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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:NTN4-CCT2

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: NTN4-CCT2
FusionPDB ID: 60675
FusionGDB2.0 ID: 60675
HgeneTgene
Gene symbol

NTN4

CCT2

Gene ID

59277

10576

Gene namenetrin 4chaperonin containing TCP1 subunit 2
SynonymsPRO309199D8.1|CCT-beta|CCTB|HEL-S-100n|PRO1633|TCP-1-beta
Cytomap

12q22

12q15

Type of geneprotein-codingprotein-coding
Descriptionnetrin-4beta-netrinhepar-derived netrin-like proteinT-complex protein 1 subunit betaT-complex protein 1, beta subunitchaperonin containing TCP1, subunit 2 (beta)chaperonin containing t-complex polypeptide 1, beta subunitchaperonin containing t-complex polypeptide 1, subunit 2epididymis secretory sperm
Modification date2020031320200313
UniProtAcc.

P78371

Main function of 5'-partner protein: FUNCTION: Component of the chaperonin-containing T-complex (TRiC), a molecular chaperone complex that assists the folding of proteins upon ATP hydrolysis (PubMed:25467444). The TRiC complex mediates the folding of WRAP53/TCAB1, thereby regulating telomere maintenance (PubMed:25467444). As part of the TRiC complex may play a role in the assembly of BBSome, a complex involved in ciliogenesis regulating transports vesicles to the cilia (PubMed:20080638). The TRiC complex plays a role in the folding of actin and tubulin (Probable). {ECO:0000269|PubMed:20080638, ECO:0000269|PubMed:25467444, ECO:0000305}.
Ensembl transtripts involved in fusion geneENST idsENST00000538383, ENST00000343702, 
ENST00000344911, ENST00000553059, 
ENST00000552603, 
ENST00000299300, 
ENST00000543146, ENST00000544368, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score11 X 10 X 5=55014 X 13 X 9=1638
# samples 1116
** MAII scorelog2(11/550*10)=-2.32192809488736
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(16/1638*10)=-3.35579154675365
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: NTN4 [Title/Abstract] AND CCT2 [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: NTN4 [Title/Abstract] AND CCT2 [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)NTN4(96106990)-CCT2(69990936), # samples:1
Anticipated loss of major functional domain due to fusion event.NTN4-CCT2 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.
NTN4-CCT2 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.
NTN4-CCT2 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.
NTN4-CCT2 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.
NTN4-CCT2 seems lost the major protein functional domain in Hgene partner, which is a essential gene due to the frame-shifted ORF.
NTN4-CCT2 seems lost the major protein functional domain in Tgene partner, which is a cell metabolism gene due to the frame-shifted ORF.
NTN4-CCT2 seems lost the major protein functional domain in Tgene partner, which is a essential gene 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/chr12:96106990/chr12:69990936)
- 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 NTN4 (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 CCT2 (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)
ENST00000343702NTN4chr1296106990-ENST00000299300CCT2chr1269990936+231114401132065650
ENST00000343702NTN4chr1296106990-ENST00000544368CCT2chr1269990936+212414401132050645
ENST00000343702NTN4chr1296106990-ENST00000543146CCT2chr1269990936+230614401132065650
ENST00000344911NTN4chr1296106990-ENST00000299300CCT2chr1269990936+1848977431602519
ENST00000344911NTN4chr1296106990-ENST00000544368CCT2chr1269990936+1661977431587514
ENST00000344911NTN4chr1296106990-ENST00000543146CCT2chr1269990936+1843977431602519
ENST00000553059NTN4chr1296106990-ENST00000299300CCT2chr1269990936+186299101616538
ENST00000553059NTN4chr1296106990-ENST00000544368CCT2chr1269990936+167599101601533
ENST00000553059NTN4chr1296106990-ENST00000543146CCT2chr1269990936+185799101616538

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
ENST00000343702ENST00000299300NTN4chr1296106990-CCT2chr1269990936+0.0045579430.99544203
ENST00000343702ENST00000544368NTN4chr1296106990-CCT2chr1269990936+0.0046873390.9953127
ENST00000343702ENST00000543146NTN4chr1296106990-CCT2chr1269990936+0.0046111710.99538875
ENST00000344911ENST00000299300NTN4chr1296106990-CCT2chr1269990936+0.0064170030.993583
ENST00000344911ENST00000544368NTN4chr1296106990-CCT2chr1269990936+0.0068759770.99312407
ENST00000344911ENST00000543146NTN4chr1296106990-CCT2chr1269990936+0.0065180830.99348193
ENST00000553059ENST00000299300NTN4chr1296106990-CCT2chr1269990936+0.0035860020.996414
ENST00000553059ENST00000544368NTN4chr1296106990-CCT2chr1269990936+0.0036440620.996356
ENST00000553059ENST00000543146NTN4chr1296106990-CCT2chr1269990936+0.0036383470.9963617

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 NTN4-CCT2

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
NTN4chr1296106990CCT2chr12699909361440443ADGKTGAPNECRSGEIASTFDHPELV
NTN4chr1296106990CCT2chr1269990936977312ADGKTGAPNECRSGEIASTFDHPELV
NTN4chr1296106990CCT2chr1269990936991331ADGKTGAPNECRSGEIASTFDHPELV

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Potential FusionNeoAntigen Information of NTN4-CCT2 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.
NTN4-CCT2_96106990_69990936.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)
NTN4-CCT2chr1296106990chr12699909361440HLA-B57:01RSGEIASTF0.99530.99521120
NTN4-CCT2chr1296106990chr12699909361440HLA-B15:17RSGEIASTF0.9950.97921120
NTN4-CCT2chr1296106990chr12699909361440HLA-B15:16RSGEIASTF0.99380.95951120
NTN4-CCT2chr1296106990chr12699909361440HLA-B58:01RSGEIASTF0.99370.98231120
NTN4-CCT2chr1296106990chr12699909361440HLA-B58:02RSGEIASTF0.99270.98531120
NTN4-CCT2chr1296106990chr12699909361440HLA-B15:01RSGEIASTF0.98860.9541120
NTN4-CCT2chr1296106990chr12699909361440HLA-B15:25RSGEIASTF0.98530.97651120
NTN4-CCT2chr1296106990chr12699909361440HLA-B57:03RSGEIASTF0.97920.99731120
NTN4-CCT2chr1296106990chr12699909361440HLA-B45:01NECRSGEIA0.96660.7082817
NTN4-CCT2chr1296106990chr12699909361440HLA-B15:03RSGEIASTF0.87870.94171120
NTN4-CCT2chr1296106990chr12699909361440HLA-A32:13RSGEIASTF0.84210.98291120
NTN4-CCT2chr1296106990chr12699909361440HLA-A24:15RSGEIASTF0.82710.60341120
NTN4-CCT2chr1296106990chr12699909361440HLA-B46:01RSGEIASTF0.59210.77321120
NTN4-CCT2chr1296106990chr12699909361440HLA-A24:14RSGEIASTF0.41350.64231120
NTN4-CCT2chr1296106990chr12699909361440HLA-B41:01NECRSGEIA0.24950.8166817
NTN4-CCT2chr1296106990chr12699909361440HLA-B13:01RSGEIASTF0.05610.98881120
NTN4-CCT2chr1296106990chr12699909361440HLA-B27:02CRSGEIASTF0.99970.53311020
NTN4-CCT2chr1296106990chr12699909361440HLA-C15:04RSGEIASTF0.99510.96311120
NTN4-CCT2chr1296106990chr12699909361440HLA-C15:06RSGEIASTF0.97620.96591120
NTN4-CCT2chr1296106990chr12699909361440HLA-C03:14RSGEIASTF0.8230.99411120
NTN4-CCT2chr1296106990chr12699909361440HLA-B15:05RSGEIASTF0.76950.96041120
NTN4-CCT2chr1296106990chr12699909361440HLA-C12:12RSGEIASTF0.68290.95611120
NTN4-CCT2chr1296106990chr12699909361440HLA-B57:04RSGEIASTF0.99570.89481120
NTN4-CCT2chr1296106990chr12699909361440HLA-B57:10RSGEIASTF0.99530.99521120
NTN4-CCT2chr1296106990chr12699909361440HLA-C15:09RSGEIASTF0.99510.96311120
NTN4-CCT2chr1296106990chr12699909361440HLA-B58:06RSGEIASTF0.99410.97991120
NTN4-CCT2chr1296106990chr12699909361440HLA-B15:135RSGEIASTF0.98870.94961120
NTN4-CCT2chr1296106990chr12699909361440HLA-B15:34RSGEIASTF0.98860.9541120
NTN4-CCT2chr1296106990chr12699909361440HLA-B15:125RSGEIASTF0.98860.9541120
NTN4-CCT2chr1296106990chr12699909361440HLA-B15:33RSGEIASTF0.98860.9541120
NTN4-CCT2chr1296106990chr12699909361440HLA-C03:02RSGEIASTF0.98790.99331120
NTN4-CCT2chr1296106990chr12699909361440HLA-B15:39RSGEIASTF0.98470.95761120
NTN4-CCT2chr1296106990chr12699909361440HLA-B15:50RSGEIASTF0.98190.92931120
NTN4-CCT2chr1296106990chr12699909361440HLA-B15:24RSGEIASTF0.97780.98151120
NTN4-CCT2chr1296106990chr12699909361440HLA-A32:01RSGEIASTF0.97390.98991120
NTN4-CCT2chr1296106990chr12699909361440HLA-C15:05RSGEIASTF0.95940.96361120
NTN4-CCT2chr1296106990chr12699909361440HLA-B57:02RSGEIASTF0.95790.98471120
NTN4-CCT2chr1296106990chr12699909361440HLA-C16:01RSGEIASTF0.81420.99091120
NTN4-CCT2chr1296106990chr12699909361440HLA-B15:20RSGEIASTF0.76890.9691120
NTN4-CCT2chr1296106990chr12699909361440HLA-B35:28RSGEIASTF0.75280.96741120
NTN4-CCT2chr1296106990chr12699909361440HLA-C16:02RSGEIASTF0.67980.99691120
NTN4-CCT2chr1296106990chr12699909361440HLA-C12:02RSGEIASTF0.5850.97611120
NTN4-CCT2chr1296106990chr12699909361440HLA-C02:10RSGEIASTF0.11460.98351120
NTN4-CCT2chr1296106990chr12699909361440HLA-C02:02RSGEIASTF0.11460.98351120

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Potential FusionNeoAntigen Information of NTN4-CCT2 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 NTN4-CCT2

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
492APNECRSGEIASTFNTN4CCT2chr1296106990chr12699909361440

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of NTN4-CCT2

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-B14:023BVN492APNECRSGEIASTF-5.83198-6.86728
HLA-B14:023BVN492APNECRSGEIASTF-5.03097-5.14437
HLA-B52:013W39492APNECRSGEIASTF-7.29527-7.40867
HLA-B52:013W39492APNECRSGEIASTF-4.78622-5.82152
HLA-A24:025HGA492APNECRSGEIASTF-8.15475-9.19005
HLA-A24:025HGA492APNECRSGEIASTF-7.37652-7.48992
HLA-B44:053DX8492APNECRSGEIASTF-8.1574-8.2708
HLA-B44:053DX8492APNECRSGEIASTF-4.13743-5.17273

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Vaccine Design for the FusionNeoAntigens of NTN4-CCT2

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
NTN4-CCT2chr1296106990chr12699909361020CRSGEIASTFAGTGCAGAAGTGGTGAAATTGCCTCTACCT
NTN4-CCT2chr1296106990chr12699909361120RSGEIASTFGCAGAAGTGGTGAAATTGCCTCTACCT
NTN4-CCT2chr1296106990chr1269990936817NECRSGEIACCAACGAGTGCAGAAGTGGTGAAATTG

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 NTN4-CCT2

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
SARCNTN4-CCT2chr1296106990ENST00000343702chr1269990936ENST00000299300TCGA-WK-A8XO-01A

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Potential target of CAR-T therapy development for NTN4-CCT2

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 NTN4-CCT2

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 NTN4-CCT2

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