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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)


Alias (NCBI)LAF4 (lymphoid nuclear protein related to AF4)
MLLT2-related protein, lymphoid nuclear protein 4
HGNC (Hugo) AFF3
HGNC Alias symbMLLT2-like
HGNC Previous nameLAF4
HGNC Previous name"lymphoid nuclear protein related to AF4
 AF4/FMR2 family, member 3"
LocusID (NCBI) 3899
Atlas_Id 315
Location 2q11.2  [Link to chromosome band 2q11]
Location_base_pair Starts at 99545419 and ends at 100142590 bp from pter ( according to GRCh38/hg38-Dec_2013)  [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 ]

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 ]
  AFF3/NPAS2 (2q11)
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    AF4/FMR2 family member 3
AliasesLAF4; MLLT2-like
GeneCards (Weizmann)AFF3
Ensembl hg19 (Hinxton)ENSG00000144218 [Gene_View]
Ensembl hg38 (Hinxton)ENSG00000144218 [Gene_View]  ENSG00000144218 [Sequence]  chr2:99545419-100142590 [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  -     chr2:99545419-100142590 -  2q11.2   [Description]    (hg38-Dec_2013)
GoldenPath hg19 (UCSC)AFF3  -     2q11.2   [Description]    (hg19-Feb_2009)
GoldenPathAFF3 - 2q11.2 [CytoView hg19]  AFF3 - 2q11.2 [CytoView hg38]
genome Data Viewer NCBIAFF3 [Mapview hg19]  
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
Alternative Splicing GalleryENSG00000144218
Gene ExpressionAFF3 [ NCBI-GEO ]   AFF3 [ EBI - ARRAY_EXPRESS ]   AFF3 [ SEEK ]   AFF3 [ MEM ]
Gene Expression Viewer (FireBrowse)AFF3 [ Firebrowse - Broad ]
GenevisibleExpression of AFF3 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
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  nucleus  nucleoplasm  cytosol  transcription elongation factor complex  regulation of gene expression  nuclear body  ELL-EAF complex  response to tumor necrosis factor  embryonic hindlimb morphogenesis  
Ontology : EGO-EBIdouble-stranded DNA binding  nucleus  nucleus  nucleoplasm  cytosol  transcription elongation factor complex  regulation of gene expression  nuclear body  ELL-EAF complex  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]  
Fusion : MitelmanAFF3/HDAC5 [2q11.2/17q21.31]  
Fusion : MitelmanAFF3/NPAS2 [2q11.2/2q11.2]  
Fusion : MitelmanAFF3/TMEM182 [2q11.2/2q12.1]  
Fusion : MitelmanFGFR2/AFF3 [10q26.13/2q11.2]  
Fusion : MitelmanRUNX1/AFF3 [21q22.12/2q11.2]  
Fusion : COSMICKMT2A [11q23.3]  -  AFF3 [2q11.2]  [fusion_1784]  [fusion_1816]  [fusion_2030]  [fusion_2032]  
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 : Fusion_HubABI2--AFF3    AFF3--ASZ1    AFF3--ATP5B    AFF3--BCL2    AFF3--BTN3A3    AFF3--CDH3    AFF3--CDV3    AFF3--EIF5B    AFF3--FGFR2    AFF3--HDAC5    AFF3--KMT2A    AFF3--LRRC49    AFF3--MAP4K4    AFF3--MLL    AFF3--NPAS2   
AFF3--OCLN    AFF3--PHF1    AFF3--POLG    AFF3--RAB12    AFF3--RTN4    AFF3--RUNX1    AFF3--SAP130    AFF3--SFMBT1    AFF3--TMEM182    AML1--AFF3    CPSF6--AFF3    CRIM1--AFF3    EPAS1--AFF3    KMT2A--AFF3    MLL--AFF3   
PHF1--AFF3    POLR1A--AFF3    REV1--AFF3    RGS3--AFF3    RP9--AFF3    RUNX1--AFF3    SEMA4C--AFF3   
Fusion : QuiverAFF3
Polymorphisms : SNP and Copy number variants
NCBI Variation ViewerAFF3 [hg38]
Exome Variant ServerAFF3
GNOMAD BrowserENSG00000144218
Varsome BrowserAFF3
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]  
Somatic Mutations in Cancer : COSMIC3DAFF3
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)
NCG6 (London) select AFF3
Cancer3DAFF3(select the gene name)
Impact of mutations[PolyPhen2] [Provean] [Buck Institute : MutDB] [Mutation Assessor] [Mutanalyser]
Genetic Testing Registry AFF3
NextProtP51826 [Medical]
Target ValidationAFF3
Huge Navigator AFF3 [HugePedia]
Clinical trials, drugs, therapy
Protein Interactions : CTD
Pharm GKB GenePA30264
Clinical trialAFF3
canSAR (ICR)AFF3 (select the gene name)
DataMed IndexAFF3
PubMed42 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 : Fri Feb 19 17:53:40 CET 2021

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