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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:SIK3-CNTN5

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: SIK3-CNTN5
FusionPDB ID: 81863
FusionGDB2.0 ID: 81863
HgeneTgene
Gene symbol

SIK3

CNTN5

Gene ID

23387

53942

Gene nameSIK family kinase 3contactin 5
SynonymsL19|QSK|SEMDK|SIK-3HNB-2s|NB-2
Cytomap

11q23.3

11q22.1

Type of geneprotein-codingprotein-coding
Descriptionserine/threonine-protein kinase SIK3salt-inducible kinase 3serine/threonine-protein kinase QSKcontactin-5neural adhesion moleculeneural recognition molecule NB-2
Modification date2020032020200329
UniProtAcc.

O94779

Main function of 5'-partner protein: FUNCTION: Contactins mediate cell surface interactions during nervous system development. Has some neurite outgrowth-promoting activity in the cerebral cortical neurons but not in hippocampal neurons. Probably involved in neuronal activity in the auditory system (By similarity). {ECO:0000250}.
Ensembl transtripts involved in fusion geneENST idsENST00000292055, ENST00000375300, 
ENST00000434315, ENST00000446921, 
ENST00000542607, ENST00000375288, 
ENST00000488337, 
ENST00000524560, 
ENST00000279463, ENST00000418526, 
ENST00000524871, ENST00000527185, 
ENST00000528682, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score17 X 12 X 10=204018 X 15 X 12=3240
# samples 2319
** MAII scorelog2(23/2040*10)=-3.14886338591448
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(19/3240*10)=-4.09192248944104
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: SIK3 [Title/Abstract] AND CNTN5 [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: SIK3 [Title/Abstract] AND CNTN5 [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)SIK3(116797935)-CNTN5(100126492), # samples:1
Anticipated loss of major functional domain due to fusion event.SIK3-CNTN5 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.
SIK3-CNTN5 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.
SIK3-CNTN5 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.
SIK3-CNTN5 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
HgeneSIK3

GO:0006468

protein phosphorylation

14976552



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/chr11:116797935/chr11:100126492)
- 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 SIK3 (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 CNTN5 (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)
ENST00000375300SIK3chr11116797935-ENST00000527185CNTN5chr11100126492+258162261352448
ENST00000375300SIK3chr11116797935-ENST00000528682CNTN5chr11100126492+226662261919637
ENST00000375300SIK3chr11116797935-ENST00000524871CNTN5chr11100126492+458562261919637
ENST00000375300SIK3chr11116797935-ENST00000418526CNTN5chr11100126492+244262261919637
ENST00000375300SIK3chr11116797935-ENST00000279463CNTN5chr11100126492+192062261919637
ENST00000292055SIK3chr11116797935-ENST00000527185CNTN5chr11100126492+2437478361208390
ENST00000292055SIK3chr11116797935-ENST00000528682CNTN5chr11100126492+2122478361775579
ENST00000292055SIK3chr11116797935-ENST00000524871CNTN5chr11100126492+4441478361775579
ENST00000292055SIK3chr11116797935-ENST00000418526CNTN5chr11100126492+2298478361775579
ENST00000292055SIK3chr11116797935-ENST00000279463CNTN5chr11100126492+1776478361775579
ENST00000434315SIK3chr11116797935-ENST00000527185CNTN5chr11100126492+25555964391326295
ENST00000434315SIK3chr11116797935-ENST00000528682CNTN5chr11100126492+22405964391893484
ENST00000434315SIK3chr11116797935-ENST00000524871CNTN5chr11100126492+45595964391893484
ENST00000434315SIK3chr11116797935-ENST00000418526CNTN5chr11100126492+24165964391893484
ENST00000434315SIK3chr11116797935-ENST00000279463CNTN5chr11100126492+18945964391893485
ENST00000542607SIK3chr11116797935-ENST00000527185CNTN5chr11100126492+2437478361208390
ENST00000542607SIK3chr11116797935-ENST00000528682CNTN5chr11100126492+2122478361775579
ENST00000542607SIK3chr11116797935-ENST00000524871CNTN5chr11100126492+4441478361775579
ENST00000542607SIK3chr11116797935-ENST00000418526CNTN5chr11100126492+2298478361775579
ENST00000542607SIK3chr11116797935-ENST00000279463CNTN5chr11100126492+1776478361775579
ENST00000446921SIK3chr11116797935-ENST00000527185CNTN5chr11100126492+2597638101368452
ENST00000446921SIK3chr11116797935-ENST00000528682CNTN5chr11100126492+2282638101935641
ENST00000446921SIK3chr11116797935-ENST00000524871CNTN5chr11100126492+4601638101935641
ENST00000446921SIK3chr11116797935-ENST00000418526CNTN5chr11100126492+2458638101935641
ENST00000446921SIK3chr11116797935-ENST00000279463CNTN5chr11100126492+1936638101935642

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
ENST00000375300ENST00000527185SIK3chr11116797935-CNTN5chr11100126492+0.0001984780.9998016
ENST00000375300ENST00000528682SIK3chr11116797935-CNTN5chr11100126492+0.0008599220.99914
ENST00000375300ENST00000524871SIK3chr11116797935-CNTN5chr11100126492+0.0002188270.9997812
ENST00000375300ENST00000418526SIK3chr11116797935-CNTN5chr11100126492+0.0006842980.99931574
ENST00000375300ENST00000279463SIK3chr11116797935-CNTN5chr11100126492+0.0028037370.9971962
ENST00000292055ENST00000527185SIK3chr11116797935-CNTN5chr11100126492+0.0006627040.99933726
ENST00000292055ENST00000528682SIK3chr11116797935-CNTN5chr11100126492+0.0018241030.99817586
ENST00000292055ENST00000524871SIK3chr11116797935-CNTN5chr11100126492+0.0008315670.9991685
ENST00000292055ENST00000418526SIK3chr11116797935-CNTN5chr11100126492+0.0015951720.9984048
ENST00000292055ENST00000279463SIK3chr11116797935-CNTN5chr11100126492+0.0055610710.9944389
ENST00000434315ENST00000527185SIK3chr11116797935-CNTN5chr11100126492+0.001012520.9989875
ENST00000434315ENST00000528682SIK3chr11116797935-CNTN5chr11100126492+0.001096350.99890363
ENST00000434315ENST00000524871SIK3chr11116797935-CNTN5chr11100126492+0.0003008890.9996991
ENST00000434315ENST00000418526SIK3chr11116797935-CNTN5chr11100126492+0.0009042410.9990958
ENST00000434315ENST00000279463SIK3chr11116797935-CNTN5chr11100126492+0.0034594830.9965405
ENST00000542607ENST00000527185SIK3chr11116797935-CNTN5chr11100126492+0.0006627040.99933726
ENST00000542607ENST00000528682SIK3chr11116797935-CNTN5chr11100126492+0.0018241030.99817586
ENST00000542607ENST00000524871SIK3chr11116797935-CNTN5chr11100126492+0.0008315670.9991685
ENST00000542607ENST00000418526SIK3chr11116797935-CNTN5chr11100126492+0.0015951720.9984048
ENST00000542607ENST00000279463SIK3chr11116797935-CNTN5chr11100126492+0.0055610710.9944389
ENST00000446921ENST00000527185SIK3chr11116797935-CNTN5chr11100126492+0.0002028020.99979717
ENST00000446921ENST00000528682SIK3chr11116797935-CNTN5chr11100126492+0.0009084910.9990915
ENST00000446921ENST00000524871SIK3chr11116797935-CNTN5chr11100126492+0.0002248450.9997751
ENST00000446921ENST00000418526SIK3chr11116797935-CNTN5chr11100126492+0.0007252140.9992748
ENST00000446921ENST00000279463SIK3chr11116797935-CNTN5chr11100126492+0.0030074040.9969926

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 SIK3-CNTN5

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
SIK3chr11116797935CNTN5chr11100126492478147NLLLDANLNIKIAGPPGPPGIVIVEE
SIK3chr11116797935CNTN5chr1110012649259652NLLLDANLNIKIAGPPGPPGIVIVEE
SIK3chr11116797935CNTN5chr11100126492622205NLLLDANLNIKIAGPPGPPGIVIVEE
SIK3chr11116797935CNTN5chr11100126492638209NLLLDANLNIKIAGPPGPPGIVIVEE

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Potential FusionNeoAntigen Information of SIK3-CNTN5 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.
SIK3-CNTN5_116797935_100126492.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)
SIK3-CNTN5chr11116797935chr11100126492478HLA-B07:05AGPPGPPGIVI0.97090.58721223
SIK3-CNTN5chr11116797935chr11100126492478HLA-C01:30AGPPGPPGI0.55150.97871221
SIK3-CNTN5chr11116797935chr11100126492478HLA-C01:17AGPPGPPGI0.32440.9751221
SIK3-CNTN5chr11116797935chr11100126492478HLA-C01:17IAGPPGPPGI0.98380.96391121
SIK3-CNTN5chr11116797935chr11100126492478HLA-B07:12AGPPGPPGIVI0.96670.641223
SIK3-CNTN5chr11116797935chr11100126492478HLA-C01:02AGPPGPPGI0.31890.97491221
SIK3-CNTN5chr11116797935chr11100126492478HLA-C01:03AGPPGPPGI0.16510.97091221
SIK3-CNTN5chr11116797935chr11100126492478HLA-C01:02IAGPPGPPGI0.98770.96281121

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Potential FusionNeoAntigen Information of SIK3-CNTN5 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.
SIK3-CNTN5_116797935_100126492.msa

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)
SIK3-CNTN5chr11116797935chr11100126492478DRB3-0301NLLLDANLNIKIAGP015

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Fusion breakpoint peptide structures of SIK3-CNTN5

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
6259NLNIKIAGPPGPPGSIK3CNTN5chr11116797935chr11100126492478

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of SIK3-CNTN5

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-B14:023BVN6259NLNIKIAGPPGPPG-7.9962-8.1096
HLA-B14:023BVN6259NLNIKIAGPPGPPG-5.70842-6.74372
HLA-B52:013W396259NLNIKIAGPPGPPG-6.83737-6.95077
HLA-B52:013W396259NLNIKIAGPPGPPG-4.4836-5.5189
HLA-A11:014UQ26259NLNIKIAGPPGPPG-10.0067-10.1201
HLA-A11:014UQ26259NLNIKIAGPPGPPG-9.03915-10.0745
HLA-A24:025HGA6259NLNIKIAGPPGPPG-6.56204-6.67544
HLA-A24:025HGA6259NLNIKIAGPPGPPG-5.42271-6.45801
HLA-B44:053DX86259NLNIKIAGPPGPPG-7.85648-8.89178
HLA-B44:053DX86259NLNIKIAGPPGPPG-5.3978-5.5112
HLA-A02:016TDR6259NLNIKIAGPPGPPG-3.37154-4.40684

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Vaccine Design for the FusionNeoAntigens of SIK3-CNTN5

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
SIK3-CNTN5chr11116797935chr111001264921121IAGPPGPPGITAGCAGGACCCCCAGGCCCACCTGGGATAG
SIK3-CNTN5chr11116797935chr111001264921221AGPPGPPGICAGGACCCCCAGGCCCACCTGGGATAG
SIK3-CNTN5chr11116797935chr111001264921223AGPPGPPGIVICAGGACCCCCAGGCCCACCTGGGATAGTAATTG

check button mRNA and peptide sequences of FusionNeoAntigens that have potential interaction with HLA-IIs.
Fusion geneHchrHbpTchrTbpStart in +/-13AAEnd in +/-13AAFusionNeoAntigen peptideFusionNEoAntigen RNA sequence
SIK3-CNTN5chr11116797935chr11100126492015NLLLDANLNIKIAGPATTTACTTCTGGATGCCAATCTGAATATCAAAATAGCAGGACCCC

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Information of the samples that have these potential fusion neoantigens of SIK3-CNTN5

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
HNSCSIK3-CNTN5chr11116797935ENST00000292055chr11100126492ENST00000279463TCGA-CQ-A4C7-01A

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Potential target of CAR-T therapy development for SIK3-CNTN5

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 SIK3-CNTN5

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 SIK3-CNTN5

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