-glycoproteome analysis by immunoaffinity subtraction, hydrazide chemistry, and mass spectrometry. (PubMed id 16335952)1, 2 Liu T.... Smith R.D. (2005)
    10. Mutation analysis of the Sonic hedgehog promoter and putative enhancer elements in Parkinson's disease patients. (PubMed id 15249145)1, 4 Bak M....Tommerup N. (2004)

    External Searches for SHH gene

    (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)

    Genome Databases showing SHH gene

    (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

    Other Databases showing SHH gene

    (According to HUGE)
    About This Section
    		   --

    Specialized Databases showing SHH gene

    (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/

    Intellectual Property
    for SHH gene

    (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



    Products
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    About This Section

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