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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:MCC-PPAP2A

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: MCC-PPAP2A
FusionPDB ID: 52157
FusionGDB2.0 ID: 52157
HgeneTgene
Gene symbol

MCC

PPAP2A

Gene ID

4163

8611

Gene nameMCC regulator of WNT signaling pathwayphospholipid phosphatase 1
SynonymsMCC1LLP1a|LPP1|PAP-2a|PAP2|PPAP2A
Cytomap

5q22.2

5q11.2

Type of geneprotein-codingprotein-coding
Descriptioncolorectal mutant cancer proteinMCC, WNT signaling pathway regulatormutated in colorectal cancersphospholipid phosphatase 1lipid phosphate phosphohydrolase 1aphosphatidate phosphohydrolase type 2aphosphatidic acid phosphatase 2aphosphatidic acid phosphatase type 2Aphosphatidic acid phosphohydrolase type 2atype-2 phosphatidic acid phosphatase al
Modification date2020031320200313
UniProtAcc

Q9HCC0

Main function of 5'-partner protein: FUNCTION: Carboxyltransferase subunit of the 3-methylcrotonyl-CoA carboxylase, an enzyme that catalyzes the conversion of 3-methylcrotonyl-CoA to 3-methylglutaconyl-CoA, a critical step for leucine and isovaleric acid catabolism. {ECO:0000269|PubMed:17360195}.
.
Ensembl transtripts involved in fusion geneENST idsENST00000302475, ENST00000514701, 
ENST00000408903, ENST00000515367, 
ENST00000515132, ENST00000264775, 
ENST00000307259, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score11 X 8 X 5=44010 X 5 X 6=300
# samples 1210
** MAII scorelog2(12/440*10)=-1.87446911791614
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(10/300*10)=-1.58496250072116
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: MCC [Title/Abstract] AND PPAP2A [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: MCC [Title/Abstract] AND PPAP2A [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)MCC(112630026)-PPAP2A(54763977), # samples:1
Anticipated loss of major functional domain due to fusion event.MCC-PPAP2A 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.
MCC-PPAP2A 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.
MCC-PPAP2A 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.
MCC-PPAP2A 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
HgeneMCC

GO:0045184

establishment of protein localization

18591935

HgeneMCC

GO:0050680

negative regulation of epithelial cell proliferation

18591935

HgeneMCC

GO:0090090

negative regulation of canonical Wnt signaling pathway

18591935

TgenePPAP2A

GO:0006644

phospholipid metabolic process

9305923|9705349|15461590

TgenePPAP2A

GO:0006670

sphingosine metabolic process

9705349

TgenePPAP2A

GO:0006672

ceramide metabolic process

9305923|9705349

TgenePPAP2A

GO:0046839

phospholipid dephosphorylation

9305923|9705349|15461590|16464866



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/chr5:112630026/chr5:54763977)
- 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 MCC (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 PPAP2A (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)
ENST00000302475MCCchr5112630026-ENST00000264775PPAP2Achr554763977-16186215641265233
ENST00000302475MCCchr5112630026-ENST00000307259PPAP2Achr554763977-15876215641265233

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
ENST00000302475ENST00000264775MCCchr5112630026-PPAP2Achr554763977-0.0056751170.99432486
ENST00000302475ENST00000307259MCCchr5112630026-PPAP2Achr554763977-0.0059209380.9940791

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 MCC-PPAP2A

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
MCCchr5112630026PPAP2Achr55476397762119MKYGNDSSAELSEIILGETLSVYCNL

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Potential FusionNeoAntigen Information of MCC-PPAP2A 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.
MCC-PPAP2A_112630026_54763977.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)
MCC-PPAP2Achr5112630026chr554763977621HLA-B39:13AELSEIIL0.94270.8793816
MCC-PPAP2Achr5112630026chr554763977621HLA-B13:01SEIILGETL0.99410.85261120
MCC-PPAP2Achr5112630026chr554763977621HLA-B44:03SEIILGETL0.98410.91061120
MCC-PPAP2Achr5112630026chr554763977621HLA-B45:01SEIILGETL0.90260.64031120
MCC-PPAP2Achr5112630026chr554763977621HLA-B47:01SEIILGETL0.89670.52731120
MCC-PPAP2Achr5112630026chr554763977621HLA-B18:01SEIILGETL0.87850.96551120
MCC-PPAP2Achr5112630026chr554763977621HLA-B35:02SAELSEIIL0.71120.9427716
MCC-PPAP2Achr5112630026chr554763977621HLA-B35:04SAELSEIIL0.71120.9427716
MCC-PPAP2Achr5112630026chr554763977621HLA-B39:13SEIILGETL0.50740.88811120
MCC-PPAP2Achr5112630026chr554763977621HLA-B38:02SEIILGETL0.43930.9481120
MCC-PPAP2Achr5112630026chr554763977621HLA-B41:01SEIILGETL0.42720.83551120
MCC-PPAP2Achr5112630026chr554763977621HLA-B50:01SEIILGETL0.3480.65071120
MCC-PPAP2Achr5112630026chr554763977621HLA-B15:02EIILGETLSVY0.99610.8881223
MCC-PPAP2Achr5112630026chr554763977621HLA-B39:08AELSEIIL0.9720.7415816
MCC-PPAP2Achr5112630026chr554763977621HLA-C05:09SAELSEIIL0.99980.9255716
MCC-PPAP2Achr5112630026chr554763977621HLA-C08:15SAELSEIIL0.99960.9538716
MCC-PPAP2Achr5112630026chr554763977621HLA-C08:04SAELSEIIL0.96070.9528716
MCC-PPAP2Achr5112630026chr554763977621HLA-C08:13SAELSEIIL0.96070.9528716
MCC-PPAP2Achr5112630026chr554763977621HLA-C08:03SAELSEIIL0.85040.979716
MCC-PPAP2Achr5112630026chr554763977621HLA-B35:12SAELSEIIL0.71120.9427716
MCC-PPAP2Achr5112630026chr554763977621HLA-B39:08SEIILGETL0.62270.73871120
MCC-PPAP2Achr5112630026chr554763977621HLA-B39:09SEIILGETL0.53970.74481120
MCC-PPAP2Achr5112630026chr554763977621HLA-B39:05SEIILGETL0.44350.93811120
MCC-PPAP2Achr5112630026chr554763977621HLA-B40:04AELSEIIL0.99980.6821816
MCC-PPAP2Achr5112630026chr554763977621HLA-B41:03AELSEIIL0.93990.6367816
MCC-PPAP2Achr5112630026chr554763977621HLA-C04:03SAELSEIIL0.99980.8698716
MCC-PPAP2Achr5112630026chr554763977621HLA-C05:01SAELSEIIL0.99980.9255716
MCC-PPAP2Achr5112630026chr554763977621HLA-C08:02SAELSEIIL0.99960.9538716
MCC-PPAP2Achr5112630026chr554763977621HLA-B40:04SEIILGETL0.99840.64581120
MCC-PPAP2Achr5112630026chr554763977621HLA-B44:26SEIILGETL0.98410.91061120
MCC-PPAP2Achr5112630026chr554763977621HLA-B44:07SEIILGETL0.98410.91061120
MCC-PPAP2Achr5112630026chr554763977621HLA-B44:13SEIILGETL0.98410.91061120
MCC-PPAP2Achr5112630026chr554763977621HLA-B18:04SEIILGETL0.93640.96771120
MCC-PPAP2Achr5112630026chr554763977621HLA-C03:06SAELSEIIL0.92880.9913716
MCC-PPAP2Achr5112630026chr554763977621HLA-B18:07SEIILGETL0.91120.94531120
MCC-PPAP2Achr5112630026chr554763977621HLA-B18:08SEIILGETL0.88490.9441120
MCC-PPAP2Achr5112630026chr554763977621HLA-B18:05SEIILGETL0.87850.96551120
MCC-PPAP2Achr5112630026chr554763977621HLA-B18:06SEIILGETL0.87690.9721120
MCC-PPAP2Achr5112630026chr554763977621HLA-C08:01SAELSEIIL0.85040.979716
MCC-PPAP2Achr5112630026chr554763977621HLA-B35:13SAELSEIIL0.84260.901716
MCC-PPAP2Achr5112630026chr554763977621HLA-B18:03SEIILGETL0.78290.96191120
MCC-PPAP2Achr5112630026chr554763977621HLA-B35:09SAELSEIIL0.71120.9427716
MCC-PPAP2Achr5112630026chr554763977621HLA-B18:11SEIILGETL0.70040.93681120
MCC-PPAP2Achr5112630026chr554763977621HLA-B39:11SEIILGETL0.60850.72241120
MCC-PPAP2Achr5112630026chr554763977621HLA-B39:31SEIILGETL0.52460.95251120
MCC-PPAP2Achr5112630026chr554763977621HLA-B39:02SEIILGETL0.51420.90251120
MCC-PPAP2Achr5112630026chr554763977621HLA-B50:05SEIILGETL0.3480.65071120
MCC-PPAP2Achr5112630026chr554763977621HLA-B50:04SEIILGETL0.3480.65071120
MCC-PPAP2Achr5112630026chr554763977621HLA-B48:02SEIILGETL0.25340.90541120
MCC-PPAP2Achr5112630026chr554763977621HLA-B15:53SEIILGETL0.08110.88571120
MCC-PPAP2Achr5112630026chr554763977621HLA-B07:13SAELSEIIL0.07290.851716
MCC-PPAP2Achr5112630026chr554763977621HLA-A68:02EIILGETLSV0.99420.76011222
MCC-PPAP2Achr5112630026chr554763977621HLA-A69:01EIILGETLSV0.98790.78581222
MCC-PPAP2Achr5112630026chr554763977621HLA-B40:04SEIILGETLSV0.99940.74891122
MCC-PPAP2Achr5112630026chr554763977621HLA-A25:01EIILGETLSVY0.97430.8991223

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Potential FusionNeoAntigen Information of MCC-PPAP2A 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 MCC-PPAP2A

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
8994SSAELSEIILGETLMCCPPAP2Achr5112630026chr554763977621

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of MCC-PPAP2A

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-B14:023BVN8994SSAELSEIILGETL-7.15543-7.26883
HLA-B14:023BVN8994SSAELSEIILGETL-4.77435-5.80965
HLA-B52:013W398994SSAELSEIILGETL-6.80875-6.92215
HLA-B52:013W398994SSAELSEIILGETL-4.20386-5.23916
HLA-A11:014UQ28994SSAELSEIILGETL-7.5194-8.5547
HLA-A11:014UQ28994SSAELSEIILGETL-6.9601-7.0735
HLA-A24:025HGA8994SSAELSEIILGETL-7.52403-7.63743
HLA-A24:025HGA8994SSAELSEIILGETL-5.82433-6.85963
HLA-B27:056PYJ8994SSAELSEIILGETL-3.28285-4.31815
HLA-B44:053DX88994SSAELSEIILGETL-5.91172-6.94702
HLA-B44:053DX88994SSAELSEIILGETL-4.24346-4.35686

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Vaccine Design for the FusionNeoAntigens of MCC-PPAP2A

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
MCC-PPAP2Achr5112630026chr5547639771120SEIILGETLAGTGAGATTATTCTTGGAGAAACCCTG
MCC-PPAP2Achr5112630026chr5547639771122SEIILGETLSVAGTGAGATTATTCTTGGAGAAACCCTGTCTGTT
MCC-PPAP2Achr5112630026chr5547639771222EIILGETLSVGAGATTATTCTTGGAGAAACCCTGTCTGTT
MCC-PPAP2Achr5112630026chr5547639771223EIILGETLSVYGAGATTATTCTTGGAGAAACCCTGTCTGTTTAC
MCC-PPAP2Achr5112630026chr554763977716SAELSEIILTCGGCCGAGCTGAGTGAGATTATTCTT
MCC-PPAP2Achr5112630026chr554763977816AELSEIILGCCGAGCTGAGTGAGATTATTCTT

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 MCC-PPAP2A

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
Non-CancerMCC-PPAP2Achr5112630026ENST00000302475chr554763977ENST00000264775ERR315482

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Potential target of CAR-T therapy development for MCC-PPAP2A

check button Predicted 3D structure. We used RoseTTAFold.
272_MCC-PPAP2A_cd44c_pred.pdb


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
TgenePPAP2Achr5:112630026chr5:54763977ENST0000026477516165_1850286.0TransmembraneHelical
TgenePPAP2Achr5:112630026chr5:54763977ENST0000026477516200_2200286.0TransmembraneHelical
TgenePPAP2Achr5:112630026chr5:54763977ENST0000026477516230_2500286.0TransmembraneHelical
TgenePPAP2Achr5:112630026chr5:54763977ENST000002647751695_1150286.0TransmembraneHelical
TgenePPAP2Achr5:112630026chr5:54763977ENST0000030725916165_1850285.0TransmembraneHelical
TgenePPAP2Achr5:112630026chr5:54763977ENST0000030725916200_2200285.0TransmembraneHelical
TgenePPAP2Achr5:112630026chr5:54763977ENST0000030725916230_2500285.0TransmembraneHelical
TgenePPAP2Achr5:112630026chr5:54763977ENST000003072591695_1150285.0TransmembraneHelical

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
MCCchr5112630026ENST00000302475PPAP2Achr554763977ENST00000264775

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Related Drugs to MCC-PPAP2A

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 MCC-PPAP2A

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