AFF3 (lymphoid nuclear protein related to AF4)

2003-08-01   Anne RM von Bergh  

Afdeling Klinische Genetica, Erasmus MC, Dr. Molewaterplein 50, 3015 GE Rotterdam, The Netherlands

Identity

HGNC
AFF3
LOCATION
2q11.2
LOCUSID
3899
ALIAS
KINS,LAF4,MLLT2-like
FUSION GENES
Show Gene Fusions

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

Homology

Belongs to the AF4/LAF4/FMR2/AF5q31 family.

Implicated in

Entity name
t(2;11)(q11;q23) . --> KMT2A- LAF4
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.
Atlas Image
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

Atlas Image

Bibliography

Pubmed IDLast YearTitleAuthors
126610122003Occurrence 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
127436082003Fusion of an AF4-related gene, LAF4, to MLL in childhood acute lymphoblastic leukemia with t(2;11)(q11;q23).Hiwatari M et al
85554981996LAF-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
122037952002LAF4, 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

Gene IDTranscript IDUniprot
ENSG00000144218ENST00000317233P51826
ENSG00000144218ENST00000409236P51826
ENSG00000144218ENST00000409579P51826
ENSG00000144218ENST00000415384C9JUY1
ENSG00000144218ENST00000416492C9JMS1
ENSG00000144218ENST00000423966C9JC67
ENSG00000144218ENST00000424600C9J847
ENSG00000144218ENST00000427118C9JIB1
ENSG00000144218ENST00000430789H7C3W3
ENSG00000144218ENST00000432037C9J622
ENSG00000144218ENST00000440445C9JUC4
ENSG00000144218ENST00000441400C9JZ66
ENSG00000144218ENST00000445815H7C4C2

Expression (GTEx)

0
5
10
15
20
25
Adipose - Subcutaneous
Adipose - Visceral
Adrenal Gland
Artery - Aorta
Artery - Tibial
Bladder
Brain - Amygdala
Brain - Anterior cingulate cortex
Brain - Caudate
Brain - Cerebellar Hemisphere
Brain - Cerebellum
Brain - Cortex
Brain - Frontal Cortex
Brain - Hippocampus
Brain - Hypothalamus
Brain - Nucleus accumbens
Brain - Putamen
Brain - Spinal cord
Brain - Substantia nigra
Breast - Mammary Tissue
Cells - Cultured fibroblasts
Cells - EBV - transformed lymphocytes
Cervix - Ectocervix
Cervix - Endocervix
Colon - Sigmoid
Colon - Transverse
Esophagus - Gastroesophageal Junction
Esophagus - Mucosa
Esophagus - Muscularis
Fallopian Tube
Heart - Atrial Appendage
Heart - Left Ventricle
Kidney - Cortex
Kidney - Medulla
Liver
Lung
Minor Salivary Gland
Muscle - Skeletal
Nerve - Tibial
Ovary
Pancreas
Pituitary
Prostate
Skin - Not Sun Exposed
Skin - Sun Exposed
Small Intestine - Terminal Ileum
Spleen
Stomach
Testis
Thyroid
Uterus
Vagina
Whole Blood

Protein levels (Protein atlas)

Not detected
Low
Medium
High
cerebral cortex
cerebellum
hippocampus
caudate
thyroid gland
parathyroid gland
adrenal gland
nasopharynx
bronchus
lung
salivary gland
esophagus
stomach 1
stomach 2
duodenum
small intestine
colon
rectum
liver
gallbladder
pancreas
kidney
urinary bladder
testis
epididymis
seminal vesicle
prostate
vagina
ovary
fallopian tube
endometrium 1
endometrium 2
cervix, uterine
placenta
breast
heart muscle
smooth muscle
skeletal muscle
soft tissue 1
soft tissue 2
adipose tissue
skin 1
skin 2
appendix
spleen
lymph node
tonsil
bone marrow

References

Pubmed IDYearTitleCitations
388119452024Variant-specific pathophysiological mechanisms of AFF3 differently influence transcriptome profiles.0
388867302024Integrated mendelian randomization analyses highlight AFF3 as a novel eQTL-mediated susceptibility gene in renal cancer and its potential mechanisms.0
388119452024Variant-specific pathophysiological mechanisms of AFF3 differently influence transcriptome profiles.0
388867302024Integrated mendelian randomization analyses highlight AFF3 as a novel eQTL-mediated susceptibility gene in renal cancer and its potential mechanisms.0
362733792023A novel variant in AFF3 underlying isolated syndactyly.2
365761402023Three KINSSHIP syndrome patients with mosaic and germline AFF3 variants.2
362733792023A novel variant in AFF3 underlying isolated syndactyly.2
365761402023Three KINSSHIP syndrome patients with mosaic and germline AFF3 variants.2
339617792021Variants in the degron of AFF3 are associated with intellectual disability, mesomelic dysplasia, horseshoe kidney, and epileptic encephalopathy.14
341041182021Association of AFF3 Gene Polymorphism rs10865035 with Rheumatoid Arthritis: A Population-Based Case-Control Study on a Pakistani Cohort.4
339617792021Variants in the degron of AFF3 are associated with intellectual disability, mesomelic dysplasia, horseshoe kidney, and epileptic encephalopathy.14
341041182021Association of AFF3 Gene Polymorphism rs10865035 with Rheumatoid Arthritis: A Population-Based Case-Control Study on a Pakistani Cohort.4
303269372018AFF3 upregulation mediates tamoxifen resistance in breast cancers.15
303269372018AFF3 upregulation mediates tamoxifen resistance in breast cancers.15
284019702017Integrating 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/js/gene-fusions/?id=315