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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:CMTR1-ATG4B

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: CMTR1-ATG4B
FusionPDB ID: 17595
FusionGDB2.0 ID: 17595
HgeneTgene
Gene symbol

CMTR1

ATG4B

Gene ID

23070

23192

Gene namecap methyltransferase 1autophagy related 4B cysteine peptidase
SynonymsFTSJD2|KIAA0082|MTr1|hMTr1APG4B|AUTL1
Cytomap

6p21.2

2q37.3

Type of geneprotein-codingprotein-coding
Descriptioncap-specific mRNA (nucleoside-2'-O-)-methyltransferase 1FtsJ methyltransferase domain containing 2ISG95S-adenosyl-L-methionine-dependent methyltransferase FTSJD2cap1 2'O-ribose methyltransferase 1ftsJ methyltransferase domain-containing protein 2intcysteine protease ATG4BAPG4 autophagy 4 homolog BATG4 autophagy related 4 homolog BAUT-like 1 cysteine endopeptidaseautophagin-1autophagy-related cysteine endopeptidase 1autophagy-related protein 4 homolog BhAPG4B
Modification date2020031320200329
UniProtAcc

Q8N1G2

Main function of 5'-partner protein: FUNCTION: S-adenosyl-L-methionine-dependent methyltransferase that mediates mRNA cap1 2'-O-ribose methylation to the 5'-cap structure of mRNAs. Methylates the ribose of the first nucleotide of a m(7)GpppG-capped mRNA and small nuclear RNA (snRNA) to produce m(7)GpppRm (cap1). Displays a preference for cap0 transcripts. Cap1 modification is linked to higher levels of translation. May be involved in the interferon response pathway. {ECO:0000269|PubMed:18533109, ECO:0000269|PubMed:20713356, ECO:0000269|PubMed:21310715}.

Q9Y4P1

Main function of 5'-partner protein: FUNCTION: Cysteine protease required for the cytoplasm to vacuole transport (Cvt) and autophagy. Cleaves the C-terminal amino acid of ATG8 family proteins MAP1LC3, GABARAPL1, GABARAPL2 and GABARAP, to reveal a C-terminal glycine. Exposure of the glycine at the C-terminus is essential for ATG8 proteins conjugation to phosphatidylethanolamine (PE) and insertion to membranes, which is necessary for autophagy. Has also an activity of delipidating enzyme for the PE-conjugated forms. {ECO:0000269|PubMed:15169837, ECO:0000269|PubMed:15187094, ECO:0000269|PubMed:17347651, ECO:0000269|PubMed:19322194, ECO:0000269|PubMed:21177865, ECO:0000269|PubMed:22302004}.
Ensembl transtripts involved in fusion geneENST idsENST00000493656, ENST00000373451, 
ENST00000402096, ENST00000404914, 
ENST00000405546, ENST00000396411, 
ENST00000474739, ENST00000491867, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score6 X 6 X 6=2164 X 4 X 3=48
# samples 65
** MAII scorelog2(6/216*10)=-1.84799690655495
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: CMTR1 [Title/Abstract] AND ATG4B [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: CMTR1 [Title/Abstract] AND ATG4B [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)CMTR1(37429421)-ATG4B(242594686), # samples:1
Anticipated loss of major functional domain due to fusion event.CMTR1-ATG4B 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.
CMTR1-ATG4B 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.
CMTR1-ATG4B 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.
CMTR1-ATG4B 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
HgeneCMTR1

GO:0006370

7-methylguanosine mRNA capping

21310715

HgeneCMTR1

GO:0080009

mRNA methylation

20713356

HgeneCMTR1

GO:0097309

cap1 mRNA methylation

21310715

TgeneATG4B

GO:0006508

proteolysis

15169837|18387192

TgeneATG4B

GO:0006914

autophagy

18387192

TgeneATG4B

GO:0051697

protein delipidation

25327288



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/chr6:37429421/chr2:242594686)
- 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 CMTR1 (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 ATG4B (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)
ENST00000373451CMTR1chr637429421+ENST00000405546ATG4Bchr2242594686+37631356502113687
ENST00000373451CMTR1chr637429421+ENST00000402096ATG4Bchr2242594686+25531356502188712
ENST00000373451CMTR1chr637429421+ENST00000404914ATG4Bchr2242594686+37461356502152700

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
ENST00000373451ENST00000405546CMTR1chr637429421+ATG4Bchr2242594686+0.0021023490.9978976
ENST00000373451ENST00000402096CMTR1chr637429421+ATG4Bchr2242594686+0.0038638020.9961361
ENST00000373451ENST00000404914CMTR1chr637429421+ATG4Bchr2242594686+0.0020847380.9979152

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 CMTR1-ATG4B

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
CMTR1chr637429421ATG4Bchr22425946861356435LCQFLMALSIVRTAQMGVGEGKSIGQ

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Potential FusionNeoAntigen Information of CMTR1-ATG4B 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.
CMTR1-ATG4B_37429421_242594686.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)
CMTR1-ATG4Bchr637429421chr22425946861356HLA-B15:17LSIVRTAQM0.9950.7011716
CMTR1-ATG4Bchr637429421chr22425946861356HLA-B15:16LSIVRTAQM0.9920.5036716
CMTR1-ATG4Bchr637429421chr22425946861356HLA-B08:09MALSIVRTA0.97180.7439514
CMTR1-ATG4Bchr637429421chr22425946861356HLA-A30:08IVRTAQMGV0.94340.8804918
CMTR1-ATG4Bchr637429421chr22425946861356HLA-C03:08LSIVRTAQM0.99950.7712716
CMTR1-ATG4Bchr637429421chr22425946861356HLA-C15:04LSIVRTAQM0.99940.726716
CMTR1-ATG4Bchr637429421chr22425946861356HLA-C03:19LSIVRTAQM0.99910.9778716
CMTR1-ATG4Bchr637429421chr22425946861356HLA-C03:07LSIVRTAQM0.99870.9002716
CMTR1-ATG4Bchr637429421chr22425946861356HLA-C12:12LSIVRTAQM0.99780.8439716
CMTR1-ATG4Bchr637429421chr22425946861356HLA-C15:06LSIVRTAQM0.99740.7124716
CMTR1-ATG4Bchr637429421chr22425946861356HLA-C12:04LSIVRTAQM0.99140.9853716
CMTR1-ATG4Bchr637429421chr22425946861356HLA-C06:03LSIVRTAQM0.99130.9804716
CMTR1-ATG4Bchr637429421chr22425946861356HLA-B78:01MALSIVRTA0.95770.5954514
CMTR1-ATG4Bchr637429421chr22425946861356HLA-C03:03LSIVRTAQM0.99950.9768716
CMTR1-ATG4Bchr637429421chr22425946861356HLA-C03:04LSIVRTAQM0.99950.9768716
CMTR1-ATG4Bchr637429421chr22425946861356HLA-C15:09LSIVRTAQM0.99940.726716
CMTR1-ATG4Bchr637429421chr22425946861356HLA-C03:05LSIVRTAQM0.99930.8047716
CMTR1-ATG4Bchr637429421chr22425946861356HLA-C03:02LSIVRTAQM0.99930.935716
CMTR1-ATG4Bchr637429421chr22425946861356HLA-C03:17LSIVRTAQM0.99850.9114716
CMTR1-ATG4Bchr637429421chr22425946861356HLA-C12:03LSIVRTAQM0.99770.9505716
CMTR1-ATG4Bchr637429421chr22425946861356HLA-C16:04LSIVRTAQM0.99560.9475716
CMTR1-ATG4Bchr637429421chr22425946861356HLA-C15:05LSIVRTAQM0.99540.7413716
CMTR1-ATG4Bchr637429421chr22425946861356HLA-C15:02LSIVRTAQM0.99270.6917716
CMTR1-ATG4Bchr637429421chr22425946861356HLA-B56:05MALSIVRTA0.98980.5534514
CMTR1-ATG4Bchr637429421chr22425946861356HLA-C12:03MALSIVRTA0.98590.9633514
CMTR1-ATG4Bchr637429421chr22425946861356HLA-B78:02MALSIVRTA0.95830.6537514
CMTR1-ATG4Bchr637429421chr22425946861356HLA-A30:01IVRTAQMGV0.95130.943918
CMTR1-ATG4Bchr637429421chr22425946861356HLA-C16:01LSIVRTAQM0.92040.9635716
CMTR1-ATG4Bchr637429421chr22425946861356HLA-B51:09MALSIVRTA0.90620.5195514
CMTR1-ATG4Bchr637429421chr22425946861356HLA-C16:02LSIVRTAQM0.84970.9811716

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Potential FusionNeoAntigen Information of CMTR1-ATG4B 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 CMTR1-ATG4B

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
408ALSIVRTAQMGVGECMTR1ATG4Bchr637429421chr22425946861356

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of CMTR1-ATG4B

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-B53:011A1O408ALSIVRTAQMGVGE-1.54455-2.57985
HLA-B51:011E28408ALSIVRTAQMGVGE-3.9567-4.992
HLA-B51:011E28408ALSIVRTAQMGVGE-2.78017-2.89357
HLA-B57:032BVO408ALSIVRTAQMGVGE-2.28399-2.39739
HLA-A03:012XPG408ALSIVRTAQMGVGE-5.29375-6.32905
HLA-A03:012XPG408ALSIVRTAQMGVGE-5.13376-5.24716
HLA-B14:023BVN408ALSIVRTAQMGVGE-5.94457-6.05797
HLA-B14:023BVN408ALSIVRTAQMGVGE-4.02623-5.06153
HLA-B27:093CZF408ALSIVRTAQMGVGE1.938620.90332
HLA-B52:013W39408ALSIVRTAQMGVGE-4.85197-4.96537
HLA-B52:013W39408ALSIVRTAQMGVGE-3.54046-4.57576
HLA-B18:014JQV408ALSIVRTAQMGVGE-2.48822-2.60162
HLA-B18:014JQV408ALSIVRTAQMGVGE-1.14207-2.17737
HLA-A11:014UQ2408ALSIVRTAQMGVGE-7.94504-8.05844
HLA-A11:014UQ2408ALSIVRTAQMGVGE-6.28371-7.31901
HLA-A24:025HGA408ALSIVRTAQMGVGE-5.26524-5.37864
HLA-A24:025HGA408ALSIVRTAQMGVGE-5.08104-6.11634
HLA-B57:015VUD408ALSIVRTAQMGVGE-1.4053-2.4406
HLA-C08:026JTP408ALSIVRTAQMGVGE-3.55917-3.67257
HLA-C08:026JTP408ALSIVRTAQMGVGE-2.30839-3.34369
HLA-B27:056PYJ408ALSIVRTAQMGVGE-3.69179-4.72709
HLA-B27:056PYJ408ALSIVRTAQMGVGE-2.46172-2.57512
HLA-B27:036PZ5408ALSIVRTAQMGVGE-2.34314-3.37844
HLA-B27:036PZ5408ALSIVRTAQMGVGE-1.78038-1.89378
HLA-B44:053DX8408ALSIVRTAQMGVGE-5.34386-5.45726
HLA-B44:053DX8408ALSIVRTAQMGVGE-3.58277-4.61807
HLA-B44:021M6O408ALSIVRTAQMGVGE-2.22341-2.33681
HLA-B44:021M6O408ALSIVRTAQMGVGE-1.22324-2.25854
HLA-A02:016TDR408ALSIVRTAQMGVGE-5.40572-5.51912
HLA-A02:016TDR408ALSIVRTAQMGVGE-3.93841-4.97371

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Vaccine Design for the FusionNeoAntigens of CMTR1-ATG4B

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
CMTR1-ATG4Bchr637429421chr2242594686514MALSIVRTATGGCGCTGTCCATTGTCCGGACAGCGC
CMTR1-ATG4Bchr637429421chr2242594686716LSIVRTAQMTGTCCATTGTCCGGACAGCGCAAATGG
CMTR1-ATG4Bchr637429421chr2242594686918IVRTAQMGVTTGTCCGGACAGCGCAAATGGGAGTTG

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 CMTR1-ATG4B

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
STADCMTR1-ATG4Bchr637429421ENST00000373451chr2242594686ENST00000402096TCGA-BR-8078-01A

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Potential target of CAR-T therapy development for CMTR1-ATG4B

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 CMTR1-ATG4B

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 CMTR1-ATG4B

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