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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:PINX1-MSRA

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: PINX1-MSRA
FusionPDB ID: 65466
FusionGDB2.0 ID: 65466
HgeneTgene
Gene symbol

PINX1

MSRA

Gene ID

54984

4482

Gene namePIN2 (TERF1) interacting telomerase inhibitor 1methionine sulfoxide reductase A
SynonymsGno1|LPTL|LPTS|Pxr1PMSR
Cytomap

8p23.1

8p23.1

Type of geneprotein-codingprotein-coding
DescriptionPIN2/TERF1-interacting telomerase inhibitor 167-11-3 proteinPIN2-interacting protein 1TRF1-interacting protein 1hepatocellular carcinoma-related putative tumor suppressorliver-related putative tumor suppressorpin2-interacting protein X1protein 67-1mitochondrial peptide methionine sulfoxide reductasecytosolic methionine-S-sulfoxide reductasepeptide Met(O) reductasepeptide met (O) reductasepeptide-methionine (S)-S-oxide reductase
Modification date2020032720200313
UniProtAcc.

Q9UJ68

Main function of 5'-partner protein: FUNCTION: Has an important function as a repair enzyme for proteins that have been inactivated by oxidation. Catalyzes the reversible oxidation-reduction of methionine sulfoxide in proteins to methionine.
Ensembl transtripts involved in fusion geneENST idsENST00000314787, ENST00000426190, 
ENST00000519088, ENST00000520018, 
ENST00000382490, ENST00000521209, 
ENST00000528246, ENST00000517594, 
ENST00000317173, ENST00000441698, 
ENST00000518255, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score7 X 7 X 5=24511 X 9 X 5=495
# samples 812
** MAII scorelog2(8/245*10)=-1.61470984411521
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(12/495*10)=-2.04439411935845
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: PINX1 [Title/Abstract] AND MSRA [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: PINX1 [Title/Abstract] AND MSRA [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)PINX1(10689174)-MSRA(10065342), # samples:1
PINX1(10689175)-MSRA(10065343), # samples:1
Anticipated loss of major functional domain due to fusion event.PINX1-MSRA 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.
PINX1-MSRA 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.
PINX1-MSRA 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.
PINX1-MSRA 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
HgenePINX1

GO:0007004

telomere maintenance via telomerase

11701125

HgenePINX1

GO:0010972

negative regulation of G2/M transition of mitotic cell cycle

11701125

HgenePINX1

GO:0032211

negative regulation of telomere maintenance via telomerase

11701125

HgenePINX1

GO:0051974

negative regulation of telomerase activity

11701125

HgenePINX1

GO:1902570

protein localization to nucleolus

24415760

HgenePINX1

GO:1904744

positive regulation of telomeric DNA binding

19265708|24415760

HgenePINX1

GO:1904751

positive regulation of protein localization to nucleolus

19265708



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/chr8:10689174/chr8:10065342)
- 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 PINX1 (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 MSRA (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)
ENST00000314787PINX1chr810689174-ENST00000317173MSRAchr810065342+15664216986326
ENST00000314787PINX1chr810689174-ENST00000441698MSRAchr810065342+9204216866286
ENST00000314787PINX1chr810689174-ENST00000518255MSRAchr810065342+9374216920304
ENST00000426190PINX1chr810689174-ENST00000317173MSRAchr810065342+15664216986326
ENST00000426190PINX1chr810689174-ENST00000441698MSRAchr810065342+9204216866286
ENST00000426190PINX1chr810689174-ENST00000518255MSRAchr810065342+9374216920304
ENST00000519088PINX1chr810689174-ENST00000317173MSRAchr810065342+15664216986326
ENST00000519088PINX1chr810689174-ENST00000441698MSRAchr810065342+9204216866286
ENST00000519088PINX1chr810689174-ENST00000518255MSRAchr810065342+9374216920304
ENST00000314787PINX1chr810689175-ENST00000317173MSRAchr810065343+15664216986326
ENST00000314787PINX1chr810689175-ENST00000441698MSRAchr810065343+9204216866286
ENST00000314787PINX1chr810689175-ENST00000518255MSRAchr810065343+9374216920304
ENST00000426190PINX1chr810689175-ENST00000317173MSRAchr810065343+15664216986326
ENST00000426190PINX1chr810689175-ENST00000441698MSRAchr810065343+9204216866286
ENST00000426190PINX1chr810689175-ENST00000518255MSRAchr810065343+9374216920304
ENST00000519088PINX1chr810689175-ENST00000317173MSRAchr810065343+15664216986326
ENST00000519088PINX1chr810689175-ENST00000441698MSRAchr810065343+9204216866286
ENST00000519088PINX1chr810689175-ENST00000518255MSRAchr810065343+9374216920304

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
ENST00000314787ENST00000317173PINX1chr810689174-MSRAchr810065342+0.0016434280.9983565
ENST00000314787ENST00000441698PINX1chr810689174-MSRAchr810065342+0.0052360520.994764
ENST00000314787ENST00000518255PINX1chr810689174-MSRAchr810065342+0.0062294910.99377054
ENST00000426190ENST00000317173PINX1chr810689174-MSRAchr810065342+0.0016434280.9983565
ENST00000426190ENST00000441698PINX1chr810689174-MSRAchr810065342+0.0052360520.994764
ENST00000426190ENST00000518255PINX1chr810689174-MSRAchr810065342+0.0062294910.99377054
ENST00000519088ENST00000317173PINX1chr810689174-MSRAchr810065342+0.0016434280.9983565
ENST00000519088ENST00000441698PINX1chr810689174-MSRAchr810065342+0.0052360520.994764
ENST00000519088ENST00000518255PINX1chr810689174-MSRAchr810065342+0.0062294910.99377054
ENST00000314787ENST00000317173PINX1chr810689175-MSRAchr810065343+0.0016434280.9983565
ENST00000314787ENST00000441698PINX1chr810689175-MSRAchr810065343+0.0052360520.994764
ENST00000314787ENST00000518255PINX1chr810689175-MSRAchr810065343+0.0062294910.99377054
ENST00000426190ENST00000317173PINX1chr810689175-MSRAchr810065343+0.0016434280.9983565
ENST00000426190ENST00000441698PINX1chr810689175-MSRAchr810065343+0.0052360520.994764
ENST00000426190ENST00000518255PINX1chr810689175-MSRAchr810065343+0.0062294910.99377054
ENST00000519088ENST00000317173PINX1chr810689175-MSRAchr810065343+0.0016434280.9983565
ENST00000519088ENST00000441698PINX1chr810689175-MSRAchr810065343+0.0052360520.994764
ENST00000519088ENST00000518255PINX1chr810689175-MSRAchr810065343+0.0062294910.99377054

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 PINX1-MSRA

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
PINX1chr810689174MSRAchr810065342421138LAELNTCHGQETTAKHHVNGNRTVEP
PINX1chr810689175MSRAchr810065343421138LAELNTCHGQETTAKHHVNGNRTVEP

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Potential FusionNeoAntigen Information of PINX1-MSRA 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.
PINX1-MSRA_10689174_10065342.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)
PINX1-MSRAchr810689174chr810065342421HLA-B45:01QETTAKHHV0.99840.9179918
PINX1-MSRAchr810689174chr810065342421HLA-B50:02QETTAKHHV0.99720.6541918
PINX1-MSRAchr810689174chr810065342421HLA-B44:05QETTAKHHV0.93130.5795918
PINX1-MSRAchr810689174chr810065342421HLA-B44:03QETTAKHHV0.91130.9758918
PINX1-MSRAchr810689174chr810065342421HLA-B41:01QETTAKHHV0.77990.8935918
PINX1-MSRAchr810689174chr810065342421HLA-B40:06QETTAKHHV0.99720.9238918
PINX1-MSRAchr810689174chr810065342421HLA-B44:10QETTAKHHV0.96440.6968918
PINX1-MSRAchr810689174chr810065342421HLA-B44:08QETTAKHHV0.94210.5503918
PINX1-MSRAchr810689174chr810065342421HLA-B44:09QETTAKHHV0.94010.6966918
PINX1-MSRAchr810689174chr810065342421HLA-B40:04QETTAKHHV0.97830.865918
PINX1-MSRAchr810689174chr810065342421HLA-B44:13QETTAKHHV0.91130.9758918
PINX1-MSRAchr810689174chr810065342421HLA-B44:26QETTAKHHV0.91130.9758918
PINX1-MSRAchr810689174chr810065342421HLA-B44:07QETTAKHHV0.91130.9758918
PINX1-MSRAchr810689174chr810065342421HLA-B41:03QETTAKHHV0.90950.797918

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Potential FusionNeoAntigen Information of PINX1-MSRA 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 PINX1-MSRA

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
833CHGQETTAKHHVNGPINX1MSRAchr810689174chr810065342421

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of PINX1-MSRA

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-B14:023BVN833CHGQETTAKHHVNG-7.15543-7.26883
HLA-B14:023BVN833CHGQETTAKHHVNG-4.77435-5.80965
HLA-B52:013W39833CHGQETTAKHHVNG-6.80875-6.92215
HLA-B52:013W39833CHGQETTAKHHVNG-4.20386-5.23916
HLA-A11:014UQ2833CHGQETTAKHHVNG-7.5194-8.5547
HLA-A11:014UQ2833CHGQETTAKHHVNG-6.9601-7.0735
HLA-A24:025HGA833CHGQETTAKHHVNG-7.52403-7.63743
HLA-A24:025HGA833CHGQETTAKHHVNG-5.82433-6.85963
HLA-B27:056PYJ833CHGQETTAKHHVNG-3.28285-4.31815
HLA-B44:053DX8833CHGQETTAKHHVNG-5.91172-6.94702
HLA-B44:053DX8833CHGQETTAKHHVNG-4.24346-4.35686

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Vaccine Design for the FusionNeoAntigens of PINX1-MSRA

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
PINX1-MSRAchr810689174chr810065342918QETTAKHHVAGGAAACCACAGCCAAACATCATGTCA

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 PINX1-MSRA

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
STADPINX1-MSRAchr810689174ENST00000314787chr810065342ENST00000317173TCGA-VQ-A91N

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Potential target of CAR-T therapy development for PINX1-MSRA

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 PINX1-MSRA

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 PINX1-MSRA

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