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Symbol GLIS3 contributors: mct/pgu - updated : 11-04-2015
HGNC name GLIS family zinc finger 3
HGNC id 28510
TYPE functioning gene
STRUCTURE 475.91 kb     11 Exon(s)
MAPPING cloned Y linked N status provisional
TRANSCRIPTS type messenger
identificationnb exonstypebpproduct
ProteinkDaAAspecific expressionYearPubmed
11 - 7656 99.4 930 - 2003 14500813
10 - 6672 83.5 775 - 2003 14500813
Type widely
   expressed in (based on citations)
SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
Digestivestomach   highly
Endocrinepancreas   highly Homo sapiens
 thyroid   highly
Reproductivefemale systemuterus   
SystemCellPubmedSpeciesStageRna symbol
Endocrineislet cell (alpha,beta...) Homo sapiens
Skeletonosteoblast Homo sapiensAdult
cell lineage
cell lines
physiological period embryo
Text specific regions in kidney, pancreas and testis
  • N terminus playing a critical role in modulating the stability and transcriptional activity of GLIS3 and part of this regulation is mediated through interactions with SUFU and CUL3 within the N terminus
  • a DNA binding domain consisting of five C2H2-type zinc finger motifs that share a high degree of homology with members of the GLI and ZIC subfamilies of transcription factors
  • a P/LPXY motif in the C terminus, part of the transcription activation domain of GLIS3, and DNA-binding domain and transcriptional activation domain are localized in the center and within the C terminus of GLIS3
    interspecies homolog to murine Glis3 (84.6pc)
  • Krüppel-like family of transcription factors
  • CATEGORY regulatory , transcription factor
    SUBCELLULAR LOCALIZATION     intracellular
  • localizes to the primary cilium, suggesting that it is part of a cilium-associated signaling pathway
  • upon activation by a primary cilium-associated signaling pathway, GLIS3 is transported by intraflagellar transport into the cytoplasm and subsequently into the nucleus
  • GLIS2 and GLIS3 proteins have been demonstrated to localize to the primary cilium, a signaling organelle that has been implicated in several pathologies, including cystic renal diseases
  • GLIS3 and SUFU co-localize to the nucleus
  • basic FUNCTION
  • acting as a repressor and activator of transcription
  • playing a critical role in the regulation of a variety of cellular processes during development
  • regulatory role for GLIS3 in osteoblast differentiation
  • role of GLIS3 for regulation of insulin gene expression and expands our understanding of its role in the beta cell
  • interacts with the transcriptional modulator WWTR1/TAZ, which itself has been implicated in glomerulocystic kidney disease
  • plays a key role in pancreatic development, particularly in the generation of beta-cells and in the regulation of insulin gene expression
  • essential for the development of pancreatic beta-cells and the maintenance of normal renal functions
  • controls potentially fetal islet differentiation via direct transactivation of NEUROG3 1)
  • controls beta cell proliferation in response to high-fat feeding at least partly by regulating CCND2 transcription
  • normal GLIS3 expression is required for pancreatic beta cell function and mass maintenance during adulthood, which impairment leads to diabetes in adults
  • CELLULAR PROCESS nucleotide, transcription, regulation
    a component
    DNA binding
    small molecule metal binding,
  • ions Zn2+
  • protein
  • acts synergistically with BMP2 and SHH in inducing osteoblast differentiation
  • the promotion of osteoblast differentiation by GLIS3 involves increased expression of FGF18, a positive regulator of osteogenesis
  • interacts with and functions as a coactivator of WWTR1(GLIS3 and WWTR1 are part of overlapping transcription regulatory networks that play a critical role in the maintenance of normal renal architecture and function)
  • regulate FGF18 (fibroblast growth factor 18) and INS (insulin) gene expression by binding to GlisBS (DNA binding site) within the respective promoters
  • interacts with SUFU, which involves a VYGHF motif located within this conserved region
  • NDRG1 upregulates neural precursor cell expressed developmentally downregulated 4-like (NEDD4L) and GLI-similar-3 (GLIS3)
  • regulates NEUROG3 through its distal promoter region
  • can interact directly with ONECUT1 (N-terminus in GLIS3 and the homeodomain of ONECUT1 are critical and this interaction may play an important role in the regulation of NEUROG3 during pancreatic endocrine progenitor cell specification and development)
  • cell & other
    Other modulation of GLIS3 activity by SUFU and CUL3 may play an important role in the mechanism by which Glis3 regulates the maintenance of pancreatic beta-cell function and insulin gene expression
    corresponding disease(s) NDH
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional       loss of function
    leads to the development of cystic renal disease, suggesting that it plays a critical role in maintaining normal renal functions
    constitutional       gain of function
    involves a primary cilium-associated signal pathway
    constitutional       loss of function
    leads to the development of neonatal diabetes and polycystic kidney disease
  • to type 2 diabetes
  • to decreased glucose-stimulated insulin response
  • Variant & Polymorphism SNP
  • rs7034200 displayed evidence for association with type 2 diabetes
  • variants at the DGKB/AGMO, ADRA2A, GLIS3 and C2CD4B loci were associated with decreased glucose-stimulated insulin response
  • Candidate gene
    Therapy target
    Glis3 mutant mice exhibit abnormalities very similar to those displayed by NDH1 patients,
    including a greatly reduced life span and development of polycystic kidneys and neonatal diabetes