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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
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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

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_000193.4NP_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:198363
    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:187448
    Hint; Hint module
    pfam01085
    Location:39184
    HH_signal; Hedgehog amino-terminal signalling domain
  2. NM_001310462.2NP_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:1297
    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_047420718.1XP_047276674.1  sonic hedgehog protein isoform X2

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

    See identical proteins and their annotated locations for XP_011514781.1

    Conserved Domains (3) summary
    cd00081
    Location:111276
    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:100361
    Hint; Hint module
    pfam01085
    Location:1297
    HH_signal; Hedgehog amino-terminal signalling domain
  3. XM_011516480.3XP_011514782.1  sonic hedgehog protein isoform X1

    See identical proteins and their annotated locations for XP_011514782.1

    Conserved Domains (3) summary
    cd00081
    Location:111276
    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:100361
    Hint; Hint module
    pfam01085
    Location:1297
    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_054358808.1XP_054214783.1  sonic hedgehog protein isoform X2

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

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

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