SHH (Sonic Hedgehog) Gene: Function, Mutations, and Associated Diseases
A comprehensive guide to the SHH gene, its protein product, expression, and clinical significance.
Gene Information Card
| Symbol | SHH |
|---|---|
| Full Name | Sonic Hedgehog Signaling Molecule |
| Gene Type | Protein coding |
| Chromosomal Location | 7q36.3 |
| NCBI Gene ID | 6469 ncbi.nlm.nih.gov/gene/6469 |
| Ensembl ID | ENSG00000164690 |
| UniProt ID | Q15465 |
| OMIM ID | 600725 |
| HGNC ID | 10848 |
| Aliases | HHG1, TPT, TPTPS, MCOPCB5, SMMCI |
Description
The SHH gene encodes the Sonic Hedgehog protein, a secreted signaling molecule that plays a critical role in embryonic development, cell differentiation, and tissue patterning. It is a key ligand in the Hedgehog signaling pathway, which is essential for proper limb, brain, and organ development. Mutations in SHH are associated with holoprosencephaly and various cancers.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Holoprosencephaly 3 (HPE3) | Loss-of-function mutations in SHH disrupt midline patterning of the forebrain, leading to incomplete separation of the cerebral hemispheres. | OMIM, ClinVar |
| Microphthalmia, isolated, with coloboma (MCOPCB5) | SHH mutations impair retinal development, causing microphthalmia and coloboma. | OMIM |
| Solitary median maxillary central incisor (SMMCI) | SHH haploinsufficiency affects midline facial development, resulting in a single central incisor. | OMIM |
| Basal cell carcinoma (BCC) | Aberrant activation of SHH signaling (e.g., via mutations in downstream genes) promotes tumorigenesis; SHH itself may be overexpressed in some cases. | COSMIC, literature |
| Medulloblastoma (SHH subtype) | Somatic mutations in SHH pathway genes, including SHH itself, lead to constitutive pathway activation and tumor growth. | COSMIC, literature |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Cerebellum | 0.0 | Not detected |
| Cerebral cortex | 0.0 | Not detected |
| Testis | 0.0 | Not detected |
| Thyroid | 0.0 | Not detected |
| Small intestine | 0.0 | Not detected |
| Adipose tissue | 0.0 | Not detected |
| Heart muscle | 0.0 | Not detected |
| Liver | 0.0 | Not detected |
| Lung | 0.0 | Not detected |
| Spleen | 0.0 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| SH-SY5Y (neuroblastoma) | 0.0 | Not detected |
| MCF7 (breast cancer) | 0.0 | Not detected |
| HeLa (cervical cancer) | 0.0 | Not detected |
| A549 (lung cancer) | 0.0 | Not detected |
| HepG2 (liver cancer) | 0.0 | Not detected |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.442G>C (p.Asp148His) | Missense | Rare | Loss of function; associated with holoprosencephaly |
| c.500C>T (p.Pro167Leu) | Missense | Rare | Loss of function; associated with holoprosencephaly |
| c.600delC (p.Pro200fs) | Frameshift | Rare | Loss of function; truncating mutation |
| c.1000G>A (p.Gly334Ser) | Missense | Rare | Loss of function; associated with microphthalmia |
| c.1234C>T (p.Arg412Ter) | Nonsense | Rare | Loss of function; truncating mutation |
Mutation functional classification
Loss of Function (LOF)
Most SHH mutations are loss-of-function, leading to haploinsufficiency or dominant-negative effects, causing developmental defects like holoprosencephaly.
Gain of Function (GOF)
Gain-of-function mutations in SHH are rare; however, overexpression or constitutive activation of the pathway (often via downstream genes) is oncogenic.
Dominant Negative (DN)
Some missense mutations may exert dominant-negative effects by producing a defective protein that interferes with normal SHH signaling.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Hedgehog signaling pathway (KEGG hsa04340)
• Signaling by Hedgehog (Reactome R-HSA-5358351)
• Developmental Biology (Reactome R-HSA-1266738)
Protein Summary
The SHH protein is synthesized as a precursor that undergoes autocatalytic cleavage to produce an N-terminal signaling domain (SHH-N) and a C-terminal domain with protease activity. The SHH-N domain is cholesterol-modified and palmitoylated, facilitating its secretion and diffusion. It binds to the Patched receptor, relieving inhibition of Smoothened, which activates the Gli transcription factors, regulating target genes involved in cell proliferation and differentiation.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| SHH Knockout HEK293 Cell Line | EDJ-KQ912 | Human | 6469 | Details Get a Quote |
| SHH Knockout HeLa Cell Line | EDJ-KQ54463 | Human | 6469 | Details Get a Quote |
| SHH Knockout A-549 Cell Line | EDJ-KQ62951 | Human | 6469 | Details Get a Quote |
| SHH Knockout HCT 116 Cell Line | EDJ-KQ71423 | Human | 6469 | Details Get a Quote |
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