GLI1 GLI family zinc finger 1 [Homo sapiens (human)] - Gene

Summary

Official Symbol: GLI1provided by HGNC
Official Full Name: GLI family zinc finger 1provided by HGNC
Primary source: HGNC:HGNC:4317
See related: Ensembl:ENSG00000111087 MIM:165220
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: GLI; PAPA8
Summary: This gene encodes a member of the Kruppel family of zinc finger proteins. The encoded transcription factor is activated by the sonic hedgehog signal transduction cascade and regulates stem cell proliferation. The activity and nuclear localization of this protein is negatively regulated by p53 in an inhibitory loop. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, May 2009]
Expression: Broad expression in endometrium (RPKM 5.6), testis (RPKM 2.9) and 15 other tissues See more
Orthologs: mouse all

Genomic context

Location:: 12q13.3

Exon count:: 13

Annotation release	Status	Assembly	Chr	Location
109	current	GRCh38.p12 (GCF_000001405.38)	12	NC_000012.12 (57460135..57472451)
105	previous assembly	GRCh37.p13 (GCF_000001405.25)	12	NC_000012.11 (57853918..57866051)

Chromosome 12 - NC_000012.12 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into FunctionsWhat's a GeneRIF?

This study found the expression of GLI1/p-S6K was apparently close with lymph node metastasis and TNM stage and patients with positive GLI1/p-S6K expression had shorter survival time and patients with both GLI1 and p-S6K positive expression had an even worse overall survival than those with single positive expression.
Title: The influence of aberrant expression of GLI1/p-S6K on colorectal cancer.
Study showed the expression levels of Gli1 and HER2 were significantly higher in gastric cancer, and they are positively related. Gli1 positive patients live a shorter survival time independently of HER2 status. In addition, suppressing the expression level of Gli1 can decrease the cell viability and migration ability in cells and subcutaneous tumors.
Title: Correlation of Gli1 and HER2 expression in gastric cancer: Identification of novel target.
The results provide new evidence of Numb and Gli1 on the clinical characteristics of Malignant pleural mesothelioma, which may be helpful in clinical diagnosis and targeted therapy. Further research with larger sample size is needed
Title: Expression of Numb and Gli1 in malignant pleural mesothelioma and their clinical significance.
Frameshift Mutation of GLI1 is associated with Colorectal Cancer.
Title: Intratumoral Heterogeneity of Frameshift Mutations of GLI1 Encoding a Hedgehog Signaling Protein in Colorectal Cancers.
Histone deacetylase 6 (HDAC6) inhibition enhanced glioma stem cells (GSCs) radiosensitivity via inactivating sonic hedgehog protein (SHH)/glioma-associated oncogene homolog 1 (Gli1) pathway.
Title: HDAC6 inhibition induces glioma stem cells differentiation and enhances cellular radiation sensitivity through the SHH/Gli1 signaling pathway.
HPI-1 worked more effectively than GANT-58 against breast carcinoma cells. In conclusion, HPI-1 could inhibit cell proliferation, reduce cell invasion and decrease cancer stem cell population in breast cancer cells. To target Gli-1 could be a potential strategy to suppress breast cancer stem cells.
Title: Glioma-Associated Oncogene Homolog Inhibitors Have the Potential of Suppressing Cancer Stem Cells of Breast Cancer.
High GLI1 expression is associated with unfavorable OS and FPS in patients with gastric cancer. As a member of the Hedgehog signaling pathway, GLI1 co-expressed genes are also largely enriched in PI3K/AKT pathway in gastric cancer.
Title: Bioinformatic Analysis of GLI1 and Related Signaling Pathways in Chemosensitivity of Gastric Cancer.
the results suggest that aberrant expression of Gli1 serves a role in HSCR by targeting EDNRB.
Title: Gli family zinc finger 1 is associated with endothelin receptor type B in Hirschsprung disease.
High GLI1 expression is associated with Small Cell Lung Cancer.
Title: Clinical Significance of Gli-1 And Caveolin-1 Expression in the Human Small Cell Lung Cancer
Abnormal elevation of Gli1 and decrease of miR-361 were found in esophageal cancer tissues. MiR-361 weakened invasion of cancer cells and impeded EMT process via the inhibition of Gli1.
Title: The targeted regulation of Gli1 by miR-361 to inhibit epithelia-mesenchymal transition and invasion of esophageal carcinoma cells.

Submit: New GeneRIF Correction See all GeneRIFs (289)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description	Tests
POLYDACTYLY, POSTAXIAL, TYPE A8 MedGen: CN253836 OMIM: 618123 GeneReviews: Not available	not available

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Pathways from BioSystems

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Basal cell carcinoma, organism-specific biosystem (from KEGG)
Basal cell carcinoma, organism-specific biosystemCancer of the skin is the most common cancer in Caucasians and basal cell carcinomas (BCC) account for 90% of all skin cancers. The vast majority of BCC cases are sporadic, though there is a rare fam...
Basal cell carcinoma, conserved biosystem (from KEGG)
Basal cell carcinoma, conserved biosystemCancer of the skin is the most common cancer in Caucasians and basal cell carcinomas (BCC) account for 90% of all skin cancers. The vast majority of BCC cases are sporadic, though there is a rare fam...
Degradation of GLI1 by the proteasome, organism-specific biosystem (from REACTOME)
Degradation of GLI1 by the proteasome, organism-specific biosystemGLI1 is the most divergent of the 3 mammalian GLI transcription factors and lacks a transcriptional repressor domain. Although GLI1 is dispensible for development, the gene is an early transcription...
Dopaminergic Neurogenesis, organism-specific biosystem (from WikiPathways)
Dopaminergic Neurogenesis, organism-specific biosystemConverted to human from mouse: http://www.wikipathways.org/index.php/Pathway:WP1498
GLI proteins bind promoters of Hh responsive genes to promote transcription, organism-specific biosystem (from REACTOME)
GLI proteins bind promoters of Hh responsive genes to promote transcription, organism-specific biosystemGLI proteins are bifunctional DNA-binding proteins that recognize consensus GLI sites 5'-GACCACCC-3' in the promoters of target genes (Kinzler and Vogelstein, 1990). Pathway induction upon ligand-bi...
Hedgehog 'off' state, organism-specific biosystem (from REACTOME)
Hedgehog 'off' state, organism-specific biosystemHedgehog is a secreted morphogen that has evolutionarily conserved roles in body organization by regulating the activity of the Ci/Gli transcription factor family. In Drosophila in the absence of Hh ...
Hedgehog 'on' state, organism-specific biosystem (from REACTOME)
Hedgehog 'on' state, organism-specific biosystemHedgehog is a secreted morphogen that has evolutionarily conserved roles in body organization by regulating the activity of the Ci/Gli transcription factor family. In Drosophila in the absence of Hh ...
Hedgehog Signaling Pathway, organism-specific biosystem (from WikiPathways)
Hedgehog Signaling Pathway, organism-specific biosystemThe Hedgehog family of proteins are signaling proteins that are crucial for a number of physiological processes including morphogenesis during development. In adult organisms, it is also involved in ...
Hedgehog signaling, organism-specific biosystem (from KEGG)
Hedgehog signaling, organism-specific biosystemFunctional set; Cellular processes; Cell signaling
Hedgehog signaling, conserved biosystem (from KEGG)
Hedgehog signaling, conserved biosystemFunctional set; Cellular processes; Cell signaling
Hedgehog signaling events mediated by Gli proteins, organism-specific biosystem (from Pathway Interaction Database)
Hedgehog signaling events mediated by Gli proteins, organism-specific biosystem
Hedgehog signaling events mediated by Gli proteins
Hedgehog signaling pathway, organism-specific biosystem (from KEGG)
Hedgehog signaling pathway, organism-specific biosystemThe Hedgehog (Hh) signaling pathway has numerous roles in the control of cell proliferation, tissue patterning, stem cell maintenance and development. The primary cilium is an important center for tr...
Hedgehog signaling pathway, conserved biosystem (from KEGG)
Hedgehog signaling pathway, conserved biosystemThe Hedgehog (Hh) signaling pathway has numerous roles in the control of cell proliferation, tissue patterning, stem cell maintenance and development. The primary cilium is an important center for tr...
Pathways in cancer, organism-specific biosystem (from KEGG)
Pathways in cancer, organism-specific biosystem
Pathways in cancer
Signal Transduction, organism-specific biosystem (from REACTOME)
Signal Transduction, organism-specific biosystemSignal transduction is a process in which extracellular signals elicit changes in cell state and activity. Transmembrane receptors sense changes in the cellular environment by binding ligands, such a...
Signaling by Hedgehog, organism-specific biosystem (from REACTOME)
Signaling by Hedgehog, organism-specific biosystemHedgehog (Hh) is a secreted morphogen that regulates developmental processes in vertebrates including limb bud formation, neural tube patterning, cell growth and differentiation (reviewed in Hui and ...
cAMP signaling pathway, organism-specific biosystem (from KEGG)
cAMP signaling pathway, organism-specific biosystemcAMP is one of the most common and universal second messengers, and its formation is promoted by adenylyl cyclase (AC) activation after ligation of G protein-coupled receptors (GPCRs) by ligands incl...
cAMP signaling pathway, conserved biosystem (from KEGG)
cAMP signaling pathway, conserved biosystemcAMP is one of the most common and universal second messengers, and its formation is promoted by adenylyl cyclase (AC) activation after ligation of G protein-coupled receptors (GPCRs) by ligands incl...

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

RH102952 (e-PCR)
- UniSTS:97286

GLI_108 (e-PCR)
- UniSTS:277285

PMC156767P1 (e-PCR)
- UniSTS:271429

STS-X07384 (e-PCR)
- UniSTS:51623

GDB:384866 (e-PCR)
- UniSTS:157113

D12S1934 (e-PCR)
- UniSTS:12266

Homology

Homologs of the GLI1 gene: The GLI1 gene is conserved in chimpanzee, Rhesus monkey, dog, cow, mouse, and rat.
Orthologs from Annotation Pipeline: 237 organisms have orthologs with human gene GLI1
Orthologs

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
DNA binding	IDA Inferred from Direct Assay more info	PubMed
DNA-binding transcription factor activity, RNA polymerase II-specific	ISA Inferred from Sequence Alignment more info
DNA-binding transcription factor activity, RNA polymerase II-specific	NAS Non-traceable Author Statement more info	PubMed
RNA polymerase II proximal promoter sequence-specific DNA binding	IEA Inferred from Electronic Annotation more info
RNA polymerase II regulatory region sequence-specific DNA binding	IDA Inferred from Direct Assay more info	PubMed
chromatin binding	IEA Inferred from Electronic Annotation more info
metal ion binding	IEA Inferred from Electronic Annotation more info
microtubule binding	IEA Inferred from Electronic Annotation more info
protein binding	IPI Inferred from Physical Interaction more info	PubMed
transcription regulatory region DNA binding	IDA Inferred from Direct Assay more info	PubMed

Process	Evidence Code	Pubs
canonical Wnt signaling pathway	IEA Inferred from Electronic Annotation more info
cerebellar cortex morphogenesis	IEA Inferred from Electronic Annotation more info
digestive tract morphogenesis	TAS Traceable Author Statement more info	PubMed
dorsal/ventral pattern formation	IEA Inferred from Electronic Annotation more info
epidermal cell differentiation	IDA Inferred from Direct Assay more info	PubMed
liver regeneration	IEA Inferred from Electronic Annotation more info
lung development	IEA Inferred from Electronic Annotation more info
negative regulation of canonical Wnt signaling pathway	IMP Inferred from Mutant Phenotype more info	PubMed
notochord regression	IEA Inferred from Electronic Annotation more info
osteoblast differentiation	IDA Inferred from Direct Assay more info	PubMed
pituitary gland development	IEA Inferred from Electronic Annotation more info
positive regulation of DNA replication	IDA Inferred from Direct Assay more info	PubMed
positive regulation of cardiac muscle cell proliferation	IDA Inferred from Direct Assay more info	PubMed
positive regulation of cell cycle G1/S phase transition	IDA Inferred from Direct Assay more info	PubMed
positive regulation of cell proliferation	IMP Inferred from Mutant Phenotype more info	PubMed
positive regulation of smoothened signaling pathway	IDA Inferred from Direct Assay more info	PubMed
positive regulation of transcription by RNA polymerase II	IDA Inferred from Direct Assay more info	PubMed
positive regulation of transcription, DNA-templated	IDA Inferred from Direct Assay more info	PubMed
prostate gland development	IEA Inferred from Electronic Annotation more info
proximal/distal pattern formation	IEA Inferred from Electronic Annotation more info
regulation of hepatocyte proliferation	IEA Inferred from Electronic Annotation more info
regulation of osteoblast differentiation	IEA Inferred from Electronic Annotation more info
regulation of smoothened signaling pathway	TAS Traceable Author Statement more info	PubMed
response to wounding	IEA Inferred from Electronic Annotation more info
smoothened signaling pathway	IDA Inferred from Direct Assay more info	PubMed
smoothened signaling pathway	TAS Traceable Author Statement more info	PubMed
smoothened signaling pathway involved in regulation of cerebellar granule cell precursor cell proliferation	IEA Inferred from Electronic Annotation more info
spermatogenesis	IEA Inferred from Electronic Annotation more info
ventral midline development	IEA Inferred from Electronic Annotation more info

Component	Evidence Code	Pubs
axoneme	IEA Inferred from Electronic Annotation more info
ciliary base	TAS Traceable Author Statement more info
ciliary tip	TAS Traceable Author Statement more info
cytoplasm	IDA Inferred from Direct Assay more info	PubMed
cytosol	IDA Inferred from Direct Assay more info	PubMed
cytosol	TAS Traceable Author Statement more info
nucleoplasm	IDA Inferred from Direct Assay more info
nucleoplasm	TAS Traceable Author Statement more info
nucleus	IDA Inferred from Direct Assay more info	PubMed

General protein information

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Preferred Names: zinc finger protein GLI1

Names: GLI-Kruppel family member GLI1; glioma-associated oncogene 1; glioma-associated oncogene homolog 1 (zinc finger protein); oncogene GLI

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

NG_029564.1 RefSeqGene

Range

5017..17134

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_001160045.1 → NP_001153517.1 zinc finger protein GLI1 isoform 2

See identical proteins and their annotated locations for NP_001153517.1

Status: REVIEWED

Description

Transcript Variant: This variant (1) omits the first two coding exons, compared to variant 1, resulting in transcription initiation from an internal AUG site and a N-terminally truncated protein isoform (2), also know as GLI1DeltaN. This variant reflects the transcript and protein described by Shimokawa (PubMed ID 18378682).

Source sequence(s)

AC022506, AK297899, BC013000

Consensus CDS

CCDS53807.1

UniProtKB/Swiss-Prot

P08151

UniProtKB/TrEMBL

B4DNF7

Related

ENSP00000437607.1, ENST00000543426.5

Conserved Domains (3) summary

sd00017
Location:175 → 197

ZF_C2H2; C2H2 Zn finger [structural motif]

pfam13465
Location:189 → 216

zf-H2C2_2; Zinc-finger double domain

pfam16159
Location:109 → 137

FOXP-CC; FOXP coiled-coil domain
NM_001167609.1 → NP_001161081.1 zinc finger protein GLI1 isoform 3

Status: REVIEWED

Description

Transcript Variant: This variant (3) lacks an in-frame segment in the 5' coding region, compared to variant 1, resulting in a shorter protein isoform (3), also known as tGLI1. This variant reflects the transcript and protein described by Lo (PubMed ID 19706761).

Source sequence(s)

AC022506

Consensus CDS

CCDS53806.1

UniProtKB/Swiss-Prot

P08151

Related

ENSP00000441006.1, ENST00000546141.5

Conserved Domains (3) summary

sd00017
Location:262 → 284

ZF_C2H2; C2H2 Zn finger [structural motif]

pfam13465
Location:276 → 303

zf-H2C2_2; Zinc-finger double domain

pfam16159
Location:196 → 224

FOXP-CC; FOXP coiled-coil domain
NM_005269.3 → NP_005260.1 zinc finger protein GLI1 isoform 1

See identical proteins and their annotated locations for NP_005260.1

Status: REVIEWED

Description

Transcript Variant: This variant (1) encodes the full length protein (isoform 1).

Source sequence(s)

AC022506, BC013000, X07384

Consensus CDS

CCDS8940.1

UniProtKB/Swiss-Prot

P08151

Related

ENSP00000228682.2, ENST00000228682.6

Conserved Domains (3) summary

sd00017
Location:303 → 325

ZF_C2H2; C2H2 Zn finger [structural motif]

pfam13465
Location:317 → 344

zf-H2C2_2; Zinc-finger double domain

pfam16159
Location:237 → 265

FOXP-CC; FOXP coiled-coil domain

RefSeqs of Annotated Genomes: Homo sapiens Annotation Release 109

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p12 Primary Assembly

Genomic

NC_000012.12 Reference GRCh38.p12 Primary Assembly

Range

57460135..57472451

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_011538190.2 → XP_011536492.1 zinc finger protein GLI1 isoform X2

Conserved Domains (4) summary

COG5048
Location:291 → 368

COG5048; FOG: Zn-finger [General function prediction only]

sd00017
Location:303 → 325

ZF_C2H2; C2H2 Zn finger [structural motif]

pfam13465
Location:317 → 344

zf-H2C2_2; Zinc-finger double domain

pfam16159
Location:237 → 265

FOXP-CC; FOXP coiled-coil domain
XM_011538189.2 → XP_011536491.1 zinc finger protein GLI1 isoform X1

See identical proteins and their annotated locations for XP_011536491.1

UniProtKB/Swiss-Prot

P08151

Conserved Domains (3) summary

sd00017
Location:303 → 325

ZF_C2H2; C2H2 Zn finger [structural motif]

pfam13465
Location:317 → 344

zf-H2C2_2; Zinc-finger double domain

pfam16159
Location:237 → 265

FOXP-CC; FOXP coiled-coil domain