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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:PPM1H-WIF1

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: PPM1H-WIF1
FusionPDB ID: 67669
FusionGDB2.0 ID: 67669
HgeneTgene
Gene symbol

PPM1H

WIF1

Gene ID

57460

11197

Gene nameprotein phosphatase, Mg2+/Mn2+ dependent 1HWNT inhibitory factor 1
SynonymsARHCL1|NERPP-2C|URCC2WIF-1
Cytomap

12q14.1-q14.2

12q14.3

Type of geneprotein-codingprotein-coding
Descriptionprotein phosphatase 1Hneurite extension-related protein phosphatase related to PP2Cprotein phosphatase 1H (PP2C domain containing)ras homolog gene family, member C like 1wnt inhibitory factor 1
Modification date2020032720200313
UniProtAcc.

Q9Y5W5

Main function of 5'-partner protein: FUNCTION: Binds to WNT proteins and inhibits their activities. May be involved in mesoderm segmentation.
Ensembl transtripts involved in fusion geneENST idsENST00000551214, ENST00000228705, 
ENST00000286574, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score23 X 21 X 11=53137 X 11 X 6=462
# samples 2914
** MAII scorelog2(29/5313*10)=-4.19540190745814
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(14/462*10)=-1.72246602447109
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: PPM1H [Title/Abstract] AND WIF1 [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: PPM1H [Title/Abstract] AND WIF1 [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)PPM1H(63131282)-WIF1(65462684), # samples:3
Anticipated loss of major functional domain due to fusion event.PPM1H-WIF1 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.
PPM1H-WIF1 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.
PPM1H-WIF1 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.
PPM1H-WIF1 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.
PPM1H-WIF1 seems lost the major protein functional domain in Tgene partner, which is a CGC due to the frame-shifted ORF.
PPM1H-WIF1 seems lost the major protein functional domain in Tgene partner, which is a essential gene due to the frame-shifted ORF.
PPM1H-WIF1 seems lost the major protein functional domain in Tgene 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


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/chr12:63131282/chr12:65462684)
- 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 PPM1H (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 WIF1 (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)
ENST00000228705PPM1Hchr1263087715-ENST00000286574WIF1chr1265471634-301314381602289709

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
ENST00000228705ENST00000286574PPM1Hchr1263087715-WIF1chr1265471634-0.0063880970.9936119

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 PPM1H-WIF1

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
PPM1Hchr1263087715WIF1chr12654716341438426DLKFPLIYGEGKKAEYFYEFLSLRSL

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Potential FusionNeoAntigen Information of PPM1H-WIF1 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.
PPM1H-WIF1_63087715_65471634.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)
PPM1H-WIF1chr1263087715chr12654716341438HLA-B27:02KKAEYFYEF0.9920.65491120
PPM1H-WIF1chr1263087715chr12654716341438HLA-B44:03GEGKKAEYF0.98130.9493817
PPM1H-WIF1chr1263087715chr12654716341438HLA-B47:01GEGKKAEYF0.78490.6402817
PPM1H-WIF1chr1263087715chr12654716341438HLA-B15:03KKAEYFYEF0.61660.74131120
PPM1H-WIF1chr1263087715chr12654716341438HLA-B15:18KKAEYFYEF0.57110.70791120
PPM1H-WIF1chr1263087715chr12654716341438HLA-B47:01KKAEYFYEF0.42490.5971120
PPM1H-WIF1chr1263087715chr12654716341438HLA-B44:03GEGKKAEYFY0.99430.9343818
PPM1H-WIF1chr1263087715chr12654716341438HLA-B15:01LIYGEGKKAEY10.8281516
PPM1H-WIF1chr1263087715chr12654716341438HLA-B15:02LIYGEGKKAEY0.99990.8693516
PPM1H-WIF1chr1263087715chr12654716341438HLA-B15:25LIYGEGKKAEY0.99990.8643516
PPM1H-WIF1chr1263087715chr12654716341438HLA-C07:95KKAEYFYEF0.99860.83461120
PPM1H-WIF1chr1263087715chr12654716341438HLA-C07:05KKAEYFYEF0.99710.97381120
PPM1H-WIF1chr1263087715chr12654716341438HLA-C07:27KKAEYFYEF0.99280.97541120
PPM1H-WIF1chr1263087715chr12654716341438HLA-C07:29KKAEYFYEF0.98480.96741120
PPM1H-WIF1chr1263087715chr12654716341438HLA-C07:67KKAEYFYEF0.94250.96761120
PPM1H-WIF1chr1263087715chr12654716341438HLA-C07:80KKAEYFYEF0.94250.96761120
PPM1H-WIF1chr1263087715chr12654716341438HLA-C07:19KKAEYFYEF0.92920.86491120
PPM1H-WIF1chr1263087715chr12654716341438HLA-C07:13KKAEYFYEF0.92520.95231120
PPM1H-WIF1chr1263087715chr12654716341438HLA-C07:46KKAEYFYEF0.90470.93441120
PPM1H-WIF1chr1263087715chr12654716341438HLA-C07:10KKAEYFYEF0.90240.9771120
PPM1H-WIF1chr1263087715chr12654716341438HLA-C12:16KKAEYFYEF0.24650.97041120
PPM1H-WIF1chr1263087715chr12654716341438HLA-B15:07LIYGEGKKAEY10.5636516
PPM1H-WIF1chr1263087715chr12654716341438HLA-C07:01KKAEYFYEF0.99860.83741120
PPM1H-WIF1chr1263087715chr12654716341438HLA-B44:13GEGKKAEYF0.98130.9493817
PPM1H-WIF1chr1263087715chr12654716341438HLA-B44:26GEGKKAEYF0.98130.9493817
PPM1H-WIF1chr1263087715chr12654716341438HLA-B44:07GEGKKAEYF0.98130.9493817
PPM1H-WIF1chr1263087715chr12654716341438HLA-C07:02KKAEYFYEF0.94250.96761120
PPM1H-WIF1chr1263087715chr12654716341438HLA-C07:17KKAEYFYEF0.91560.97361120
PPM1H-WIF1chr1263087715chr12654716341438HLA-C07:22KKAEYFYEF0.87770.80831120
PPM1H-WIF1chr1263087715chr12654716341438HLA-B39:02KKAEYFYEF0.7640.95641120
PPM1H-WIF1chr1263087715chr12654716341438HLA-C03:02YGEGKKAEY0.62570.952716
PPM1H-WIF1chr1263087715chr12654716341438HLA-B48:02KKAEYFYEF0.60940.90211120
PPM1H-WIF1chr1263087715chr12654716341438HLA-C06:08KKAEYFYEF0.42060.98461120
PPM1H-WIF1chr1263087715chr12654716341438HLA-C06:06KKAEYFYEF0.3780.98961120
PPM1H-WIF1chr1263087715chr12654716341438HLA-B15:53KKAEYFYEF0.31140.87381120
PPM1H-WIF1chr1263087715chr12654716341438HLA-B15:68KKAEYFYEF0.28340.69411120
PPM1H-WIF1chr1263087715chr12654716341438HLA-B15:54KKAEYFYEF0.27950.84531120
PPM1H-WIF1chr1263087715chr12654716341438HLA-B41:03GEGKKAEYF0.18430.5399817
PPM1H-WIF1chr1263087715chr12654716341438HLA-C06:17KKAEYFYEF0.17730.99391120
PPM1H-WIF1chr1263087715chr12654716341438HLA-C06:02KKAEYFYEF0.17730.99391120
PPM1H-WIF1chr1263087715chr12654716341438HLA-B44:26GEGKKAEYFY0.99430.9343818
PPM1H-WIF1chr1263087715chr12654716341438HLA-B44:13GEGKKAEYFY0.99430.9343818
PPM1H-WIF1chr1263087715chr12654716341438HLA-B44:07GEGKKAEYFY0.99430.9343818
PPM1H-WIF1chr1263087715chr12654716341438HLA-C14:02IYGEGKKAEY0.92640.9529616
PPM1H-WIF1chr1263087715chr12654716341438HLA-C14:03IYGEGKKAEY0.92640.9529616
PPM1H-WIF1chr1263087715chr12654716341438HLA-B15:34LIYGEGKKAEY10.8281516
PPM1H-WIF1chr1263087715chr12654716341438HLA-B15:35LIYGEGKKAEY10.8051516
PPM1H-WIF1chr1263087715chr12654716341438HLA-B15:27LIYGEGKKAEY10.8736516
PPM1H-WIF1chr1263087715chr12654716341438HLA-B15:135LIYGEGKKAEY10.8299516
PPM1H-WIF1chr1263087715chr12654716341438HLA-B15:33LIYGEGKKAEY10.8281516
PPM1H-WIF1chr1263087715chr12654716341438HLA-B15:125LIYGEGKKAEY10.8281516
PPM1H-WIF1chr1263087715chr12654716341438HLA-B15:39LIYGEGKKAEY0.99990.7218516
PPM1H-WIF1chr1263087715chr12654716341438HLA-B78:02FPLIYGEGKKA0.98920.6884314

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Potential FusionNeoAntigen Information of PPM1H-WIF1 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 PPM1H-WIF1

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
4075IYGEGKKAEYFYEFPPM1HWIF1chr1263087715chr12654716341438

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of PPM1H-WIF1

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-B14:023BVN4075IYGEGKKAEYFYEF-6.79696-7.03106
HLA-B14:023BVN4075IYGEGKKAEYFYEF-6.51774-6.75184
HLA-B14:023BVN4075IYGEGKKAEYFYEF-4.89046-5.55426
HLA-B14:023BVN4075IYGEGKKAEYFYEF-4.88068-5.54448
HLA-B52:013W394075IYGEGKKAEYFYEF-6.53074-6.76484
HLA-B52:013W394075IYGEGKKAEYFYEF-6.00911-6.24321
HLA-B52:013W394075IYGEGKKAEYFYEF-5.00064-5.66444
HLA-B52:013W394075IYGEGKKAEYFYEF-4.7387-5.4025
HLA-A11:014UQ24075IYGEGKKAEYFYEF-11.0905-11.3246
HLA-A11:014UQ24075IYGEGKKAEYFYEF-9.4236-10.0874
HLA-A11:014UQ24075IYGEGKKAEYFYEF-8.73076-8.96486
HLA-A11:014UQ24075IYGEGKKAEYFYEF-1.64432-2.30812
HLA-A24:025HGA4075IYGEGKKAEYFYEF-7.19585-7.85965
HLA-A24:025HGA4075IYGEGKKAEYFYEF-7.19044-7.85424
HLA-A24:025HGA4075IYGEGKKAEYFYEF-6.58933-6.82343
HLA-A24:025HGA4075IYGEGKKAEYFYEF-6.45869-6.69279
HLA-B27:056PYJ4075IYGEGKKAEYFYEF-5.39862-6.06242
HLA-B44:053DX84075IYGEGKKAEYFYEF-6.76851-7.00261
HLA-B44:053DX84075IYGEGKKAEYFYEF-6.46869-6.70279
HLA-B44:053DX84075IYGEGKKAEYFYEF-4.17942-4.84322
HLA-B44:053DX84075IYGEGKKAEYFYEF-3.79418-4.45798
HLA-A02:016TDR4075IYGEGKKAEYFYEF-4.13159-4.36569

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Vaccine Design for the FusionNeoAntigens of PPM1H-WIF1

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
PPM1H-WIF1chr1263087715chr12654716341120KKAEYFYEFAAGAAGGCAGAATACTTCTATGAATTC
PPM1H-WIF1chr1263087715chr1265471634314FPLIYGEGKKATTCCCCCTTATATATGGAGAAGGCAAGAAGGCA
PPM1H-WIF1chr1263087715chr1265471634516LIYGEGKKAEYCTTATATATGGAGAAGGCAAGAAGGCAGAATAC
PPM1H-WIF1chr1263087715chr1265471634616IYGEGKKAEYATATATGGAGAAGGCAAGAAGGCAGAATAC
PPM1H-WIF1chr1263087715chr1265471634716YGEGKKAEYTATGGAGAAGGCAAGAAGGCAGAATAC
PPM1H-WIF1chr1263087715chr1265471634817GEGKKAEYFGGAGAAGGCAAGAAGGCAGAATACTTC
PPM1H-WIF1chr1263087715chr1265471634818GEGKKAEYFYGGAGAAGGCAAGAAGGCAGAATACTTCTAT

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 PPM1H-WIF1

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
ESCAPPM1H-WIF1chr1263087715ENST00000228705chr1265471634ENST00000286574TCGA-L5-A43M

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Potential target of CAR-T therapy development for PPM1H-WIF1

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 PPM1H-WIF1

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 PPM1H-WIF1

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
TgeneWIF1C0009402Colorectal Carcinoma1CTD_human
TgeneWIF1C0009404Colorectal Neoplasms1CTD_human
TgeneWIF1C0014859Esophageal Neoplasms1CTD_human
TgeneWIF1C0024623Malignant neoplasm of stomach1CTD_human
TgeneWIF1C0027439Nasopharyngeal Neoplasms1CTD_human
TgeneWIF1C0038356Stomach Neoplasms1CTD_human
TgeneWIF1C0238301Cancer of Nasopharynx1CTD_human
TgeneWIF1C0546837Malignant neoplasm of esophagus1CTD_human
TgeneWIF1C1708349Hereditary Diffuse Gastric Cancer1CTD_human