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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:LUC7L-TPM4

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: LUC7L-TPM4
FusionPDB ID: 50378
FusionGDB2.0 ID: 50378
HgeneTgene
Gene symbol

LUC7L

TPM4

Gene ID

55692

7171

Gene nameLUC7 liketropomyosin 4
SynonymsLUC7B1|Luc7|SR+89|hLuc7B1HEL-S-108
Cytomap

16p13.3

19p13.12-p13.11

Type of geneprotein-codingprotein-coding
Descriptionputative RNA-binding protein Luc7-like 1putative SR protein LUC7B1sarcoplasmic reticulum protein LUC7B1tropomyosin alpha-4 chainTM30p1epididymis secretory protein Li 108
Modification date2020032020200320
UniProtAcc

O95232

Main function of 5'-partner protein: FUNCTION: Binds cAMP regulatory element DNA sequence. May play a role in RNA splicing. {ECO:0000269|PubMed:16462885}.

P67936

Main function of 5'-partner protein: FUNCTION: Binds to actin filaments in muscle and non-muscle cells. Plays a central role, in association with the troponin complex, in the calcium dependent regulation of vertebrate striated muscle contraction. Smooth muscle contraction is regulated by interaction with caldesmon. In non-muscle cells is implicated in stabilizing cytoskeleton actin filaments (By similarity). Binds calcium (PubMed:1836432). {ECO:0000250|UniProtKB:P09495, ECO:0000269|PubMed:1836432}.
Ensembl transtripts involved in fusion geneENST idsENST00000293872, ENST00000337351, 
ENST00000397783, ENST00000397780, 
ENST00000494366, 
ENST00000591645, 
ENST00000300933, ENST00000344824, 
ENST00000538887, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score19 X 17 X 10=323014 X 12 X 6=1008
# samples 2514
** MAII scorelog2(25/3230*10)=-3.6915341649192
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(14/1008*10)=-2.84799690655495
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: LUC7L [Title/Abstract] AND TPM4 [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: LUC7L [Title/Abstract] AND TPM4 [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)LUC7L(279277)-TPM4(16192722), # samples:1
Anticipated loss of major functional domain due to fusion event.LUC7L-TPM4 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.
LUC7L-TPM4 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


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/chr16:279277/chr19:16192722)
- 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 LUC7L (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 TPM4 (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)
ENST00000293872LUC7Lchr16279277-ENST00000344824TPM4chr1916192722+123117261786241
ENST00000293872LUC7Lchr16279277-ENST00000538887TPM4chr1916192722+138717261786241
ENST00000293872LUC7Lchr16279277-ENST00000300933TPM4chr1916192722+232217261786241
ENST00000337351LUC7Lchr16279277-ENST00000344824TPM4chr1916192722+124418574799241
ENST00000337351LUC7Lchr16279277-ENST00000538887TPM4chr1916192722+140018574799241
ENST00000337351LUC7Lchr16279277-ENST00000300933TPM4chr1916192722+233518574799241
ENST00000397783LUC7Lchr16279277-ENST00000344824TPM4chr1916192722+124418574799241
ENST00000397783LUC7Lchr16279277-ENST00000538887TPM4chr1916192722+140018574799241
ENST00000397783LUC7Lchr16279277-ENST00000300933TPM4chr1916192722+233518574799241

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
ENST00000293872ENST00000344824LUC7Lchr16279277-TPM4chr1916192722+0.0009040940.9990959
ENST00000293872ENST00000538887LUC7Lchr16279277-TPM4chr1916192722+0.000923140.99907684
ENST00000293872ENST00000300933LUC7Lchr16279277-TPM4chr1916192722+0.0012879760.99871206
ENST00000337351ENST00000344824LUC7Lchr16279277-TPM4chr1916192722+0.0010591590.9989409
ENST00000337351ENST00000538887LUC7Lchr16279277-TPM4chr1916192722+0.0010818170.9989182
ENST00000337351ENST00000300933LUC7Lchr16279277-TPM4chr1916192722+0.0011016460.9988984
ENST00000397783ENST00000344824LUC7Lchr16279277-TPM4chr1916192722+0.0010591590.9989409
ENST00000397783ENST00000538887LUC7Lchr16279277-TPM4chr1916192722+0.0010818170.9989182
ENST00000397783ENST00000300933LUC7Lchr16279277-TPM4chr1916192722+0.0011016460.9988984

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 LUC7L-TPM4

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

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Potential FusionNeoAntigen Information of LUC7L-TPM4 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.

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)

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Potential FusionNeoAntigen Information of LUC7L-TPM4 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 LUC7L-TPM4

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.

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of LUC7L-TPM4

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

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Vaccine Design for the FusionNeoAntigens of LUC7L-TPM4

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

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 LUC7L-TPM4

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

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Potential target of CAR-T therapy development for LUC7L-TPM4

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 LUC7L-TPM4

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 LUC7L-TPM4

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
TgeneTPM4C0001787Osteoporosis, Age-Related1CTD_human
TgeneTPM4C0003949Asbestosis1CTD_human
TgeneTPM4C0005818Blood Platelet Disorders1GENOMICS_ENGLAND
TgeneTPM4C0014859Esophageal Neoplasms1CTD_human
TgeneTPM4C0023893Liver Cirrhosis, Experimental1CTD_human
TgeneTPM4C0027627Neoplasm Metastasis1CTD_human
TgeneTPM4C0029456Osteoporosis1CTD_human
TgeneTPM4C0029459Osteoporosis, Senile1CTD_human
TgeneTPM4C0032927Precancerous Conditions1CTD_human
TgeneTPM4C0043094Weight Gain1CTD_human
TgeneTPM4C0282313Condition, Preneoplastic1CTD_human
TgeneTPM4C0334121Inflammatory Myofibroblastic Tumor1ORPHANET
TgeneTPM4C0546837Malignant neoplasm of esophagus1CTD_human
TgeneTPM4C0751406Post-Traumatic Osteoporosis1CTD_human
TgeneTPM4C0948089Acute Coronary Syndrome1CTD_human
TgeneTPM4C2751260Macrothrombocytopenia1GENOMICS_ENGLAND
TgeneTPM4C2930617Pulmonary Fibrosis - from Asbestos Exposure1CTD_human
TgeneTPM4C4304021Autosomal dominant macrothrombocytopenia1ORPHANET