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AFF1 (AF4/FMR2 family, member 1)

Written1997-12Jean-Loup Huret
Genetics, Dept Medical Information, University of Poitiers, CHU Poitiers Hospital, F-86021 Poitiers, France
Updated2002-12Rolf Marschalek
Instituts für Pharmazeutische Biologie, JWG Universitaet Frankfurt/Main, Biozentrum, N230, 303, Marie Curie Str. 9, D-60439 Frankfurt/Main, Germany

(Note : for Links provided by Atlas : click)


myeloid/lymphoid or mixed-lineage leukemia (trithorax (Drosophila) homolog); translocated to, 2
pre-B-cell monocytic leukemia partner 1
AF4/FMR2 family, member 1
Alias_symbol (synonym)AF-4
Other aliasFEL
MLLT2 (myeloid/lymphoid leukemia translocated to, 2).
HGNC (Hugo) AFF1
LocusID (NCBI) 4299
Atlas_Id 3
Location 4q21.3  [Link to chromosome band 4q21]
Location_base_pair Starts at 86935002 and ends at 87141054 bp from pter ( according to hg19-Feb_2009)  [Mapping AFF1.png]
  MLLT2 (4q21) - Courtesy Mariano Rocchi, Resources for Molecular Cytogenetics.
Fusion genes
(updated 2016)
AFF1 (4q21.3) / ADAM12 (10q26.2)AFF1 (4q21.3) / AFF1 (4q21.3)AFF1 (4q21.3) / ARHGAP17 (16p12.1)
AFF1 (4q21.3) / CCDC84 (11q23.3)AFF1 (4q21.3) / DSCAML1 (11q23.3)AFF1 (4q21.3) / ELF2 (4q31.1)
AFF1 (4q21.3) / FXYD6 (11q23.3)AFF1 (4q21.3) / KMT2A (11q23.3)AFF1 (4q21.3) / PAIP2 (5q31.2)
AFF1 (4q21.3) / PBX1 (1q23.3)AFF1 (4q21.3) / PHACTR2 (6q24.2)AFF1 (4q21.3) / PTPN13 (4q21.3)
AFF1 (4q21.3) / RABGAP1L (1q25.1)AFF1 (4q21.3) / RAD51B (14q24.1)AFF1 (4q21.3) / TRIM33 (1p13.2)
AFF1 (4q21.3) / UBE2D3 (4q24)AFF3 (2q11.2) / AFF1 (4q21.3)ALL1 () / AFF1 (4q21.3)
C1QTNF1 (17q25.3) / AFF1 (4q21.3)GAS7 (17p13.1) / AFF1 (4q21.3)IL10RB (21q22.11) / AFF1 (4q21.3)
KMT2A (11q23.3) / AFF1 (4q21.3)KMT2B (19q13.12) / AFF1 (4q21.3)LYZ (12q15) / AFF1 (4q21.3)
SRSF11 (1p31.1) / AFF1 (4q21.3)


  Gene structure of AF4, containing the exon/intron structure as well as the distances of all three first exons (1a is encoded by two exons; 1b and 1c) and their distances from each other (unpublished data). There is also a stop in intron 3 (as designated) and an alternative splice of exon 18 to the 3'-NTR, skipping exon 19 and 20. Therefore this protein comes in different flavors, as there are presumably three independent promotor, and one carboxy-terminal exon skipping.
Transcription alternate splicing in 5' -> 10.5 and 12 kb; coding sequences: 3.6 kb. In addition, there are three independent first exons 1a, 1b and 1c (yet unpublished).


Description 1210 amino acids; 140 KDa; contains many serine and proline rich sequences, a nuclear targeting sequence and a concensus sequence for ATP/GTP binding
Expression widely expressed
Localisation nuclear
Function transcription activator
Homology LAF4, AF5 and FMR-2

Implicated in

Entity t(4;11)(q21;q23)/acute leukaemias. --> MLL -AF4
Disease typically CD19+ B-ALL, biphenotypic AL, at times AML (M4/M5); may be congenital; treatment related leukaemia (secondary to epipodophyllotoxins)
Prognosis median survival < 1yr
Cytogenetics additional chromosome anomalies are found in 1/4 of cases of which is the i(7q)
Hybrid/Mutated Gene 5' MLL-3' AF4; 12kb
Abnormal Protein 240 kDa protein with about 1400 aminoacids from NH2 MLL and 850 from COOH AF4 (variable breakpoints); the reciprocal may or may not be expressed


Molecular basis of 11q23 rearrangements in hematopoietic malignant proliferations.
Bernard OA, Berger R
Genes, chromosomes & cancer. 1995 ; 13 (2) : 75-85.
PMID 7542910
The t(4;11) chromosome translocation of human acute leukemias fuses the ALL-1 gene, related to Drosophila trithorax, to the AF-4 gene.
Gu Y, Nakamura T, Alder H, Prasad R, Canaani O, Cimino G, Croce CM, Canaani E
Cell. 1992 ; 71 (4) : 701-708.
PMID 1423625
A serine/proline-rich protein is fused to HRX in t(4;11) acute leukemias.
Morrissey J, Tkachuk DC, Milatovich A, Francke U, Link M, Cleary ML
Blood. 1993 ; 81 (5) : 1124-1131.
PMID 8443374
Exon/intron structure of the human AF-4 gene, a member of the AF-4/LAF-4/FMR-2 gene family coding for a nuclear protein with structural alterations in acute leukaemia.
Nilson I, Reichel M, Ennas MG, Greim R, Knörr C, Siegler G, Greil J, Fey GH, Marschalek R
British journal of haematology. 1997 ; 98 (1) : 157-169.
PMID 9233580
11q23 rearrangements in acute leukemia.
Rubnitz JE, Behm FG, Downing JR
Leukemia : official journal of the Leukemia Society of America, Leukemia Research Fund, U.K. 1996 ; 10 (1) : 74-82.
PMID 8558942
Chromosome abnormalities in leukaemia: the 11q23 paradigm.
Young BD, Saha V
Cancer surveys. 1996 ; 28 : 225-245.
PMID 8977038


This paper should be referenced as such :
Marschalek, R
AF4 (ALL1 fused gene from chromosome 4) - AFF1 (AF4/FMR2 family, member 1)
Atlas Genet Cytogenet Oncol Haematol. 2003;7(1):19-20.
Free journal version : [ pdf ]   [ DOI ]
On line version :
History of this paper:
Huret, JL. AF4 (ALL1 fused gene from chromosome 4). Atlas Genet Cytogenet Oncol Haematol. 1997;1(2):54-55.

Other Leukemias implicated (Data extracted from papers in the Atlas) [ 12 ]
  11q23 rearrangements (KMT2A) in childhood acute lymphoblastic leukemia
11q23 rearrangements (KMT2A) in leukaemia
11q23 rearrangements (KMT2A) in therapy related leukaemias
Infant leukaemias::Congenital leukaemias::Neonatal leukaemias
ins(5;11)(q31;q13q23) KMT2A/AFF4
i(Xq10) in female patients
t(2;11)(q11;q23) KMT2A/AFF3
t(2;18)(q11;q21) AFF3/BCL2
t(4;11)(q21;q23) KMT2A/AFF1
t(4;11)(q23;p15) NUP98/RAP1GDS1
t(11;16)(q23;p13.3) KMT2A/CREBBP

External links

HGNC (Hugo)AFF1   7135
Entrez_Gene (NCBI)AFF1  4299  AF4/FMR2 family member 1
AliasesAF4; MLLT2; PBM1
GeneCards (Weizmann)AFF1
Ensembl hg19 (Hinxton)ENSG00000172493 [Gene_View]
Ensembl hg38 (Hinxton)ENSG00000172493 [Gene_View]  chr4:86935002-87141054 [Contig_View]  AFF1 [Vega]
ICGC DataPortalENSG00000172493
TCGA cBioPortalAFF1
AceView (NCBI)AFF1
Genatlas (Paris)AFF1
SOURCE (Princeton)AFF1
Genetics Home Reference (NIH)AFF1
Genomic and cartography
GoldenPath hg38 (UCSC)AFF1  -     chr4:86935002-87141054 +  4q21.3-q22.1   [Description]    (hg38-Dec_2013)
GoldenPath hg19 (UCSC)AFF1  -     4q21.3-q22.1   [Description]    (hg19-Feb_2009)
EnsemblAFF1 - 4q21.3-q22.1 [CytoView hg19]  AFF1 - 4q21.3-q22.1 [CytoView hg38]
Mapping of homologs : NCBIAFF1 [Mapview hg19]  AFF1 [Mapview hg38]
Gene and transcription
Genbank (Entrez)AF024541 AF177236 AF177237 AF177238 AF177239
RefSeq transcript (Entrez)NM_001166693 NM_001313959 NM_001313960 NM_005935
RefSeq genomic (Entrez)
Consensus coding sequences : CCDS (NCBI)AFF1
Cluster EST : UnigeneHs.480190 [ NCBI ]
CGAP (NCI)Hs.480190
Alternative Splicing GalleryENSG00000172493
Gene ExpressionAFF1 [ NCBI-GEO ]   AFF1 [ EBI - ARRAY_EXPRESS ]   AFF1 [ SEEK ]   AFF1 [ MEM ]
Gene Expression Viewer (FireBrowse)AFF1 [ Firebrowse - Broad ]
SOURCE (Princeton)Expression in : [Datasets]   [Normal Tissue Atlas]  [carcinoma Classsification]  [NCI60]
GenevisibleExpression in : [tissues]  [cell-lines]  [cancer]  [perturbations]  
BioGPS (Tissue expression)4299
GTEX Portal (Tissue expression)AFF1
Protein : pattern, domain, 3D structure
UniProt/SwissProtP51825   [function]  [subcellular_location]  [family_and_domains]  [pathology_and_biotech]  [ptm_processing]  [expression]  [interaction]
NextProtP51825  [Sequence]  [Exons]  [Medical]  [Publications]
With graphics : InterProP51825
Splice isoforms : SwissVarP51825
Domains : Interpro (EBI)TF_AF4/FMR2   
Domain families : Pfam (Sanger)AF-4 (PF05110)   
Domain families : Pfam (NCBI)pfam05110   
Conserved Domain (NCBI)AFF1
DMDM Disease mutations4299
Blocks (Seattle)AFF1
PDB (SRS)2LM0   
PDB (PDBSum)2LM0   
PDB (IMB)2LM0   
Structural Biology KnowledgeBase2LM0   
SCOP (Structural Classification of Proteins)2LM0   
CATH (Classification of proteins structures)2LM0   
Human Protein AtlasENSG00000172493
Peptide AtlasP51825
IPIIPI00873029   IPI00908935   IPI00965976   IPI01010992   IPI00164675   IPI00396310   IPI00968090   
Protein Interaction databases
IntAct (EBI)P51825
Ontologies - Pathways
Ontology : AmiGOtranscription factor activity, sequence-specific DNA binding  protein binding  regulation of transcription, DNA-templated  transcription elongation factor complex  
Ontology : EGO-EBItranscription factor activity, sequence-specific DNA binding  protein binding  regulation of transcription, DNA-templated  transcription elongation factor complex  
Pathways : KEGGTranscriptional misregulation in cancer   
NDEx NetworkAFF1
Atlas of Cancer Signalling NetworkAFF1
Wikipedia pathwaysAFF1
Orthology - Evolution
GeneTree (enSembl)ENSG00000172493
Phylogenetic Trees/Animal Genes : TreeFamAFF1
Homologs : HomoloGeneAFF1
Homology/Alignments : Family Browser (UCSC)AFF1
Gene fusions - Rearrangements
Fusion : MitelmanAFF1/DSCAML1 [4q21.3/11q23.3]  
Fusion : MitelmanAFF1/ELF2 [4q21.3/4q31.1]  [ins(11;4)(q23;q21q31)]  
Fusion : MitelmanAFF1/FXYD6 [4q21.3/11q23.3]  [ins(4;11)(q21;q23q23)]  
Fusion : MitelmanAFF1/PBX1 [4q21.3/1q23.3]  [t(1;4;11)(q23;q21;q23)]  
Fusion : MitelmanAFF1/PTPN13 [4q21.3/4q21.3]  [t(4;4)(q21;q21)]  
Fusion : MitelmanAFF1/RABGAP1L [4q21.3/1q25.1]  [t(1;4;11)(q25;q21;q23)]  
Fusion : COSMICAFF1 [4q21.3]  -  KMT2A [11q23.3]  [fusion_1831]  [fusion_1832]  [fusion_2075]  [fusion_2076]  
Fusion : COSMICKMT2A [11q23.3]  -  AFF1 [4q21.3]  [fusion_1799]  [fusion_1800]  [fusion_1801]  [fusion_1802]  [fusion_1827]  [fusion_1828]  [fusion_1829]  
[fusion_1830]  [fusion_1947]  [fusion_1948]  [fusion_1949]  [fusion_1951]  [fusion_1953]  [fusion_1954]  [fusion_1955]  [fusion_1956]  [fusion_1957]  
[fusion_1958]  [fusion_2023]  [fusion_2024]  [fusion_2066]  [fusion_2067]  [fusion_2068]  [fusion_2073]  [fusion_2074]  [fusion_2090]  [fusion_2091]  
Fusion: TCGAAFF1 4q21.3 PTPN13 4q21.3 BLCA LUAD LUSC
Fusion : TICdbKMT2A [11q23.3]  -  AFF1 [4q21.3]
Polymorphisms : SNP and Copy number variants
NCBI Variation ViewerAFF1 [hg38]
dbSNP Single Nucleotide Polymorphism (NCBI)AFF1
Exome Variant ServerAFF1
ExAC (Exome Aggregation Consortium)AFF1 (select the gene name)
Genetic variants : HAPMAP4299
Genomic Variants (DGV)AFF1 [DGVbeta]
DECIPHERAFF1 [patients]   [syndromes]   [variants]   [genes]  
CONAN: Copy Number AnalysisAFF1 
ICGC Data PortalAFF1 
TCGA Data PortalAFF1 
Broad Tumor PortalAFF1
OASIS PortalAFF1 [ Somatic mutations - Copy number]
Cancer Gene: CensusAFF1 
Somatic Mutations in Cancer : COSMICAFF1  [overview]  [genome browser]  [tissue]  [distribution]  
Mutations and Diseases : HGMDAFF1
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 AFF1
DgiDB (Drug Gene Interaction Database)AFF1
DoCM (Curated mutations)AFF1 (select the gene name)
CIViC (Clinical Interpretations of Variants in Cancer)AFF1 (select a term)
NCG5 (London)AFF1
Cancer3DAFF1(select the gene name)
Impact of mutations[PolyPhen2] [SIFT Human Coding SNP] [Buck Institute : MutDB] [Mutation Assessor] [Mutanalyser]
Genetic Testing Registry AFF1
NextProtP51825 [Medical]
Target ValidationAFF1
Huge Navigator AFF1 [HugePedia]
snp3D : Map Gene to Disease4299
BioCentury BCIQAFF1
Clinical trials, drugs, therapy
Chemical/Protein Interactions : CTD4299
Chemical/Pharm GKB GenePA30851
Clinical trialAFF1
canSAR (ICR)AFF1 (select the gene name)
PubMed72 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 Jun 7 11:55:38 CEST 2017

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