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GLI1 (glioma-associated oncogene homolog 1)

Written2005-03Anna Dahlén, Fredrik Mertens, Nils Mandahl, Ioannis Panagopoulos
Department of Clinical Genetics, University Hospital, SE-221 85 Lund, Sweden

(Note : for Links provided by Atlas : click)

Identity

Other namesGLI
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 57853918 and ends at 57866047 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 2016)
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) [ 2 ]
  Nervous system: Astrocytic tumors
Soft Tissues: Pericytoma with t(7;12)(p22;q13) ACTB/GLI1
Soft tissue tumors: an overview

External links

Nomenclature
HGNC (Hugo)GLI1   4317
Cards
AtlasGLIID310ch12q13
Entrez_Gene (NCBI)GLI1  2735  GLI family zinc finger 1
AliasesGLI
GeneCards (Weizmann)GLI1
Ensembl hg19 (Hinxton)ENSG00000111087 [Gene_View]  chr12:57853918-57866047 [Contig_View]  GLI1 [Vega]
Ensembl hg38 (Hinxton)ENSG00000111087 [Gene_View]  chr12:57853918-57866047 [Contig_View]  GLI1 [Vega]
ICGC DataPortalENSG00000111087
TCGA cBioPortalGLI1
AceView (NCBI)GLI1
Genatlas (Paris)GLI1
WikiGenes2735
SOURCE (Princeton)GLI1
Genomic and cartography
GoldenPath hg19 (UCSC)GLI1  -     chr12:57853918-57866047 +  12q13.3   [Description]    (hg19-Feb_2009)
GoldenPath hg38 (UCSC)GLI1  -     12q13.3   [Description]    (hg38-Dec_2013)
EnsemblGLI1 - 12q13.3 [CytoView hg19]  GLI1 - 12q13.3 [CytoView hg38]
Mapping of homologs : NCBIGLI1 [Mapview hg19]  GLI1 [Mapview hg38]
OMIM165220   
Gene and transcription
Genbank (Entrez)AB239135 AB239136 AB239328 AB558490 AK297899
RefSeq transcript (Entrez)NM_001160045 NM_001167609 NM_005269
RefSeq genomic (Entrez)NC_000012 NC_018923 NG_029564 NT_029419 NW_004929384
Consensus coding sequences : CCDS (NCBI)GLI1
Cluster EST : UnigeneHs.632702 [ NCBI ]
CGAP (NCI)Hs.632702
Alternative Splicing GalleryENSG00000111087
Gene ExpressionGLI1 [ NCBI-GEO ]   GLI1 [ EBI - ARRAY_EXPRESS ]   GLI1 [ SEEK ]   GLI1 [ MEM ]
Gene Expression Viewer (FireBrowse)GLI1 [ Firebrowse - Broad ]
SOURCE (Princeton)Expression in : [Datasets]   [Normal Tissue Atlas]  [carcinoma Classsification]  [NCI60]
GenevisibleExpression in : [tissues]  [cell-lines]  [cancer]  [perturbations]  
BioGPS (Tissue expression)2735
GTEX Portal (Tissue expression)GLI1
Protein : pattern, domain, 3D structure
UniProt/SwissProtP08151 (Uniprot)
NextProtP08151  [Sequence]  [Exons]  [Medical]  [Publications]
With graphics : InterProP08151
Splice isoforms : SwissVarP08151 (Swissvar)
PhosPhoSitePlusP08151
Domaine pattern : Prosite (Expaxy)ZINC_FINGER_C2H2_1 (PS00028)    ZINC_FINGER_C2H2_2 (PS50157)   
Domains : Interpro (EBI)GLI1    Znf_C2H2    Znf_C2H2-like    Znf_C2H2/integrase_DNA-bd   
Domain families : Pfam (Sanger)
Domain families : Pfam (NCBI)
Domain families : Smart (EMBL)ZnF_C2H2 (SM00355)  
DMDM Disease mutations2735
Blocks (Seattle)GLI1
PDB (SRS)2GLI    4BLB    4KMD   
PDB (PDBSum)2GLI    4BLB    4KMD   
PDB (IMB)2GLI    4BLB    4KMD   
PDB (RSDB)2GLI    4BLB    4KMD   
Structural Biology KnowledgeBase2GLI    4BLB    4KMD   
SCOP (Structural Classification of Proteins)2GLI    4BLB    4KMD   
CATH (Classification of proteins structures)2GLI    4BLB    4KMD   
SuperfamilyP08151
Human Protein AtlasENSG00000111087
Peptide AtlasP08151
HPRD01311
IPIIPI00027451   IPI00910721   IPI00930112   IPI00982527   IPI00954134   
Protein Interaction databases
DIP (DOE-UCLA)P08151
IntAct (EBI)P08151
FunCoupENSG00000111087
BioGRIDGLI1
STRING (EMBL)GLI1
ZODIACGLI1
Ontologies - Pathways
QuickGOP08151
Ontology : AmiGORNA polymerase II regulatory region sequence-specific DNA binding  RNA polymerase II core promoter proximal region sequence-specific DNA binding  osteoblast differentiation  DNA binding  chromatin binding  chromatin binding  transcription factor activity, RNA polymerase II distal enhancer sequence-specific binding  protein binding  nucleus  nucleoplasm  nucleoplasm  cytoplasm  cytosol  cytosol  axoneme  transcription, DNA-templated  smoothened signaling pathway  smoothened signaling pathway  spermatogenesis  ventral midline development  microtubule binding  positive regulation of cell proliferation  regulation of smoothened signaling pathway  response to wounding  epidermal cell differentiation  dorsal/ventral pattern formation  proximal/distal pattern formation  cerebellar cortex morphogenesis  smoothened signaling pathway involved in regulation of cerebellar granule cell precursor cell proliferation  pituitary gland development  lung development  positive regulation of cell migration  intracellular membrane-bounded organelle  sequence-specific DNA binding  transcription regulatory region DNA binding  regulation of osteoblast differentiation  positive regulation of DNA replication  positive regulation of smoothened signaling pathway  positive regulation of transcription, DNA-templated  positive regulation of transcription from RNA polymerase II promoter  metal ion binding  digestive tract morphogenesis  notochord regression  canonical Wnt signaling pathway  primary cilium  negative regulation of canonical Wnt signaling pathway  liver regeneration  ciliary tip  ciliary base  regulation of hepatocyte proliferation  
Ontology : EGO-EBIRNA polymerase II regulatory region sequence-specific DNA binding  RNA polymerase II core promoter proximal region sequence-specific DNA binding  osteoblast differentiation  DNA binding  chromatin binding  chromatin binding  transcription factor activity, RNA polymerase II distal enhancer sequence-specific binding  protein binding  nucleus  nucleoplasm  nucleoplasm  cytoplasm  cytosol  cytosol  axoneme  transcription, DNA-templated  smoothened signaling pathway  smoothened signaling pathway  spermatogenesis  ventral midline development  microtubule binding  positive regulation of cell proliferation  regulation of smoothened signaling pathway  response to wounding  epidermal cell differentiation  dorsal/ventral pattern formation  proximal/distal pattern formation  cerebellar cortex morphogenesis  smoothened signaling pathway involved in regulation of cerebellar granule cell precursor cell proliferation  pituitary gland development  lung development  positive regulation of cell migration  intracellular membrane-bounded organelle  sequence-specific DNA binding  transcription regulatory region DNA binding  regulation of osteoblast differentiation  positive regulation of DNA replication  positive regulation of smoothened signaling pathway  positive regulation of transcription, DNA-templated  positive regulation of transcription from RNA polymerase II promoter  metal ion binding  digestive tract morphogenesis  notochord regression  canonical Wnt signaling pathway  primary cilium  negative regulation of canonical Wnt signaling pathway  liver regeneration  ciliary tip  ciliary base  regulation of hepatocyte proliferation  
Pathways : BIOCARTASonic Hedgehog (Shh) Pathway [Genes]   
Pathways : KEGGHedgehog signaling pathway    Pathways in cancer    Basal cell carcinoma   
REACTOMEP08151 [protein]
REACTOME PathwaysR-HSA-5610787 Hedgehog 'off' state [pathway]
REACTOME PathwaysR-HSA-5632684 Hedgehog 'on' state [pathway]
REACTOME PathwaysR-HSA-5610780 Degradation of GLI1 by the proteasome [pathway]
REACTOME PathwaysR-HSA-5635851 GLI proteins bind promoters of Hh responsive genes to promote transcription [pathway]
NDEx Network
Atlas of Cancer Signalling NetworkGLI1
Wikipedia pathwaysGLI1
Orthology - Evolution
OrthoDB2735
GeneTree (enSembl)ENSG00000111087
Phylogenetic Trees/Animal Genes : TreeFamGLI1
Homologs : HomoloGeneGLI1
Homology/Alignments : Family Browser (UCSC)GLI1
Gene fusions - Rearrangements
Fusion : MitelmanACTB/GLI1 [7p22.1/12q13.3]  [t(7;12)(p22;q13)]  
Fusion : MitelmanDDIT3/GLI1 [12q13.3/12q13.3]  [t(12;12)(q13;q13)]  
Fusion : COSMICGLI1 [12q13.3]  -  ACTB [7p22.1]  [fusion_1387]  [fusion_1388]  [fusion_1390]  [fusion_1395]  
Fusion: TCGADDIT3 12q13.3 GLI1 12q13.3 GBM
Fusion : TICdbPOTEF [2q21.1]  -  GLI1 [12q13.3]
Polymorphisms : SNP, variants
NCBI Variation ViewerGLI1 [hg38]
dbSNP Single Nucleotide Polymorphism (NCBI)GLI1
dbVarGLI1
ClinVarGLI1
1000_GenomesGLI1 
Exome Variant ServerGLI1
ExAC (Exome Aggregation Consortium)GLI1 (select the gene name)
Genetic variants : HAPMAP2735
Genomic Variants (DGV)GLI1 [DGVbeta]
Mutations
ICGC Data PortalGLI1 
TCGA Data PortalGLI1 
Broad Tumor PortalGLI1
OASIS PortalGLI1 [ Somatic mutations - Copy number]
Somatic Mutations in Cancer : COSMICGLI1 
LOVD (Leiden Open Variation Database)Whole genome datasets
LOVD (Leiden Open Variation Database)LOVD - Leiden Open Variation Database
LOVD (Leiden Open Variation Database)LOVD 3.0 shared installation
BioMutasearch GLI1
DgiDB (Drug Gene Interaction Database)GLI1
DoCM (Curated mutations)GLI1 (select the gene name)
CIViC (Clinical Interpretations of Variants in Cancer)GLI1 (select a term)
intoGenGLI1
Impact of mutations[PolyPhen2] [SIFT Human Coding SNP] [Buck Institute : MutDB] [Mutation Assessor] 
Diseases
DECIPHER (Syndromes)12:57853918-57866047  ENSG00000111087
CONAN: Copy Number AnalysisGLI1 
Mutations and Diseases : HGMDGLI1
OMIM165220   
MedgenGLI1
Genetic Testing Registry GLI1
NextProtP08151 [Medical]
TSGene2735
GENETestsGLI1
Huge Navigator GLI1 [HugePedia]
snp3D : Map Gene to Disease2735
BioCentury BCIQGLI1
ClinGenGLI1
Clinical trials, drugs, therapy
Chemical/Protein Interactions : CTD2735
Chemical/Pharm GKB GenePA28720
Clinical trialGLI1
Miscellaneous
canSAR (ICR)GLI1 (select the gene name)
Probes
Probeprobes 181L23 (AC022506) and 772E1 (AC063917) spanning the GLI1 locus.
Litterature
PubMed250 Pubmed reference(s) in Entrez
GeneRIFsGene References Into Functions (Entrez)
CoreMineGLI1
EVEXGLI1
GoPubMedGLI1
iHOPGLI1
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

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indexed on : Wed Aug 10 18:43:18 CEST 2016

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