This gene is a member of the GLI-similar zinc finger protein family and encodes a nuclear transcription factor with five C2H2-type zinc finger domains. The protein encoded by this gene is widely expressed at low levels in the neural tube and peripheral nervous system and likely promotes neuronal differentiation. It is abundantly expressed in the kidney and may have a role in th... See more...

Aliases for GLIS2 Gene

Aliases for GLIS2 Gene

  • GLIS Family Zinc Finger 2 2 3 5
  • Neuronal Krueppel-Like Protein 3 4
  • Zinc Finger Protein GLIS2 3 4
  • Nephrocystin-7 2 3
  • GLI-Similar 2 3 4
  • NPHP7 2 3
  • NKL 3 4
  • Kruppel-Like Zinc Finger Protein GLIS2 3
  • Gli-Similar 2 2
  • GLIS2 5

External Ids for GLIS2 Gene

Previous GeneCards Identifiers for GLIS2 Gene

  • GC16P004405
  • GC16P004382
  • GC16P004304
  • GC16P004365

Summaries for GLIS2 Gene

Entrez Gene Summary for GLIS2 Gene

  • This gene is a member of the GLI-similar zinc finger protein family and encodes a nuclear transcription factor with five C2H2-type zinc finger domains. The protein encoded by this gene is widely expressed at low levels in the neural tube and peripheral nervous system and likely promotes neuronal differentiation. It is abundantly expressed in the kidney and may have a role in the regulation of kidney morphogenesis. p120 regulates the expression level of this protein and induces the cleavage of this protein's C-terminal zinc finger domain. This protein also promotes the nuclear translocation of p120. Mutations in this gene cause nephronophthisis (NPHP), an autosomal recessive kidney disease characterized by tubular basement membrane disruption, interstitial lymphohistiocytic cell infiltration, and development of cysts at the corticomedullary border of the kidneys.[provided by RefSeq, Jan 2010]

GeneCards Summary for GLIS2 Gene

GLIS2 (GLIS Family Zinc Finger 2) is a Protein Coding gene. Diseases associated with GLIS2 include Nephronophthisis 7 and Acute Megakaryoblastic Leukemia Without Down Syndrome. Gene Ontology (GO) annotations related to this gene include transcription regulatory region DNA binding and proximal promoter DNA-binding transcription activator activity, RNA polymerase II-specific. An important paralog of this gene is GLI2.

UniProtKB/Swiss-Prot Summary for GLIS2 Gene

  • Can act either as a transcriptional repressor or as a transcriptional activator, depending on the cell context. Acts as a repressor of the Hedgehog signaling pathway (By similarity). Represses the Hedgehog-dependent expression of Wnt4 (By similarity). Necessary to maintain the differentiated epithelial phenotype in renal cells through the inhibition of SNAI1, which itself induces the epithelial-to-mesenchymal transition (By similarity). Represses transcriptional activation mediated by CTNNB1 in the Wnt signaling pathway. May act by recruiting the corepressors CTBP1 and HDAC3. May be involved in neuron differentiation (By similarity).

No data available for CIViC Summary , Tocris Summary , Gene Wiki entry , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for GLIS2 Gene

Genomics for GLIS2 Gene

GeneHancer (GH) Regulatory Elements Pubs

Promoters and enhancers for GLIS2 Gene
GeneHancer (GH) Identifier GH Type GH
Score
GH Sources Gene Association Score Total Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor
Binding Sites
Gene Targets
GH16J004332 Promoter 0.3 EPDnew 600.4 +17.3 17347 0.1 GLIS2 GLIS2-AS1 ENSG00000262712 PAM16
GH16J004368 Promoter/Enhancer 2.5 EPDnew FANTOM5 Ensembl ENCODE CraniofacialAtlas dbSUPER 1.9 +59.5 59547 11 HNRNPL CREB1 GATAD2A CTCF TEAD4 PRDM10 REST TFE3 IKZF1 NFKBIZ VASN NMRAL1 CREBBP HMOX2 MGRN1 UBN1 PAM16 GLIS2 CORO7 piR-36362-003
GH16J004044 Enhancer 0.8 Ensembl ENCODE 4.7 -270.0 -270006 1.5 PRDM10 PATZ1 ZNF600 ZBTB44 ZBTB20 ZXDB BHLHE40 OSR2 ZBTB17 ZFHX2 RF00017-1941 GLIS2 ZNF205-AS1 ENSG00000263159 ADCY9 CREBBP
GH16J004313 Promoter/Enhancer 2 Ensembl ENCODE CraniofacialAtlas dbSUPER 0.7 +4.8 4805 12.3 HNRNPL CTCF ZBTB33 PRDM10 ZNF629 ZNF512 IKZF1 KDM1A ZNF692 BACH1 ZNF500 PAM16 VASN CREBBP ENSG00000261938 NMRAL1 LINC01569 HMOX2 CORO7 GLIS2
GH16J004305 Promoter/Enhancer 2.3 EPDnew FANTOM5 ENCODE CraniofacialAtlas dbSUPER 0.4 -6.3 -6327 5.1 SP1 HNRNPL GATAD2A CTCF ZBTB33 TEAD4 PRDM10 ZNF629 LEF1 IKZF1 lnc-TFAP4-3 TFAP4 LINC01569 CORO7 GLIS2
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around GLIS2 on the GeneHancer Hub at the UCSC Golden Path

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for GLIS2

Top Transcription factor binding sites by QIAGEN in the GLIS2 gene promoter:
  • COUP
  • COUP-TF
  • COUP-TF1
  • E2F-2
  • HNF-4alpha1
  • HNF-4alpha2

Genomic Locations for GLIS2 Gene

Genomic Locations for GLIS2 Gene
chr16:4,314,761-4,339,597
(GRCh38/hg38)
Size:
24,837 bases
Orientation:
Plus strand
chr16:4,364,762-4,389,598
(GRCh37/hg19)
Size:
24,837 bases
Orientation:
Plus strand

Genomic View for GLIS2 Gene

Genes around GLIS2 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
GLIS2 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for GLIS2 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for GLIS2 Gene

Proteins for GLIS2 Gene

  • Protein details for GLIS2 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q9BZE0-GLIS2_HUMAN
    Recommended name:
    Zinc finger protein GLIS2
    Protein Accession:
    Q9BZE0
    Secondary Accessions:
    • B3KX84

    Protein attributes for GLIS2 Gene

    Size:
    524 amino acids
    Molecular mass:
    55689 Da
    Quaternary structure:
    • Interacts with CTBP1 and HDAC3 (By similarity). Interacts with CTNNB1 (By similarity). Interacts with SUFU (By similarity). Interacts with CTNND1.

neXtProt entry for GLIS2 Gene

Post-translational modifications for GLIS2 Gene

  • C-terminus cleavage is induced by interaction with CTNND1 and enhanced by Src tyrosine kinase.
  • Modification sites at PhosphoSitePlus
  • Modification sites at neXtProt

Other Protein References for GLIS2 Gene

ENSEMBL proteins:
REFSEQ proteins:

No data available for DME Specific Peptides for GLIS2 Gene

Domains & Families for GLIS2 Gene

Gene Families for GLIS2 Gene

HGNC:
Human Protein Atlas (HPA):
  • Disease related genes
  • Predicted intracellular proteins
  • Transcription factors

Protein Domains for GLIS2 Gene

InterPro:
ProtoNet:

Suggested Antigen Peptide Sequences for GLIS2 Gene

GenScript: Design optimal peptide antigens:
  • Neuronal Krueppel-like protein (GLIS2_HUMAN)

Graphical View of Domain Structure for InterPro Entry

Q9BZE0

UniProtKB/Swiss-Prot:

GLIS2_HUMAN :
  • The C2H2-type zinc finger 1 has a major repressor function and is required for CTNNB1 binding.
  • Belongs to the GLI C2H2-type zinc-finger protein family.
Domain:
  • The C2H2-type zinc finger 1 has a major repressor function and is required for CTNNB1 binding.
Family:
  • Belongs to the GLI C2H2-type zinc-finger protein family.
genes like me logo Genes that share domains with GLIS2: view

Function for GLIS2 Gene

Molecular function for GLIS2 Gene

UniProtKB/Swiss-Prot Function:
Can act either as a transcriptional repressor or as a transcriptional activator, depending on the cell context. Acts as a repressor of the Hedgehog signaling pathway (By similarity). Represses the Hedgehog-dependent expression of Wnt4 (By similarity). Necessary to maintain the differentiated epithelial phenotype in renal cells through the inhibition of SNAI1, which itself induces the epithelial-to-mesenchymal transition (By similarity). Represses transcriptional activation mediated by CTNNB1 in the Wnt signaling pathway. May act by recruiting the corepressors CTBP1 and HDAC3. May be involved in neuron differentiation (By similarity).

Phenotypes From GWAS Catalog for GLIS2 Gene

Gene Ontology (GO) - Molecular Function for GLIS2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000976 transcription regulatory region sequence-specific DNA binding ISS --
GO:0000977 RNA polymerase II regulatory region sequence-specific DNA binding IBA 21873635
GO:0000981 DNA-binding transcription factor activity, RNA polymerase II-specific IBA 21873635
GO:0001228 DNA-binding transcription activator activity, RNA polymerase II-specific ISS --
GO:0003676 nucleic acid binding IEA --
genes like me logo Genes that share ontologies with GLIS2: view
genes like me logo Genes that share phenotypes with GLIS2: view

Human Phenotype Ontology for GLIS2 Gene

HPO Id HPO Name Alternative Ids Definition Synonyms

Animal Models for GLIS2 Gene

MGI Knock Outs for GLIS2:

Animal Model Products

CRISPR Products

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for GLIS2

No data available for Enzyme Numbers (IUBMB) , Transcription Factor Targets and HOMER Transcription for GLIS2 Gene

Localization for GLIS2 Gene

Subcellular locations from UniProtKB/Swiss-Prot for GLIS2 Gene

Nucleus speckle. Cytoplasm.

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for GLIS2 gene
Compartment Confidence
nucleus 5
plasma membrane 2
extracellular 2
cytoskeleton 2
lysosome 2
mitochondrion 1
peroxisome 1
endoplasmic reticulum 1
endosome 1
cytosol 1
golgi apparatus 1

Subcellular locations from the

Human Protein Atlas (HPA)
  • Cytosol (2)
  • Nucleoplasm (2)
  • Plasma membrane (2)
See all subcellular structures

Gene Ontology (GO) - Cellular Components for GLIS2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005634 nucleus IBA,ISS --
GO:0005737 cytoplasm IEA --
GO:0016607 nuclear speck ISS --
GO:0097730 non-motile cilium IEA --
genes like me logo Genes that share ontologies with GLIS2: view

Pathways & Interactions for GLIS2 Gene

PathCards logo

SuperPathways for GLIS2 Gene

No Data Available

SIGNOR curated interactions for GLIS2 Gene

Is activated by:
Is inactivated by:

Gene Ontology (GO) - Biological Process for GLIS2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000122 negative regulation of transcription by RNA polymerase II ISS --
GO:0001822 kidney development IEA --
GO:0006357 regulation of transcription by RNA polymerase II IBA 21873635
GO:0007275 multicellular organism development IEA --
GO:0007399 nervous system development IEA --
genes like me logo Genes that share ontologies with GLIS2: view

No data available for Pathways by source for GLIS2 Gene

Drugs & Compounds for GLIS2 Gene

No Compound Related Data Available

Transcripts for GLIS2 Gene

mRNA/cDNA for GLIS2 Gene

2 REFSEQ mRNAs :
7 NCBI additional mRNA sequence :
2 Ensembl transcripts including schematic representations, and UCSC links to gene/alias where relevant :

CRISPR Products

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for GLIS2

Alternative Splicing Database (ASD) splice patterns (SP) for GLIS2 Gene

No ASD Table

Relevant External Links for GLIS2 Gene

GeneLoc Exon Structure for
GLIS2

Expression for GLIS2 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for GLIS2 Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

Protein differential expression in normal tissues from HIPED for GLIS2 Gene

This gene is overexpressed in Plasma (45.6) and Heart (20.8).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB and MOPED for GLIS2 Gene



Protein tissue co-expression partners for GLIS2 Gene

Transcriptomic regulation report from SPP (The Signaling Pathways Project) for GLIS2

SOURCE GeneReport for Unigene cluster for GLIS2 Gene:

Hs.592087

mRNA Expression by UniProt/SwissProt for GLIS2 Gene:

Q9BZE0-GLIS2_HUMAN
Tissue specificity: Expressed at high levels in kidney and at low levels in heart, lung and placenta. Expressed in colon.

Evidence on tissue expression from TISSUES for GLIS2 Gene

  • Kidney(4.7)
  • Nervous system(4.6)
  • Blood(2.3)
  • Heart(2.2)
  • Intestine(2.2)

Phenotype-based relationships between genes and organs from Gene ORGANizer for GLIS2 Gene

Germ Layers:
  • mesoderm
Systems:
  • urinary
Regions:
Abdomen:
  • kidney
genes like me logo Genes that share expression patterns with GLIS2: view

No data available for mRNA differential expression in normal tissues for GLIS2 Gene

Orthologs for GLIS2 Gene

This gene was present in the common ancestor of animals and fungi.

Orthologs for GLIS2 Gene

Organism Taxonomy Gene Similarity Type Details
Chimpanzee
(Pan troglodytes)
Mammalia GLIS2 30 31
  • 99.24 (n)
OneToOne
Dog
(Canis familiaris)
Mammalia GLIS2 30 31
  • 92.05 (n)
OneToOne
Cow
(Bos Taurus)
Mammalia GLIS2 30 31
  • 90.39 (n)
OneToOne
Rat
(Rattus norvegicus)
Mammalia Glis2 30
  • 87.84 (n)
Mouse
(Mus musculus)
Mammalia Glis2 30 17 31
  • 87.33 (n)
OneToOne
Oppossum
(Monodelphis domestica)
Mammalia GLIS2 31
  • 84 (a)
OneToOne
Platypus
(Ornithorhynchus anatinus)
Mammalia GLIS2 31
  • 83 (a)
OneToOne
Tropical Clawed Frog
(Silurana tropicalis)
Amphibia glis2 30
  • 65.65 (n)
African clawed frog
(Xenopus laevis)
Amphibia NKL 30
Zebrafish
(Danio rerio)
Actinopterygii LOC568488 30
  • 60.88 (n)
OTTDARG00000032278 31
  • 57 (a)
OneToMany
GLIS2 (2 of 2) 31
  • 56 (a)
OneToMany
Dr.11559 30
Fruit Fly
(Drosophila melanogaster)
Insecta CG3850 32
  • 58 (a)
lmd 32
  • 54 (a)
sug 31
  • 30 (a)
OneToOne
Worm
(Caenorhabditis elegans)
Secernentea tra-1 32
  • 54 (a)
Baker's yeast
(Saccharomyces cerevisiae)
Saccharomycetes RIM101 33
Species where no ortholog for GLIS2 was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Eremothecium gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • Alpha proteobacteria (Wolbachia pipientis)
  • Amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • Barley (Hordeum vulgare)
  • Beta proteobacteria (Neisseria meningitidis)
  • Bread mold (Neurospora crassa)
  • Chicken (Gallus gallus)
  • Chromalveolata (Phytophthora infestans)
  • Common water flea (Daphnia pulex)
  • Corn (Zea mays)
  • E. coli (Escherichia coli)
  • Filamentous fungi (Aspergillus nidulans)
  • Firmicute Bacteria (Streptococcus pneumoniae)
  • Fission Yeast (Schizosaccharomyces pombe)
  • Green Algae (Chlamydomonas reinhardtii)
  • Honey Bee (Apis mellifera)
  • K. Lactis Yeast (Kluyveromyces lactis)
  • Lizard (Anolis carolinensis)
  • Loblloly Pine (Pinus taeda)
  • Malaria Parasite (Plasmodium falciparum)
  • Medicago Trunc (Medicago Truncatula)
  • Moss (Physcomitrella patens)
  • Orangutan (Pongo pygmaeus)
  • Pig (Sus scrofa)
  • Rainbow Trout (Oncorhynchus mykiss)
  • Rice (Oryza sativa)
  • Rice Blast Fungus (Magnaporthe grisea)
  • Schistosome Parasite (Schistosoma mansoni)
  • Sea Anemone (Nematostella vectensis)
  • Sea Vase (Ciona intestinalis)
  • Sea Squirt (Ciona savignyi)
  • Sea Urchin (Strongylocentrotus purpuratus)
  • Sorghum (Sorghum bicolor)
  • Soybean (Glycine max)
  • Stem Rust Fungus (Puccinia graminis)
  • Sugarcane (Saccharum officinarum)
  • Thale Cress (Arabidopsis thaliana)
  • Tomato (Lycopersicon esculentum)
  • Toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • Wheat (Triticum aestivum)

Evolution for GLIS2 Gene

ENSEMBL:
Gene Tree for GLIS2 (if available)
TreeFam:
Gene Tree for GLIS2 (if available)
Aminode:
Evolutionary constrained regions (ECRs) for GLIS2: view image

Paralogs for GLIS2 Gene

Paralogs for GLIS2 Gene

(2) SIMAP similar genes for GLIS2 Gene using alignment to 1 proteins:

  • GLIS2_HUMAN
genes like me logo Genes that share paralogs with GLIS2: view

Variants for GLIS2 Gene

Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for GLIS2 Gene

SNP ID Clinical significance and condition Chr 16 pos Variation AA Info Type
640688 Uncertain Significance: Nephronophthisis 4,337,337(+) C/T MISSENSE_VARIANT
696768 Likely Benign: not provided 4,336,864(+) G/A SYNONYMOUS_VARIANT
696775 Likely Benign: not provided 4,336,738(+) C/T SYNONYMOUS_VARIANT
697002 Likely Benign: not provided 4,337,233(+) G/A SYNONYMOUS_VARIANT
697059 Benign: Nephronophthisis 4,336,798(+) C/T SYNONYMOUS_VARIANT

Additional dbSNP identifiers (rs#s) for GLIS2 Gene

Structural Variations from Database of Genomic Variants (DGV) for GLIS2 Gene

Variant ID Type Subtype PubMed ID
esv3584924 CNV gain 24956385
nsv1046986 CNV gain 25217958
nsv471075 CNV loss 18288195
nsv527866 CNV loss 19592680
nsv571274 CNV gain 21841781
nsv571282 CNV gain 21841781
nsv571300 CNV loss 21841781

Variation tolerance for GLIS2 Gene

Residual Variation Intolerance Score: 38.7% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 5.01; 68.44% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for GLIS2 Gene

Human Gene Mutation Database (HGMD)
GLIS2
SNPedia medical, phenotypic, and genealogical associations of SNPs for
GLIS2

SNP Genotyping and Copy Number Assay Products

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for GLIS2 Gene

Disorders for GLIS2 Gene

MalaCards: The human disease database

(16) MalaCards diseases for GLIS2 Gene - From: OMIM, ClinVar, GTR, Orphanet, DISEASES, and GeneCards

Disorder Aliases PubMed IDs
nephronophthisis 7
  • nphp7
acute megakaryoblastic leukemia without down syndrome
  • non-ds-amkl
nephronophthisis
  • medullary cystic disease
juvenile nephronophthisis
  • nephronophthisis, familial juvenile
cd3zeta deficiency
- elite association - COSMIC cancer census association via MalaCards
Search GLIS2 in MalaCards View complete list of genes associated with diseases

UniProtKB/Swiss-Prot

GLIS2_HUMAN
  • Nephronophthisis 7 (NPHP7) [MIM:611498]: An autosomal recessive disorder resulting in end-stage renal disease during childhood or adolescence. It is a progressive tubulo-interstitial kidney disorder histologically characterized by modifications of the tubules with thickening of the basement membrane, interstitial fibrosis and, in the advanced stages, medullary cysts. {ECO:0000269 PubMed:17618285}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Additional Disease Information for GLIS2

genes like me logo Genes that share disorders with GLIS2: view

No data available for Genatlas for GLIS2 Gene

Publications for GLIS2 Gene

  1. Loss of GLIS2 causes nephronophthisis in humans and mice by increased apoptosis and fibrosis. (PMID: 17618285) Attanasio M … Treier M (Nature genetics 2007) 2 3 4
  2. Genomic structure of the gene encoding the human GLI-related, Krüppel-like zinc finger protein GLIS2. (PMID: 11738817) Zhang F … Jetten AM (Gene 2001) 3 4 23
  3. The transcriptional repressor Glis2 is a novel binding partner for p120 catenin. (PMID: 17344476) Hosking CR … Fujita Y (Molecular biology of the cell 2007) 3 4
  4. The Krüppel-like zinc finger protein Glis2 functions as a negative modulator of the Wnt/beta-catenin signaling pathway. (PMID: 17289029) Kim YS … Jetten AM (FEBS letters 2007) 3 4
  5. Complete sequencing and characterization of 21,243 full-length human cDNAs. (PMID: 14702039) Ota T … Sugano S (Nature genetics 2004) 3 4

Products for GLIS2 Gene

Sources for GLIS2 Gene