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AFF1 (AF4/FMR2 family, member 1)


Other namesFEL
MLLT2 (myeloid/lymphoid leukemia translocated to, 2).
HGNC (Hugo) AFF1
LocusID (NCBI) 4299
Location 4q21.3
Location_base_pair Starts at 87856154 and ends at 88062206 bp from pter ( according to hg19-Feb_2009)  [Mapping]
  MLLT2 (4q21) - Courtesy Mariano Rocchi, Resources for Molecular Cytogenetics.


  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as the distances of all three first exons (1a is encoded by two exons; 1b and 1c) and their distances from each other (unpublished data).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 In addition, there are three independent first exons 1a, 1b and 1c (yet unpublished).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 ANLL (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

Other Leukemias implicated (Data extracted from papers in the Atlas)

Leukemias 11q23ChildAMLID1615 11q23ID1030 11q23secondLeukID1131 t1119ELLID1029 t0812q24q22ID2057
t0814ID1050 8p11inMPDID1091 inv8p11q13ID1189

External links

HGNC (Hugo)AFF1   7135
Entrez_Gene (NCBI)AFF1  4299  AF4/FMR2 family, member 1
GeneCards (Weizmann)AFF1
Ensembl (Hinxton)ENSG00000172493 [Gene_View]  chr4:87856154-88062206 [Contig_View]  AFF1 [Vega]
ICGC DataPortalENSG00000172493
AceView (NCBI)AFF1
Genatlas (Paris)AFF1
SOURCE (Princeton)NM_001166693 NM_005935
Genomic and cartography
GoldenPath (UCSC)AFF1  -  4q21.3   chr4:87856154-88062206 +  4q21.3   [Description]    (hg19-Feb_2009)
EnsemblAFF1 - 4q21.3 [CytoView]
Mapping of homologs : NCBIAFF1 [Mapview]
Gene and transcription
Genbank (Entrez)AF024541 AF177236 AF177237 AF177238 AF177239
RefSeq transcript (Entrez)NM_001166693 NM_005935
RefSeq genomic (Entrez)AC_000136 NC_000004 NC_018915 NT_016354 NW_001838915 NW_004929320
Consensus coding sequences : CCDS (NCBI)AFF1
Cluster EST : UnigeneHs.480190 [ NCBI ]
CGAP (NCI)Hs.480190
Alternative Splicing : Fast-db (Paris)GSHG0022708
Alternative Splicing GalleryENSG00000172493
Gene ExpressionAFF1 [ NCBI-GEO ]     AFF1 [ SEEK ]   AFF1 [ MEM ]
Protein : pattern, domain, 3D structure
UniProt/SwissProtP51825 (Uniprot)
NextProtP51825  [Medical]
With graphics : InterProP51825
Splice isoforms : SwissVarP51825 (Swissvar)
Domains : Interpro (EBI)TF_AF4/FMR2 [organisation]  
Related proteins : CluSTrP51825
Domain families : Pfam (Sanger)AF-4 (PF05110)   
Domain families : Pfam (NCBI)pfam05110   
DMDM Disease mutations4299
Blocks (Seattle)P51825
PDB (SRS)2LM0   
PDB (PDBSum)2LM0   
PDB (IMB)2LM0   
Human Protein AtlasENSG00000172493 [gene] [tissue] [antibody] [cell] [cancer]
Peptide AtlasP51825
IPIIPI00873029   IPI00908935   IPI00965976   IPI01010992   IPI00164675   IPI00396310   IPI00968090   
Protein Interaction databases
IntAct (EBI)P51825
Interologous Interaction database P51825
Ontologies - Pathways
Ontology : AmiGOsequence-specific DNA binding transcription factor activity  protein binding  nucleus  positive regulation of transcription, DNA-templated  
Ontology : EGO-EBIsequence-specific DNA binding transcription factor activity  protein binding  nucleus  positive regulation of transcription, DNA-templated  
Pathways : KEGGTranscriptional misregulation in cancer   
Protein Interaction DatabaseAFF1
Wikipedia pathwaysAFF1
Gene fusion - rearrangments
Rearrangement : TICdbKMT2A [11q23.3]  -  AFF1 [3q13.13]
Polymorphisms : SNP, mutations, diseases
SNP Single Nucleotide Polymorphism (NCBI)AFF1
snp3D : Map Gene to Disease4299
SNP (GeneSNP Utah)AFF1
Genetic variants : HAPMAPAFF1
Exome VariantAFF1
ICGC programENSG00000172493 
Cancer Gene: CensusAFF1 
Somatic Mutations in Cancer : COSMICAFF1 
CONAN: Copy Number AnalysisAFF1 
Mutations and Diseases : HGMDAFF1
Mutations and Diseases : intOGenAFF1
Genomic VariantsAFF1  AFF1 [DGVbeta]
Pred. of missensesPolyPhen-2  SIFT(SG)  SIFT(JCVI)  Align-GVGD  MutAssessor  Mutanalyser  
Pred. splicesGeneSplicer  Human Splicing Finder  MaxEntScan  
Disease Genetic AssociationAFF1
Huge Navigator AFF1 [HugePedia]  AFF1 [HugeCancerGEM]
General knowledge
Homologs : HomoloGeneAFF1
Homology/Alignments : Family Browser (UCSC)AFF1
Phylogenetic Trees/Animal Genes : TreeFamAFF1
Chemical/Protein Interactions : CTD4299
Chemical/Pharm GKB GenePA30851
Clinical trialAFF1
Cancer Resource (Charite)ENSG00000172493
Other databases
ProbeCancer Cytogenetics (Bari)
PubMed64 Pubmed reference(s) in Entrez


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
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
Chromosome abnormalities in leukaemia: the 11q23 paradigm.
Young BD, Saha V
Cancer surveys. 1996 ; 28 : 225-245.
PMID 8977038
Molecular basis of 11q23 rearrangements in hematopoietic malignant proliferations.
Bernard OA, Berger R
Genes, chromosomes & cancer. 1995 ; 13 (2) : 75-85.
PMID 7542910
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
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, Knrr C, Siegler G, Greil J, Fey GH, Marschalek R
British journal of haematology. 1997 ; 98 (1) : 157-169.
PMID 9233580
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

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Written12-1997Jean-Loup Huret
Updated12-2002Rolf Marschalek


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 online version   Free pdf version   [Bibliographic record ]
Atlas Genet Cytogenet Oncol Haematol. December 1997

© Atlas of Genetics and Cytogenetics in Oncology and Haematology
indexed on : Tue Aug 26 15:26:28 CEST 2014

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