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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:MTAP-EXOC6B

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: MTAP-EXOC6B
FusionPDB ID: 55507
FusionGDB2.0 ID: 55507
HgeneTgene
Gene symbol

MTAP

EXOC6B

Gene ID

4507

23233

Gene namemethylthioadenosine phosphorylaseexocyst complex component 6B
SynonymsBDMF|DMSFH|DMSMFH|HEL-249|LGMBF|MSAP|c86fusSEC15B|SEC15L2|SEMDJL3
Cytomap

9p21.3

2p13.2

Type of geneprotein-codingprotein-coding
DescriptionS-methyl-5'-thioadenosine phosphorylase5'-methylthioadenosine phosphorylaseMTA phosphorylaseMTAPaseMeSAdo phosphorylaseepididymis luminal protein 249epididymis secretory sperm binding proteinexocyst complex component 6BSEC15 homolog BSEC15-like protein 2exocyst complex component Sec15B
Modification date2020031320200313
UniProtAcc

Q13126

Main function of 5'-partner protein: FUNCTION: Catalyzes the reversible phosphorylation of S-methyl-5'-thioadenosine (MTA) to adenine and 5-methylthioribose-1-phosphate. Involved in the breakdown of MTA, a major by-product of polyamine biosynthesis. Responsible for the first step in the methionine salvage pathway after MTA has been generated from S-adenosylmethionine. Has broad substrate specificity with 6-aminopurine nucleosides as preferred substrates. {ECO:0000255|HAMAP-Rule:MF_03155, ECO:0000269|PubMed:3091600}.

Q9Y2D4

Main function of 5'-partner protein: FUNCTION: Component of the exocyst complex involved in the docking of exocytic vesicles with fusion sites on the plasma membrane.
Ensembl transtripts involved in fusion geneENST idsENST00000380172, ENST00000460874, 
ENST00000580900, ENST00000427788, 
ENST00000410104, ENST00000490919, 
ENST00000272427, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score13 X 9 X 9=105310 X 8 X 6=480
# samples 1711
** MAII scorelog2(17/1053*10)=-2.63089878488802
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(11/480*10)=-2.12553088208386
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: MTAP [Title/Abstract] AND EXOC6B [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: MTAP [Title/Abstract] AND EXOC6B [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)MTAP(21854869)-EXOC6B(72606999), # samples:1
Anticipated loss of major functional domain due to fusion event.MTAP-EXOC6B 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.
MTAP-EXOC6B 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
HgeneMTAP

GO:0006738

nicotinamide riboside catabolic process

19001417



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/chr9:21854869/chr2:72606999)
- 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 MTAP (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 EXOC6B (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)
ENST00000580900MTAPchr921854869-ENST00000272427EXOC6Bchr272606999-45977901001245381
ENST00000380172MTAPchr921854869-ENST00000272427EXOC6Bchr272606999-47038962061351381
ENST00000460874MTAPchr921854869-ENST00000272427EXOC6Bchr272606999-47739661741421415

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
ENST00000580900ENST00000272427MTAPchr921854869-EXOC6Bchr272606999-0.0041435940.99585634
ENST00000380172ENST00000272427MTAPchr921854869-EXOC6Bchr272606999-0.004313060.99568695
ENST00000460874ENST00000272427MTAPchr921854869-EXOC6Bchr272606999-0.0010874740.9989126

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 MTAP-EXOC6B

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
MTAPchr921854869EXOC6Bchr272606999790230ATDYDCWKEHEEAGKVAQTACMSACK
MTAPchr921854869EXOC6Bchr272606999896230ATDYDCWKEHEEAGKVAQTACMSACK
MTAPchr921854869EXOC6Bchr272606999966264ATDYDCWKEHEEAGKVAQTACMSACK

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Potential FusionNeoAntigen Information of MTAP-EXOC6B 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.
MTAP-EXOC6B_21854869_72606999.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)
MTAP-EXOC6Bchr921854869chr272606999896HLA-B50:02HEEAGKVA0.99930.8095917
MTAP-EXOC6Bchr921854869chr272606999896HLA-B41:01HEEAGKVA0.98850.9785917
MTAP-EXOC6Bchr921854869chr272606999896HLA-B50:01HEEAGKVA0.97430.9676917
MTAP-EXOC6Bchr921854869chr272606999896HLA-B45:01KEHEEAGKV0.99650.8665716
MTAP-EXOC6Bchr921854869chr272606999896HLA-B50:02KEHEEAGKV0.9950.7603716
MTAP-EXOC6Bchr921854869chr272606999896HLA-B45:01EEAGKVAQT0.98940.93021019
MTAP-EXOC6Bchr921854869chr272606999896HLA-B39:01EHEEAGKVA0.98170.9798817
MTAP-EXOC6Bchr921854869chr272606999896HLA-B50:02EEAGKVAQT0.97770.73611019
MTAP-EXOC6Bchr921854869chr272606999896HLA-B39:06EHEEAGKVA0.96780.9718817
MTAP-EXOC6Bchr921854869chr272606999896HLA-B15:37EHEEAGKVA0.41460.8125817
MTAP-EXOC6Bchr921854869chr272606999896HLA-B41:01KEHEEAGKV0.40710.9553716
MTAP-EXOC6Bchr921854869chr272606999896HLA-B50:01KEHEEAGKV0.25030.8193716
MTAP-EXOC6Bchr921854869chr272606999896HLA-B39:13KEHEEAGKV0.13590.9767716
MTAP-EXOC6Bchr921854869chr272606999896HLA-B45:01EEAGKVAQTA0.99710.9691020
MTAP-EXOC6Bchr921854869chr272606999896HLA-B45:01KEHEEAGKVA0.99250.8437717
MTAP-EXOC6Bchr921854869chr272606999896HLA-B50:02EEAGKVAQTA0.990.81771020
MTAP-EXOC6Bchr921854869chr272606999896HLA-B50:02KEHEEAGKVA0.98910.8034717
MTAP-EXOC6Bchr921854869chr272606999896HLA-B41:01EEAGKVAQTA0.92920.92551020
MTAP-EXOC6Bchr921854869chr272606999896HLA-B41:01KEHEEAGKVA0.90380.9535717
MTAP-EXOC6Bchr921854869chr272606999896HLA-B50:01KEHEEAGKVA0.83680.9238717
MTAP-EXOC6Bchr921854869chr272606999896HLA-B45:01HEEAGKVAQTA0.99950.9846920
MTAP-EXOC6Bchr921854869chr272606999896HLA-B50:02HEEAGKVAQTA0.99930.9107920
MTAP-EXOC6Bchr921854869chr272606999896HLA-B41:01HEEAGKVAQTA0.9990.9702920
MTAP-EXOC6Bchr921854869chr272606999896HLA-B40:06KEHEEAGKV0.99950.7359716
MTAP-EXOC6Bchr921854869chr272606999896HLA-B39:05EHEEAGKVA0.95970.9774817
MTAP-EXOC6Bchr921854869chr272606999896HLA-B54:01EAGKVAQTA0.95870.80251120
MTAP-EXOC6Bchr921854869chr272606999896HLA-B39:08KEHEEAGKV0.30610.927716
MTAP-EXOC6Bchr921854869chr272606999896HLA-B40:06KEHEEAGKVA0.9970.7632717
MTAP-EXOC6Bchr921854869chr272606999896HLA-B50:05HEEAGKVA0.97430.9676917
MTAP-EXOC6Bchr921854869chr272606999896HLA-B50:04HEEAGKVA0.97430.9676917
MTAP-EXOC6Bchr921854869chr272606999896HLA-B40:04KEHEEAGKV0.99550.8033716
MTAP-EXOC6Bchr921854869chr272606999896HLA-B39:31EHEEAGKVA0.98250.9795817
MTAP-EXOC6Bchr921854869chr272606999896HLA-B15:09EHEEAGKVA0.75070.7854817
MTAP-EXOC6Bchr921854869chr272606999896HLA-B39:11EHEEAGKVA0.53580.9084817
MTAP-EXOC6Bchr921854869chr272606999896HLA-B41:03KEHEEAGKV0.46220.6373716
MTAP-EXOC6Bchr921854869chr272606999896HLA-B50:05KEHEEAGKV0.25030.8193716
MTAP-EXOC6Bchr921854869chr272606999896HLA-B50:04KEHEEAGKV0.25030.8193716
MTAP-EXOC6Bchr921854869chr272606999896HLA-B50:05KEHEEAGKVA0.83680.9238717
MTAP-EXOC6Bchr921854869chr272606999896HLA-B50:04KEHEEAGKVA0.83680.9238717

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Potential FusionNeoAntigen Information of MTAP-EXOC6B 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 MTAP-EXOC6B

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
10488WKEHEEAGKVAQTAMTAPEXOC6Bchr921854869chr272606999896

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of MTAP-EXOC6B

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-B14:023BVN10488WKEHEEAGKVAQTA-7.10743-7.22083
HLA-B14:023BVN10488WKEHEEAGKVAQTA-3.79488-4.83018
HLA-B52:013W3910488WKEHEEAGKVAQTA-6.78681-6.90021
HLA-B52:013W3910488WKEHEEAGKVAQTA-3.75119-4.78649
HLA-A11:014UQ210488WKEHEEAGKVAQTA-10.1888-11.2241
HLA-A11:014UQ210488WKEHEEAGKVAQTA-6.59241-6.70581
HLA-A24:025HGA10488WKEHEEAGKVAQTA-8.29771-9.33301
HLA-A24:025HGA10488WKEHEEAGKVAQTA-8.23185-8.34525
HLA-B44:053DX810488WKEHEEAGKVAQTA-7.25218-7.36558
HLA-B44:053DX810488WKEHEEAGKVAQTA-3.76181-4.79711
HLA-A02:016TDR10488WKEHEEAGKVAQTA-2.73959-3.77489

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Vaccine Design for the FusionNeoAntigens of MTAP-EXOC6B

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
MTAP-EXOC6Bchr921854869chr2726069991019EEAGKVAQTGAGGAAGCAGGAAAGGTGGCCCAGACA
MTAP-EXOC6Bchr921854869chr2726069991020EEAGKVAQTAGAGGAAGCAGGAAAGGTGGCCCAGACAGCG
MTAP-EXOC6Bchr921854869chr2726069991120EAGKVAQTAGAAGCAGGAAAGGTGGCCCAGACAGCG
MTAP-EXOC6Bchr921854869chr272606999716KEHEEAGKVAAGGAGCACGAGGAAGCAGGAAAGGTG
MTAP-EXOC6Bchr921854869chr272606999717KEHEEAGKVAAAGGAGCACGAGGAAGCAGGAAAGGTGGCC
MTAP-EXOC6Bchr921854869chr272606999817EHEEAGKVAGAGCACGAGGAAGCAGGAAAGGTGGCC
MTAP-EXOC6Bchr921854869chr272606999917HEEAGKVACACGAGGAAGCAGGAAAGGTGGCC
MTAP-EXOC6Bchr921854869chr272606999920HEEAGKVAQTACACGAGGAAGCAGGAAAGGTGGCCCAGACAGCG

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 MTAP-EXOC6B

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
LUADMTAP-EXOC6Bchr921854869ENST00000380172chr272606999ENST00000272427TCGA-97-8176-01A

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Potential target of CAR-T therapy development for MTAP-EXOC6B

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 MTAP-EXOC6B

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 MTAP-EXOC6B

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