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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:IQGAP1-MESP2

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: IQGAP1-MESP2
FusionPDB ID: 40162
FusionGDB2.0 ID: 40162
HgeneTgene
Gene symbol

IQGAP1

MESP2

Gene ID

8826

145873

Gene nameIQ motif containing GTPase activating protein 1mesoderm posterior bHLH transcription factor 2
SynonymsHUMORFA01|SAR1|p195SCDO2|bHLHc6
Cytomap

15q26.1

15q26.1

Type of geneprotein-codingprotein-coding
Descriptionras GTPase-activating-like protein IQGAP1RasGAP-like with IQ motifsmesoderm posterior protein 2class C basic helix-loop-helix protein 6mesoderm posterior 2 homologmesoderm posterior basic helix-loop-helix transcription factor 2
Modification date2020032720200313
UniProtAcc

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}.

Q0VG99

Main function of 5'-partner protein: FUNCTION: Transcription factor with important role in somitogenesis. Defines the rostrocaudal patterning of the somite by participating in distinct Notch pathways. Regulates also the FGF signaling pathway. Specifies the rostral half of the somites. Generates rostro-caudal polarity of somites by down-regulating in the presumptive rostral domain DLL1, a Notch ligand. Participates in the segment border formation by activating in the anterior presomitic mesoderm LFNG, a negative regulator of DLL1-Notch signaling. Acts as a strong suppressor of Notch activity. Together with MESP1 is involved in the epithelialization of somitic mesoderm and in the development of cardiac mesoderm.
Ensembl transtripts involved in fusion geneENST idsENST00000268182, ENST00000560020, 
ENST00000560738, 
ENST00000341735, 
ENST00000558723, ENST00000560219, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score27 X 20 X 12=64805 X 4 X 4=80
# samples 325
** MAII scorelog2(32/6480*10)=-4.33985000288463
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(5/80*10)=-0.678071905112638
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: IQGAP1 [Title/Abstract] AND MESP2 [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: IQGAP1 [Title/Abstract] AND MESP2 [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)IQGAP1(90972898)-MESP2(90321296), # samples:1
Anticipated loss of major functional domain due to fusion event.IQGAP1-MESP2 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.
IQGAP1-MESP2 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
HgeneIQGAP1

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/chr15:90972898/chr15:90321296)
- 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 IQGAP1 (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 MESP2 (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)
ENST00000268182IQGAP1chr1590972898-ENST00000560219MESP2chr1590321296+1201514124783219

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
ENST00000268182ENST00000560219IQGAP1chr1590972898-MESP2chr1590321296+0.0085835130.9914165

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 IQGAP1-MESP2

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
IQGAP1chr1590972898MESP2chr1590321296514130QWLNAMDEIGLPKGLSVSPEPCLSLG

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Potential FusionNeoAntigen Information of IQGAP1-MESP2 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.
IQGAP1-MESP2_90972898_90321296.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)
IQGAP1-MESP2chr1590972898chr1590321296514HLA-B18:01DEIGLPKGL0.98080.9593615
IQGAP1-MESP2chr1590972898chr1590321296514HLA-B52:01IGLPKGLSV0.96630.9969817
IQGAP1-MESP2chr1590972898chr1590321296514HLA-B08:09IGLPKGLSV0.95990.896817
IQGAP1-MESP2chr1590972898chr1590321296514HLA-B44:03DEIGLPKGL0.9590.9544615
IQGAP1-MESP2chr1590972898chr1590321296514HLA-B44:03AMDEIGLPKGL0.98880.981415
IQGAP1-MESP2chr1590972898chr1590321296514HLA-C15:06IGLPKGLSV0.99770.9768817
IQGAP1-MESP2chr1590972898chr1590321296514HLA-B78:01LPKGLSVSP0.76490.61091019
IQGAP1-MESP2chr1590972898chr1590321296514HLA-A02:07AMDEIGLPKGL0.99430.6639415
IQGAP1-MESP2chr1590972898chr1590321296514HLA-B44:10AMDEIGLPKGL0.97430.5874415
IQGAP1-MESP2chr1590972898chr1590321296514HLA-C15:02IGLPKGLSV0.99840.978817
IQGAP1-MESP2chr1590972898chr1590321296514HLA-C15:05IGLPKGLSV0.9980.9866817
IQGAP1-MESP2chr1590972898chr1590321296514HLA-B40:04DEIGLPKGL0.98960.7502615
IQGAP1-MESP2chr1590972898chr1590321296514HLA-B18:04DEIGLPKGL0.98910.9649615
IQGAP1-MESP2chr1590972898chr1590321296514HLA-B18:07DEIGLPKGL0.98470.9167615
IQGAP1-MESP2chr1590972898chr1590321296514HLA-B18:08DEIGLPKGL0.9820.9491615
IQGAP1-MESP2chr1590972898chr1590321296514HLA-B18:05DEIGLPKGL0.98080.9593615
IQGAP1-MESP2chr1590972898chr1590321296514HLA-B18:03DEIGLPKGL0.96210.9565615
IQGAP1-MESP2chr1590972898chr1590321296514HLA-B18:06DEIGLPKGL0.96180.9633615
IQGAP1-MESP2chr1590972898chr1590321296514HLA-B44:26DEIGLPKGL0.9590.9544615
IQGAP1-MESP2chr1590972898chr1590321296514HLA-B44:13DEIGLPKGL0.9590.9544615
IQGAP1-MESP2chr1590972898chr1590321296514HLA-B44:07DEIGLPKGL0.9590.9544615
IQGAP1-MESP2chr1590972898chr1590321296514HLA-B78:02LPKGLSVSP0.74020.63761019
IQGAP1-MESP2chr1590972898chr1590321296514HLA-B18:11DEIGLPKGL0.66090.9542615
IQGAP1-MESP2chr1590972898chr1590321296514HLA-B39:31DEIGLPKGL0.35530.9582615
IQGAP1-MESP2chr1590972898chr1590321296514HLA-B07:13IGLPKGLSV0.31370.8723817
IQGAP1-MESP2chr1590972898chr1590321296514HLA-B44:26AMDEIGLPKGL0.98880.981415
IQGAP1-MESP2chr1590972898chr1590321296514HLA-B44:13AMDEIGLPKGL0.98880.981415
IQGAP1-MESP2chr1590972898chr1590321296514HLA-B44:07AMDEIGLPKGL0.98880.981415
IQGAP1-MESP2chr1590972898chr1590321296514HLA-B18:03DEIGLPKGLSV0.98690.9547617

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Potential FusionNeoAntigen Information of IQGAP1-MESP2 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.

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)

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Fusion breakpoint peptide structures of IQGAP1-MESP2

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
1066DEIGLPKGLSVSPEIQGAP1MESP2chr1590972898chr1590321296514

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of IQGAP1-MESP2

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-B14:023BVN1066DEIGLPKGLSVSPE-6.46878-6.66328
HLA-B14:023BVN1066DEIGLPKGLSVSPE-4.33704-5.09154
HLA-B52:013W391066DEIGLPKGLSVSPE-6.45088-7.20538
HLA-B52:013W391066DEIGLPKGLSVSPE-6.08714-6.28164
HLA-A11:014UQ21066DEIGLPKGLSVSPE-7.67344-8.42794
HLA-A24:025HGA1066DEIGLPKGLSVSPE-7.49907-7.69357
HLA-A24:025HGA1066DEIGLPKGLSVSPE-4.36357-5.11807
HLA-B27:056PYJ1066DEIGLPKGLSVSPE-8.53231-9.28681
HLA-B44:053DX81066DEIGLPKGLSVSPE-5.69992-5.89442
HLA-B44:053DX81066DEIGLPKGLSVSPE-3.58931-4.34381
HLA-A02:016TDR1066DEIGLPKGLSVSPE-7.78181-7.97631

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Vaccine Design for the FusionNeoAntigens of IQGAP1-MESP2

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
IQGAP1-MESP2chr1590972898chr15903212961019LPKGLSVSPTTGCCTAAGGGTCTCTCTGTGTCTCCA
IQGAP1-MESP2chr1590972898chr1590321296415AMDEIGLPKGLGCCATGGATGAGATTGGATTGCCTAAGGGTCTC
IQGAP1-MESP2chr1590972898chr1590321296615DEIGLPKGLGATGAGATTGGATTGCCTAAGGGTCTC
IQGAP1-MESP2chr1590972898chr1590321296617DEIGLPKGLSVGATGAGATTGGATTGCCTAAGGGTCTCTCTGTG
IQGAP1-MESP2chr1590972898chr1590321296817IGLPKGLSVATTGGATTGCCTAAGGGTCTCTCTGTG

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

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Information of the samples that have these potential fusion neoantigens of IQGAP1-MESP2

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
BRCAIQGAP1-MESP2chr1590972898ENST00000268182chr1590321296ENST00000560219TCGA-BH-A0C0-01A

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Potential target of CAR-T therapy development for IQGAP1-MESP2

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 IQGAP1-MESP2

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 IQGAP1-MESP2

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