MLF1 Gene

Name	myeloid leukemia factor 1
Description	This gene encodes an oncoprotein which is thought to play a role in the phenotypic determination of hemopoetic cells. Translocations between this gene and nucleophosmin have been associated with myelodysplastic syndrome and acute myeloid leukemia. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2010]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nRecent studies have revealed that myeloid leukemia factor 1 (MLF1) plays multifaceted roles in tumorigenesis, particularly in hematologic malignancies and neuroblastoma. Elevated MLF1 expression and common DNA variants upstream of its locus contribute to neuroblastoma susceptibility, while aberrant forms—such as the NPM‐MLF1 fusion protein—disrupt p53 regulation through its altered nucleocytoplasmic shuttling, thereby promoting cell proliferation and oncogenic transformation in acute myeloid leukemia and myelodysplastic syndromes."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "5"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nStructural and localization studies show that a phosphorylated segment of MLF1 binds to 14-3-3 adapter proteins—although intriguingly, full-length human MLF1 appears to achieve subcellular localization independent of this 14-3-3 interaction. In addition, MLF1’s association with adaptor proteins such as Madm modulates differentiation processes, highlighting the importance of protein–protein interactions in its regulatory functions."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond its role in cell growth and differentiation, MLF1 is implicated in transcriptional regulation. It is a component of a nuclear chaperone complex that associates with chromatin at promoters and enhancers, thereby influencing the stability of transcription factors like RUNX and modulating gene expression. Moreover, MLF1 interacts with mutant huntingtin aggregates to release sequestered transcriptional regulators such as p53, and its abundance is tightly controlled by opposing actions of ubiquitin ligase complexes and deubiquitinating enzymes."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "8", "end_ref": "10"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn addition, MLF1 influences apoptotic pathways by interacting with mitochondrial proteins. It can displace HtrA2 from the HAX1-associated HOP complex, resulting in impaired activation of proapoptotic signals and enhanced cell death. Furthermore, while overexpression of MLF1 in muscle leads to the formation of protein aggregates without overt functional deficits, emerging evidence also suggests a potential role in intrahepatic cholangiocarcinoma, emphasizing its diverse involvement in disease processes."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "11", "end_ref": "13"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Lee D McDaniel, Karina L Conkrite, Xiao Chang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Common variants upstream of MLF1 at 3q25 and within CPZ at 4p16 associated with neuroblastoma."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS Genet (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.pgen.1006787"}], "href": "https://doi.org/10.1371/journal.pgen.1006787"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28545128"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28545128"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Raelene Lim, Louise N Winteringham, James H Williams, et al. "}, {"type": "b", "children": [{"type": "t", "text": "MADM, a novel adaptor protein that mediates phosphorylation of the 14-3-3 binding site of myeloid leukemia factor 1."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2002)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M206041200"}], "href": "https://doi.org/10.1074/jbc.M206041200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12176995"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12176995"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Noriko Yoneda-Kato, Jun-Ya Kato "}, {"type": "b", "children": [{"type": "t", "text": "Shuttling imbalance of MLF1 results in p53 instability and increases susceptibility to oncogenic transformation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cell Biol (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1128/MCB.02335-06"}], "href": "https://doi.org/10.1128/MCB.02335-06"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17967869"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17967869"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Daniel A Arber, Karen L Chang, Mark H Lyda, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Detection of NPM/MLF1 fusion in t(3;5)-positive acute myeloid leukemia and myelodysplasia."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Hum Pathol (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/s0046-8177(03)00251-x"}], "href": "https://doi.org/10.1016/s0046-8177(03"}, {"type": "t", "text": "00251-x) PMID: "}, {"type": "a", "children": [{"type": "t", "text": "14506644"}], "href": "https://pubmed.ncbi.nlm.nih.gov/14506644"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Gayoung Lim, Jong Rak Choi, Min Jin Kim, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Detection of t(3;5) and NPM1/MLF1 rearrangement in an elderly patient with acute myeloid leukemia: clinical and laboratory study with review of the literature."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cancer Genet Cytogenet (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.cancergencyto.2010.02.009"}], "href": "https://doi.org/10.1016/j.cancergencyto.2010.02.009"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20471513"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20471513"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Manuela Molzan, Michael Weyand, Rolf Rose, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Structural insights of the MLF1/14-3-3 interaction."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "FEBS J (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/j.1742-4658.2011.08445.x"}], "href": "https://doi.org/10.1111/j.1742-4658.2011.08445.x"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22151054"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22151054"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Manuela Molzan, Christian Ottmann "}, {"type": "b", "children": [{"type": "t", "text": "Subcellular localization of full-length human myeloid leukemia factor 1 (MLF1) is independent of 14-3-3 proteins."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Mol Biol Lett (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.2478/s11658-012-0044-1"}], "href": "https://doi.org/10.2478/s11658-012-0044-1"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23271436"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23271436"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Manisha Banerjee, Moumita Datta, Nitai P Bhattacharyya "}, {"type": "b", "children": [{"type": "t", "text": "Modulation of mutant Huntingtin aggregates and toxicity by human myeloid leukemia factors."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Int J Biochem Cell Biol (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.biocel.2016.11.008"}], "href": "https://doi.org/10.1016/j.biocel.2016.11.008"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27840155"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27840155"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Jamie O Dyer, Arnob Dutta, Madelaine Gogol, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Myeloid Leukemia Factor Acts in a Chaperone Complex to Regulate Transcription Factor Stability and Gene Expression."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Mol Biol (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.jmb.2016.10.026"}], "href": "https://doi.org/10.1016/j.jmb.2016.10.026"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27984043"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27984043"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "Daoyuan Huang, Cheng Liu, Xiwen Sun, et al. "}, {"type": "b", "children": [{"type": "t", "text": "CRL4"}, {"type": "a", "children": [{"type": "t", "text": "sup"}], "href": "sup"}, {"type": "t", "text": "DCAF8"}, {"type": "a", "children": [{"type": "t", "text": "/sup"}], "href": "/sup"}, {"type": "t", "text": " and USP11 oppositely regulate the stability of myeloid leukemia factors (MLFs)."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochem Biophys Res Commun (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.bbrc.2020.05.186"}], "href": "https://doi.org/10.1016/j.bbrc.2020.05.186"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32703400"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32703400"}]}, {"type": "r", "ref": 11, "children": [{"type": "t", "text": "Zhi-Fang Li, Xiaohua Wu, Yun Jiang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Non-pathogenic protein aggregates in skeletal muscle in MLF1 transgenic mice."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Neurol Sci (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.jns.2007.07.027"}], "href": "https://doi.org/10.1016/j.jns.2007.07.027"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17854834"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17854834"}]}, {"type": "r", "ref": 12, "children": [{"type": "t", "text": "Yi Sun, Jyh-Rong Chao, Wu Xu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "MLF1 is a proapoptotic antagonist of HOP complex-mediated survival."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochim Biophys Acta Mol Cell Res (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.bbamcr.2017.01.016"}], "href": "https://doi.org/10.1016/j.bbamcr.2017.01.016"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28137643"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28137643"}]}, {"type": "r", "ref": 13, "children": [{"type": "t", "text": "Zengwei Tang, Yuan Yang, Wen Chen, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Epigenetic deregulation of MLF1 drives intrahepatic cholangiocarcinoma progression through EGFR/AKT and Wnt/β-catenin signaling."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Hepatol Commun (2023)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1097/HC9.0000000000000204"}], "href": "https://doi.org/10.1097/HC9.0000000000000204"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "37486965"}], "href": "https://pubmed.ncbi.nlm.nih.gov/37486965"}]}]}]}
Proteins	MLF1_HUMAN
NCBI Gene ID	4291
API
Download Associations
Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

MLF1 has 7,643 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 120 datasets.

Click the + buttons to view associations for MLF1 from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

MLF1 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 MLF1 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 MLF1 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 MLF1 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 MLF1 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 MLF1 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 MLF1 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 MLF1 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 MLF1 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 MLF1 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 MLF1 gene from the Carcinogenome Chemical Perturbation Carcinogenicity Signatures dataset.
	CCLE Cell Line Gene CNV Profiles	cell lines with high or low copy number of MLF1 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 MLF1 gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CCLE Cell Line Gene Mutation Profiles	cell lines with MLF1 gene mutations from the CCLE Cell Line Gene Mutation Profiles dataset.
	CCLE Cell Line Proteomics	Cell lines associated with MLF1 protein from the CCLE Cell Line Proteomics dataset.
	CellMarker Gene-Cell Type Associations	cell types associated with MLF1 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 MLF1 gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of MLF1 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 MLF1 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 MLF1 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 MLF1 gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing MLF1 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores 2025	cellular components containing MLF1 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores	cellular components co-occuring with MLF1 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 MLF1 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 MLF1 gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with MLF1 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Disease Associations	diseases associated with MLF1 gene/protein from the curated CTD Gene-Disease Associations dataset.
	DeepCoverMOA Drug Mechanisms of Action	small molecule perturbations with high or low expression of MLF1 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 MLF1 gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset.
	DISEASES Experimental Gene-Disease Association Evidence Scores 2025	diseases associated with MLF1 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 MLF1 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 MLF1 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 MLF1 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with MLF1 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 MLF1 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 MLF1 gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of MLF1 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 MLF1 from the ESCAPE Omics Signatures of Genes and Proteins for Stem Cells dataset.
	GAD Gene-Disease Associations	diseases associated with MLF1 gene in GWAS and other genetic association datasets from the GAD Gene-Disease Associations dataset.
	GAD High Level Gene-Disease Associations	diseases associated with MLF1 gene in GWAS and other genetic association datasets from the GAD High Level Gene-Disease Associations dataset.