GLI1 (glioma-associated oncogene homolog 1)
2005-03-01 Anna Dahlén , Fredrik Mertens , Nils Mandahl , Ioannis Panagopoulos AffiliationDepartment of Clinical Genetics, University Hospital, SE-221 85 Lund, Sweden
Identity
HGNC
LOCATION
12q13.3
LOCUSID
ALIAS
GLI,PAPA8,PPD1
FUSION GENES
DNA/RNA
Genomic organization of the GLI1 gene.
Description
12 exons, spans approximately 12 kb of genomic DNA in the centromere-to-telomere orientation. The translation initiation codon is located to exon 2, and the stop codon to exon 12.
Transcription
mRNA of 3.6 kb
Proteins
Description
The open reading frame encodes a 1106 amino acid protein, with an estimated molecular weight of approximately 118 kDa. The protein contains five DNA-binding zinc fingers between amino acids 235 and 393 (encoded by exons 7-10), and a transactivating domain constituted by amino acids 1020-1091 (encoded by exon 12).
Expression
GLI proteins function as direct effectors of sonic hedgehog-signaling during embryogenesis. GLI1 (also GLI2 and GLI3) are therefore likely to be involved in the tissue-specific proliferation of the central nervous system, the zones of polarizing activity in the developing limb, and of the gut. In the adult human, GLI1 expression has been demonstrated in the testes, myometrium and Fallopian tubes.
Localisation
Nuclear. Might be fluctuating between the cytoplasm and the nucleus.
Function
DNA-binding transcription factor
Mutations
Germinal
An abnormal activity of GLI, caused by mutations affecting upstream components of the sonic hedgehog-signaling pathway (sonic hedgehog, patched or smoothened) are associated with developmental disorders.
Somatic
Various tumors of mesenchymal and lymphocytic origin.
Implicated in
Note
Rearrangement and fusion of the GLI1 gene.
Disease
Prognosis
Benign or low-malignant
Cytogenetics
t(7;12)(p22;q13)
Hybrid gene
ACTB-GLI1 fusion gene. The breakpoints reported so far have been located to introns 1, 2 or 3 within the ACTB gene, and to introns 5 or 6 or to exon 7 within the GLI1 gene. Reciprocal GLI1-ACTB gene fusions have also been detected. The breakpoints have been located to introns 5 or 7 within the GLI1 gene, and to intron 3 of the ACTB gene.
Representative G-banded partial karyotype of the t(7;12)(p22;q13).
Fusion protein
The ACTB-GLI1 fusion protein contains the N-terminal of ACTB and the C-terminal of GLI1, including the DNA-binding zinc finger motifs (encoded by exons 7-10) and transactivating motifs (exon 12).
Oncogenesis
It is suggested that the strong ACTB promoter causes an overexpression of GLI1 sequences important for transcriptional activation of downstream target genes, akin to the oncogenic mechanisms of the COL1A1-PDGFB fusion gene detected in dermatofibrosarcoma protuberans.
Note
Amplification of the GLI1 gene
Disease
Glioma, B-cell lymphoma, sarcoma
Prognosis
Depends on tumor type
Oncogenesis
Overexpression of GLI1 sequences. Might be of prognostic importance.
Article Bibliography
| Pubmed ID | Last Year | Title | Authors |
|---|---|---|---|
| 2497059 | 1989 | In situ hybridization localizes the human putative oncogene GLI to chromosome subbands 12q13.3-14.1. | Arheden K et al |
| 15555571 | 2004 | Molecular genetic characterization of the genomic ACTB-GLI fusion in pericytoma with t(7;12). | Dahlén A et al |
| 8641133 | 1996 | Assignment of the gene encoding human Krüppel-related zinc finger protein 4 (GLI4) to 8q24.3 by fluorescent in situ hybridization. | Kas K et al |
| 2105456 | 1990 | The GLI gene encodes a nuclear protein which binds specific sequences in the human genome. | Kinzler KW et al |
| 9524201 | 1998 | Characterization of the promoter region and genomic organization of GLI, a member of the Sonic hedgehog-Patched signaling pathway. | Liu CZ et al |
| 8812445 | 1996 | Assignment of the human GLI2 gene to 2q14 by fluorescence in situ hybridization. | Matsumoto N et al |
| 10441331 | 1999 | Expression of the Sonic hedgehog (SHH ) gene during early human development and phenotypic expression of new mutations causing holoprosencephaly. | Odent S et al |
| 2766305 | 1989 | Amplification of the gli gene in childhood sarcomas. | Roberts WM et al |
| 2118997 | 1990 | GLI3 encodes a 190-kilodalton protein with multiple regions of GLI similarity. | Ruppert JM et al |
| 8988177 | 1997 | Deregulation of the platelet-derived growth factor B-chain gene via fusion with collagen gene COL1A1 in dermatofibrosarcoma protuberans and giant-cell fibroblastoma. | Simon MP et al |
| 11001584 | 2000 | The sonic hedgehog-patched-gli pathway in human development and disease. | Villavicencio EH et al |
| 9250147 | 1997 | High-level DNA amplifications are common genetic aberrations in B-cell neoplasms. | Werner CA et al |
Other Information
Locus ID:
NCBI: 2735
MIM: 165220
HGNC: 4317
Ensembl: ENSG00000111087
Variants:
dbSNP: 2735
ClinVar: 2735
TCGA: ENSG00000111087
COSMIC: GLI1
RNA/Proteins
Expression (GTEx)
Pathways
Protein levels (Protein atlas)
References
| Pubmed ID | Year | Title | Citations |
|---|---|---|---|
| 36683360 | 2024 | Enhanced mitophagy driven by ADAR1-GLI1 editing supports the self-renewal of cancer stem cells in HCC. | 4 |
| 38278602 | 2024 | GLI1-Altered Mesenchymal Tumors. | 0 |
| 38307877 | 2024 | Phosphorylation of human glioma-associated oncogene 1 on Ser937 regulates Sonic Hedgehog signaling in medulloblastoma. | 0 |
| 38621503 | 2024 | GLI1 Coamplification in Well-Differentiated/Dedifferentiated Liposarcomas: Clinicopathologic and Molecular Analysis of 92 Cases. | 0 |
| 38676765 | 2024 | GLI1 polymorphisms influence remission rate and prognosis of young de novo acute myeloid leukemia patients treated with cytarabine-based chemotherapy. | 0 |
| 36683360 | 2024 | Enhanced mitophagy driven by ADAR1-GLI1 editing supports the self-renewal of cancer stem cells in HCC. | 4 |
| 38278602 | 2024 | GLI1-Altered Mesenchymal Tumors. | 0 |
| 38307877 | 2024 | Phosphorylation of human glioma-associated oncogene 1 on Ser937 regulates Sonic Hedgehog signaling in medulloblastoma. | 0 |
| 38621503 | 2024 | GLI1 Coamplification in Well-Differentiated/Dedifferentiated Liposarcomas: Clinicopathologic and Molecular Analysis of 92 Cases. | 0 |
| 38676765 | 2024 | GLI1 polymorphisms influence remission rate and prognosis of young de novo acute myeloid leukemia patients treated with cytarabine-based chemotherapy. | 0 |
| 37107627 | 2023 | Identification of GLI1 and KIAA0825 Variants in Two Families with Postaxial Polydactyly. | 0 |
| 37151880 | 2023 | Gli1 promotes the phenotypic transformation of valve interstitial cells through Hedgehog pathway activation exacerbating calcific aortic valve disease. | 3 |
| 37165307 | 2023 | MALAT1 functions as a transcriptional promoter of MALAT1::GLI1 fusion for truncated GLI1 protein expression in cancer. | 2 |
| 37700593 | 2023 | FUNDC2, a mitochondrial outer membrane protein, mediates triple-negative breast cancer progression via the AKT/GSK3β/GLI1 pathway. | 1 |
| 37890593 | 2023 | FOXS1 promotes prostate cancer progression through the Hedgehog/Gli1 pathway. | 2 |
Citation
Anna Dahlén ; Fredrik Mertens ; Nils Mandahl ; Ioannis Panagopoulos
GLI1 (glioma-associated oncogene homolog 1)
Atlas Genet Cytogenet Oncol Haematol. 2005-03-01
Online version: http://atlasgeneticsoncology.org/gene/310
