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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:ALG8-MAP6

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: ALG8-MAP6
FusionPDB ID: 4036
FusionGDB2.0 ID: 4036
HgeneTgene
Gene symbol

ALG8

MAP6

Gene ID

79053

4135

Gene nameALG8 alpha-1,3-glucosyltransferasemicrotubule associated protein 6
SynonymsCDG1H|PCLD3MAP6-N|MTAP6|N-STOP|STOP
Cytomap

11q14.1

11q13.5

Type of geneprotein-codingprotein-coding
Descriptionprobable dolichyl pyrophosphate Glc1Man9GlcNAc2 alpha-1,3-glucosyltransferaseHUSSY-02asparagine-linked glycosylation 8 alpha-13-glucosyltransferase-like proteinasparagine-linked glycosylation 8 homolog (S. cerevisiae, alpha-1,3-glucosyltransferase)aspmicrotubule-associated protein 6CTD-2530H12.7MAP-6stable tubule-only polypeptide
Modification date2020031320200313
UniProtAcc

Q9BVK2

Main function of 5'-partner protein: FUNCTION: Adds the second glucose residue to the lipid-linked oligosaccharide precursor for N-linked glycosylation. Transfers glucose from dolichyl phosphate glucose (Dol-P-Glc) onto the lipid-linked oligosaccharide Glc(1)Man(9)GlcNAc(2)-PP-Dol before it is transferred to the nascent peptide (By similarity). Required for PKD1/Polycystin-1 maturation and localization to the plasma membrane of the primary cilia (By similarity). {ECO:0000250|UniProtKB:P40351, ECO:0000250|UniProtKB:Q6P8H8}.

Q96JE9

Main function of 5'-partner protein: FUNCTION: Involved in microtubule stabilization in many cell types, including neuronal cells (By similarity). Specifically has microtubule cold stabilizing activity (By similarity). Involved in dendrite morphogenesis and maintenance by regulating lysosomal trafficking via its interaction with TMEM106B (PubMed:24357581). Regulates KIF5A-mediated axonal cargo transport (By similarity). Regulates axonal growth during neuron polarization (By similarity). {ECO:0000250|UniProtKB:Q63560, ECO:0000269|PubMed:24357581}.
Ensembl transtripts involved in fusion geneENST idsENST00000299626, ENST00000376156, 
ENST00000532552, 
ENST00000526689, 
ENST00000434603, ENST00000304771, 
ENST00000526740, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score6 X 7 X 4=1684 X 4 X 4=64
# samples 77
** MAII scorelog2(7/168*10)=-1.26303440583379
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(7/64*10)=0.129283016944966
effective Gene in Pan-Cancer Fusion Genes (eGinPCFGs).
DoF>8 and MAII>0
Fusion gene context

PubMed: ALG8 [Title/Abstract] AND MAP6 [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: ALG8 [Title/Abstract] AND MAP6 [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)ALG8(77850539)-MAP6(75299229), # samples:1
Anticipated loss of major functional domain due to fusion event.ALG8-MAP6 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.
ALG8-MAP6 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.
ALG8-MAP6 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.
ALG8-MAP6 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


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/chr11:77850539/chr11:75299229)
- 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 ALG8 (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 MAP6 (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)
ENST00000299626ALG8chr1177850539-ENST00000304771MAP6chr1175299229-14341671711292373
ENST00000299626ALG8chr1177850539-ENST00000526740MAP6chr1175299229-14331671711292373
ENST00000376156ALG8chr1177850539-ENST00000304771MAP6chr1175299229-1366991031224373
ENST00000376156ALG8chr1177850539-ENST00000526740MAP6chr1175299229-1365991031224373

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
ENST00000299626ENST00000304771ALG8chr1177850539-MAP6chr1175299229-0.0006064020.9993936
ENST00000299626ENST00000526740ALG8chr1177850539-MAP6chr1175299229-0.0005986030.99940145
ENST00000376156ENST00000304771ALG8chr1177850539-MAP6chr1175299229-0.0005652680.99943477
ENST00000376156ENST00000526740ALG8chr1177850539-MAP6chr1175299229-0.0005564440.9994436

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 ALG8-MAP6

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
ALG8chr1177850539MAP6chr117529922916726PVATEPDKDQGSVVPGLLKGQGPMVQ
ALG8chr1177850539MAP6chr11752992299926PVATEPDKDQGSVVPGLLKGQGPMVQ

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Potential FusionNeoAntigen Information of ALG8-MAP6 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.
ALG8-MAP6_77850539_75299229.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)
ALG8-MAP6chr1177850539chr1175299229167HLA-A30:08GSVVPGLLK0.94880.72221019
ALG8-MAP6chr1177850539chr1175299229167HLA-B82:01EPDKDQGSVV0.47770.5082414
ALG8-MAP6chr1177850539chr1175299229167HLA-B51:07DQGSVVPGL0.23430.9663817
ALG8-MAP6chr1177850539chr1175299229167HLA-A30:01GSVVPGLLK0.94260.86161019
ALG8-MAP6chr1177850539chr1175299229167HLA-B82:02EPDKDQGSVV0.47770.5082414
ALG8-MAP6chr1177850539chr1175299229167HLA-B39:11DKDQGSVVPGL0.98660.8448617

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Potential FusionNeoAntigen Information of ALG8-MAP6 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 ALG8-MAP6

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
1169DKDQGSVVPGLLKGALG8MAP6chr1177850539chr1175299229167

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of ALG8-MAP6

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-B14:023BVN1169DKDQGSVVPGLLKG-7.9962-8.1096
HLA-B14:023BVN1169DKDQGSVVPGLLKG-5.70842-6.74372
HLA-B52:013W391169DKDQGSVVPGLLKG-6.83737-6.95077
HLA-B52:013W391169DKDQGSVVPGLLKG-4.4836-5.5189
HLA-A11:014UQ21169DKDQGSVVPGLLKG-10.0067-10.1201
HLA-A11:014UQ21169DKDQGSVVPGLLKG-9.03915-10.0745
HLA-A24:025HGA1169DKDQGSVVPGLLKG-6.56204-6.67544
HLA-A24:025HGA1169DKDQGSVVPGLLKG-5.42271-6.45801
HLA-B44:053DX81169DKDQGSVVPGLLKG-7.85648-8.89178
HLA-B44:053DX81169DKDQGSVVPGLLKG-5.3978-5.5112
HLA-A02:016TDR1169DKDQGSVVPGLLKG-3.37154-4.40684

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Vaccine Design for the FusionNeoAntigens of ALG8-MAP6

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
ALG8-MAP6chr1177850539chr11752992291019GSVVPGLLKCCCCACATAGAGCCTGGCTCAACCCGT
ALG8-MAP6chr1177850539chr1175299229414EPDKDQGSVVTCTCAAATGCCTTCTCATCCCCACATAGAG
ALG8-MAP6chr1177850539chr1175299229617DKDQGSVVPGLATGCCTTCTCATCCCCACATAGAGCCTGGCTCA
ALG8-MAP6chr1177850539chr1175299229817DQGSVVPGLTCTCATCCCCACATAGAGCCTGGCTCA

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 ALG8-MAP6

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
LGGALG8-MAP6chr1177850539ENST00000299626chr1175299229ENST00000526740TCGA-FG-8181

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Potential target of CAR-T therapy development for ALG8-MAP6

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
HgeneALG8chr11:77850539chr11:75299229ENST00000299626-1134_2431527.0TransmembraneHelical
HgeneALG8chr11:77850539chr11:75299229ENST00000376156-1144_2431516.6666666666666TransmembraneHelical

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 ALG8-MAP6

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 ALG8-MAP6

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