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FLASH GENE
Symbol GLI3 contributors: mct/shn - updated : 18-12-2013
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,
    DNA
    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
    Physical map
    LOC393012 7 similar to Trypsin III, cationic precursor (Pretrypsinogen III) LOC393013 7 similar to V_segment translation product LOC393014 7 similar to V_segment translation product LOC393015 7 similar to T cell receptor beta chain {clone BL25} LOC392803 7 similar to T-cell receptor beta chain V region CTL-L17 precursor LOC392804 7 similar to V_segment translation product LOC392805 7 similar to T-cell receptor beta chain (V-beta 6.10) precursor - human LOC392806 7 similar to T cell receptor beta chain LOC392807 7 similar to TCR V-beta 13.2 INHBA 7p15-p13 inhibin, beta A (activin A, activin AB alpha polypeptide) LOC393016 7 similar to T-cell receptor beta chain, TCR beta {TLC RB2} LOC392808 7 similar to V_segment translation product LOC393017 7 similar to This CDS feature is included to show the translation of the corresponding V_region. Presently translation qualifiers on V_region features are illegal LOC392809 7 similar to TCR V-beta 13.5 LOC393018 7 similar to T-cell receptor beta chain V region CTL-L17 precursor LOC392810 7 similar to T-cell receptor beta chain V region CTL-L17 precursor LOC392811 7 similar to V_segment translation product LOC392812 7 similar to T cell receptor beta chain precursor LOC393019 7 similar to T cell receptor beta chain variable region LOC392813 7 similar to V_segment translation product LOC392814 7 similar to T-cell receptor beta chain V region CTL-L17 precursor LOC392815 7 similar to T cell receptor variable region beta chain; TcR Vbeta LOC392816 7 similar to V_segment translation product LOC392817 7 similar to V_segment translation product LOC393020 7 similar to TCRBV13S7 LOC393021 7 similar to TCR V-beta 13.4 LOC392818 7 similar to V_segment translation product LOC392819 7 similar to V_segment translation product LOC393022 7 similar to V_segment translation product LOC392820 7 similar to V_segment translation product LOC392821 7 similar to T-cell receptor beta chain V region YT35 precursor LOC392822 7 similar to V_segment translation product LOC392823 7 similar to T cell receptor beta chain GLI3 7p14.1-p13 GLI-Kruppel family member GLI3 (Greig cephalopolysyndactyly syndrome) LOC393023 7 similar to V_segment translation product LOC393024 7 similar to T-cell receptor beta chain V region precursor LOC392824 7 similar to T cell receptor beta chain LOC392825 7 similar to T cell receptor beta chain BV20S1 BJ1-5 BC1 LOC393025 7 similar to T-cell receptor beta chain, TCR beta {TLC RB113} LOC393026 7 similar to bA255A11.10 (putative novel T cell receptor beta chain V region protein) LOC392826 7 similar to T-cell receptor beta LOC393027 7 similar to V_segment translation product LOC393028 7 similar to T-cell receptor beta-chain (V11-D-J-C) precursor LOC393029 7 similar to T-cell receptor beta chain LOC392827 7 similar to T-cell receptor beta chain V region PHDS203 precursor LOC392828 7 similar to T-cell receptor beta chain - human (fragment) LOC393030 7 similar to T cell receptor V-beta 4 precursor PRSS1 7q35 protease, serine, 1 (trypsin 1) LOC393031 7 similar to protease serine 2 isoform B TRY6 7q34 trypsinogen C LOC393032 7 similar to protease serine 2 isoform B PRSS2 7q35 protease, serine, 2 (trypsin 2) LOC392829 7 similar to T cell receptor beta LOC392830 7 similar to T-cell receptor beta 2 chain LOC392831 7 similar to V_segment translation product
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    15 - 8228 169.8 1580 - 2008 17764085
    EXPRESSION
    Type widely
       expressed in (based on citations)
    organ(s)
    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
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Connectiveadipose  highly
    Connectivebone  highly
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    physiological period fetal, pregnancy
    Text developing cerebellum, limbs, lung, trachea, placenta
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • 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)
  • HOMOLOGY
    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
    Homologene
    FAMILY
  • GLI-Kr
  • ppel family
  • GLI C2H2-type zinc-finger protein family
  • CATEGORY regulatory , transcription factor
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,cytosolic
    intracellular,cytoplasm,cytoskeleton,microtubule
    intracellular,nucleus,nucleoplasm,nuclear bodies,nuclear speckles
    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
    text
  • morphogenesis
  • protein-nucleus import, translocation
  • PATHWAY
    metabolism
    signaling signal transduction
    a component
    INTERACTION
    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
  • 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
  • SOST and its paralog SOSTDC1 coordinate digit number in a GLI3-dependent manner
  • cell & other
    REGULATION
    activated by SHH to produce an anterior/posterior gradient to the developing limb, and to regulate digit number and identity
    ASSOCIATED DISORDERS
    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
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    ANIMAL & CELL MODELS
  • 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