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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:PAN2-MIP

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: PAN2-MIP
FusionPDB ID: 62515
FusionGDB2.0 ID: 62515
HgeneTgene
Gene symbol

PAN2

MIP

Gene ID

147945

4285

Gene nameNLR family pyrin domain containing 4mitochondrial intermediate peptidase
SynonymsCLR19.5|CT58|NALP4|PAN2|PYPAF4|RNH2COXPD31|HMIP|MIP
Cytomap

19q13.43

13q12.12

Type of geneprotein-codingprotein-coding
DescriptionNACHT, LRR and PYD domains-containing protein 4NACHT, leucine rich repeat and PYD containing 4PAAD and NACHT-containing protein 2PYRIN and NACHT-containing protein 2PYRIN-containing APAF1-like protein 4cancer/testis antigen 58nucleotide-binding oligmitochondrial intermediate peptidase
Modification date2020031320200313
UniProtAcc

PAN3

Main function of 5'-partner protein: 283

Q8TD10

Main function of 5'-partner protein:
Ensembl transtripts involved in fusion geneENST idsENST00000257931, ENST00000425394, 
ENST00000440411, ENST00000548043, 
ENST00000549090, 
ENST00000555551, 
ENST00000257979, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score2 X 2 X 2=83 X 2 X 2=12
# samples 24
** MAII scorelog2(2/8*10)=1.32192809488736log2(4/12*10)=1.73696559416621
effective Gene in Pan-Cancer Fusion Genes (eGinPCFGs).
DoF>8 and MAII>0
Fusion gene context

PubMed: PAN2 [Title/Abstract] AND MIP [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: PAN2 [Title/Abstract] AND MIP [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)PAN2(56726597)-MIP(56847539), # samples:3
Anticipated loss of major functional domain due to fusion event.PAN2-MIP 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.
PAN2-MIP 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.
PAN2-MIP 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.
PAN2-MIP 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.
PAN2-MIP seems lost the major protein functional domain in Hgene partner, which is a essential gene due to the frame-shifted ORF.
PAN2-MIP seems lost the major protein functional domain in Tgene partner, which is a IUPHAR drug target 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/chr12:56726597/chr12:56847539)
- 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 PAN2 (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 MIP (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)
ENST00000548043PAN2chr1256726597-ENST00000257979MIPchr1256847539-28626523701083237

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
ENST00000548043ENST00000257979PAN2chr1256726597-MIPchr1256847539-0.0040571930.9959428

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 PAN2-MIP

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
PAN2chr1256726597MIPchr125684753965294DLHEEMLWVGSHGLHPAVSVGQATTV

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Potential FusionNeoAntigen Information of PAN2-MIP 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.
PAN2-MIP_56726597_56847539.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)
PAN2-MIPchr1256726597chr1256847539652HLA-B39:24SHGLHPAV0.99970.95831018
PAN2-MIPchr1256726597chr1256847539652HLA-B39:06SHGLHPAV0.99960.98761018
PAN2-MIPchr1256726597chr1256847539652HLA-B39:01SHGLHPAV0.99880.98861018
PAN2-MIPchr1256726597chr1256847539652HLA-B15:10SHGLHPAV0.99760.91351018
PAN2-MIPchr1256726597chr1256847539652HLA-A02:22MLWVGSHGL0.98740.5874514
PAN2-MIPchr1256726597chr1256847539652HLA-A02:60MLWVGSHGL0.98210.506514
PAN2-MIPchr1256726597chr1256847539652HLA-A02:21MLWVGSHGL0.97960.5501514
PAN2-MIPchr1256726597chr1256847539652HLA-A02:27MLWVGSHGL0.97780.6347514
PAN2-MIPchr1256726597chr1256847539652HLA-A02:13MLWVGSHGL0.9770.7067514
PAN2-MIPchr1256726597chr1256847539652HLA-A02:04MLWVGSHGL0.96680.7543514
PAN2-MIPchr1256726597chr1256847539652HLA-A02:17MLWVGSHGL0.96040.5967514
PAN2-MIPchr1256726597chr1256847539652HLA-A02:38MLWVGSHGL0.960.698514
PAN2-MIPchr1256726597chr1256847539652HLA-A02:19MLWVGSHGL0.89820.6065514
PAN2-MIPchr1256726597chr1256847539652HLA-B39:06SHGLHPAVSV0.99860.97321020
PAN2-MIPchr1256726597chr1256847539652HLA-B39:05SHGLHPAV0.99750.98541018
PAN2-MIPchr1256726597chr1256847539652HLA-A02:02MLWVGSHGL0.98750.5258514
PAN2-MIPchr1256726597chr1256847539652HLA-A02:07MLWVGSHGL0.98280.5174514
PAN2-MIPchr1256726597chr1256847539652HLA-B39:05SHGLHPAVSV0.99770.95561020
PAN2-MIPchr1256726597chr1256847539652HLA-B44:10EEMLWVGSHGL0.99440.7175314
PAN2-MIPchr1256726597chr1256847539652HLA-B15:09SHGLHPAV0.9920.98611018
PAN2-MIPchr1256726597chr1256847539652HLA-B39:11SHGLHPAV0.86450.96571018
PAN2-MIPchr1256726597chr1256847539652HLA-C15:02GSHGLHPAV0.99930.9724918
PAN2-MIPchr1256726597chr1256847539652HLA-A02:14MLWVGSHGL0.980.5031514
PAN2-MIPchr1256726597chr1256847539652HLA-A02:06MLWVGSHGL0.97960.5501514
PAN2-MIPchr1256726597chr1256847539652HLA-B40:21MLWVGSHGL0.06060.6268514

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Potential FusionNeoAntigen Information of PAN2-MIP 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.
PAN2-MIP_56726597_56847539.msa

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)
PAN2-MIPchr1256726597chr1256847539652DRB1-0437SHGLHPAVSVGQATT1025
PAN2-MIPchr1256726597chr1256847539652DRB1-0458SHGLHPAVSVGQATT1025
PAN2-MIPchr1256726597chr1256847539652DRB1-0478SHGLHPAVSVGQATT1025

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Fusion breakpoint peptide structures of PAN2-MIP

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
5820LWVGSHGLHPAVSVPAN2MIPchr1256726597chr1256847539652

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of PAN2-MIP

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-B14:023BVN5820LWVGSHGLHPAVSV-7.9962-8.1096
HLA-B14:023BVN5820LWVGSHGLHPAVSV-5.70842-6.74372
HLA-B52:013W395820LWVGSHGLHPAVSV-6.83737-6.95077
HLA-B52:013W395820LWVGSHGLHPAVSV-4.4836-5.5189
HLA-A11:014UQ25820LWVGSHGLHPAVSV-10.0067-10.1201
HLA-A11:014UQ25820LWVGSHGLHPAVSV-9.03915-10.0745
HLA-A24:025HGA5820LWVGSHGLHPAVSV-6.56204-6.67544
HLA-A24:025HGA5820LWVGSHGLHPAVSV-5.42271-6.45801
HLA-B44:053DX85820LWVGSHGLHPAVSV-7.85648-8.89178
HLA-B44:053DX85820LWVGSHGLHPAVSV-5.3978-5.5112
HLA-A02:016TDR5820LWVGSHGLHPAVSV-3.37154-4.40684

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Vaccine Design for the FusionNeoAntigens of PAN2-MIP

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
PAN2-MIPchr1256726597chr12568475391018SHGLHPAVAGCCACGGGTTGCACCCTGCGGTG
PAN2-MIPchr1256726597chr12568475391020SHGLHPAVSVAGCCACGGGTTGCACCCTGCGGTGAGCGTG
PAN2-MIPchr1256726597chr1256847539314EEMLWVGSHGLGAGGAGATGCTGTGGGTGGGGAGCCACGGGTTG
PAN2-MIPchr1256726597chr1256847539514MLWVGSHGLATGCTGTGGGTGGGGAGCCACGGGTTG
PAN2-MIPchr1256726597chr1256847539918GSHGLHPAVGGGAGCCACGGGTTGCACCCTGCGGTG

check button mRNA and peptide sequences of FusionNeoAntigens that have potential interaction with HLA-IIs.
Fusion geneHchrHbpTchrTbpStart in +/-13AAEnd in +/-13AAFusionNeoAntigen peptideFusionNEoAntigen RNA sequence
PAN2-MIPchr1256726597chr12568475391025SHGLHPAVSVGQATTAGCCACGGGTTGCACCCTGCGGTGAGCGTGGGCCAGGCAACCACA

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Information of the samples that have these potential fusion neoantigens of PAN2-MIP

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
OVPAN2-MIPchr1256726597ENST00000548043chr1256847539ENST00000257979TCGA-24-1553-01A

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Potential target of CAR-T therapy development for PAN2-MIP

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
TgeneMIPchr12:56726597chr12:56847539ENST0000025797904177_1830264.0IntramembraneOntology_term=ECO:0000250
TgeneMIPchr12:56726597chr12:56847539ENST0000025797904184_1940264.0IntramembraneHelical
TgeneMIPchr12:56726597chr12:56847539ENST0000025797904127_1470264.0TransmembraneHelical
TgeneMIPchr12:56726597chr12:56847539ENST0000025797904160_1760264.0TransmembraneHelical
TgeneMIPchr12:56726597chr12:56847539ENST0000025797904201_2190264.0TransmembraneHelical

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

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Related Drugs to PAN2-MIP

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 PAN2-MIP

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