AFF3 (lymphoid nuclear protein related to AF4)
2003-08-01 Anne RM von Bergh AffiliationAfdeling Klinische Genetica, Erasmus MC, Dr. Molewaterplein 50, 3015 GE Rotterdam, The Netherlands
Identity
HGNC
LOCATION
2q11.2
LOCUSID
ALIAS
KINS,LAF4,MLLT2-like
FUSION GENES
DNA/RNA
Description
at least 17 exons.
Transcription
in a telomere to centromere direction; 3857 bp mRNA; 3684 bp open reading frame.
Proteins
Description
1227 amino acids; 133734 Da.
Expression
Preferentially expressed in lymphoid tissues, highest levels being found in the thymus. Lower expression in brain and lung.
Localisation
Nuclear
Function
Putative transcription activator that may function in lymphoid development and oncogenesis. Binds in vitro to double-stranded DNA
Implicated in
Entity name
Note
MLL fusion partner at chromosome 2 in infant ALL
Disease
The three cases reported to date were all infant-ALL with proB phenotype
Prognosis
Prognosis is poor, although based on only three cases.
Cytogenetics
The three reported cases harboured different rearrangements involving chromosomes 2 and 11: t(2;11)(q11;q23), t(2;11)(p15;p14), and ins(11;2)(q23;q11.2q11.2).
Fusion protein
The MLL-LAF4 fusion protein includes the transactivation domain of LAF4 that is part of the AF4/LAF4/FMR2 homology domain.
Coding sequence of LAF4 compared to AF4 and site of fusion. Schematic representation of MLL, LAF4, AF4, and the putative MLL-LAF4 fusion protein. Domains in MLL are shaded: MT, DNA methyltransferase homology region; TRX, Drosophila trithorax homology. The percentage of amino acid homology between corresponding regions of LAF4 and AF4 is indicated: NHD, N-terminal homology domain; ALF, AF4/LAF4/FMR2 homology domain; TAD, transactivation domain; NLS, nuclear localization sequence; CHD, C-terminal homology domain. Arrows indicate the fusion sites with MLL. The breakpoint in LAF4 corresponds to one of the known breakpoints in AF4.
Breakpoints
Article Bibliography
| Pubmed ID | Last Year | Title | Authors |
|---|---|---|---|
| 12661012 | 2003 | Occurrence of an MLL/LAF4 fusion gene caused by the insertion ins(11;2)(q23;q11.2q11.2) in an infant with acute lymphoblastic leukemia. | Bruch J et al |
| 12743608 | 2003 | Fusion of an AF4-related gene, LAF4, to MLL in childhood acute lymphoblastic leukemia with t(2;11)(q11;q23). | Hiwatari M et al |
| 8555498 | 1996 | LAF-4 encodes a lymphoid nuclear protein with transactivation potential that is homologous to AF-4, the gene fused to MLL in t(4;11) leukemias. | Ma C et al |
| 12203795 | 2002 | LAF4, an AF4-related gene, is fused to MLL in infant acute lymphoblastic leukemia. | von Bergh AR et al |
Other Information
Locus ID:
NCBI: 3899
MIM: 601464
HGNC: 6473
Ensembl: ENSG00000144218
Variants:
dbSNP: 3899
ClinVar: 3899
TCGA: ENSG00000144218
COSMIC: AFF3
RNA/Proteins
Expression (GTEx)
Protein levels (Protein atlas)
References
| Pubmed ID | Year | Title | Citations |
|---|---|---|---|
| 38811945 | 2024 | Variant-specific pathophysiological mechanisms of AFF3 differently influence transcriptome profiles. | 0 |
| 38886730 | 2024 | Integrated mendelian randomization analyses highlight AFF3 as a novel eQTL-mediated susceptibility gene in renal cancer and its potential mechanisms. | 0 |
| 38811945 | 2024 | Variant-specific pathophysiological mechanisms of AFF3 differently influence transcriptome profiles. | 0 |
| 38886730 | 2024 | Integrated mendelian randomization analyses highlight AFF3 as a novel eQTL-mediated susceptibility gene in renal cancer and its potential mechanisms. | 0 |
| 36273379 | 2023 | A novel variant in AFF3 underlying isolated syndactyly. | 2 |
| 36576140 | 2023 | Three KINSSHIP syndrome patients with mosaic and germline AFF3 variants. | 2 |
| 36273379 | 2023 | A novel variant in AFF3 underlying isolated syndactyly. | 2 |
| 36576140 | 2023 | Three KINSSHIP syndrome patients with mosaic and germline AFF3 variants. | 2 |
| 33961779 | 2021 | Variants in the degron of AFF3 are associated with intellectual disability, mesomelic dysplasia, horseshoe kidney, and epileptic encephalopathy. | 14 |
| 34104118 | 2021 | Association of AFF3 Gene Polymorphism rs10865035 with Rheumatoid Arthritis: A Population-Based Case-Control Study on a Pakistani Cohort. | 4 |
| 33961779 | 2021 | Variants in the degron of AFF3 are associated with intellectual disability, mesomelic dysplasia, horseshoe kidney, and epileptic encephalopathy. | 14 |
| 34104118 | 2021 | Association of AFF3 Gene Polymorphism rs10865035 with Rheumatoid Arthritis: A Population-Based Case-Control Study on a Pakistani Cohort. | 4 |
| 30326937 | 2018 | AFF3 upregulation mediates tamoxifen resistance in breast cancers. | 15 |
| 30326937 | 2018 | AFF3 upregulation mediates tamoxifen resistance in breast cancers. | 15 |
| 28401970 | 2017 | Integrating multiple omics data for the discovery of potential Beclin-1 interactions in breast cancer. | 7 |
Citation
Anne RM von Bergh
AFF3 (lymphoid nuclear protein related to AF4)
Atlas Genet Cytogenet Oncol Haematol. 2003-08-01
Online version: http://atlasgeneticsoncology.org/gene/315/aff3-(lymphoid-nuclear-protein-related-to-af4)
