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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:ENAH-LIN9

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: ENAH-LIN9
FusionPDB ID: 26535
FusionGDB2.0 ID: 26535
HgeneTgene
Gene symbol

ENAH

LIN9

Gene ID

55740

286826

Gene nameENAH actin regulatorlin-9 DREAM MuvB core complex component
SynonymsENA|MENA|NDPP1BARA|BARPsv|Lin-9|TGS|TGS1|TGS2
Cytomap

1q42.12

1q42.12

Type of geneprotein-codingprotein-coding
Descriptionprotein enabled homologenabled homologmammalian enabled variant 11amammalian enabled variant panprotein lin-9 homologTUDOR gene similar proteinbeta subunit-associated regulator of apoptosislin-9 homologpRB-associated proteinrb related pathway actortype I interferon receptor beta chain-associated protein
Modification date2020031320200313
UniProtAcc

Q8N8S7

Main function of 5'-partner protein: FUNCTION: Ena/VASP proteins are actin-associated proteins involved in a range of processes dependent on cytoskeleton remodeling and cell polarity such as axon guidance and lamellipodial and filopodial dynamics in migrating cells. ENAH induces the formation of F-actin rich outgrowths in fibroblasts. Acts synergistically with BAIAP2-alpha and downstream of NTN1 to promote filipodia formation (By similarity). {ECO:0000250, ECO:0000269|PubMed:11696321, ECO:0000269|PubMed:18158903}.

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}.
Ensembl transtripts involved in fusion geneENST idsENST00000391874, ENST00000284563, 
ENST00000366843, ENST00000366844, 
ENST00000328205, ENST00000366801, 
ENST00000481685, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score12 X 11 X 8=10566 X 4 X 5=120
# samples 167
** MAII scorelog2(16/1056*10)=-2.72246602447109
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(7/120*10)=-0.777607578663552
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

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

Fusion neoantigen context

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

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)ENAH(225840388)-LIN9(226438620), # samples:2
Anticipated loss of major functional domain due to fusion event.ENAH-LIN9 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.
ENAH-LIN9 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.
ENAH-LIN9 seems lost the major protein functional domain in Hgene partner, which is a essential gene due to the frame-shifted ORF.
ENAH-LIN9 seems lost the major protein functional domain in Tgene partner, which is a essential gene due to the frame-shifted ORF.
ENAH-LIN9 seems lost the major protein functional domain in Tgene partner, which is a tumor suppressor due to the frame-shifted 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/chr1:225840388/chr1:226438620)
- 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 ENAH (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 LIN9 (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)
ENST00000366844ENAHchr1225840388-ENST00000328205LIN9chr1226438620-23924571991047282
ENST00000366844ENAHchr1225840388-ENST00000366801LIN9chr1226438620-23854571991047282
ENST00000366844ENAHchr1225840388-ENST00000481685LIN9chr1226438620-1325457199945248
ENST00000366843ENAHchr1225840388-ENST00000328205LIN9chr1226438620-2295360102950282
ENST00000366843ENAHchr1225840388-ENST00000366801LIN9chr1226438620-2288360102950282
ENST00000366843ENAHchr1225840388-ENST00000481685LIN9chr1226438620-1228360102848248
ENST00000284563ENAHchr1225840388-ENST00000328205LIN9chr1226438620-19663110621203
ENST00000284563ENAHchr1225840388-ENST00000366801LIN9chr1226438620-19593110621203
ENST00000284563ENAHchr1225840388-ENST00000481685LIN9chr1226438620-8993110519169

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
ENST00000366844ENST00000328205ENAHchr1225840388-LIN9chr1226438620-0.001759130.9982408
ENST00000366844ENST00000366801ENAHchr1225840388-LIN9chr1226438620-0.0017022660.99829775
ENST00000366844ENST00000481685ENAHchr1225840388-LIN9chr1226438620-0.0055666780.99443334
ENST00000366843ENST00000328205ENAHchr1225840388-LIN9chr1226438620-0.0010180050.998982
ENST00000366843ENST00000366801ENAHchr1225840388-LIN9chr1226438620-0.0010324150.99896765
ENST00000366843ENST00000481685ENAHchr1225840388-LIN9chr1226438620-0.0040873460.9959126
ENST00000284563ENST00000328205ENAHchr1225840388-LIN9chr1226438620-0.0012833250.9987167
ENST00000284563ENST00000366801ENAHchr1225840388-LIN9chr1226438620-0.0012591740.99874085
ENST00000284563ENST00000481685ENAHchr1225840388-LIN9chr1226438620-0.0031494750.99685055

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 ENAH-LIN9

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
ENAHchr1225840388LIN9chr122643862036086RLVGKPLRRRHHETRLSKILMIKKEH
ENAHchr1225840388LIN9chr122643862045786RLVGKPLRRRHHETRLSKILMIKKEH

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Potential FusionNeoAntigen Information of ENAH-LIN9 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.
ENAH-LIN9_225840388_226438620.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)
ENAH-LIN9chr1225840388chr1226438620360HLA-B27:05RRRHHETRL0.99850.7303716
ENAH-LIN9chr1225840388chr1226438620360HLA-B27:04RRRHHETRL0.99780.7365716
ENAH-LIN9chr1225840388chr1226438620360HLA-B27:07RRRHHETRL0.9970.5357716
ENAH-LIN9chr1225840388chr1226438620360HLA-B39:06HHETRLSKI0.99040.68371019
ENAH-LIN9chr1225840388chr1226438620360HLA-B39:01HHETRLSKI0.98740.85061019
ENAH-LIN9chr1225840388chr1226438620360HLA-B38:01HHETRLSKI0.97990.90971019
ENAH-LIN9chr1225840388chr1226438620360HLA-B38:02HHETRLSKI0.97930.92311019
ENAH-LIN9chr1225840388chr1226438620360HLA-B44:03HETRLSKIL0.87520.94541120
ENAH-LIN9chr1225840388chr1226438620360HLA-B39:13HETRLSKIL0.64210.88261120
ENAH-LIN9chr1225840388chr1226438620360HLA-B07:10RRRHHETRL0.02440.6261716
ENAH-LIN9chr1225840388chr1226438620360HLA-B27:05RRHHETRLSK0.99950.7664818
ENAH-LIN9chr1225840388chr1226438620360HLA-B27:04RRHHETRLSK0.99510.7031818
ENAH-LIN9chr1225840388chr1226438620360HLA-B39:01HHETRLSKIL0.97280.84621020
ENAH-LIN9chr1225840388chr1226438620360HLA-B38:02HHETRLSKIL0.96020.93411020
ENAH-LIN9chr1225840388chr1226438620360HLA-B38:01HHETRLSKIL0.95330.92311020
ENAH-LIN9chr1225840388chr1226438620360HLA-B27:05RRRHHETRLSK0.99790.6342718
ENAH-LIN9chr1225840388chr1226438620360HLA-B38:01HHETRLSKILM0.99610.90481021
ENAH-LIN9chr1225840388chr1226438620360HLA-B38:02HHETRLSKILM0.99540.91991021
ENAH-LIN9chr1225840388chr1226438620360HLA-B39:01RHHETRLSKIL0.98450.7671920
ENAH-LIN9chr1225840388chr1226438620360HLA-B38:01RHHETRLSKIL0.96220.8832920
ENAH-LIN9chr1225840388chr1226438620360HLA-B38:02RHHETRLSKIL0.96160.8889920
ENAH-LIN9chr1225840388chr1226438620360HLA-B15:10RHHETRLSKIL0.92370.5077920
ENAH-LIN9chr1225840388chr1226438620360HLA-B27:14RRRHHETRL0.99820.6985716
ENAH-LIN9chr1225840388chr1226438620360HLA-B39:12HHETRLSKI0.98250.86531019
ENAH-LIN9chr1225840388chr1226438620360HLA-C07:05RRRHHETRL0.97880.8542716
ENAH-LIN9chr1225840388chr1226438620360HLA-B39:05HHETRLSKI0.9770.83311019
ENAH-LIN9chr1225840388chr1226438620360HLA-C07:95RRRHHETRL0.97620.6905716
ENAH-LIN9chr1225840388chr1226438620360HLA-C07:27RRRHHETRL0.96940.9051716
ENAH-LIN9chr1225840388chr1226438620360HLA-B27:03RRRHHETRL0.85850.7518716
ENAH-LIN9chr1225840388chr1226438620360HLA-C07:46RRRHHETRL0.85170.8733716
ENAH-LIN9chr1225840388chr1226438620360HLA-C07:19RRRHHETRL0.83570.7235716
ENAH-LIN9chr1225840388chr1226438620360HLA-B39:08HETRLSKIL0.61390.73081120
ENAH-LIN9chr1225840388chr1226438620360HLA-B14:03HHETRLSKI0.36670.61341019
ENAH-LIN9chr1225840388chr1226438620360HLA-B27:14RRHHETRLSK0.99890.7044818
ENAH-LIN9chr1225840388chr1226438620360HLA-B27:03RRHHETRLSK0.98730.7923818
ENAH-LIN9chr1225840388chr1226438620360HLA-B39:05HHETRLSKIL0.95470.83171020
ENAH-LIN9chr1225840388chr1226438620360HLA-B27:14RRRHHETRLSK0.99750.6079718
ENAH-LIN9chr1225840388chr1226438620360HLA-B39:05HHETRLSKILM0.99520.83751021
ENAH-LIN9chr1225840388chr1226438620360HLA-B39:05RHHETRLSKIL0.95470.7516920
ENAH-LIN9chr1225840388chr1226438620360HLA-B27:03RRRHHETRLSK0.9370.6592718
ENAH-LIN9chr1225840388chr1226438620360HLA-B27:08RRRHHETRL0.99840.6506716
ENAH-LIN9chr1225840388chr1226438620360HLA-B27:06RRRHHETRL0.99790.7378716
ENAH-LIN9chr1225840388chr1226438620360HLA-B27:10RRRHHETRL0.99780.805716
ENAH-LIN9chr1225840388chr1226438620360HLA-B40:04HETRLSKIL0.99510.53821120
ENAH-LIN9chr1225840388chr1226438620360HLA-B27:09RRRHHETRL0.99510.6842716
ENAH-LIN9chr1225840388chr1226438620360HLA-C07:01RRRHHETRL0.98920.6805716
ENAH-LIN9chr1225840388chr1226438620360HLA-B38:05HHETRLSKI0.97990.90971019
ENAH-LIN9chr1225840388chr1226438620360HLA-B44:13HETRLSKIL0.87520.94541120
ENAH-LIN9chr1225840388chr1226438620360HLA-B44:07HETRLSKIL0.87520.94541120
ENAH-LIN9chr1225840388chr1226438620360HLA-B44:26HETRLSKIL0.87520.94541120
ENAH-LIN9chr1225840388chr1226438620360HLA-A30:01RHHETRLSK0.80050.7842918
ENAH-LIN9chr1225840388chr1226438620360HLA-B18:11HETRLSKIL0.71490.88341120
ENAH-LIN9chr1225840388chr1226438620360HLA-C07:22RRRHHETRL0.71120.7072716
ENAH-LIN9chr1225840388chr1226438620360HLA-B39:11HHETRLSKI0.69850.65221019
ENAH-LIN9chr1225840388chr1226438620360HLA-B18:03HETRLSKIL0.69230.85251120
ENAH-LIN9chr1225840388chr1226438620360HLA-C06:08RRRHHETRL0.67910.9882716
ENAH-LIN9chr1225840388chr1226438620360HLA-B39:31HETRLSKIL0.63340.86241120
ENAH-LIN9chr1225840388chr1226438620360HLA-B39:02HETRLSKIL0.62680.88351120
ENAH-LIN9chr1225840388chr1226438620360HLA-C06:02RRRHHETRL0.06690.9927716
ENAH-LIN9chr1225840388chr1226438620360HLA-C06:17RRRHHETRL0.06690.9927716
ENAH-LIN9chr1225840388chr1226438620360HLA-B27:10RRHHETRLSK0.99920.7882818
ENAH-LIN9chr1225840388chr1226438620360HLA-B38:05HHETRLSKIL0.95330.92311020
ENAH-LIN9chr1225840388chr1226438620360HLA-B39:11HHETRLSKIL0.89140.67191020
ENAH-LIN9chr1225840388chr1226438620360HLA-B27:10RRRHHETRLSK0.99640.7188718
ENAH-LIN9chr1225840388chr1226438620360HLA-B38:05HHETRLSKILM0.99610.90481021
ENAH-LIN9chr1225840388chr1226438620360HLA-B39:11HHETRLSKILM0.98150.66291021
ENAH-LIN9chr1225840388chr1226438620360HLA-B38:05RHHETRLSKIL0.96220.8832920

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Potential FusionNeoAntigen Information of ENAH-LIN9 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 ENAH-LIN9

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
5559LRRRHHETRLSKILENAHLIN9chr1225840388chr1226438620360

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

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-B14:023BVN5559LRRRHHETRLSKIL-6.33173-6.44513
HLA-B14:023BVN5559LRRRHHETRLSKIL-1.81046-2.84576
HLA-B52:013W395559LRRRHHETRLSKIL-5.92784-6.04124
HLA-B52:013W395559LRRRHHETRLSKIL-4.3074-5.3427
HLA-A24:025HGA5559LRRRHHETRLSKIL-6.68795-7.72325
HLA-A24:025HGA5559LRRRHHETRLSKIL-5.73606-5.84946
HLA-B44:053DX85559LRRRHHETRLSKIL-6.99493-8.03023
HLA-B44:053DX85559LRRRHHETRLSKIL-6.82556-6.93896
HLA-A02:016TDR5559LRRRHHETRLSKIL-4.47214-5.50744

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Vaccine Design for the FusionNeoAntigens of ENAH-LIN9

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
ENAH-LIN9chr1225840388chr12264386201019HHETRLSKICACCATGAGACCAGATTATCAAAAATT
ENAH-LIN9chr1225840388chr12264386201020HHETRLSKILCACCATGAGACCAGATTATCAAAAATTCTC
ENAH-LIN9chr1225840388chr12264386201021HHETRLSKILMCACCATGAGACCAGATTATCAAAAATTCTCATG
ENAH-LIN9chr1225840388chr12264386201120HETRLSKILCATGAGACCAGATTATCAAAAATTCTC
ENAH-LIN9chr1225840388chr1226438620716RRRHHETRLCGCCGCCGGCACCATGAGACCAGATTA
ENAH-LIN9chr1225840388chr1226438620718RRRHHETRLSKCGCCGCCGGCACCATGAGACCAGATTATCAAAA
ENAH-LIN9chr1225840388chr1226438620818RRHHETRLSKCGCCGGCACCATGAGACCAGATTATCAAAA
ENAH-LIN9chr1225840388chr1226438620918RHHETRLSKCGGCACCATGAGACCAGATTATCAAAA
ENAH-LIN9chr1225840388chr1226438620920RHHETRLSKILCGGCACCATGAGACCAGATTATCAAAAATTCTC

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 ENAH-LIN9

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
SKCMENAH-LIN9chr1225840388ENST00000366843chr1226438620ENST00000328205TCGA-FR-A7U8-06A

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

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 ENAH-LIN9

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 ENAH-LIN9

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