GLI1 (glioma-associated oncogene homolog 1)

2005-03-01   Anna Dahlén  , Fredrik Mertens  , Nils Mandahl  , Ioannis Panagopoulos  

Department of Clinical Genetics, University Hospital, SE-221 85 Lund, Sweden

Identity

HGNC
GLI1
LOCATION
12q13.3
LOCUSID
2735
ALIAS
GLI,PAPA8,PPD1
FUSION GENES
Show Gene Fusions

DNA/RNA

Atlas Image
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
Pericytoma with t(7;12)
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.
Atlas Image
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 IDLast YearTitleAuthors
24970591989In situ hybridization localizes the human putative oncogene GLI to chromosome subbands 12q13.3-14.1.Arheden K et al
155555712004Molecular genetic characterization of the genomic ACTB-GLI fusion in pericytoma with t(7;12).Dahlén A et al
86411331996Assignment of the gene encoding human Krüppel-related zinc finger protein 4 (GLI4) to 8q24.3 by fluorescent in situ hybridization.Kas K et al
21054561990The GLI gene encodes a nuclear protein which binds specific sequences in the human genome.Kinzler KW et al
95242011998Characterization of the promoter region and genomic organization of GLI, a member of the Sonic hedgehog-Patched signaling pathway.Liu CZ et al
88124451996Assignment of the human GLI2 gene to 2q14 by fluorescence in situ hybridization.Matsumoto N et al
104413311999Expression of the Sonic hedgehog (SHH ) gene during early human development and phenotypic expression of new mutations causing holoprosencephaly.Odent S et al
27663051989Amplification of the gli gene in childhood sarcomas.Roberts WM et al
21189971990GLI3 encodes a 190-kilodalton protein with multiple regions of GLI similarity.Ruppert JM et al
89881771997Deregulation 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
110015842000The sonic hedgehog-patched-gli pathway in human development and disease.Villavicencio EH et al
92501471997High-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

Gene IDTranscript IDUniprot
ENSG00000111087ENST00000228682P08151
ENSG00000111087ENST00000528432E9PQQ1
ENSG00000111087ENST00000528467P08151
ENSG00000111087ENST00000532291E9PIB9
ENSG00000111087ENST00000543426P08151
ENSG00000111087ENST00000546141P08151

Expression (GTEx)

0
5
10
15
20
25
30
35
40
45
50
Adipose - Subcutaneous
Adipose - Visceral
Adrenal Gland
Artery - Aorta
Artery - Tibial
Bladder
Brain - Amygdala
Brain - Anterior cingulate cortex
Brain - Caudate
Brain - Cerebellar Hemisphere
Brain - Cerebellum
Brain - Cortex
Brain - Frontal Cortex
Brain - Hippocampus
Brain - Hypothalamus
Brain - Nucleus accumbens
Brain - Putamen
Brain - Spinal cord
Brain - Substantia nigra
Breast - Mammary Tissue
Cells - Cultured fibroblasts
Cells - EBV - transformed lymphocytes
Cervix - Ectocervix
Cervix - Endocervix
Colon - Sigmoid
Colon - Transverse
Esophagus - Gastroesophageal Junction
Esophagus - Mucosa
Esophagus - Muscularis
Fallopian Tube
Heart - Atrial Appendage
Heart - Left Ventricle
Kidney - Cortex
Kidney - Medulla
Liver
Lung
Minor Salivary Gland
Muscle - Skeletal
Nerve - Tibial
Ovary
Pancreas
Pituitary
Prostate
Skin - Not Sun Exposed
Skin - Sun Exposed
Small Intestine - Terminal Ileum
Spleen
Stomach
Testis
Thyroid
Uterus
Vagina
Whole Blood

Pathways

PathwaySourceExternal ID
Hedgehog signaling pathwayKEGGko04340
Basal cell carcinomaKEGGko05217
Hedgehog signaling pathwayKEGGhsa04340
Pathways in cancerKEGGhsa05200
Basal cell carcinomaKEGGhsa05217
cAMP signaling pathwayKEGGhsa04024
cAMP signaling pathwayKEGGko04024
Hedgehog signalingKEGGhsa_M00678
Hedgehog signalingKEGGM00678
Signal TransductionREACTOMER-HSA-162582
Signaling by HedgehogREACTOMER-HSA-5358351
Hedgehog 'off' stateREACTOMER-HSA-5610787
Degradation of GLI1 by the proteasomeREACTOMER-HSA-5610780
Hedgehog 'on' stateREACTOMER-HSA-5632684
GLI proteins bind promoters of Hh responsive genes to promote transcriptionREACTOMER-HSA-5635851

Protein levels (Protein atlas)

Not detected
Low
Medium
High
cerebral cortex
cerebellum
hippocampus
caudate
thyroid gland
parathyroid gland
adrenal gland
nasopharynx
bronchus
lung
oral mucosa
salivary gland
esophagus
stomach 1
stomach 2
duodenum
small intestine
colon
rectum
liver
gallbladder
pancreas
kidney
urinary bladder
testis
epididymis
seminal vesicle
prostate
vagina
ovary
fallopian tube
endometrium 1
endometrium 2
cervix, uterine
placenta
breast
heart muscle
smooth muscle
skeletal muscle
soft tissue 1
soft tissue 2
adipose tissue
skin 1
skin 2
appendix
spleen
lymph node
tonsil
bone marrow

References

Pubmed IDYearTitleCitations
366833602024Enhanced mitophagy driven by ADAR1-GLI1 editing supports the self-renewal of cancer stem cells in HCC.4
382786022024GLI1-Altered Mesenchymal Tumors.0
383078772024Phosphorylation of human glioma-associated oncogene 1 on Ser937 regulates Sonic Hedgehog signaling in medulloblastoma.0
386215032024GLI1 Coamplification in Well-Differentiated/Dedifferentiated Liposarcomas: Clinicopathologic and Molecular Analysis of 92 Cases.0
386767652024GLI1 polymorphisms influence remission rate and prognosis of young de novo acute myeloid leukemia patients treated with cytarabine-based chemotherapy.0
366833602024Enhanced mitophagy driven by ADAR1-GLI1 editing supports the self-renewal of cancer stem cells in HCC.4
382786022024GLI1-Altered Mesenchymal Tumors.0
383078772024Phosphorylation of human glioma-associated oncogene 1 on Ser937 regulates Sonic Hedgehog signaling in medulloblastoma.0
386215032024GLI1 Coamplification in Well-Differentiated/Dedifferentiated Liposarcomas: Clinicopathologic and Molecular Analysis of 92 Cases.0
386767652024GLI1 polymorphisms influence remission rate and prognosis of young de novo acute myeloid leukemia patients treated with cytarabine-based chemotherapy.0
371076272023Identification of GLI1 and KIAA0825 Variants in Two Families with Postaxial Polydactyly.0
371518802023Gli1 promotes the phenotypic transformation of valve interstitial cells through Hedgehog pathway activation exacerbating calcific aortic valve disease.3
371653072023MALAT1 functions as a transcriptional promoter of MALAT1::GLI1 fusion for truncated GLI1 protein expression in cancer.2
377005932023FUNDC2, a mitochondrial outer membrane protein, mediates triple-negative breast cancer progression via the AKT/GSK3β/GLI1 pathway.1
378905932023FOXS1 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/favicon/css/js/_common.js