AFF3 (lymphoid nuclear protein related to AF4)

2003-08-01 Anne RM von Bergh Affiliation

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.

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

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

Gene ID	Transcript ID	Uniprot
ENSG00000144218	ENST00000317233	P51826
ENSG00000144218	ENST00000409236	P51826
ENSG00000144218	ENST00000409579	P51826
ENSG00000144218	ENST00000415384	C9JUY1
ENSG00000144218	ENST00000416492	C9JMS1
ENSG00000144218	ENST00000423966	C9JC67
ENSG00000144218	ENST00000424600	C9J847
ENSG00000144218	ENST00000427118	C9JIB1
ENSG00000144218	ENST00000430789	H7C3W3
ENSG00000144218	ENST00000432037	C9J622
ENSG00000144218	ENST00000440445	C9JUC4
ENSG00000144218	ENST00000441400	C9JZ66
ENSG00000144218	ENST00000445815	H7C4C2

Expression (GTEx)

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

References

Pubmed ID	Year	Title	Citations
19240061	2009	Coeliac disease-associated risk variants in TNFAIP3 and REL implicate altered NF-kappaB signalling.	75
20379614	2010	Personalized smoking cessation: interactions between nicotine dose, dependence and quit-success genotype score.	62
19359276	2009	Identification of AF4/FMR2 family, member 3 (AFF3) as a novel rheumatoid arthritis susceptibility locus and confirmation of two further pan-autoimmune susceptibility genes.	35
20498205	2010	Investigation of potential non-HLA rheumatoid arthritis susceptibility loci in a European cohort increases the evidence for nine markers.	23
20072139	2010	Association of the AFF3 gene and IL2/IL21 gene region with juvenile idiopathic arthritis.	21
21330300	2011	Functional characterization of the AFF (AF4/FMR2) family of RNA-binding proteins: insights into the molecular pathology of FRAXE intellectual disability.	21
12203795	2002	LAF4, an AF4-related gene, is fused to MLL in infant acute lymphoblastic leukemia.	15
20219786	2011	The role of rheumatoid arthritis genetic susceptibility markers in the prediction of erosive disease in patients with early inflammatory polyarthritis: results from the Norfolk Arthritis Register.	13
12743608	2003	Fusion of an AF4-related gene, LAF4, to MLL in childhood acute lymphoblastic leukemia with t(2;11)(q11;q23).	11
24763282	2014	FRA2A is a CGG repeat expansion associated with silencing of AFF3.	11

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