AFF1 Gene

Name	AF4/FMR2 family, member 1
Description	This gene encodes a member of the AF4/ lymphoid nuclear protein related to the Fragile X E syndrome (FRAXE) family of proteins, which have been implicated in human childhood lymphoblastic leukemia, fragile chromosome X intellectual disability, and ataxia. It is the prevalent mixed-lineage leukemia fusion gene associated with spontaneous acute lymphoblastic leukemia. Members of this family have three conserved domains: an N-terminal homology domain, an AF4/ lymphoid nuclear protein domain, and a C-terminal homology domain. The protein functions as a regulator of RNA polymerase II-mediated transcription through elongation and chromatin remodeling functions. Through RNA interference screens, this gene has been shown to promote the expression of CD133, a plasma membrane glycoprotein required for leukemia cell survival. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2017]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n AFF1 (also known as AF4) is a multifunctional transcriptional regulator that plays a central role in transcription elongation. As a member of the AF4/FMR2 family, AFF1 functions within larger complexes—most notably within the super elongation complex (SEC)—where it helps bridge components such as positive transcription elongation factor b (P‐TEFb) and other elongation factors. In doing so, AFF1 enhances the processivity of RNA polymerase II, thereby facilitating the efficient transcription of critical genes (for instance, HOX and MEIS1) that are necessary for hematopoietic development. Notably, AFF1 is one of the most common fusion partners for the mixed‐lineage leukemia (MLL) gene; the resultant MLL–AFF1 fusion proteins dysregulate normal transcriptional programs and contribute strongly to leukemogenesis (see."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n AFF1’s role is further underscored by its participation in complexes that activate transcription in response to viral regulatory factors. For example, in the context of HIV-1 transcription, AFF1 is assembled with other elongation factors within a Tat-associated complex that potentiates transcriptional activation (see."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": " In this regard, AFF1 not only contributes to normal gene regulation but also, when derailed by chromosomal translocation or aberrant recruitment, can lead to dramatic shifts in cellular gene expression programs.\n "}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Beyond its well‐documented involvement in leukemia, genetic studies have revealed that variation in the AFF1 gene is associated with susceptibility to autoimmune conditions such as systemic lupus erythematosus (SLE). Enhanced expression of AFF1 in key lymphocyte populations hints at a broader role in modulating immune cell gene expression that may contribute to disease onset (see."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n In summary, AFF1 is a critical mediator of transcription elongation through its integration into multi‐protein complexes that regulate RNA polymerase II activity. Its involvement in MLL fusion events that drive leukemogenesis and its emerging links to immune dysregulation underscore its importance in both normal cellular physiology and disease pathology.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Emmanuelle Bitoun, Peter L Oliver, Kay E Davies "}, {"type": "b", "children": [{"type": "t", "text": "The mixed-lineage leukemia fusion partner AF4 stimulates RNA polymerase II transcriptional elongation and mediates coordinated chromatin remodeling."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Hum Mol Genet (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/hmg/ddl444"}], "href": "https://doi.org/10.1093/hmg/ddl444"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17135274"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17135274"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "C Meyer, T Burmeister, D Gröger, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The MLL recombinome of acute leukemias in 2017."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Leukemia (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/leu.2017.213"}], "href": "https://doi.org/10.1038/leu.2017.213"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28701730"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28701730"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Bijan Sobhian, Nadine Laguette, Ahmad Yatim, et al. "}, {"type": "b", "children": [{"type": "t", "text": "HIV-1 Tat assembles a multifunctional transcription elongation complex and stably associates with the 7SK snRNP."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cell (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.molcel.2010.04.012"}], "href": "https://doi.org/10.1016/j.molcel.2010.04.012"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20471949"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20471949"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Yukinori Okada, Kenichi Shimane, Yuta Kochi, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A genome-wide association study identified AFF1 as a susceptibility locus for systemic lupus eyrthematosus in Japanese."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS Genet (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.pgen.1002455"}], "href": "https://doi.org/10.1371/journal.pgen.1002455"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22291604"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22291604"}]}]}]}
Synonyms	PBM1, MLLT2, AF4
Proteins	AFF1_HUMAN
NCBI Gene ID	4299
API
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Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

AFF1 has 10,267 functional associations with biological entities spanning 9 categories (molecular profile, organism, functional term, phrase or reference, chemical, disease, phenotype or trait, structural feature, cell line, cell type or tissue, gene, protein or microRNA, sequence feature) extracted from 127 datasets.

Click the + buttons to view associations for AFF1 from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

AFF1 Gene

Functional Associations

Please acknowledge the Harmonizome in your publications by citing the following reference(s):

	Dataset	Summary
	Achilles Cell Line Gene Essentiality Profiles	cell lines with fitness changed by AFF1 gene knockdown relative to other cell lines from the Achilles Cell Line Gene Essentiality Profiles dataset.
	Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles	tissues with high or low expression of AFF1 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 AFF1 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 AFF1 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 AFF1 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 AFF1 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 AFF1 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 AFF1 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 AFF1 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 AFF1 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 AFF1 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 AFF1 gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CCLE Cell Line Gene Mutation Profiles	cell lines with AFF1 gene mutations from the CCLE Cell Line Gene Mutation Profiles dataset.
	CCLE Cell Line Proteomics	Cell lines associated with AFF1 protein from the CCLE Cell Line Proteomics dataset.
	CellMarker Gene-Cell Type Associations	cell types associated with AFF1 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 AFF1 gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of AFF1 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 AFF1 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 AFF1 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 AFF1 gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing AFF1 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores 2025	cellular components containing AFF1 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores	cellular components co-occuring with AFF1 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 AFF1 protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025 dataset.
	CORUM Protein Complexes	protein complexs containing AFF1 protein from the CORUM Protein Complexes dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with AFF1 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Chemical Interactions	chemicals interacting with AFF1 gene/protein from the curated CTD Gene-Chemical Interactions dataset.
	CTD Gene-Disease Associations	diseases associated with AFF1 gene/protein from the curated CTD Gene-Disease Associations dataset.
	dbGAP Gene-Trait Associations	traits associated with AFF1 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 AFF1 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 AFF1 gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset.
	DISEASES Curated Gene-Disease Association Evidence Scores	diseases involving AFF1 gene from the DISEASES Curated Gene-Disease Assocation Evidence Scores dataset.
	DISEASES Curated Gene-Disease Association Evidence Scores 2025	diseases involving AFF1 gene from the DISEASES Curated Gene-Disease Association Evidence Scores 2025 dataset.
	DISEASES Experimental Gene-Disease Association Evidence Scores	diseases associated with AFF1 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 AFF1 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 AFF1 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 AFF1 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 AFF1 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with AFF1 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 AFF1 gene from the ENCODE Histone Modification Site Profiles dataset.