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Symbol GLI3 contributors: mct/shn - updated : 18-12-2015
HGNC name GLI family zinc finger 3
HGNC id 4319
Corresponding disease
ACLS1 acrocallosal syndrome 1
GCPS Greig cephalopolysyndactyly syndrome
PAPA1 polydactyly, postaxial, type A1
PHS Pallister-Hall syndrome 1
PPA4 polydactyly preaxial IV
Location 7p14.1      Physical location : 42.000.549 - 42.276.618
Synonym name
  • glioma-associated oncogene homolog 3
  • zinc finger protein GLI3
  • GLI-Kruppel family member GLI3
  • DNA-binding protein
  • oncogene GLI3
  • Synonym symbol(s) PAPA, PAPB, PHS, PPDIV, ACLS, GCPS, GLI3-190, GLI3FL, PAP-A, PAPA1,
    TYPE functioning gene
    STRUCTURE 276.07 kb     15 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    MAPPING cloned Y linked N status confirmed
    Map pter - D7S2548 - D7S671 - GLI3 - D7S2428 - D7S678 - cen
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    15 - 8228 169.8 1580 - 2008 17764085
    Type widely
       expressed in (based on citations)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Digestivemouthtongue  highly
    Hearing/Equilibriumear   highly
    Nervousbrain   lowly
    Reproductivefemale systembreastmammary gland predominantly
     female systemplacenta  highly
    Respiratoryrespiratory tracttrachea  highly
    Urinarykidney   lowly
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Connectiveadipose  highly
    Connectivebone  highly
    cell lineage
    cell lines
    at STAGE
    physiological period fetal, pregnancy
    Text developing cerebellum, limbs, lung, trachea, placenta
  • a regulator region including a CBP (CREBBP)-binding domain
  • the phosphorylation sites of cAMP-dependent protein kinase
  • five C2H2-type zinc fingers
  • a GLI consensus binding site (GLIBS)
    interspecies homolog to Drosophila segment polarity gene Cubitus interruptus (CI)
    ortholog to Gli3, mus musculus
    ortholog to gli3, danio rerio
    ortholog to Gli3, Rattus norvegicus
    ortholog to GLI3, Pan troglodytes
  • GLI-Kr
  • ppel family
  • GLI C2H2-type zinc-finger protein family
  • CATEGORY regulatory , transcription factor
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,nucleus,nucleoplasm,nuclear bodies,nuclear speckles
  • TBX3 is present in primary cilia where it colocalizes with GLI3
  • basic FUNCTION
  • involved in the development of the CNS, craniofacial structure, lung, trachea and oesophagus
  • more generatly acting both as an activator and a repressor as does CI (cubitus interruptus) in sonic hedgehog signaling, and regulating digit number and identity
  • inducing GLT1 transcription in response to SHH
  • activating BMP4 and BMP7 gene promoters
  • GLI2 and GLI3 collectively mediate all major aspects of IHH function during endochondral skeletal development
  • acting as a downstream mediator of the Sonic hedgehog signal-transduction pathway, essential for early development and playing a role in cell growth, specialization, and patterning of structures such as the brain and limbs
  • required for maintaining the cortical progenitors in active cell cycle, suggesting that cells may acquire differentiated status as they turn off GLI3 expression during neurogenesis
  • a GLI3 proteolytic processing is involved in primary cilia control telencephalic patterning and morphogenesis
  • GLI3 activity is regulated through the primary cilium to control cell cycle length in the cortex and thus determine cortical size
  • complete range of anterior-posterior positional identities in the limb requires integration of the spatial distribution, timing, and dosage of GLI2 and GLI3 activators and repressors
  • distinct roles of GLI2 and GLI3 in intestine development, suggesting small leucine-rich glycoproteins (SLRPs) as novel regulators of smooth muscle cell differentiation
  • GLI3-regulated postnatal myogenesis is necessary for muscle repair-associated angiogenesis
  • during vertebrate evolution its expression control acquired multiple, independently acting, intronic enhancers for spatiotemporal patterning of CNS, limbs, craniofacial structures and internal organs
  • suppresses a potential Fgf/Wnt signaling source in the forebrain
  • performs a dual role in regulating both osteoprogenitor proliferation and osteoblast differentiation during intramembranous ossification
  • CELLULAR PROCESS nucleotide, transcription, regulation
    PHYSIOLOGICAL PROCESS development , cellular trafficking transport
  • morphogenesis
  • protein-nucleus import, translocation
    signaling signal transduction
    a component
    DNA binding to GLT1 promoter
  • binds to the promoter of TNFRSF10A and Hedgehog requires an intact GLI3-repression activity to silence TNFRSF10A expression)
  • RNA
    small molecule metal binding,
  • Zn2+
  • protein
  • binding to CREBBP with SHH to regulate many processes in cells
  • bind to ZIC3 through the GLI consensus binding site (GLIBS)
  • Zic
  • Ski
  • betaTrCP
  • MED12
  • KIF7
  • SUFU
  • PIAS1-dependent SUMOylation influences GLI1, GLI2, GLI3 protein activity and thereby identifies SUMOylation as a post-translational mechanism that regulates the hedgehog signaling pathway
  • unappreciated function of HOXD13 in regulating digit number through its interaction with GLI3
  • potentially, upon Hedgehog input, GLI1 functions collectively with GLI2 and GLI3 in osteogenesis
  • TMEM107 acts in combination with GLI2 and GLI3 to pattern ventral and intermediate neuronal cell types
  • EVC2 promotes recruitment of GLI3 to the tips of cilia
  • role for enzymatically active CDK8 in suppression of GLI3 transactivation activity
  • enzymatically active CDK8 is responsible for suppression of GLI3 transactivation activity, and further, MED12 most likely contributes to this suppression through its role as an anchor for CDK8 in Mediator
  • DZIP1 interacts with GLI3, a transcriptional regulator for Hedgehog signaling, and prevents GLI3 from entering the nucleus
  • SOST and its paralog SOSTDC1 coordinate digit number in a GLI3-dependent manner
  • GLI1, GLI2, GLI3 interacts synergistically with KIFAP3 and KIF3A
  • activated NOTCH1 leads to pronounced accumulation of SMO within primary cilia and elevated levels of full-length GLI3
  • SPOP targets GLI2 and GLI3 for degradation and negatively regulates Hedgehog (Hh) signaling
  • SUFU controls cerebellar neuronal differentiation in a manner modulated by GLI3 repressor and FGF19
  • cell & other
    activated by SHH to produce an anterior/posterior gradient to the developing limb, and to regulate digit number and identity
    corresponding disease(s) GCPS , PAPA1 , PHS , ACLS1 , PPA4
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral somatic mutation      
    somatic chromosomal abnormality in 15 percent of hypothalamic hamartoma at GLI3 locus
    tumoral   LOH    
    in sporadic, nonsyndromic patients with hypothalamic hamartomas and intractable epilepsy
    constitutional     --other  
    dysregulated GLI3-dependent SHH signaling contributes to phenotypes of individuals with FG and Lujan syndromes
    constitutional       gain of function
    results in defective hippocampal growth
    tumoral somatic mutation      
    in hypothalamic hamartoma with gelastic epilepsy
    Variant & Polymorphism
    Candidate gene
    Therapy target
  • Shh(-/-) Gli3(-/-) limbs are distally complete and polydactylous, but completely lack wild-type digit identities
  • Gli3-mutant mice displayed a central polydactyly, a wide range of developmental abnormalities encompassing almost all of the common PHS features, including imperforate anus, gastrointestinal, epiglottis and larynx defects, abnormal kidney development, and absence of adrenal glands
  • Gli3Xt-J/Xt-J mice, which represent a Gli3-null allele, exhibit craniosynostosis of the lambdoid sutures accompanied by increased osteoprogenitor proliferation and differentiation