FUS (fusion involved in t (12;16) in malignant liposarcoma)

2004-07-01 PA Pérez-Mancera , Isidro Sánchez-Garía Affiliation

Laboratorio 13, Instituto de Biologia Molecular y Celular del Cancer (IBMCC), Centro de Investigacion del Cancer, Campus Unamuno, 37.007-Salamanca, Spain

Identity

HGNC

FUS

LOCATION

16p11.2

LOCUSID

2521

ALIAS

ALS6,ETM4,FUS1,HNRNPP2,POMP75,TLS,altFUS

FUSION GENES

Show Gene Fusions

DNA/RNA

Description

The gene has 15 exons, and the total genomic sequence spanning the FUS gene is approx. 12 Kb.

Transcription

Transcript lenght: 1,9 Kb. There are two isoforms produced by an alternative splicing that involved the exon 4a (145 bp) or the exon 4b (142 bp).

Proteins

Description

526 amino acids (isoform with the exon 4a) or 525 aa (isoform with the exon 4b), 68 Kda. The protein contains different domains:

a N-terminal SYQG-rich region;

a RGG-rich region;

a RNA binding domain;

a RGG-rich region;

a Cys2/Cys2-zinc finger motif and;

a C-terminal RGG-rich region.

Expression

FUS is expressed in a housekeeping pattern.

Localisation

Nuclear, although FUS shuttles from the nucleus to the cytoplasm in a large complex that contains mRNA and hnRNPs.

Function

FUS is a RNA-binding protein that is identical to hnRNP P2 and may be implicated in mRNA metabolism. FUS seems to have a function as a heterogeneous ribonuclear protein (hnRNP)-like chaperone of RNA. In addition, it has been suggested that FUS might have a role in the BCR/ABL-mediated leukemogenesis.

Homology

FUS forms a sub-family of RNA binding proteins with EWS and RBP56/hTAFII68. FUS has homologous in mouse (fus), rat (pigpen) and Drosophila (Cabeza/SARFH).

Mutations

Germinal

In the mouse, germline mutation in the fus gene produces male sterility, sensitivity to radiation, defective B-lymphocyte development and activation, chromosomal instability and perinatal death.

Implicated in

Note

The FUS gene is implicated in several chromosomal translocations associated to both solid tumors and leukemias. The result of these chromosomal translocations are gene fusions. FUS contributes to these fusions with its N-terminal part, just before the RNA-binding domain. This domain confers to the fusion protein a transcriptional activation domain. These fusion genes generated as a result of chromosomal rearragements are used to monitor diagnosis and treatment.

Entity name

t(12;16)(q13;p11) chromosomal translocation. It produces the fusion protein FUS/ATF-1.

Disease

Angiomatoid fibrous histiocytoma (AFH).

Hybrid gene

FUS was interrupted at codon 175 (exon 5) and fused to codon 110 (exon 5) of ATF-1, resulting in an in-frame junction with a glycine to valine (GGT to GTT) transition.

Entity name

t(7;16)(q33;p11) chromosomal translocation. It produces the fusion protein FUS/CREB3L2 (also known as BBF2H7).

Disease

Low grade fibromyxoid sarcoma (LGFMS).

Hybrid gene

The breakpoints in the fusion transcripts are produced between the exons 6 or 7 of FUS and the exon 5 of CREB3L2.

Entity name

t(12;16)(q13;p11) chromosomal translocation. It produces the fusion protein FUS/DDIT3 (also known as CHOP).

Disease

Myxoid liposarcoma (MLS).

Hybrid gene

9 different types of fusions between the genes FUS and DDIT3 have been reported. The most frequent rearragements join the exons 5, 7 or 8 of FUS with the exon 2 of DDIT3.

Oncogenesis

The unequivocally relation between FUS/DDIT3 and the MLS was shown by the generation of a transgenic mouse model expressing FUS/DDIT3 from a housekeeping promoter.

Entity name

t(16;21)(p11;q22) chromosomal translocation. It produces the fusion protein FUS/ERG.

Disease

Acute myeloid leukemia (AML).

Hybrid gene

The junction of both genes is produced between the exons 6 or 7 of FUS and the exon 9 of ERG,or between the exon 8 of FUS and the exon 7 of ERG.

Breakpoints

Bibliography

Pubmed ID	Last Year	Title	Authors

Other Information

Locus ID:

NCBI: 2521
MIM: 137070
HGNC: 4010
Ensembl: ENSG00000089280

Variants:

dbSNP: 2521
ClinVar: 2521
TCGA: ENSG00000089280
COSMIC: FUS

RNA/Proteins

Gene ID	Transcript ID	Uniprot
ENSG00000089280	ENST00000254108	P35637
ENSG00000089280	ENST00000254108	Q6IBQ5
ENSG00000089280	ENST00000380244	P35637
ENSG00000089280	ENST00000566605	H3BNZ4
ENSG00000089280	ENST00000568685	H3BPE7

Expression (GTEx)

100

150

200

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

Pathways

Pathway	Source	External ID
Transcriptional misregulation in cancer	KEGG	ko05202
Transcriptional misregulation in cancer	KEGG	hsa05202
Gene Expression	REACTOME	R-HSA-74160
Processing of Capped Intron-Containing Pre-mRNA	REACTOME	R-HSA-72203
mRNA Splicing	REACTOME	R-HSA-72172
mRNA Splicing - Major Pathway	REACTOME	R-HSA-72163

Protein levels (Protein atlas)

Not detected

Low

Medium

High

References

Pubmed ID	Year	Title	Citations
19251627	2009	Mutations in the FUS/TLS gene on chromosome 16 cause familial amyotrophic lateral sclerosis.	851
19251628	2009	Mutations in FUS, an RNA processing protein, cause familial amyotrophic lateral sclerosis type 6.	816
18509338	2008	Induced ncRNAs allosterically modify RNA-binding proteins in cis to inhibit transcription.	390
20606625	2010	ALS-associated fused in sarcoma (FUS) mutations disrupt Transportin-mediated nuclear import.	282
20864052	2010	TDP-43 and FUS in amyotrophic lateral sclerosis and frontotemporal dementia.	263
23023293	2012	Divergent roles of ALS-linked proteins FUS/TLS and TDP-43 intersect in processing long pre-mRNAs.	261
19303844	2009	Rethinking ALS: the FUS about TDP-43.	224
19674978	2009	A new subtype of frontotemporal lobar degeneration with FUS pathology.	219
20699327	2010	Mutant FUS proteins that cause amyotrophic lateral sclerosis incorporate into stress granules.	200
21541367	2011	Molecular determinants and genetic modifiers of aggregation and toxicity for the ALS disease protein FUS/TLS.	186

Citation

PA Pérez-Mancera ; Isidro Sánchez-Garía

FUS (fusion involved in t (12;16) in malignant liposarcoma)

Atlas Genet Cytogenet Oncol Haematol. 2004-07-01

Online version: http://atlasgeneticsoncology.org/gene/44/case-report-explorer/haematological-explorer/