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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:LRP3-LSM14A

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: LRP3-LSM14A
FusionPDB ID: 49770
FusionGDB2.0 ID: 49770
HgeneTgene
Gene symbol

LRP3

LSM14A

Gene ID

4037

26065

Gene nameLDL receptor related protein 3LSM14A mRNA processing body assembly factor
Synonyms-C19orf13|FAM61A|RAP55|RAP55A
Cytomap

19q13.11

19q13.11

Type of geneprotein-codingprotein-coding
Descriptionlow-density lipoprotein receptor-related protein 3105 kDa low-density lipoprotein receptor-related proteinCTD-2540B15.13LRP-3hLRp105protein LSM14 homolog ALSM14 homolog ALSM14A, SCD6 homolog ARNA-associated protein 55RNA-associated protein 55AalphaSNBPfamily with sequence similarity 61, member AhRAP55hRAP55Aprotein SCD6 homologputative alpha-synuclein-binding protein
Modification date2020031320200327
UniProtAcc

O75074

Main function of 5'-partner protein: FUNCTION: Probable receptor, which may be involved in the internalization of lipophilic molecules and/or signal transduction. Its precise role is however unclear, since it does not bind to very low density lipoprotein (VLDL) or to LRPAP1 in vitro.

Q8ND56

Main function of 5'-partner protein: FUNCTION: Essential for formation of P-bodies, cytoplasmic structures that provide storage sites for translationally inactive mRNAs and protect them from degradation (PubMed:16484376, PubMed:17074753, PubMed:29510985). Acts as a repressor of mRNA translation (PubMed:29510985). May play a role in mitotic spindle assembly (PubMed:26339800). {ECO:0000269|PubMed:16484376, ECO:0000269|PubMed:17074753, ECO:0000269|PubMed:26339800, ECO:0000269|PubMed:29510985}.
Ensembl transtripts involved in fusion geneENST idsENST00000253193, ENST00000433627, 
ENST00000540746, ENST00000544216, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score6 X 6 X 4=14416 X 15 X 8=1920
# samples 720
** MAII scorelog2(7/144*10)=-1.04064198449735
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(20/1920*10)=-3.26303440583379
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: LRP3 [Title/Abstract] AND LSM14A [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: LRP3 [Title/Abstract] AND LSM14A [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)LRP3(33685764)-LSM14A(34685382), # samples:2
Anticipated loss of major functional domain due to fusion event.LRP3-LSM14A 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.
LRP3-LSM14A 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.
LRP3-LSM14A 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.
LRP3-LSM14A 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
TgeneLSM14A

GO:0033962

cytoplasmic mRNA processing body assembly

16484376



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/chr19:33685764/chr19:34685382)
- 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 LRP3 (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 LSM14A (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)
ENST00000253193LRP3chr1933685764+ENST00000540746LSM14Achr1934685383+21882752021422406
ENST00000253193LRP3chr1933685764+ENST00000544216LSM14Achr1934685383+36732752021545447
ENST00000253193LRP3chr1933685764+ENST00000433627LSM14Achr1934685383+35032752021545447
ENST00000253193LRP3chr1933685764+ENST00000540746LSM14Achr1934685382+21882752021422406
ENST00000253193LRP3chr1933685764+ENST00000544216LSM14Achr1934685382+36732752021545447
ENST00000253193LRP3chr1933685764+ENST00000433627LSM14Achr1934685382+35032752021545447

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
ENST00000253193ENST00000540746LRP3chr1933685764+LSM14Achr1934685383+0.0008580110.99914193
ENST00000253193ENST00000544216LRP3chr1933685764+LSM14Achr1934685383+0.0003832130.99961674
ENST00000253193ENST00000433627LRP3chr1933685764+LSM14Achr1934685383+0.0005924720.99940753
ENST00000253193ENST00000540746LRP3chr1933685764+LSM14Achr1934685382+0.0008580110.99914193
ENST00000253193ENST00000544216LRP3chr1933685764+LSM14Achr1934685382+0.0003832130.99961674
ENST00000253193ENST00000433627LRP3chr1933685764+LSM14Achr1934685382+0.0005924720.99940753

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 LRP3-LSM14A

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
LRP3chr1933685764LSM14Achr193468538227524APGARAQLAVVCLVRSFGTEDRPTDR
LRP3chr1933685764LSM14Achr193468538327524APGARAQLAVVCLVRSFGTEDRPTDR

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Potential FusionNeoAntigen Information of LRP3-LSM14A 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.
LRP3-LSM14A_33685764_34685382.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)
LRP3-LSM14Achr1933685764chr1934685382275HLA-A02:21AQLAVVCLV0.98560.7423514
LRP3-LSM14Achr1933685764chr1934685382275HLA-B46:01AVVCLVRSF0.95470.5675817
LRP3-LSM14Achr1933685764chr1934685382275HLA-B13:02AQLAVVCLV0.8320.8194514
LRP3-LSM14Achr1933685764chr1934685382275HLA-B52:01AQLAVVCLV0.01410.9926514
LRP3-LSM14Achr1933685764chr1934685382275HLA-A02:06AQLAVVCLV0.98560.7423514
LRP3-LSM14Achr1933685764chr1934685382275HLA-A02:14AQLAVVCLV0.98560.711514
LRP3-LSM14Achr1933685764chr1934685382275HLA-A32:01AVVCLVRSF0.98110.979817
LRP3-LSM14Achr1933685764chr1934685382275HLA-A25:01AVVCLVRSF0.95380.9465817

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Potential FusionNeoAntigen Information of LRP3-LSM14A 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.
LRP3-LSM14A_33685764_34685382.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)
LRP3-LSM14Achr1933685764chr1934685382275DRB1-0840CLVRSFGTEDRPTDR1126
LRP3-LSM14Achr1933685764chr1934685382275DRB1-1303CLVRSFGTEDRPTDR1126
LRP3-LSM14Achr1933685764chr1934685382275DRB1-13101CLVRSFGTEDRPTDR1126
LRP3-LSM14Achr1933685764chr1934685382275DRB1-1310CLVRSFGTEDRPTDR1126
LRP3-LSM14Achr1933685764chr1934685382275DRB1-1333CLVRSFGTEDRPTDR1126
LRP3-LSM14Achr1933685764chr1934685382275DRB1-1366CLVRSFGTEDRPTDR1126
LRP3-LSM14Achr1933685764chr1934685382275DRB1-1388CLVRSFGTEDRPTDR1126
LRP3-LSM14Achr1933685764chr1934685382275DRB1-1390CLVRSFGTEDRPTDR1126
LRP3-LSM14Achr1933685764chr1934685382275DRB1-1395CLVRSFGTEDRPTDR1126

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Fusion breakpoint peptide structures of LRP3-LSM14A

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
7373QLAVVCLVRSFGTELRP3LSM14Achr1933685764chr1934685382275

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of LRP3-LSM14A

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-B14:023BVN7373QLAVVCLVRSFGTE-6.81784-6.93724
HLA-B14:023BVN7373QLAVVCLVRSFGTE-5.72956-6.77086
HLA-B52:013W397373QLAVVCLVRSFGTE-7.39683-7.51623
HLA-B52:013W397373QLAVVCLVRSFGTE-6.35068-7.39198
HLA-A11:014UQ27373QLAVVCLVRSFGTE-2.93775-3.05715
HLA-A24:025HGA7373QLAVVCLVRSFGTE-8.28894-8.40834
HLA-A24:025HGA7373QLAVVCLVRSFGTE-6.60463-7.64593
HLA-B44:053DX87373QLAVVCLVRSFGTE-6.05305-6.17245
HLA-B44:053DX87373QLAVVCLVRSFGTE-2.83839-3.87969
HLA-A02:016TDR7373QLAVVCLVRSFGTE-7.33893-7.45833

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Vaccine Design for the FusionNeoAntigens of LRP3-LSM14A

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
LRP3-LSM14Achr1933685764chr1934685382514AQLAVVCLVCGCAGCTGGCCGTCGTCTGTCTGGTTC
LRP3-LSM14Achr1933685764chr1934685382817AVVCLVRSFCCGTCGTCTGTCTGGTTCGATCCTTTG

check button mRNA and peptide sequences of FusionNeoAntigens that have potential interaction with HLA-IIs.
Fusion geneHchrHbpTchrTbpStart in +/-13AAEnd in +/-13AAFusionNeoAntigen peptideFusionNEoAntigen RNA sequence
LRP3-LSM14Achr1933685764chr19346853821126CLVRSFGTEDRPTDRGTCTGGTTCGATCCTTTGGTACAGAAGACAGACCGACAGATCGTC

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Information of the samples that have these potential fusion neoantigens of LRP3-LSM14A

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
PRADLRP3-LSM14Achr1933685764ENST00000253193chr1934685382ENST00000433627TCGA-J4-A83I

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Potential target of CAR-T therapy development for LRP3-LSM14A

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 LRP3-LSM14A

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 LRP3-LSM14A

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