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Aliases for SHH Gene

Aliases for SHH Gene

  • Sonic Hedgehog 2 3 5
  • Shh Unprocessed N-Terminal Signaling And C-Terminal Autoprocessing Domains 3 4
  • ShhNC 3 4
  • Sonic Hedgehog (Drosophila) Homolog 2
  • Sonic Hedgehog Homolog (Drosophila) 2
  • Sonic Hedgehog Homolog 3
  • Sonic Hedgehog Protein 3
  • MCOPCB5 3
  • SMMCI 3
  • TPTPS 3
  • HHG-1 4
  • HHG1 3
  • HLP3 3
  • HPE3 3
  • TPT 3

External Ids for SHH Gene

Previous HGNC Symbols for SHH Gene

  • HPE3
  • HLP3

Previous GeneCards Identifiers for SHH Gene

  • GC07M153825
  • GC07M154898
  • GC07M155013
  • GC07M155014
  • GC07M155095
  • GC07M155288
  • GC07M155592
  • GC07M149327

Summaries for SHH Gene

Entrez Gene Summary for SHH Gene

  • This gene encodes a protein that is instrumental in patterning the early embryo. It has been implicated as the key inductive signal in patterning of the ventral neural tube, the anterior-posterior limb axis, and the ventral somites. Of three human proteins showing sequence and functional similarity to the sonic hedgehog protein of Drosophila, this protein is the most similar. The protein is made as a precursor that is autocatalytically cleaved; the N-terminal portion is soluble and contains the signalling activity while the C-terminal portion is involved in precursor processing. More importantly, the C-terminal product covalently attaches a cholesterol moiety to the N-terminal product, restricting the N-terminal product to the cell surface and preventing it from freely diffusing throughout the developing embryo. Defects in this protein or in its signalling pathway are a cause of holoprosencephaly (HPE), a disorder in which the developing forebrain fails to correctly separate into right and left hemispheres. HPE is manifested by facial deformities. It is also thought that mutations in this gene or in its signalling pathway may be responsible for VACTERL syndrome, which is characterized by vertebral defects, anal atresia, tracheoesophageal fistula with esophageal atresia, radial and renal dysplasia, cardiac anomalies, and limb abnormalities. Additionally, mutations in a long range enhancer located approximately 1 megabase upstream of this gene disrupt limb patterning and can result in preaxial polydactyly. [provided by RefSeq, Jul 2008]

GeneCards Summary for SHH Gene

SHH (Sonic Hedgehog) is a Protein Coding gene. Diseases associated with SHH include Solitary Median Maxillary Central Incisor and Holoprosencephaly 3. Among its related pathways are Ectoderm Differentiation and CDK-mediated phosphorylation and removal of Cdc6. Gene Ontology (GO) annotations related to this gene include calcium ion binding. An important paralog of this gene is IHH.

UniProtKB/Swiss-Prot for SHH Gene

  • Sonic hedgehog protein: The C-terminal part of the sonic hedgehog protein precursor displays an autoproteolysis and a cholesterol transferase activity (By similarity). Both activities result in the cleavage of the full-length protein into two parts (ShhN and ShhC) followed by the covalent attachment of a cholesterol moiety to the C-terminal of the newly generated ShhN (By similarity). Both activities occur in the reticulum endoplasmic (By similarity). Once cleaved, ShhC is degraded in the endoplasmic reticulum (By similarity).

  • Sonic hedgehog protein N-product: The dually lipidated sonic hedgehog protein N-product (ShhNp) is a morphogen which is essential for a variety of patterning events during development. Induces ventral cell fate in the neural tube and somites (PubMed:24863049). Involved in the patterning of the anterior-posterior axis of the developing limb bud (By similarity). Essential for axon guidance (By similarity). Binds to the patched (PTCH1) receptor, which functions in association with smoothened (SMO), to activate the transcription of target genes (PubMed:10753901). In the absence of SHH, PTCH1 represses the constitutive signaling activity of SMO (PubMed:10753901).

Tocris Summary for SHH Gene

  • The Hedgehog (Hh) signaling pathway is crucial in the development of all 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 known human Hh proteins: Shh, Dhh and Ihh.

Gene Wiki entry for SHH Gene

Additional gene information for SHH Gene

No data available for CIViC summary , PharmGKB "VIP" Summary , fRNAdb sequence ontologies and piRNA Summary for SHH Gene

Genomics for SHH Gene

GeneHancer (GH) Regulatory Elements for SHH Gene

Promoters and enhancers for SHH Gene
GeneHancer (GH) Identifier GH Type GH
Score
GH Sources Gene Association Score Total Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor
Binding Sites
Gene Targets
GH07I155812 Promoter/Enhancer 1.1 EPDnew dbSUPER 550.8 0.0 -24 0.1 MXI1 ZNF189 SUZ12 POLR2A HDAC2 PRDM1 ZBTB26 ZBTB17 EZH2 SHH GC07M155822
GH07I155811 Enhancer 0.6 ENCODE 550.8 +1.2 1191 0.2 ATF4 KLF1 GLIS1 HLF ZNF341 CEBPB ZNF398 EZH2 SHH GC07M155785
GH07I155813 Enhancer 0.5 ENCODE 550.8 +0.6 551 0.2 ZFHX2 KLF1 SUZ12 GLIS1 KLF17 ZBTB26 EZH2 SHH GC07M155785
GH07I155203 Enhancer 1.5 Ensembl ENCODE dbSUPER 5.9 +605.5 605489 6 FEZF1 YBX1 IRF4 YY1 ZNF213 E2F8 ZNF143 MCM3 SP3 MEF2D PAXIP1-AS2 PAXIP1 RBM33 ENSG00000273183 PAXIP1-AS1 LOC105375586 INSIG1 SHH ENSG00000278998
GH07I155213 Enhancer 1.6 FANTOM5 Ensembl ENCODE dbSUPER 5.3 +598.0 597954 1.8 HDAC1 ATF1 NFIB KLF17 ZNF76 RAD21 YY1 ZNF335 GLIS2 GATA2 INSIG1 LOC105375586 SHH ENSG00000278998
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data dump

GeneHancers around SHH on UCSC Golden Path with GeneCards custom track

Top Transcription factor binding sites by QIAGEN in the SHH gene promoter:

Genomic Locations for SHH Gene

Genomic Locations for SHH Gene
chr7:155,799,986-155,812,273
(GRCh38/hg38)
Size:
12,288 bases
Orientation:
Minus strand
chr7:155,592,680-155,604,967
(GRCh37/hg19)

Genomic View for SHH Gene

Genes around SHH on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
SHH Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for SHH Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for SHH Gene

Proteins for SHH Gene

  • Protein details for SHH Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q15465-SHH_HUMAN
    Recommended name:
    Sonic hedgehog protein
    Protein Accession:
    Q15465
    Secondary Accessions:
    • A4D247
    • Q75MC9

    Protein attributes for SHH Gene

    Size:
    462 amino acids
    Molecular mass:
    49607 Da
    Quaternary structure:
    • Interacts with HHATL/GUP1 which negatively regulates HHAT-mediated palmitoylation of the SHH N-terminus (By similarity). ShhNp is active as a multimer (PubMed:24522195). Interacts with BOC and CDON (By similarity). Interacts with HHIP (PubMed:19561609). Interacts with DISP1 via its cholesterol anchor (PubMed:22902404, PubMed:22677548). Interacts with SCUBE2 (PubMed:24522195, PubMed:22677548).

    Three dimensional structures from OCA and Proteopedia for SHH Gene

neXtProt entry for SHH Gene

Post-translational modifications for SHH Gene

  • Sonic hedgehog protein N-product: N-palmitoylation by HHAT of ShhN is required for sonic hedgehog protein N-product multimerization and full activity (By similarity). It is a prerequisite for the membrane-proximal positioning and the subsequent shedding of this N-terminal peptide (PubMed:24522195).
  • Sonic hedgehog protein N-product: The lipidated N- and C-terminal peptides of ShhNp can be cleaved (shedding)(PubMed:24522195). The N-terminal palmitoylated peptide is cleaved at the Cardin-Weintraub (CW) motif site (PubMed:24522195). The cleavage reduced the interactions with heparan sulfate. The cleavage is enhanced by SCUBE2 (PubMed:24522195, PubMed:23118222).
  • Sonic hedgehog protein: The C-terminal domain displays an autoproteolysis activity and a cholesterol transferase activity (By similarity). 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 (ShhN) (By similarity). Cholesterylation is required for the sonic hedgehog protein N-product targeting to lipid rafts and multimerization (PubMed:24522195, PubMed:26875496). ShhN is the active species in both local and long-range signaling, whereas the C-product (ShhC) is degraded in the reticulum endoplasmic (By similarity).
  • Glycosylation at posLast=278278
  • Modification sites at PhosphoSitePlus

Other Protein References for SHH Gene

No data available for DME Specific Peptides for SHH Gene

Domains & Families for SHH Gene

Gene Families for SHH Gene

HGNC:
Human Protein Atlas (HPA):
  • Disease related genes
  • Predicted intracellular proteins
  • Predicted secreted proteins

Suggested Antigen Peptide Sequences for SHH Gene

GenScript: Design optimal peptide antigens:

Graphical View of Domain Structure for InterPro Entry

Q15465

UniProtKB/Swiss-Prot:

SHH_HUMAN :
  • Sonic hedgehog protein N-product: Binds calcium and zinc ions; this stabilizes the protein fold and is essential for protein-protein interactions mediated by this domain.
  • Belongs to the hedgehog family.
Domain:
  • Sonic hedgehog protein N-product: Binds calcium and zinc ions; this stabilizes the protein fold and is essential for protein-protein interactions mediated by this domain.
  • Sonic hedgehog protein N-product: The Cardin-Weintraub (CW) motif is required for heparan sulfate binding of the solubilized ShhNp (PubMed:23118222). The N-terminal palmitoylated peptide is cleaved at the heparan sulfate-binding Cardin-Weintraub (CW) motif site (PubMed:24522195). The cleavage reduced the interactions with heparan sulfate. The cleavage is enhanced by SCUBE2 (PubMed:24522195).
Family:
  • Belongs to the hedgehog family.
genes like me logo Genes that share domains with SHH: view

Function for SHH Gene

Molecular function for SHH Gene

GENATLAS Biochemistry:
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
UniProtKB/Swiss-Prot Function:
Sonic hedgehog protein: The C-terminal part of the sonic hedgehog protein precursor displays an autoproteolysis and a cholesterol transferase activity (By similarity). Both activities result in the cleavage of the full-length protein into two parts (ShhN and ShhC) followed by the covalent attachment of a cholesterol moiety to the C-terminal of the newly generated ShhN (By similarity). Both activities occur in the reticulum endoplasmic (By similarity). Once cleaved, ShhC is degraded in the endoplasmic reticulum (By similarity).
UniProtKB/Swiss-Prot Function:
Sonic hedgehog protein N-product: The dually lipidated sonic hedgehog protein N-product (ShhNp) is a morphogen which is essential for a variety of patterning events during development. Induces ventral cell fate in the neural tube and somites (PubMed:24863049). Involved in the patterning of the anterior-posterior axis of the developing limb bud (By similarity). Essential for axon guidance (By similarity). Binds to the patched (PTCH1) receptor, which functions in association with smoothened (SMO), to activate the transcription of target genes (PubMed:10753901). In the absence of SHH, PTCH1 represses the constitutive signaling activity of SMO (PubMed:10753901).

LifeMap Function Summary for SHH Gene

During embryonic development, SHH as signaling molecule is secreted from the following cells
It affects the following cells:
SHH as growth factor is involved in stem cell differentiation protocols towards the derivation of the following cells:

Phenotypes From GWAS Catalog for SHH Gene

Gene Ontology (GO) - Molecular Function for SHH Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005113 patched binding IEA,IDA 8906787
GO:0005509 calcium ion binding IDA 19561609
GO:0005515 protein binding IPI 19561609
GO:0005539 glycosaminoglycan binding IEA --
GO:0008233 peptidase activity IEA --
genes like me logo Genes that share ontologies with SHH: view
genes like me logo Genes that share phenotypes with SHH: view

Human Phenotype Ontology for SHH Gene

HPO Id HPO Name Alternative Ids Definition Synonyms

Animal Models for SHH Gene

MGI Knock Outs for SHH:

Clone Products

  • Addgene plasmids for SHH

No data available for Enzyme Numbers (IUBMB) , Transcription Factor Targets and HOMER Transcription for SHH Gene

Localization for SHH Gene

Subcellular locations from UniProtKB/Swiss-Prot for SHH Gene

Sonic hedgehog protein N-product: Cell membrane; Lipid-anchor. Note=The dual-lipidated sonic hedgehog protein N-product (ShhNp) is firmly tethered to the cell membrane where it forms multimers (PubMed:24522195). Further solubilization and release from the cell surface seem to be achieved through different mechanisms, including the interaction with DISP1 and SCUBE2, movement by lipoprotein particles, transport by cellular extensions called cytonemes or by the proteolytic removal of both terminal lipidated peptides (PubMed:26875496, PubMed:24522195). {ECO:0000305 PubMed:24522195, ECO:0000305 PubMed:26875496}.

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for SHH gene
Compartment Confidence
plasma membrane 5
extracellular 5
endoplasmic reticulum 5
cytosol 5
cytoskeleton 2
nucleus 2
mitochondrion 1
lysosome 1
golgi apparatus 1

Gene Ontology (GO) - Cellular Components for SHH Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005576 extracellular region TAS --
GO:0005578 proteinaceous extracellular matrix IEA --
GO:0005615 extracellular space ISS,IEA --
GO:0005788 endoplasmic reticulum lumen TAS --
GO:0005829 cytosol TAS --
genes like me logo Genes that share ontologies with SHH: view

No data available for Subcellular locations from the Human Protein Atlas (HPA) for SHH Gene

Pathways & Interactions for SHH Gene

genes like me logo Genes that share pathways with SHH: view

SIGNOR curated interactions for SHH Gene

Activates:
Inactivates:
Is activated by:
Is inactivated by:

Gene Ontology (GO) - Biological Process for SHH Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000122 negative regulation of transcription by RNA polymerase II ISS --
GO:0001525 angiogenesis IEA --
GO:0001569 branching involved in blood vessel morphogenesis IEA,ISS --
GO:0001570 vasculogenesis IEA,ISS --
GO:0001656 metanephros development ISS,IEA --
genes like me logo Genes that share ontologies with SHH: view

Drugs & Compounds for SHH Gene

(44) Drugs for SHH Gene - From: ClinicalTrials, ApexBio, Tocris, and Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
Cisplatin Approved Pharma Inhibits DNA synthesis,chemotherapy drug, Potent pro-apoptotic anticancer agent; activates caspase-3, Platinum 2906
Cyclophosphamide Approved, Investigational Pharma Nitrogen mustard alkylating agent and prodrug. 3113
Epinephrine Approved, Vet_approved Pharma 1095
Gemcitabine Approved Pharma Ribonucleotide reductase and DNA synthesis inhibitor, Nucleoside Analogs 2100
Pemetrexed Approved, Investigational Pharma TS, DHFR,GARFT and AICARFT inhibitor, DHFR and Thymidylate synthase inhibitor, Anti-Folates 674

(5) Tocris Compounds for SHH Gene

Compound Action Cas Number
20(S)-Hydroxycholesterol Allosteric activator of Hedgehog (Hh) signaling; induces Smo accumulation 516-72-3
Cyclopamine Inhibitor of Hedgehog (Hh) signaling 4449-51-8
Jervine Inhibitor of Hedgehog (Hh) signaling; binds directly to Smo 469-59-0
SANT-1 Inhibitor of hedgehog (Hh) signaling; antagonizes smoothened activity 304909-07-7
SANT-2 Inhibitor of Hedgehog (Hh) signaling; antagonizes smoothened activity 329196-48-7

(18) ApexBio Compounds for SHH Gene

Compound Action Cas Number
20(S)-Hydroxycholesterol 516-72-3
AY 9944 dihydrochloride Hedgehog Inhibitor 366-93-8
AZ 12080282 dihydrochloride Hedgehog inhibitor
Ciliobrevin A Hh pathway antagonist 302803-72-1
Cyclopamine Hedgehog (Hh) signaling Inhibitor 4449-51-8
GANT61 GLI antagonist 500579-04-4
GDC-0449 (Vismodegib) Hedgehog antagonist,potent and selective 879085-55-9
HPI 1 Hh signaling inhibitor 599150-20-6
Jervine Hedgehog signaling Inhibitor 469-59-0
JK 184 Hh signaling inhibitor 315703-52-7
LY2940680 Hedgehog/SMO antagonist,inhibits Hh signaling 1258861-20-9
PF-5274857 Smo antagonist,potent and selective 1373615-35-0
Purmorphamine Hedgehog agonist 483367-10-8
RU-SKI 43 1043797-53-0
SAG Hh and Smo agonist 912545-86-9
SANT-1 Shh inhibitor,potent and cell-permeable 304909-07-7
SANT-2 329196-48-7
U 18666A inhibitor of cholesterol transport and synthesis 3039-71-2
genes like me logo Genes that share compounds with SHH: view

Drug Products

Transcripts for SHH Gene

mRNA/cDNA for SHH Gene

(4) REFSEQ mRNAs :
(6) Additional mRNA sequences :
(4) Selected AceView cDNA sequences:
(5) Ensembl transcripts including schematic representations, and UCSC links where relevant :

Unigene Clusters for SHH Gene

Sonic hedgehog:
Representative Sequences:

Clone Products

  • Addgene plasmids for SHH

Alternative Splicing Database (ASD) splice patterns (SP) for SHH Gene

No ASD Table

Relevant External Links for SHH Gene

GeneLoc Exon Structure for
SHH
ECgene alternative splicing isoforms for
SHH

Expression for SHH Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and CGAP SAGE for SHH Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

mRNA differential expression in normal tissues according to GTEx for SHH Gene

This gene is overexpressed in Liver (x9.8), Bladder (x8.4), Nerve - Tibial (x6.5), and Adrenal Gland (x6.3).

Protein differential expression in normal tissues from HIPED for SHH Gene

This gene is overexpressed in Fetal Liver (26.4), Placenta (24.3), and Peripheral blood mononuclear cells (12.0).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, PaxDb, MaxQB, and MOPED for SHH Gene



Protein tissue co-expression partners for SHH Gene

NURSA nuclear receptor signaling pathways regulating expression of SHH Gene:

SHH

SOURCE GeneReport for Unigene cluster for SHH Gene:

Hs.164537

Evidence on tissue expression from TISSUES for SHH Gene

  • Lung(4.4)
  • Bone marrow(4.3)
  • Nervous system(3.4)
  • Skin(2.4)
  • Intestine(2.3)
  • Stomach(2.3)
  • Bone(2.2)
  • Kidney(2.2)
  • Muscle(2)
  • Pancreas(2)

Phenotype-based relationships between genes and organs from Gene ORGANizer for SHH Gene

Germ Layers:
  • ectoderm
  • endoderm
  • mesoderm
Systems:
  • cardiovascular
  • digestive
  • endocrine
  • integumentary
  • lymphatic
  • nervous
  • reproductive
  • respiratory
  • skeletal muscle
  • skeleton
  • urinary
Regions:
Head and neck:
  • brain
  • cheek
  • chin
  • cranial nerve
  • ear
  • eye
  • eyelid
  • face
  • head
  • jaw
  • lip
  • mandible
  • maxilla
  • mouth
  • nose
  • pharynx
  • pituitary gland
  • skull
  • tooth
Thorax:
  • aorta
  • clavicle
  • diaphragm
  • heart
  • heart valve
  • lung
Abdomen:
  • abdominal wall
  • intestine
  • kidney
  • large intestine
  • liver
  • small intestine
  • spleen
  • stomach
Pelvis:
  • testicle
  • ureter
  • uterus
Limb:
  • arm
  • digit
  • femur
  • fibula
  • finger
  • foot
  • forearm
  • hand
  • humerus
  • knee
  • lower limb
  • nail
  • radius
  • shin
  • thigh
  • tibia
  • toe
  • ulna
  • upper limb
General:
  • blood
  • blood vessel
  • peripheral nerve
  • peripheral nervous system
  • skin
  • spinal cord
genes like me logo Genes that share expression patterns with SHH: view

No data available for mRNA Expression by UniProt/SwissProt for SHH Gene

Orthologs for SHH Gene

This gene was present in the common ancestor of animals.

Orthologs for SHH Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
Mammalia SHH 33
  • 99.71 (n)
-- 34
  • 75 (a)
ManyToMany
dog
(Canis familiaris)
Mammalia SHH 33 34
  • 89.15 (n)
mouse
(Mus musculus)
Mammalia Shh 33 16 34
  • 87.9 (n)
rat
(Rattus norvegicus)
Mammalia Shh 33
  • 87.02 (n)
oppossum
(Monodelphis domestica)
Mammalia SHH 34
  • 83 (a)
OneToOne
cow
(Bos Taurus)
Mammalia SHH 33 34
  • 82.68 (n)
platypus
(Ornithorhynchus anatinus)
Mammalia -- 34
  • 72 (a)
ManyToMany
chicken
(Gallus gallus)
Aves SHH 33 34
  • 81.17 (n)
lizard
(Anolis carolinensis)
Reptilia SHH 34
  • 79 (a)
OneToOne
tropical clawed frog
(Silurana tropicalis)
Amphibia shh 33
  • 67.53 (n)
African clawed frog
(Xenopus laevis)
Amphibia LOC398047 33
zebrafish
(Danio rerio)
Actinopterygii shha 34
  • 71 (a)
OneToMany
shhb 33 34
  • 65.3 (n)
shh 33
African malaria mosquito
(Anopheles gambiae)
Insecta AgaP_AGAP001412 33
  • 60 (n)
fruit fly
(Drosophila melanogaster)
Insecta hh 35 33 34
  • 58.71 (n)
sea squirt
(Ciona savignyi)
Ascidiacea -- 34
  • 43 (a)
ManyToMany
-- 34
  • 31 (a)
ManyToMany
Species where no ortholog for SHH was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • Alicante grape (Vitis vinifera)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • baker's yeast (Saccharomyces cerevisiae)
  • barley (Hordeum vulgare)
  • beta proteobacteria (Neisseria meningitidis)
  • bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • common water flea (Daphnia pulex)
  • corn (Zea mays)
  • E. coli (Escherichia coli)
  • filamentous fungi (Aspergillus nidulans)
  • Firmicute bacteria (Streptococcus pneumoniae)
  • fission yeast (Schizosaccharomyces pombe)
  • green algae (Chlamydomonas reinhardtii)
  • honey bee (Apis mellifera)
  • K. lactis yeast (Kluyveromyces lactis)
  • loblloly pine (Pinus taeda)
  • malaria parasite (Plasmodium falciparum)
  • medicago trunc (Medicago Truncatula)
  • moss (Physcomitrella patens)
  • orangutan (Pongo pygmaeus)
  • pig (Sus scrofa)
  • rainbow trout (Oncorhynchus mykiss)
  • rice (Oryza sativa)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea urchin (Strongylocentrotus purpuratus)
  • sorghum (Sorghum bicolor)
  • soybean (Glycine max)
  • stem rust fungus (Puccinia graminis)
  • sugarcane (Saccharum officinarum)
  • thale cress (Arabidopsis thaliana)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • wheat (Triticum aestivum)
  • worm (Caenorhabditis elegans)

Evolution for SHH Gene

ENSEMBL:
Gene Tree for SHH (if available)
TreeFam:
Gene Tree for SHH (if available)

Paralogs for SHH Gene

Paralogs for SHH Gene

(2) SIMAP similar genes for SHH Gene using alignment to 5 proteins:

genes like me logo Genes that share paralogs with SHH: view

Variants for SHH Gene

Sequence variations from dbSNP and Humsavar for SHH Gene

SNP ID Clin Chr 07 pos Variation AA Info Type
rs104894040 pathogenic, Holoprosencephaly 3, Holoprosencephaly 3 (HPE3) [MIM:142945], Holoprosencephaly 3 (HPE3) [MIM:142945] 155,806,509(-) A/C/G coding_sequence_variant, missense_variant, non_coding_transcript_variant
rs104894042 pathogenic, Holoprosencephaly 3, Holoprosencephaly 3 (HPE3) [MIM:142945] 155,803,618(-) A/T coding_sequence_variant, intron_variant, missense_variant
rs104894043 pathogenic, Holoprosencephaly 3, Holoprosencephaly 3 (HPE3) [MIM:142945] 155,803,613(-) C/T coding_sequence_variant, intron_variant, missense_variant
rs104894044 pathogenic, Holoprosencephaly 3 155,811,825(-) G/A coding_sequence_variant, genic_upstream_transcript_variant, stop_gained, upstream_transcript_variant
rs104894045 pathogenic, Holoprosencephaly 3 155,806,545(-) T/A coding_sequence_variant, non_coding_transcript_variant, stop_gained

Structural Variations from Database of Genomic Variants (DGV) for SHH Gene

Variant ID Type Subtype PubMed ID
esv2663062 CNV deletion 23128226
nsv1075489 CNV deletion 25765185
nsv509227 CNV insertion 20534489
nsv951662 CNV deletion 24416366

Variation tolerance for SHH Gene

Residual Variation Intolerance Score: 23.4% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 0.69; 14.70% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for SHH Gene

Human Gene Mutation Database (HGMD)
SHH
SNPedia medical, phenotypic, and genealogical associations of SNPs for
SHH

SNP Genotyping and Copy Number Assay Products

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for SHH Gene

Disorders for SHH Gene

MalaCards: The human disease database

(80) MalaCards diseases for SHH Gene - From: HGMD, OMIM, ClinVar, GTR, Orphanet, Swiss-Prot, DISEASES, Novoseek, and GeneCards

- elite association - COSMIC cancer census association via MalaCards
Search SHH in MalaCards View complete list of genes associated with diseases

UniProtKB/Swiss-Prot

SHH_HUMAN
  • Holoprosencephaly 3 (HPE3) [MIM:142945]: A structural anomaly of the brain, in which the developing forebrain fails to correctly separate into right and left hemispheres. Holoprosencephaly is genetically heterogeneous and associated with several distinct facies and phenotypic variability. The majority of holoprosencephaly type 3 cases are apparently sporadic, although clear examples of autosomal dominant inheritance have been described. {ECO:0000269 PubMed:10441331, ECO:0000269 PubMed:10556296, ECO:0000269 PubMed:11479728, ECO:0000269 PubMed:15107988, ECO:0000269 PubMed:15221788, ECO:0000269 PubMed:15942952, ECO:0000269 PubMed:15942953, ECO:0000269 PubMed:16282375, ECO:0000269 PubMed:17001669, ECO:0000269 PubMed:19603532, ECO:0000269 PubMed:8896572, ECO:0000269 PubMed:9302262}. Note=The disease is caused by mutations affecting the gene represented in this entry.
  • Hypoplasia or aplasia of tibia with polydactyly (THYP) [MIM:188740]: An autosomal dominant disease characterized by hypoplastic or absent tibia, and polydactyly. {ECO:0000269 PubMed:19847792, ECO:0000269 PubMed:24965254}. Note=The gene represented in this entry is involved in disease pathogenesis. Mutations located in intron 5 of LMBR1 disrupt a long-range, cis-regulatory element of SHH and result in abnormal, ectopic SHH expression with pathological consequences. {ECO:0000303 PubMed:19847792, ECO:0000303 PubMed:24965254}.
  • Laurin-Sandrow syndrome (LSS) [MIM:135750]: A rare autosomal dominant disorder characterized by polysyndactyly of hands and/or feet, mirror image duplication of the feet, nasal defects, and loss of identity between fibula and tibia. Some patients do not have nasal abnormalities (segmental Laurin-Sandrow syndrome). {ECO:0000269 PubMed:24456159}. Note=The gene represented in this entry is involved in disease pathogenesis. Abnormal SHH limb expression with pathological consequences is caused by duplications (16-75 kb) involving the ZPA regulatory sequence (ZRS), a SHH long-range cis-regulatory element, located in LMBR1 intron 5 (PubMed:24456159).
  • Microphthalmia, isolated, with coloboma, 5 (MCOPCB5) [MIM:611638]: A disorder of eye formation, ranging from small size of a single eye to complete bilateral absence of ocular tissues. Ocular abnormalities like opacities of the cornea and lens, scaring of the retina and choroid, and other abnormalities may also be present. Ocular colobomas are a set of malformations resulting from abnormal morphogenesis of the optic cup and stalk, and the fusion of the fetal fissure (optic fissure). {ECO:0000269 PubMed:12503095}. Note=The disease is caused by mutations affecting the gene represented in this entry.
  • Preaxial polydactyly 2 (PPD2) [MIM:174500]: Polydactyly consists of duplication of the distal phalanx. The thumb in PPD2 is usually opposable and possesses a normal metacarpal. {ECO:0000269 PubMed:12837695}. Note=The gene represented in this entry is involved in disease pathogenesis. Mutations located in intron 5 of LMBR1 disrupt a long-range, cis-regulatory element of SHH and result in abnormal, ectopic SHH expression with pathological consequences (PubMed:12837695). {ECO:0000269 PubMed:12837695}.
  • Solitary median maxillary central incisor (SMMCI) [MIM:147250]: Rare dental anomaly characterized by the congenital absence of one maxillary central incisor. {ECO:0000269 PubMed:11471164, ECO:0000269 PubMed:15103725}. Note=The disease is caused by mutations affecting the gene represented in this entry.
  • Triphalangeal thumb-polysyndactyly syndrome (TPTPS) [MIM:174500]: Autosomal dominant syndrome. It is characterized by a wide spectrum of pre- and post-axial abnormalities due to altered SHH expression pattern during limb development. {ECO:0000269 PubMed:12837695, ECO:0000269 PubMed:18417549}. Note=The gene represented in this entry is involved in disease pathogenesis. Mutations located in intron 5 of LMBR1 disrupt a long-range, cis-regulatory element of SHH expression.

Additional Disease Information for SHH

Genetic Association Database
(GAD)
Human Genome Epidemiology Navigator
(HuGE)
ATLAS of Genetics and Cytogenetics in Oncology and Haematology
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No data available for Genatlas for SHH Gene

Publications for SHH Gene

  1. Cloning, expression, and chromosomal location of SHH and IHH: two human homologues of the Drosophila segment polarity gene hedgehog. (PMID: 7590746) Marigo V … Seidman CE (Genomics 1995) 2 3 4 22 58
  2. The mutational spectrum of holoprosencephaly-associated changes within the SHH gene in humans predicts loss-of-function through either key structural alterations of the ligand or its altered synthesis. (PMID: 19603532) Roessler E … Muenke M (Human mutation 2009) 3 4 22 58
  3. Molecular mechanisms of Sonic hedgehog mutant effects in holoprosencephaly. (PMID: 16282375) Maity T … Beachy PA (Proceedings of the National Academy of Sciences of the United States of America 2005) 3 4 22 58
  4. Molecular screening of SHH, ZIC2, SIX3, and TGIF genes in patients with features of holoprosencephaly spectrum: Mutation review and genotype-phenotype correlations. (PMID: 15221788) Dubourg C … David V (Human mutation 2004) 3 4 22 58
  5. SONIC HEDGEHOG mutations causing human holoprosencephaly impair neural patterning activity. (PMID: 12709790) Schell-Apacik C … Ming JE (Human genetics 2003) 3 22 44 58

Products for SHH Gene

  • Addgene plasmids for SHH

Sources for SHH Gene