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FLASH GENE
Symbol SHH contributors: shn/ - updated : 18-12-2018
HGNC name sonic hedgehog
HGNC id 10848
ASSOCIATED DISORDERS
corresponding disease(s) HPE3 , NSOC , DEL7Q36 , TPT , PPD2 , MMDW
Other morbid association(s)
TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
constitutional     --other  
abnormal expression in the floor plate of embryos with craniorachischisis and spinabifida
tumoral       gain of function
activated in sporadic basal cell carcinomas and medulloblastomas
tumoral     --over  
overexpressed in pancreatic cancer and in distal trisomy 7q
Susceptibility
  • to combined pituitary hormone deficiency
  • to orofacial cleft
  • Variant & Polymorphism SNP
  • SNP in two Hedgehog genes, SHH and HHIP, are genetic cause of combined pituitary hormone deficiency
  • variants in SHH, RORA, MRPL53, ACVR1, and GDF11 may contribute to risk of orofacial clefts
  • Candidate gene
    Marker
    Therapy target
    ANIMAL & CELL MODELS
  • disruption of mouse Sonic hedgehog gene leads to early defects: establishment or maintenance of midline structures, such as the notochord and the floorplate, and later defects: absence of distal limb structures, cyclopia, ventral cell types within the neural tube, spinal column and most of the ribs
  • transgenic mice overexpressing SHH in the skin develop many features of basal cell nevus syndrome
  • mice with a targeted deletion of Sonic hedgehog have foregut defects and homozygous Shh-null mutant mice show oesophageal atresia/stenosis, tracheo-oesophageal fistula and tracheal and lung anomalies
  • Sonic hedgehog mutant mice display intestinal transformation of the stomach, duodenal stenosis (obstruction), abnormal innervation of the gut and imperforate anus. Indian hedgehog mutant mice show reduced epithelial stem cell proliferation and differentiation, together with features typical of Hirschsprung's disease
  • administration of ethanol to chick embryos results in a dramatic loss of Shh and a loss of transcripts involved in Shh signaling pathways exhibit a highly characteristic pattern of cell death. Embryos display dying cells in the premigratory and migratory neural crest cells that normally populate most facial structures
  • Shh(-/-) mice exhibit an arrest in hair follicle development with reduced cell proliferation
  • pancreata of Pdx-Shh mice, in which Shh is misexpressed in the pancreatic endoderm, develop abnormal tubular structures, a phenocopy of human PanIN-1 and -2
  • hh gene expression at the embryonic midline controls eye degeneration in blind cavefish
  • functional interaction between beta-arrestin 2 and Smoothened may be critical to regulate Hh signaling in zebrafish development
  • homozygous Short digits (Dsh) mutant mice display dysregulation of Shh expression causing local upregulation of hedgehog target genes; Gli1-3, patched, and Pthlh, and the downregulation of Ihh and Gdf5, which results in shortening of the digits through an arrest of chondrocyte differentiation and the disruption of joint development
  • Shh mutant embryos display a hypoplastic first pharyngeal arch and the growth of the maxillary arch and proximal mandibular arch is severely defective
  • in the Shh(-/-) thymus the ratio of CD4/CD8 cells and both positive and negative selection of a transgenic TCR were increased
  • elevated ectopic Shh signaling in mice can impair dorsal telencephalic midline morphogenesis and lead to non-cleavage of midline structures
  • the third ventricle is blocked in mice Shh null mutants similar to human holoprosencephaly
  • a malformed telencephalic/diencephalic junction in the mouse Shh mutant forebrain