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    SHH sonic hedgehog signaling molecule [ Homo sapiens (human) ]

    Gene ID: 6469, updated on 18-Jan-2025

    Summary

    Official Symbol
    SHHprovided by HGNC
    Official Full Name
    sonic hedgehog signaling moleculeprovided by HGNC
    Primary source
    HGNC:HGNC:10848
    See related
    Ensembl:ENSG00000164690 MIM:600725; AllianceGenome:HGNC:10848
    Gene type
    protein coding
    RefSeq status
    REVIEWED
    Organism
    Homo sapiens
    Lineage
    Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
    Also known as
    TPT; HHG1; HLP3; HPE3; SMMCI; ShhNC; TPTPS; MCOPCB5
    Summary
    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]
    Expression
    Biased expression in stomach (RPKM 3.1), urinary bladder (RPKM 2.9) and 10 other tissues See more
    Orthologs
    NEW
    Try the new Gene table
    Try the new Transcript table

    Genomic context

    See SHH in Genome Data Viewer
    Location:
    7q36.3
    Exon count:
    7
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 7 NC_000007.14 (155799980..155812463, complement)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 7 NC_060931.1 (156983127..156995607, complement)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 7 NC_000007.13 (155592674..155605157, complement)

    Chromosome 7 - NC_000007.14Genomic Context describing neighboring genes Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr7:155436294-155437248 Neighboring gene RBM33 divergent transcript Neighboring gene RNA binding motif protein 33 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 26899 Neighboring gene H3K27ac hESC enhancer GRCh37_chr7:155520719-155521219 Neighboring gene MED14-independent group 3 enhancer GRCh37_chr7:155534138-155535337 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 26901 Neighboring gene VISTA enhancer hs1268 Neighboring gene Sharpr-MPRA regulatory region 9615 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 26902 Neighboring gene ReSE screen-validated silencer GRCh37_chr7:155561116-155561309 Neighboring gene CDK7 strongly-dependent group 2 enhancer GRCh37_chr7:155567610-155568809 Neighboring gene Sharpr-MPRA regulatory region 3765 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr7:155574696-155575231 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr7:155575232-155575766 Neighboring gene MPRA-validated peak6863 silencer Neighboring gene ATAC-STARR-seq lymphoblastoid active region 26903 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr7:155597860-155598829 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr7:155598830-155599798 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr7:155607457-155608100 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr7:155608399-155608900 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr7:155628074-155629066 Neighboring gene BRD4-independent group 4 enhancer GRCh37_chr7:155632935-155634134 Neighboring gene ReSE screen-validated silencer GRCh37_chr7:155638472-155638619 Neighboring gene MPRA-validated peak6864 silencer Neighboring gene BRD4-independent group 4 enhancer GRCh37_chr7:155661375-155662574 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 26904 Neighboring gene CDK7 strongly-dependent group 2 enhancer GRCh37_chr7:155678617-155679816 Neighboring gene P300/CBP strongly-dependent group 1 enhancer GRCh37_chr7:155743904-155745103 Neighboring gene uncharacterized LOC124901788 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr7:155745489-155745989 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr7:155747182-155747910 Neighboring gene P300/CBP strongly-dependent group 1 enhancer GRCh37_chr7:155754590-155755789 Neighboring gene uncharacterized LOC389602

    Genomic regions, transcripts, and products

    Expression

    • Project title: Tissue-specific circular RNA induction during human fetal development
    • Description: 35 human fetal samples from 6 tissues (3 - 7 replicates per tissue) collected between 10 and 20 weeks gestational time were sequenced using Illumina TruSeq Stranded Total RNA
    • BioProject: PRJNA270632
    • Publication: PMID 26076956
    • Analysis date: Mon Apr 2 22:54:59 2018

    Bibliography

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?

    Phenotypes

    BioGRID CRISPR Screen Phenotypes (14 hits/1262 screens)

    Associated conditions

    Copy number response

    Description
    Copy number response
    Triplosensitivity

    No evidence available (Last evaluated 2020-06-24)

    ClinGen Genome Curation PagePubMed
    Haploinsufficency

    Sufficient evidence for dosage pathogenicity (Last evaluated 2020-06-24)

    ClinGen Genome Curation PagePubMed

    EBI GWAS Catalog

    Description
    Genome-wide meta-analyses identifies seven loci associated with platelet aggregation in response to agonists.
    EBI GWAS Catalog
    Identification of a candidate gene for astigmatism.
    EBI GWAS Catalog

    Pathways from PubChem

    Interactions

    General gene information

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables calcium ion binding  
    enables calcium ion binding PubMed 
    enables cholesterol-protein transferase activity  
    enables endopeptidase activity  
    enables glycosaminoglycan binding  
    enables laminin-1 binding  
    enables morphogen activity PubMed 
    enables morphogen activity PubMed 
    enables patched binding  
    enables patched binding PubMed 
    enables peptidase activity  
    enables protein binding PubMed 
    enables zinc ion binding PubMed 
    Items 1 - 25 of 163
    Process Evidence Code Pubs
    involved_in Bergmann glial cell differentiation  
    involved_in CD4-positive or CD8-positive, alpha-beta T cell lineage commitment PubMed 
    involved_in T cell differentiation in thymus  
    involved_in T cell proliferation  
    involved_in alpha-beta T cell differentiation  
    involved_in androgen metabolic process  
    involved_in animal organ formation  
    involved_in apoptotic signaling pathway  
    involved_in artery development  
    involved_in axon guidance  
    involved_in blood coagulation  
    involved_in branching involved in blood vessel morphogenesis  
    involved_in branching involved in salivary gland morphogenesis  
    involved_in branching involved in ureteric bud morphogenesis  
    involved_in branching morphogenesis of an epithelial tube  
    involved_in bud outgrowth involved in lung branching  
    involved_in camera-type eye development  
    involved_in canonical Wnt signaling pathway  
    involved_in cell development  
    involved_in cell fate specification  
    involved_in cell fate specification  
    involved_in cell-cell signaling  
    involved_in cellular response to lithium ion  
    involved_in central nervous system development  
    involved_in cerebellar granule cell precursor proliferation  
    involved_in determination of left/right asymmetry in lateral mesoderm  
    involved_in determination of left/right asymmetry in lateral mesoderm PubMed 
    involved_in dopaminergic neuron differentiation PubMed 
    involved_in dorsal/ventral neural tube patterning  
    involved_in dorsal/ventral pattern formation  
    involved_in ectoderm development  
    involved_in embryonic digestive tract morphogenesis  
    involved_in embryonic digit morphogenesis  
    involved_in embryonic foregut morphogenesis  
    involved_in embryonic forelimb morphogenesis  
    involved_in embryonic hindlimb morphogenesis  
    involved_in embryonic limb morphogenesis  
    involved_in embryonic pattern specification PubMed 
    involved_in embryonic skeletal system development  
    involved_in endocytosis  
    involved_in epithelial cell proliferation involved in prostate gland development  
    involved_in epithelial cell proliferation involved in salivary gland morphogenesis  
    acts_upstream_of_or_within epithelial-mesenchymal cell signaling PubMed 
    involved_in establishment of epithelial cell polarity  
    involved_in forebrain development  
    involved_in formation of anatomical boundary  
    involved_in hair follicle morphogenesis  
    involved_in heart development  
    involved_in heart looping  
    involved_in hindbrain development  
    involved_in hindgut morphogenesis  
    involved_in inner ear development  
    involved_in intein-mediated protein splicing  
    involved_in intermediate filament organization  
    involved_in left lung development  
    involved_in limb bud formation  
    involved_in lung development  
    involved_in lung epithelium development  
    involved_in lung lobe morphogenesis  
    involved_in lung-associated mesenchyme development  
    involved_in lymphoid progenitor cell differentiation PubMed 
    involved_in male genitalia development  
    involved_in mesenchymal cell apoptotic process  
    involved_in mesenchymal cell proliferation involved in lung development  
    involved_in mesenchymal smoothened signaling pathway involved in prostate gland development  
    involved_in metanephric collecting duct development PubMed 
    involved_in metanephric mesenchymal cell proliferation involved in metanephros development  
    involved_in metanephros development  
    involved_in midbrain development  
    involved_in myoblast differentiation  
    involved_in negative regulation of T cell differentiation in thymus  
    involved_in negative regulation of T cell proliferation  
    involved_in negative regulation of alpha-beta T cell differentiation  
    involved_in negative regulation of apoptotic process  
    involved_in negative regulation of canonical Wnt signaling pathway  
    involved_in negative regulation of cell differentiation  
    involved_in negative regulation of cell migration  
    involved_in negative regulation of cholesterol efflux  
    involved_in negative regulation of dopaminergic neuron differentiation  
    involved_in negative regulation of gene expression  
    involved_in negative regulation of kidney smooth muscle cell differentiation  
    involved_in negative regulation of mesenchymal cell apoptotic process  
    involved_in negative regulation of proteasomal ubiquitin-dependent protein catabolic process  
    involved_in negative regulation of transcription by RNA polymerase II  
    involved_in negative regulation of transcription elongation by RNA polymerase II  
    involved_in negative regulation of ureter smooth muscle cell differentiation  
    involved_in negative thymic T cell selection  
    involved_in neural crest cell migration  
    involved_in neuroblast proliferation  
    involved_in neuron fate commitment  
    involved_in odontogenesis of dentin-containing tooth  
    involved_in oligodendrocyte development  
    involved_in oligodendrocyte differentiation  
    involved_in osteoblast development  
    involved_in pancreas development  
    involved_in pattern specification process  
    involved_in polarity specification of anterior/posterior axis  
    involved_in positive regulation of DNA-templated transcription PubMed 
    involved_in positive regulation of T cell differentiation in thymus  
    involved_in positive regulation of Wnt signaling pathway  
    involved_in positive regulation of alpha-beta T cell differentiation  
    involved_in positive regulation of astrocyte differentiation  
    involved_in positive regulation of cell division PubMed 
    involved_in positive regulation of cell population proliferation PubMed 
    involved_in positive regulation of cell population proliferation  
    involved_in positive regulation of cerebellar granule cell precursor proliferation  
    involved_in positive regulation of epithelial cell proliferation involved in prostate gland development  
    involved_in positive regulation of gene expression  
    involved_in positive regulation of immature T cell proliferation in thymus  
    involved_in positive regulation of kidney smooth muscle cell differentiation  
    involved_in positive regulation of mesenchymal cell proliferation involved in ureter development  
    involved_in positive regulation of neuroblast proliferation  
    involved_in positive regulation of oligodendrocyte differentiation  
    involved_in positive regulation of protein import into nucleus  
    involved_in positive regulation of sclerotome development PubMed 
    involved_in positive regulation of skeletal muscle cell proliferation  
    involved_in positive regulation of skeletal muscle tissue development  
    involved_in positive regulation of smoothened signaling pathway PubMed 
    involved_in positive regulation of striated muscle cell differentiation  
    acts_upstream_of positive regulation of transcription by RNA polymerase II  
    involved_in positive regulation of transcription by RNA polymerase II  
    involved_in positive regulation of ureter smooth muscle cell differentiation  
    involved_in positive thymic T cell selection  
    involved_in primary prostatic bud elongation  
    involved_in prostate epithelial cord elongation  
    involved_in prostate gland development  
    involved_in protein autoprocessing  
    involved_in protein import into nucleus  
    involved_in regulation of cell population proliferation  
    involved_in regulation of gene expression  
    involved_in regulation of glial cell proliferation  
    involved_in regulation of mesenchymal cell proliferation involved in prostate gland development  
    involved_in regulation of nodal signaling pathway PubMed 
    involved_in regulation of odontogenesis  
    involved_in regulation of prostatic bud formation  
    involved_in regulation of protein localization to nucleus PubMed 
    involved_in regulation of proteolysis  
    involved_in regulation of stem cell proliferation  
    involved_in right lung development  
    involved_in roof of mouth development  
    involved_in salivary gland cavitation  
    involved_in self proteolysis  
    involved_in skeletal muscle cell proliferation  
    involved_in skeletal muscle fiber differentiation  
    involved_in smooth muscle tissue development PubMed 
    involved_in smoothened signaling pathway  
    involved_in smoothened signaling pathway PubMed 
    involved_in smoothened signaling pathway PubMed 
    involved_in smoothened signaling pathway  
    involved_in somite development  
    involved_in spinal cord dorsal/ventral patterning  
    involved_in spinal cord motor neuron differentiation  
    involved_in stem cell development  
    involved_in stem cell proliferation  
    involved_in telencephalon regionalization  
    involved_in thalamus development  
    involved_in thymus development  
    involved_in thyroid gland development  
    involved_in trachea morphogenesis  
    involved_in tracheoesophageal septum formation  
    involved_in trunk neural crest cell migration  
    involved_in vasculogenesis  
    involved_in ventral midline development PubMed 
    Items 1 - 25 of 163
    Component Evidence Code Pubs
    located_in Golgi apparatus PubMed 
    located_in Golgi membrane  
    located_in cell surface  
    located_in collagen-containing extracellular matrix PubMed 
    located_in cytosol  
    located_in endoplasmic reticulum PubMed 
    located_in endoplasmic reticulum lumen  
    located_in endoplasmic reticulum membrane  
    located_in extracellular region PubMed 
    located_in extracellular region  
    is_active_in extracellular space  
    located_in extracellular space PubMed 
    located_in extracellular space  
    located_in membrane raft  
    located_in plasma membrane  

    General protein information

    Preferred Names
    sonic hedgehog protein
    Names
    shh unprocessed N-terminal signaling and C-terminal autoprocessing domains
    sonic hedgehog homolog

    NCBI Reference Sequences (RefSeq)

    NEW Try the new Transcript table

    RefSeqs maintained independently of Annotated Genomes

    These reference sequences exist independently of genome builds. Explain

    These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

    Genomic

    1. NG_007504.2 RefSeqGene

      Range
      4811..17294
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. NM_000193.4 → NP_000184.1  sonic hedgehog protein isoform 1 preproprotein

      See identical proteins and their annotated locations for NP_000184.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) represents the longest transcript and encodes the longer isoform (1).
      Source sequence(s)
      AC078834, BX109787, BX452210, BY797055, L38518
      Consensus CDS
      CCDS5942.1
      UniProtKB/Swiss-Prot
      A4D247, Q15465, Q75MC9
      UniProtKB/TrEMBL
      D9ZGF9
      Related
      ENSP00000297261.2, ENST00000297261.7
      Conserved Domains (3) summary
      cd00081
      Location:198 → 363
      Hint; Hedgehog/Intein domain, found in Hedgehog proteins as well as proteins which contain inteins and undergo protein splicing (e.g. DnaB, RIR1-2, GyrA and Pol). In protein splicing an intervening polypeptide sequence - the intein - is excised from a protein, ...
      pfam01079
      Location:187 → 448
      Hint; Hint module
      pfam01085
      Location:39 → 184
      HH_signal; Hedgehog amino-terminal signalling domain
    2. NM_001310462.2 → NP_001297391.1  sonic hedgehog protein isoform 2

      Status: REVIEWED

      Description
      Transcript Variant: This variant (2) differs in the 5' and 3' UTRs and has multiple coding region differences, compared to variant 1. It encodes isoform 2 which has a shorter and distinct N-terminus and a shorter and distinct C-terminus, compared to isoform 1.
      Source sequence(s)
      AC078834, AI192528, AY927452, AY927455
      UniProtKB/TrEMBL
      C9JC48
      Related
      ENSP00000396621.1, ENST00000430104.5
      Conserved Domains (1) summary
      pfam01085
      Location:12 → 97
      HH_signal; Hedgehog amino-terminal signalling domain

    RNA

    1. NR_132318.2 RNA Sequence

      Status: REVIEWED

      Description
      Transcript Variant: This variant (3) uses an alternate 5' and 3' exon structure, compared to variant 1. This variant is represented as non-coding because the use of the 5'-most expected translational start codon renders the transcript a candidate for nonsense-mediated mRNA decay (NMD).
      Source sequence(s)
      AC078834, AI192528, AY927453, AY927454, L38518
      Related
      ENST00000441114.5
    2. NR_132319.2 RNA Sequence

      Status: REVIEWED

      Description
      Transcript Variant: This variant (4) uses an alternate 5' and 3' exon structure, compared to variant 1. This variant is represented as non-coding because the use of the 5'-most expected translational start codon renders the transcript a candidate for nonsense-mediated mRNA decay (NMD).
      Source sequence(s)
      AC078834, AI192528, AY927453
      Related
      ENST00000435425.1

    RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

    The following sections contain reference sequences that belong to a specific genome build. Explain

    Reference GRCh38.p14 Primary Assembly

    Genomic

    1. NC_000007.14 Reference GRCh38.p14 Primary Assembly

      Range
      155799980..155812463 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_047420718.1 → XP_047276674.1  sonic hedgehog protein isoform X2

    2. XM_011516479.3 → XP_011514781.1  sonic hedgehog protein isoform X1

      See identical proteins and their annotated locations for XP_011514781.1

      Conserved Domains (3) summary
      cd00081
      Location:111 → 276
      Hint; Hedgehog/Intein domain, found in Hedgehog proteins as well as proteins which contain inteins and undergo protein splicing (e.g. DnaB, RIR1-2, GyrA and Pol). In protein splicing an intervening polypeptide sequence - the intein - is excised from a protein, ...
      pfam01079
      Location:100 → 361
      Hint; Hint module
      pfam01085
      Location:12 → 97
      HH_signal; Hedgehog amino-terminal signalling domain
    3. XM_011516480.3 → XP_011514782.1  sonic hedgehog protein isoform X1

      See identical proteins and their annotated locations for XP_011514782.1

      Conserved Domains (3) summary
      cd00081
      Location:111 → 276
      Hint; Hedgehog/Intein domain, found in Hedgehog proteins as well as proteins which contain inteins and undergo protein splicing (e.g. DnaB, RIR1-2, GyrA and Pol). In protein splicing an intervening polypeptide sequence - the intein - is excised from a protein, ...
      pfam01079
      Location:100 → 361
      Hint; Hint module
      pfam01085
      Location:12 → 97
      HH_signal; Hedgehog amino-terminal signalling domain

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060931.1 Alternate T2T-CHM13v2.0

      Range
      156983127..156995607 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_054358808.1 → XP_054214783.1  sonic hedgehog protein isoform X2

    2. XM_054358806.1 → XP_054214781.1  sonic hedgehog protein isoform X1

    3. XM_054358807.1 → XP_054214782.1  sonic hedgehog protein isoform X1

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