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Center for Computational Systems Medicine
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Fusion Gene and Fusion Protein Summary

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Fusion Amino Acid Sequences (multiple BPs and multiple gene isoforms)

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Fusion Protein Breakpoint Sequences - (for the Screening of the FusionNeoAntigens)

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Potential FusionNeoAntigens in HLA I - (netMHCpan v4.1 + deepHLApan v1.1)

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Potential FusionNeoAntigens in HLA II - (netMHCIIpan v4.1)

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Fusion Breakpoint 14 AA Peptide Structure - (RoseTTAFold)

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D - (Glide)

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Vaccine Design for the FusionNeoAntigens (RNA/protein sequences)

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Potential target of CAR-T therapy development

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Information on the samples that have these potential fusion neoantigens

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Fusion Protein Targeting Drugs - (Manual Curation)

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Fusion Protein Related diseases - (Manual Curation)

Fusion Protein:LSM7-IQGAP1

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: LSM7-IQGAP1
FusionPDB ID: 50228
FusionGDB2.0 ID: 50228
HgeneTgene
Gene symbol

LSM7

IQGAP1

Gene ID

51690

8826

Gene nameLSM7 homolog, U6 small nuclear RNA and mRNA degradation associatedIQ motif containing GTPase activating protein 1
SynonymsYNL147WHUMORFA01|SAR1|p195
Cytomap

19p13.3

15q26.1

Type of geneprotein-codingprotein-coding
DescriptionU6 snRNA-associated Sm-like protein LSm7LSM7 U6 small nuclear RNA and mRNA degradation associatedLSM7 homolog, U6 small nuclear RNA associatedras GTPase-activating-like protein IQGAP1RasGAP-like with IQ motifs
Modification date2020031320200327
UniProtAcc

Q9UK45

Main function of 5'-partner protein: FUNCTION: Plays role in pre-mRNA splicing as component of the U4/U6-U5 tri-snRNP complex that is involved in spliceosome assembly, and as component of the precatalytic spliceosome (spliceosome B complex) (PubMed:28781166). The heptameric LSM2-8 complex binds specifically to the 3'-terminal U-tract of U6 snRNA (PubMed:10523320). {ECO:0000269|PubMed:10523320, ECO:0000269|PubMed:28781166}.

P46940

Main function of 5'-partner protein: FUNCTION: Plays a crucial role in regulating the dynamics and assembly of the actin cytoskeleton. Binds to activated CDC42 but does not stimulate its GTPase activity. It associates with calmodulin. Could serve as an assembly scaffold for the organization of a multimolecular complex that would interface incoming signals to the reorganization of the actin cytoskeleton at the plasma membrane. May promote neurite outgrowth (PubMed:15695813). May play a possible role in cell cycle regulation by contributing to cell cycle progression after DNA replication arrest (PubMed:20883816). {ECO:0000269|PubMed:15695813, ECO:0000269|PubMed:20883816}.
Ensembl transtripts involved in fusion geneENST idsENST00000252622, ENST00000589532, 
ENST00000560020, ENST00000268182, 
ENST00000560738, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score3 X 3 X 3=2717 X 15 X 7=1785
# samples 419
** MAII scorelog2(4/27*10)=0.567040592723894
effective Gene in Pan-Cancer Fusion Genes (eGinPCFGs).
DoF>8 and MAII>0
log2(19/1785*10)=-3.23185275058551
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: LSM7 [Title/Abstract] AND IQGAP1 [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: LSM7 [Title/Abstract] AND IQGAP1 [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)LSM7(2328386)-IQGAP1(91030186), # samples:1
Anticipated loss of major functional domain due to fusion event.LSM7-IQGAP1 seems lost the major protein functional domain in Hgene partner, which is a CGC by not retaining the major functional domain in the partially deleted in-frame ORF.
LSM7-IQGAP1 seems lost the major protein functional domain in Hgene partner, which is a essential gene by not retaining the major functional domain in the partially deleted in-frame ORF.
* DoF score (Degree of Frequency) = # partners X # break points X # cancer types
** MAII score (Major Active Isofusion Index) = log2(# samples/DoF score*10)

check button Gene ontology of each fusion partner gene with evidence of Inferred from Direct Assay (IDA) from Entrez
PartnerGeneGO IDGO termPubMed ID
HgeneLSM7

GO:0000398

mRNA splicing, via spliceosome

28781166

TgeneIQGAP1

GO:0071277

cellular response to calcium ion

18567582



check button Four levels of functional features of fusion genes
Go to FGviewer search page for the most frequent breakpoint (https://ccsmweb.uth.edu/FGviewer/chr19:2328386/chr15:91030186)
- FGviewer provides the online visualization of the retention search of the protein functional features across DNA, RNA, protein, and pathological levels.
- How to search
1. Put your fusion gene symbol.
2. Press the tab key until there will be shown the breakpoint information filled.
4. Go down and press 'Search' tab twice.
4. Go down to have the hyperlink of the search result.
5. Click the hyperlink.
6. See the FGviewer result for your fusion gene.
FGviewer

check buttonRetention analysis results of each fusion partner protein across 39 protein features of UniProt such as six molecule processing features, 13 region features, four site features, six amino acid modification features, two natural variation features, five experimental info features, and 3 secondary structure features, are available here.

check buttonFusion gene breakpoints across LSM7 (5'-gene)
* Click on the image to open the UCSC genome browser with custom track showing this image in a new window.
all structure

check buttonFusion gene breakpoints across IQGAP1 (3'-gene)
* Click on the image to open the UCSC genome browser with custom track showing this image in a new window.
all structure


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Fusion Amino Acid Sequences


check buttonFusion information from ORFfinder translation from full-length transcript sequence from FusionPDB.
HenstTenstHgeneHchrHbpHstrandTgeneTchrTbpTstrandSeq length
(transcript)
BP loci
(transcript)
Predicted start
(transcript)
Predicted stop
(transcript)
Seq length
(amino acids)
ENST00000252622LSM7chr192328386-ENST00000268182IQGAP1chr1591030186+3236151271100357
ENST00000252622LSM7chr192328386-ENST00000560738IQGAP1chr1591030186+1364151271100357

check buttonDeepORF prediction of the coding potential based on the fusion transcript sequence of in-frame fusion genes. DeepORF is a coding potential classifier based on convolutional neural network by comparing the real Ribo-seq data. If the no-coding score < 0.5 and coding score > 0.5, then the in-frame fusion transcript is predicted as being likely translated.
HenstTenstHgeneHchrHbpHstrandTgeneTchrTbpTstrandNo-coding scoreCoding score
ENST00000252622ENST00000268182LSM7chr192328386-IQGAP1chr1591030186+0.0002263780.9997737
ENST00000252622ENST00000560738LSM7chr192328386-IQGAP1chr1591030186+0.0017112210.9982888

check button Predicted full-length fusion amino acid sequences. For individual full-length fusion transcript sequence from FusionPDB, we ran ORFfinder and chose the longest ORF among all the predicted ones.

Get the fusion protein sequences from here.

Fusion protein sequence information is available in the fasta format.
>FusionGDB ID_FusionGDB isoform ID_FGname_Hgene_Hchr_Hbp_Henst_Tgene_Tchr_Tbp_Tenst_length(fusion AA) seq_BP

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Fusion Protein Breakpoint Sequences for LSM7-IQGAP1

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
LSM7chr192328386IQGAP1chr159103018615141DKTIRVKFQGGREGESSGNLNDPNKE

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Potential FusionNeoAntigen Information of LSM7-IQGAP1 in HLA I

check button Multiple sequence alignments of the potential FusionNeoAntigens per fusion breakpoints. If the MSA is empty, then it means that there were predicted fusion neoantigens in this fusion breakpoint, but those predicted fusion neoantigens were not across the breakpoint, which is not fusion-specific.
LSM7-IQGAP1_2328386_91030186.msa

check button Potential FusionNeoAntigen Information
* We used NetMHCpan v4.1 (%rank<0.5) and deepHLApan v1.1 (immunogenic score>0.5)
Fusion geneHchrHbpTgeneTchrTbpHLA IFusionNeoAntigen peptideBinding scoreImmunogenic scoreNeoantigen start (at BP 13)Neoantigen end (at BP 13)
LSM7-IQGAP1chr192328386chr1591030186151HLA-B47:01REGESSGNL0.6620.63181120
LSM7-IQGAP1chr192328386chr1591030186151HLA-B39:13REGESSGNL0.14260.97441120
LSM7-IQGAP1chr192328386chr1591030186151HLA-B39:08REGESSGNL0.2880.92131120
LSM7-IQGAP1chr192328386chr1591030186151HLA-B40:04REGESSGNL0.98930.76351120
LSM7-IQGAP1chr192328386chr1591030186151HLA-B41:03REGESSGNL0.27510.60951120
LSM7-IQGAP1chr192328386chr1591030186151HLA-B39:02REGESSGNL0.13150.97381120

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Potential FusionNeoAntigen Information of LSM7-IQGAP1 in HLA II

check button Multiple sequence alignments of the potential FusionNeoAntigens per fusion breakpoints. If the MSA is empty, then it means that there were predicted fusion neoantigens in this fusion breakpoint, but those predicted fusion neoantigens were not across the breakpoint, which is not fusion-specific.
LSM7-IQGAP1_2328386_91030186.msa

check button Potential FusionNeoAntigen Information
* We used NetMHCIIpan v4.1 (%rank<0.5).
Fusion geneHchrHbpTgeneTchrTbpHLA IIFusionNeoAntigen peptideNeoantigen start (at BP 13)Neoantigen end (at BP 13)
LSM7-IQGAP1chr192328386chr1591030186151DRB1-1136DKTIRVKFQGGREGE015
LSM7-IQGAP1chr192328386chr1591030186151DRB1-1155DKTIRVKFQGGREGE015
LSM7-IQGAP1chr192328386chr1591030186151DRB1-1170DKTIRVKFQGGREGE015
LSM7-IQGAP1chr192328386chr1591030186151DRB1-1315DKTIRVKFQGGREGE015
LSM7-IQGAP1chr192328386chr1591030186151DRB1-1317DKTIRVKFQGGREGE015
LSM7-IQGAP1chr192328386chr1591030186151DRB1-1319DKTIRVKFQGGREGE015
LSM7-IQGAP1chr192328386chr1591030186151DRB1-1320DKTIRVKFQGGREGE015
LSM7-IQGAP1chr192328386chr1591030186151DRB1-1353DKTIRVKFQGGREGE015
LSM7-IQGAP1chr192328386chr1591030186151DRB1-1357DKTIRVKFQGGREGE015
LSM7-IQGAP1chr192328386chr1591030186151DRB1-1371DKTIRVKFQGGREGE015
LSM7-IQGAP1chr192328386chr1591030186151DRB1-1378DKTIRVKFQGGREGE015

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Fusion breakpoint peptide structures of LSM7-IQGAP1

check button3D structures of the fusion breakpoint peptide of 14AA sequence that have potential fusion neoantigens
* The minimum length of the amino acid sequence in RoseTTAFold is 14AA. Here, we predicted the 14AA fusion protein breakpoint sequence not the fusion neoantigen peptide, which is shorter than 14 AA.
File nameBPseqHgeneTgeneHchrHbpTchrTbpAAlen
4232KFQGGREGESSGNLLSM7IQGAP1chr192328386chr1591030186151

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of LSM7-IQGAP1

check buttonVirtual screening between 25 HLAs (from PDB) and FusionNeoAntigens
* We used Glide to predict the interaction between HLAs and neoantigens.
HLA allelePDB IDFile nameBPseqDocking scoreGlide score
HLA-B14:023BVN4232KFQGGREGESSGNL-7.9962-8.1096
HLA-B14:023BVN4232KFQGGREGESSGNL-5.70842-6.74372
HLA-B52:013W394232KFQGGREGESSGNL-6.83737-6.95077
HLA-B52:013W394232KFQGGREGESSGNL-4.4836-5.5189
HLA-A11:014UQ24232KFQGGREGESSGNL-10.0067-10.1201
HLA-A11:014UQ24232KFQGGREGESSGNL-9.03915-10.0745
HLA-A24:025HGA4232KFQGGREGESSGNL-6.56204-6.67544
HLA-A24:025HGA4232KFQGGREGESSGNL-5.42271-6.45801
HLA-B44:053DX84232KFQGGREGESSGNL-7.85648-8.89178
HLA-B44:053DX84232KFQGGREGESSGNL-5.3978-5.5112
HLA-A02:016TDR4232KFQGGREGESSGNL-3.37154-4.40684

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Vaccine Design for the FusionNeoAntigens of LSM7-IQGAP1

check button mRNA and peptide sequences of FusionNeoAntigens that have potential interaction with HLA-Is.
Fusion geneHchrHbpTchrTbpStart in +/-13AAEnd in +/-13AAFusionNeoAntigen peptide sequenceFusionNeoAntigen RNA sequence
LSM7-IQGAP1chr192328386chr15910301861120REGESSGNLGCGAAGGGGAAAGCTCTGGCAATTTAA

check button mRNA and peptide sequences of FusionNeoAntigens that have potential interaction with HLA-IIs.
Fusion geneHchrHbpTchrTbpStart in +/-13AAEnd in +/-13AAFusionNeoAntigen peptideFusionNEoAntigen RNA sequence
LSM7-IQGAP1chr192328386chr1591030186015DKTIRVKFQGGREGEACAAGACGATCCGGGTAAAGTTCCAGGGAGGCCGCGAAGGGGAAA

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Information of the samples that have these potential fusion neoantigens of LSM7-IQGAP1

check button These samples were reported as having these fusion breakpoints. For individual breakpoints, we checked the open reading frames considering multiple gene isoforms and chose the in-frame fusion genes only. Then, we made fusion protein sequences and predicted the fusion neoantigens. These fusion-positive samples may have these potential fusion neoantigens.
Cancer typeFusion geneHchrHbpHenstTchrTbpTenstSample
Non-CancerLSM7-IQGAP1chr192328386ENST00000252622chr1591030186ENST00000268182ERR315349

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Potential target of CAR-T therapy development for LSM7-IQGAP1

check button Predicted 3D structure. We used RoseTTAFold.

check buttonRetention analysis result of each fusion partner protein across 39 protein features of UniProt such as six molecule processing features, 13 region features, four site features, six amino acid modification features, two natural variation features, five experimental info features, and 3 secondary structure features. Here, to provide the retention of the transmembrane domain, we only show the protein feature retention information of those transmembrane features


* Minus value of BPloci means that the break point is located before the CDS.
- In-frame and retained 'Transmembrane'.
PartnerGeneHbpTbpENSTStrandBPexonTotalExonProtein feature loci*BPlociTotalLenProtein featureProtein feature note

check button Subcellular localization prediction of the transmembrane domain retained fusion proteins
* We used DeepLoc 1.0. The order of the X-axis of the barplot is as follows: Entry_ID, Localization, Type, Nucleus, Cytoplasm, Extracellular, Mitochondrion, Cell_membrane, Endoplasmic_reticulum, Plastid, Golgi.apparatus, Lysosome.Vacuole, Peroxisome. Y-axis is the output score of DeepLoc. Clicking the image will open a new tab with a large image.
HgeneHchrHbpHenstTgeneTchrTbpTenstDeepLoc result

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Related Drugs to LSM7-IQGAP1

check button Drugs used for this fusion-positive patient.
(Manual curation of PubMed, 04-30-2022 + MyCancerGenome)
HgeneTgeneDrugSourcePMID

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Related Diseases to LSM7-IQGAP1

check button Diseases that have this fusion gene.
(Manual curation of PubMed, 04-30-2022 + MyCancerGenome)
HgeneTgeneDiseaseSourcePMID

check button Diseases associated with fusion partners.
(DisGeNet 4.0)
PartnerGeneDisease IDDisease name# pubmedsSource