KDM6B Gene

HGNC Family	Chromatin-modifying enzymes
Name	lysine (K)-specific demethylase 6B
Description	The protein encoded by this gene is a lysine-specific demethylase that specifically demethylates di- or tri-methylated lysine 27 of histone H3 (H3K27me2 or H3K27me3). H3K27 trimethylation is a repressive epigenetic mark controlling chromatin organization and gene silencing. This protein can also demethylate non-histone proteins such as retinoblastoma protein. Through its demethylation actvity this gene influences cellular differentiation and development, tumorigenesis, inflammatory diseases, and neurodegenerative diseases. This protein has two classical nuclear localization signals at its N-terminus. Alternative splicing results in multiple transcript variants encoding distinct isoforms. [provided by RefSeq, Feb 2017]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n KDM6B (also known as JMJD3) is a histone demethylase that specifically removes trimethylation on lysine 27 of histone H3 (H3K27me3), a repressive chromatin mark deposited by Polycomb repressive complexes. Through this activity, KDM6B facilitates the activation of key developmental and lineage‐specific genes that are otherwise silenced, thereby driving proper embryogenesis and differentiation. For example, its demethylation of H3K27me3 at HOX and other developmental loci is critical for stem cell fate transitions and neural, epidermal, and mesenchymal lineage commitment."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "3"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n In the immune system, KDM6B is rapidly induced in response to inflammatory cues. It plays a pivotal role in macrophage polarization by promoting the transition toward an anti‐inflammatory (M2) phenotype and by fine‐tuning the transcriptional output of inflammatory genes. Interestingly, KDM6B functions both through its canonical demethylase activity to remove H3K27me3 as well as via demethylase‐independent mechanisms that modulate RNA polymerase II recruitment and downstream gene expression."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "4", "end_ref": "7"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Moreover, KDM6B contributes to cellular senescence and tumorigenesis. Its activity facilitates the activation of tumor suppressor genes such as p16INK4A, thus contributing to senescence programs; yet in other contexts – as seen in T‐cell acute lymphoblastic leukemia, prostate cancer, and HPV‐associated cervical malignancies – aberrant regulation of KDM6B reprograms the epigenome, modulating oncogenic gene expression and impacting disease progression."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "8", "end_ref": "10"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Finally, in mesenchymal stem cells, KDM6B helps determine cell fate by promoting osteogenic differentiation while suppressing adipogenic programs through epigenetic remodeling of lineage‐specific gene networks."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "11"}]}, {"type": "t", "text": " Overall, these findings underscore KDM6B’s multifaceted role as an integrator of extrinsic signals—ranging from developmental cues to inflammatory and stress responses—with chromatin modifications, thereby governing cell fate decisions and contributing to both normal physiology and disease pathogenesis.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Karl Agger, Paul A C Cloos, Jesper Christensen, et al. "}, {"type": "b", "children": [{"type": "t", "text": "UTX and JMJD3 are histone H3K27 demethylases involved in HOX gene regulation and development."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nature (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/nature06145"}], "href": "https://doi.org/10.1038/nature06145"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17713478"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17713478"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Sunhwa Hong, Young-Wook Cho, Li-Rong Yu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Identification of JmjC domain-containing UTX and JMJD3 as histone H3 lysine 27 demethylases."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.0707292104"}], "href": "https://doi.org/10.1073/pnas.0707292104"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18003914"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18003914"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "George L Sen, Daniel E Webster, Deborah I Barragan, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Control of differentiation in a self-renewing mammalian tissue by the histone demethylase JMJD3."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Genes Dev (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1101/gad.1673508"}], "href": "https://doi.org/10.1101/gad.1673508"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18628393"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18628393"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Takashi Satoh, Osamu Takeuchi, Alexis Vandenbon, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The Jmjd3-Irf4 axis regulates M2 macrophage polarization and host responses against helminth infection."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Immunol (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/ni.1920"}], "href": "https://doi.org/10.1038/ni.1920"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20729857"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20729857"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Francesca De Santa, Maria Grazia Totaro, Elena Prosperini, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The histone H3 lysine-27 demethylase Jmjd3 links inflammation to inhibition of polycomb-mediated gene silencing."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.cell.2007.08.019"}], "href": "https://doi.org/10.1016/j.cell.2007.08.019"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17825402"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17825402"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Francesca De Santa, Vipin Narang, Zhei Hwee Yap, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Jmjd3 contributes to the control of gene expression in LPS-activated macrophages."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "EMBO J (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/emboj.2009.271"}], "href": "https://doi.org/10.1038/emboj.2009.271"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19779457"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19779457"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Y Tang, T Li, J Li, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Jmjd3 is essential for the epigenetic modulation of microglia phenotypes in the immune pathogenesis of Parkinson's disease."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Death Differ (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/cdd.2013.159"}], "href": "https://doi.org/10.1038/cdd.2013.159"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24212761"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24212761"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Karl Agger, Paul A C Cloos, Lise Rudkjaer, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The H3K27me3 demethylase JMJD3 contributes to the activation of the INK4A-ARF locus in response to oncogene- and stress-induced senescence."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Genes Dev (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1101/gad.510809"}], "href": "https://doi.org/10.1101/gad.510809"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19451217"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19451217"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Yang Xiang, Ziqi Zhu, Gang Han, et al. "}, {"type": "b", "children": [{"type": "t", "text": "JMJD3 is a histone H3K27 demethylase."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Res (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/cr.2007.83"}], "href": "https://doi.org/10.1038/cr.2007.83"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17923864"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17923864"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "Margaret E McLaughlin-Drubin, Christopher P Crum, Karl Münger "}, {"type": "b", "children": [{"type": "t", "text": "Human papillomavirus E7 oncoprotein induces KDM6A and KDM6B histone demethylase expression and causes epigenetic reprogramming."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.1009933108"}], "href": "https://doi.org/10.1073/pnas.1009933108"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21245294"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21245294"}]}, {"type": "r", "ref": 11, "children": [{"type": "t", "text": "Ling Ye, Zhipeng Fan, Bo Yu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Histone demethylases KDM4B and KDM6B promotes osteogenic differentiation of human MSCs."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Stem Cell (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.stem.2012.04.009"}], "href": "https://doi.org/10.1016/j.stem.2012.04.009"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22770241"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22770241"}]}]}]}
Synonyms	JMJD3
Proteins	KDM6B_HUMAN
NCBI Gene ID	23135
API
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Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

KDM6B has 8,986 functional associations with biological entities spanning 9 categories (molecular profile, organism, chemical, disease, phenotype or trait, functional term, phrase or reference, structural feature, cell line, cell type or tissue, gene, protein or microRNA, sequence feature) extracted from 119 datasets.

Click the + buttons to view associations for KDM6B from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

KDM6B 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 KDM6B 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 KDM6B 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 KDM6B 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 KDM6B 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 KDM6B 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 KDM6B 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 KDM6B 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 KDM6B gene relative to other cell types and tissues from the BioGPS Human Cell Type and Tissue Gene Expression Profiles dataset.
	Carcinogenome Chemical Perturbation Carcinogenicity Signatures	small molecule perturbations changing expression of KDM6B gene from the Carcinogenome Chemical Perturbation Carcinogenicity Signatures dataset.
	CCLE Cell Line Gene CNV Profiles	cell lines with high or low copy number of KDM6B 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 KDM6B gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CCLE Cell Line Proteomics	Cell lines associated with KDM6B protein from the CCLE Cell Line Proteomics dataset.
	CellMarker Gene-Cell Type Associations	cell types associated with KDM6B 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 KDM6B gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of KDM6B 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 KDM6B gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets 2022 dataset.
	ClinVar Gene-Phenotype Associations 2025	phenotypes associated with KDM6B gene from the curated ClinVar Gene-Phenotype Associations 2025 dataset.
	CM4AI KOLF21J CRISPRi Gene Perturbation Atlas	gene perturbations changing expression of KDM6B gene from the CM4AI KOLF21J CRISPRi Gene Perturbation Atlas dataset.
	CMAP Signatures of Differentially Expressed Genes for Small Molecules	small molecule perturbations changing expression of KDM6B gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing KDM6B protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores 2025	cellular components containing KDM6B protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Experimental Protein Localization Evidence Scores 2025	cellular components containing KDM6B 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 KDM6B 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 KDM6B 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 KDM6B gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with KDM6B gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Disease Associations	diseases associated with KDM6B gene/protein from the curated CTD Gene-Disease Associations dataset.
	DeepCoverMOA Drug Mechanisms of Action	small molecule perturbations with high or low expression of KDM6B 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 KDM6B gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset.
	DGIdb Drug Targets 2026	interacting drugs for KDM6B protein from the DGIdb Drug Targets 2026 dataset.
	DISEASES Experimental Gene-Disease Association Evidence Scores 2025	diseases associated with KDM6B 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 KDM6B 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 KDM6B 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 KDM6B gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with KDM6B 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 KDM6B 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 KDM6B gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of KDM6B 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 KDM6B 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 KDM6B gene relative to other cell lines from the GDSC Cell Line Gene Expression Profiles dataset.