| Written | 2005-03 | Anna Dahlén, Fredrik Mertens, Nils Mandahl, Ioannis Panagopoulos |
| Department of Clinical Genetics, University Hospital, SE-221 85 Lund, Sweden |
| Identity |
| Alias_names | GLI |
| glioma-associated oncogene homolog 1 (zinc finger protein) | |
| glioma-associated oncogene family zinc finger 1 | |
| Other alias | Zinc finger protein GLI1 (glioma-associated oncogene) |
| Oncogene GLI | |
| Glioma-associated oncogene homolog 1 | |
| HGNC (Hugo) | GLI1 |
| LocusID (NCBI) | 2735 |
| Atlas_Id | 310 |
| Location | 12q13.3 [Link to chromosome band 12q13] |
| Location_base_pair | Starts at 57460151 and ends at 57472264 bp from pter ( according to hg19-Feb_2009) [Mapping GLI1.png] |
| Local_order | Telomeric to the ATF1 gene; centromeric to the OS-9, SAS and CDK4 genes. |
| Fusion genes (updated 2017) | Data from Atlas, Mitelman, Cosmic Fusion, Fusion Cancer, TCGA fusion databases with official HUGO symbols (see references in chromosomal bands) |
| ACTB (7p22.1) / GLI1 (12q13.3) | DDIT3 (12q13.3) / GLI1 (12q13.3) | GLI1 (12q13.3) / ACTB (7p22.1) | |
| POTEF (2q21.1) / GLI1 (12q13.3) |
| Note | GLI1 was the first human member of the Krüppel zinc finger proteins to be identified, and constitutes the archetype of this family of human genes. Other members are GLI2 (2q14) and GLI3 (7p13). GLI4/HKR4 (8q24) was misclassified as member of the human GLI gene family. |
| 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 |
| Protein |
| 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 | |
| Note | Rearrangement and fusion of the GLI1 gene. |
| Disease | Pericytoma with t(7;12) |
| Prognosis | Benign or low-malignant |
| Cytogenetics | t(7;12)(p22;q13) |
| Hybrid/Mutated 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). | |
| Abnormal 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. |
| Bibliography |
| In situ hybridization localizes the human putative oncogene GLI to chromosome subbands 12q13.3-14.1. |
| Arheden K, R&oring;nne M, Mandahl N, Heim S, Kinzler KW, Vogelstein B, Mitelman F |
| Human genetics. 1989 ; 82 (1) : 1-2. |
| PMID 2497059 |
| Molecular genetic characterization of the genomic ACTB-GLI fusion in pericytoma with t(7;12). |
| Dahlén A, Mertens F, Mandahl N, Panagopoulos I |
| Biochemical and biophysical research communications. 2004 ; 325 (4) : 1318-1323. |
| PMID 15555571 |
| Assignment of the gene encoding human Krüppel-related zinc finger protein 4 (GLI4) to 8q24.3 by fluorescent in situ hybridization. |
| Kas K, Wlodarska I, Meyen E, Van den Berghe H, Van de Ven WJ |
| Cytogenetics and cell genetics. 1996 ; 72 (4) : 297-298. |
| PMID 8641133 |
| The GLI gene encodes a nuclear protein which binds specific sequences in the human genome. |
| Kinzler KW, Vogelstein B |
| Molecular and cellular biology. 1990 ; 10 (2) : 634-642. |
| PMID 2105456 |
| Characterization of the promoter region and genomic organization of GLI, a member of the Sonic hedgehog-Patched signaling pathway. |
| Liu CZ, Yang JT, Yoon JW, Villavicencio E, Pfendler K, Walterhouse D, Iannaccone P |
| Gene. 1998 ; 209 (1-2) : 1-11. |
| PMID 9524201 |
| Assignment of the human GLI2 gene to 2q14 by fluorescence in situ hybridization. |
| Matsumoto N, Fujimoto M, Kato R, Niikawa N |
| Genomics. 1996 ; 36 (1) : 220-221. |
| PMID 8812445 |
| Expression of the Sonic hedgehog (SHH ) gene during early human development and phenotypic expression of new mutations causing holoprosencephaly. |
| Odent S, Atti-Bitach T, Blayau M, Mathieu M, Aug J, Delezo de AL, Gall JY, Le Marec B, Munnich A, David V, Vekemans M |
| Human molecular genetics. 1999 ; 8 (9) : 1683-1689. |
| PMID 10441331 |
| Amplification of the gli gene in childhood sarcomas. |
| Roberts WM, Douglass EC, Peiper SC, Houghton PJ, Look AT |
| Cancer research. 1989 ; 49 (19) : 5407-5413. |
| PMID 2766305 |
| GLI3 encodes a 190-kilodalton protein with multiple regions of GLI similarity. |
| Ruppert JM, Vogelstein B, Arheden K, Kinzler KW |
| Molecular and cellular biology. 1990 ; 10 (10) : 5408-5415. |
| PMID 2118997 |
| 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, Pedeutour F, Sirvent N, Grosgeorge J, Minoletti F, Coindre JM, Terrier-Lacombe MJ, Mandahl N, Craver RD, Blin N, Sozzi G, Turc-Carel C, O'Brien KP, Kedra D, Fransson I, Guilbaud C, Dumanski JP |
| Nature genetics. 1997 ; 15 (1) : 95-98. |
| PMID 8988177 |
| The sonic hedgehog-patched-gli pathway in human development and disease. |
| Villavicencio EH, Walterhouse DO, Iannaccone PM |
| American journal of human genetics. 2000 ; 67 (5) : 1047-1054. |
| PMID 11001584 |
| High-level DNA amplifications are common genetic aberrations in B-cell neoplasms. |
| Werner CA, Döhner H, Joos S, Trümper LH, Baudis M, Barth TF, Ott G, Möller P, Lichter P, Bentz M |
| The American journal of pathology. 1997 ; 151 (2) : 335-342. |
| PMID 9250147 |
| Citation |
| This paper should be referenced as such : |
| Dahlén, A ; Mertens, F ; Mandahl, N ; Panagopoulos, I |
| GLI1 (glioma-associated oncogene homolog 1) |
| Atlas Genet Cytogenet Oncol Haematol. 2005;9(2):134-136. |
| Free journal version : [ pdf ] [ DOI ] |
| On line version : http://AtlasGeneticsOncology.org/Genes/GLIID310ch12q13.html |
| Other Solid tumors implicated (Data extracted from papers in the Atlas) [ 4 ] |
|
Soft Tissues: Pericytoma with t(7;12)(p22;q13) ACTB/GLI1
Soft tissue tumors: an overview t(11;12)(q13;q13) MALAT1/GLI1 DDIT3/GLI1 (12q13) |
| External links |
| REVIEW articles | automatic search in PubMed |
| Last year publications | automatic search in PubMed |
| © Atlas of Genetics and Cytogenetics in Oncology and Haematology | indexed on : Wed Nov 13 21:24:31 CET 2019 |
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