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as the distances of all three first exons (1a is encoded by two exons; 1b and 1c) and their distances from each other (unpublished data).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 In addition, there are three independent first exons 1a, 1b and 1c (yet unpublished).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

Bibliography

Pubmed IDLast YearTitleAuthors

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
189773252008H3K79 methylation profiles define murine and human MLL-AF4 leukemias.203
208646722010Genetic variants influencing circulating lipid levels and risk of coronary artery disease.180
199131212009Gene-centric association signals for lipids and apolipoproteins identified via the HumanCVD BeadChip.85
203796142010Personalized smoking cessation: interactions between nicotine dose, dependence and quit-success genotype score.62
165519732006A murine Mll-AF4 knock-in model results in lymphoid and myeloid deregulation and hematologic malignancy.42
243671032014AFF1 is a ubiquitous P-TEFb partner to enable Tat extraction of P-TEFb from 7SK snRNP and formation of SECs for HIV transactivation.37
210309822011The leukemogenic AF4-MLL fusion protein causes P-TEFb kinase activation and altered epigenetic signatures.36
222916042012A genome-wide association study identified AFF1 as a susceptibility locus for systemic lupus eyrthematosus in Japanese.36
232606552013Leukemia fusion target AF9 is an intrinsically disordered transcriptional regulator that recruits multiple partners via coupled folding and binding.34
175818652007Oncogenic All1 fusion proteins target Drosha-mediated microRNA processing.31

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

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