KMT2D Gene

HGNC Family Zinc fingers, Trinucleotide repeat containing (TNRC), Chromatin-modifying enzymes
Name lysine (K)-specific methyltransferase 2D
Description The protein encoded by this gene is a histone methyltransferase that methylates the Lys-4 position of histone H3. The encoded protein is part of a large protein complex called ASCOM, which has been shown to be a transcriptional regulator of the beta-globin and estrogen receptor genes. Mutations in this gene have been shown to be a cause of Kabuki syndrome. [provided by RefSeq, Oct 2010]
Summary
{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n KMT2D (also known as MLL2) is a SET1/MLL-family histone methyltransferase that catalyzes the mono‐, di‐, and trimethylation of histone H3 lysine 4 (H3K4), a key epigenetic modification associated with open chromatin, enhancer activation, and active transcription. In developmental contexts, loss‐of‐function mutations in KMT2D are a major cause of Kabuki syndrome, underscoring its essential role in orchestrating gene expression programs required for normal embryogenesis and tissue differentiation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " In addition, recurrent mutations in KMT2D have been identified in several cancers including follicular lymphoma and diffuse large B‐cell lymphoma where inactivation of its methyltransferase activity leads to diminished global H3K4 methylation, deregulation of genes involved in cell proliferation and differentiation, and an enhanced propensity for lymphomagenesis."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "2", "end_ref": "4"}]}, {"type": "t", "text": " Together, these findings indicate that KMT2D functions as a pivotal epigenetic regulator whose proper activity is required for both normal developmental processes and the suppression of tumor initiation.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Sarah B Ng, Abigail W Bigham, Kati J Buckingham, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Exome sequencing identifies MLL2 mutations as a cause of Kabuki syndrome."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Genet (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/ng.646"}], "href": "https://doi.org/10.1038/ng.646"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20711175"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20711175"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Ryan D Morin, Maria Mendez-Lago, Andrew J Mungall, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Frequent mutation of histone-modifying genes in non-Hodgkin lymphoma."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nature (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/nature10351"}], "href": "https://doi.org/10.1038/nature10351"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21796119"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21796119"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Jiyuan Zhang, David Dominguez-Sola, Shafinaz Hussein, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Disruption of KMT2D perturbs germinal center B cell development and promotes lymphomagenesis."}]}, {"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.3940"}], "href": "https://doi.org/10.1038/nm.3940"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26366712"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26366712"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Ana Ortega-Molina, Isaac W Boss, Andres Canela, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The histone lysine methyltransferase KMT2D sustains a gene expression program that represses B cell lymphoma development."}]}, {"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.3943"}], "href": "https://doi.org/10.1038/nm.3943"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26366710"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26366710"}]}]}]}
Synonyms KABUK1, MLL4, MLL2, CAGL114, AAD10, TNRC21
Proteins KMT2D_HUMAN
NCBI Gene ID 8085
API
Download Associations
Predicted Functions View KMT2D's ARCHS4 Predicted Functions.
Co-expressed Genes View KMT2D's ARCHS4 Predicted Functions.
Expression in Tissues and Cell Lines View KMT2D's ARCHS4 Predicted Functions.

Functional Associations

KMT2D has 8,070 functional associations with biological entities spanning 7 categories (molecular profile, chemical, disease, phenotype or trait, functional term, phrase or reference, structural feature, cell line, cell type or tissue, gene, protein or microRNA) extracted from 104 datasets.

Click the + buttons to view associations for KMT2D from the datasets below.

If available, associations are ranked by standardized value

Dataset Summary
Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles tissues with high or low expression of KMT2D gene relative to other tissues from the Allen Brain Atlas Adult Human 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 KMT2D 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 KMT2D 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 KMT2D 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 KMT2D gene relative to other tissues from the Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles dataset.
BioGPS Mouse Cell Type and Tissue Gene Expression Profiles cell types and tissues with high or low expression of KMT2D gene relative to other cell types and tissues from the BioGPS Mouse Cell Type and Tissue Gene Expression Profiles dataset.
Carcinogenome Chemical Perturbation Carcinogenicity Signatures small molecule perturbations changing expression of KMT2D gene from the Carcinogenome Chemical Perturbation Carcinogenicity Signatures dataset.
CCLE Cell Line Gene CNV Profiles cell lines with high or low copy number of KMT2D gene relative to other cell lines from the CCLE Cell Line Gene CNV Profiles dataset.
CCLE Cell Line Proteomics Cell lines associated with KMT2D protein from the CCLE Cell Line Proteomics dataset.
ChEA Transcription Factor Binding Site Profiles transcription factor binding site profiles with transcription factor binding evidence at the promoter of KMT2D gene from the CHEA Transcription Factor Binding Site Profiles dataset.
ChEA Transcription Factor Targets transcription factors binding the promoter of KMT2D 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 KMT2D gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets 2022 dataset.
ClinVar Gene-Phenotype Associations phenotypes associated with KMT2D gene from the curated ClinVar Gene-Phenotype Associations dataset.
ClinVar Gene-Phenotype Associations 2025 phenotypes associated with KMT2D gene from the curated ClinVar Gene-Phenotype Associations 2025 dataset.
CM4AI U2OS Cell Map Protein Localization Assemblies assemblies containing KMT2D protein from integrated AP-MS and IF data from the CM4AI U2OS Cell Map Protein Localization Assemblies dataset.
COMPARTMENTS Curated Protein Localization Evidence Scores 2025 cellular components containing KMT2D protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
COMPARTMENTS Experimental Protein Localization Evidence Scores 2025 cellular components containing KMT2D 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 2025 cellular components co-occuring with KMT2D protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025 dataset.
CORUM Protein Complexes protein complexs containing KMT2D protein from the CORUM Protein Complexes dataset.
COSMIC Cell Line Gene CNV Profiles cell lines with high or low copy number of KMT2D gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
COSMIC Cell Line Gene Mutation Profiles cell lines with KMT2D gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
CTD Gene-Disease Associations diseases associated with KMT2D gene/protein from the curated CTD Gene-Disease Associations dataset.
DISEASES Curated Gene-Disease Association Evidence Scores 2025 diseases involving KMT2D gene from the DISEASES Curated Gene-Disease Association Evidence Scores 2025 dataset.
DISEASES Experimental Gene-Disease Association Evidence Scores 2025 diseases associated with KMT2D gene in GWAS datasets from the DISEASES Experimental Gene-Disease Assocation Evidence Scores 2025 dataset.
DISEASES Text-mining Gene-Disease Association Evidence Scores 2025 diseases co-occuring with KMT2D 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 KMT2D gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
DisGeNET Gene-Phenotype Associations phenotypes associated with KMT2D 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 KMT2D 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 KMT2D gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
ENCODE Transcription Factor Targets transcription factors binding the promoter of KMT2D 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 KMT2D 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 KMT2D gene relative to other cell lines from the GDSC Cell Line Gene Expression Profiles dataset.
GeneRIF Biological Term Annotations biological terms co-occuring with KMT2D gene in literature-supported statements describing functions of genes from the GeneRIF Biological Term Annotations dataset.
GEO Signatures of Differentially Expressed Genes for Kinase Perturbations kinase perturbations changing expression of KMT2D gene from the GEO Signatures of Differentially Expressed Genes for Kinase Perturbations dataset.
GEO Signatures of Differentially Expressed Genes for Small Molecules small molecule perturbations changing expression of KMT2D gene from the GEO Signatures of Differentially Expressed Genes for Small Molecules dataset.
GEO Signatures of Differentially Expressed Genes for Transcription Factor Perturbations transcription factor perturbations changing expression of KMT2D gene from the GEO Signatures of Differentially Expressed Genes for Transcription Factor Perturbations dataset.
GO Biological Process Annotations 2015 biological processes involving KMT2D gene from the curated GO Biological Process Annotations 2015 dataset.
GO Biological Process Annotations 2023 biological processes involving KMT2D gene from the curated GO Biological Process Annotations 2023 dataset.
GO Biological Process Annotations 2025 biological processes involving KMT2D gene from the curated GO Biological Process Annotations2025 dataset.
GO Cellular Component Annotations 2015 cellular components containing KMT2D protein from the curated GO Cellular Component Annotations 2015 dataset.
GO Cellular Component Annotations 2023 cellular components containing KMT2D protein from the curated GO Cellular Component Annotations 2023 dataset.
GO Cellular Component Annotations 2025 cellular components containing KMT2D protein from the curated GO Cellular Component Annotations 2025 dataset.
GO Molecular Function Annotations 2015 molecular functions performed by KMT2D gene from the curated GO Molecular Function Annotations 2015 dataset.
GO Molecular Function Annotations 2023 molecular functions performed by KMT2D gene from the curated GO Molecular Function Annotations 2023 dataset.
GO Molecular Function Annotations 2025 molecular functions performed by KMT2D gene from the curated GO Molecular Function Annotations 2025 dataset.
GTEx Tissue Gene Expression Profiles tissues with high or low expression of KMT2D gene relative to other tissues from the GTEx Tissue Gene Expression Profiles dataset.
GTEx Tissue Gene Expression Profiles 2023 tissues with high or low expression of KMT2D gene relative to other tissues from the GTEx Tissue Gene Expression Profiles 2023 dataset.
GTEx Tissue Sample Gene Expression Profiles tissue samples with high or low expression of KMT2D gene relative to other tissue samples from the GTEx Tissue Sample Gene Expression Profiles dataset.
GTEx Tissue-Specific Aging Signatures tissue samples with high or low expression of KMT2D gene relative to other tissue samples from the GTEx Tissue-Specific Aging Signatures dataset.
GWAS Catalog SNP-Phenotype Associations 2025 phenotypes associated with KMT2D gene in GWAS datasets from the GWAS Catalog SNP-Phenotype Associations 2025 dataset.
HPA Cell Line Gene Expression Profiles cell lines with high or low expression of KMT2D gene relative to other cell lines from the HPA Cell Line Gene Expression Profiles dataset.
HPA Tissue Gene Expression Profiles tissues with high or low expression of KMT2D gene relative to other tissues from the HPA Tissue Gene Expression Profiles dataset.
HPA Tissue Protein Expression Profiles tissues with high or low expression of KMT2D protein relative to other tissues from the HPA Tissue Protein Expression Profiles dataset.
HPA Tissue Sample Gene Expression Profiles tissue samples with high or low expression of KMT2D gene relative to other tissue samples from the HPA Tissue Sample Gene Expression Profiles dataset.
HPO Gene-Disease Associations phenotypes associated with KMT2D gene by mapping known disease genes to disease phenotypes from the HPO Gene-Disease Associations dataset.
Hub Proteins Protein-Protein Interactions interacting hub proteins for KMT2D from the curated Hub Proteins Protein-Protein Interactions dataset.
HuGE Navigator Gene-Phenotype Associations phenotypes associated with KMT2D gene by text-mining GWAS publications from the HuGE Navigator Gene-Phenotype Associations dataset.
IMPC Knockout Mouse Phenotypes phenotypes of mice caused by KMT2D gene knockout from the IMPC Knockout Mouse Phenotypes dataset.
InterPro Predicted Protein Domain Annotations protein domains predicted for KMT2D protein from the InterPro Predicted Protein Domain Annotations dataset.
JASPAR Predicted Human Transcription Factor Targets 2025 transcription factors regulating expression of KMT2D gene predicted using known transcription factor binding site motifs from the JASPAR Predicted Human Transcription Factor Targets dataset.
JASPAR Predicted Mouse Transcription Factor Targets 2025 transcription factors regulating expression of KMT2D gene predicted using known transcription factor binding site motifs from the JASPAR Predicted Mouse Transcription Factor Targets 2025 dataset.
JASPAR Predicted Transcription Factor Targets transcription factors regulating expression of KMT2D gene predicted using known transcription factor binding site motifs from the JASPAR Predicted Transcription Factor Targets dataset.
KEA Substrates of Kinases kinases that phosphorylate KMT2D protein from the curated KEA Substrates of Kinases dataset.
KEGG Pathways 2026 pathways involving KMT2D protein from the KEGG Pathways 2026 dataset.
Kinase Library Serine Threonine Kinome Atlas kinases that phosphorylate KMT2D protein from the Kinase Library Serine Threonine Atlas dataset.
Klijn et al., Nat. Biotechnol., 2015 Cell Line Gene CNV Profiles cell lines with high or low copy number of KMT2D gene relative to other cell lines from the Klijn et al., Nat. Biotechnol., 2015 Cell Line Gene CNV Profiles dataset.
Klijn et al., Nat. Biotechnol., 2015 Cell Line Gene Expression Profiles cell lines with high or low expression of KMT2D gene relative to other cell lines from the Klijn et al., Nat. Biotechnol., 2015 Cell Line Gene Expression Profiles dataset.
Klijn et al., Nat. Biotechnol., 2015 Cell Line Gene Mutation Profiles cell lines with KMT2D gene mutations from the Klijn et al., Nat. Biotechnol., 2015 Cell Line Gene Mutation Profiles dataset.
LINCS L1000 CMAP Chemical Perturbation Consensus Signatures small molecule perturbations changing expression of KMT2D gene from the LINCS L1000 CMAP Chemical Perturbations Consensus Signatures dataset.
LINCS L1000 CMAP CRISPR Knockout Consensus Signatures gene perturbations changing expression of KMT2D gene from the LINCS L1000 CMAP CRISPR Knockout Consensus Signatures dataset.
LOCATE Curated Protein Localization Annotations cellular components containing KMT2D protein in low- or high-throughput protein localization assays from the LOCATE Curated Protein Localization Annotations dataset.
LOCATE Predicted Protein Localization Annotations cellular components predicted to contain KMT2D protein from the LOCATE Predicted Protein Localization Annotations dataset.
MGI Mouse Phenotype Associations 2023 phenotypes of transgenic mice caused by KMT2D gene mutations from the MGI Mouse Phenotype Associations 2023 dataset.
MiRTarBase microRNA Targets microRNAs targeting KMT2D gene in low- or high-throughput microRNA targeting studies from the MiRTarBase microRNA Targets dataset.
MotifMap Predicted Transcription Factor Targets transcription factors regulating expression of KMT2D gene predicted using known transcription factor binding site motifs from the MotifMap Predicted Transcription Factor Targets dataset.
MPO Gene-Phenotype Associations phenotypes of transgenic mice caused by KMT2D gene mutations from the MPO Gene-Phenotype Associations dataset.
MW Enzyme Metabolite Associations interacting metabolites for KMT2D protein from the MW Gene Metabolite Associations dataset.
NIBR DRUG-seq U2OS MoA Box Gene Expression Profiles drug perturbations changing expression of KMT2D gene from the NIBR DRUG-seq U2OS MoA Box dataset.
OMIM Gene-Disease Associations phenotypes associated with KMT2D gene from the curated OMIM Gene-Disease Associations dataset.
Pathway Commons Protein-Protein Interactions interacting proteins for KMT2D from the Pathway Commons Protein-Protein Interactions dataset.
PerturbAtlas Signatures of Differentially Expressed Genes for Gene Perturbations gene perturbations changing expression of KMT2D gene from the PerturbAtlas Signatures of Differentially Expressed Genes for Gene Perturbations dataset.
PerturbAtlas Signatures of Differentially Expressed Genes for Mouse Gene Perturbations gene perturbations changing expression of KMT2D gene from the PerturbAtlas Signatures of Differentially Expressed Genes for Gene Perturbations dataset.
PFOCR Pathway Figure Associations 2023 pathways involving KMT2D protein from the PFOCR Pathway Figure Associations 2023 dataset.
PFOCR Pathway Figure Associations 2024 pathways involving KMT2D protein from the Wikipathways PFOCR 2024 dataset.
PhosphoSitePlus Substrates of Kinases kinases that phosphorylate KMT2D protein from the curated PhosphoSitePlus Substrates of Kinases dataset.
Reactome Pathways 2014 pathways involving KMT2D protein from the Reactome Pathways dataset.
Reactome Pathways 2024 pathways involving KMT2D protein from the Reactome Pathways 2024 dataset.
Replogle et al., Cell, 2022 K562 Essential Perturb-seq Gene Perturbation Signatures gene perturbations changing expression of KMT2D gene from the Replogle et al., Cell, 2022 K562 Essential Perturb-seq Gene Perturbation Signatures dataset.
Replogle et al., Cell, 2022 K562 Genome-wide Perturb-seq Gene Perturbation Signatures gene perturbations changing expression of KMT2D gene from the Replogle et al., Cell, 2022 K562 Genome-wide Perturb-seq Gene Perturbation Signatures dataset.
Replogle et al., Cell, 2022 RPE1 Essential Perturb-seq Gene Perturbation Signatures gene perturbations changing expression of KMT2D gene from the Replogle et al., Cell, 2022 RPE1 Essential Perturb-seq Gene Perturbation Signatures dataset.
Roadmap Epigenomics Cell and Tissue DNA Methylation Profiles cell types and tissues with high or low DNA methylation of KMT2D gene relative to other cell types and tissues from the Roadmap Epigenomics Cell and Tissue DNA Methylation Profiles dataset.
RummaGEO Drug Perturbation Signatures drug perturbations changing expression of KMT2D gene from the RummaGEO Drug Perturbation Signatures dataset.
RummaGEO Gene Perturbation Signatures gene perturbations changing expression of KMT2D gene from the RummaGEO Gene Perturbation Signatures dataset.
Sanger Dependency Map Cancer Cell Line Proteomics cell lines associated with KMT2D protein from the Sanger Dependency Map Cancer Cell Line Proteomics dataset.
Sci-Plex Drug Perturbation Signatures drug perturbations changing expression of KMT2D gene from the Sci-Plex Drug Perturbation Signatures dataset.
SILAC Phosphoproteomics Signatures of Differentially Phosphorylated Proteins for Protein Ligands ligand (protein) perturbations changing phosphorylation of KMT2D protein from the SILAC Phosphoproteomics Signatures of Differentially Phosphorylated Proteins for Protein Ligands dataset.
Tahoe Therapeutics Tahoe 100M Perturbation Atlas drug perturbations changing expression of KMT2D gene from the Tahoe Therapeutics Tahoe 100M Perturbation Atlas dataset.
TargetScan Predicted Conserved microRNA Targets microRNAs regulating expression of KMT2D gene predicted using conserved miRNA seed sequences from the TargetScan Predicted Conserved microRNA Targets dataset.
TargetScan Predicted Nonconserved microRNA Targets microRNAs regulating expression of KMT2D gene predicted using nonconserved miRNA seed sequences from the TargetScan Predicted Nonconserved microRNA Targets dataset.
TISSUES Curated Tissue Protein Expression Evidence Scores 2025 tissues with high expression of KMT2D protein from the TISSUES Curated Tissue Protein Expression Evidence Scores 2025 dataset.
TISSUES Experimental Tissue Protein Expression Evidence Scores 2025 tissues with high expression of KMT2D protein in proteomics datasets from the TISSUES Experimental Tissue Protein Expression Evidence Scores 2025 dataset.
TISSUES Text-mining Tissue Protein Expression Evidence Scores 2025 tissues co-occuring with KMT2D protein in abstracts of biomedical publications from the TISSUES Text-mining Tissue Protein Expression Evidence Scores 2025 dataset.
WikiPathways Pathways 2014 pathways involving KMT2D protein from the Wikipathways Pathways 2014 dataset.
WikiPathways Pathways 2024 pathways involving KMT2D protein from the WikiPathways Pathways 2024 dataset.