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GLI3 GLI family zinc finger 3 [ Homo sapiens (human) ]

Gene ID: 2737, updated on 3-May-2025

Summary

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Official Symbol: GLI3provided by HGNC
Official Full Name: GLI family zinc finger 3provided by HGNC
Primary source: HGNC:HGNC:4319
See related: Ensembl:ENSG00000106571 MIM:165240; AllianceGenome:HGNC:4319
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: PHS; ACLS; GCPS; PAPA; PAPB; PAP-A; PAPA1; PPDIV; GLI3FL; GLI3-190
Summary: This gene encodes a protein which belongs to the C2H2-type zinc finger proteins subclass of the Gli family. They are characterized as DNA-binding transcription factors and are mediators of Sonic hedgehog (Shh) signaling. The protein encoded by this gene localizes in the cytoplasm and activates patched Drosophila homolog (PTCH) gene expression. It is also thought to play a role during embryogenesis. Mutations in this gene have been associated with several diseases, including Greig cephalopolysyndactyly syndrome, Pallister-Hall syndrome, preaxial polydactyly type IV, and postaxial polydactyly types A1 and B. [provided by RefSeq, Jul 2008]
Expression: Broad expression in ovary (RPKM 4.0), endometrium (RPKM 3.1) and 22 other tissues See more
Orthologs: mouse all
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Genomic context

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See GLI3 in Genome Data Viewer

Location:: 7p14.1

Exon count:: 22

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	7	NC_000007.14 (41960949..42264268, complement)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	7	NC_060931.1 (42119298..42422619, complement)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	7	NC_000007.13 (42000547..42276808, complement)

Chromosome 7 - NC_000007.14 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: Tissue-specific circular RNA induction during human fetal development
Description: 35 human fetal samples from 6 tissues (3 - 7 replicates per tissue) collected between 10 and 20 weeks gestational time were sequenced using Illumina TruSeq Stranded Total RNA
BioProject: PRJNA270632
Publication: PMID 26076956
Analysis date: Mon Apr 2 22:54:59 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

A novel missense variant located within the zinc finger domain of the GLI3 gene was identified in a Vietnamese pedigree with index finger polydactyly.
Title: A novel missense variant located within the zinc finger domain of the GLI3 gene was identified in a Vietnamese pedigree with index finger polydactyly.
Identification of truncated variants in GLI family zinc finger 3 (GLI3) associated with polydactyly.
Title: Identification of truncated variants in GLI family zinc finger 3 (GLI3) associated with polydactyly.
Positive regulation of Hedgehog signaling via phosphorylation of GLI2/GLI3 by DYRK2 kinase.
Title: Positive regulation of Hedgehog signaling via phosphorylation of GLI2/GLI3 by DYRK2 kinase.
Conclusion of diagnostic odysseys due to inversions disrupting GLI3 and FBN1.
Title: Conclusion of diagnostic odysseys due to inversions disrupting GLI3 and FBN1.
A novel mechanism of regulation of the oncogenic transcription factor GLI3 by toll-like receptor signaling.
Title: A novel mechanism of regulation of the oncogenic transcription factor GLI3 by toll-like receptor signaling.
A novel variant of GLI3, p.Asp1514Thrfs*5, is identified in a Chinese family affected by polydactyly.
Title: A novel variant of GLI3, p.Asp1514Thrfs*5, is identified in a Chinese family affected by polydactyly.
GLI3 Is Stabilized by SPOP Mutations and Promotes Castration Resistance via Functional Cooperation with Androgen Receptor in Prostate Cancer.
Title: GLI3 Is Stabilized by SPOP Mutations and Promotes Castration Resistance via Functional Cooperation with Androgen Receptor in Prostate Cancer.
Two nonsense GLI3 variants are associated with polydactyly and syndactyly in two families by affecting the sonic hedgehog signaling pathway.
Title: Two nonsense GLI3 variants are associated with polydactyly and syndactyly in two families by affecting the sonic hedgehog signaling pathway.
GLI3 and androgen receptor are mutually dependent for their malignancy-promoting activity in ovarian and breast cancer cells.
Title: GLI3 and androgen receptor are mutually dependent for their malignancy-promoting activity in ovarian and breast cancer cells.
Homozygous GLI3 variants observed in three unrelated patients presenting with syndromic polydactyly.
Title: Homozygous GLI3 variants observed in three unrelated patients presenting with syndromic polydactyly.

Submit: New GeneRIF Correction See all GeneRIFs (118)

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
Greig cephalopolysyndactyly syndrome MedGen: C0265306 OMIM: 175700 GeneReviews: Greig Cephalopolysyndactyly Syndrome	Compare labs
Pallister-Hall syndrome MedGen: C0265220 OMIM: 146510 GeneReviews: GLI3-Related Pallister-Hall Syndrome	Compare labs
Polydactyly, postaxial, type A1 MedGen: C4282400 OMIM: 174200 GeneReviews: Not available	Compare labs
Polysyndactyly 4 MedGen: C1868111 OMIM: 174700 GeneReviews: Not available	Compare labs

Copy number response

Description
Copy number response Triplosensitivity No evidence available (Last evaluated 2021-01-12) ClinGen Genome Curation Page Haploinsufficency Sufficient evidence for dosage pathogenicity (Last evaluated 2021-01-12) ClinGen Genome Curation PagePubMed

EBI GWAS Catalog

Description
A genome-wide meta-analysis of genetic variants associated with allergic rhinitis and grass sensitization and their interaction with birth order. EBI GWAS Catalog EBI GWAS CatalogPubMed
Gene-alcohol interactions identify several novel blood pressure loci including a promising locus near SLC16A9. EBI GWAS Catalog EBI GWAS CatalogPubMed
Insights into the genetic architecture of early stage age-related macular degeneration: a genome-wide association study meta-analysis. EBI GWAS Catalog EBI GWAS CatalogPubMed
Loci associated with N-glycosylation of human immunoglobulin G show pleiotropy with autoimmune diseases and haematological cancers. EBI GWAS Catalog EBI GWAS CatalogPubMed

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

RH123527 (e-PCR)
- UniSTS:135945

GDB:435308 (e-PCR)
- UniSTS:157225

SHGC-106357 (e-PCR)
- UniSTS:169770

Gli3 (e-PCR), detects polymorphism
- UniSTS:143219

GLI3_V241 (e-PCR)
- UniSTS:280699

GLI3_973.2 (e-PCR)
- UniSTS:280699

GLI3 (e-PCR)
- UniSTS:39311

RH46965 (e-PCR)
- UniSTS:60822

D7S691 (e-PCR), detects polymorphism
- UniSTS:51099

D7S691 (e-PCR), detects polymorphism
- UniSTS:54698

D7S2746 (e-PCR)
- UniSTS:44209

GDB:1317516 (e-PCR)
- UniSTS:21187

GDB:1317704 (e-PCR)
- UniSTS:56011

GDB:1318579 (e-PCR)
- UniSTS:56033

SHGC-152225 (e-PCR)
- UniSTS:182246

RH65647 (e-PCR)
- UniSTS:77802

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables DNA binding	IEA Inferred from Electronic Annotation more info
enables DNA-binding transcription factor activity	IDA Inferred from Direct Assay more info	PubMed
enables DNA-binding transcription factor activity	IEA Inferred from Electronic Annotation more info
enables DNA-binding transcription factor activity, RNA polymerase II-specific	IBA Inferred from Biological aspect of Ancestor more info
enables RNA polymerase II cis-regulatory region sequence-specific DNA binding	IBA Inferred from Biological aspect of Ancestor more info
enables RNA polymerase II cis-regulatory region sequence-specific DNA binding	IDA Inferred from Direct Assay more info	PubMed
enables RNA polymerase II transcription regulatory region sequence-specific DNA binding	IDA Inferred from Direct Assay more info	PubMed
enables RNA polymerase II transcription regulatory region sequence-specific DNA binding	IEA Inferred from Electronic Annotation more info
enables beta-catenin binding	IPI Inferred from Physical Interaction more info	PubMed
enables chromatin binding	IEA Inferred from Electronic Annotation more info
enables histone acetyltransferase binding	IPI Inferred from Physical Interaction more info	PubMed
enables histone deacetylase binding	IDA Inferred from Direct Assay more info	PubMed
enables mediator complex binding	IDA Inferred from Direct Assay more info	PubMed
enables metal ion binding	IEA Inferred from Electronic Annotation more info
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables sequence-specific DNA binding	IEA Inferred from Electronic Annotation more info
enables sequence-specific double-stranded DNA binding	IDA Inferred from Direct Assay more info	PubMed
enables zinc ion binding	IEA Inferred from Electronic Annotation more info

Process	Evidence Code	Pubs
involved_in T cell differentiation in thymus	IEA Inferred from Electronic Annotation more info
involved_in T cell differentiation in thymus	ISS Inferred from Sequence or Structural Similarity more info
acts_upstream_of_or_within alpha-beta T cell differentiation	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within anatomical structure formation involved in morphogenesis	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within anterior semicircular canal development	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within anterior/posterior pattern specification	IEA Inferred from Electronic Annotation more info
acts_upstream_of apoptotic process	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within artery development	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within axon guidance	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within brain development	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within branching involved in ureteric bud morphogenesis	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within branching morphogenesis of an epithelial tube	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within camera-type eye development	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within camera-type eye morphogenesis	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within cell differentiation involved in kidney development	IEA Inferred from Electronic Annotation more info
acts_upstream_of cell population proliferation	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within central nervous system development	IEA Inferred from Electronic Annotation more info
acts_upstream_of central nervous system neuron differentiation	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within cerebral cortex radial glia-guided migration	IEA Inferred from Electronic Annotation more info
acts_upstream_of chondrocyte differentiation	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within developmental growth	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within dorsal/ventral pattern formation	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within embryonic digestive tract development	IEA Inferred from Electronic Annotation more info
involved_in embryonic digestive tract development	TAS Traceable Author Statement more info	PubMed
acts_upstream_of_or_within embryonic digestive tract morphogenesis	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within embryonic digit morphogenesis	IEA Inferred from Electronic Annotation more info
involved_in embryonic digit morphogenesis	TAS Traceable Author Statement more info	PubMed
acts_upstream_of_or_within embryonic limb morphogenesis	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within embryonic morphogenesis	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within embryonic neurocranium morphogenesis	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within embryonic skeletal system morphogenesis	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within forebrain development	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within forebrain dorsal/ventral pattern formation	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within forebrain radial glial cell differentiation	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within frontal suture morphogenesis	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within gene expression	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within heart development	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within hindgut morphogenesis	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within hippocampus development	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within in utero embryonic development	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within inner ear development	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within kidney development	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within lambdoid suture morphogenesis	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within larynx morphogenesis	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within lateral ganglionic eminence cell proliferation	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within lateral semicircular canal development	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within layer formation in cerebral cortex	IEA Inferred from Electronic Annotation more info
involved_in limb development	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within limb morphogenesis	IEA Inferred from Electronic Annotation more info
involved_in limb morphogenesis	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within lung development	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within mammary gland development	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within mammary gland specification	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within melanocyte differentiation	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within metanephros development	IEA Inferred from Electronic Annotation more info
involved_in negative regulation of DNA-templated transcription	IDA Inferred from Direct Assay more info	PubMed
acts_upstream_of_or_within negative regulation of DNA-templated transcription	IEA Inferred from Electronic Annotation more info
involved_in negative regulation of alpha-beta T cell differentiation	IEA Inferred from Electronic Annotation more info
involved_in negative regulation of alpha-beta T cell differentiation	ISS Inferred from Sequence or Structural Similarity more info
acts_upstream_of_or_within negative regulation of apoptotic process	IEA Inferred from Electronic Annotation more info
involved_in negative regulation of canonical Wnt signaling pathway	IDA Inferred from Direct Assay more info	PubMed
acts_upstream_of_or_within negative regulation of cell population proliferation	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within negative regulation of chondrocyte differentiation	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within negative regulation of neuron differentiation	IEA Inferred from Electronic Annotation more info
involved_in negative regulation of smoothened signaling pathway	IEA Inferred from Electronic Annotation more info
involved_in negative regulation of smoothened signaling pathway	ISS Inferred from Sequence or Structural Similarity more info
acts_upstream_of_or_within negative regulation of stem cell proliferation	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within negative regulation of transcription by RNA polymerase II	IDA Inferred from Direct Assay more info	PubMed
involved_in negative regulation of transcription by RNA polymerase II	IDA Inferred from Direct Assay more info	PubMed
involved_in negative thymic T cell selection	IEA Inferred from Electronic Annotation more info
involved_in negative thymic T cell selection	ISS Inferred from Sequence or Structural Similarity more info
acts_upstream_of_or_within neural tube development	IEA Inferred from Electronic Annotation more info
acts_upstream_of neuroblast proliferation	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within neuron fate commitment	IEA Inferred from Electronic Annotation more info
involved_in nose morphogenesis	TAS Traceable Author Statement more info	PubMed
acts_upstream_of_or_within odontogenesis of dentin-containing tooth	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within oligodendrocyte differentiation	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within optic nerve morphogenesis	IEA Inferred from Electronic Annotation more info
acts_upstream_of osteoblast differentiation	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within pallium development	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within pattern specification process	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within positive regulation of DNA-templated transcription	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of DNA-templated transcription	ISS Inferred from Sequence or Structural Similarity more info
involved_in positive regulation of alpha-beta T cell differentiation	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of alpha-beta T cell differentiation	ISS Inferred from Sequence or Structural Similarity more info
acts_upstream_of_or_within positive regulation of chondrocyte differentiation	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within positive regulation of neuroblast proliferation	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within positive regulation of osteoblast differentiation	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within positive regulation of protein import into nucleus	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of transcription by RNA polymerase II	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of transcription by RNA polymerase II	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of transcription by RNA polymerase II	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of protein import into nucleus	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within protein processing	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within proximal/distal pattern formation	IEA Inferred from Electronic Annotation more info
involved_in regulation of DNA-templated transcription	IDA Inferred from Direct Assay more info	PubMed
acts_upstream_of_or_within regulation of DNA-templated transcription	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within regulation of apoptotic process	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within regulation of bone development	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within regulation of cell differentiation	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within regulation of cell population proliferation	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within regulation of gene expression	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within regulation of smoothened signaling pathway	IEA Inferred from Electronic Annotation more info
involved_in regulation of transcription by RNA polymerase II	IBA Inferred from Biological aspect of Ancestor more info
involved_in regulation of transcription by RNA polymerase II	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within roof of mouth development	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within sagittal suture morphogenesis	IEA Inferred from Electronic Annotation more info
involved_in smoothened signaling pathway	IBA Inferred from Biological aspect of Ancestor more info
involved_in smoothened signaling pathway	IDA Inferred from Direct Assay more info	PubMed
acts_upstream_of_or_within smoothened signaling pathway	IEA Inferred from Electronic Annotation more info
involved_in smoothened signaling pathway	TAS Traceable Author Statement more info	PubMed
acts_upstream_of_or_within smoothened signaling pathway involved in dorsal/ventral neural tube patterning	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within smoothened signaling pathway involved in spinal cord motor neuron cell fate specification	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within smoothened signaling pathway involved in ventral spinal cord interneuron specification	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within spinal cord dorsal/ventral patterning	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within spinal cord motor neuron differentiation	IEA Inferred from Electronic Annotation more info
acts_upstream_of stem cell proliferation	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within subpallium development	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within telencephalon development	IEA Inferred from Electronic Annotation more info
involved_in thymocyte apoptotic process	IEA Inferred from Electronic Annotation more info
involved_in thymocyte apoptotic process	ISS Inferred from Sequence or Structural Similarity more info
acts_upstream_of_or_within tongue development	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within tube development	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within vocalization behavior	IEA Inferred from Electronic Annotation more info

Component	Evidence Code	Pubs
part_of GLI-SUFU complex	IPI Inferred from Physical Interaction more info	PubMed
located_in axoneme	IEA Inferred from Electronic Annotation more info
located_in cell projection	IEA Inferred from Electronic Annotation more info
located_in ciliary base	TAS Traceable Author Statement more info
located_in ciliary tip	TAS Traceable Author Statement more info
located_in cilium	IDA Inferred from Direct Assay more info	PubMed
located_in cilium	IEA Inferred from Electronic Annotation more info
located_in cytoplasm	IDA Inferred from Direct Assay more info	PubMed
located_in cytoplasm	IEA Inferred from Electronic Annotation more info
located_in cytosol	IDA Inferred from Direct Assay more info	PubMed
located_in cytosol	TAS Traceable Author Statement more info
located_in intracellular membrane-bounded organelle	IDA Inferred from Direct Assay more info
located_in nuclear speck	IEA Inferred from Electronic Annotation more info
located_in nucleolus	IDA Inferred from Direct Assay more info
located_in nucleoplasm	IDA Inferred from Direct Assay more info
located_in nucleoplasm	TAS Traceable Author Statement more info
is_active_in nucleus	IBA Inferred from Biological aspect of Ancestor more info
located_in nucleus	IDA Inferred from Direct Assay more info	PubMed
located_in nucleus	IEA Inferred from Electronic Annotation more info
part_of transcription repressor complex	IEA Inferred from Electronic Annotation more info

General protein information

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Preferred Names: transcriptional activator GLI3

Names: GLI-Kruppel family member GLI3; glioma-associated oncogene family zinc finger 3; oncogene GLI3; zinc finger protein GLI3

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.