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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:MAX-APOC1

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: MAX-APOC1
FusionPDB ID: 51936
FusionGDB2.0 ID: 51936
HgeneTgene
Gene symbol

MAX

APOC1

Gene ID

4149

341

Gene nameMYC associated factor Xapolipoprotein C1
SynonymsbHLHd4Apo-CI|ApoC-I|apo-CIB|apoC-IB
Cytomap

14q23.3

19q13.32

Type of geneprotein-codingprotein-coding
Descriptionprotein maxclass D basic helix-loop-helix protein 4apolipoprotein C-I
Modification date2020031320200313
UniProtAcc

P61244

Main function of 5'-partner protein: FUNCTION: Transcription regulator. Forms a sequence-specific DNA-binding protein complex with MYC or MAD which recognizes the core sequence 5'-CAC[GA]TG-3'. The MYC:MAX complex is a transcriptional activator, whereas the MAD:MAX complex is a repressor. May repress transcription via the recruitment of a chromatin remodeling complex containing H3 'Lys-9' histone methyltransferase activity. Represses MYC transcriptional activity from E-box elements. {ECO:0000269|PubMed:26070438}.

P02654

Main function of 5'-partner protein: FUNCTION: Inhibitor of lipoprotein binding to the low density lipoprotein (LDL) receptor, LDL receptor-related protein, and very low density lipoprotein (VLDL) receptor. Associates with high density lipoproteins (HDL) and the triacylglycerol-rich lipoproteins in the plasma and makes up about 10% of the protein of the VLDL and 2% of that of HDL. Appears to interfere directly with fatty acid uptake and is also the major plasma inhibitor of cholesteryl ester transfer protein (CETP). Binds free fatty acids and reduces their intracellular esterification. Modulates the interaction of APOE with beta-migrating VLDL and inhibits binding of beta-VLDL to the LDL receptor-related protein. {ECO:0000269|PubMed:17339654, ECO:0000303|PubMed:25160599}.
Ensembl transtripts involved in fusion geneENST idsENST00000358402, ENST00000358664, 
ENST00000555419, ENST00000555667, 
ENST00000556979, ENST00000557277, 
ENST00000557746, ENST00000246163, 
ENST00000284165, ENST00000341653, 
ENST00000555932, ENST00000556443, 
ENST00000586638, ENST00000589781, 
ENST00000252491, ENST00000588750, 
ENST00000588802, ENST00000592885, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score6 X 4 X 6=1444 X 5 X 3=60
# samples 65
** MAII scorelog2(6/144*10)=-1.26303440583379
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(5/60*10)=-0.263034405833794
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: MAX [Title/Abstract] AND APOC1 [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: MAX [Title/Abstract] AND APOC1 [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)MAX(65544631)-APOC1(45419447), # samples:1
Anticipated loss of major functional domain due to fusion event.MAX-APOC1 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.
MAX-APOC1 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.
MAX-APOC1 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.
MAX-APOC1 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.
MAX-APOC1 seems lost the major protein functional domain in Hgene partner, which is a CGC due to the frame-shifted ORF.
MAX-APOC1 seems lost the major protein functional domain in Hgene partner, which is a epigenetic factor due to the frame-shifted ORF.
MAX-APOC1 seems lost the major protein functional domain in Hgene partner, which is a transcription factor due to the frame-shifted ORF.
MAX-APOC1 seems lost the major protein functional domain in Hgene partner, which is a tumor suppressor 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
HgeneMAX

GO:0000122

negative regulation of transcription by RNA polymerase II

8521822

TgeneAPOC1

GO:0010900

negative regulation of phosphatidylcholine catabolic process

2302419

TgeneAPOC1

GO:0010916

negative regulation of very-low-density lipoprotein particle clearance

1917954

TgeneAPOC1

GO:0032375

negative regulation of cholesterol transport

10978346

TgeneAPOC1

GO:0033344

cholesterol efflux

11162594

TgeneAPOC1

GO:0033700

phospholipid efflux

11162594

TgeneAPOC1

GO:0034369

plasma lipoprotein particle remodeling

10978346

TgeneAPOC1

GO:0034382

chylomicron remnant clearance

4020294

TgeneAPOC1

GO:0045717

negative regulation of fatty acid biosynthetic process

15576844

TgeneAPOC1

GO:0045833

negative regulation of lipid metabolic process

182536

TgeneAPOC1

GO:0048261

negative regulation of receptor-mediated endocytosis

1917954

TgeneAPOC1

GO:0050995

negative regulation of lipid catabolic process

15576844

TgeneAPOC1

GO:0051005

negative regulation of lipoprotein lipase activity

15576844



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/chr14:65544631/chr19:45419447)
- 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 MAX (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 APOC1 (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)
ENST00000358402MAXchr1465544631-ENST00000588750APOC1chr1945419447+739433165626153
ENST00000358402MAXchr1465544631-ENST00000588802APOC1chr1945419447+743433165626153
ENST00000358402MAXchr1465544631-ENST00000252491APOC1chr1945419447+746433165626153
ENST00000358402MAXchr1465544631-ENST00000592885APOC1chr1945419447+886433165764199
ENST00000358664MAXchr1465544631-ENST00000588750APOC1chr1945419447+732426131619162
ENST00000358664MAXchr1465544631-ENST00000588802APOC1chr1945419447+736426131619162
ENST00000358664MAXchr1465544631-ENST00000252491APOC1chr1945419447+739426131619162
ENST00000358664MAXchr1465544631-ENST00000592885APOC1chr1945419447+879426131757208
ENST00000555419MAXchr1465544631-ENST00000588750APOC1chr1945419447+4931870380126
ENST00000555419MAXchr1465544631-ENST00000588802APOC1chr1945419447+4971870380126
ENST00000555419MAXchr1465544631-ENST00000252491APOC1chr1945419447+5001870380126
ENST00000555419MAXchr1465544631-ENST00000592885APOC1chr1945419447+6401870518172
ENST00000556979MAXchr1465544631-ENST00000588750APOC1chr1945419447+779473178666162
ENST00000556979MAXchr1465544631-ENST00000588802APOC1chr1945419447+783473178666162
ENST00000556979MAXchr1465544631-ENST00000252491APOC1chr1945419447+786473178666162
ENST00000556979MAXchr1465544631-ENST00000592885APOC1chr1945419447+926473178804208
ENST00000555667MAXchr1465544631-ENST00000588750APOC1chr1945419447+752446178639153
ENST00000555667MAXchr1465544631-ENST00000588802APOC1chr1945419447+756446178639153
ENST00000555667MAXchr1465544631-ENST00000252491APOC1chr1945419447+759446178639153
ENST00000555667MAXchr1465544631-ENST00000592885APOC1chr1945419447+899446178777199
ENST00000557746MAXchr1465544631-ENST00000588750APOC1chr1945419447+752446178639153
ENST00000557746MAXchr1465544631-ENST00000588802APOC1chr1945419447+756446178639153
ENST00000557746MAXchr1465544631-ENST00000252491APOC1chr1945419447+759446178639153
ENST00000557746MAXchr1465544631-ENST00000592885APOC1chr1945419447+899446178777199

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
ENST00000358402ENST00000588750MAXchr1465544631-APOC1chr1945419447+0.0163818520.9836181
ENST00000358402ENST00000588802MAXchr1465544631-APOC1chr1945419447+0.016171630.9838284
ENST00000358402ENST00000252491MAXchr1465544631-APOC1chr1945419447+0.0169031660.98309684
ENST00000358402ENST00000592885MAXchr1465544631-APOC1chr1945419447+0.0076141160.99238586
ENST00000358664ENST00000588750MAXchr1465544631-APOC1chr1945419447+0.0139890040.986011
ENST00000358664ENST00000588802MAXchr1465544631-APOC1chr1945419447+0.0140232090.9859768
ENST00000358664ENST00000252491MAXchr1465544631-APOC1chr1945419447+0.0145983330.98540163
ENST00000358664ENST00000592885MAXchr1465544631-APOC1chr1945419447+0.0088240990.9911759
ENST00000555419ENST00000588750MAXchr1465544631-APOC1chr1945419447+0.018406650.9815933
ENST00000555419ENST00000588802MAXchr1465544631-APOC1chr1945419447+0.0194779910.98052204
ENST00000555419ENST00000252491MAXchr1465544631-APOC1chr1945419447+0.0200660020.979934
ENST00000555419ENST00000592885MAXchr1465544631-APOC1chr1945419447+0.0056951610.99430484
ENST00000556979ENST00000588750MAXchr1465544631-APOC1chr1945419447+0.019228990.980771
ENST00000556979ENST00000588802MAXchr1465544631-APOC1chr1945419447+0.0187831150.9812169
ENST00000556979ENST00000252491MAXchr1465544631-APOC1chr1945419447+0.0198647510.98013526
ENST00000556979ENST00000592885MAXchr1465544631-APOC1chr1945419447+0.0111855030.98881453
ENST00000555667ENST00000588750MAXchr1465544631-APOC1chr1945419447+0.0177788340.9822212
ENST00000555667ENST00000588802MAXchr1465544631-APOC1chr1945419447+0.017662970.982337
ENST00000555667ENST00000252491MAXchr1465544631-APOC1chr1945419447+0.0183325970.9816674
ENST00000555667ENST00000592885MAXchr1465544631-APOC1chr1945419447+0.0077102440.9922897
ENST00000557746ENST00000588750MAXchr1465544631-APOC1chr1945419447+0.0177788340.9822212
ENST00000557746ENST00000588802MAXchr1465544631-APOC1chr1945419447+0.017662970.982337
ENST00000557746ENST00000252491MAXchr1465544631-APOC1chr1945419447+0.0183325970.9816674
ENST00000557746ENST00000592885MAXchr1465544631-APOC1chr1945419447+0.0077102440.9922897

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 MAX-APOC1

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
MAXchr1465544631APOC1chr194541944718762DDLKRQNALLEQQGPAPAQGTPDVSS
MAXchr1465544631APOC1chr194541944742698DDLKRQNALLEQQGPAPAQGTPDVSS
MAXchr1465544631APOC1chr194541944743389DDLKRQNALLEQQGPAPAQGTPDVSS
MAXchr1465544631APOC1chr194541944744689DDLKRQNALLEQQGPAPAQGTPDVSS
MAXchr1465544631APOC1chr194541944747398DDLKRQNALLEQQGPAPAQGTPDVSS

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Potential FusionNeoAntigen Information of MAX-APOC1 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.
MAX-APOC1_65544631_45419447.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)
MAX-APOC1chr1465544631chr1945419447433HLA-B45:01LEQQGPAPA0.99390.9945918
MAX-APOC1chr1465544631chr1945419447433HLA-B50:02LEQQGPAPA0.98990.8435918
MAX-APOC1chr1465544631chr1945419447433HLA-B50:01LEQQGPAPA0.84550.9668918
MAX-APOC1chr1465544631chr1945419447433HLA-B41:01LEQQGPAPA0.64360.9942918
MAX-APOC1chr1465544631chr1945419447433HLA-B45:01ALLEQQGPAPA0.92720.998718
MAX-APOC1chr1465544631chr1945419447433HLA-B41:01ALLEQQGPAPA0.86820.9938718
MAX-APOC1chr1465544631chr1945419447433HLA-B50:02ALLEQQGPAPA0.85850.9379718
MAX-APOC1chr1465544631chr1945419447433HLA-B40:06LEQQGPAPA0.99830.9821918
MAX-APOC1chr1465544631chr1945419447433HLA-B50:04LEQQGPAPA0.84550.9668918
MAX-APOC1chr1465544631chr1945419447433HLA-B50:05LEQQGPAPA0.84550.9668918

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Potential FusionNeoAntigen Information of MAX-APOC1 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 MAX-APOC1

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
6083NALLEQQGPAPAQGMAXAPOC1chr1465544631chr1945419447433

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of MAX-APOC1

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-B52:013W396083NALLEQQGPAPAQG-5.65082-5.65082
HLA-B44:053DX86083NALLEQQGPAPAQG-5.99276-5.99276
HLA-A02:016TDR6083NALLEQQGPAPAQG-3.84642-3.84642

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Vaccine Design for the FusionNeoAntigens of MAX-APOC1

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
MAX-APOC1chr1465544631chr1945419447718ALLEQQGPAPACTCTTCTGGAGCAGCAAGGCCCAGCCCCAGCCC
MAX-APOC1chr1465544631chr1945419447918LEQQGPAPATGGAGCAGCAAGGCCCAGCCCCAGCCC

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 MAX-APOC1

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
GBMMAX-APOC1chr1465544631ENST00000358402chr1945419447ENST00000252491TCGA-06-5411-01A

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Potential target of CAR-T therapy development for MAX-APOC1

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 MAX-APOC1

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 MAX-APOC1

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