Details for: GLIS2

Gene ID: 84662

Gene Type:  Protein-coding  - A gene that serves as a template for producing a messenger RNA (mRNA) molecule, which is then translated into a functional protein.

Symbol: GLIS2

Ensembl ID: ENSG00000126603

Description: GLIS family zinc finger 2

Cell Significance Landscape

Associated with

  • Cell differentiation involved in kidney development
    (GO:0061005)
  • Central nervous system development
    (GO:0007417)
  • Cytoplasm
    (GO:0005737)
  • Dna-binding transcription activator activity, rna polymerase ii-specific
    (GO:0001228)
  • Dna-binding transcription factor activity, rna polymerase ii-specific
    (GO:0000981)
  • Hematopoietic stem cell homeostasis
    (GO:0061484)
  • Metal ion binding
    (GO:0046872)
  • Negative regulation of dna-binding transcription factor activity
    (GO:0043433)
  • Negative regulation of dna-templated transcription
    (GO:0045892)
  • Negative regulation of smoothened signaling pathway
    (GO:0045879)
  • Negative regulation of transcription by rna polymerase ii
    (GO:0000122)
  • Non-motile cilium
    (GO:0097730)
  • Nuclear speck
    (GO:0016607)
  • Nucleoplasm
    (GO:0005654)
  • Nucleus
    (GO:0005634)
  • Positive regulation of dna-templated transcription
    (GO:0045893)
  • Positive regulation of protein localization to nucleus
    (GO:1900182)
  • Positive regulation of transcription by rna polymerase ii
    (GO:0045944)
  • Protein binding
    (GO:0005515)
  • Rna polymerase ii cis-regulatory region sequence-specific dna binding
    (GO:0000978)
  • Sequence-specific double-stranded dna binding
    (GO:1990837)
  • Transcription cis-regulatory region binding
    (GO:0000976)

Significant Cells

Cell Significance Index (CSI) scores for the chosen context(s)

  • conventional dendritic cell CL0000990
    CSI 31.35
    rCSI 26.17%
    PRS 98.83
  • regulatory T cell CL0000815
    CSI 22.67
    rCSI 26.29%
    PRS 98.92
  • chondrocyte CL0000138
    CSI 19.97
    rCSI 31.77%
    PRS 99.39
  • innate lymphoid cell CL0001065
    CSI 17.08
    rCSI 35.26%
    PRS 99.12
  • mast cell CL0000097
    CSI 16.6
    rCSI 35.84%
    PRS 98.53
  • helper T cell CL0000912
    CSI 16.23
    rCSI 22.94%
    PRS 99.18
  • CD8-positive, alpha-beta memory T cell, CD45RO-positive CL0001203
    CSI 16.15
    rCSI 19.56%
    PRS 97.13
  • melanocyte of skin CL1000458
    CSI 14.88
    rCSI 20.28%
    PRS 97.07
  • basal cell of epidermis CL0002187
    CSI 13.81
    rCSI 24.47%
    PRS 96.2
  • suprabasal keratinocyte CL4033013
    CSI 12.84
    rCSI 20.96%
    PRS 97.64
  • bronchus fibroblast of lung CL2000093
    CSI 11.77
    rCSI 9.57%
    PRS 99.93
  • perivascular cell CL4033054
    CSI 10.67
    rCSI 14.58%
    PRS 99.98
  • vascular associated smooth muscle cell CL0000359
    CSI 10.22
    rCSI 33.16%
    PRS 99.96
  • epithelial cell of proximal tubule CL0002306
    CSI 9.01
    rCSI 22.01%
    PRS 99.53
  • epithelial cell of lung CL0000082
    CSI 9.01
    rCSI 7.47%
    PRS 100
  • endothelial cell of vascular tree CL0002139
    CSI 8.34
    rCSI 45.61%
    PRS 99.44
  • pancreatic A cell CL0000171
    CSI 8.34
    rCSI 8.74%
    PRS 99.93
  • kidney loop of Henle thin descending limb epithelial cell CL1001111
    CSI 7.89
    rCSI 11.19%
    PRS 99.89
  • type B pancreatic cell CL0000169
    CSI 7.43
    rCSI 16.45%
    PRS 99.84
  • mesenchymal cell CL0008019
    CSI 5.36
    rCSI 13.62%
    PRS 99.93
  • kidney connecting tubule epithelial cell CL1000768
    CSI 4.78
    rCSI 12.12%
    PRS 99.81
  • cytotoxic T cell CL0000910
    CSI 3.18
    rCSI 18.24%
    PRS 99.29
  • pancreatic PP cell CL0002275
    CSI 2.21
    rCSI 8.78%
    PRS 99.91

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this specific cell.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.
Network Configuration

Explore relationships of the current gene. Select an Interaction Source: 'ONTOLOGY' for shared pathways (GO/Reactome) or 'STRING' for protein-protein interactions. Further refine by selecting context genes and comparing Cell Significance Index (CSI) scores between baseline and target cell types and their specific contexts.

Comma-separated if multiple.
Comma-separated if multiple.
Legend:
  • Query Gene
  • Node Color (Target Cell CSI, relative to current network):
    • Very High
    • High
    • Medium
    • Low
    • Very Low
    • CSI N/A
  • Node Size: Proportional to Target Cell CSI magnitude
  • STRING PPI Edge
  • Shared Pathway Edge (ONTOLOGY)

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Other Information

This section provides additional information about the gene, including a description generated by an AI language model and details about associated proteins.

## Summary [GLIS2](/details-gene/84662), or GLIS family zinc finger 2, is a protein-coding gene located on chromosome 16p13.3. It encodes a Kruppel-like zinc finger transcription factor that plays a crucial, dual role as both a transcriptional activator and repressor. Functionally, [GLIS2](/details-gene/84662) is implicated in a variety of fundamental biological processes, including the development of the kidney and central nervous system, as well as the regulation of hematopoietic stem cell homeostasis. Expression data from the **Overall** context reveals its significance across diverse cell lineages, with particularly high importance in immune cells such as [conventional dendritic cell](/details-cell/CL0000990)s and [regulatory T cell](/details-cell/CL0000815)s, as well as in structural cells like [chondrocyte](/details-cell/CL0000138)s. Loss-of-function mutations in [GLIS2](/details-gene/84662) are causally linked to nephronophthisis, a form of hereditary cystic kidney disease, underscoring its essential role in maintaining renal tissue integrity [Link](https://doi.org/10.1038/ng2072). ## Cellular Roles and Expression Landscape The expression profile of [GLIS2](/details-gene/84662) highlights its multifaceted role across the immune, structural, and epithelial compartments. **Overall**, the gene exhibits its highest significance in the immune system, particularly in antigen-presenting and regulatory lineages. It is the top marker for [conventional dendritic cell](/details-cell/CL0000990) (CSI: 31.35) and shows high significance in [regulatory T cell](/details-cell/CL0000815) (CSI: 22.67), [innate lymphoid cell](/details-cell/CL0001065) (CSI: 17.08), [mast cell](/details-cell/CL0000097) (CSI: 16.60), and various T helper and memory T cell populations. This pattern suggests a pivotal role for [GLIS2](/details-gene/84662) in orchestrating immune responses, potentially governing cell differentiation, activation, or tolerance, which is consistent with its annotated function in [hematopoietic stem cell homeostasis](/details-go/GO:0061484). Beyond the immune system, [GLIS2](/details-gene/84662) demonstrates significant expression in a variety of stromal and developmental cell types. It is a key marker in [chondrocyte](/details-cell/CL0000138) (CSI: 19.97), indicating a potential role in cartilage development or maintenance. Its relevance is also noted in multiple skin cell types, including [melanocyte of skin](/details-cell/CL1000458) and [basal cell of epidermis](/details-cell/CL0002187), as well as in mesenchymal cells like [bronchus fibroblast of lung](/details-cell/CL2000093) and [perivascular cell](/details-cell/CL4033054). Furthermore, its expression in [epithelial cell of proximal tubule](/details-cell/CL0002306) directly aligns with its established critical function in kidney development and pathology. ## Pathways and Molecular Function [GLIS2](/details-gene/84662) functions as a sequence-specific, DNA-binding transcription factor ([GO:0000981](https://www.ebi.ac.uk/QuickGO/term/GO:0000981)), localizing primarily to the [nucleus](/details-go/GO:0005634) where it binds to cis-regulatory regions of target genes. Its activity is pleiotropic, as it can both positively ([GO:0045893](https://www.ebi.ac.uk/QuickGO/term/GO:0045893)) and negatively ([GO:0045892](https://www.ebi.ac.uk/QuickGO/term/GO:0045892)) regulate transcription by RNA polymerase II. The functional annotations align closely with its observed cellular expression patterns and clinical relevance. Its involvement in [cell differentiation involved in kidney development](/details-go/GO:0061005) is clinically significant, as loss-of-function mutations lead to nephronophthisis through mechanisms involving increased apoptosis and fibrosis [Link](https://doi.org/10.1038/ng2072). The gene's role in [central nervous system development](/details-go/GO:0007417) is supported by research identifying it as a promoter of neuronal differentiation [Link](https://doi.org/10.1242/dev.128.8.1335). Mechanistically, [GLIS2](/details-gene/84662) has been shown to act as a [negative regulation of smoothened signaling pathway](/details-go/GO:0045879) and as a negative modulator of the Wnt/beta-catenin signaling pathway [Link](https://doi.org/10.1016/j.febslet.2007.01.058), a fundamental pathway in development and disease. Its function in [hematopoietic stem cell homeostasis](/details-go/GO:0061484) provides a molecular basis for its high significance in diverse immune cell populations, including dendritic cells and T cells. ## Research Directions The widespread yet specific expression of [GLIS2](/details-gene/84662) in critical regulatory cell types, combined with its known role as a transcriptional modulator, presents several avenues for future investigation. ### Proposed Hypotheses 1. Given its high significance in both [conventional dendritic cell](/details-cell/CL0000990)s and [regulatory T cell](/details-cell/CL0000815)s, [GLIS2](/details-gene/84662) may function as a master regulator of immune tolerance by controlling the differentiation programs or suppressive functions of these key cell types, possibly by repressing pro-inflammatory gene networks. 2. Based on its function as a negative modulator of Wnt/beta-catenin signaling and its expression in stromal cells like [bronchus fibroblast of lung](/details-cell/CL2000093), [GLIS2](/details-gene/84662) may play a protective role against fibrosis in tissues beyond the kidney by suppressing pro-fibrotic transcriptional programs activated by the Wnt pathway. ### Experimental Approach To test the first hypothesis regarding the role of [GLIS2](/details-gene/84662) in immune tolerance, a cell-type-specific knockout approach would be informative. One could generate a conditional knockout mouse model where [GLIS2](/details-gene/84662) is specifically deleted in dendritic cells (e.g., *Itgax*-Cre;*Glis2*fl/fl mice). These mice, along with littermate controls, could be subjected to an induced autoimmune disease model, such as experimental autoimmune encephalomyelitis (EAE). The role of [GLIS2](/details-gene/84662) would be assessed by monitoring disease severity, characterizing the T cell responses, and performing single-cell RNA-sequencing on dendritic cell populations from lymphoid organs to define the specific transcriptional networks regulated by [GLIS2](/details-gene/84662) during the maintenance of peripheral tolerance. ### Therapeutic Potential The primary clinical relevance of [GLIS2](/details-gene/84662) is linked to loss-of-function mutations causing nephronophthisis. This indicates that therapeutic strategies should focus on **activation or restoration** of its function rather than inhibition. For monogenic diseases like nephronophthisis, gene therapy to restore [GLIS2](/details-gene/84662) expression in the affected kidney cells could be a long-term therapeutic goal. Furthermore, its role as a repressor of pro-fibrotic and oncogenic pathways like Wnt/beta-catenin suggests that small-molecule activators of [GLIS2](/details-gene/84662) could have therapeutic potential in certain fibrotic diseases or cancers where this pathway is aberrantly activated. However, its broad expression pattern would necessitate highly targeted delivery to avoid undesirable effects in other tissues.

Genular Protein ID: 1548695426

Symbol: GLIS2_HUMAN

Name: Zinc finger protein GLIS2

UniProtKB Accession Codes:

Q9BZE0 B3KX84

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BindingDB 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 1 CORUM 1 CTD 1 ChiTaRS 1 DMDM 1 DNASU 1 DisGeNET 1 EMBL 6 Ensembl 4 GO 21 Gene3D 1 GeneCards 1 GeneReviews 1 GeneTree 1 GenomeRNAi 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 3 KEGG 1 MANE-Select 1 MIM 3 MINT 1 MalaCards 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 Orphanet 2 OrthoDB 1 PANTHER 2 PRO 1 PROSITE 2 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 1 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 1 RNAct 1 RefSeq 3 SIGNOR 1 SMART 1 SMR 1 STRING 1 SUPFAM 1 SignaLink 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 jPOST 1 neXtProt 1

Citations:

PubMed ID: 11738817

Title: Genomic structure of the gene encoding the human GLI-related, Kruppel-like zinc finger protein GLIS2.

PubMed ID: 11738817

DOI: 10.1016/s0378-1119(01)00764-8

PubMed ID: 14702039

Title: Complete sequencing and characterization of 21,243 full-length human cDNAs.

PubMed ID: 14702039

DOI: 10.1038/ng1285

PubMed ID: 15616553

Title: The sequence and analysis of duplication-rich human chromosome 16.

PubMed ID: 15616553

DOI: 10.1038/nature03187

PubMed ID: 11262234

Title: Identification of NKL, a novel Gli-Kruppel zinc-finger protein that promotes neuronal differentiation.

PubMed ID: 11262234

DOI: 10.1242/dev.128.8.1335

PubMed ID: 17289029

Title: The Kruppel-like zinc finger protein Glis2 functions as a negative modulator of the Wnt/beta-catenin signaling pathway.

PubMed ID: 17289029

DOI: 10.1016/j.febslet.2007.01.058

PubMed ID: 17344476

Title: The transcriptional repressor Glis2 is a novel binding partner for p120 catenin.

PubMed ID: 17344476

DOI: 10.1091/mbc.e06-10-0941

PubMed ID: 17618285

Title: Loss of GLIS2 causes nephronophthisis in humans and mice by increased apoptosis and fibrosis.

PubMed ID: 17618285

DOI: 10.1038/ng2072

Sequence Information:

  • Length: 524
  • Mass: 55689
  • Checksum: F38BA80C477FDC24
  • Sequence:
    • MHSLDEPLDL KLSITKLRAA REKRERTLGV VRPRALHREL GLVDDSPTPG SPGSPPSGFL 
LNSKFPEKVE GRFSAAPLVD LSLSPPSGLD SPNGSSSLSP ERQGNGDLPP VPSASDFQPL 
RYLDGVPSSF QFFLPLGSGG ALHLPASSFL TPPKDKCLSP DLPLPKQLVC RWAKCNQLFE 
LLQDLVDHVN DYHVKPEKDA GYCCHWEGCA RHGRGFNARY KMLIHIRTHT NEKPHRCPTC 
SKSFSRLENL KIHNRSHTGE KPYVCPYEGC NKRYSNSSDR FKHTRTHYVD KPYYCKMPGC 
HKRYTDPSSL RKHIKAHGHF VSHEQQELLQ LRPPPKPPLP APDGGPYVSG AQIIIPNPAA 
LFGGPGLPGL PLPLAPGPLD LSALACGNGG GSGGGGGMGP GLPGPVLPLN LAKNPLLPSP 
FGAGGLGLPV VSLLAGAAGG KAEGEKGRGS VPTRALGMEG HKTPLERTES SCSRPSPDGL 
PLLPGTVLDL STGVNSAASS PEALAPGWVV IPPGSVLLKP AVVN

Genular Protein ID: 686402647

Symbol: B3KTH4_HUMAN

Name: N/A

UniProtKB Accession Codes:

B3KTH4

Database IDs:

ARBA 8 AlphaFoldDB 1 BioGRID-ORCS 1 CTD 1 DNASU 1 DisGeNET 1 EMBL 2 GO 4 Gene3D 1 InterPro 3 KEGG 1 NCBI Taxonomy 1 PANTHER 2 PROSITE 3 PROSITE-ProRule 1 PeptideAtlas 1 Pfam 1 RefSeq 1 SAM 1 SMART 1 SUPFAM 1

Citations:

PubMed ID: 14702039

Title: Complete sequencing and characterization of 21,243 full-length human cDNAs.

PubMed ID: 14702039

DOI: 10.1038/ng1285

Sequence Information:

  • Length: 303
  • Mass: 31562
  • Checksum: 48D6269A8A1D4063
  • Sequence:
    • MLIHIRTHTN EKPHRCPTCS KSFSRLENLK IHNRSHTGEK PYVCPYEGCN KRYSNSSDRF 
KHTRTHYVDK PYYCKMPGCH KRYTDPSSLR KHIKAHGHFV SHEQQELLQL RPPPKPPLPA 
PDGGPYVSGA QIIIPNPAAL FGGPGLPGLP LPLAPGPLDL SALACGNGGG SGGGGGMGPG 
LPGPVLPLNL AKNPLLPSPF GAGGLGLPVV SLLAGAAGGK AEGEKGRGSV PTRALGMEGH 
KTPLERTESS CSRPSPDGLP LLPGTVLDLS TGVNSAASSP EALAPGWVVI PPGSVLLKPA 
VVN