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; PPD1; 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
109.20190607	current	GRCh38.p13 (GCF_000001405.39)	12	NC_000012.12 (57459785..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?

the increase of GLI1 transcription in PTCH1 knockdown cells is associated with nuclear SMO function, a mechanism insensitive to pharmacologic inhibition.
Title: A Novel Mechanism for Activation of GLI1 by Nuclear SMO That Escapes Anti-SMO Inhibitors.
The authors report that truncated glioma-associated oncogene homolog 1 (tGLI1) is a tumor-specific transcription factor that facilitates glioblastoma growth, is enriched in the mesenchymal subtype of glioblastoma and glioma stem cells (GSC), and promotes mesenchymal GSC by upregulating transcription of CD44.
Title: Truncated Glioma-Associated Oncogene Homolog 1 (tGLI1) Mediates Mesenchymal Glioblastoma via Transcriptional Activation of CD44.
Data found that elevated GLI1 and GLI2 is required for the acquired gemcitabine resistance in pancreatic cancer both in vivo and in vitro.
Title: The role of GLI-SOX2 signaling axis for gemcitabine resistance in pancreatic cancer.
Active serum response factor (SRF) along with its coactivator megakaryoblastic leukemia 1 (MKL1) binds DNA near hedgehog target genes and forms a previously unknown protein complex with the hedgehog transcription factor glioma-associated oncogene family zinc finger-1 (GLI1), causing amplification of GLI1 transcriptional activity.
Title: Noncanonical hedgehog pathway activation through SRF-MKL1 promotes drug resistance in basal cell carcinomas.
The inhibition of miR-873 increased gefitinib resistance of NSCLC cells via the upregulation of GLI1. These results indicate that miR-873-GLI1 signaling is involved in gefitinib resistance in NSCLC.
Title: MiR-873 inhibition enhances gefitinib resistance in non-small cell lung cancer cells by targeting glioma-associated oncogene homolog 1.
Of note, the enforced expression of MEKK1 or the exposure of medulloblastoma cells to the MEKK1 activator, Nocodazole, resulted in a marked inhibitory effect on GLI1 activity and tumor cell proliferation and viability. Taken together, the results of this study shed light on a novel regulatory mechanism of HH signaling, with potentially relevant implications in cancer therapy.
Title: Mitogen-activated kinase kinase kinase 1 inhibits hedgehog signaling and medulloblastoma growth through GLI1 phosphorylation.
The upregulation of Twist is involved in Gli1 induced migration and invasion of hepatocellular carcinoma (HCC) cells.
Title: Upregulation of Twist is involved in Gli1 induced migration and invasion of hepatocarcinoma cells.
The underlying mechanism was associated with the Gli1-mediated EMT.
Title: Pseudopod-associated protein KIF20B promotes Gli1-induced epithelial-mesenchymal transition modulated by pseudopodial actin dynamic in human colorectal cancer.
ASS1 expression was highly correlated with GLI1 expression in hepatocellular adenomas.
Title: Argininosuccinate synthase 1 and periportal gene expression in sonic hedgehog hepatocellular adenomas.
Report recurrent GLI1-related gene fusions in a group of malignant mesenchymal neoplasms involving soft tissue, and occasionally bone, with an often nested epithelioid phenotype and strong S100 immunoreactivity.
Title: A Distinct Malignant Epithelioid Neoplasm With GLI1 Gene Rearrangements, Frequent S100 Protein Expression, and Metastatic Potential: Expanding the Spectrum of Pathologic Entities With ACTB/MALAT1/PTCH1-GLI1 Fusions.

Submit: New GeneRIF Correction See all GeneRIFs (304)

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: C4748277 OMIM: 618123 GeneReviews: Not available	not available
Polydactyly, preaxial I MedGen: C1868116 OMIM: 174400 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: 255 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, ENST00000228682.7

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.p13 Primary Assembly

Genomic

NC_000012.12 Reference GRCh38.p13 Primary Assembly

Range

57459785..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