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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:FAS-CTNND2

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: FAS-CTNND2
FusionPDB ID: 29427
FusionGDB2.0 ID: 29427
HgeneTgene
Gene symbol

FAS

CTNND2

Gene ID

2194

1501

Gene namefatty acid synthasecatenin delta 2
SynonymsFAS|OA-519|SDR27X1GT24|NPRAP
Cytomap

17q25.3

5p15.2

Type of geneprotein-codingprotein-coding
Descriptionfatty acid synthaseshort chain dehydrogenase/reductase family 27X, member 1catenin delta-2T-cell delta-catenincatenin (cadherin-associated protein), delta 2 (neural plakophilin-related arm-repeat protein)neurojungin
Modification date2020032920200320
UniProtAcc

Q7L8L6

Main function of 5'-partner protein: FUNCTION: Plays an important role in the processing of non-canonical mitochondrial mRNA precursors (PubMed:25683715). {ECO:0000269|PubMed:25683715}.

Q9UQB3

Main function of 5'-partner protein: FUNCTION: Has a critical role in neuronal development, particularly in the formation and/or maintenance of dendritic spines and synapses (PubMed:25807484). Involved in the regulation of Wnt signaling (PubMed:25807484). It probably acts on beta-catenin turnover, facilitating beta-catenin interaction with GSK3B, phosphorylation, ubiquitination and degradation (By similarity). Functions as a transcriptional activator when bound to ZBTB33 (By similarity). May be involved in neuronal cell adhesion and tissue morphogenesis and integrity by regulating adhesion molecules. {ECO:0000250|UniProtKB:O35927, ECO:0000269|PubMed:25807484, ECO:0000269|PubMed:9971746}.
Ensembl transtripts involved in fusion geneENST idsENST00000313771, ENST00000352159, 
ENST00000355279, ENST00000355740, 
ENST00000357339, 
ENST00000304623, 
ENST00000359640, ENST00000458100, 
ENST00000503622, ENST00000511377, 
ENST00000495388, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score2 X 2 X 2=816 X 9 X 9=1296
# samples 217
** MAII scorelog2(2/8*10)=1.32192809488736log2(17/1296*10)=-2.93045906674692
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: FAS [Title/Abstract] AND CTNND2 [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: FAS [Title/Abstract] AND CTNND2 [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)FAS(90762951)-CTNND2(11023091), # samples:2
Anticipated loss of major functional domain due to fusion event.FAS-CTNND2 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.
FAS-CTNND2 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/chr10:90762951/chr5:11023091)
- 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 FAS (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 CTNND2 (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)
ENST00000355740FASchr1090762951+ENST00000304623CTNND2chr511023091-29194162201305361
ENST00000355740FASchr1090762951+ENST00000359640CTNND2chr511023091-28934162201305361
ENST00000355740FASchr1090762951+ENST00000511377CTNND2chr511023091-18644162201305361
ENST00000355740FASchr1090762951+ENST00000458100CTNND2chr511023091-15704162201305361
ENST00000355740FASchr1090762951+ENST00000503622CTNND2chr511023091-14194162201305361
ENST00000352159FASchr1090762951+ENST00000304623CTNND2chr511023091-28893861901275361
ENST00000352159FASchr1090762951+ENST00000359640CTNND2chr511023091-28633861901275361
ENST00000352159FASchr1090762951+ENST00000511377CTNND2chr511023091-18343861901275361
ENST00000352159FASchr1090762951+ENST00000458100CTNND2chr511023091-15403861901275361
ENST00000352159FASchr1090762951+ENST00000503622CTNND2chr511023091-13893861901275361
ENST00000357339FASchr1090762951+ENST00000304623CTNND2chr511023091-2798295991184361
ENST00000357339FASchr1090762951+ENST00000359640CTNND2chr511023091-2772295991184361
ENST00000357339FASchr1090762951+ENST00000511377CTNND2chr511023091-1743295991184361
ENST00000357339FASchr1090762951+ENST00000458100CTNND2chr511023091-1449295991184361
ENST00000357339FASchr1090762951+ENST00000503622CTNND2chr511023091-1298295991184361
ENST00000355279FASchr1090762951+ENST00000304623CTNND2chr511023091-269919601085361
ENST00000355279FASchr1090762951+ENST00000359640CTNND2chr511023091-267319601085361
ENST00000355279FASchr1090762951+ENST00000511377CTNND2chr511023091-164419601085361
ENST00000355279FASchr1090762951+ENST00000458100CTNND2chr511023091-135019601085361
ENST00000355279FASchr1090762951+ENST00000503622CTNND2chr511023091-119919601085361

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
ENST00000355740ENST00000304623FASchr1090762951+CTNND2chr511023091-0.0006314280.9993686
ENST00000355740ENST00000359640FASchr1090762951+CTNND2chr511023091-0.0006947970.99930525
ENST00000355740ENST00000511377FASchr1090762951+CTNND2chr511023091-0.0041308090.9958692
ENST00000355740ENST00000458100FASchr1090762951+CTNND2chr511023091-0.010531570.9894684
ENST00000355740ENST00000503622FASchr1090762951+CTNND2chr511023091-0.0065409340.99345905
ENST00000352159ENST00000304623FASchr1090762951+CTNND2chr511023091-0.0005961570.99940383
ENST00000352159ENST00000359640FASchr1090762951+CTNND2chr511023091-0.0006571680.99934286
ENST00000352159ENST00000511377FASchr1090762951+CTNND2chr511023091-0.0042141930.9957858
ENST00000352159ENST00000458100FASchr1090762951+CTNND2chr511023091-0.0097898840.9902102
ENST00000352159ENST00000503622FASchr1090762951+CTNND2chr511023091-0.00549760.9945024
ENST00000357339ENST00000304623FASchr1090762951+CTNND2chr511023091-0.0005024330.99949753
ENST00000357339ENST00000359640FASchr1090762951+CTNND2chr511023091-0.0005543490.9994456
ENST00000357339ENST00000511377FASchr1090762951+CTNND2chr511023091-0.0038229340.9961771
ENST00000357339ENST00000458100FASchr1090762951+CTNND2chr511023091-0.0077885030.99221146
ENST00000357339ENST00000503622FASchr1090762951+CTNND2chr511023091-0.0040573540.99594265
ENST00000355279ENST00000304623FASchr1090762951+CTNND2chr511023091-0.0004552850.9995447
ENST00000355279ENST00000359640FASchr1090762951+CTNND2chr511023091-0.0004973630.99950266
ENST00000355279ENST00000511377FASchr1090762951+CTNND2chr511023091-0.0034620840.9965379
ENST00000355279ENST00000458100FASchr1090762951+CTNND2chr511023091-0.0075517320.9924482
ENST00000355279ENST00000503622FASchr1090762951+CTNND2chr511023091-0.0036613130.9963387

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 FAS-CTNND2

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
FASchr1090762951CTNND2chr51102309119664LHHDGQFCHKPCPPGKYAMRDLVHRL
FASchr1090762951CTNND2chr51102309129564LHHDGQFCHKPCPPGKYAMRDLVHRL
FASchr1090762951CTNND2chr51102309138664LHHDGQFCHKPCPPGKYAMRDLVHRL
FASchr1090762951CTNND2chr51102309141664LHHDGQFCHKPCPPGKYAMRDLVHRL

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Potential FusionNeoAntigen Information of FAS-CTNND2 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.
FAS-CTNND2_90762951_11023091.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)
FAS-CTNND2chr1090762951chr511023091386HLA-B15:18HKPCPPGKY0.19090.7258817
FAS-CTNND2chr1090762951chr511023091386HLA-B15:18CHKPCPPGKY0.87830.7245717
FAS-CTNND2chr1090762951chr511023091386HLA-B42:02KPCPPGKYAM0.86950.7052919
FAS-CTNND2chr1090762951chr511023091386HLA-B42:01KPCPPGKYAM0.82480.6976919
FAS-CTNND2chr1090762951chr511023091386HLA-B39:10KPCPPGKYAM0.54380.9545919
FAS-CTNND2chr1090762951chr511023091386HLA-B15:54HKPCPPGKY0.01170.8975817
FAS-CTNND2chr1090762951chr511023091386HLA-B55:04KPCPPGKYAM0.77040.5413919
FAS-CTNND2chr1090762951chr511023091386HLA-B67:01KPCPPGKYAM0.54060.9373919

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Potential FusionNeoAntigen Information of FAS-CTNND2 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 FAS-CTNND2

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
2308FCHKPCPPGKYAMRFASCTNND2chr1090762951chr511023091386

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of FAS-CTNND2

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-B14:023BVN2308FCHKPCPPGKYAMR-7.38756-7.50096
HLA-B14:023BVN2308FCHKPCPPGKYAMR-6.17376-7.20906
HLA-B52:013W392308FCHKPCPPGKYAMR-6.82178-6.93518
HLA-B52:013W392308FCHKPCPPGKYAMR-5.12185-6.15715
HLA-A11:014UQ22308FCHKPCPPGKYAMR-9.73713-9.85053
HLA-A24:025HGA2308FCHKPCPPGKYAMR-6.9463-7.0597
HLA-A24:025HGA2308FCHKPCPPGKYAMR-5.98739-7.02269
HLA-B44:053DX82308FCHKPCPPGKYAMR-5.60116-6.63646
HLA-B44:053DX82308FCHKPCPPGKYAMR-4.76903-4.88243

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Vaccine Design for the FusionNeoAntigens of FAS-CTNND2

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
FAS-CTNND2chr1090762951chr511023091717CHKPCPPGKYATAAGCCCTGTCCTCCAGGCAAATACGCCA
FAS-CTNND2chr1090762951chr511023091817HKPCPPGKYAGCCCTGTCCTCCAGGCAAATACGCCA
FAS-CTNND2chr1090762951chr511023091919KPCPPGKYAMCCTGTCCTCCAGGCAAATACGCCATGCGAG

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 FAS-CTNND2

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
BRCAFAS-CTNND2chr1090762951ENST00000352159chr511023091ENST00000304623TCGA-E9-A247-01A

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Potential target of CAR-T therapy development for FAS-CTNND2

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 FAS-CTNND2

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 FAS-CTNND2

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