AFF3 Gene

Name	AF4/FMR2 family, member 3
Description	This gene encodes a tissue-restricted nuclear transcriptional activator that is preferentially expressed in lymphoid tissue. Isolation of this protein initially defined a highly conserved LAF4/MLLT2 gene family of nuclear transcription factors that may function in lymphoid development and oncogenesis. In some ALL patients, this gene has been found fused to the gene for MLL. Multiple alternatively spliced transcript variants that encode different proteins have been found for this gene. [provided by RefSeq, Jul 2008]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n Recent studies have implicated the AFF3 gene (also known as LAF4) as a critical transcriptional regulator with diverse roles in immune function, oncogenesis, and development. Genome‐wide association analyses have repeatedly identified AFF3 as a susceptibility locus for autoimmune diseases such as rheumatoid arthritis and juvenile idiopathic arthritis, with risk alleles in AFF3 associating with increased disease susceptibility and, in some studies, with measures of disease severity and treatment response."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "4"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n As a member of the AF4/FMR2 gene family, AFF3 functions as a putative transcriptional activator that modulates transcriptional elongation and possibly alternative splicing. Its deregulation is implicated in oncogenic processes; for example, chromosomal rearrangements that fuse AFF family members with MLL have been described in infant acute lymphoblastic leukemia, while overexpression of AFF3 in breast cancer cells has been shown to transcriptionally activate estrogen receptor–dependent genes, resulting in tamoxifen resistance."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Beyond its roles in autoimmunity and cancer, AFF3 is essential during normal development. Functional studies in murine models have demonstrated that AFF3 activity is required for proper cortical cell migration, acting at least in part by regulating target genes such as Mdga2."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": " Furthermore, microdeletions affecting AFF3 (LAF4) have been associated with limb, brain, and urogenital malformations, underscoring its developmental importance."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": " Recent mechanistic insights also indicate that AFF3 can bind in an allele‐specific manner to differentially methylated regions and enhancers—such as those found in imprinted loci (e.g., the Dlk1-Dio3 region)—thereby controlling dosage‐sensitive gene expression."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n In summary, AFF3 serves as a multifaceted regulator of transcription whose normal function is crucial for immune regulation, proper development, and cellular homeostasis; its dysregulation contributes to autoimmune susceptibility, aberrant transcriptional programs in cancer, and developmental anomalies.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Eli A Stahl, Soumya Raychaudhuri, Elaine F Remmers, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Genome-wide association study meta-analysis identifies seven new rheumatoid arthritis risk loci."}]}, {"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.582"}], "href": "https://doi.org/10.1038/ng.582"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20453842"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20453842"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Anne Barton, Steve Eyre, Xiayi Ke, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Identification of AF4/FMR2 family, member 3 (AFF3) as a novel rheumatoid arthritis susceptibility locus and confirmation of two further pan-autoimmune susceptibility genes."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Hum Mol Genet (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/hmg/ddp177"}], "href": "https://doi.org/10.1093/hmg/ddp177"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19359276"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19359276"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Darren Plant, Edward Flynn, Hamdi Mbarek, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Investigation of potential non-HLA rheumatoid arthritis susceptibility loci in a European cohort increases the evidence for nine markers."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Ann Rheum Dis (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1136/ard.2009.121020"}], "href": "https://doi.org/10.1136/ard.2009.121020"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20498205"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20498205"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "A Hinks, S Eyre, X Ke, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Association of the AFF3 gene and IL2/IL21 gene region with juvenile idiopathic arthritis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Genes Immun (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/gene.2009.105"}], "href": "https://doi.org/10.1038/gene.2009.105"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20072139"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20072139"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Yawei Shi, Yang Zhao, Yunjian Zhang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "AFF3 upregulation mediates tamoxifen resistance in breast cancers."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Exp Clin Cancer Res (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1186/s13046-018-0928-7"}], "href": "https://doi.org/10.1186/s13046-018-0928-7"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30326937"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30326937"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Justin M Moore, Peter L Oliver, Mattéa J Finelli, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Laf4/Aff3, a gene involved in intellectual disability, is required for cellular migration in the mouse cerebral cortex."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS One (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.pone.0105933"}], "href": "https://doi.org/10.1371/journal.pone.0105933"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25162227"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25162227"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "E Steichen-Gersdorf, I Gassner, A Superti-Furga, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Triangular tibia with fibular aplasia associated with a microdeletion on 2q11.2 encompassing LAF4."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Clin Genet (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/j.1399-0004.2008.01050.x"}], "href": "https://doi.org/10.1111/j.1399-0004.2008.01050.x"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18616733"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18616733"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Zhuojuan Luo, Chengqi Lin, Ashley R Woodfin, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Regulation of the imprinted Dlk1-Dio3 locus by allele-specific enhancer activity."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Genes Dev (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1101/gad.270413.115"}], "href": "https://doi.org/10.1101/gad.270413.115"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26728555"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26728555"}]}]}]}
Synonyms	MLLT2-LIKE, LAF4
Proteins	AFF3_HUMAN
NCBI Gene ID	3899
API
Download Associations
Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

AFF3 has 6,695 functional associations with biological entities spanning 9 categories (molecular profile, organism, disease, phenotype or trait, chemical, functional term, phrase or reference, structural feature, cell line, cell type or tissue, gene, protein or microRNA, sequence feature) extracted from 117 datasets.

Click the + buttons to view associations for AFF3 from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

AFF3 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 AFF3 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 AFF3 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 AFF3 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 AFF3 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 AFF3 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 AFF3 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 AFF3 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 AFF3 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 AFF3 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 AFF3 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 AFF3 gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CCLE Cell Line Gene Mutation Profiles	cell lines with AFF3 gene mutations from the CCLE Cell Line Gene Mutation Profiles dataset.
	CCLE Cell Line Proteomics	Cell lines associated with AFF3 protein from the CCLE Cell Line Proteomics dataset.
	CellMarker Gene-Cell Type Associations	cell types associated with AFF3 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 AFF3 gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of AFF3 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 AFF3 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 AFF3 gene from the curated ClinVar Gene-Phenotype Associations 2025 dataset.
	CMAP Signatures of Differentially Expressed Genes for Small Molecules	small molecule perturbations changing expression of AFF3 gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing AFF3 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores 2025	cellular components containing AFF3 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores	cellular components co-occuring with AFF3 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 AFF3 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 AFF3 gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with AFF3 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Disease Associations	diseases associated with AFF3 gene/protein from the curated CTD Gene-Disease Associations dataset.
	dbGAP Gene-Trait Associations	traits associated with AFF3 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 AFF3 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 AFF3 gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset.
	DISEASES Curated Gene-Disease Association Evidence Scores	diseases involving AFF3 gene from the DISEASES Curated Gene-Disease Assocation Evidence Scores dataset.
	DISEASES Curated Gene-Disease Association Evidence Scores 2025	diseases involving AFF3 gene from the DISEASES Curated Gene-Disease Association Evidence Scores 2025 dataset.
	DISEASES Experimental Gene-Disease Association Evidence Scores	diseases associated with AFF3 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 AFF3 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 AFF3 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 AFF3 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 AFF3 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with AFF3 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 AFF3 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 AFF3 gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of AFF3 gene in ChIP-seq datasets from the ENCODE Transcription Factor Targets dataset.