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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:LAPTM4B-CPQ

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: LAPTM4B-CPQ
FusionPDB ID: 44054
FusionGDB2.0 ID: 44054
HgeneTgene
Gene symbol

LAPTM4B

CPQ

Gene ID

55353

10404

Gene namelysosomal protein transmembrane 4 betacarboxypeptidase Q
SynonymsLAPTM4beta|LC27LDP|PGCP
Cytomap

8q22.1

8q22.1

Type of geneprotein-codingprotein-coding
Descriptionlysosomal-associated transmembrane protein 4Blysosomal associated protein transmembrane 4 betalysosome-associated transmembrane protein 4-betacarboxypeptidase QSer-Met dipeptidaseaminopeptidaseblood plasma glutamate carboxypeptidaselysosomal dipeptidase
Modification date2020031320200313
UniProtAcc

Q86VI4

Main function of 5'-partner protein: FUNCTION: Required for optimal lysosomal function (PubMed:21224396). Blocks EGF-stimulated EGFR intraluminal sorting and degradation. Conversely by binding with the phosphatidylinositol 4,5-bisphosphate, regulates its PIP5K1C interaction, inhibits HGS ubiquitination and relieves LAPTM4B inhibition of EGFR degradation (PubMed:25588945). Recruits SLC3A2 and SLC7A5 (the Leu transporter) to the lysosome, promoting entry of leucine and other essential amino acid (EAA) into the lysosome, stimulating activation of proton-transporting vacuolar (V)-ATPase protein pump (V-ATPase) and hence mTORC1 activation (PubMed:25998567). Plays a role as negative regulator of TGFB1 production in regulatory T cells (PubMed:26126825). Binds ceramide and facilitates its exit from late endosome in order to control cell death pathways (PubMed:26280656). {ECO:0000269|PubMed:21224396, ECO:0000269|PubMed:25588945, ECO:0000269|PubMed:25998567, ECO:0000269|PubMed:26126825, ECO:0000269|PubMed:26280656}.

Q9Y646

Main function of 5'-partner protein: FUNCTION: Carboxypeptidase that may play an important role in the hydrolysis of circulating peptides. Catalyzes the hydrolysis of dipeptides with unsubstituted terminals into amino acids. May play a role in the liberation of thyroxine hormone from its thyroglobulin (Tg) precursor.
Ensembl transtripts involved in fusion geneENST idsENST00000445593, ENST00000521545, 
ENST00000529551, ENST00000220763, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score10 X 5 X 9=45016 X 14 X 11=2464
# samples 1619
** MAII scorelog2(16/450*10)=-1.49185309632967
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(19/2464*10)=-3.69693093236395
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: LAPTM4B [Title/Abstract] AND CPQ [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: LAPTM4B [Title/Abstract] AND CPQ [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)LAPTM4B(98788336)-CPQ(98155248), # samples:2
Anticipated loss of major functional domain due to fusion event.LAPTM4B-CPQ 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.
LAPTM4B-CPQ 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
HgeneLAPTM4B

GO:0032509

endosome transport via multivesicular body sorting pathway

25588945

HgeneLAPTM4B

GO:0032911

negative regulation of transforming growth factor beta1 production

26126825

TgeneCPQ

GO:0006508

proteolysis

10206990

TgeneCPQ

GO:0043171

peptide catabolic process

10206990



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/chr8:98788336/chr8:98155248)
- 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 LAPTM4B (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 CPQ (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)
ENST00000445593LAPTM4Bchr898788336+ENST00000220763CPQchr898155248+153410526251215196
ENST00000521545LAPTM4Bchr898788336+ENST00000220763CPQchr898155248+8153333601120

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
ENST00000445593ENST00000220763LAPTM4Bchr898788336+CPQchr898155248+0.0174262370.9825738
ENST00000521545ENST00000220763LAPTM4Bchr898788336+CPQchr898155248+0.119411810.8805882

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 LAPTM4B-CPQ

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
LAPTM4Bchr898788336CPQchr8981552481052142CPHRHHPARRLVSGASLLDDLYKYFF

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Potential FusionNeoAntigen Information of LAPTM4B-CPQ 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.
LAPTM4B-CPQ_98788336_98155248.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)
LAPTM4B-CPQchr898788336chr8981552481052HLA-B27:05RRLVSGASL0.99980.7083817
LAPTM4B-CPQchr898788336chr8981552481052HLA-B27:04RRLVSGASL0.99980.8218817
LAPTM4B-CPQchr898788336chr8981552481052HLA-B27:07RRLVSGASL0.99970.5733817
LAPTM4B-CPQchr898788336chr8981552481052HLA-B39:24RRLVSGASL0.98880.756817
LAPTM4B-CPQchr898788336chr8981552481052HLA-B14:01RRLVSGASL0.9830.9101817
LAPTM4B-CPQchr898788336chr8981552481052HLA-B14:02RRLVSGASL0.9830.9101817
LAPTM4B-CPQchr898788336chr8981552481052HLA-B39:01RRLVSGASL0.98180.9454817
LAPTM4B-CPQchr898788336chr8981552481052HLA-A02:13RLVSGASLL0.96030.6991918
LAPTM4B-CPQchr898788336chr8981552481052HLA-A02:38RLVSGASLL0.93010.6766918
LAPTM4B-CPQchr898788336chr8981552481052HLA-B48:01RRLVSGASL0.69710.7018817
LAPTM4B-CPQchr898788336chr8981552481052HLA-B07:10RRLVSGASL0.30470.7748817
LAPTM4B-CPQchr898788336chr8981552481052HLA-B48:01RLVSGASLL0.17210.6662918
LAPTM4B-CPQchr898788336chr8981552481052HLA-B13:01RLVSGASLL0.05610.9751918
LAPTM4B-CPQchr898788336chr8981552481052HLA-B13:02RLVSGASLL0.05230.7407918
LAPTM4B-CPQchr898788336chr8981552481052HLA-B27:05RRLVSGASLL0.99990.5537818
LAPTM4B-CPQchr898788336chr8981552481052HLA-B27:04RRLVSGASLL0.99990.7195818
LAPTM4B-CPQchr898788336chr8981552481052HLA-B27:07RRLVSGASLL0.99970.6155818
LAPTM4B-CPQchr898788336chr8981552481052HLA-B27:07ARRLVSGASL0.99920.5862717
LAPTM4B-CPQchr898788336chr8981552481052HLA-B07:10ARRLVSGASL0.8790.8025717
LAPTM4B-CPQchr898788336chr8981552481052HLA-B27:07ARRLVSGASLL0.99980.6462718
LAPTM4B-CPQchr898788336chr8981552481052HLA-B27:14RRLVSGASL0.99980.6992817
LAPTM4B-CPQchr898788336chr8981552481052HLA-C07:05RRLVSGASL0.99770.9443817
LAPTM4B-CPQchr898788336chr8981552481052HLA-C07:95RRLVSGASL0.99760.6927817
LAPTM4B-CPQchr898788336chr8981552481052HLA-C07:13RRLVSGASL0.99440.9569817
LAPTM4B-CPQchr898788336chr8981552481052HLA-C07:27RRLVSGASL0.9930.9461817
LAPTM4B-CPQchr898788336chr8981552481052HLA-C07:29RRLVSGASL0.9920.8956817
LAPTM4B-CPQchr898788336chr8981552481052HLA-B27:03RRLVSGASL0.99190.7305817
LAPTM4B-CPQchr898788336chr8981552481052HLA-B39:09RRLVSGASL0.9820.8623817
LAPTM4B-CPQchr898788336chr8981552481052HLA-B39:12RRLVSGASL0.98130.9488817
LAPTM4B-CPQchr898788336chr8981552481052HLA-C07:46RRLVSGASL0.95780.9206817
LAPTM4B-CPQchr898788336chr8981552481052HLA-C07:19RRLVSGASL0.89950.8249817
LAPTM4B-CPQchr898788336chr8981552481052HLA-B15:04RLVSGASLL0.86390.8979918
LAPTM4B-CPQchr898788336chr8981552481052HLA-B14:03RRLVSGASL0.6610.9222817
LAPTM4B-CPQchr898788336chr8981552481052HLA-C12:16RRLVSGASL0.12190.9596817
LAPTM4B-CPQchr898788336chr8981552481052HLA-B27:14RRLVSGASLL0.99990.5766818
LAPTM4B-CPQchr898788336chr8981552481052HLA-B27:03RRLVSGASLL0.99780.5884818
LAPTM4B-CPQchr898788336chr8981552481052HLA-B27:08RRLVSGASL0.99980.6496817
LAPTM4B-CPQchr898788336chr8981552481052HLA-B27:10RRLVSGASL0.99980.8891817
LAPTM4B-CPQchr898788336chr8981552481052HLA-B27:06RRLVSGASL0.99980.8526817
LAPTM4B-CPQchr898788336chr8981552481052HLA-B27:09RRLVSGASL0.99960.6679817
LAPTM4B-CPQchr898788336chr8981552481052HLA-C07:01RRLVSGASL0.99820.6855817
LAPTM4B-CPQchr898788336chr8981552481052HLA-A02:03RLVSGASLL0.9820.6176918
LAPTM4B-CPQchr898788336chr8981552481052HLA-B39:31RRLVSGASL0.9680.9468817
LAPTM4B-CPQchr898788336chr8981552481052HLA-C07:22RRLVSGASL0.88020.7126817
LAPTM4B-CPQchr898788336chr8981552481052HLA-B15:73RLVSGASLL0.84030.9605918
LAPTM4B-CPQchr898788336chr8981552481052HLA-B15:30RLVSGASLL0.69630.9188918
LAPTM4B-CPQchr898788336chr8981552481052HLA-B48:05RRLVSGASL0.42780.7029817
LAPTM4B-CPQchr898788336chr8981552481052HLA-B40:21RLVSGASLL0.03050.6577918
LAPTM4B-CPQchr898788336chr8981552481052HLA-B27:10RRLVSGASLL0.99990.7895818
LAPTM4B-CPQchr898788336chr8981552481052HLA-B27:06RRLVSGASLL0.99980.7729818
LAPTM4B-CPQchr898788336chr8981552481052HLA-B27:09RRLVSGASLL0.99970.5468818
LAPTM4B-CPQchr898788336chr8981552481052HLA-B27:08ARRLVSGASL0.99950.5948717
LAPTM4B-CPQchr898788336chr8981552481052HLA-B27:06ARRLVSGASL0.99940.8357717
LAPTM4B-CPQchr898788336chr8981552481052HLA-B27:09ARRLVSGASL0.99830.6309717
LAPTM4B-CPQchr898788336chr8981552481052HLA-B27:06ARRLVSGASLL0.99990.7843718

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Potential FusionNeoAntigen Information of LAPTM4B-CPQ 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 LAPTM4B-CPQ

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
6506PARRLVSGASLLDDLAPTM4BCPQchr898788336chr8981552481052

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of LAPTM4B-CPQ

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-B14:023BVN6506PARRLVSGASLLDD-7.15543-7.26883
HLA-B14:023BVN6506PARRLVSGASLLDD-4.77435-5.80965
HLA-B52:013W396506PARRLVSGASLLDD-6.80875-6.92215
HLA-B52:013W396506PARRLVSGASLLDD-4.20386-5.23916
HLA-A11:014UQ26506PARRLVSGASLLDD-7.5194-8.5547
HLA-A11:014UQ26506PARRLVSGASLLDD-6.9601-7.0735
HLA-A24:025HGA6506PARRLVSGASLLDD-7.52403-7.63743
HLA-A24:025HGA6506PARRLVSGASLLDD-5.82433-6.85963
HLA-B27:056PYJ6506PARRLVSGASLLDD-3.28285-4.31815
HLA-B44:053DX86506PARRLVSGASLLDD-5.91172-6.94702
HLA-B44:053DX86506PARRLVSGASLLDD-4.24346-4.35686

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Vaccine Design for the FusionNeoAntigens of LAPTM4B-CPQ

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
LAPTM4B-CPQchr898788336chr898155248717ARRLVSGASLCTCGGCGTCTGGTATCTGGAGCCAGTCTAC
LAPTM4B-CPQchr898788336chr898155248718ARRLVSGASLLCTCGGCGTCTGGTATCTGGAGCCAGTCTACTTG
LAPTM4B-CPQchr898788336chr898155248817RRLVSGASLGGCGTCTGGTATCTGGAGCCAGTCTAC
LAPTM4B-CPQchr898788336chr898155248818RRLVSGASLLGGCGTCTGGTATCTGGAGCCAGTCTACTTG
LAPTM4B-CPQchr898788336chr898155248918RLVSGASLLGTCTGGTATCTGGAGCCAGTCTACTTG

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 LAPTM4B-CPQ

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
OVLAPTM4B-CPQchr898788336ENST00000445593chr898155248ENST00000220763TCGA-23-2078-01A

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Potential target of CAR-T therapy development for LAPTM4B-CPQ

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 LAPTM4B-CPQ

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 LAPTM4B-CPQ

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