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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:MLLT6-TCAP

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: MLLT6-TCAP
FusionPDB ID: 54330
FusionGDB2.0 ID: 54330
HgeneTgene
Gene symbol

MLLT6

TCAP

Gene ID

4302

8557

Gene nameMLLT6, PHD finger containingtitin-cap
SynonymsAF17CMD1N|CMH25|LGMD2G|LGMDR7|T-cap|TELE|telethonin
Cytomap

17q12

17q12

Type of geneprotein-codingprotein-coding
Descriptionprotein AF-17ALL1-fused gene from chromosome 17 proteinMLLT6, PHD finger domain containingMyeloid/lymphoid or mixed-lineage leukemia, translocated to, 6myeloid/lymphoid or mixed-lineage leukemia (trithorax homolog); translocated to, 6myeloid/lymphoidtelethonin19 kDa sarcomeric proteinlimb girdle muscular dystrophy 2G (autosomal recessive)teneurin C-terminal associated peptidetitin cap protein
Modification date2020031320200327
UniProtAcc

P55198

Main function of 5'-partner protein:
.
Ensembl transtripts involved in fusion geneENST idsENST00000325718, ENST00000378137, 
ENST00000579179, 
ENST00000309889, 
ENST00000578283, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score11 X 10 X 7=7706 X 6 X 6=216
# samples 108
** MAII scorelog2(10/770*10)=-2.94485844580754
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(8/216*10)=-1.43295940727611
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: MLLT6 [Title/Abstract] AND TCAP [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: MLLT6 [Title/Abstract] AND TCAP [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)MLLT6(36861994)-TCAP(37821626), # samples:2
Anticipated loss of major functional domain due to fusion event.MLLT6-TCAP 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.
MLLT6-TCAP 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.
MLLT6-TCAP seems lost the major protein functional domain in Hgene partner, which is a CGC due to the frame-shifted ORF.
MLLT6-TCAP seems lost the major protein functional domain in Hgene partner, which is a epigenetic factor due to the frame-shifted ORF.
MLLT6-TCAP seems lost the major protein functional domain in Hgene partner, which is a essential gene due to the frame-shifted 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/chr17:36861994/chr17:37821626)
- 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 MLLT6 (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 TCAP (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)
ENST00000378137MLLT6chr1736861994+ENST00000578283TCAPchr1737821626+75820030617195
ENST00000325718MLLT6chr1736861994+ENST00000578283TCAPchr1737821626+75820030617195
ENST00000378137MLLT6chr1736861994+ENST00000309889TCAPchr1737821969+104020030593187
ENST00000325718MLLT6chr1736861994+ENST00000309889TCAPchr1737821969+104020030593187

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
ENST00000378137ENST00000578283MLLT6chr1736861994+TCAPchr1737821626+0.281488060.71851194
ENST00000325718ENST00000578283MLLT6chr1736861994+TCAPchr1737821626+0.281488060.71851194
ENST00000378137ENST00000309889MLLT6chr1736861994+TCAPchr1737821969+0.342868270.65713173
ENST00000325718ENST00000309889MLLT6chr1736861994+TCAPchr1737821969+0.342868270.65713173

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 MLLT6-TCAP

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
MLLT6chr1736861994TCAPchr173782196920055GLLRWARVQRGRPPSCSLHEEDTQRH

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Potential FusionNeoAntigen Information of MLLT6-TCAP 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.
MLLT6-TCAP_36861994_37821969.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)
MLLT6-TCAPchr1736861994chr1737821969200HLA-B07:05RGRPPSCSL0.99890.7407918
MLLT6-TCAPchr1736861994chr1737821969200HLA-B07:10RGRPPSCSL0.99880.7819918
MLLT6-TCAPchr1736861994chr1737821969200HLA-B07:02RGRPPSCSL0.99880.7584918
MLLT6-TCAPchr1736861994chr1737821969200HLA-A30:08RGRPPSCSL0.9130.8047918
MLLT6-TCAPchr1736861994chr1737821969200HLA-B08:09VQRGRPPSC0.42630.8488716
MLLT6-TCAPchr1736861994chr1737821969200HLA-B81:01RGRPPSCSL0.41870.7848918
MLLT6-TCAPchr1736861994chr1737821969200HLA-B07:10QRGRPPSCSL0.92870.7732818
MLLT6-TCAPchr1736861994chr1737821969200HLA-B48:01VQRGRPPSCSL0.9580.7917718
MLLT6-TCAPchr1736861994chr1737821969200HLA-C07:29GRPPSCSL0.98760.97161018
MLLT6-TCAPchr1736861994chr1737821969200HLA-B07:12RGRPPSCSL0.99320.8417918
MLLT6-TCAPchr1736861994chr1737821969200HLA-B07:04RGRPPSCSL0.97980.7059918
MLLT6-TCAPchr1736861994chr1737821969200HLA-B42:02RGRPPSCSL0.79760.7506918
MLLT6-TCAPchr1736861994chr1737821969200HLA-B15:04VQRGRPPSCSL0.99710.7837718
MLLT6-TCAPchr1736861994chr1737821969200HLA-B07:13RGRPPSCSL0.99930.9536918
MLLT6-TCAPchr1736861994chr1737821969200HLA-B07:09RGRPPSCSL0.99920.7569918
MLLT6-TCAPchr1736861994chr1737821969200HLA-B07:22RGRPPSCSL0.99880.7584918
MLLT6-TCAPchr1736861994chr1737821969200HLA-B48:05RGRPPSCSL0.99880.6616918
MLLT6-TCAPchr1736861994chr1737821969200HLA-A30:01RVQRGRPPS0.95570.7459615
MLLT6-TCAPchr1736861994chr1737821969200HLA-A30:01RGRPPSCSL0.91740.9264918
MLLT6-TCAPchr1736861994chr1737821969200HLA-C03:05RGRPPSCSL0.91430.9497918
MLLT6-TCAPchr1736861994chr1737821969200HLA-C03:17RGRPPSCSL0.8650.9793918
MLLT6-TCAPchr1736861994chr1737821969200HLA-B07:26RGRPPSCSL0.7660.6157918
MLLT6-TCAPchr1736861994chr1737821969200HLA-B27:06QRGRPPSCSL0.99890.6327818
MLLT6-TCAPchr1736861994chr1737821969200HLA-B15:73VQRGRPPSCSL0.99870.9061718
MLLT6-TCAPchr1736861994chr1737821969200HLA-B15:30VQRGRPPSCSL0.99790.8634718

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Potential FusionNeoAntigen Information of MLLT6-TCAP 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 MLLT6-TCAP

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
8327RVQRGRPPSCSLHEMLLT6TCAPchr1736861994chr1737821969200

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of MLLT6-TCAP

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-B14:023BVN8327RVQRGRPPSCSLHE-7.15543-7.26883
HLA-B14:023BVN8327RVQRGRPPSCSLHE-4.77435-5.80965
HLA-B52:013W398327RVQRGRPPSCSLHE-6.80875-6.92215
HLA-B52:013W398327RVQRGRPPSCSLHE-4.20386-5.23916
HLA-A11:014UQ28327RVQRGRPPSCSLHE-7.5194-8.5547
HLA-A11:014UQ28327RVQRGRPPSCSLHE-6.9601-7.0735
HLA-A24:025HGA8327RVQRGRPPSCSLHE-7.52403-7.63743
HLA-A24:025HGA8327RVQRGRPPSCSLHE-5.82433-6.85963
HLA-B27:056PYJ8327RVQRGRPPSCSLHE-3.28285-4.31815
HLA-B44:053DX88327RVQRGRPPSCSLHE-5.91172-6.94702
HLA-B44:053DX88327RVQRGRPPSCSLHE-4.24346-4.35686

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Vaccine Design for the FusionNeoAntigens of MLLT6-TCAP

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
MLLT6-TCAPchr1736861994chr17378219691018GRPPSCSLTCCACCAAGCTGCTCCCTGCATGA
MLLT6-TCAPchr1736861994chr1737821969615RVQRGRPPSGCAGCGTGGTCGTCCACCAAGCTGCTC
MLLT6-TCAPchr1736861994chr1737821969716VQRGRPPSCGCGTGGTCGTCCACCAAGCTGCTCCCT
MLLT6-TCAPchr1736861994chr1737821969718VQRGRPPSCSLGCGTGGTCGTCCACCAAGCTGCTCCCTGCATGA
MLLT6-TCAPchr1736861994chr1737821969818QRGRPPSCSLTGGTCGTCCACCAAGCTGCTCCCTGCATGA
MLLT6-TCAPchr1736861994chr1737821969918RGRPPSCSLTCGTCCACCAAGCTGCTCCCTGCATGA

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 MLLT6-TCAP

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
BLCAMLLT6-TCAPchr1736861994ENST00000325718chr1737821969ENST00000309889TCGA-ZF-AA4T-01A

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Potential target of CAR-T therapy development for MLLT6-TCAP

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 MLLT6-TCAP

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 MLLT6-TCAP

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