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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:NIN-CASP10

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: NIN-CASP10
FusionPDB ID: 59143
FusionGDB2.0 ID: 59143
HgeneTgene
Gene symbol

NIN

CASP10

Gene ID

51199

843

Gene namenineincaspase 10
SynonymsSCKL7ALPS2|FLICE2|MCH4
Cytomap

14q22.1

2q33.1

Type of geneprotein-codingprotein-coding
Descriptionnineinglycogen synthase kinase 3 beta-interacting proteinhNineinninein (GSK3B interacting protein)ninein centrosomal proteincaspase-10CASP-10FADD-like ICE2FAS-associated death domain protein interleukin-1B-converting enzyme 2ICE-like apoptotic protease 4apoptotic protease MCH-4caspase 10 apoptosis-related cysteine peptidasecaspase 10, apoptosis-related cysteine protease
Modification date2020032820200313
UniProtAcc

Q9Y2I6

Main function of 5'-partner protein: FUNCTION: Involved in the microtubule organization in interphase cells. Overexpression induces the fragmentation of the Golgi, and causes lysosomes to disperse toward the cell periphery; it also interferes with mitotic spindle assembly. May play a role in ovarian carcinogenesis. {ECO:0000269|PubMed:12852856, ECO:0000269|PubMed:16254247, ECO:0000269|PubMed:18538832}.

Q92851

Main function of 5'-partner protein: FUNCTION: Involved in the activation cascade of caspases responsible for apoptosis execution. Recruited to both Fas- and TNFR-1 receptors in a FADD dependent manner. May participate in the granzyme B apoptotic pathways. Cleaves and activates caspase-3, -4, -6, -7, -8, and -9. Hydrolyzes the small- molecule substrates, Tyr-Val-Ala-Asp-|-AMC and Asp-Glu-Val-Asp-|-AMC. {ECO:0000269|PubMed:11717445}.; FUNCTION: Isoform 7 can enhance NF-kappaB activity but promotes only slight apoptosis. {ECO:0000269|PubMed:17822854}.; FUNCTION: Isoform C is proteolytically inactive. {ECO:0000269|PubMed:11717445}.
Ensembl transtripts involved in fusion geneENST idsENST00000245441, ENST00000324330, 
ENST00000382041, ENST00000382043, 
ENST00000389868, ENST00000453196, 
ENST00000530997, ENST00000486200, 
ENST00000492363, ENST00000313728, 
ENST00000346817, ENST00000374650, 
ENST00000448480, ENST00000360132, 
ENST00000272879, ENST00000286186, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score16 X 18 X 9=25925 X 3 X 3=45
# samples 204
** MAII scorelog2(20/2592*10)=-3.6959938131099
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(4/45*10)=-0.169925001442312
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: NIN [Title/Abstract] AND CASP10 [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: NIN [Title/Abstract] AND CASP10 [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)NIN(51239019)-CASP10(202072798), # samples:1
Anticipated loss of major functional domain due to fusion event.NIN-CASP10 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.
NIN-CASP10 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.
NIN-CASP10 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.
NIN-CASP10 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.
NIN-CASP10 seems lost the major protein functional domain in Hgene partner, which is a CGC due to the frame-shifted ORF.
NIN-CASP10 seems lost the major protein functional domain in Hgene partner, which is a essential gene due to the frame-shifted ORF.
NIN-CASP10 seems lost the major protein functional domain in Tgene partner, which is a IUPHAR drug target 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/chr14:51239019/chr2:202072798)
- 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 NIN (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 CASP10 (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)
ENST00000245441NINchr1451239019-ENST00000286186CASP10chr2202072798+585211721311927598
ENST00000245441NINchr1451239019-ENST00000272879CASP10chr2202072798+224811721311924597
ENST00000389868NINchr1451239019-ENST00000286186CASP10chr2202072798+585211721311927598
ENST00000389868NINchr1451239019-ENST00000272879CASP10chr2202072798+224811721311924597
ENST00000530997NINchr1451239019-ENST00000286186CASP10chr2202072798+566198101736578
ENST00000530997NINchr1451239019-ENST00000272879CASP10chr2202072798+205798101733577
ENST00000382041NINchr1451239019-ENST00000286186CASP10chr2202072798+585211721311927598
ENST00000382041NINchr1451239019-ENST00000272879CASP10chr2202072798+224811721311924597
ENST00000324330NINchr1451239019-ENST00000286186CASP10chr2202072798+585211721311927598
ENST00000324330NINchr1451239019-ENST00000272879CASP10chr2202072798+224811721311924597
ENST00000453196NINchr1451239019-ENST00000286186CASP10chr2202072798+585211721311927598
ENST00000453196NINchr1451239019-ENST00000272879CASP10chr2202072798+224811721311924597

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
ENST00000245441ENST00000286186NINchr1451239019-CASP10chr2202072798+0.0005684740.99943155
ENST00000245441ENST00000272879NINchr1451239019-CASP10chr2202072798+0.0021852730.99781466
ENST00000389868ENST00000286186NINchr1451239019-CASP10chr2202072798+0.0005684740.99943155
ENST00000389868ENST00000272879NINchr1451239019-CASP10chr2202072798+0.0021852730.99781466
ENST00000530997ENST00000286186NINchr1451239019-CASP10chr2202072798+0.0004788670.99952114
ENST00000530997ENST00000272879NINchr1451239019-CASP10chr2202072798+0.0015681890.99843174
ENST00000382041ENST00000286186NINchr1451239019-CASP10chr2202072798+0.0005684740.99943155
ENST00000382041ENST00000272879NINchr1451239019-CASP10chr2202072798+0.0021852730.99781466
ENST00000324330ENST00000286186NINchr1451239019-CASP10chr2202072798+0.0005684740.99943155
ENST00000324330ENST00000272879NINchr1451239019-CASP10chr2202072798+0.0021852730.99781466
ENST00000453196ENST00000286186NINchr1451239019-CASP10chr2202072798+0.0005684740.99943155
ENST00000453196ENST00000272879NINchr1451239019-CASP10chr2202072798+0.0021852730.99781466

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 NIN-CASP10

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
NINchr1451239019CASP10chr22020727981172341RILDTWQEEGIENSQEILKRAAVYRM
NINchr1451239019CASP10chr2202072798981321RILDTWQEEGIENSQEILKRAAVYRM

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Potential FusionNeoAntigen Information of NIN-CASP10 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.
NIN-CASP10_51239019_202072798.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)
NIN-CASP10chr1451239019chr22020727981172HLA-B39:13IENSQEIL0.9420.76411018
NIN-CASP10chr1451239019chr22020727981172HLA-B44:03EEGIENSQEI0.91040.959717
NIN-CASP10chr1451239019chr22020727981172HLA-B44:03QEEGIENSQEI0.98870.9756617
NIN-CASP10chr1451239019chr22020727981172HLA-B39:08IENSQEIL0.9830.73461018
NIN-CASP10chr1451239019chr22020727981172HLA-B44:10QEEGIENSQEI0.99390.5603617
NIN-CASP10chr1451239019chr22020727981172HLA-B40:04IENSQEIL0.99960.6711018
NIN-CASP10chr1451239019chr22020727981172HLA-B41:03IENSQEIL0.94540.5541018
NIN-CASP10chr1451239019chr22020727981172HLA-B44:26EEGIENSQEI0.91040.959717
NIN-CASP10chr1451239019chr22020727981172HLA-B44:13EEGIENSQEI0.91040.959717
NIN-CASP10chr1451239019chr22020727981172HLA-B44:07EEGIENSQEI0.91040.959717
NIN-CASP10chr1451239019chr22020727981172HLA-B44:07QEEGIENSQEI0.98870.9756617
NIN-CASP10chr1451239019chr22020727981172HLA-B44:26QEEGIENSQEI0.98870.9756617
NIN-CASP10chr1451239019chr22020727981172HLA-B44:13QEEGIENSQEI0.98870.9756617

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Potential FusionNeoAntigen Information of NIN-CASP10 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 NIN-CASP10

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
7216QEEGIENSQEILKRNINCASP10chr1451239019chr22020727981172

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of NIN-CASP10

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-B14:023BVN7216QEEGIENSQEILKR-7.9962-8.1096
HLA-B14:023BVN7216QEEGIENSQEILKR-5.70842-6.74372
HLA-B52:013W397216QEEGIENSQEILKR-6.83737-6.95077
HLA-B52:013W397216QEEGIENSQEILKR-4.4836-5.5189
HLA-A11:014UQ27216QEEGIENSQEILKR-10.0067-10.1201
HLA-A11:014UQ27216QEEGIENSQEILKR-9.03915-10.0745
HLA-A24:025HGA7216QEEGIENSQEILKR-6.56204-6.67544
HLA-A24:025HGA7216QEEGIENSQEILKR-5.42271-6.45801
HLA-B44:053DX87216QEEGIENSQEILKR-7.85648-8.89178
HLA-B44:053DX87216QEEGIENSQEILKR-5.3978-5.5112
HLA-A02:016TDR7216QEEGIENSQEILKR-3.37154-4.40684

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Vaccine Design for the FusionNeoAntigens of NIN-CASP10

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
NIN-CASP10chr1451239019chr22020727981018IENSQEILATCCTGAAGAGGGCAGCTGTGTAC
NIN-CASP10chr1451239019chr2202072798617QEEGIENSQEIAACAGCCAGGAGATCCTGAAGAGGGCAGCTGTG
NIN-CASP10chr1451239019chr2202072798717EEGIENSQEIAGCCAGGAGATCCTGAAGAGGGCAGCTGTG

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 NIN-CASP10

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
STADNIN-CASP10chr1451239019ENST00000245441chr2202072798ENST00000272879TCGA-BR-8078-01A

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Potential target of CAR-T therapy development for NIN-CASP10

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 NIN-CASP10

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 NIN-CASP10

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
HgeneNINC3553870SECKEL SYNDROME 72GENOMICS_ENGLAND;ORPHANET;UNIPROT