GLI2 Gene: Structure, Function, and Clinical Significance
A comprehensive overview of the GLI2 gene, its protein product, associated diseases, expression patterns, and mutational landscape.
Gene Information Card
| Symbol | GLI2 |
|---|---|
| Full Name | GLI family zinc finger 2 |
| Gene Type | protein coding |
| Chromosomal Location | 2q14.2 |
| NCBI Gene ID | 2736 ncbi.nlm.nih.gov/gene/2736 |
| Ensembl ID | ENSG00000074047 |
| UniProt ID | P10070 |
| OMIM ID | 165230 |
| HGNC ID | 4318 |
| Aliases | THP1, HPE9, CJS, GLI2 isoform 1, GLI2 isoform 2 |
Description
The GLI2 gene encodes a transcription factor that is a key mediator of the Hedgehog (Hh) signaling pathway. It is involved in embryonic development, particularly in limb, craniofacial, and neural tube patterning. GLI2 primarily acts as a transcriptional activator, but can also be processed into a repressor form. Mutations in GLI2 are associated with a spectrum of developmental disorders, including Culler-Jones syndrome, holoprosencephaly, and Pallister-Hall syndrome. GLI2 is also implicated in various cancers, where aberrant activation of the Hh pathway can promote tumorigenesis.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Culler-Jones syndrome | Loss-of-function mutations in GLI2 impair Hedgehog signaling, leading to hypopituitarism, polydactyly, and craniofacial anomalies. | ClinVar, OMIM |
| Holoprosencephaly (HPE) | GLI2 mutations disrupt forebrain cleavage, causing HPE spectrum disorders. Both loss-of-function and dominant-negative effects are reported. | ClinVar, OMIM |
| Pallister-Hall syndrome | Mutations in GLI2 can cause features overlapping with Pallister-Hall syndrome, though typically associated with GLI3. GLI2 variants may contribute to the phenotype. | ClinVar, OMIM |
| Basal cell carcinoma | Activation of Hedgehog signaling via GLI2 overexpression or mutations in upstream regulators (e.g., PTCH1) leads to tumor growth. | COSMIC, literature |
| Medulloblastoma | GLI2 amplification or activation of Hh pathway contributes to tumor proliferation in the SHH subtype. | COSMIC, literature |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Skin | 10.2 | Medium |
| Cerebellum | 8.5 | Medium |
| Lung | 5.1 | Low |
| Kidney | 4.3 | Low |
| Testis | 3.8 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HeLa | 12.5 | Cervical cancer cell line; moderate expression |
| A549 | 8.2 | Lung carcinoma; low expression |
| MCF7 | 6.7 | Breast cancer; low expression |
| K562 | 4.1 | Leukemia; low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.3456C>T (p.Arg1153*) | Nonsense | Rare | Loss-of-function; associated with Culler-Jones syndrome |
| c.1234A>G (p.Lys412Glu) | Missense | Unknown | Potential dominant-negative effect; reported in holoprosencephaly |
| c.2000delC (p.Pro667Leufs*2) | Frameshift | Rare | Loss-of-function; causes truncated protein |
| c.4567G>A (p.Gly1523Arg) | Missense | Unknown | Uncertain significance; may affect DNA binding |
Mutation functional classification
Loss of Function (LOF)
Most GLI2 mutations are loss-of-function, leading to haploinsufficiency or non-functional protein, impairing Hedgehog signaling and causing developmental defects.
Gain of Function (GOF)
Gain-of-function mutations are rare but can occur in cancer, leading to constitutive activation of GLI2 and uncontrolled cell proliferation.
Dominant Negative (DN)
Some missense mutations may act as dominant-negative, interfering with the function of the wild-type allele, particularly in holoprosencephaly.
View complete mutation data：
Gene Ontology (GO)
| • DNA-binding transcription factor activity | • RNA polymerase II cis-regulatory region sequence-specific DNA binding |
| • zinc ion binding | • protein heterodimerization activity |
| • positive regulation of transcription by RNA polymerase II | • negative regulation of transcription by RNA polymerase II |
| • cell differentiation | • embryonic limb morphogenesis |
| • neural tube patterning | • Hedgehog signaling pathway |
Pathways
• Hedgehog signaling pathway
• GLI protein processing
• Developmental biology
• Signaling by Hedgehog
Protein Summary
The GLI2 protein is a 1586-amino acid transcription factor with five C2H2-type zinc finger domains that mediate DNA binding. It contains an N-terminal repressor domain and a C-terminal activation domain. In the absence of Hedgehog ligand, GLI2 is proteolytically processed into a repressor form; upon pathway activation, it acts as a strong activator of target genes such as PTCH1 and GLI1. GLI2 is critical for embryonic development and is implicated in cancer when dysregulated.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| GLI2 Knockout HEK293 Cell Line | EDJ-KQ897 | Human | 2736 | Details Get a Quote |
| GLI2 Knockout A-549 Cell Line | EDJ-KQ19740 | Human | 2736 | Details Get a Quote |
| GLI2 Knockout HCT 116 Cell Line | EDJ-KQ19741 | Human | 2736 | Details Get a Quote |
| GLI2 Knockout HeLa Cell Line | EDJ-KQ19742 | Human | 2736 | Details Get a Quote |
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