MLLT3 Gene

Name	myeloid/lymphoid or mixed-lineage leukemia (trithorax homolog, Drosophila); translocated to, 3
Description	Enables chromatin binding activity; lysine-acetylated histone binding activity; and molecular adaptor activity. Involved in several processes, including hematopoietic stem cell differentiation; positive regulation of DNA-templated transcription; and regulation of stem cell division. Acts upstream of or within negative regulation of canonical Wnt signaling pathway and positive regulation of Wnt signaling pathway, planar cell polarity pathway. Located in cytosol and nucleoplasm. Part of transcription elongation factor complex. [provided by Alliance of Genome Resources, Mar 2025]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nMLLT3, also known as AF9, is an essential regulator in normal hematopoiesis. It is highly enriched in fetal, neonatal, and adult hematopoietic stem and progenitor cells where it safeguards the stem cell transcriptional program, sustains appropriate histone methylation (e.g. H3K79me2), and promotes early cell fate decisions—such as favoring erythroid and megakaryocytic lineages—thereby ensuring proper self‐renewal and differentiation."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "4"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nAt the molecular level, MLLT3 functions as a multifaceted epigenetic regulator. Its evolutionarily conserved YEATS domain serves as a “reader” of histone acylation marks by selectively binding acetylated and crotonylated lysines—discriminating among distinct acyl modifications—to link chromatin state with active transcription. In addition, its intrinsically disordered ANC1 homology domain mediates dynamic interactions with key transcriptional co-regulators such as DOT1L, BCOR, and CBX8, and is involved in modulating transcription elongation and initiation. Furthermore, MLLT3 participates in wider transcriptional control by interacting with factors like Diversin and influencing stress‐response gene expression (e.g. Hsp70), collectively integrating histone modification signals with transcriptional and post‐transcriptional regulatory networks."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "5", "end_ref": "16"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nPathologically, aberrations involving MLLT3—most notably as part of MLL-AF9 fusion proteins—misdirect its normal transcriptional regulatory activity, thereby driving the initiation and propagation of aggressive leukemias with diverse lineage phenotypes. In these malignant contexts the fusion hijacks MLLT3’s ability to coordinate chromatin modifications, leading to deregulated transcription and altered gene expression programs that are prognostically significant in acute myeloid leukemia. Moreover, dysregulated MLLT3 function also appears to influence tumor cell behavior in solid malignancies, where reduced AF9 activity has been associated with enhanced cell invasion and metastasis."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "17", "end_ref": "20"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Tatsuya Nakamura, Eli Canaani, Carlo M Croce "}, {"type": "b", "children": [{"type": "t", "text": "Oncogenic All1 fusion proteins target Drosha-mediated microRNA processing."}]}, {"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.0704559104"}], "href": "https://doi.org/10.1073/pnas.0704559104"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17581865"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17581865"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Cristina Pina, Gillian May, Shamit Soneji, et al. "}, {"type": "b", "children": [{"type": "t", "text": "MLLT3 regulates early human erythroid and megakaryocytic cell fate."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Stem Cell (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.stem.2008.01.013"}], "href": "https://doi.org/10.1016/j.stem.2008.01.013"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18371451"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18371451"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Vincenzo Calvanese, Andrew T Nguyen, Timothy J Bolan, et al. "}, {"type": "b", "children": [{"type": "t", "text": "MLLT3 governs human haematopoietic stem-cell self-renewal and engraftment."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nature (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41586-019-1790-2"}], "href": "https://doi.org/10.1038/s41586-019-1790-2"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31776511"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31776511"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Ashish Kabra, John Bushweller "}, {"type": "b", "children": [{"type": "t", "text": "The Intrinsically Disordered Proteins MLLT3 (AF9) and MLLT1 (ENL) - Multimodal Transcriptional Switches With Roles in Normal Hematopoiesis, MLL Fusion Leukemia, and Kidney Cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Mol Biol (2022)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.jmb.2021.167117"}], "href": "https://doi.org/10.1016/j.jmb.2021.167117"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "34174329"}], "href": "https://pubmed.ncbi.nlm.nih.gov/34174329"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Ramachandran Haribaskar, Michael Pütz, Birte Schupp, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The planar cell polarity (PCP) protein Diversin translocates to the nucleus to interact with the transcription factor AF9."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochem Biophys Res Commun (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.bbrc.2009.07.012"}], "href": "https://doi.org/10.1016/j.bbrc.2009.07.012"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19591803"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19591803"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Mary Rose Reisenauer, Marc Anderson, Le Huang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "AF17 competes with AF9 for binding to Dot1a to up-regulate transcription of epithelial Na+ channel alpha."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M109.038448"}], "href": "https://doi.org/10.1074/jbc.M109.038448"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19864429"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19864429"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Benjamin I Leach, Aravinda Kuntimaddi, Charles R Schmidt, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Leukemia fusion target AF9 is an intrinsically disordered transcriptional regulator that recruits multiple partners via coupled folding and binding."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Structure (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.str.2012.11.011"}], "href": "https://doi.org/10.1016/j.str.2012.11.011"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23260655"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23260655"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Yuanyuan Li, Hong Wen, Yuanxin Xi, et al. "}, {"type": "b", "children": [{"type": "t", "text": "AF9 YEATS domain links histone acetylation to DOT1L-mediated H3K79 methylation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.cell.2014.09.049"}], "href": "https://doi.org/10.1016/j.cell.2014.09.049"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25417107"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25417107"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Nisha N Barretto, Dean S Karahalios, Dewen You, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "Structural Insights into Histone Crotonyl-Lysine Recognition by the AF9 YEATS Domain."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Structure (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.str.2016.05.023"}], "href": "https://doi.org/10.1016/j.str.2016.05.023"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27545619"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27545619"}]}, {"type": "r", "ref": 14, "children": [{"type": "t", "text": "Charles R Schmidt, Nicholas J Achille, Aravinda Kuntimaddi, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "Sequential array comparative genomic hybridization analysis identifies copy number changes during blastic transformation of chronic myeloid leukemia."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Leuk Res (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.leukres.2011.12.021"}], "href": "https://doi.org/10.1016/j.leukres.2011.12.021"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22309891"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22309891"}]}, {"type": "r", "ref": 19, "children": [{"type": "t", "text": "Xin Tian, Hua Yu, Dong Li, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "AF9 sustains glycolysis in colorectal cancer via H3K9ac-mediated PCK2 and FBP1 transcription."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Clin Transl Med (2023)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/ctm2.1352"}], "href": "https://doi.org/10.1002/ctm2.1352"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "37565737"}], "href": "https://pubmed.ncbi.nlm.nih.gov/37565737"}]}]}]}
Synonyms	AF9, YEATS3
Proteins	AF9_HUMAN
NCBI Gene ID	4300
API
Download Associations
Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

MLLT3 has 8,266 functional associations with biological entities spanning 9 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, sequence feature) extracted from 133 datasets.

Click the + buttons to view associations for MLLT3 from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

MLLT3 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 MLLT3 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 MLLT3 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 MLLT3 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 MLLT3 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 MLLT3 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 MLLT3 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 MLLT3 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 MLLT3 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 MLLT3 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 MLLT3 gene from the Carcinogenome Chemical Perturbation Carcinogenicity Signatures dataset.
	CCLE Cell Line Gene CNV Profiles	cell lines with high or low copy number of MLLT3 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 MLLT3 gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CCLE Cell Line Gene Mutation Profiles	cell lines with MLLT3 gene mutations from the CCLE Cell Line Gene Mutation Profiles dataset.
	CCLE Cell Line Proteomics	Cell lines associated with MLLT3 protein from the CCLE Cell Line Proteomics dataset.
	CellMarker Gene-Cell Type Associations	cell types associated with MLLT3 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 MLLT3 gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of MLLT3 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 MLLT3 gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets 2022 dataset.
	CM4AI U2OS Cell Map Protein Localization Assemblies	assemblies containing MLLT3 protein from integrated AP-MS and IF data from the CM4AI U2OS Cell Map Protein Localization Assemblies dataset.
	CMAP Signatures of Differentially Expressed Genes for Small Molecules	small molecule perturbations changing expression of MLLT3 gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing MLLT3 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Experimental Protein Localization Evidence Scores	cellular components containing MLLT3 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 MLLT3 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 MLLT3 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 MLLT3 gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with MLLT3 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Disease Associations	diseases associated with MLLT3 gene/protein from the curated CTD Gene-Disease Associations dataset.
	dbGAP Gene-Trait Associations	traits associated with MLLT3 gene in GWAS and other genetic association datasets from the dbGAP Gene-Trait Associations dataset.
	DeepCoverMOA Drug Mechanisms of Action	small molecule perturbations with high or low expression of MLLT3 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 MLLT3 gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset.
	DISEASES Curated Gene-Disease Association Evidence Scores	diseases involving MLLT3 gene from the DISEASES Curated Gene-Disease Assocation Evidence Scores dataset.
	DISEASES Curated Gene-Disease Association Evidence Scores 2025	diseases involving MLLT3 gene from the DISEASES Curated Gene-Disease Association Evidence Scores 2025 dataset.
	DISEASES Experimental Gene-Disease Association Evidence Scores	diseases associated with MLLT3 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 MLLT3 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 MLLT3 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 MLLT3 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 MLLT3 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with MLLT3 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 MLLT3 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 MLLT3 gene from the ENCODE Transcription Factor Binding Site Profiles dataset.