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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:LIN9-EZR

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: LIN9-EZR
FusionPDB ID: 44787
FusionGDB2.0 ID: 44787
HgeneTgene
Gene symbol

LIN9

EZR

Gene ID

286826

7430

Gene namelin-9 DREAM MuvB core complex componentezrin
SynonymsBARA|BARPsv|Lin-9|TGS|TGS1|TGS2CVIL|CVL|HEL-S-105|VIL2
Cytomap

1q42.12

6q25.3

Type of geneprotein-codingprotein-coding
Descriptionprotein lin-9 homologTUDOR gene similar proteinbeta subunit-associated regulator of apoptosislin-9 homologpRB-associated proteinrb related pathway actortype I interferon receptor beta chain-associated proteinezrincytovillin 2epididymis secretory protein Li 105p81villin 2 (ezrin)
Modification date2020031320200322
UniProtAcc

Q5TKA1

Main function of 5'-partner protein: FUNCTION: Acts as a tumor suppressor. Inhibits DNA synthesis. Its ability to inhibit oncogenic transformation is mediated through its association with RB1. Plays a role in the expression of genes required for the G1/S transition. {ECO:0000269|PubMed:15538385, ECO:0000269|PubMed:16730350}.

P15311

Main function of 5'-partner protein: FUNCTION: Probably involved in connections of major cytoskeletal structures to the plasma membrane. In epithelial cells, required for the formation of microvilli and membrane ruffles on the apical pole. Along with PLEKHG6, required for normal macropinocytosis. {ECO:0000269|PubMed:17881735, ECO:0000269|PubMed:18270268, ECO:0000269|PubMed:19111582}.
Ensembl transtripts involved in fusion geneENST idsENST00000328205, ENST00000366801, 
ENST00000481685, 
ENST00000476189, 
ENST00000337147, ENST00000367075, 
ENST00000392177, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score6 X 6 X 4=14425 X 24 X 6=3600
# samples 627
** MAII scorelog2(6/144*10)=-1.26303440583379
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(27/3600*10)=-3.73696559416621
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: LIN9 [Title/Abstract] AND EZR [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: LIN9 [Title/Abstract] AND EZR [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)LIN9(226485419)-EZR(159210403), # samples:1
Anticipated loss of major functional domain due to fusion event.LIN9-EZR 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.
LIN9-EZR 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.
LIN9-EZR 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.
LIN9-EZR 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
TgeneEZR

GO:0048015

phosphatidylinositol-mediated signaling

25591774

TgeneEZR

GO:0051017

actin filament bundle assembly

10793131



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/chr1:226485419/chr6:159210403)
- 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 LIN9 (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 EZR (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)
ENST00000328205LIN9chr1226485419-ENST00000337147EZRchr6159210403-36757531442501785
ENST00000328205LIN9chr1226485419-ENST00000367075EZRchr6159210403-36687531442501785
ENST00000328205LIN9chr1226485419-ENST00000392177EZRchr6159210403-24247531442405753
ENST00000366801LIN9chr1226485419-ENST00000337147EZRchr6159210403-34395173102265651
ENST00000366801LIN9chr1226485419-ENST00000367075EZRchr6159210403-34325173102265651
ENST00000366801LIN9chr1226485419-ENST00000392177EZRchr6159210403-21885173102169619
ENST00000481685LIN9chr1226485419-ENST00000337147EZRchr6159210403-3196274672022651
ENST00000481685LIN9chr1226485419-ENST00000367075EZRchr6159210403-3189274672022651
ENST00000481685LIN9chr1226485419-ENST00000392177EZRchr6159210403-1945274671926619

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
ENST00000328205ENST00000337147LIN9chr1226485419-EZRchr6159210403-0.0044487260.99555135
ENST00000328205ENST00000367075LIN9chr1226485419-EZRchr6159210403-0.0043198980.9956801
ENST00000328205ENST00000392177LIN9chr1226485419-EZRchr6159210403-0.0215083060.97849166
ENST00000366801ENST00000337147LIN9chr1226485419-EZRchr6159210403-0.0031549880.996845
ENST00000366801ENST00000367075LIN9chr1226485419-EZRchr6159210403-0.0030704780.9969296
ENST00000366801ENST00000392177LIN9chr1226485419-EZRchr6159210403-0.0127859630.98721397
ENST00000481685ENST00000337147LIN9chr1226485419-EZRchr6159210403-0.0026804710.9973195
ENST00000481685ENST00000367075LIN9chr1226485419-EZRchr6159210403-0.0025893490.9974107
ENST00000481685ENST00000392177LIN9chr1226485419-EZRchr6159210403-0.0146148060.98538524

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 LIN9-EZR

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
LIN9chr1226485419EZRchr615921040327469VWKGRNTSSAVEMINVRVTTMDAELE
LIN9chr1226485419EZRchr615921040351769VWKGRNTSSAVEMINVRVTTMDAELE
LIN9chr1226485419EZRchr6159210403753203VWKGRNTSSAVEMINVRVTTMDAELE

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Potential FusionNeoAntigen Information of LIN9-EZR 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.
LIN9-EZR_226485419_159210403.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)
LIN9-EZRchr1226485419chr6159210403753HLA-B08:01MINVRVTTM0.99830.83161221
LIN9-EZRchr1226485419chr6159210403753HLA-B08:09MINVRVTTM0.99730.7981221
LIN9-EZRchr1226485419chr6159210403753HLA-B15:02MINVRVTTM0.98940.97271221
LIN9-EZRchr1226485419chr6159210403753HLA-B45:01VEMINVRVT0.98240.90561019
LIN9-EZRchr1226485419chr6159210403753HLA-B14:02MINVRVTTM0.98130.7271221
LIN9-EZRchr1226485419chr6159210403753HLA-B14:01MINVRVTTM0.98130.7271221
LIN9-EZRchr1226485419chr6159210403753HLA-B46:01MINVRVTTM0.96190.65611221
LIN9-EZRchr1226485419chr6159210403753HLA-B50:02VEMINVRVT0.94880.64911019
LIN9-EZRchr1226485419chr6159210403753HLA-B50:01VEMINVRVT0.16980.77161019
LIN9-EZRchr1226485419chr6159210403753HLA-B40:06VEMINVRV0.99990.69581018
LIN9-EZRchr1226485419chr6159210403753HLA-B42:02MINVRVTTM0.9980.8251221
LIN9-EZRchr1226485419chr6159210403753HLA-B40:06VEMINVRVT0.99210.74471019
LIN9-EZRchr1226485419chr6159210403753HLA-B15:21MINVRVTTM0.98960.96611221
LIN9-EZRchr1226485419chr6159210403753HLA-B15:04MINVRVTTM0.98790.93971221
LIN9-EZRchr1226485419chr6159210403753HLA-C03:14MINVRVTTM0.9790.98471221
LIN9-EZRchr1226485419chr6159210403753HLA-B14:03MINVRVTTM0.94620.84771221
LIN9-EZRchr1226485419chr6159210403753HLA-C15:02SSAVEMINV0.99950.8696716
LIN9-EZRchr1226485419chr6159210403753HLA-C15:05SSAVEMINV0.99940.9103716
LIN9-EZRchr1226485419chr6159210403753HLA-C12:02MINVRVTTM0.99890.9871221
LIN9-EZRchr1226485419chr6159210403753HLA-C03:02MINVRVTTM0.99870.98261221
LIN9-EZRchr1226485419chr6159210403753HLA-B08:18MINVRVTTM0.99830.83161221
LIN9-EZRchr1226485419chr6159210403753HLA-C03:67MINVRVTTM0.9980.98971221
LIN9-EZRchr1226485419chr6159210403753HLA-C03:05MINVRVTTM0.99740.94041221
LIN9-EZRchr1226485419chr6159210403753HLA-B15:08MINVRVTTM0.99710.92661221
LIN9-EZRchr1226485419chr6159210403753HLA-B15:11MINVRVTTM0.99670.9121221
LIN9-EZRchr1226485419chr6159210403753HLA-B35:43MINVRVTTM0.99620.92781221
LIN9-EZRchr1226485419chr6159210403753HLA-A69:01SSAVEMINV0.99090.742716
LIN9-EZRchr1226485419chr6159210403753HLA-B08:12MINVRVTTM0.98890.94011221
LIN9-EZRchr1226485419chr6159210403753HLA-C16:01MINVRVTTM0.98860.98721221
LIN9-EZRchr1226485419chr6159210403753HLA-A69:01NTSSAVEMI0.97640.5921514
LIN9-EZRchr1226485419chr6159210403753HLA-B15:73MINVRVTTM0.93490.95941221
LIN9-EZRchr1226485419chr6159210403753HLA-B15:30MINVRVTTM0.89790.96431221
LIN9-EZRchr1226485419chr6159210403753HLA-B50:04VEMINVRVT0.16980.77161019
LIN9-EZRchr1226485419chr6159210403753HLA-B50:05VEMINVRVT0.16980.77161019
LIN9-EZRchr1226485419chr6159210403753HLA-A68:02SAVEMINVRV0.99310.6362818

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Potential FusionNeoAntigen Information of LIN9-EZR 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 LIN9-EZR

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
9666TSSAVEMINVRVTTLIN9EZRchr1226485419chr6159210403753

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of LIN9-EZR

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-B14:023BVN9666TSSAVEMINVRVTT-5.34942-6.38472
HLA-B14:023BVN9666TSSAVEMINVRVTT-5.0153-5.1287
HLA-B52:013W399666TSSAVEMINVRVTT-7.47358-7.58698
HLA-B52:013W399666TSSAVEMINVRVTT-4.5023-5.5376
HLA-A11:014UQ29666TSSAVEMINVRVTT-7.49832-7.61172
HLA-A24:025HGA9666TSSAVEMINVRVTT-8.30687-8.42027
HLA-A24:025HGA9666TSSAVEMINVRVTT-5.37786-6.41316
HLA-B27:056PYJ9666TSSAVEMINVRVTT-6.81213-7.84743
HLA-B44:053DX89666TSSAVEMINVRVTT-9.00919-9.12259
HLA-B44:053DX89666TSSAVEMINVRVTT-3.81824-4.85354

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Vaccine Design for the FusionNeoAntigens of LIN9-EZR

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
LIN9-EZRchr1226485419chr61592104031018VEMINVRVGTGGAAATGATCAATGTCCGAGTT
LIN9-EZRchr1226485419chr61592104031019VEMINVRVTGTGGAAATGATCAATGTCCGAGTTACC
LIN9-EZRchr1226485419chr61592104031221MINVRVTTMATGATCAATGTCCGAGTTACCACCATG
LIN9-EZRchr1226485419chr6159210403514NTSSAVEMIAATACAAGCTCTGCTGTGGAAATGATC
LIN9-EZRchr1226485419chr6159210403716SSAVEMINVAGCTCTGCTGTGGAAATGATCAATGTC
LIN9-EZRchr1226485419chr6159210403818SAVEMINVRVTCTGCTGTGGAAATGATCAATGTCCGAGTT

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 LIN9-EZR

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
STADLIN9-EZRchr1226485419ENST00000328205chr6159210403ENST00000337147TCGA-D7-A4YV

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Potential target of CAR-T therapy development for LIN9-EZR

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 LIN9-EZR

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 LIN9-EZR

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
TgeneEZRC0033578Prostatic Neoplasms3CTD_human
TgeneEZRC0376358Malignant neoplasm of prostate3CTD_human
TgeneEZRC0007097Carcinoma1CTD_human
TgeneEZRC0023893Liver Cirrhosis, Experimental1CTD_human
TgeneEZRC0024667Animal Mammary Neoplasms1CTD_human
TgeneEZRC0024668Mammary Neoplasms, Experimental1CTD_human
TgeneEZRC0027627Neoplasm Metastasis1CTD_human
TgeneEZRC0029408Degenerative polyarthritis1CTD_human
TgeneEZRC0086743Osteoarthrosis Deformans1CTD_human
TgeneEZRC0205696Anaplastic carcinoma1CTD_human
TgeneEZRC0205697Carcinoma, Spindle-Cell1CTD_human
TgeneEZRC0205698Undifferentiated carcinoma1CTD_human
TgeneEZRC0205699Carcinomatosis1CTD_human
TgeneEZRC1257925Mammary Carcinoma, Animal1CTD_human