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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:SPINK5-NCOA3

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: SPINK5-NCOA3
FusionPDB ID: 85832
FusionGDB2.0 ID: 85832
HgeneTgene
Gene symbol

SPINK5

NCOA3

Gene ID

11005

8202

Gene nameserine peptidase inhibitor Kazal type 5nuclear receptor coactivator 3
SynonymsLEKTI|LETKI|NETS|NS|VAKTIACTR|AIB-1|AIB1|CAGH16|CTG26|KAT13B|RAC3|SRC-3|SRC3|TNRC14|TNRC16|TRAM-1|bHLHe42|pCIP
Cytomap

5q32

20q13.12

Type of geneprotein-codingprotein-coding
Descriptionserine protease inhibitor Kazal-type 5lympho-epithelial Kazal-type-related inhibitorlymphoepithelial Kazal-type-related inhibitornuclear receptor coactivator 3CBP-interacting proteinamplified in breast cancer 1 proteinclass E basic helix-loop-helix protein 42receptor-associated coactivator 3steroid receptor coactivator protein 3thyroid hormone receptor activator molecule 1
Modification date2020031320200313
UniProtAcc.

Q9Y6Q9

Main function of 5'-partner protein: FUNCTION: Nuclear receptor coactivator that directly binds nuclear receptors and stimulates the transcriptional activities in a hormone-dependent fashion. Plays a central role in creating a multisubunit coactivator complex, which probably acts via remodeling of chromatin. Involved in the coactivation of different nuclear receptors, such as for steroids (GR and ER), retinoids (RARs and RXRs), thyroid hormone (TRs), vitamin D3 (VDR) and prostanoids (PPARs). Displays histone acetyltransferase activity. Also involved in the coactivation of the NF-kappa-B pathway via its interaction with the NFKB1 subunit.
Ensembl transtripts involved in fusion geneENST idsENST00000256084, ENST00000359874, 
ENST00000398454, ENST00000476608, 
ENST00000497292, ENST00000341724, 
ENST00000371997, ENST00000371998, 
ENST00000372004, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score2 X 2 X 2=814 X 13 X 5=910
# samples 215
** MAII scorelog2(2/8*10)=1.32192809488736log2(15/910*10)=-2.60090404459018
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: SPINK5 [Title/Abstract] AND NCOA3 [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: SPINK5 [Title/Abstract] AND NCOA3 [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)SPINK5(147506642)-NCOA3(46277748), # samples:2
Anticipated loss of major functional domain due to fusion event.SPINK5-NCOA3 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.
SPINK5-NCOA3 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.
SPINK5-NCOA3 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.
SPINK5-NCOA3 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
HgeneSPINK5

GO:0009913

epidermal cell differentiation

12915442

TgeneNCOA3

GO:0045944

positive regulation of transcription by RNA polymerase II

9267036

TgeneNCOA3

GO:0071392

cellular response to estradiol stimulus

15831516



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/chr5:147506642/chr20:46277748)
- 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 SPINK5 (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 NCOA3 (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)
ENST00000359874SPINK5chr5147506642+ENST00000341724NCOA3chr2046277748+730431277338431256
ENST00000359874SPINK5chr5147506642+ENST00000372004NCOA3chr2046277748+730431277338431256
ENST00000359874SPINK5chr5147506642+ENST00000371998NCOA3chr2046277748+405831277338551260
ENST00000359874SPINK5chr5147506642+ENST00000371997NCOA3chr2046277748+616931277338431256
ENST00000256084SPINK5chr5147506642+ENST00000341724NCOA3chr2046277748+718330064237221226
ENST00000256084SPINK5chr5147506642+ENST00000372004NCOA3chr2046277748+718330064237221226
ENST00000256084SPINK5chr5147506642+ENST00000371998NCOA3chr2046277748+393730064237341230
ENST00000256084SPINK5chr5147506642+ENST00000371997NCOA3chr2046277748+604830064237221226

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
ENST00000359874ENST00000341724SPINK5chr5147506642+NCOA3chr2046277748+8.55E-050.9999145
ENST00000359874ENST00000372004SPINK5chr5147506642+NCOA3chr2046277748+8.55E-050.9999145
ENST00000359874ENST00000371998SPINK5chr5147506642+NCOA3chr2046277748+0.0008303640.9991697
ENST00000359874ENST00000371997SPINK5chr5147506642+NCOA3chr2046277748+0.000151860.9998481
ENST00000256084ENST00000341724SPINK5chr5147506642+NCOA3chr2046277748+9.66E-050.99990344
ENST00000256084ENST00000372004SPINK5chr5147506642+NCOA3chr2046277748+9.66E-050.99990344
ENST00000256084ENST00000371998SPINK5chr5147506642+NCOA3chr2046277748+0.0012944990.9987055
ENST00000256084ENST00000371997SPINK5chr5147506642+NCOA3chr2046277748+0.0001721340.99982786

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 SPINK5-NCOA3

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
SPINK5chr5147506642NCOA3chr20462777483006988SQEEDSPDSFSSLFLNQSRQALELKM
SPINK5chr5147506642NCOA3chr204627774831271018SQEEDSPDSFSSLFLNQSRQALELKM

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Potential FusionNeoAntigen Information of SPINK5-NCOA3 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.
SPINK5-NCOA3_147506642_46277748.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)
SPINK5-NCOA3chr5147506642chr20462777483006HLA-B35:01SPDSFSSLF0.99480.7059514
SPINK5-NCOA3chr5147506642chr20462777483006HLA-B35:08SPDSFSSLF0.99190.7769514
SPINK5-NCOA3chr5147506642chr20462777483006HLA-B35:03SPDSFSSLF0.95210.778514
SPINK5-NCOA3chr5147506642chr20462777483006HLA-A74:09SSLFLNQSR0.94720.65381019
SPINK5-NCOA3chr5147506642chr20462777483006HLA-A74:11SSLFLNQSR0.94720.65381019
SPINK5-NCOA3chr5147506642chr20462777483006HLA-A74:03SSLFLNQSR0.94720.65381019
SPINK5-NCOA3chr5147506642chr20462777483006HLA-A31:02SSLFLNQSR0.89450.58471019
SPINK5-NCOA3chr5147506642chr20462777483006HLA-B35:02SPDSFSSLF0.71260.7932514
SPINK5-NCOA3chr5147506642chr20462777483006HLA-B35:04SPDSFSSLF0.71260.7932514
SPINK5-NCOA3chr5147506642chr20462777483006HLA-B35:08DSPDSFSSLF0.96880.7289414
SPINK5-NCOA3chr5147506642chr20462777483006HLA-B35:03SPDSFSSLFL0.88610.8416515
SPINK5-NCOA3chr5147506642chr20462777483006HLA-B35:04SPDSFSSLFL0.74480.8458515
SPINK5-NCOA3chr5147506642chr20462777483006HLA-B35:02SPDSFSSLFL0.74480.8458515
SPINK5-NCOA3chr5147506642chr20462777483006HLA-B35:08EDSPDSFSSLF0.99540.6744314
SPINK5-NCOA3chr5147506642chr20462777483006HLA-A31:02SFSSLFLNQSR0.96970.7262819
SPINK5-NCOA3chr5147506642chr20462777483006HLA-B51:07DSFSSLFL0.99890.5701715
SPINK5-NCOA3chr5147506642chr20462777483006HLA-C04:10SPDSFSSLF0.99620.7245514
SPINK5-NCOA3chr5147506642chr20462777483006HLA-C04:07SPDSFSSLF0.99620.7567514
SPINK5-NCOA3chr5147506642chr20462777483006HLA-C05:09SPDSFSSLF0.99590.8286514
SPINK5-NCOA3chr5147506642chr20462777483006HLA-B15:31SPDSFSSLF0.9940.666514
SPINK5-NCOA3chr5147506642chr20462777483006HLA-C08:15SPDSFSSLF0.98740.9346514
SPINK5-NCOA3chr5147506642chr20462777483006HLA-A31:01SSLFLNQSR0.96330.56151019
SPINK5-NCOA3chr5147506642chr20462777483006HLA-B35:12SPDSFSSLF0.71260.7932514
SPINK5-NCOA3chr5147506642chr20462777483006HLA-B39:08SPDSFSSLF0.46480.6687514
SPINK5-NCOA3chr5147506642chr20462777483006HLA-B39:10SPDSFSSLF0.35640.8643514
SPINK5-NCOA3chr5147506642chr20462777483006HLA-C08:03SPDSFSSLF0.3090.9647514
SPINK5-NCOA3chr5147506642chr20462777483006HLA-C04:14SPDSFSSLF0.22290.7514
SPINK5-NCOA3chr5147506642chr20462777483006HLA-B07:12SPDSFSSLFL0.9610.5123515
SPINK5-NCOA3chr5147506642chr20462777483006HLA-B39:10SPDSFSSLFL0.79020.9128515
SPINK5-NCOA3chr5147506642chr20462777483006HLA-B35:12SPDSFSSLFL0.74480.8458515
SPINK5-NCOA3chr5147506642chr20462777483006HLA-C04:01SPDSFSSLF0.99620.7567514
SPINK5-NCOA3chr5147506642chr20462777483006HLA-C04:03SPDSFSSLF0.99620.7898514
SPINK5-NCOA3chr5147506642chr20462777483006HLA-C05:01SPDSFSSLF0.99590.8286514
SPINK5-NCOA3chr5147506642chr20462777483006HLA-B35:77SPDSFSSLF0.99480.7059514
SPINK5-NCOA3chr5147506642chr20462777483006HLA-B35:23SPDSFSSLF0.99410.6506514
SPINK5-NCOA3chr5147506642chr20462777483006HLA-C18:01SPDSFSSLF0.99380.7484514
SPINK5-NCOA3chr5147506642chr20462777483006HLA-B35:20SPDSFSSLF0.99330.7711514
SPINK5-NCOA3chr5147506642chr20462777483006HLA-C08:02SPDSFSSLF0.98740.9346514
SPINK5-NCOA3chr5147506642chr20462777483006HLA-B07:13SPDSFSSLF0.98030.7861514
SPINK5-NCOA3chr5147506642chr20462777483006HLA-A74:01SSLFLNQSR0.94720.65381019
SPINK5-NCOA3chr5147506642chr20462777483006HLA-B35:11SPDSFSSLF0.93530.7581514
SPINK5-NCOA3chr5147506642chr20462777483006HLA-B35:24SPDSFSSLF0.92830.7875514
SPINK5-NCOA3chr5147506642chr20462777483006HLA-B35:13SPDSFSSLF0.92150.7862514
SPINK5-NCOA3chr5147506642chr20462777483006HLA-B35:09SPDSFSSLF0.71260.7932514
SPINK5-NCOA3chr5147506642chr20462777483006HLA-B39:11SPDSFSSLF0.48420.6588514
SPINK5-NCOA3chr5147506642chr20462777483006HLA-B18:04SPDSFSSLF0.38190.8627514
SPINK5-NCOA3chr5147506642chr20462777483006HLA-B67:01SPDSFSSLF0.38030.6074514
SPINK5-NCOA3chr5147506642chr20462777483006HLA-C08:01SPDSFSSLF0.3090.9647514
SPINK5-NCOA3chr5147506642chr20462777483006HLA-C04:04SPDSFSSLF0.30190.7672514
SPINK5-NCOA3chr5147506642chr20462777483006HLA-B18:07SPDSFSSLF0.20690.7928514
SPINK5-NCOA3chr5147506642chr20462777483006HLA-B18:08SPDSFSSLF0.14870.6753514
SPINK5-NCOA3chr5147506642chr20462777483006HLA-B35:43SPDSFSSLF0.12280.7194514
SPINK5-NCOA3chr5147506642chr20462777483006HLA-B15:08SPDSFSSLF0.11390.7088514
SPINK5-NCOA3chr5147506642chr20462777483006HLA-B15:11SPDSFSSLF0.10640.7132514
SPINK5-NCOA3chr5147506642chr20462777483006HLA-A25:01DSPDSFSSLF0.98990.7509414
SPINK5-NCOA3chr5147506642chr20462777483006HLA-B67:01SPDSFSSLFL0.78580.6929515
SPINK5-NCOA3chr5147506642chr20462777483006HLA-B35:09SPDSFSSLFL0.74480.8458515

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Potential FusionNeoAntigen Information of SPINK5-NCOA3 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 SPINK5-NCOA3

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
6553PDSFSSLFLNQSRQSPINK5NCOA3chr5147506642chr20462777483006

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of SPINK5-NCOA3

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-B14:023BVN6553PDSFSSLFLNQSRQ-5.47913-5.67113
HLA-B14:023BVN6553PDSFSSLFLNQSRQ-3.84443-4.60543
HLA-B52:013W396553PDSFSSLFLNQSRQ-6.76995-6.96195
HLA-B52:013W396553PDSFSSLFLNQSRQ-5.58751-6.34851
HLA-A11:014UQ26553PDSFSSLFLNQSRQ-5.74663-6.50763
HLA-A11:014UQ26553PDSFSSLFLNQSRQ-5.69582-5.88782
HLA-A24:025HGA6553PDSFSSLFLNQSRQ-8.42283-9.18383
HLA-A24:025HGA6553PDSFSSLFLNQSRQ-7.2103-7.4023
HLA-B27:056PYJ6553PDSFSSLFLNQSRQ-7.69112-7.88312
HLA-B44:053DX86553PDSFSSLFLNQSRQ-5.89348-6.08548
HLA-B44:053DX86553PDSFSSLFLNQSRQ-3.81554-4.57654
HLA-A02:016TDR6553PDSFSSLFLNQSRQ-3.68024-4.44124

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Vaccine Design for the FusionNeoAntigens of SPINK5-NCOA3

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
SPINK5-NCOA3chr5147506642chr20462777481019SSLFLNQSRAGTTCTCTGTTTTTGAATCAGAGCCGA
SPINK5-NCOA3chr5147506642chr2046277748314EDSPDSFSSLFGAAGACAGCCCAGACTCTTTCAGTTCTCTGTTT
SPINK5-NCOA3chr5147506642chr2046277748414DSPDSFSSLFGACAGCCCAGACTCTTTCAGTTCTCTGTTT
SPINK5-NCOA3chr5147506642chr2046277748514SPDSFSSLFAGCCCAGACTCTTTCAGTTCTCTGTTT
SPINK5-NCOA3chr5147506642chr2046277748515SPDSFSSLFLAGCCCAGACTCTTTCAGTTCTCTGTTTTTG
SPINK5-NCOA3chr5147506642chr2046277748715DSFSSLFLGACTCTTTCAGTTCTCTGTTTTTG
SPINK5-NCOA3chr5147506642chr2046277748819SFSSLFLNQSRTCTTTCAGTTCTCTGTTTTTGAATCAGAGCCGA

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 SPINK5-NCOA3

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
Non-CancerSPINK5-NCOA3chr5147506642ENST00000256084chr2046277748ENST00000341724TCGA-CV-7177-11A

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Potential target of CAR-T therapy development for SPINK5-NCOA3

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 SPINK5-NCOA3

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 SPINK5-NCOA3

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