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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:CALU-LAP3

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: CALU-LAP3
FusionPDB ID: 12626
FusionGDB2.0 ID: 12626
HgeneTgene
Gene symbol

CALU

LAP3

Gene ID

813

51056

Gene namecalumeninleucine aminopeptidase 3
Synonyms-HEL-S-106|LAP|LAPEP|PEPS
Cytomap

7q32.1

4p15.32

Type of geneprotein-codingprotein-coding
DescriptioncalumeninIEF SSP 9302crocalbin-like proteinmultiple EF-hand proteincytosol aminopeptidaseLAP-3epididymis secretory protein Li 106leucyl aminopeptidasepeptidase Sproline aminopeptidaseprolyl aminopeptidase
Modification date2020031320200313
UniProtAcc

O43852

Main function of 5'-partner protein: FUNCTION: Involved in regulation of vitamin K-dependent carboxylation of multiple N-terminal glutamate residues. Seems to inhibit gamma-carboxylase GGCX. Binds 7 calcium ions with a low affinity (By similarity). {ECO:0000250}.

P28838

Main function of 5'-partner protein: FUNCTION: Cytolosic metallopeptidase that catalyzes the removal of unsubstituted N-terminal hydrophobic amino acids from various peptides. The presence of Zn(2+) ions is essential for the peptidase activity, and the association with other cofactors can modulate the substrate spectificity of the enzyme. For instance, in the presence of Mn(2+), it displays a specific Cys-Gly hydrolyzing activity of Cys-Gly-S-conjugates. Involved in the metabolism of glutathione and in the degradation of glutathione S-conjugates, which may play a role in the control of the cell redox status. {ECO:0000250|UniProtKB:P00727}.
Ensembl transtripts involved in fusion geneENST idsENST00000535623, ENST00000249364, 
ENST00000449187, ENST00000479257, 
ENST00000538546, ENST00000542996, 
ENST00000535011, 
ENST00000226299, 
ENST00000606142, ENST00000503467, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score12 X 13 X 3=4688 X 7 X 7=392
# samples 188
** MAII scorelog2(18/468*10)=-1.37851162325373
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(8/392*10)=-2.29278174922785
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: CALU [Title/Abstract] AND LAP3 [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: CALU [Title/Abstract] AND LAP3 [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)CALU(128407709)-LAP3(17600079), # samples:1
Anticipated loss of major functional domain due to fusion event.CALU-LAP3 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.
CALU-LAP3 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.
CALU-LAP3 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.
CALU-LAP3 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/chr7:128407709/chr4:17600079)
- 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 CALU (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 LAP3 (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)
ENST00000538546CALUchr7128407709+ENST00000226299LAP3chr417600079+14315691791051290
ENST00000538546CALUchr7128407709+ENST00000606142LAP3chr417600079+13975691791051290
ENST00000542996CALUchr7128407709+ENST00000226299LAP3chr417600079+267218108742292472
ENST00000542996CALUchr7128407709+ENST00000606142LAP3chr417600079+263818108742292472
ENST00000249364CALUchr7128407709+ENST00000226299LAP3chr417600079+18079451021427441
ENST00000249364CALUchr7128407709+ENST00000606142LAP3chr417600079+17739451021427441
ENST00000449187CALUchr7128407709+ENST00000226299LAP3chr417600079+1786924811406441
ENST00000449187CALUchr7128407709+ENST00000606142LAP3chr417600079+1752924811406441
ENST00000479257CALUchr7128407709+ENST00000226299LAP3chr417600079+256016987622180472
ENST00000479257CALUchr7128407709+ENST00000606142LAP3chr417600079+252616987622180472

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
ENST00000538546ENST00000226299CALUchr7128407709+LAP3chr417600079+0.0005585830.99944144
ENST00000538546ENST00000606142CALUchr7128407709+LAP3chr417600079+0.0005599370.99944
ENST00000542996ENST00000226299CALUchr7128407709+LAP3chr417600079+0.0001724260.9998275
ENST00000542996ENST00000606142CALUchr7128407709+LAP3chr417600079+0.0001737930.99982625
ENST00000249364ENST00000226299CALUchr7128407709+LAP3chr417600079+0.0005926160.9994074
ENST00000249364ENST00000606142CALUchr7128407709+LAP3chr417600079+0.0005885390.99941146
ENST00000449187ENST00000226299CALUchr7128407709+LAP3chr417600079+0.0005423790.99945766
ENST00000449187ENST00000606142CALUchr7128407709+LAP3chr417600079+0.0005471850.99945277
ENST00000479257ENST00000226299CALUchr7128407709+LAP3chr417600079+0.0001892550.99981076
ENST00000479257ENST00000606142CALUchr7128407709+LAP3chr417600079+0.0001953680.9998047

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 CALU-LAP3

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
CALUchr7128407709LAP3chr4176000791698312EARHLVYESDQNKVDNTDAEGRLILA
CALUchr7128407709LAP3chr4176000791810312EARHLVYESDQNKVDNTDAEGRLILA
CALUchr7128407709LAP3chr417600079569130EARHLVYESDQNKVDNTDAEGRLILA
CALUchr7128407709LAP3chr417600079924281EARHLVYESDQNKVDNTDAEGRLILA
CALUchr7128407709LAP3chr417600079945281EARHLVYESDQNKVDNTDAEGRLILA

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Potential FusionNeoAntigen Information of CALU-LAP3 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.
CALU-LAP3_128407709_17600079.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)
CALU-LAP3chr7128407709chr417600079945HLA-C04:10VYESDQNKV0.99030.7904514
CALU-LAP3chr7128407709chr417600079945HLA-C04:07VYESDQNKV0.98730.8151514
CALU-LAP3chr7128407709chr417600079945HLA-C04:14VYESDQNKV0.60270.7906514
CALU-LAP3chr7128407709chr417600079945HLA-C04:01VYESDQNKV0.98730.8151514
CALU-LAP3chr7128407709chr417600079945HLA-C18:01VYESDQNKV0.95950.8347514
CALU-LAP3chr7128407709chr417600079945HLA-C04:04VYESDQNKV0.80720.6514514

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Potential FusionNeoAntigen Information of CALU-LAP3 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.
CALU-LAP3_128407709_17600079.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)
CALU-LAP3chr7128407709chr417600079945DRB1-0405HLVYESDQNKVDNTD318
CALU-LAP3chr7128407709chr417600079945DRB1-0409HLVYESDQNKVDNTD318
CALU-LAP3chr7128407709chr417600079945DRB1-0409RHLVYESDQNKVDNT217
CALU-LAP3chr7128407709chr417600079945DRB1-0409ARHLVYESDQNKVDN116
CALU-LAP3chr7128407709chr417600079945DRB1-0409LVYESDQNKVDNTDA419
CALU-LAP3chr7128407709chr417600079945DRB1-0417HLVYESDQNKVDNTD318
CALU-LAP3chr7128407709chr417600079945DRB1-0429HLVYESDQNKVDNTD318
CALU-LAP3chr7128407709chr417600079945DRB1-0430HLVYESDQNKVDNTD318
CALU-LAP3chr7128407709chr417600079945DRB1-0445HLVYESDQNKVDNTD318
CALU-LAP3chr7128407709chr417600079945DRB1-0448HLVYESDQNKVDNTD318
CALU-LAP3chr7128407709chr417600079945DRB1-0457HLVYESDQNKVDNTD318
CALU-LAP3chr7128407709chr417600079945DRB1-0462HLVYESDQNKVDNTD318
CALU-LAP3chr7128407709chr417600079945DRB1-0462RHLVYESDQNKVDNT217
CALU-LAP3chr7128407709chr417600079945DRB1-0462ARHLVYESDQNKVDN116
CALU-LAP3chr7128407709chr417600079945DRB1-0477HLVYESDQNKVDNTD318
CALU-LAP3chr7128407709chr417600079945DRB1-0483HLVYESDQNKVDNTD318
CALU-LAP3chr7128407709chr417600079945DRB1-0484HLVYESDQNKVDNTD318
CALU-LAP3chr7128407709chr417600079945DRB1-0487HLVYESDQNKVDNTD318
CALU-LAP3chr7128407709chr417600079945DRB1-0489HLVYESDQNKVDNTD318
CALU-LAP3chr7128407709chr417600079945DRB1-0906RHLVYESDQNKVDNT217
CALU-LAP3chr7128407709chr417600079945DRB1-0906ARHLVYESDQNKVDN116
CALU-LAP3chr7128407709chr417600079945DRB1-1333HLVYESDQNKVDNTD318

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Fusion breakpoint peptide structures of CALU-LAP3

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
10617YESDQNKVDNTDAECALULAP3chr7128407709chr417600079945

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of CALU-LAP3

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-B14:023BVN10617YESDQNKVDNTDAE-6.15238-6.26578
HLA-B14:023BVN10617YESDQNKVDNTDAE-5.35203-6.38733
HLA-B52:013W3910617YESDQNKVDNTDAE-5.804-6.8393
HLA-B52:013W3910617YESDQNKVDNTDAE-5.45277-5.56617
HLA-A11:014UQ210617YESDQNKVDNTDAE-8.28119-9.31649
HLA-A24:025HGA10617YESDQNKVDNTDAE-9.93626-10.0497
HLA-A24:025HGA10617YESDQNKVDNTDAE-5.67154-6.70684
HLA-B27:056PYJ10617YESDQNKVDNTDAE-4.30966-5.34496
HLA-B44:053DX810617YESDQNKVDNTDAE-7.17842-7.29182
HLA-B44:053DX810617YESDQNKVDNTDAE-4.14208-5.17738
HLA-A02:016TDR10617YESDQNKVDNTDAE-5.17192-5.28532

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Vaccine Design for the FusionNeoAntigens of CALU-LAP3

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
CALU-LAP3chr7128407709chr417600079514VYESDQNKVGTCTATGAATCAGACCAAAACAAGGTT

check button mRNA and peptide sequences of FusionNeoAntigens that have potential interaction with HLA-IIs.
Fusion geneHchrHbpTchrTbpStart in +/-13AAEnd in +/-13AAFusionNeoAntigen peptideFusionNEoAntigen RNA sequence
CALU-LAP3chr7128407709chr417600079116ARHLVYESDQNKVDNGCCAGGCACCTGGTCTATGAATCAGACCAAAACAAGGTTGATAAC
CALU-LAP3chr7128407709chr417600079217RHLVYESDQNKVDNTAGGCACCTGGTCTATGAATCAGACCAAAACAAGGTTGATAACACT
CALU-LAP3chr7128407709chr417600079318HLVYESDQNKVDNTDCACCTGGTCTATGAATCAGACCAAAACAAGGTTGATAACACTGAT
CALU-LAP3chr7128407709chr417600079419LVYESDQNKVDNTDACTGGTCTATGAATCAGACCAAAACAAGGTTGATAACACTGATGCT

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Information of the samples that have these potential fusion neoantigens of CALU-LAP3

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
KIRPCALU-LAP3chr7128407709ENST00000249364chr417600079ENST00000226299TCGA-PJ-A5Z8-01A

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Potential target of CAR-T therapy development for CALU-LAP3

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 CALU-LAP3

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 CALU-LAP3

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