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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:ALG14-JAK1

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: ALG14-JAK1
FusionPDB ID: 4005
FusionGDB2.0 ID: 4005
HgeneTgene
Gene symbol

ALG14

JAK1

Gene ID

199857

3716

Gene nameALG14 UDP-N-acetylglucosaminyltransferase subunitJanus kinase 1
SynonymsCMS15JAK1A|JAK1B|JTK3
Cytomap

1p21.3

1p31.3

Type of geneprotein-codingprotein-coding
DescriptionUDP-N-acetylglucosamine transferase subunit ALG14 homologtyrosine-protein kinase JAK1
Modification date2020031320200327
UniProtAcc

Q96F25

Main function of 5'-partner protein: FUNCTION: May be involved in protein N-glycosylation. May play a role in the second step of the dolichol-linked oligosaccharide pathway. May anchor the catalytic subunit ALG13 to the ER. {ECO:0000269|PubMed:16100110}.

P23458

Main function of 5'-partner protein: FUNCTION: Tyrosine kinase of the non-receptor type, involved in the IFN-alpha/beta/gamma signal pathway (PubMed:7615558). Kinase partner for the interleukin (IL)-2 receptor (PubMed:11909529) as well as interleukin (IL)-10 receptor (PubMed:12133952). {ECO:0000269|PubMed:11909529, ECO:0000269|PubMed:7615558}.
Ensembl transtripts involved in fusion geneENST idsENST00000370205, ENST00000495856, 
ENST00000465376, ENST00000342505, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score8 X 5 X 5=20019 X 18 X 6=2052
# samples 819
** MAII scorelog2(8/200*10)=-1.32192809488736
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(19/2052*10)=-3.43295940727611
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: ALG14 [Title/Abstract] AND JAK1 [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: ALG14 [Title/Abstract] AND JAK1 [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)ALG14(95492685)-JAK1(65313358), # samples:2
Anticipated loss of major functional domain due to fusion event.ALG14-JAK1 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.
ALG14-JAK1 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.
ALG14-JAK1 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.
ALG14-JAK1 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
TgeneJAK1

GO:0038110

interleukin-2-mediated signaling pathway

11909529

TgeneJAK1

GO:0046677

response to antibiotic

16280321



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/chr1:95492685/chr1:65313358)
- 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 ALG14 (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 JAK1 (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)
ENST00000370205ALG14chr195492685-ENST00000342505JAK1chr165313358-351046782176722

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
ENST00000370205ENST00000342505ALG14chr195492685-JAK1chr165313358-0.0006026720.9993973

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 ALG14-JAK1

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
ALG14chr195492685JAK1chr165313358467153LSFPLIHRVKPDLGEHLGRGTRTHIY

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Potential FusionNeoAntigen Information of ALG14-JAK1 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.
ALG14-JAK1_95492685_65313358.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)
ALG14-JAK1chr195492685chr165313358467HLA-B27:04HRVKPDLGEHL10.6453617
ALG14-JAK1chr195492685chr165313358467HLA-B27:07HRVKPDLGEHL0.99990.7107617
ALG14-JAK1chr195492685chr165313358467HLA-C04:07KPDLGEHL0.99990.8669917
ALG14-JAK1chr195492685chr165313358467HLA-B39:10KPDLGEHL0.80720.9291917
ALG14-JAK1chr195492685chr165313358467HLA-B39:09VKPDLGEHL0.95740.5267817
ALG14-JAK1chr195492685chr165313358467HLA-B15:04RVKPDLGEH0.91060.8679716
ALG14-JAK1chr195492685chr165313358467HLA-C07:13VKPDLGEHL0.71380.9195817
ALG14-JAK1chr195492685chr165313358467HLA-C07:29VKPDLGEHL0.66230.9393817
ALG14-JAK1chr195492685chr165313358467HLA-C01:17RVKPDLGEHL0.98280.935717
ALG14-JAK1chr195492685chr165313358467HLA-B27:03HRVKPDLGEHL0.99920.5426617
ALG14-JAK1chr195492685chr165313358467HLA-C04:01KPDLGEHL0.99990.8669917
ALG14-JAK1chr195492685chr165313358467HLA-B67:01KPDLGEHL0.78020.7785917
ALG14-JAK1chr195492685chr165313358467HLA-C01:03RVKPDLGEHL0.99110.9169717
ALG14-JAK1chr195492685chr165313358467HLA-B15:73RVKPDLGEHL0.99060.9588717
ALG14-JAK1chr195492685chr165313358467HLA-B15:30RVKPDLGEHL0.98710.9469717
ALG14-JAK1chr195492685chr165313358467HLA-C01:02RVKPDLGEHL0.97790.9333717
ALG14-JAK1chr195492685chr165313358467HLA-B27:06HRVKPDLGEHL10.7004617

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Potential FusionNeoAntigen Information of ALG14-JAK1 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.
ALG14-JAK1_95492685_65313358.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)
ALG14-JAK1chr195492685chr165313358467DRB1-1525IHRVKPDLGEHLGRG520
ALG14-JAK1chr195492685chr165313358467DRB1-1525LIHRVKPDLGEHLGR419
ALG14-JAK1chr195492685chr165313358467DRB4-0101SFPLIHRVKPDLGEH116
ALG14-JAK1chr195492685chr165313358467DRB4-0101FPLIHRVKPDLGEHL217
ALG14-JAK1chr195492685chr165313358467DRB4-0101PLIHRVKPDLGEHLG318
ALG14-JAK1chr195492685chr165313358467DRB4-0101LSFPLIHRVKPDLGE015
ALG14-JAK1chr195492685chr165313358467DRB4-0103SFPLIHRVKPDLGEH116
ALG14-JAK1chr195492685chr165313358467DRB4-0103FPLIHRVKPDLGEHL217
ALG14-JAK1chr195492685chr165313358467DRB4-0103PLIHRVKPDLGEHLG318
ALG14-JAK1chr195492685chr165313358467DRB4-0103LSFPLIHRVKPDLGE015
ALG14-JAK1chr195492685chr165313358467DRB4-0104SFPLIHRVKPDLGEH116
ALG14-JAK1chr195492685chr165313358467DRB4-0104FPLIHRVKPDLGEHL217
ALG14-JAK1chr195492685chr165313358467DRB4-0104PLIHRVKPDLGEHLG318
ALG14-JAK1chr195492685chr165313358467DRB4-0104LSFPLIHRVKPDLGE015
ALG14-JAK1chr195492685chr165313358467DRB4-0106SFPLIHRVKPDLGEH116
ALG14-JAK1chr195492685chr165313358467DRB4-0106FPLIHRVKPDLGEHL217
ALG14-JAK1chr195492685chr165313358467DRB4-0106PLIHRVKPDLGEHLG318
ALG14-JAK1chr195492685chr165313358467DRB4-0106LSFPLIHRVKPDLGE015
ALG14-JAK1chr195492685chr165313358467DRB4-0107SFPLIHRVKPDLGEH116
ALG14-JAK1chr195492685chr165313358467DRB4-0107FPLIHRVKPDLGEHL217
ALG14-JAK1chr195492685chr165313358467DRB4-0107PLIHRVKPDLGEHLG318
ALG14-JAK1chr195492685chr165313358467DRB4-0107LSFPLIHRVKPDLGE015
ALG14-JAK1chr195492685chr165313358467DRB4-0108SFPLIHRVKPDLGEH116
ALG14-JAK1chr195492685chr165313358467DRB4-0108FPLIHRVKPDLGEHL217
ALG14-JAK1chr195492685chr165313358467DRB4-0108PLIHRVKPDLGEHLG318
ALG14-JAK1chr195492685chr165313358467DRB4-0108LSFPLIHRVKPDLGE015

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Fusion breakpoint peptide structures of ALG14-JAK1

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
3494HRVKPDLGEHLGRGALG14JAK1chr195492685chr165313358467

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of ALG14-JAK1

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-B14:023BVN3494HRVKPDLGEHLGRG-5.86293-5.97633
HLA-B14:023BVN3494HRVKPDLGEHLGRG-4.7505-5.7858
HLA-B52:013W393494HRVKPDLGEHLGRG-7.16929-7.28269
HLA-B52:013W393494HRVKPDLGEHLGRG-6.22817-7.26347
HLA-A11:014UQ23494HRVKPDLGEHLGRG1000110000
HLA-A24:025HGA3494HRVKPDLGEHLGRG-7.90199-8.01539
HLA-A24:025HGA3494HRVKPDLGEHLGRG-7.88373-8.91903
HLA-B44:053DX83494HRVKPDLGEHLGRG-5.57367-5.68707
HLA-B44:053DX83494HRVKPDLGEHLGRG-4.76642-5.80172

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Vaccine Design for the FusionNeoAntigens of ALG14-JAK1

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
ALG14-JAK1chr195492685chr165313358617HRVKPDLGEHLCACAGGGTGAAGCCAGATTTGGGCGAGCACCTT
ALG14-JAK1chr195492685chr165313358716RVKPDLGEHAGGGTGAAGCCAGATTTGGGCGAGCAC
ALG14-JAK1chr195492685chr165313358717RVKPDLGEHLAGGGTGAAGCCAGATTTGGGCGAGCACCTT
ALG14-JAK1chr195492685chr165313358817VKPDLGEHLGTGAAGCCAGATTTGGGCGAGCACCTT
ALG14-JAK1chr195492685chr165313358917KPDLGEHLAAGCCAGATTTGGGCGAGCACCTT

check button mRNA and peptide sequences of FusionNeoAntigens that have potential interaction with HLA-IIs.
Fusion geneHchrHbpTchrTbpStart in +/-13AAEnd in +/-13AAFusionNeoAntigen peptideFusionNEoAntigen RNA sequence
ALG14-JAK1chr195492685chr165313358015LSFPLIHRVKPDLGECTCTCCTTTCCCCTAATTCACAGGGTGAAGCCAGATTTGGGCGAG
ALG14-JAK1chr195492685chr165313358116SFPLIHRVKPDLGEHTCCTTTCCCCTAATTCACAGGGTGAAGCCAGATTTGGGCGAGCAC
ALG14-JAK1chr195492685chr165313358217FPLIHRVKPDLGEHLTTTCCCCTAATTCACAGGGTGAAGCCAGATTTGGGCGAGCACCTT
ALG14-JAK1chr195492685chr165313358318PLIHRVKPDLGEHLGCCCCTAATTCACAGGGTGAAGCCAGATTTGGGCGAGCACCTTGGG
ALG14-JAK1chr195492685chr165313358419LIHRVKPDLGEHLGRCTAATTCACAGGGTGAAGCCAGATTTGGGCGAGCACCTTGGGAGA
ALG14-JAK1chr195492685chr165313358520IHRVKPDLGEHLGRGATTCACAGGGTGAAGCCAGATTTGGGCGAGCACCTTGGGAGAGGC

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Information of the samples that have these potential fusion neoantigens of ALG14-JAK1

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
BLCAALG14-JAK1chr195492685ENST00000370205chr165313358ENST00000342505TCGA-DK-AA6R-01A

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Potential target of CAR-T therapy development for ALG14-JAK1

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
HgeneALG14chr1:95492685chr1:65313358ENST00000370205-344_24140217.0TransmembraneHelical

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 ALG14-JAK1

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 ALG14-JAK1

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