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SEPT9 (MLL septin-like fusion)

Written2000-04Jean-Loup Huret
Genetics, Dept Medical Information, University of Poitiers, CHU Poitiers Hospital, F-86021 Poitiers, France
Updated2001-08Linda M. Kalikin, Elizabeth M. Petty
Research Investigator, Department of Internal Medicine, The University of Michigan, USA

(Note : for Links provided by Atlas : click)


MLL septin-like fusion
Alias_symbol (synonym)MSF1
Other aliasMSF (MLL septin-like fusion)
AF17q25 (ALL1 fused gene from chromosome 17q25)
LocusID (NCBI) 10801
Atlas_Id 208
Location 17q25.2  [Link to chromosome band 17q25]
Location_base_pair Starts at 77281410 and ends at 77500596 bp from pter ( according to hg19-Feb_2009)  [Mapping SEPT9.png]
Local_order Maps to chromosome 17 interval D17S785-D17S836
Fusion genes
(updated 2017)
Data from Atlas, Mitelman, Cosmic Fusion, Fusion Cancer, TCGA fusion databases with official HUGO symbols (see references in chromosomal bands)
APPBP2 (17q23.2) / SEPT9 (17q25.2)APPBP2 (17q23.2) / SEPT9 (17q25.3)FCMR (1q32.1) / SEPT9 (17q25.2)
IFI27L2 (14q32.12) / SEPT9 (17q25.2)ITM2C (2q37.1) / SEPT9 (17q25.2)ITM2C (2q37.1) / SEPT9 (17q25.3)
KMT2A (11q23.3) / SEPT9 ()KMT2A (11q23.3) / SEPT9 (17q25.2)KMT2A (11q23.3) / SEPT9 (17q25.3)
SEPT9 (17q25.2) / ADGRA2 (8p11.23)SEPT9 (17q25.2) / DNAH17 (17q25.3)SEPT9 (17q25.2) / JMJD6 (17q25.1)
SEPT9 (17q25.2) / KMT2A (11q23.3)SEPT9 (17q25.2) / KRT32 (17q21.2)SEPT9 (17q25.2) / LPP (3q28)
SEPT9 (17q25.2) / MPO (17q22)SEPT9 (17q25.2) / NARF (17q25.3)SEPT9 (17q25.2) / SEC14L1 (17q25.2)
SEPT9 (17q25.2) / SEPT9 (17q25.2)SEPT9 (17q25.2) / TANC2 (17q23.2)SEPT9 (17q25.2) / THBS1 (15q14)
SEPT9 (17q25.3) / ADGRA2 (8p11.23)SEPT9 (17q25.3) / CYHR1 (8q24.3)SEPT9 (17q25.3) / DNAH17 (17q25.3)
SEPT9 (17q25.3) / JMJD6 (17q25.1)SEPT9 (17q25.3) / KRT32 (17q21.2)SEPT9 (17q25.3) / LPP (3q28)
SEPT9 (17q25.3) / MPO (17q22)SEPT9 (17q25.3) / NARF (17q25.3)SEPT9 (17q25.3) / SEC14L1 (17q25.2)
SEPT9 (17q25.3) / TANC2 (17q23.2)SEPT9 (17q25.3) / VAV1 (19p13.3)SINHCAF (12p11.21) / SEPT9 (17q25.3)
SLC34A3 (9q34.3) / SEPT9 (17q25.2)TYMS (18p11.32) / SEPT9 (17q25.2)UBAP1 (9p13.3) / SEPT9 (17q25.2)


  Genomic structure of published MSF alternatively spliced transcripts. Boxes indicate exons with coding regions colored in yellow and are drawn to scale. Exons are tentatively positioned in relative genomic order with overlapping exons indicating identical sequences. Translation start sites are indicated by an arrows and proceeds centromere to telomere on 17q25.
Transcription MSF exhibits 5' and 3' alternative splicing. The variable exons encode different translational start and stop sequences and are spliced on to a core of 8 coding exons. It is unclear the splicing mechanism between exon 12 and exon 13 subsets as splicing does not occur at traditional GT/AG conserved sequences. Multiple reports are consistent in observing expression of an approximately 4.0 kb transcript in all fetal and adult tissues. Additional transcripts at approximately 3.0 kb and 1.7 kb are variably reported and may reflect differences in probe sequence and experimental conditions between laboratories. MSF spans approximately 260 kb of DNA based on NotI PFGE mapping.


  Structure of MSF protein isoforms. Coding regions are indicated between red arrows. Like colors denote identical sequences. Domains are marked by light purple boxes for xylose isomerase, orange for polybasic, and red for GTPase. Gaps indicate missing sequences in that variant. References for a-c match those in the exon/intron figure. Figure is not drawn to scale.
Description Alternative transcript splicing results in translation of multiple MSF isoforms with distinct amino-and carboxy-termini. MSF-B and MSF-C proteins are identical and are sub-sequences within the other larger isoforms. All isoforms contain a GTPase domain, a xylose isomerase domain of unknown mammalian function but previously identified for sugar interconversion in some microorganisms, and a semi-conserved polybasic domain shown in the septin H5 to be necessary for membrane phospholipid binding.
Expression The MSF protein is believed to be widely expressed based on ubiquitous adult and fetal transcript expression, although individual isoforms may have tissue specific expression.
Localisation The MSF protein, like other septin family members, contains no subcellular localization signals and is thought to be largely cytoplasmic. Despite this, mammalian septins have been found in the mitochondria, in the nucleus, and associated with the plasma membrane and brain synaptic vesicles.
Function Although little information is currently available for MSF itself, research on other members of this highly conserved septin GTPase subfamily provides insight into potential functional roles of MSF. The original family members, Saccharomyces cerevisiae CDC3, CDC10, CDC11, and CDC12, were identified by rescue of temperature sensitive mutants exhibiting the near identical phenotypes of cell-cycle arrest, elongated bud growth, and impaired cytokinesis. They localize to the cleavage furrow, co-immunoprecipitate, and polymerize into filaments. Septins have since been broadly identified in most eukaryotic organisms except for plants. Despite the distinct mechanistic differences in cell division between yeast and animal cells, animal septins similarly localize to the contractile ring and polymerize into filaments. These filaments are composed of homo- and heteromultimers of septins, require GTP hydrolysis to assemble, and interact with anillin, an actin binding protein found at the contractile ring during cytokinesis. Like yeast, multinucleated cells are produced when septins are mutated. Isolation of the yeast septins SPR3 and SPR28 with roles in sporulation, however, provided the initial evidence for other septin functions in addition to cytokinesis. Binding of Cdc12p to the mating hormone induced Afr1p and of Cdc10p to the chitin associated Bni4p, suggests roles for septins in determining the site of fusion in yeast in chitin deposition, respectively. Identification of interacting proteins implicates yeast septins in cell cycle regulation based on binding to the mitosis-inducing protein kinase Gin4p (Cdc3p, Cdc10p, Cdc11p, Cdc12p, Sep7p), to the mitotic checkpoint Bub2p (Cdc3p), and to the cyclin Clb2p degrading polo kinase Cdc5p (Cdc11p and Cdc12p). In addition, yeast septins Cdc3p and Cdc11p are cell-cycle specific substrates for conjugation to the ubiquitin-related SUMOp. Of the mammalian septins, the ARTS protein translocates from the mitochondria to the nucleus and enhances cell death in response to TGF-b. CDC10, NEDD5, H5, E-septin and Septin 6 associate with the rat SEC6/SEC8 multimer, a key conserved complex in targeting exocytosis at the plasma membrane. H5 binds in a GDP-associated form to membrane phospholipids through a polybasic domain, and CDCREL-1 and NEDD5 co-purify with brain synaptic vesicles and interact with syntaxin, a key protein for vesicle-membrane fusion. Given that cytokinesis is one highly conserved role of septins, this later observation is somewhat unexpected given that brain typically exhibits minimal cell division activity. However, further evidence for septin roles in neuronal development are suggested by the degradation of CDCREL-1 after ubiquitination by the Parkinson's disease gene parkin and by the association of NEDD5, H5, and DIFF6 septins with neurofibrillary tangles in Alzheimer's disease. Thus, these data present a myriad of functions for members of the septin protein family that can be more broadly grouped into integral roles in cell cycle regulation, signal transduction, and protein/vesicle trafficking through cytoskeletal scaffolding. These functions are probably partially determined by tissue- and temporal-specific expression levels of individual septins and their isoforms and provide a framework for further characterization of MSF.
Homology MSF exhibits protein homology (% identity/% similarity) to the following orthologous septin family members: S. cerevisiae CDC10 47%/67%, D. melanogaster Pnut 39%/57%, R. norvegicus E-septin short 96%/97%, M. musculus SINT1 96%/98%, and to the following human septins also found as fusion proteins with MLL in leukemia patients: hCDCRel-1 in 22q11 45%/66%, Septin 6/KIAA0128 in Xq24 43%/66%.

Implicated in

Entity t(11;17)(q23;q25) acute non lymphocytic leukemia (AML) --> KMT2A - MSF
Disease de novo and treatment related leukemia
Prognosis poor
Hybrid/Mutated Gene in-frame transcript joining the 5' of MLL through exon 5 to MSF at the start of exon 3 through the 3' terminus. A reciprocal transcript was amplified in one patient joining the 5' of MSF through exon 1 to exon 7 of MLL but was out of frame. No 5' MSF-3' MLL transcript was amplified in another patient.
Abnormal Protein fusion protein of an amino protein terminus MLL, including the nuclear localization signal, the A-T hook DNA binding domain, and the DNA methyltransferase-like DNA binding domain, and a carboxy terminus MSF, including the xylose isomerase, the polybasic and GTPase domains. Lost from the carboxy terminus of MLL is the PHD zinc finger protein-protein interaction domain and the SET domain thought to regulate gene expression through chromatin remodeling. It has been suggested that MLL is the sole clinical culprit in leukemias with 11q23 rearrangements as it is fused to a wide variety of other genes. However, these translocations produce an in-frame fusion protein, suggesting selection for a translatable protein. In addition, the general observations of phenotypic variability with different translocations, including patient age, leukemia types, and prognostic outcomes, provide further evidence that proteins at the varying reciprocally translocated chromosomes are essential contributors to the pathogenesis of leukemia. Thus, speculation on the contributions of MLL-MSF fusion protein expression to haematopoetic cellular transformation would include potential mislocalization of MSF from the cytoplasm to the nucleus, aberrant expression of MLL target proteins and altered activation of MSF GTPase signaling pathways.
Oncogenesis In addition to the involvement of various septins in leukemia patients, the MSF mouse ortholog SINT1 was identified by virtue of its presence at a provirus insertion site in SL3-3 MLV-induced lymphomas suggesting a subgroup of septins may play a more specific role in leukemogenesis.

To be noted

MSF maps within a 300 kb candidate breast and ovarian tumor suppressor gene region on 17q25 previously defined by allelic imbalance studies in matched normal and tumor samples. Given the role GTPases have been shown to play in cellular proliferation and the proposed role of the highly conserved septin family in cell cycle regulation, MSF is an obvious candidate gene. Preliminary analysis of the MSF coding region in breast and ovarian tumors have only revealed polymorphic variants of no proven clinical relevence.


Genomic and expression analyses of alternatively spliced transcripts of the MLL septin-like fusion gene (MSF) that map to a 17q25 region of loss in breast and ovarian tumors.
Kalikin LM, Sims HL, Petty EM
Genomics. 2000 ; 63 (2) : 165-172.
PMID 10673329
MSF (MLL septin-like fusion), a fusion partner gene of MLL, in a therapy-related acute myeloid leukemia with a t(11;17)(q23;q25).
Osaka M, Rowley JD, Zeleznik-Le NJ
Proceedings of the National Academy of Sciences of the United States of America. 1999 ; 96 (11) : 6428-6433.
PMID 10339604
Isolation and mapping of a human septin gene to a region on chromosome 17q, commonly deleted in sporadic epithelial ovarian tumors.
Russell SE, McIlhatton MA, Burrows JF, Donaghy PG, Chanduloy S, Petty EM, Kalikin LM, Church SW, McIlroy S, Harkin DP, Keilty GW, Cranston AN, Weissenbach J, Hickey I, Johnston PG
Cancer research. 2000 ; 60 (17) : 4729-4734.
PMID 10987277
AF17q25, a putative septin family gene, fuses the MLL gene in acute myeloid leukemia with t(11;17)(q23;q25).
Taki T, Ohnishi H, Shinohara K, Sako M, Bessho F, Yanagisawa M, Hayashi Y
Cancer research. 1999 ; 59 (17) : 4261-4265.
PMID 10485469


This paper should be referenced as such :
Kalikin, LM ; Petty, EM
MSF (MLL septin-like fusion)
Atlas Genet Cytogenet Oncol Haematol. 2001;5(4):259-162.
Free journal version : [ pdf ]   [ DOI ]
On line version :
History of this paper:
Huret, JL. MSF (MLL septin-like fusion). Atlas Genet Cytogenet Oncol Haematol. 2000;4(2):62-62.

Other Leukemias implicated (Data extracted from papers in the Atlas) [ 3 ]
  11q23 rearrangements (KMT2A) in leukaemia
t(X;11)(q24;q23) KMT2A/SEPT6
t(11;17)(q23;q25) KMT2A/SEPT9

External links

HGNC (Hugo)SEPT9   7323
LRG (Locus Reference Genomic)LRG_370
Entrez_Gene (NCBI)SEPT9  10801  septin 9
AliasesAF17q25; MSF; MSF1; NAPB; 
GeneCards (Weizmann)SEPT9
Ensembl hg19 (Hinxton)ENSG00000184640 [Gene_View]
Ensembl hg38 (Hinxton)ENSG00000184640 [Gene_View]  chr17:77281410-77500596 [Contig_View]  SEPT9 [Vega]
ICGC DataPortalENSG00000184640
TCGA cBioPortalSEPT9
Genatlas (Paris)SEPT9
SOURCE (Princeton)SEPT9
Genetics Home Reference (NIH)SEPT9
Genomic and cartography
GoldenPath hg38 (UCSC)SEPT9  -     chr17:77281410-77500596 +  17q25.3   [Description]    (hg38-Dec_2013)
GoldenPath hg19 (UCSC)SEPT9  -     17q25.3   [Description]    (hg19-Feb_2009)
EnsemblSEPT9 - 17q25.3 [CytoView hg19]  SEPT9 - 17q25.3 [CytoView hg38]
Mapping of homologs : NCBISEPT9 [Mapview hg19]  SEPT9 [Mapview hg38]
OMIM162100   604061   
Gene and transcription
Genbank (Entrez)###############################################################################################################################################################################################################################################################
RefSeq transcript (Entrez)NM_001113491 NM_001113492 NM_001113493 NM_001113494 NM_001113495 NM_001113496 NM_001293695 NM_001293696 NM_001293697 NM_001293698 NM_006640
RefSeq genomic (Entrez)
Consensus coding sequences : CCDS (NCBI)SEPT9
Cluster EST : UnigeneHs.440932 [ NCBI ]
CGAP (NCI)Hs.440932
Alternative Splicing GalleryENSG00000184640
Gene ExpressionSEPT9 [ NCBI-GEO ]   SEPT9 [ EBI - ARRAY_EXPRESS ]   SEPT9 [ SEEK ]   SEPT9 [ MEM ]
Gene Expression Viewer (FireBrowse)SEPT9 [ Firebrowse - Broad ]
SOURCE (Princeton)Expression in : [Datasets]   [Normal Tissue Atlas]  [carcinoma Classsification]  [NCI60]
GenevisibleExpression in : [tissues]  [cell-lines]  [cancer]  [perturbations]  
BioGPS (Tissue expression)10801
GTEX Portal (Tissue expression)SEPT9
Human Protein AtlasENSG00000184640-SEPT9 [pathology]   [cell]   [tissue]
Protein : pattern, domain, 3D structure
UniProt/SwissProtQ9UHD8   [function]  [subcellular_location]  [family_and_domains]  [pathology_and_biotech]  [ptm_processing]  [expression]  [interaction]
NextProtQ9UHD8  [Sequence]  [Exons]  [Medical]  [Publications]
With graphics : InterProQ9UHD8
Splice isoforms : SwissVarQ9UHD8
Domaine pattern : Prosite (Expaxy)G_SEPTIN (PS51719)   
Domains : Interpro (EBI)G_SEPTIN_dom    P-loop_NTPase    SEPT9    Septin   
Domain families : Pfam (Sanger)Septin (PF00735)   
Domain families : Pfam (NCBI)pfam00735   
Conserved Domain (NCBI)SEPT9
DMDM Disease mutations10801
Blocks (Seattle)SEPT9
PDB (SRS)4YQF    5CYO    5CYP   
PDB (PDBSum)4YQF    5CYO    5CYP   
PDB (IMB)4YQF    5CYO    5CYP   
PDB (RSDB)4YQF    5CYO    5CYP   
Structural Biology KnowledgeBase4YQF    5CYO    5CYP   
SCOP (Structural Classification of Proteins)4YQF    5CYO    5CYP   
CATH (Classification of proteins structures)4YQF    5CYO    5CYP   
Human Protein Atlas [tissue]ENSG00000184640-SEPT9 [tissue]
Peptide AtlasQ9UHD8
IPIIPI00871679   IPI00030173   IPI01010880   IPI00784614   IPI00455033   IPI00784808   IPI00883870   IPI00784835   IPI00784936   
Protein Interaction databases
IntAct (EBI)Q9UHD8
Ontologies - Pathways
Ontology : AmiGOstress fiber  GTPase activity  protein binding  GTP binding  cytoplasm  microtubule  axoneme  cell cycle  actin cytoskeleton  septin complex  cadherin binding  perinuclear region of cytoplasm  protein heterooligomerization  cell division  non-motile cilium  positive regulation of non-motile cilium assembly  
Ontology : EGO-EBIstress fiber  GTPase activity  protein binding  GTP binding  cytoplasm  microtubule  axoneme  cell cycle  actin cytoskeleton  septin complex  cadherin binding  perinuclear region of cytoplasm  protein heterooligomerization  cell division  non-motile cilium  positive regulation of non-motile cilium assembly  
Pathways : KEGGBacterial invasion of epithelial cells   
NDEx NetworkSEPT9
Atlas of Cancer Signalling NetworkSEPT9
Wikipedia pathwaysSEPT9
Orthology - Evolution
GeneTree (enSembl)ENSG00000184640
Phylogenetic Trees/Animal Genes : TreeFamSEPT9
Homologs : HomoloGeneSEPT9
Homology/Alignments : Family Browser (UCSC)SEPT9
Gene fusions - Rearrangements
Fusion : MitelmanAPPBP2/SEPT9 [17q23.2/17q25.2]  [t(17;17)(q23;q25)]  
Fusion : MitelmanITM2C/SEPT9 [2q37.1/17q25.2]  [t(2;17)(q37;q25)]  
Fusion : MitelmanSEPT9/DNAH17 [17q25.2/17q25.3]  [t(17;17)(q25;q25)]  
Fusion : MitelmanSEPT9/JMJD6 [17q25.2/17q25.1]  [t(17;17)(q25;q25)]  
Fusion : MitelmanSEPT9/KRT32 [17q25.2/17q21.2]  [t(17;17)(q21;q25)]  
Fusion : MitelmanSEPT9/LPP [17q25.2/3q28]  [t(3;17)(q28;q25)]  
Fusion : MitelmanSEPT9/MPO [17q25.2/17q22]  [t(17;17)(q22;q25)]  
Fusion : MitelmanSEPT9/NARF [17q25.2/17q25.3]  [t(17;17)(q25;q25)]  
Fusion : MitelmanSEPT9/SEC14L1 [17q25.2/17q25.2]  [t(17;17)(q25;q25)]  
Fusion : MitelmanSEPT9/TANC2 [17q25.2/17q23.2]  [t(17;17)(q23;q25)]  
Fusion : COSMICKMT2A [11q23.3]  -  SEPT9 [17q25.3]  [fusion_1927]  [fusion_1928]  [fusion_1929]  [fusion_1930]  [fusion_1931]  [fusion_1932]  [fusion_1933]  
[fusion_1934]  [fusion_1935]  [fusion_2065]  
Fusion: TCGAAPPBP2 17q23.2 SEPT9 17q25.2 BRCA
Fusion: TCGAITM2C 2q37.1 SEPT9 17q25.2 LGG
Fusion: TCGASEPT9 17q25.2 AC217773.1 BRCA
Fusion: TCGASEPT9 17q25.2 DNAH17 17q25.3 LUAD
Fusion: TCGASEPT9 17q25.2 JMJD6 17q25.1 BRCA
Fusion: TCGASEPT9 17q25.2 KRT32 17q21.2 THCA
Fusion: TCGASEPT9 17q25.2 LPP 3q28 BRCA
Fusion: TCGASEPT9 17q25.2 MPO 17q22 LUAD
Fusion: TCGASEPT9 17q25.2 NARF 17q25.3 BRCA
Fusion: TCGASEPT9 17q25.2 SEC14L1 17q25.2 BRCA OV
Fusion: TCGASEPT9 17q25.2 TANC2 17q23.2 BRCA
Fusion : TICdbKMT2A [11q23.3]  -  SEPT9 [17q25.2]
Polymorphisms : SNP and Copy number variants
NCBI Variation ViewerSEPT9 [hg38]
dbSNP Single Nucleotide Polymorphism (NCBI)SEPT9
Exome Variant ServerSEPT9
ExAC (Exome Aggregation Consortium)ENSG00000184640
GNOMAD BrowserENSG00000184640
Genetic variants : HAPMAP10801
Genomic Variants (DGV)SEPT9 [DGVbeta]
DECIPHERSEPT9 [patients]   [syndromes]   [variants]   [genes]  
CONAN: Copy Number AnalysisSEPT9 
ICGC Data PortalSEPT9 
TCGA Data PortalSEPT9 
Broad Tumor PortalSEPT9
OASIS PortalSEPT9 [ Somatic mutations - Copy number]
Cancer Gene: CensusSEPT9 
Somatic Mutations in Cancer : COSMICSEPT9  [overview]  [genome browser]  [tissue]  [distribution]  
Mutations and Diseases : HGMDSEPT9
LOVD (Leiden Open Variation Database)Whole genome datasets
LOVD (Leiden Open Variation Database)LOVD - Leiden Open Variation Database
LOVD (Leiden Open Variation Database)Leiden Muscular Dystrophy pages
LOVD (Leiden Open Variation Database)LOVD 3.0 shared installation
BioMutasearch SEPT9
DgiDB (Drug Gene Interaction Database)SEPT9
DoCM (Curated mutations)SEPT9 (select the gene name)
CIViC (Clinical Interpretations of Variants in Cancer)SEPT9 (select a term)
NCG5 (London)SEPT9
Cancer3DSEPT9(select the gene name)
Impact of mutations[PolyPhen2] [SIFT Human Coding SNP] [Buck Institute : MutDB] [Mutation Assessor] [Mutanalyser]
OMIM162100    604061   
Genetic Testing Registry SEPT9
NextProtQ9UHD8 [Medical]
Target ValidationSEPT9
Huge Navigator SEPT9 [HugePedia]
snp3D : Map Gene to Disease10801
BioCentury BCIQSEPT9
Clinical trials, drugs, therapy
Chemical/Protein Interactions : CTD10801
Chemical/Pharm GKB GenePA31132
Clinical trialSEPT9
canSAR (ICR)SEPT9 (select the gene name)
PubMed113 Pubmed reference(s) in Entrez
GeneRIFsGene References Into Functions (Entrez)
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

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indexed on : Thu Oct 12 16:27:55 CEST 2017

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