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

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

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





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


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).


Atlas Image


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.


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


    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.


    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).



    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

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


    Atlas Image


    Pubmed IDLast YearTitleAuthors
    89213631996Expression patterns of the human sarcoma-associated genes FUS and EWS and the genomic structure of FUS.Aman P et al
    12833161992Rearrangement of the transcription factor gene CHOP in myxoid liposarcomas with t(12;16)(q13;p11).Aman P et al
    75852571995Identification of hnRNP P2 as TLS/FUS using electrospray mass spectrometry.Calvio C et al
    85107581993Fusion of CHOP to a novel RNA-binding protein in human myxoid liposarcoma.Crozat A et al
    106550652000Fus deficiency in mice results in defective B-lymphocyte development and activation, high levels of chromosomal instability and perinatal death.Hicks GG et al
    105236521999Dual transforming activities of the FUS (TLS)-ERG leukemia fusion protein conferred by two N-terminal domains of FUS (TLS).Ichikawa H et al
    78050341995Translocation t(12;16)(q13;p11) in myxoid liposarcoma and round cell liposarcoma: molecular and cytogenetic analysis.Knight JC et al
    92425521997Consistent detection of TLS/FUS-ERG chimeric transcripts in acute myeloid leukemia with t(16;21)(p11;q22) and identification of a novel transcript.Kong XT et al
    106549432000Male sterility and enhanced radiation sensitivity in TLS(-/-) mice.Kuroda M et al
    97952131998Genomic structure of the human RBP56/hTAFII68 and FUS/TLS genes.Morohoshi F et al
    173448592007Genome-wide analysis of genetic alterations in acute lymphoblastic leukaemia.Mullighan CG et al
    118965992002Expression of the FUS domain restores liposarcoma development in CHOP transgenic mice.Pérez-Mancera PA et al
    151390012004The chimeric FUS/CREB3l2 gene is specific for low-grade fibromyxoid sarcoma.Panagopoulos I et al
    96875111998TLS/FUS, a pro-oncogene involved in multiple chromosomal translocations, is a novel regulator of BCR/ABL-mediated leukemogenesis.Perrotti D et al
    79707321994TLS/FUS fusion domain of TLS/FUS-erg chimeric protein resulting from the t(16;21) chromosomal translocation in human myeloid leukemia functions as a transcriptional activation domain.Prasad DD et al
    75038111993Fusion of the dominant negative transcription regulator CHOP with a novel gene FUS by translocation t(12;16) in malignant liposarcoma.Rabbitts TH et al
    80587261994Transcriptional activation by TAL1 and FUS-CHOP proteins expressed in acute malignancies as a result of chromosomal abnormalities.Sánchez-García I et al
    129154802003Fusion of the FUS and BBF2H7 genes in low grade fibromyxoid sarcoma.Storlazzi CT et al
    110637922000Genetic characterization of angiomatoid fibrous histiocytoma identifies fusion of the FUS and ATF-1 genes induced by a chromosomal translocation involving bands 12q13 and 16p11.Waters BL et al
    92644611997TLS (FUS) binds RNA in vivo and engages in nucleo-cytoplasmic shuttling.Zinszner H et al

    Other Information

    Locus ID:

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


    dbSNP: 2521
    ClinVar: 2521
    TCGA: ENSG00000089280


    Gene IDTranscript IDUniprot

    Expression (GTEx)



    PathwaySourceExternal ID
    Transcriptional misregulation in cancerKEGGko05202
    Transcriptional misregulation in cancerKEGGhsa05202
    Gene ExpressionREACTOMER-HSA-74160
    Processing of Capped Intron-Containing Pre-mRNAREACTOMER-HSA-72203
    mRNA SplicingREACTOMER-HSA-72172
    mRNA Splicing - Major PathwayREACTOMER-HSA-72163

    Protein levels (Protein atlas)

    Not detected


    Pubmed IDYearTitleCitations
    192516272009Mutations in the FUS/TLS gene on chromosome 16 cause familial amyotrophic lateral sclerosis.851
    192516282009Mutations in FUS, an RNA processing protein, cause familial amyotrophic lateral sclerosis type 6.816
    185093382008Induced ncRNAs allosterically modify RNA-binding proteins in cis to inhibit transcription.390
    206066252010ALS-associated fused in sarcoma (FUS) mutations disrupt Transportin-mediated nuclear import.282
    208640522010TDP-43 and FUS in amyotrophic lateral sclerosis and frontotemporal dementia.263
    230232932012Divergent roles of ALS-linked proteins FUS/TLS and TDP-43 intersect in processing long pre-mRNAs.261
    193038442009Rethinking ALS: the FUS about TDP-43.224
    196749782009A new subtype of frontotemporal lobar degeneration with FUS pathology.219
    206993272010Mutant FUS proteins that cause amyotrophic lateral sclerosis incorporate into stress granules.200
    215413672011Molecular determinants and genetic modifiers of aggregation and toxicity for the ALS disease protein FUS/TLS.186


    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/fus-(fusion-involved-in-t-(12;16)-in-malignant-liposarcoma)