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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:LTBP1-ZDHHC2

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: LTBP1-ZDHHC2
FusionPDB ID: 50278
FusionGDB2.0 ID: 50278
HgeneTgene
Gene symbol

LTBP1

ZDHHC2

Gene ID

4052

51201

Gene namelatent transforming growth factor beta binding protein 1zinc finger DHHC-type palmitoyltransferase 2
Synonyms-DHHC2|ZNF372
Cytomap

2p22.3

8p22

Type of geneprotein-codingprotein-coding
Descriptionlatent-transforming growth factor beta-binding protein 1LTBP-1TGF-beta1-BP-1transforming growth factor beta-1-binding protein 1palmitoyltransferase ZDHHC2DHHC-2reamrecreduced expression associated with metastasis proteinreduced expression in cancer proteintestis tissue sperm-binding protein Li 56ezinc finger DHHC domain-containing protein 2zinc finger DHHC-type containing
Modification date2020032920200327
UniProtAcc

Q14766

Main function of 5'-partner protein: FUNCTION: Key regulator of transforming growth factor beta (TGFB1, TGFB2 and TGFB3) that controls TGF-beta activation by maintaining it in a latent state during storage in extracellular space (PubMed:2022183, PubMed:8617200, PubMed:8939931). Associates specifically via disulfide bonds with the Latency-associated peptide (LAP), which is the regulatory chain of TGF-beta, and regulates integrin-dependent activation of TGF-beta (PubMed:8617200, PubMed:8939931, PubMed:15184403). Outcompeted by LRRC32/GARP for binding to LAP regulatory chain of TGF-beta (PubMed:22278742). {ECO:0000269|PubMed:15184403, ECO:0000269|PubMed:2022183, ECO:0000269|PubMed:22278742, ECO:0000269|PubMed:8617200, ECO:0000269|PubMed:8939931}.
.
Ensembl transtripts involved in fusion geneENST idsENST00000272273, ENST00000354476, 
ENST00000390003, ENST00000402934, 
ENST00000404525, ENST00000404816, 
ENST00000407925, ENST00000418533, 
ENST00000498013, 
ENST00000262096, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score19 X 16 X 9=27367 X 8 X 5=280
# samples 298
** MAII scorelog2(29/2736*10)=-3.23794342487096
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(8/280*10)=-1.8073549220576
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: LTBP1 [Title/Abstract] AND ZDHHC2 [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: LTBP1 [Title/Abstract] AND ZDHHC2 [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)ZDHHC2(17014362)-LTBP1(33572434), # samples:2
LTBP1(33540336)-ZDHHC2(17042298), # samples:2
Anticipated loss of major functional domain due to fusion event.LTBP1-ZDHHC2 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.
LTBP1-ZDHHC2 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.
LTBP1-ZDHHC2 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.
LTBP1-ZDHHC2 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.
ZDHHC2-LTBP1 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.
ZDHHC2-LTBP1 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
HgeneLTBP1

GO:0035583

sequestering of TGFbeta in extracellular matrix

2022183|8617200

HgeneLTBP1

GO:1901388

regulation of transforming growth factor beta activation

2022183|8617200

TgeneZDHHC2

GO:0018345

protein palmitoylation

23034182



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/chr2:17014362/chr8:33572434)
- 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 LTBP1 (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 ZDHHC2 (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)
ENST00000404816LTBP1chr233540336+ENST00000262096ZDHHC2chr817042298+963540833250561674
ENST00000354476LTBP1chr233540336+ENST00000262096ZDHHC2chr817042298+930837561147291572
ENST00000390003LTBP1chr233540336+ENST00000262096ZDHHC2chr817042298+8448289614138691242
ENST00000418533LTBP1chr233540336+ENST00000262096ZDHHC2chr817042298+8445289314138661241
ENST00000402934LTBP1chr233540336+ENST00000262096ZDHHC2chr817042298+8258270611336791188
ENST00000404525LTBP1chr233540336+ENST00000262096ZDHHC2chr817042298+824426929936651188
ENST00000407925LTBP1chr233540336+ENST00000262096ZDHHC2chr817042298+838528338138061241
ENST00000272273LTBP1chr233540336+ENST00000262096ZDHHC2chr817042298+63107581541731525

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
ENST00000404816ENST00000262096LTBP1chr233540336+ZDHHC2chr817042298+0.0001026640.99989736
ENST00000354476ENST00000262096LTBP1chr233540336+ZDHHC2chr817042298+0.0001228180.9998772
ENST00000390003ENST00000262096LTBP1chr233540336+ZDHHC2chr817042298+7.07E-050.9999293
ENST00000418533ENST00000262096LTBP1chr233540336+ZDHHC2chr817042298+3.14E-050.99996865
ENST00000402934ENST00000262096LTBP1chr233540336+ZDHHC2chr817042298+6.89E-050.9999311
ENST00000404525ENST00000262096LTBP1chr233540336+ZDHHC2chr817042298+6.75E-050.9999325
ENST00000407925ENST00000262096LTBP1chr233540336+ZDHHC2chr817042298+2.86E-050.9999714
ENST00000272273ENST00000262096LTBP1chr233540336+ZDHHC2chr817042298+9.76E-050.99990237

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 LTBP1-ZDHHC2

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
LTBP1chr233540336ZDHHC2chr8170422982692864QGFSISADGRTCEVSMENTGEQVVCL
LTBP1chr233540336ZDHHC2chr8170422982706864QGFSISADGRTCEVSMENTGEQVVCL
LTBP1chr233540336ZDHHC2chr8170422982833917QGFSISADGRTCEVSMENTGEQVVCL
LTBP1chr233540336ZDHHC2chr8170422982893917QGFSISADGRTCEVSMENTGEQVVCL
LTBP1chr233540336ZDHHC2chr8170422982896918QGFSISADGRTCEVSMENTGEQVVCL
LTBP1chr233540336ZDHHC2chr81704229837561248QGFSISADGRTCEVSMENTGEQVVCL
LTBP1chr233540336ZDHHC2chr81704229840831350QGFSISADGRTCEVSMENTGEQVVCL
LTBP1chr233540336ZDHHC2chr817042298758201QGFSISADGRTCEVSMENTGEQVVCL

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Potential FusionNeoAntigen Information of LTBP1-ZDHHC2 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.
LTBP1-ZDHHC2_33540336_17042298.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)
LTBP1-ZDHHC2chr233540336chr817042298758HLA-C04:10SADGRTCEV0.99990.9715514
LTBP1-ZDHHC2chr233540336chr817042298758HLA-C05:09SADGRTCEV0.99990.9834514
LTBP1-ZDHHC2chr233540336chr817042298758HLA-C04:07SADGRTCEV0.99980.974514
LTBP1-ZDHHC2chr233540336chr817042298758HLA-C08:15SADGRTCEV0.99950.9884514
LTBP1-ZDHHC2chr233540336chr817042298758HLA-C01:17SADGRTCEV0.99840.9733514
LTBP1-ZDHHC2chr233540336chr817042298758HLA-C15:06SADGRTCEV0.99810.9088514
LTBP1-ZDHHC2chr233540336chr817042298758HLA-C04:06SADGRTCEV0.99740.9891514
LTBP1-ZDHHC2chr233540336chr817042298758HLA-C03:19SADGRTCEV0.98510.9698514
LTBP1-ZDHHC2chr233540336chr817042298758HLA-C04:14SADGRTCEV0.98090.9806514
LTBP1-ZDHHC2chr233540336chr817042298758HLA-C08:13SADGRTCEV0.97220.9923514
LTBP1-ZDHHC2chr233540336chr817042298758HLA-C08:04SADGRTCEV0.97220.9923514
LTBP1-ZDHHC2chr233540336chr817042298758HLA-C02:06SADGRTCEV0.86770.9653514
LTBP1-ZDHHC2chr233540336chr817042298758HLA-C08:03SADGRTCEV0.78670.9889514
LTBP1-ZDHHC2chr233540336chr817042298758HLA-C08:15SADGRTCEVSM10.9881516
LTBP1-ZDHHC2chr233540336chr817042298758HLA-C05:09SADGRTCEVSM10.975516
LTBP1-ZDHHC2chr233540336chr817042298758HLA-C08:04SADGRTCEVSM0.99860.9837516
LTBP1-ZDHHC2chr233540336chr817042298758HLA-C08:13SADGRTCEVSM0.99860.9837516
LTBP1-ZDHHC2chr233540336chr817042298758HLA-C04:03SADGRTCEV0.99990.9789514
LTBP1-ZDHHC2chr233540336chr817042298758HLA-C05:01SADGRTCEV0.99990.9834514
LTBP1-ZDHHC2chr233540336chr817042298758HLA-C04:01SADGRTCEV0.99980.974514
LTBP1-ZDHHC2chr233540336chr817042298758HLA-C18:01SADGRTCEV0.99980.9723514
LTBP1-ZDHHC2chr233540336chr817042298758HLA-C01:03SADGRTCEV0.99970.9813514
LTBP1-ZDHHC2chr233540336chr817042298758HLA-C08:02SADGRTCEV0.99950.9884514
LTBP1-ZDHHC2chr233540336chr817042298758HLA-C15:02SADGRTCEV0.99890.9144514
LTBP1-ZDHHC2chr233540336chr817042298758HLA-C15:05SADGRTCEV0.99850.9603514
LTBP1-ZDHHC2chr233540336chr817042298758HLA-C03:06SADGRTCEV0.97360.971514
LTBP1-ZDHHC2chr233540336chr817042298758HLA-C17:01SADGRTCEV0.83070.9902514
LTBP1-ZDHHC2chr233540336chr817042298758HLA-C08:01SADGRTCEV0.78670.9889514
LTBP1-ZDHHC2chr233540336chr817042298758HLA-B07:13SADGRTCEV0.44080.9317514
LTBP1-ZDHHC2chr233540336chr817042298758HLA-C07:04SADGRTCEV0.31430.9563514
LTBP1-ZDHHC2chr233540336chr817042298758HLA-C08:02SADGRTCEVSM10.9881516
LTBP1-ZDHHC2chr233540336chr817042298758HLA-C05:01SADGRTCEVSM10.975516

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Potential FusionNeoAntigen Information of LTBP1-ZDHHC2 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 LTBP1-ZDHHC2

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
111ADGRTCEVSMENTGLTBP1ZDHHC2chr233540336chr817042298758

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of LTBP1-ZDHHC2

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-B14:023BVN111ADGRTCEVSMENTG-7.3601-7.4735
HLA-B14:023BVN111ADGRTCEVSMENTG-6.01154-7.04684
HLA-B52:013W39111ADGRTCEVSMENTG-6.56455-6.67795
HLA-B52:013W39111ADGRTCEVSMENTG-5.63926-6.67456
HLA-A11:014UQ2111ADGRTCEVSMENTG-7.8741-8.9094
HLA-A24:025HGA111ADGRTCEVSMENTG-9.41287-9.52627
HLA-A24:025HGA111ADGRTCEVSMENTG-5.67638-6.71168
HLA-B27:056PYJ111ADGRTCEVSMENTG-7.01166-7.12506
HLA-B44:053DX8111ADGRTCEVSMENTG-6.78889-6.90229
HLA-B44:053DX8111ADGRTCEVSMENTG-3.94389-4.97919
HLA-A02:016TDR111ADGRTCEVSMENTG-7.42945-7.54285

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Vaccine Design for the FusionNeoAntigens of LTBP1-ZDHHC2

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
LTBP1-ZDHHC2chr233540336chr817042298514SADGRTCEVCTGCAGATGGCCGTACGTGTGAAGTGT
LTBP1-ZDHHC2chr233540336chr817042298516SADGRTCEVSMCTGCAGATGGCCGTACGTGTGAAGTGTCCATGG

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 LTBP1-ZDHHC2

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
BRCALTBP1-ZDHHC2chr233540336ENST00000272273chr817042298ENST00000262096TCGA-AR-A0TU-01A

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Potential target of CAR-T therapy development for LTBP1-ZDHHC2

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
TgeneZDHHC2chr2:33540336chr8:17042298ENST00000262096013171_19101607.6666666666667TransmembraneHelical
TgeneZDHHC2chr2:33540336chr8:17042298ENST00000262096013209_22901607.6666666666667TransmembraneHelical
TgeneZDHHC2chr2:33540336chr8:17042298ENST0000026209601355_7501607.6666666666667TransmembraneHelical

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 LTBP1-ZDHHC2

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 LTBP1-ZDHHC2

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