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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:SIK2-ALG9

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: SIK2-ALG9
FusionPDB ID: 81846
FusionGDB2.0 ID: 81846
HgeneTgene
Gene symbol

SIK2

ALG9

Gene ID

23235

79796

Gene namesalt inducible kinase 2ALG9 alpha-1,2-mannosyltransferase
SynonymsLOH11CR1I|QIK|SIK-2|SNF1LK2CDG1L|DIBD1|GIKANIS|LOH11CR1J
Cytomap

11q23.1

11q23.1

Type of geneprotein-codingprotein-coding
Descriptionserine/threonine-protein kinase SIK2SNF1-like kinase 2qin-induced kinasesalt-inducible protein kinase 2salt-inducible serine/threonine kinase 2serine/threonine-protein kinase SNF1-like kinase 2alpha-1,2-mannosyltransferase ALG9asparagine-linked glycosylation 9 alpha-12-mannosyltransferase-like proteinasparagine-linked glycosylation 9 homolog (S. cerevisiae, alpha- 1,2-mannosyltransferase)asparagine-linked glycosylation 9 homolog (yeast, alph
Modification date2020031320200313
UniProtAcc.

Q9H6U8

Main function of 5'-partner protein: FUNCTION: Catalyzes the transfer of mannose from Dol-P-Man to lipid-linked oligosaccharides. {ECO:0000269|PubMed:15148656, ECO:0000269|PubMed:15945070}.
Ensembl transtripts involved in fusion geneENST idsENST00000304987, ENST00000533868, 
ENST00000524880, ENST00000527228, 
ENST00000527377, ENST00000398006, 
ENST00000531154, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score13 X 7 X 10=9104 X 3 X 4=48
# samples 135
** MAII scorelog2(13/910*10)=-2.8073549220576
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(5/48*10)=0.0588936890535686
effective Gene in Pan-Cancer Fusion Genes (eGinPCFGs).
DoF>8 and MAII>0
Fusion gene context

PubMed: SIK2 [Title/Abstract] AND ALG9 [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: SIK2 [Title/Abstract] AND ALG9 [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)SIK2(111473422)-ALG9(111680497), # samples:1
Anticipated loss of major functional domain due to fusion event.SIK2-ALG9 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.
SIK2-ALG9 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
HgeneSIK2

GO:0006468

protein phosphorylation

14976552

HgeneSIK2

GO:0035556

intracellular signal transduction

14976552

HgeneSIK2

GO:0046777

protein autophosphorylation

18348280



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/chr11:111473422/chr11:111680497)
- 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 SIK2 (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 ALG9 (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)
ENST00000304987SIK2chr11111473422+ENST00000531154ALG9chr11111680497-67630835562175
ENST00000304987SIK2chr11111473422+ENST00000398006ALG9chr11111680497-67630835562175

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
ENST00000304987ENST00000531154SIK2chr11111473422+ALG9chr11111680497-0.0338979140.96610206
ENST00000304987ENST00000398006SIK2chr11111473422+ALG9chr11111680497-0.0338979140.96610206

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 SIK2-ALG9

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
SIK2chr11111473422ALG9chr1111168049730891VVKLGRHRITKTEIDISKCHYLVDLD

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Potential FusionNeoAntigen Information of SIK2-ALG9 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.
SIK2-ALG9_111473422_111680497.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)
SIK2-ALG9chr11111473422chr11111680497308HLA-B14:02HRITKTEI0.99810.5843614
SIK2-ALG9chr11111473422chr11111680497308HLA-B14:01HRITKTEI0.99810.5843614
SIK2-ALG9chr11111473422chr11111680497308HLA-B44:03TEIDISKCH0.98830.90141120
SIK2-ALG9chr11111473422chr11111680497308HLA-B18:01TEIDISKCH0.96890.89721120
SIK2-ALG9chr11111473422chr11111680497308HLA-B15:02EIDISKCHY0.81050.6051221
SIK2-ALG9chr11111473422chr11111680497308HLA-B44:03TEIDISKCHY0.99970.71241121
SIK2-ALG9chr11111473422chr11111680497308HLA-B18:01TEIDISKCHY0.99060.75921121
SIK2-ALG9chr11111473422chr11111680497308HLA-A30:08ITKTEIDISK0.97750.6787818
SIK2-ALG9chr11111473422chr11111680497308HLA-B44:03TEIDISKCHYL0.99960.8661122
SIK2-ALG9chr11111473422chr11111680497308HLA-B44:03KTEIDISKCHY0.97780.7061021
SIK2-ALG9chr11111473422chr11111680497308HLA-B39:12HRITKTEI0.99730.8393614
SIK2-ALG9chr11111473422chr11111680497308HLA-B15:31EIDISKCHY0.87960.55121221
SIK2-ALG9chr11111473422chr11111680497308HLA-B44:26TEIDISKCH0.98830.90141120
SIK2-ALG9chr11111473422chr11111680497308HLA-B44:07TEIDISKCH0.98830.90141120
SIK2-ALG9chr11111473422chr11111680497308HLA-B44:13TEIDISKCH0.98830.90141120
SIK2-ALG9chr11111473422chr11111680497308HLA-B18:08TEIDISKCH0.9690.76391120
SIK2-ALG9chr11111473422chr11111680497308HLA-B18:05TEIDISKCH0.96890.89721120
SIK2-ALG9chr11111473422chr11111680497308HLA-B18:06TEIDISKCH0.9590.88691120
SIK2-ALG9chr11111473422chr11111680497308HLA-B18:04TEIDISKCH0.95040.90831120
SIK2-ALG9chr11111473422chr11111680497308HLA-B18:03TEIDISKCH0.840.88471120
SIK2-ALG9chr11111473422chr11111680497308HLA-B18:11TEIDISKCH0.73330.87771120
SIK2-ALG9chr11111473422chr11111680497308HLA-B44:26TEIDISKCHY0.99970.71241121
SIK2-ALG9chr11111473422chr11111680497308HLA-B44:07TEIDISKCHY0.99970.71241121
SIK2-ALG9chr11111473422chr11111680497308HLA-B44:13TEIDISKCHY0.99970.71241121
SIK2-ALG9chr11111473422chr11111680497308HLA-B18:11TEIDISKCHY0.99450.69951121
SIK2-ALG9chr11111473422chr11111680497308HLA-B18:08TEIDISKCHY0.99370.52691121
SIK2-ALG9chr11111473422chr11111680497308HLA-B15:53TEIDISKCHY0.99330.72881121
SIK2-ALG9chr11111473422chr11111680497308HLA-B18:04TEIDISKCHY0.99310.78481121
SIK2-ALG9chr11111473422chr11111680497308HLA-B18:07TEIDISKCHY0.99270.72921121
SIK2-ALG9chr11111473422chr11111680497308HLA-B18:05TEIDISKCHY0.99060.75921121
SIK2-ALG9chr11111473422chr11111680497308HLA-B18:06TEIDISKCHY0.99040.74121121
SIK2-ALG9chr11111473422chr11111680497308HLA-B18:03TEIDISKCHY0.98440.74471121
SIK2-ALG9chr11111473422chr11111680497308HLA-A30:01ITKTEIDISK0.97650.8136818
SIK2-ALG9chr11111473422chr11111680497308HLA-B35:20TEIDISKCHY0.96530.66661121
SIK2-ALG9chr11111473422chr11111680497308HLA-B48:02TEIDISKCHY0.94810.63681121
SIK2-ALG9chr11111473422chr11111680497308HLA-B44:26TEIDISKCHYL0.99960.8661122
SIK2-ALG9chr11111473422chr11111680497308HLA-B44:13TEIDISKCHYL0.99960.8661122
SIK2-ALG9chr11111473422chr11111680497308HLA-B44:07TEIDISKCHYL0.99960.8661122
SIK2-ALG9chr11111473422chr11111680497308HLA-B44:13KTEIDISKCHY0.97780.7061021
SIK2-ALG9chr11111473422chr11111680497308HLA-B44:26KTEIDISKCHY0.97780.7061021
SIK2-ALG9chr11111473422chr11111680497308HLA-B44:07KTEIDISKCHY0.97780.7061021

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Potential FusionNeoAntigen Information of SIK2-ALG9 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.
SIK2-ALG9_111473422_111680497.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)
SIK2-ALG9chr11111473422chr11111680497308DRB4-0101RHRITKTEIDISKCH520
SIK2-ALG9chr11111473422chr11111680497308DRB4-0101LGRHRITKTEIDISK318
SIK2-ALG9chr11111473422chr11111680497308DRB4-0101GRHRITKTEIDISKC419
SIK2-ALG9chr11111473422chr11111680497308DRB4-0101HRITKTEIDISKCHY621
SIK2-ALG9chr11111473422chr11111680497308DRB4-0103RHRITKTEIDISKCH520
SIK2-ALG9chr11111473422chr11111680497308DRB4-0103LGRHRITKTEIDISK318
SIK2-ALG9chr11111473422chr11111680497308DRB4-0103GRHRITKTEIDISKC419
SIK2-ALG9chr11111473422chr11111680497308DRB4-0103HRITKTEIDISKCHY621
SIK2-ALG9chr11111473422chr11111680497308DRB4-0104RHRITKTEIDISKCH520
SIK2-ALG9chr11111473422chr11111680497308DRB4-0104LGRHRITKTEIDISK318
SIK2-ALG9chr11111473422chr11111680497308DRB4-0104GRHRITKTEIDISKC419
SIK2-ALG9chr11111473422chr11111680497308DRB4-0104HRITKTEIDISKCHY621
SIK2-ALG9chr11111473422chr11111680497308DRB4-0106RHRITKTEIDISKCH520
SIK2-ALG9chr11111473422chr11111680497308DRB4-0106LGRHRITKTEIDISK318
SIK2-ALG9chr11111473422chr11111680497308DRB4-0106GRHRITKTEIDISKC419
SIK2-ALG9chr11111473422chr11111680497308DRB4-0106HRITKTEIDISKCHY621
SIK2-ALG9chr11111473422chr11111680497308DRB4-0107RHRITKTEIDISKCH520
SIK2-ALG9chr11111473422chr11111680497308DRB4-0107LGRHRITKTEIDISK318
SIK2-ALG9chr11111473422chr11111680497308DRB4-0107GRHRITKTEIDISKC419
SIK2-ALG9chr11111473422chr11111680497308DRB4-0107HRITKTEIDISKCHY621
SIK2-ALG9chr11111473422chr11111680497308DRB4-0108RHRITKTEIDISKCH520
SIK2-ALG9chr11111473422chr11111680497308DRB4-0108LGRHRITKTEIDISK318
SIK2-ALG9chr11111473422chr11111680497308DRB4-0108GRHRITKTEIDISKC419
SIK2-ALG9chr11111473422chr11111680497308DRB4-0108HRITKTEIDISKCHY621

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Fusion breakpoint peptide structures of SIK2-ALG9

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
3488HRITKTEIDISKCHSIK2ALG9chr11111473422chr11111680497308

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of SIK2-ALG9

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-B14:023BVN3488HRITKTEIDISKCH-8.79968-8.91308
HLA-B14:023BVN3488HRITKTEIDISKCH-2.93446-3.96976
HLA-B52:013W393488HRITKTEIDISKCH-5.96997-6.08337
HLA-B52:013W393488HRITKTEIDISKCH-4.23042-5.26572
HLA-A11:014UQ23488HRITKTEIDISKCH-8.20522-8.31862
HLA-A11:014UQ23488HRITKTEIDISKCH-4.67476-5.71006
HLA-A24:025HGA3488HRITKTEIDISKCH-9.05525-9.16865
HLA-A24:025HGA3488HRITKTEIDISKCH-6.47443-7.50973
HLA-B44:053DX83488HRITKTEIDISKCH-6.9286-7.042
HLA-B44:053DX83488HRITKTEIDISKCH-2.31135-3.34665
HLA-A02:016TDR3488HRITKTEIDISKCH-4.18158-5.21688

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Vaccine Design for the FusionNeoAntigens of SIK2-ALG9

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
SIK2-ALG9chr11111473422chr111116804971021KTEIDISKCHYAAGACGGAGATTGATATCAGTAAATGCCATTAT
SIK2-ALG9chr11111473422chr111116804971120TEIDISKCHACGGAGATTGATATCAGTAAATGCCAT
SIK2-ALG9chr11111473422chr111116804971121TEIDISKCHYACGGAGATTGATATCAGTAAATGCCATTAT
SIK2-ALG9chr11111473422chr111116804971122TEIDISKCHYLACGGAGATTGATATCAGTAAATGCCATTATTTA
SIK2-ALG9chr11111473422chr111116804971221EIDISKCHYGAGATTGATATCAGTAAATGCCATTAT
SIK2-ALG9chr11111473422chr11111680497614HRITKTEICACCGGATCACCAAGACGGAGATT
SIK2-ALG9chr11111473422chr11111680497818ITKTEIDISKATCACCAAGACGGAGATTGATATCAGTAAA

check button mRNA and peptide sequences of FusionNeoAntigens that have potential interaction with HLA-IIs.
Fusion geneHchrHbpTchrTbpStart in +/-13AAEnd in +/-13AAFusionNeoAntigen peptideFusionNEoAntigen RNA sequence
SIK2-ALG9chr11111473422chr11111680497318LGRHRITKTEIDISKCTGGGGCGGCACCGGATCACCAAGACGGAGATTGATATCAGTAAA
SIK2-ALG9chr11111473422chr11111680497419GRHRITKTEIDISKCGGGCGGCACCGGATCACCAAGACGGAGATTGATATCAGTAAATGC
SIK2-ALG9chr11111473422chr11111680497520RHRITKTEIDISKCHCGGCACCGGATCACCAAGACGGAGATTGATATCAGTAAATGCCAT
SIK2-ALG9chr11111473422chr11111680497621HRITKTEIDISKCHYCACCGGATCACCAAGACGGAGATTGATATCAGTAAATGCCATTAT

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Information of the samples that have these potential fusion neoantigens of SIK2-ALG9

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-CancerSIK2-ALG9chr11111473422ENST00000304987chr11111680497ENST00000398006TCGA-HC-7747-11A

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Potential target of CAR-T therapy development for SIK2-ALG9

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
TgeneALG9chr11:111473422chr11:111680497ENST000003980061215371_3910441.0TransmembraneHelical
TgeneALG9chr11:111473422chr11:111680497ENST000003980061215406_4260441.0TransmembraneHelical
TgeneALG9chr11:111473422chr11:111680497ENST000005311541215371_3910448.0TransmembraneHelical
TgeneALG9chr11:111473422chr11:111680497ENST000005311541215406_4260448.0TransmembraneHelical

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 SIK2-ALG9

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 SIK2-ALG9

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