AFF1 (AF4/FMR2 family, member 1)

2002-12-01   Rolf Marschalek  

Instituts für Pharmazeutische Biologie, JWG Universitaet Frankfurt\\\/Main, Biozentrum, N230, 303, Marie Curie Str. 9, D-60439 Frankfurt\\\/Main, Germany

Identity

HGNC
LOCATION
4q21.3
IMAGE
Atlas Image
LEGEND
MLLT2 (4q21) - Courtesy Mariano Rocchi, Resources for Molecular Cytogenetics.
LOCUSID
FUSION GENES

DNA/RNA

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as the distances of all three first exons (1a is encoded by two exons; 1b and 1c) and their distances from each other (unpublished data).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 In addition, there are three independent first exons 1a, 1b and 1c (yet unpublished).

Proteins

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 name
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 gene
5 MLL-3 AF4; 12kb
Fusion 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

Article Bibliography

Pubmed IDLast YearTitleAuthors
75429101995Molecular basis of 11q23 rearrangements in hematopoietic malignant proliferations.Bernard OA et al
14236251992The 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 et al
84433741993A serine/proline-rich protein is fused to HRX in t(4;11) acute leukemias.Morrissey J et al
92335801997Exon/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 et al
8558942199611q23 rearrangements in acute leukemia.Rubnitz JE et al
89770381996Chromosome abnormalities in leukaemia: the 11q23 paradigm.Young BD et al

Other Information

Locus ID:

NCBI: 4299
MIM: 159557
HGNC: 7135
Ensembl: ENSG00000172493

Variants:

dbSNP: 4299
ClinVar: 4299
TCGA: ENSG00000172493
COSMIC: AFF1

RNA/Proteins

Gene IDTranscript IDUniprot
ENSG00000172493ENST00000307808P51825
ENSG00000172493ENST00000395146P51825
ENSG00000172493ENST00000503477E7EMC5
ENSG00000172493ENST00000507468E7ETI4
ENSG00000172493ENST00000511442D6RIZ5
ENSG00000172493ENST00000511722D6RAU0
ENSG00000172493ENST00000514970H0Y9S4
ENSG00000172493ENST00000544085F5GXF9

Expression (GTEx)

0
10
20
30
40
50
60
70
80
90
100

Pathways

PathwaySourceExternal ID
Transcriptional misregulation in cancerKEGGko05202
Transcriptional misregulation in cancerKEGGhsa05202

References

Pubmed IDYearTitleCitations
380293832024Functional relevance of circRNA aberrant expression in pediatric acute leukemia with KMT2A::AFF1 fusion.1
380293832024Functional relevance of circRNA aberrant expression in pediatric acute leukemia with KMT2A::AFF1 fusion.1
373138152023[AF4/FMR2 and IL-10 gene single nucleotide polymorphisms are correlated with disease susceptibility and immune infiltration in ankylosing spondylitis].0
373138152023[AF4/FMR2 and IL-10 gene single nucleotide polymorphisms are correlated with disease susceptibility and immune infiltration in ankylosing spondylitis].0
330697832021HOXA9/IRX1 expression pattern defines two subgroups of infant MLL-AF4-driven acute lymphoblastic leukemia.7
334935192021Suppression of the NTS-CPS1 regulatory axis by AFF1 in lung adenocarcinoma cells.1
339248502021Nuclear FGFR2 Interacts with the MLL-AF4 Oncogenic Chimera and Positively Regulates HOXA9 Gene Expression in t(4;11) Leukemia Cells.5
340480722021Prognostic impact of KMT2A-AFF1-positivity in 926 BCR-ABL1-negative B-lineage acute lymphoblastic leukemia patients treated in GIMEMA clinical trials since 1996.4
341112402021miR-130b and miR-128a are essential lineage-specific codrivers of t(4;11) MLL-AF4 acute leukemia.15
344895502021The role of reciprocal fusions in MLL-r acute leukemia: studying the chromosomal translocation t(4;11).6
345759042021Genetic and Epigenetic Characterization of a Discordant KMT2A/AFF1-Rearranged Infant Monozygotic Twin Pair.1
330697832021HOXA9/IRX1 expression pattern defines two subgroups of infant MLL-AF4-driven acute lymphoblastic leukemia.7
334935192021Suppression of the NTS-CPS1 regulatory axis by AFF1 in lung adenocarcinoma cells.1
339248502021Nuclear FGFR2 Interacts with the MLL-AF4 Oncogenic Chimera and Positively Regulates HOXA9 Gene Expression in t(4;11) Leukemia Cells.5
340480722021Prognostic impact of KMT2A-AFF1-positivity in 926 BCR-ABL1-negative B-lineage acute lymphoblastic leukemia patients treated in GIMEMA clinical trials since 1996.4

Citation

Rolf Marschalek

AFF1 (AF4/FMR2 family, member 1)

Atlas Genet Cytogenet Oncol Haematol. 2002-12-01

Online version: http://atlasgeneticsoncology.org/gene/3/aff1-(af4-fmr2-family-member-1)

Historical Card

1997-12-01 AFF1 (AF4/FMR2 family, member 1) by  Jean-Loup Huret 

Genetics, Dept Medical Information, University of Poitiers, CHU Poitiers Hospital, F-86021 Poitiers, France