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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:MMP2-DYNC1LI2

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: MMP2-DYNC1LI2
FusionPDB ID: 54428
FusionGDB2.0 ID: 54428
HgeneTgene
Gene symbol

MMP2

DYNC1LI2

Gene ID

4313

1783

Gene namematrix metallopeptidase 2dynein cytoplasmic 1 light intermediate chain 2
SynonymsCLG4|CLG4A|MMP-2|MMP-II|MONA|TBE-1DNCLI2|LIC2
Cytomap

16q12.2

16q22.1

Type of geneprotein-codingprotein-coding
Description72 kDa type IV collagenasecollagenase type IV-Amatrix metallopeptidase 2 (gelatinase A, 72kDa gelatinase, 72kDa type IV collagenase)matrix metalloproteinase-2matrix metalloproteinase-IIneutrophil gelatinasecytoplasmic dynein 1 light intermediate chain 2LIC-2LIC53/55dynein light intermediate chain 2, cytosolicdynein, cytoplasmic, light intermediate polypeptide 2
Modification date2020032920200313
UniProtAcc

Q9H239

Main function of 5'-partner protein: FUNCTION: Can degrade casein. Could play a role in tissues homeostasis and repair.

O43237

Main function of 5'-partner protein: FUNCTION: Acts as one of several non-catalytic accessory components of the cytoplasmic dynein 1 complex that are thought to be involved in linking dynein to cargos and to adapter proteins that regulate dynein function. Cytoplasmic dynein 1 acts as a motor for the intracellular retrograde motility of vesicles and organelles along microtubules. May play a role in binding dynein to membranous organelles or chromosomes.
Ensembl transtripts involved in fusion geneENST idsENST00000219070, ENST00000437642, 
ENST00000543485, ENST00000570308, 
ENST00000440564, ENST00000570201, 
ENST00000258198, ENST00000379482, 
ENST00000443351, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score8 X 8 X 2=1287 X 6 X 6=252
# samples 88
** MAII scorelog2(8/128*10)=-0.678071905112638
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(8/252*10)=-1.65535182861255
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: MMP2 [Title/Abstract] AND DYNC1LI2 [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: MMP2 [Title/Abstract] AND DYNC1LI2 [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)MMP2(55536800)-DYNC1LI2(66770147), # samples:1
Anticipated loss of major functional domain due to fusion event.MMP2-DYNC1LI2 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.
MMP2-DYNC1LI2 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.
MMP2-DYNC1LI2 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.
MMP2-DYNC1LI2 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
HgeneMMP2

GO:0006508

proteolysis

15863497



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/chr16:55536800/chr16:66770147)
- 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 MMP2 (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 DYNC1LI2 (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)
ENST00000570308MMP2chr1655536800+ENST00000258198DYNC1LI2chr1666770147-611523365353285916
ENST00000570308MMP2chr1655536800+ENST00000379482DYNC1LI2chr1666770147-243723365352436634
ENST00000570308MMP2chr1655536800+ENST00000443351DYNC1LI2chr1666770147-353023365353285916
ENST00000219070MMP2chr1655536800+ENST00000258198DYNC1LI2chr1666770147-616723885093337942
ENST00000219070MMP2chr1655536800+ENST00000379482DYNC1LI2chr1666770147-248923885092488660
ENST00000219070MMP2chr1655536800+ENST00000443351DYNC1LI2chr1666770147-358223885093337942
ENST00000543485MMP2chr1655536800+ENST00000258198DYNC1LI2chr1666770147-55701791712740889
ENST00000543485MMP2chr1655536800+ENST00000379482DYNC1LI2chr1666770147-18921791711891607
ENST00000543485MMP2chr1655536800+ENST00000443351DYNC1LI2chr1666770147-29851791712740889
ENST00000437642MMP2chr1655536800+ENST00000258198DYNC1LI2chr1666770147-582720483192997892
ENST00000437642MMP2chr1655536800+ENST00000379482DYNC1LI2chr1666770147-214920483192148610
ENST00000437642MMP2chr1655536800+ENST00000443351DYNC1LI2chr1666770147-324220483192997892

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
ENST00000570308ENST00000258198MMP2chr1655536800+DYNC1LI2chr1666770147-0.000184720.9998153
ENST00000570308ENST00000379482MMP2chr1655536800+DYNC1LI2chr1666770147-0.0039279040.99607205
ENST00000570308ENST00000443351MMP2chr1655536800+DYNC1LI2chr1666770147-0.0011735820.99882644
ENST00000219070ENST00000258198MMP2chr1655536800+DYNC1LI2chr1666770147-0.0001814530.9998186
ENST00000219070ENST00000379482MMP2chr1655536800+DYNC1LI2chr1666770147-0.0060512980.9939487
ENST00000219070ENST00000443351MMP2chr1655536800+DYNC1LI2chr1666770147-0.0012533810.99874663
ENST00000543485ENST00000258198MMP2chr1655536800+DYNC1LI2chr1666770147-0.000238080.9997619
ENST00000543485ENST00000379482MMP2chr1655536800+DYNC1LI2chr1666770147-0.0046165440.99538344
ENST00000543485ENST00000443351MMP2chr1655536800+DYNC1LI2chr1666770147-0.0016928350.9983071
ENST00000437642ENST00000258198MMP2chr1655536800+DYNC1LI2chr1666770147-0.000166120.9998338
ENST00000437642ENST00000379482MMP2chr1655536800+DYNC1LI2chr1666770147-0.003799340.9962006
ENST00000437642ENST00000443351MMP2chr1655536800+DYNC1LI2chr1666770147-0.001257370.99874264

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 MMP2-DYNC1LI2

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
MMP2chr1655536800DYNC1LI2chr16667701471791573PDNLDAVVDLQGGVVKDFQDYMEPEE
MMP2chr1655536800DYNC1LI2chr16667701472048576PDNLDAVVDLQGGVVKDFQDYMEPEE
MMP2chr1655536800DYNC1LI2chr16667701472336600PDNLDAVVDLQGGVVKDFQDYMEPEE
MMP2chr1655536800DYNC1LI2chr16667701472388626PDNLDAVVDLQGGVVKDFQDYMEPEE

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Potential FusionNeoAntigen Information of MMP2-DYNC1LI2 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.
MMP2-DYNC1LI2_55536800_66770147.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)
MMP2-DYNC1LI2chr1655536800chr16667701472388HLA-B15:01LQGGVVKDF0.99150.8629918
MMP2-DYNC1LI2chr1655536800chr16667701472388HLA-B15:01GVVKDFQDY0.91190.84371221
MMP2-DYNC1LI2chr1655536800chr16667701472388HLA-A11:03AVVDLQGGVVK0.99970.5881516
MMP2-DYNC1LI2chr1655536800chr16667701472388HLA-A03:12AVVDLQGGVVK0.99890.716516
MMP2-DYNC1LI2chr1655536800chr16667701472388HLA-A11:04AVVDLQGGVVK0.99760.6188516
MMP2-DYNC1LI2chr1655536800chr16667701472388HLA-C05:09VVDLQGGVV0.99940.9727615
MMP2-DYNC1LI2chr1655536800chr16667701472388HLA-C08:15VVDLQGGVV0.99690.9891615
MMP2-DYNC1LI2chr1655536800chr16667701472388HLA-A02:05AVVDLQGGV0.9520.5269514
MMP2-DYNC1LI2chr1655536800chr16667701472388HLA-B15:05GVVKDFQDY0.86120.86351221
MMP2-DYNC1LI2chr1655536800chr16667701472388HLA-A11:01AVVDLQGGVVK0.99970.5497516
MMP2-DYNC1LI2chr1655536800chr16667701472388HLA-C05:01VVDLQGGVV0.99940.9727615
MMP2-DYNC1LI2chr1655536800chr16667701472388HLA-C04:03VVDLQGGVV0.99930.9596615
MMP2-DYNC1LI2chr1655536800chr16667701472388HLA-C08:02VVDLQGGVV0.99690.9891615
MMP2-DYNC1LI2chr1655536800chr16667701472388HLA-B15:34LQGGVVKDF0.99150.8629918
MMP2-DYNC1LI2chr1655536800chr16667701472388HLA-B15:125LQGGVVKDF0.99150.8629918
MMP2-DYNC1LI2chr1655536800chr16667701472388HLA-B15:33LQGGVVKDF0.99150.8629918
MMP2-DYNC1LI2chr1655536800chr16667701472388HLA-B15:24LQGGVVKDF0.98140.9532918
MMP2-DYNC1LI2chr1655536800chr16667701472388HLA-A68:02AVVDLQGGV0.9790.6879514
MMP2-DYNC1LI2chr1655536800chr16667701472388HLA-B15:12LQGGVVKDF0.93740.9231918
MMP2-DYNC1LI2chr1655536800chr16667701472388HLA-B15:33GVVKDFQDY0.91190.84371221
MMP2-DYNC1LI2chr1655536800chr16667701472388HLA-B15:34GVVKDFQDY0.91190.84371221
MMP2-DYNC1LI2chr1655536800chr16667701472388HLA-B15:125GVVKDFQDY0.91190.84371221
MMP2-DYNC1LI2chr1655536800chr16667701472388HLA-B15:135GVVKDFQDY0.89780.8691221
MMP2-DYNC1LI2chr1655536800chr16667701472388HLA-B15:53LQGGVVKDF0.81520.8545918
MMP2-DYNC1LI2chr1655536800chr16667701472388HLA-B15:54LQGGVVKDF0.76790.8087918
MMP2-DYNC1LI2chr1655536800chr16667701472388HLA-B35:28LQGGVVKDF0.32320.9278918
MMP2-DYNC1LI2chr1655536800chr16667701472388HLA-A11:02AVVDLQGGVVK0.99970.5497516

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Potential FusionNeoAntigen Information of MMP2-DYNC1LI2 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.
MMP2-DYNC1LI2_55536800_66770147.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)
MMP2-DYNC1LI2chr1655536800chr16667701472388DRB1-0102LDAVVDLQGGVVKDF318
MMP2-DYNC1LI2chr1655536800chr16667701472388DRB1-0102NLDAVVDLQGGVVKD217
MMP2-DYNC1LI2chr1655536800chr16667701472388DRB1-0451PDNLDAVVDLQGGVV015
MMP2-DYNC1LI2chr1655536800chr16667701472388DRB1-0470PDNLDAVVDLQGGVV015

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Fusion breakpoint peptide structures of MMP2-DYNC1LI2

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
10341VVDLQGGVVKDFQDMMP2DYNC1LI2chr1655536800chr16667701472388

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of MMP2-DYNC1LI2

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-B14:023BVN10341VVDLQGGVVKDFQD-6.9015-7.0162
HLA-B14:023BVN10341VVDLQGGVVKDFQD-6.88733-7.92393
HLA-B52:013W3910341VVDLQGGVVKDFQD-6.20276-6.31746
HLA-B52:013W3910341VVDLQGGVVKDFQD-3.23728-4.27388
HLA-A24:025HGA10341VVDLQGGVVKDFQD-6.25402-7.29062
HLA-A24:025HGA10341VVDLQGGVVKDFQD-5.4385-5.5532
HLA-B44:053DX810341VVDLQGGVVKDFQD-6.77944-6.89414
HLA-B44:053DX810341VVDLQGGVVKDFQD-5.78397-6.82057
HLA-B35:011A1N10341VVDLQGGVVKDFQD-9.14023-9.25493
HLA-B35:011A1N10341VVDLQGGVVKDFQD-4.23727-5.27387
HLA-A02:016TDR10341VVDLQGGVVKDFQD-2.00985-3.04645

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Vaccine Design for the FusionNeoAntigens of MMP2-DYNC1LI2

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
MMP2-DYNC1LI2chr1655536800chr16667701471221GVVKDFQDYGCGTTGTGAAAGATTTTCAAGACTATA
MMP2-DYNC1LI2chr1655536800chr1666770147514AVVDLQGGVCCGTCGTGGACCTGCAGGGCGGCGTTG
MMP2-DYNC1LI2chr1655536800chr1666770147516AVVDLQGGVVKCCGTCGTGGACCTGCAGGGCGGCGTTGTGAAAG
MMP2-DYNC1LI2chr1655536800chr1666770147615VVDLQGGVVTCGTGGACCTGCAGGGCGGCGTTGTGA
MMP2-DYNC1LI2chr1655536800chr1666770147918LQGGVVKDFTGCAGGGCGGCGTTGTGAAAGATTTTC

check button mRNA and peptide sequences of FusionNeoAntigens that have potential interaction with HLA-IIs.
Fusion geneHchrHbpTchrTbpStart in +/-13AAEnd in +/-13AAFusionNeoAntigen peptideFusionNEoAntigen RNA sequence
MMP2-DYNC1LI2chr1655536800chr1666770147015PDNLDAVVDLQGGVVCCGATAACCTGGATGCCGTCGTGGACCTGCAGGGCGGCGTTGTGA
MMP2-DYNC1LI2chr1655536800chr1666770147217NLDAVVDLQGGVVKDACCTGGATGCCGTCGTGGACCTGCAGGGCGGCGTTGTGAAAGATT
MMP2-DYNC1LI2chr1655536800chr1666770147318LDAVVDLQGGVVKDFTGGATGCCGTCGTGGACCTGCAGGGCGGCGTTGTGAAAGATTTTC

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Information of the samples that have these potential fusion neoantigens of MMP2-DYNC1LI2

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
STADMMP2-DYNC1LI2chr1655536800ENST00000219070chr1666770147ENST00000258198TCGA-CD-8530

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Potential target of CAR-T therapy development for MMP2-DYNC1LI2

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 MMP2-DYNC1LI2

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 MMP2-DYNC1LI2

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