KLF4 Gene

HGNC Family	Zinc fingers
Name	Kruppel-like factor 4 (gut)
Description	This gene encodes a protein that belongs to the Kruppel family of transcription factors. The encoded zinc finger protein is required for normal development of the barrier function of skin. The encoded protein is thought to control the G1-to-S transition of the cell cycle following DNA damage by mediating the tumor suppressor gene p53. Mice lacking this gene have a normal appearance but lose weight rapidly, and die shortly after birth due to fluid evaporation resulting from compromised epidermal barrier function. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Sep 2015]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n Krüppel‐like factor 4 (KLF4) is a multifunctional transcription factor whose activity is tightly regulated in a context‐dependent manner. In pluripotent and reprogramming settings, KLF4 is one of the core factors that, together with Oct4, Sox2, and c‐Myc, can induce somatic cells to acquire a pluripotent state."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "5"}]}, {"type": "t", "text": " In this context KLF4 not only contributes to the resetting of cell identity but also collaborates with other family members to maintain embryonic stem cell self‐renewal. Moreover, post‐transcriptional regulation by microRNAs – for instance, miR‐145 directly targeting KLF4 – forms part of a double‐negative feedback loop that modulates the balance between pluripotency and differentiation."}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Outside of pluripotency, KLF4 exerts critical roles in adult tissues. In the vasculature, conditional knockout of Klf4 in smooth muscle cells leads to a reduction in mesenchymal stem cell– and macrophage–like cell phenotypes within atherosclerotic lesions, thereby impacting lesion size and plaque stability."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": " In the innate immune system, KLF4 is induced in M2-polarized macrophages and cooperates with Stat6 to promote an antiinflammatory genetic program while repressing proinflammatory responses, underscoring its importance in regulating macrophage polarization."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n\n "}, {"type": "p", "children": [{"type": "t", "text": "\n In the nervous system, KLF4 functions as a transcriptional repressor of axon growth. Its elevated expression in central nervous system neurons limits regenerative capacity, indicating that modulation of KLF4 activity may be a key determinant in neuronal repair after injury."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Furthermore, in epithelial tissues of the gastrointestinal tract, in vivo studies demonstrate that KLF4 is essential for terminal differentiation, as exemplified by its role in driving goblet cell maturation in the colon."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "9"}]}, {"type": "t", "text": " In cancer, KLF4 exhibits context-dependent functions. Depending on the cellular context, it can act either as a tumor suppressor or an oncogene. Its ability to modulate key cell-cycle regulators such as p53 and p21 underscores a dual function in governing cell proliferation and senescence. In this regard, dysregulation of KLF4 is linked to altered cancer stem cell properties when microRNA networks that target KLF4 (among other stem cell factors such as Sox2) become disrupted."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "10"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Collectively, these studies reveal that KLF4 is a pivotal transcriptional regulator that integrates signals for cellular reprogramming, maintenance of self-renewal, and lineage-specific differentiation. Its activities in controlling proliferation, determining cell fate, and influencing tissue-specific responses underscore its broad impact on development, regeneration, and disease.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "In-Hyun Park, Rui Zhao, Jason A West, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Reprogramming of human somatic cells to pluripotency with defined factors."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nature (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/nature06534"}], "href": "https://doi.org/10.1038/nature06534"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18157115"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18157115"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Na Xu, Thales Papagiannakopoulos, Guangjin Pan, et al. "}, {"type": "b", "children": [{"type": "t", "text": "MicroRNA-145 regulates OCT4, SOX2, and KLF4 and represses pluripotency in human embryonic stem cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.cell.2009.02.038"}], "href": "https://doi.org/10.1016/j.cell.2009.02.038"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19409607"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19409607"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Jianming Jiang, Yun-Shen Chan, Yuin-Han Loh, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A core Klf circuitry regulates self-renewal of embryonic stem cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Cell Biol (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/ncb1698"}], "href": "https://doi.org/10.1038/ncb1698"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18264089"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18264089"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Ge Guo, Jian Yang, Jennifer Nichols, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Klf4 reverts developmentally programmed restriction of ground state pluripotency."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Development (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1242/dev.030957"}], "href": "https://doi.org/10.1242/dev.030957"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19224983"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19224983"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Robert L Judson, Joshua E Babiarz, Monica Venere, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Embryonic stem cell-specific microRNAs promote induced pluripotency."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Biotechnol (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/nbt.1535"}], "href": "https://doi.org/10.1038/nbt.1535"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19363475"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19363475"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Laura S Shankman, Delphine Gomez, Olga A Cherepanova, et al. "}, {"type": "b", "children": [{"type": "t", "text": "KLF4-dependent phenotypic modulation of smooth muscle cells has a key role in atherosclerotic plaque pathogenesis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Med (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/nm.3866"}], "href": "https://doi.org/10.1038/nm.3866"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25985364"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25985364"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Xudong Liao, Nikunj Sharma, Fehmida Kapadia, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Krüppel-like factor 4 regulates macrophage polarization."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Clin Invest (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1172/JCI45444"}], "href": "https://doi.org/10.1172/JCI45444"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21670502"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21670502"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Darcie L Moore, Murray G Blackmore, Ying Hu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "KLF family members regulate intrinsic axon regeneration ability."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Science (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1126/science.1175737"}], "href": "https://doi.org/10.1126/science.1175737"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19815778"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19815778"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Jonathan P Katz, Nathalie Perreault, Bree G Goldstein, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The zinc-finger transcription factor Klf4 is required for terminal differentiation of goblet cells in the colon."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Development (2002)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1242/dev.129.11.2619"}], "href": "https://doi.org/10.1242/dev.129.11.2619"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12015290"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12015290"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "Benjamin D Rowland, René Bernards, Daniel S Peeper "}, {"type": "b", "children": [{"type": "t", "text": "The KLF4 tumour suppressor is a transcriptional repressor of p53 that acts as a context-dependent oncogene."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Cell Biol (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/ncb1314"}], "href": "https://doi.org/10.1038/ncb1314"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16244670"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16244670"}]}, {"type": "r", "ref": 11, "children": [{"type": "t", "text": "Ulrich Wellner, Jörg Schubert, Ulrike C Burk, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The EMT-activator ZEB1 promotes tumorigenicity by repressing stemness-inhibiting microRNAs."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Cell Biol (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/ncb1998"}], "href": "https://doi.org/10.1038/ncb1998"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19935649"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19935649"}]}]}]}
Synonyms	EZF, GKLF
Proteins	KLF4_HUMAN
NCBI Gene ID	9314
API
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Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

KLF4 has 17,610 functional associations with biological entities spanning 8 categories (molecular profile, organism, chemical, functional term, phrase or reference, disease, phenotype or trait, structural feature, cell line, cell type or tissue, gene, protein or microRNA) extracted from 123 datasets.

Click the + buttons to view associations for KLF4 from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

KLF4 Gene

Functional Associations

Please acknowledge the Harmonizome in your publications by citing the following reference(s):

	Dataset	Summary
	Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles	tissues with high or low expression of KLF4 gene relative to other tissues from the Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles dataset.
	Allen Brain Atlas Adult Mouse Brain Tissue Gene Expression Profiles	tissues with high or low expression of KLF4 gene relative to other tissues from the Allen Brain Atlas Adult Mouse Brain Tissue Gene Expression Profiles dataset.
	Allen Brain Atlas Aging Dementia and Traumatic Brain Injury Tissue Sample Gene Expression Profiles	tissue samples with high or low expression of KLF4 gene relative to other tissue samples from the Allen Brain Atlas Aging Dementia and Traumatic Brain Injury Tissue Sample Gene Expression Profiles dataset.
	Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray	tissue samples with high or low expression of KLF4 gene relative to other tissue samples from the Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray dataset.
	Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by RNA-seq	tissue samples with high or low expression of KLF4 gene relative to other tissue samples from the Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by RNA-seq dataset.
	Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles	tissues with high or low expression of KLF4 gene relative to other tissues from the Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles dataset.
	BioGPS Cell Line Gene Expression Profiles	cell lines with high or low expression of KLF4 gene relative to other cell lines from the BioGPS Cell Line Gene Expression Profiles dataset.
	BioGPS Human Cell Type and Tissue Gene Expression Profiles	cell types and tissues with high or low expression of KLF4 gene relative to other cell types and tissues from the BioGPS Human Cell Type and Tissue Gene Expression Profiles dataset.
	BioGPS Mouse Cell Type and Tissue Gene Expression Profiles	cell types and tissues with high or low expression of KLF4 gene relative to other cell types and tissues from the BioGPS Mouse Cell Type and Tissue Gene Expression Profiles dataset.
	CCLE Cell Line Gene CNV Profiles	cell lines with high or low copy number of KLF4 gene relative to other cell lines from the CCLE Cell Line Gene CNV Profiles dataset.
	CCLE Cell Line Gene Expression Profiles	cell lines with high or low expression of KLF4 gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CCLE Cell Line Proteomics	Cell lines associated with KLF4 protein from the CCLE Cell Line Proteomics dataset.
	CellMarker Gene-Cell Type Associations	cell types associated with KLF4 gene from the CellMarker Gene-Cell Type Associations dataset.
	ChEA Transcription Factor Binding Site Profiles	transcription factor binding site profiles with transcription factor binding evidence at the promoter of KLF4 gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of KLF4 gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets dataset.
	ChEA Transcription Factor Targets 2022	transcription factors binding the promoter of KLF4 gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets 2022 dataset.
	CMAP Signatures of Differentially Expressed Genes for Small Molecules	small molecule perturbations changing expression of KLF4 gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing KLF4 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores 2025	cellular components containing KLF4 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Experimental Protein Localization Evidence Scores	cellular components containing KLF4 protein in low- or high-throughput protein localization assays from the COMPARTMENTS Experimental Protein Localization Evidence Scores dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores	cellular components co-occuring with KLF4 protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025	cellular components co-occuring with KLF4 protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025 dataset.
	COSMIC Cell Line Gene CNV Profiles	cell lines with high or low copy number of KLF4 gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with KLF4 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Chemical Interactions	chemicals interacting with KLF4 gene/protein from the curated CTD Gene-Chemical Interactions dataset.
	CTD Gene-Disease Associations	diseases associated with KLF4 gene/protein from the curated CTD Gene-Disease Associations dataset.
	DeepCoverMOA Drug Mechanisms of Action	small molecule perturbations with high or low expression of KLF4 protein relative to other small molecule perturbations from the DeepCoverMOA Drug Mechanisms of Action dataset.
	DepMap CRISPR Gene Dependency	cell lines with fitness changed by KLF4 gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset.
	DISEASES Experimental Gene-Disease Association Evidence Scores	diseases associated with KLF4 gene in GWAS datasets from the DISEASES Experimental Gene-Disease Assocation Evidence Scores dataset.
	DISEASES Experimental Gene-Disease Association Evidence Scores 2025	diseases associated with KLF4 gene in GWAS datasets from the DISEASES Experimental Gene-Disease Assocation Evidence Scores 2025 dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores	diseases co-occuring with KLF4 gene in abstracts of biomedical publications from the DISEASES Text-mining Gene-Disease Assocation Evidence Scores dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores 2025	diseases co-occuring with KLF4 gene in abstracts of biomedical publications from the DISEASES Text-mining Gene-Disease Assocation Evidence Scores 2025 dataset.
	DisGeNET Gene-Disease Associations	diseases associated with KLF4 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with KLF4 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Phenoptype Associations dataset.
	ENCODE Histone Modification Site Profiles	histone modification site profiles with high histone modification abundance at KLF4 gene from the ENCODE Histone Modification Site Profiles dataset.
	ENCODE Transcription Factor Binding Site Profiles	transcription factor binding site profiles with transcription factor binding evidence at the promoter of KLF4 gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of KLF4 gene in ChIP-seq datasets from the ENCODE Transcription Factor Targets dataset.
	ESCAPE Omics Signatures of Genes and Proteins for Stem Cells	PubMedIDs of publications reporting gene signatures containing KLF4 from the ESCAPE Omics Signatures of Genes and Proteins for Stem Cells dataset.
	GAD Gene-Disease Associations	diseases associated with KLF4 gene in GWAS and other genetic association datasets from the GAD Gene-Disease Associations dataset.
	GAD High Level Gene-Disease Associations	diseases associated with KLF4 gene in GWAS and other genetic association datasets from the GAD High Level Gene-Disease Associations dataset.