Details for: KLF11

Gene ID: 8462

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: KLF11

Ensembl ID: ENSG00000172059

Description: KLF transcription factor 11

Selected Context(s):  Overall

Cell Significance Landscape

Contexts:

Associated with

Significant Cells

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

  • Kupffer cell CL0000091
    CSI 3.7
    rCSI 8.47%
    PRS 95.85
  • group 3 innate lymphoid cell CL0001071
    CSI 3.6
    rCSI 2.71%
    PRS 96.68
  • midzonal region hepatocyte CL0019028
    CSI 3.59
    rCSI 8.43%
    PRS 92.02
  • fibroblast of lung CL0002553
    CSI 3.28
    rCSI 3.06%
    PRS 96.04
  • perivascular cell CL4033054
    CSI 3.09
    rCSI 4.22%
    PRS 96.9
  • pulmonary capillary endothelial cell CL4028001
    CSI 2.94
    rCSI 5.61%
    PRS 97.7
  • cerebral cortex endothelial cell CL1001602
    CSI 2.78
    rCSI 4.8%
    PRS 91.95
  • blood vessel endothelial cell CL0000071
    CSI 2.74
    rCSI 5.69%
    PRS 93.92
  • retinal blood vessel endothelial cell CL0002585
    CSI 2.72
    rCSI 4.34%
    PRS 96.27
  • keratinocyte CL0000312
    CSI 2.67
    rCSI 2.24%
    PRS 94.62
  • hepatocyte CL0000182
    CSI 2.57
    rCSI 4.59%
    PRS 93.52
  • myeloid leukocyte CL0000766
    CSI 2.55
    rCSI 2.35%
    PRS 95.96
  • elicited macrophage CL0000861
    CSI 2.5
    rCSI 2.29%
    PRS 97.72
  • vascular associated smooth muscle cell CL0000359
    CSI 2.27
    rCSI 7.35%
    PRS 93.95
  • CD14-low, CD16-positive monocyte CL0002396
    CSI 2.26
    rCSI 1.74%
    PRS 97.18
  • centrilobular region hepatocyte CL0019029
    CSI 2.04
    rCSI 5.32%
    PRS 91.27
  • intermediate monocyte CL0002393
    CSI 2.04
    rCSI 3.07%
    PRS 97.6
  • pulmonary artery endothelial cell CL1001568
    CSI 1.98
    rCSI 2.69%
    PRS 97.36
  • CD1c-positive myeloid dendritic cell CL0002399
    CSI 1.77
    rCSI 2.13%
    PRS 97.68
  • kidney connecting tubule epithelial cell CL1000768
    CSI 1.52
    rCSI 3.86%
    PRS 91.56
  • lung macrophage CL1001603
    CSI 1.46
    rCSI 3.25%
    PRS 97.9
  • microcirculation associated smooth muscle cell CL0008035
    CSI 0.85
    rCSI 2.46%
    PRS 94.42
  • lung microvascular endothelial cell CL2000016
    CSI 0.3
    rCSI 5.85%
    PRS 97.04

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.

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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 [KLF11](/details-gene/8462) (Krueppel-like factor 11) is a protein-coding gene located on chromosome 2p25.1 that encodes a member of the Sp1-like/KLF family of zinc-finger transcription factors. Functionally, [KLF11](/details-gene/8462) acts as a sequence-specific DNA-binding protein that regulates transcription from RNA polymerase II promoters. It is implicated in fundamental cellular processes, including the negative regulation of cell proliferation ([GO:0008285](https://www.ebi.ac.uk/QuickGO/term/GO:0008285)), control of the G1/S transition of the mitotic cell cycle ([GO:2000045](https://www.ebi.ac.uk/QuickGO/term/GO:2000045)), and the induction of apoptosis ([GO:0006915](https://www.ebi.ac.uk/QuickGO/term/GO:0006915)). Its expression profile is broad, with notable significance in diverse cell types including resident liver macrophages ([Kupffer cell](/details-cell/CL0000091)), innate lymphoid cells, hepatocytes, fibroblasts, and various endothelial cells, suggesting its importance in tissue homeostasis, immunity, and vascular biology. Initial characterization identified it as a TGF-beta-inducible gene involved in regulating cell growth ([Link](https://doi.org/10.1074/jbc.273.40.25929)). ## Cellular Roles and Expression Landscape The expression pattern of [KLF11](/details-gene/8462) highlights its multifaceted role across various tissues and cell lineages. **Overall**, it shows the highest significance in several key cell populations, indicating a fundamental role in their function. [KLF11](/details-gene/8462) is a particularly significant factor in the liver, with high CSI scores in both the resident macrophage population, [Kupffer cell](/details-cell/CL0000091) (CSI: 3.70), and parenchymal cells like [midzonal region hepatocyte](/details-cell/CL0019028) (CSI: 3.59) and [hepatocyte](/details-cell/CL0000182) (CSI: 2.57). This co-expression in major hepatic cell types suggests a coordinated role in maintaining liver homeostasis. Its significance also extends to the immune system, where it is highly ranked in [group 3 innate lymphoid cell](/details-cell/CL0001071) (CSI: 3.60) and various [myeloid leukocyte](/details-cell/CL0000766) populations, including [elicited macrophage](/details-cell/CL0000861) (CSI: 2.50) and [CD14-low, CD16-positive monocyte](/details-cell/CL0002396) (CSI: 2.26). Furthermore, [KLF11](/details-gene/8462) demonstrates a prominent role in stromal and endothelial compartments. It is highly significant in [fibroblast of lung](/details-cell/CL0002553) (CSI: 3.28) and [perivascular cell](/details-cell/CL4033054) (CSI: 3.09). Its consistent high ranking across multiple endothelial cell types, including [pulmonary capillary endothelial cell](/details-cell/CL4028001) (CSI: 2.94), [cerebral cortex endothelial cell](/details-cell/CL1001602) (CSI: 2.78), and [retinal blood vessel endothelial cell](/details-cell/CL0002585) (CSI: 2.72), points towards a conserved function in regulating the vascular endothelium across different organs. ## Pathways and Molecular Function [KLF11](/details-gene/8462) functions primarily as a DNA-binding transcription factor. Its molecular activities are centered on recognizing and binding to cis-regulatory regions of DNA to modulate gene expression ([GO:0000978](https://www.ebi.ac.uk/QuickGO/term/GO:0000978), [GO:0003700](https://www.ebi.ac.uk/QuickGO/term/GO:0003700)). As expected for a transcription factor, it is predominantly localized to the [nucleus](/details-cell/CL0005634), where it associates with [chromatin](/details-cell/CL0000785) and is found within the [nucleoplasm](/details-cell/CL0005654). The biological processes regulated by [KLF11](/details-gene/8462) are critical for cellular fate decisions. It is a known negative regulator of transcription by RNA polymerase II ([GO:0000122](https://www.ebi.ac.uk/QuickGO/term/GO:0000122)) and plays a key role in suppressing cell population growth ([GO:0008285](https://www.ebi.ac.uk/QuickGO/term/GO:0008285)). This anti-proliferative function is consistent with its ability to regulate the G1/S transition of the cell cycle ([GO:2000045](https://www.ebi.ac.uk/QuickGO/term/GO:2000045)). In addition, [KLF11](/details-gene/8462) is an active participant in programmed cell death, where it positively regulates the apoptotic process ([GO:0043065](https://www.ebi.ac.uk/QuickGO/term/GO:0043065)). Research has also demonstrated a role for [KLF11](/details-gene/8462) and its genetic variants in the function of pancreatic beta cells, linking it to diabetes pathology ([Link](https://doi.org/10.1073/pnas.0409177102)). ## Research Directions The widespread and significant expression of [KLF11](/details-gene/8462) across immune, parenchymal, and endothelial cells suggests it is a central node in coordinating tissue-level responses. Its established role as a cell growth regulator and its high significance in metabolically active and immunologically critical cells provide a basis for several testable hypotheses. 1. **Hypothesis 1:** Given its high significance in [Kupffer cells](/details-cell/CL0000091) and hepatocytes, and its function in regulating apoptosis and proliferation, [KLF11](/details-gene/8462) likely acts as a critical regulator of liver homeostasis and response to injury, potentially by coordinating the crosstalk between these two cell types. 2. **Hypothesis 2:** Based on its consistent high CSI across diverse endothelial cell types and its known induction by TGF-beta, [KLF11](/details-gene/8462) may function as a key mediator of endothelial cell activation, quiescence, and barrier integrity in response to inflammatory or fibrotic signals. **Experimental Approach for Hypothesis 1:** To investigate the role of [KLF11](/details-gene/8462) in liver homeostasis, a myeloid-specific conditional knockout mouse model (`Lyz2-Cre;Klf11-flox/flox`) could be generated to delete the gene specifically in [Kupffer cells](/details-cell/CL0000091). These mice, alongside littermate controls, could be subjected to a model of chronic liver injury, such as a high-fat diet or carbon tetrachloride (CCl4) administration. The impact of [KLF11](/details-gene/8462) deletion on disease progression would be assessed by monitoring liver fibrosis (histology, qRT-PCR for collagen genes), inflammation (serum cytokine levels, immune cell infiltration via flow cytometry), and hepatocyte damage (serum ALT/AST levels). Single-cell RNA sequencing of liver tissue would further elucidate the specific changes in gene expression programs within [Kupffer cells](/details-cell/CL0000091) and the resulting impact on neighboring hepatocytes and stellate cells. **Therapeutic Potential:** As a nuclear transcription factor, [KLF11](/details-gene/8462) presents a challenging target for direct pharmacological inhibition or activation. However, its position as a regulator of critical cellular pathways makes it an important node for therapeutic consideration. If [KLF11](/details-gene/8462) dysregulation is proven to drive pathological processes like liver fibrosis or metabolic dysfunction in diabetes ([Link](https://doi.org/10.1073/pnas.0409177102)), therapeutic strategies could focus on modulating its expression or activity via upstream signaling pathways or targeting its critical downstream effectors. Such approaches could offer a more tractable route to harnessing the therapeutic potential of this transcription factor.

Genular Protein ID: 850348373

Symbol: KLF11_HUMAN

Name: Krueppel-like factor 11

UniProtKB Accession Codes:

Database IDs:

Citations:

PubMed ID: 9748269

Title: Molecular cloning and characterization of TIEG2 reveals a new subfamily of transforming growth factor-beta-inducible Sp1-like zinc finger-encoding genes involved in the regulation of cell growth.

PubMed ID: 9748269

DOI: 10.1074/jbc.273.40.25929

PubMed ID: 10207080

Title: FKLF, a novel Kruppel-like factor that activates human embryonic and fetal beta-like globin genes.

PubMed ID: 10207080

DOI: 10.1128/mcb.19.5.3571

PubMed ID: 11087666

Title: Identification of KLF13 and KLF14 (SP6), novel members of the SP/XKLF transcription factor family.

PubMed ID: 11087666

DOI: 10.1006/geno.2000.6362

PubMed ID: 14702039

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

PubMed ID: 14702039

DOI: 10.1038/ng1285

PubMed ID: 15815621

Title: Generation and annotation of the DNA sequences of human chromosomes 2 and 4.

PubMed ID: 15815621

DOI: 10.1038/nature03466

PubMed ID: 15489334

Title: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).

PubMed ID: 15489334

DOI: 10.1101/gr.2596504

PubMed ID: 16131492

Title: {gamma}-Globin gene expression in chemical inducer of dimerization (CID)-dependent multipotential cells established from human {beta}-globin locus yeast artificial chromosome ({beta}-YAC) transgenic mice.

PubMed ID: 16131492

DOI: 10.1074/jbc.m504402200

PubMed ID: 23186163

Title: Toward a comprehensive characterization of a human cancer cell phosphoproteome.

PubMed ID: 23186163

DOI: 10.1021/pr300630k

PubMed ID: 15774581

Title: Role of transcription factor KLF11 and its diabetes-associated gene variants in pancreatic beta cell function.

PubMed ID: 15774581

DOI: 10.1073/pnas.0409177102

Sequence Information:

  • Length: 512
  • Mass: 55139
  • Checksum: A69863B5467FB068
  • Sequence:
  • MHTPDFAGPD DARAVDIMDI CESILERKRH DSERSTCSIL EQTDMEAVEA LVCMSSWGQR 
    SQKGDLLRIR PLTPVSDSGD VTTTVHMDAA TPELPKDFHS LSTLCITPPQ SPDLVEPSTR 
    TPVSPQVTDS KACTATDVLQ SSAVVARALS GGAERGLLGL EPVPSSPCRA KGTSVIRHTG 
    ESPAACFPTI QTPDCRLSDS REGEEQLLGH FETLQDTHLT DSLLSTNLVS CQPCLHKSGG 
    LLLTDKGQQA GWPGAVQTCS PKNYENDLPR KTTPLISVSV PAPPVLCQMI PVTGQSSMLP 
    AFLKPPPQLS VGTVRPILAQ AAPAPQPVFV GPAVPQGAVM LVLPQGALPP PAPCAANVMA 
    AGNTKLLPLA PAPVFITSSQ NCVPQVDFSR RRNYVCSFPG CRKTYFKSSH LKAHLRTHTG 
    EKPFNCSWDG CDKKFARSDE LSRHRRTHTG EKKFVCPVCD RRFMRSDHLT KHARRHMTTK 
    KIPGWQAEVG KLNRIASAES PGSPLVSMPA SA

Genular Protein ID: 234348962

Symbol: B7ZAX4_HUMAN

Name: N/A

UniProtKB Accession Codes:

Database IDs:

Sequence Information:

  • Length: 495
  • Mass: 53357
  • Checksum: CAC8F6498B5F4B2C
  • Sequence:
  • MDICESILER KRHDSERSTC SILEQTDMEA VEALVCMSSW GQRSRKGDLL RIRPLTPVSD 
    SGDVTTTVHM DAATPELPKD FHSLSTLCIT PPQSPDLVEP STRTPVSPQV TDSKACTATD 
    VLQSSAVVAR ALSGGAERGL LGLEPVPSSP CRAKGTSVIR HTGESPAACF PTIQTPDCRL 
    SDSREGEEQL LGHFETLQDT HLTDSLLSTN LVSCQPCLHK SGGLLLTDKG QQAGWPGAVQ 
    TCSPKNYEND LPRKTTPLIS VSVPAPPVLC QMIPVTGQSS MLPAFLKPPP QLSVGTVRPI 
    LAQAAPAPQP VFVGPAVPQG AVMLVLPQGA LPPPAPCAAN VMAAGNTKLL PLAPAPVFIT 
    SSQNCVPQVD FSRRRNYVCS FPGCRKTYFK SSHLKAHLRT HTGEKPFNCS WDGCDKKFAR 
    SDELSRHRRT HTGEKKFVCP VCDRRFMRSD HLTKHARRHM TTKKIPGWQA EVGKLNRIAS 
    AESPGSPLVS MPASA