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AFF3 (lymphoid nuclear protein related to AF4)

Written2003-08Anne RM von Bergh
Afdeling Klinische Genetica, Erasmus MC, Dr. Molewaterplein 50, 3015 GE Rotterdam, The Netherlands

(Note : for Links provided by Atlas : click)


lymphoid nuclear protein related to AF4
AF4/FMR2 family, member 3
Alias_symbol (synonym)MLLT2-like
Other aliasLAF4 (lymphoid nuclear protein related to AF4)
MLLT2-related protein, lymphoid nuclear protein 4
HGNC (Hugo) AFF3
LocusID (NCBI) 3899
Atlas_Id 315
Location 2q11.2  [Link to chromosome band 2q11]
Location_base_pair Starts at 99547254 and ends at 100142575 bp from pter ( according to hg19-Feb_2009)  [Mapping AFF3.png]
Fusion genes
(updated 2017)
Data from Atlas, Mitelman, Cosmic Fusion, Fusion Cancer, TCGA fusion databases with official HUGO symbols (see references in chromosomal bands)
AFF3 (2q11.2) / AFF1 (4q21.3)AFF3 (2q11.2) / ASZ1 (7q31.2)AFF3 (2q11.2) / BCL2 (18q21.33)
AFF3 (2q11.2) / CDH3 (16q22.1)AFF3 (2q11.2) / EIF5B (2q11.2)AFF3 (2q11.2) / HDAC5 (17q21.31)
AFF3 (2q11.2) / KMT2A (11q23.3)AFF3 (2q11.2) / NPAS2 (2q11.2)AFF3 (2q11.2) / PHF1 (6p21.32)
AFF3 (2q11.2) / RTN4 (2p16.1)AFF3 (2q11.2) / RUNX1 (21q22.12)AFF3 (2q11.2) / SAP130 (2q14.3)
AFF3 (2q11.2) / TMEM182 (2q12.1)EPAS1 (2p21) / AFF3 (2q11.2)FGFR2 (10q26.13) / AFF3 (2q11.2)
KMT2A (11q23.3) / AFF3 (2q11.2)POLR1A (2p11.2) / AFF3 (2q11.2)RGS3 (9q32) / AFF3 (2q11.2)
RP9 (7p14.3) / AFF3 (2q11.2)RUNX1 (21q22.12) / AFF3 (2q11.2)


Description at least 17 exons.
Transcription in a telomere to centromere direction; 3857 bp mRNA; 3684 bp open reading frame.


Description 1227 amino acids; 133734 Da.
Expression Preferentially expressed in lymphoid tissues, highest levels being found in the thymus. Lower expression in brain and lung.
Localisation Nuclear
Function Putative transcription activator that may function in lymphoid development and oncogenesis. Binds in vitro to double-stranded DNA
Homology Belongs to the AF4/LAF4/FMR2/AF5q31 family.

Implicated in

Entity t(2;11)(q11;q23) . --> KMT2A- LAF4
Note MLL fusion partner at chromosome 2 in infant ALL
Disease The three cases reported to date were all infant-ALL with proB phenotype
Prognosis Prognosis is poor, although based on only three cases.
Cytogenetics The three reported cases harboured different rearrangements involving chromosomes 2 and 11: t(2;11)(q11;q23), t(2;11)(p15;p14), and ins(11;2)(q23;q11.2q11.2).
Abnormal Protein The MLL-LAF4 fusion protein includes the transactivation domain of LAF4 that is part of the AF4/LAF4/FMR2 homology domain.
Coding sequence of LAF4 compared to AF4 and site of fusion. Schematic representation of MLL, LAF4, AF4, and the putative MLL-LAF4 fusion protein. Domains in MLL are shaded: MT, DNA methyltransferase homology region; TRX, Drosophila trithorax homology. The percentage of amino acid homology between corresponding regions of LAF4 and AF4 is indicated: NHD, N-terminal homology domain; ALF, AF4/LAF4/FMR2 homology domain; TAD, transactivation domain; NLS, nuclear localization sequence; CHD, C-terminal homology domain. Arrows indicate the fusion sites with MLL. The breakpoint in LAF4 corresponds to one of the known breakpoints in AF4.




Occurrence of an MLL/LAF4 fusion gene caused by the insertion ins(11;2)(q23;q11.2q11.2) in an infant with acute lymphoblastic leukemia.
Bruch J, Wilda M, Teigler-Schlegel A, Harbott J, Borkhardt A, Metzler M
Genes, chromosomes & cancer. 2003 ; 37 (1) : 106-109.
PMID 12661012
Fusion of an AF4-related gene, LAF4, to MLL in childhood acute lymphoblastic leukemia with t(2;11)(q11;q23).
Hiwatari M, Taki T, Taketani T, Taniwaki M, Sugita K, Okuya M, Eguchi M, Ida K, Hayashi Y
Oncogene. 2003 ; 22 (18) : 2851-2855.
PMID 12743608
LAF-4 encodes a lymphoid nuclear protein with transactivation potential that is homologous to AF-4, the gene fused to MLL in t(4;11) leukemias.
Ma C, Staudt LM
Blood. 1996 ; 87 (2) : 734-745.
PMID 8555498
LAF4, an AF4-related gene, is fused to MLL in infant acute lymphoblastic leukemia.
von Bergh AR, Beverloo HB, Rombout P, van Wering ER, van Weel MH, Beverstock GC, Kluin PM, Slater RM, Schuuring E
Genes, chromosomes & cancer. 2002 ; 35 (1) : 92-96.
PMID 12203795


This paper should be referenced as such :
von Bergh, ARM
LAF4 (lymphoid nuclear protein related to AF4)
Atlas Genet Cytogenet Oncol Haematol. 2003;7(4):226-227.
Free journal version : [ pdf ]   [ DOI ]
On line version :

Other Leukemias implicated (Data extracted from papers in the Atlas) [ 5 ]
  11q23 rearrangements (KMT2A) in leukaemia
t(2;11)(q11;q23) KMT2A/AFF3
t(2;18)(q11;q21) AFF3/BCL2
t(2;21)(q11;q22) RUNX1/AFF3

Other Solid tumors implicated (Data extracted from papers in the Atlas) [ 6 ]
  t(2;2)(q11;q11) AFF3/NPAS2
t(2;2)(q11;q12) AFF3/TMEM182
t(2;6)(q11;p21) AFF3/PHF1
t(2;7)(q11;q31) AFF3/ASZ1
t(2;10)(q11;q26) FGFR2/AFF3
t(2;17)(q11;q21) AFF3/HDAC5

External links

HGNC (Hugo)AFF3   6473
Entrez_Gene (NCBI)AFF3  3899  AF4/FMR2 family member 3
AliasesLAF4; MLLT2-like
GeneCards (Weizmann)AFF3
Ensembl hg19 (Hinxton)ENSG00000144218 [Gene_View]
Ensembl hg38 (Hinxton)ENSG00000144218 [Gene_View]  chr2:99547254-100142575 [Contig_View]  AFF3 [Vega]
ICGC DataPortalENSG00000144218
TCGA cBioPortalAFF3
AceView (NCBI)AFF3
Genatlas (Paris)AFF3
SOURCE (Princeton)AFF3
Genetics Home Reference (NIH)AFF3
Genomic and cartography
GoldenPath hg38 (UCSC)AFF3  -     chr2:99547254-100142575 -  2q11.2   [Description]    (hg38-Dec_2013)
GoldenPath hg19 (UCSC)AFF3  -     2q11.2   [Description]    (hg19-Feb_2009)
EnsemblAFF3 - 2q11.2 [CytoView hg19]  AFF3 - 2q11.2 [CytoView hg38]
Mapping of homologs : NCBIAFF3 [Mapview hg19]  AFF3 [Mapview hg38]
Gene and transcription
Genbank (Entrez)AB209634 AK055117 AK091320 AK092327 AK290468
RefSeq transcript (Entrez)NM_001025108 NM_002285
RefSeq genomic (Entrez)
Consensus coding sequences : CCDS (NCBI)AFF3
Cluster EST : UnigeneHs.444414 [ NCBI ]
CGAP (NCI)Hs.444414
Alternative Splicing GalleryENSG00000144218
Gene ExpressionAFF3 [ NCBI-GEO ]   AFF3 [ EBI - ARRAY_EXPRESS ]   AFF3 [ SEEK ]   AFF3 [ MEM ]
Gene Expression Viewer (FireBrowse)AFF3 [ Firebrowse - Broad ]
SOURCE (Princeton)Expression in : [Datasets]   [Normal Tissue Atlas]  [carcinoma Classsification]  [NCI60]
GenevestigatorExpression in : [tissues]  [cell-lines]  [cancer]  [perturbations]  
BioGPS (Tissue expression)3899
GTEX Portal (Tissue expression)AFF3
Human Protein AtlasENSG00000144218-AFF3 [pathology]   [cell]   [tissue]
Protein : pattern, domain, 3D structure
UniProt/SwissProtP51826   [function]  [subcellular_location]  [family_and_domains]  [pathology_and_biotech]  [ptm_processing]  [expression]  [interaction]
NextProtP51826  [Sequence]  [Exons]  [Medical]  [Publications]
With graphics : InterProP51826
Splice isoforms : SwissVarP51826
Domains : Interpro (EBI)TF_AF4/FMR2   
Domain families : Pfam (Sanger)AF-4 (PF05110)   
Domain families : Pfam (NCBI)pfam05110   
Conserved Domain (NCBI)AFF3
DMDM Disease mutations3899
Blocks (Seattle)AFF3
Human Protein Atlas [tissue]ENSG00000144218-AFF3 [tissue]
Peptide AtlasP51826
IPIIPI00515069   IPI00916518   IPI00917755   IPI00915807   IPI00020918   IPI00917160   IPI00917446   IPI00917619   IPI00916078   IPI00917889   IPI00917500   IPI00916649   
Protein Interaction databases
IntAct (EBI)P51826
Ontologies - Pathways
Ontology : AmiGOdouble-stranded DNA binding  nucleus  nucleoplasm  cytosol  transcription, DNA-templated  regulation of transcription, DNA-templated  nuclear body  response to tumor necrosis factor  embryonic hindlimb morphogenesis  
Ontology : EGO-EBIdouble-stranded DNA binding  nucleus  nucleoplasm  cytosol  transcription, DNA-templated  regulation of transcription, DNA-templated  nuclear body  response to tumor necrosis factor  embryonic hindlimb morphogenesis  
NDEx NetworkAFF3
Atlas of Cancer Signalling NetworkAFF3
Wikipedia pathwaysAFF3
Orthology - Evolution
GeneTree (enSembl)ENSG00000144218
Phylogenetic Trees/Animal Genes : TreeFamAFF3
Homologs : HomoloGeneAFF3
Homology/Alignments : Family Browser (UCSC)AFF3
Gene fusions - Rearrangements
Fusion : MitelmanAFF3/ASZ1 [2q11.2/7q31.2]  
Fusion : MitelmanAFF3/BCL2 [2q11.2/18q21.33]  [t(2;18)(q11;q21)]  
Fusion : MitelmanAFF3/HDAC5 [2q11.2/17q21.31]  [t(2;17)(q11;q21)]  
Fusion : MitelmanAFF3/NPAS2 [2q11.2/2q11.2]  [t(2;2)(q11;q11)]  
Fusion : MitelmanAFF3/TMEM182 [2q11.2/2q12.1]  [t(2;2)(q11;q12)]  
Fusion : MitelmanFGFR2/AFF3 [10q26.13/2q11.2]  [t(2;10)(q11;q26)]  
Fusion : MitelmanRUNX1/AFF3 [21q22.12/2q11.2]  [t(2;21)(q11;q22)]  
Fusion : COSMICKMT2A [11q23.3]  -  AFF3 [2q11.2]  [fusion_1784]  [fusion_1785]  [fusion_1816]  [fusion_2030]  [fusion_2031]  [fusion_2032]  
Fusion: TCGA_MDACCAFF3 2q11.2 ASZ1 7q31.2 BRCA
Fusion: TCGA_MDACCAFF3 2q11.2 HDAC5 17q21.31 PRAD
Fusion: TCGA_MDACCAFF3 2q11.2 NPAS2 2q11.2 LUAD
Fusion: TCGA_MDACCAFF3 2q11.2 TMEM182 2q12.1 BRCA
Fusion PortalAFF3 2q11.2 ASZ1 7q31.2 BRCA
Fusion PortalAFF3 2q11.2 HDAC5 17q21.31 PRAD
Fusion PortalAFF3 2q11.2 NPAS2 2q11.2 LUAD
Fusion PortalAFF3 2q11.2 TMEM182 2q12.1 BRCA
Fusion : TICdbAFF3 [2q11.2]  -  BCL2 [18q21.33]
Fusion : TICdbKMT2A [11q23.3]  -  AFF3 [2q11.2]
Fusion : TICdbRUNX1 [21q22.12]  -  AFF3 [2q11.2]
Fusion : QuiverAFF3
Polymorphisms : SNP and Copy number variants
NCBI Variation ViewerAFF3 [hg38]
dbSNP Single Nucleotide Polymorphism (NCBI)AFF3
Exome Variant ServerAFF3
ExAC (Exome Aggregation Consortium)ENSG00000144218
GNOMAD BrowserENSG00000144218
Genetic variants : HAPMAP3899
Genomic Variants (DGV)AFF3 [DGVbeta]
DECIPHERAFF3 [patients]   [syndromes]   [variants]   [genes]  
CONAN: Copy Number AnalysisAFF3 
ICGC Data PortalAFF3 
TCGA Data PortalAFF3 
Broad Tumor PortalAFF3
OASIS PortalAFF3 [ Somatic mutations - Copy number]
Cancer Gene: CensusAFF3 
Somatic Mutations in Cancer : COSMICAFF3  [overview]  [genome browser]  [tissue]  [distribution]  
Mutations and Diseases : HGMDAFF3
LOVD (Leiden Open Variation Database)Whole genome datasets
LOVD (Leiden Open Variation Database)LOVD - Leiden Open Variation Database
LOVD (Leiden Open Variation Database)LOVD 3.0 shared installation
BioMutasearch AFF3
DgiDB (Drug Gene Interaction Database)AFF3
DoCM (Curated mutations)AFF3 (select the gene name)
CIViC (Clinical Interpretations of Variants in Cancer)AFF3 (select a term)
NCG5 (London)AFF3
Cancer3DAFF3(select the gene name)
Impact of mutations[PolyPhen2] [SIFT Human Coding SNP] [Buck Institute : MutDB] [Mutation Assessor] [Mutanalyser]
Genetic Testing Registry AFF3
NextProtP51826 [Medical]
Target ValidationAFF3
Huge Navigator AFF3 [HugePedia]
snp3D : Map Gene to Disease3899
BioCentury BCIQAFF3
Clinical trials, drugs, therapy
Chemical/Protein Interactions : CTD3899
Chemical/Pharm GKB GenePA30264
Clinical trialAFF3
canSAR (ICR)AFF3 (select the gene name)
PubMed38 Pubmed reference(s) in Entrez
GeneRIFsGene References Into Functions (Entrez)
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

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indexed on : Wed Feb 28 13:57:28 CET 2018

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