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].

sonic hedgehogMIM:600725Ensembl:ENSG00000164690HGNC:HGNC:10848PA357527q36.3

GO terms in SHH

Term TypeEvidence TypeGO Term IDGO Des.
MFIDAGO:0005113patched binding
MFIDAGO:0005509calcium ion binding
MFIPIGO:0005515protein binding
MFIEAGO:0005539glycosaminoglycan binding
MFIEAGO:0008233peptidase activity
MFIDAGO:0008270zinc ion binding
MFNASGO:0016015morphogen activity
MFTASGO:0016015morphogen activity
MFISSGO:0043237laminin-1 binding
BPISSGO:0000122negative regulation of transcription by RNA polymerase II
BPISSGO:0001569branching involved in blood vessel morphogenesis
BPISSGO:0001656metanephros development
BPISSGO:0001658branching involved in ureteric bud morphogenesis
BPISSGO:0001708cell fate specification
BPISSGO:0001755neural crest cell migration
BPISSGO:0001947heart looping
BPIEAGO:0002052positive regulation of neuroblast proliferation
BPIEAGO:0002076osteoblast development
BPIMPGO:0002320lymphoid progenitor cell differentiation
BPISSGO:0003140determination of left/right asymmetry in lateral mesoderm
BPIEPGO:0007224smoothened signaling pathway
BPISSGO:0007224smoothened signaling pathway
BPISSGO:0007228positive regulation of hh target transcription factor activity
BPISSGO:0007267cell-cell signaling
BPISSGO:0007389pattern specification process
BPIEAGO:0007398ectoderm development
BPISSGO:0007405neuroblast proliferation
BPISSGO:0007411axon guidance
BPISSGO:0007417central nervous system development
BPTASGO:0007418ventral midline development
BPIEAGO:0007442hindgut morphogenesis
BPISSGO:0007507heart development
BPIEAGO:0007596blood coagulation
BPISSGO:0008209androgen metabolic process
BPIDAGO:0008284positive regulation of cell proliferation
BPISSGO:0008284positive regulation of cell proliferation
BPTASGO:0009880embryonic pattern specification
BPISSGO:0009949polarity specification of anterior/posterior axis
BPISSGO:0009953dorsal/ventral pattern formation
BPIEAGO:0010469regulation of signaling receptor activity
BPIEAGO:0014003oligodendrocyte development
BPIEAGO:0014706striated muscle tissue development
BPIEAGO:0014858positive regulation of skeletal muscle cell proliferation
BPIEAGO:0014902myotube differentiation
BPIEAGO:0016539intein-mediated protein splicing
BPIEAGO:0021513spinal cord dorsal/ventral patterning
BPIEAGO:0021522spinal cord motor neuron differentiation
BPIEAGO:0021794thalamus development
BPIEAGO:0021904dorsal/ventral neural tube patterning
BPISSGO:0021930cerebellar granule cell precursor proliferation
BPIEAGO:0021938smoothened signaling pathway involved in regulation of cerebellar granule cell precursor cell proliferation
BPIEAGO:0021978telencephalon regionalization
BPIEAGO:0030010establishment of cell polarity
BPISSGO:0030162regulation of proteolysis
BPIEAGO:0030177positive regulation of Wnt signaling pathway
BPISSGO:0030324lung development
BPISSGO:0030326embryonic limb morphogenesis
BPISSGO:0030336negative regulation of cell migration
BPISSGO:0030539male genitalia development
BPISSGO:0030850prostate gland development
BPIEAGO:0030878thyroid gland development
BPISSGO:0030900forebrain development
BPISSGO:0030901midbrain development
BPISSGO:0030902hindbrain development
BPIEAGO:0031016pancreas development
BPIEAGO:0031069hair follicle morphogenesis
BPIEAGO:0032435negative regulation of proteasomal ubiquitin-dependent protein catabolic process
BPISSGO:0033077T cell differentiation in thymus
BPISSGO:0033089positive regulation of T cell differentiation in thymus
BPISSGO:0033092positive regulation of immature T cell proliferation in thymus
BPIEAGO:0034244negative regulation of transcription elongation from RNA polymerase II promoter
BPIEAGO:0034504protein localization to nucleus
BPIEAGO:0035115embryonic forelimb morphogenesis
BPIEAGO:0035116embryonic hindlimb morphogenesis
BPISSGO:0042127regulation of cell proliferation
BPIEAGO:0042130negative regulation of T cell proliferation
BPIEAGO:0042307positive regulation of protein import into nucleus
BPIEAGO:0042475odontogenesis of dentin-containing tooth
BPISSGO:0042481regulation of odontogenesis
BPISSGO:0042733embryonic digit morphogenesis
BPIEAGO:0043010camera-type eye development
BPISSGO:0043066negative regulation of apoptotic process
BPIDAGO:0043369CD4-positive or CD8-positive, alpha-beta T cell lineage commitment
BPISSGO:0045059positive thymic T cell selection
BPISSGO:0045060negative thymic T cell selection
BPIEAGO:0045109intermediate filament organization
BPIEAGO:0045445myoblast differentiation
BPISSGO:0045596negative regulation of cell differentiation
BPIDAGO:0045880positive regulation of smoothened signaling pathway
BPISSGO:0045880positive regulation of smoothened signaling pathway
BPIDAGO:0045893positive regulation of transcription, DNA-templated
BPISSGO:0045944positive regulation of transcription by RNA polymerase II
BPISSGO:0046638positive regulation of alpha-beta T cell differentiation
BPIEAGO:0046639negative regulation of alpha-beta T cell differentiation
BPISSGO:0048468cell development
BPISSGO:0048538thymus development
BPIEAGO:0048557embryonic digestive tract morphogenesis
BPIEAGO:0048617embryonic foregut morphogenesis
BPIEAGO:0048643positive regulation of skeletal muscle tissue development
BPIEAGO:0048645animal organ formation
BPISSGO:0048663neuron fate commitment
BPIEAGO:0048706embryonic skeletal system development
BPIEAGO:0048714positive regulation of oligodendrocyte differentiation
BPISSGO:0048754branching morphogenesis of an epithelial tube
BPIEAGO:0048839inner ear development
BPIEAGO:0048859formation of anatomical boundary
BPISSGO:0048864stem cell development
BPIEAGO:0051155positive regulation of striated muscle cell differentiation
BPIDAGO:0051781positive regulation of cell division
BPIEAGO:0060020Bergmann glial cell differentiation
BPIEAGO:0060021roof of mouth development
BPIEAGO:0060070canonical Wnt signaling pathway
BPIEAGO:0060174limb bud formation
BPIEAGO:0060428lung epithelium development
BPIEAGO:0060439trachea morphogenesis
BPIEAGO:0060445branching involved in salivary gland morphogenesis
BPIEAGO:0060447bud outgrowth involved in lung branching
BPIEAGO:0060458right lung development
BPIEAGO:0060459left lung development
BPIEAGO:0060463lung lobe morphogenesis
BPIEAGO:0060484lung-associated mesenchyme development
BPIEAGO:0060516primary prostatic bud elongation
BPIEAGO:0060523prostate epithelial cord elongation
BPIEAGO:0060662salivary gland cavitation
BPIEAGO:0060664epithelial cell proliferation involved in salivary gland morphogenesis
BPIEAGO:0060685regulation of prostatic bud formation
BPIDAGO:0060738epithelial-mesenchymal signaling involved in prostate gland development
BPIEAGO:0060769positive regulation of epithelial cell proliferation involved in prostate gland development
BPIEAGO:0060782regulation of mesenchymal cell proliferation involved in prostate gland development
BPIEAGO:0060783mesenchymal smoothened signaling pathway involved in prostate gland development
BPIEAGO:0060840artery development
BPIEAGO:0060916mesenchymal cell proliferation involved in lung development
BPISSGO:0061053somite development
BPIDAGO:0061189positive regulation of sclerotome development
BPIEAGO:0071285cellular response to lithium ion
BPTASGO:0071542dopaminergic neuron differentiation
BPIEPGO:0072001renal system development
BPISSGO:0072136metanephric mesenchymal cell proliferation involved in metanephros development
BPIEAGO:0090090negative regulation of canonical Wnt signaling pathway
BPISSGO:0090370negative regulation of cholesterol efflux
BPISSGO:0097190apoptotic signaling pathway
BPNASGO:1900175regulation of nodal signaling pathway involved in determination of lateral mesoderm left/right asymmetry
BPIDAGO:1900180regulation of protein localization to nucleus
BPIEAGO:1904339negative regulation of dopaminergic neuron differentiation
BPIEAGO:1905327tracheoesophageal septum formation
BPISSGO:2000062negative regulation of ureter smooth muscle cell differentiation
BPISSGO:2000063positive regulation of ureter smooth muscle cell differentiation
BPISSGO:2000357negative regulation of kidney smooth muscle cell differentiation
BPISSGO:2000358positive regulation of kidney smooth muscle cell differentiation
BPISSGO:2000729positive regulation of mesenchymal cell proliferation involved in ureter development
BPIEAGO:2001054negative regulation of mesenchymal cell apoptotic process
CCTASGO:0005576extracellular region
CCIDAGO:0005615extracellular space
CCISSGO:0005615extracellular space
CCTASGO:0005788endoplasmic reticulum lumen
CCTASGO:0005886plasma membrane
CCISSGO:0009986cell surface
CCISSGO:0045121membrane raft

Gene expression in normal tissue: SHH

Gene-model tissue-cancer distribution: Bubble Plot

Gene-drug pathway distribution

Pathways in SHH

DatabasePathway IDPathway Des.
reactomeR-HSA-162582Signal Transduction
reactomeR-HSA-162582Signal Transduction
reactomeR-HSA-372790Signaling by GPCR
reactomeR-HSA-373080Class B/2 (Secretin family receptors)
reactomeR-HSA-500792GPCR ligand binding
reactomeR-HSA-5358346Hedgehog ligand biogenesis
reactomeR-HSA-5358346Hedgehog ligand biogenesis
reactomeR-HSA-5358351Signaling by Hedgehog
reactomeR-HSA-5358351Signaling by Hedgehog
reactomeR-HSA-5362768Hh mutants that don't undergo autocatalytic processing are degraded by ERAD
reactomeR-HSA-5362798Release of Hh-Np from the secreting cell
reactomeR-HSA-5362798Release of Hh-Np from the secreting cell
reactomeR-HSA-5387390Hh mutants abrogate ligand secretion
reactomeR-HSA-5632681Ligand-receptor interactions
reactomeR-HSA-5632681Ligand-receptor interactions
reactomeR-HSA-5632684Hedgehog 'on' state
reactomeR-HSA-5632684Hedgehog 'on' state
reactomeR-HSA-5635838Activation of SMO
reactomeR-HSA-5658034HHAT G278V abrogates palmitoylation of Hh-Np
reactomeR-HSA-5663202Diseases of signal transduction
biocartaptc1pathwaysonic hedgehog receptor ptc1 regulates cell cycle
kegghsa04340Hedgehog signaling pathway - Homo sapiens (human)
kegghsa04360Axon guidance - Homo sapiens (human)
kegghsa05200Pathways in cancer - Homo sapiens (human)
kegghsa05205Proteoglycans in cancer - Homo sapiens (human)
kegghsa05217Basal cell carcinoma - Homo sapiens (human)
kegghsa05226Gastric cancer - Homo sapiens (human)
pidglypican_3pathwayGlypican 3 network
pidhedgehog_2pathwaySignaling events mediated by the Hedgehog family
pidhedgehog_glipathwayHedgehog signaling events mediated by Gli proteins
pidhnf3apathwayFOXA1 transcription factor network
pidtap63pathwayValidated transcriptional targets of TAp63 isoforms
wikipathwaysWP1591Heart Development
wikipathwaysWP2804Hair Follicle Development- Induction (Part 1 of 3)
wikipathwaysWP2848Differentiation Pathway
wikipathwaysWP2855Dopaminergic Neurogenesis
wikipathwaysWP2858Ectoderm Differentiation
wikipathwaysWP3674Tgif disruption of Shh signaling
wikipathwaysWP3927BMP Signaling Pathway in Eyelid Development
wikipathwaysWP3930EDA Signalling in Hair Follicle Development
wikipathwaysWP4249Hedgehog Signaling Pathway
wikipathwaysWP47Hedgehog Signaling Pathway

Gene-Drug: Aster Plot

Drug IDDrug NameModel Num.
iGMDRD267Oligomycin A2
iGMDRD887Compound 23 citrate3
iGMDRD420Leucascandrolide A3
iGMDRD512nutlin 33

Gene in drug-gene network: Network Plot

Gene-drug targets distribution

Gene Structure: PDB

Models in SHH