KLF9 Gene

HGNC Family	Zinc fingers
Name	Kruppel-like factor 9
Description	The protein encoded by this gene is a transcription factor that binds to GC box elements located in the promoter. Binding of the encoded protein to a single GC box inhibits mRNA expression while binding to tandemly repeated GC box elements activates transcription. [provided by RefSeq, Jul 2008]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n Krüppel‐like factor 9 (KLF9) is emerging as a context‐dependent transcriptional regulator whose functions span multiple organ systems and cellular processes. In models of oxidative stress, for example, severe elevations in reactive oxygen species trigger Nrf2‐dependent induction of KLF9. Elevated KLF9 then represses the expression of mitochondrial ROS‐eliminating enzymes, thereby establishing a feed‐forward loop that further increases oxidative stress and promotes cell death."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n In the central nervous system, thyroid hormone (T3) rapidly induces KLF9 in oligodendrocyte precursor cells – a process that is both necessary and sufficient to drive differentiation and promote remyelination in demyelinated lesions, even though its loss during developmental myelination appears minimal."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": " Similarly, in the hippocampus, activity‐dependent and T3‐regulated induction of KLF9 supports the late‐phase maturation of dentate granule neurons, thereby affecting synaptic plasticity and aspects of behavior."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n KLF9 also plays a role in the regulation of cell growth and differentiation in peripheral tissues. In the skin, KLF9 is characterized as a circadian transcription factor whose expression is regulated by cortisol and the state of keratinocyte differentiation; its activity exerts potent antiproliferative effects and influences the timing of keratinocyte maturation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": " In adipogenesis, KLF9 is markedly upregulated during the mid‐phase of 3T3‐L1 differentiation and is essential for activating adipogenic regulators such as PPARγ2 in cooperation with C/EBPα, thus promoting proper adipocyte maturation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n In cancer stem cells derived from glioblastoma, KLF9 acts as a differentiating and tumor‐suppressive factor. Its induction – notably in response to Notch1 signaling – leads to suppression of Notch1 expression and downstream signaling, thereby curtailing neurosphere formation and tumor growth."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n In reproductive tissues, KLF9 contributes to progesterone receptor (PGR)–mediated transcriptional regulation. In human endometrial stromal cells, reduced expression of KLF9 correlates with a diminished response to progesterone signaling and may underlie aspects of progesterone resistance seen in endometriosis, likely through its coregulatory actions with PGR at target gene promoters such as that of Dickkopf-1."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "10"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Finally, in liver metabolism, KLF9 is induced by glucocorticoids and fasting. It directly activates key gluconeogenic regulators like PGC1α, thereby contributing to increased hepatic glucose output and, when overexpressed, to hyperglycemia. Conversely, KLF9 deficiency promotes fasting hypoglycemia and ameliorates dexamethasone-induced hyperglycemia."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "11"}]}, {"type": "t", "text": " Moreover, in macrophages, KLF9 appears to participate in a feed-forward regulatory loop with the glucocorticoid receptor and KLF2, thereby helping to coordinate anti-inflammatory responses."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "12"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Collectively, these findings delineate KLF9 as a versatile transcription factor that modulates oxidative stress responses, drives differentiation in neural, epidermal, and adipocyte lineages, suppresses tumorigenesis in glioblastoma stem cells, and regulates metabolic and inflammatory pathways in liver and immune cells.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Shuya Kasai, Sunao Shimizu, Yota Tatara, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Regulation of Nrf2 by Mitochondrial Reactive Oxygen Species in Physiology and Pathology."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biomolecules (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3390/biom10020320"}], "href": "https://doi.org/10.3390/biom10020320"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32079324"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32079324"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Shoshanna N Zucker, Emily E Fink, Archis Bagati, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Nrf2 amplifies oxidative stress via induction of Klf9."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cell (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.molcel.2014.01.033"}], "href": "https://doi.org/10.1016/j.molcel.2014.01.033"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24613345"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24613345"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Jason C Dugas, Adiljan Ibrahim, Ben A Barres "}, {"type": "b", "children": [{"type": "t", "text": "The T3-induced gene KLF9 regulates oligodendrocyte differentiation and myelin regeneration."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cell Neurosci (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.mcn.2012.03.007"}], "href": "https://doi.org/10.1016/j.mcn.2012.03.007"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22472204"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22472204"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Kimberly N Scobie, Benjamin J Hall, Scott A Wilke, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Krüppel-like factor 9 is necessary for late-phase neuronal maturation in the developing dentate gyrus and during adult hippocampal neurogenesis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Neurosci (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1523/JNEUROSCI.2260-09.2009"}], "href": "https://doi.org/10.1523/JNEUROSCI.2260-09.2009"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19657039"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19657039"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Robert J Denver, Keith E Williamson "}, {"type": "b", "children": [{"type": "t", "text": "Identification of a thyroid hormone response element in the mouse Kruppel-like factor 9 gene to explain its postnatal expression in the brain."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Endocrinology (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1210/en.2009-0050"}], "href": "https://doi.org/10.1210/en.2009-0050"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19359381"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19359381"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Florian Spörl, Sandra Korge, Karsten Jürchott, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Krüppel-like factor 9 is a circadian transcription factor in human epidermis that controls proliferation of keratinocytes."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.1118641109"}], "href": "https://doi.org/10.1073/pnas.1118641109"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22711835"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22711835"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "H Pei, Y Yao, Y Yang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Krüppel-like factor KLF9 regulates PPARγ transactivation at the middle stage of adipogenesis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Death Differ (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/cdd.2010.100"}], "href": "https://doi.org/10.1038/cdd.2010.100"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20725087"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20725087"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Pierre-Olivier Guichet, Sophie Guelfi, Marisa Teigell, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Notch1 stimulation induces a vascularization switch with pericyte-like cell differentiation of glioblastoma stem cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Stem Cells (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/stem.1767"}], "href": "https://doi.org/10.1002/stem.1767"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24898819"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24898819"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Mingyao Ying, Yingying Sang, Yunqing Li, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Krüppel-like family of transcription factor 9, a differentiation-associated transcription factor, suppresses Notch1 signaling and inhibits glioblastoma-initiating stem cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Stem Cells (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/stem.561"}], "href": "https://doi.org/10.1002/stem.561"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21280156"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21280156"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "John Mark P Pabona, Frank A Simmen, Mikhail A Nikiforov, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Krüppel-like factor 9 and progesterone receptor coregulation of decidualizing endometrial stromal cells: implications for the pathogenesis of endometriosis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Clin Endocrinol Metab (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1210/jc.2011-2562"}], "href": "https://doi.org/10.1210/jc.2011-2562"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22259059"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22259059"}]}, {"type": "r", "ref": 11, "children": [{"type": "t", "text": "Anfang Cui, Heng Fan, Yinliang Zhang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Dexamethasone-induced Krüppel-like factor 9 expression promotes hepatic gluconeogenesis and hyperglycemia."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Clin Invest (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1172/JCI66062"}], "href": "https://doi.org/10.1172/JCI66062"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31033478"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31033478"}]}, {"type": "r", "ref": 12, "children": [{"type": "t", "text": "Yurii Chinenov, Maddalena Coppo, Rebecca Gupte, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Glucocorticoid receptor coordinates transcription factor-dominated regulatory network in macrophages."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "BMC Genomics (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1186/1471-2164-15-656"}], "href": "https://doi.org/10.1186/1471-2164-15-656"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25099603"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25099603"}]}]}]}
Synonyms	BTEB1, BTEB
Proteins	KLF9_HUMAN
NCBI Gene ID	687
API
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Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

KLF9 has 8,480 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 107 datasets.

Click the + buttons to view associations for KLF9 from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

KLF9 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 KLF9 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 KLF9 gene relative to other tissues from the Allen Brain Atlas Adult Mouse Brain Tissue Gene Expression Profiles dataset.
	Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray	tissue samples with high or low expression of KLF9 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 KLF9 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 KLF9 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 KLF9 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 KLF9 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 KLF9 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 KLF9 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 KLF9 gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CellMarker Gene-Cell Type Associations	cell types associated with KLF9 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 KLF9 gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of KLF9 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 KLF9 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 KLF9 gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing KLF9 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Experimental Protein Localization Evidence Scores	cellular components containing KLF9 protein in low- or high-throughput protein localization assays from the COMPARTMENTS Experimental Protein Localization Evidence Scores dataset.
	COMPARTMENTS Experimental Protein Localization Evidence Scores 2025	cellular components containing KLF9 protein in low- or high-throughput protein localization assays from the COMPARTMENTS Experimental Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores	cellular components co-occuring with KLF9 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 KLF9 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 KLF9 gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with KLF9 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Chemical Interactions	chemicals interacting with KLF9 gene/protein from the curated CTD Gene-Chemical Interactions dataset.
	CTD Gene-Disease Associations	diseases associated with KLF9 gene/protein from the curated CTD Gene-Disease Associations dataset.
	DepMap CRISPR Gene Dependency	cell lines with fitness changed by KLF9 gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset.
	DISEASES Experimental Gene-Disease Association Evidence Scores	diseases associated with KLF9 gene in GWAS datasets from the DISEASES Experimental Gene-Disease Assocation Evidence Scores dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores	diseases co-occuring with KLF9 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 KLF9 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 KLF9 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with KLF9 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 KLF9 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 KLF9 gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of KLF9 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 KLF9 from the ESCAPE Omics Signatures of Genes and Proteins for Stem Cells dataset.
	GDSC Cell Line Gene Expression Profiles	cell lines with high or low expression of KLF9 gene relative to other cell lines from the GDSC Cell Line Gene Expression Profiles dataset.
	GeneRIF Biological Term Annotations	biological terms co-occuring with KLF9 gene in literature-supported statements describing functions of genes from the GeneRIF Biological Term Annotations dataset.
	GeneSigDB Published Gene Signatures	PubMedIDs of publications reporting gene signatures containing KLF9 from the GeneSigDB Published Gene Signatures dataset.
	GEO Signatures of Differentially Expressed Genes for Diseases	disease perturbations changing expression of KLF9 gene from the GEO Signatures of Differentially Expressed Genes for Diseases dataset.
	GEO Signatures of Differentially Expressed Genes for Gene Perturbations	gene perturbations changing expression of KLF9 gene from the GEO Signatures of Differentially Expressed Genes for Gene Perturbations dataset.
	GEO Signatures of Differentially Expressed Genes for Kinase Perturbations	kinase perturbations changing expression of KLF9 gene from the GEO Signatures of Differentially Expressed Genes for Kinase Perturbations dataset.