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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)

Identity

Alias_namesPBM1
MLLT2
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
AF4
Other aliasFEL
ALL1
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 87007001 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 2017)
Data from Atlas, Mitelman, Cosmic Fusion, Fusion Cancer, TCGA fusion databases with official HUGO symbols (see references in chromosomal bands)
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)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)

DNA/RNA

 
  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as the distances of all three first exons (1a is encoded by two exons; 1b and 1c) and their distances from each other (unpublished data).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).

Protein

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

Note
  
Entity t(4;11)(q21;q23)/acute leukaemias. --> KMT2A - AFF1
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
  

Bibliography

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
 

Citation

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 : http://AtlasGeneticsOncology.org/Genes/AF4ID3.html
History of this paper:
Huret, JL. AF4 (ALL1 fused gene from chromosome 4). Atlas Genet Cytogenet Oncol Haematol. 1997;1(2):54-55.
http://documents.irevues.inist.fr/bitstream/handle/2042/32048/12-1997-AF4ID3.pdf


Other Leukemias implicated (Data extracted from papers in the Atlas) [ 8 ]
  11q23 rearrangements (KMT2A) in therapy related leukaemias
t(4;11)(q21;q23) KMT2A/AFF1
ins(4;11)(q21;q23q23) AFF1/DSCAML1
ins(4;11)(q21;q23q23) AFF1/FXYD6
t(4;11)(q21;q23) AFF1/CCDC84
AFF1/PBX1 ()
AFF1/RABGAP1L ()
t(4;14)(q21;q24) AFF1/RAD51B


Other Solid tumors implicated (Data extracted from papers in the Atlas) [ 1 ]
  AFF1/PTPN13 (4q21)


External links

Nomenclature
HGNC (Hugo)AFF1   7135
Cards
AtlasAF4ID3
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]  ENSG00000172493 [Sequence]  chr4:87007001-87141054 [Contig_View]  AFF1 [Vega]
ICGC DataPortalENSG00000172493
TCGA cBioPortalAFF1
AceView (NCBI)AFF1
Genatlas (Paris)AFF1
WikiGenes4299
SOURCE (Princeton)AFF1
Genetics Home Reference (NIH)AFF1
Genomic and cartography
GoldenPath hg38 (UCSC)AFF1  -     chr4:87007001-87141054 +  4q21.3-q22.1   [Description]    (hg38-Dec_2013)
GoldenPath hg19 (UCSC)AFF1  -     4q21.3-q22.1   [Description]    (hg19-Feb_2009)
GoldenPathAFF1 - 4q21.3-q22.1 [CytoView hg19]  AFF1 - 4q21.3-q22.1 [CytoView hg38]
ImmunoBaseENSG00000172493
Mapping of homologs : NCBIAFF1 [Mapview hg19]  AFF1 [Mapview hg38]
OMIM159557   
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]
GenevestigatorExpression in : [tissues]  [cell-lines]  [cancer]  [perturbations]  
BioGPS (Tissue expression)4299
GTEX Portal (Tissue expression)AFF1
Human Protein AtlasENSG00000172493-AFF1 [pathology]   [cell]   [tissue]
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
PhosPhoSitePlusP51825
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 (RSDB)2LM0   
PDB Europe2LM0   
PDB (PDBSum)2LM0   
PDB (IMB)2LM0   
Structural Biology KnowledgeBase2LM0   
SCOP (Structural Classification of Proteins)2LM0   
CATH (Classification of proteins structures)2LM0   
SuperfamilyP51825
Human Protein Atlas [tissue]ENSG00000172493-AFF1 [tissue]
Peptide AtlasP51825
HPRD08871
IPIIPI00873029   IPI00908935   IPI00965976   IPI01010992   IPI00164675   IPI00396310   IPI00968090   
Protein Interaction databases
DIP (DOE-UCLA)P51825
IntAct (EBI)P51825
FunCoupENSG00000172493
BioGRIDAFF1
STRING (EMBL)AFF1
ZODIACAFF1
Ontologies - Pathways
QuickGOP51825
Ontology : AmiGOdouble-stranded DNA binding  DNA-binding transcription factor activity  protein binding  nucleus  regulation of transcription, DNA-templated  transcription elongation factor complex  transcription elongation factor complex  ELL-EAF complex  
Ontology : EGO-EBIdouble-stranded DNA binding  DNA-binding transcription factor activity  protein binding  nucleus  regulation of transcription, DNA-templated  transcription elongation factor complex  transcription elongation factor complex  ELL-EAF complex  
Pathways : KEGGTranscriptional misregulation in cancer   
NDEx NetworkAFF1
Atlas of Cancer Signalling NetworkAFF1
Wikipedia pathwaysAFF1
Orthology - Evolution
OrthoDB4299
GeneTree (enSembl)ENSG00000172493
Phylogenetic Trees/Animal Genes : TreeFamAFF1
HOGENOMP51825
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 : COSMICKMT2A [11q23.3]  -  AFF1 [4q21.3]  [fusion_1799]  [fusion_1801]  [fusion_1827]  [fusion_1828]  [fusion_1829]  [fusion_1830]  [fusion_1947]  
[fusion_1948]  [fusion_1951]  [fusion_1953]  [fusion_1954]  [fusion_1955]  [fusion_1956]  [fusion_1958]  [fusion_2023]  [fusion_2066]  [fusion_2068]  
[fusion_2073]  [fusion_2091]  
Fusion PortalAFF1 4q21.3 PTPN13 4q21.3 BLCA LUAD LUSC
Fusion : TICdbKMT2A [11q23.3]  -  AFF1 [4q21.3]
Fusion : FusionGDB1000    1001    1002    1003    1004    1005    1006    1007    1008    1009    1010    14407    16121    17341    19083   
20470    29419    36081    4819    6064    995    996    997    998    999   
Fusion : Fusion_HubADAM12--AFF1    AFF1--ADAM12    AFF1--AFF1    AFF1--AMFR    AFF1--ANO6    AFF1--ARHGAP10    AFF1--ARHGAP17    AFF1--ATP9B    AFF1--C1QTNF1    AFF1--C4ORF36    AFF1--CCDC84    AFF1--CCNI    AFF1--CDC16    AFF1--CEP63    AFF1--CHTF8   
AFF1--CUX1    AFF1--DAD1    AFF1--DHRS13    AFF1--DOM    AFF1--DSCAML1    AFF1--ELF2    AFF1--EXOC2    AFF1--FAM13A    AFF1--FBXL5    AFF1--FNDC3B    AFF1--FXYD6    AFF1--GAS7    AFF1--GAST    AFF1--GCC2    AFF1--GPRIN3   
AFF1--HMGB1    AFF1--HOXA13    AFF1--HSD17B11    AFF1--IL10RB    AFF1--KIAA1109    AFF1--KLHL8    AFF1--KMT2A    AFF1--LPIN1    AFF1--LYZ    AFF1--MLL    AFF1--MRPS21    AFF1--NDUFC1    AFF1--NFKB1    AFF1--NPM1    AFF1--PAIP2   
AFF1--PAQR3    AFF1--PARD3    AFF1--PBX1    AFF1--PHACTR2    AFF1--PIM1    AFF1--PTPN13    AFF1--RABGAP1L    AFF1--RBFOX1    AFF1--RP11-138I17.1.1    AFF1--SEPT2    AFF1--SH3RF2    AFF1--SLC25A12    AFF1--SLTM    AFF1--SNRNP48    AFF1--SPARCL1   
AFF1--SRSF11    AFF1--SSBP2    AFF1--STARD13    AFF1--TAX1BP1    AFF1--TFRC    AFF1--TG    AFF1--TRIM33    AFF1--UBB    AFF1--UBE2D3    AFF1--UBE2K    AFF1--USP53    AFF1--WWOX    AFF1--ZFAND3    AFF1--ZNF684    ARFIP1--AFF1   
ATF7IP--AFF1    C1QTNF1--AFF1    CHD2--AFF1    FAM190A--AFF1    GAS7--AFF1    HERC3--AFF1    HIVEP3--AFF1    IL10RB--AFF1    KMT2A--AFF1    LPIN1--AFF1    LYZ--AFF1    MLL--AFF1    PPP2R5A--AFF1    PTPN13--AFF1    RNF150--AFF1   
SRSF11--AFF1    SYNC--AFF1    USP53--AFF1   
Fusion : QuiverAFF1
Polymorphisms : SNP and Copy number variants
NCBI Variation ViewerAFF1 [hg38]
dbSNP Single Nucleotide Polymorphism (NCBI)AFF1
dbVarAFF1
ClinVarAFF1
1000_GenomesAFF1 
Exome Variant ServerAFF1
ExAC (Exome Aggregation Consortium)ENSG00000172493
GNOMAD BrowserENSG00000172493
Varsome BrowserAFF1
Genetic variants : HAPMAP4299
Genomic Variants (DGV)AFF1 [DGVbeta]
DECIPHERAFF1 [patients]   [syndromes]   [variants]   [genes]  
CONAN: Copy Number AnalysisAFF1 
Mutations
ICGC Data PortalAFF1 
TCGA Data PortalAFF1 
Broad Tumor PortalAFF1
OASIS PortalAFF1 [ Somatic mutations - Copy number]
Somatic Mutations in Cancer : COSMICAFF1  [overview]  [genome browser]  [tissue]  [distribution]  
Somatic Mutations in Cancer : COSMIC3DAFF1
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)
intoGenAFF1
NCG5 (London)AFF1
Cancer3DAFF1(select the gene name)
Impact of mutations[PolyPhen2] [Provean] [Buck Institute : MutDB] [Mutation Assessor] [Mutanalyser]
Diseases
OMIM159557   
Orphanet14433   
DisGeNETAFF1
MedgenAFF1
Genetic Testing Registry AFF1
NextProtP51825 [Medical]
TSGene4299
GENETestsAFF1
Target ValidationAFF1
Huge Navigator AFF1 [HugePedia]
snp3D : Map Gene to Disease4299
BioCentury BCIQAFF1
ClinGenAFF1
Clinical trials, drugs, therapy
Chemical/Protein Interactions : CTD4299
Chemical/Pharm GKB GenePA30851
Clinical trialAFF1
Miscellaneous
canSAR (ICR)AFF1 (select the gene name)
DataMed IndexAFF1
Probes
Litterature
PubMed87 Pubmed reference(s) in Entrez
GeneRIFsGene References Into Functions (Entrez)
CoreMineAFF1
EVEXAFF1
GoPubMedAFF1
iHOPAFF1
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

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indexed on : Wed Nov 13 20:59:11 CET 2019

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