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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:PDHX-CAT

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: PDHX-CAT
FusionPDB ID: 63872
FusionGDB2.0 ID: 63872
HgeneTgene
Gene symbol

PDHX

CAT

Gene ID

8050

10249

Gene namepyruvate dehydrogenase complex component Xglycine-N-acyltransferase
SynonymsDLDBP|E3BP|OPDX|PDHXD|PDX1|proXACGNAT|CAT|GAT
Cytomap

11p13

11q12.1

Type of geneprotein-codingprotein-coding
Descriptionpyruvate dehydrogenase protein X component, mitochondrialdihydrolipoamide dehydrogenase-binding protein of pyruvate dehydrogenase complexlipoyl-containing pyruvate dehydrogenase complex component Xpyruvate dehydrogenase complex, E3-binding protein subuglycine N-acyltransferaseAAcHRP-1(CLP)acyl-CoA:glycine N-acyltransferasearalkyl acyl-CoA N-acyltransferasearalkyl acyl-CoA:amino acid N-acyltransferasearalkyl-CoA N-acyltransferasebenzoyl-coenzyme A:glycine N-acyltransferaseepididymis secretory sp
Modification date2020031320200313
UniProtAcc.

Q6ZRH7

Main function of 5'-partner protein: FUNCTION: Probably involved in sperm cell hyperactivation via its association with CATSPER1. Sperm cell hyperactivation is needed for sperm motility which is essential late in the preparation of sperm for fertilization. {ECO:0000250|UniProtKB:C6KI89}.
Ensembl transtripts involved in fusion geneENST idsENST00000227868, ENST00000448838, 
ENST00000430469, ENST00000477173, 
ENST00000534710, ENST00000241052, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score13 X 11 X 6=85814 X 11 X 8=1232
# samples 1718
** MAII scorelog2(17/858*10)=-2.33544290136184
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(18/1232*10)=-2.77493344436523
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: PDHX [Title/Abstract] AND CAT [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: PDHX [Title/Abstract] AND CAT [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)PDHX(34982065)-CAT(34492505), # samples:3
PDHX(34999729)-CAT(34477558), # samples:3
Anticipated loss of major functional domain due to fusion event.PDHX-CAT 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.
PDHX-CAT 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.
PDHX-CAT 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.
PDHX-CAT 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.
PDHX-CAT seems lost the major protein functional domain in Hgene partner, which is a cell metabolism gene due to the frame-shifted ORF.
PDHX-CAT seems lost the major protein functional domain in Tgene partner, which is a cell metabolism gene due to the frame-shifted ORF.
PDHX-CAT seems lost the major protein functional domain in Tgene partner, which is a IUPHAR drug target due to the frame-shifted ORF.
PDHX-CAT 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
TgeneCAT

GO:0006544

glycine metabolic process

22475485

TgeneCAT

GO:1901787

benzoyl-CoA metabolic process

22475485



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/chr11:34982065/chr11:34492505)
- 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 PDHX (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 CAT (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)
ENST00000448838PDHXchr1134999729+ENST00000241052CATchr1134477558+27221220982092664
ENST00000227868PDHXchr1134999729+ENST00000241052CATchr1134477558+26091107541979641

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
ENST00000448838ENST00000241052PDHXchr1134999729+CATchr1134477558+0.0016287440.9983713
ENST00000227868ENST00000241052PDHXchr1134999729+CATchr1134477558+0.0011794110.9988206

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 PDHX-CAT

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
PDHXchr1134999729CATchr11344775581107349SVNDFIIKAAAVTLKTDQGIKNLSVE
PDHXchr1134999729CATchr11344775581220372SVNDFIIKAAAVTLKTDQGIKNLSVE

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Potential FusionNeoAntigen Information of PDHX-CAT 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.
PDHX-CAT_34999729_34477558.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)
PDHX-CATchr1134999729chr11344775581107HLA-B08:01IIKAAAVTL0.93910.7894514
PDHX-CATchr1134999729chr11344775581107HLA-B15:04IIKAAAVTL0.99280.9528514
PDHX-CATchr1134999729chr11344775581107HLA-C03:08IIKAAAVTL0.99020.9185514
PDHX-CATchr1134999729chr11344775581107HLA-C01:30IIKAAAVTL0.49440.9765514
PDHX-CATchr1134999729chr11344775581107HLA-C03:03IIKAAAVTL0.99110.9898514
PDHX-CATchr1134999729chr11344775581107HLA-C03:04IIKAAAVTL0.99110.9898514
PDHX-CATchr1134999729chr11344775581107HLA-C03:17IIKAAAVTL0.98420.9602514
PDHX-CATchr1134999729chr11344775581107HLA-C03:05IIKAAAVTL0.97880.9021514
PDHX-CATchr1134999729chr11344775581107HLA-B15:73IIKAAAVTL0.9770.9782514
PDHX-CATchr1134999729chr11344775581107HLA-B15:30IIKAAAVTL0.96490.9304514
PDHX-CATchr1134999729chr11344775581107HLA-B08:18IIKAAAVTL0.93910.7894514
PDHX-CATchr1134999729chr11344775581107HLA-B08:12IIKAAAVTL0.79930.8938514

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Potential FusionNeoAntigen Information of PDHX-CAT 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.
PDHX-CAT_34999729_34477558.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)
PDHX-CATchr1134999729chr11344775581107DRB1-0101NDFIIKAAAVTLKTD217
PDHX-CATchr1134999729chr11344775581107DRB1-0102NDFIIKAAAVTLKTD217
PDHX-CATchr1134999729chr11344775581107DRB1-0102VNDFIIKAAAVTLKT116
PDHX-CATchr1134999729chr11344775581107DRB1-0103NDFIIKAAAVTLKTD217
PDHX-CATchr1134999729chr11344775581107DRB1-0103VNDFIIKAAAVTLKT116
PDHX-CATchr1134999729chr11344775581107DRB1-0105NDFIIKAAAVTLKTD217
PDHX-CATchr1134999729chr11344775581107DRB1-0107NDFIIKAAAVTLKTD217
PDHX-CATchr1134999729chr11344775581107DRB1-0109NDFIIKAAAVTLKTD217
PDHX-CATchr1134999729chr11344775581107DRB1-0111NDFIIKAAAVTLKTD217
PDHX-CATchr1134999729chr11344775581107DRB1-0111VNDFIIKAAAVTLKT116
PDHX-CATchr1134999729chr11344775581107DRB1-0113NDFIIKAAAVTLKTD217
PDHX-CATchr1134999729chr11344775581107DRB1-0115NDFIIKAAAVTLKTD217
PDHX-CATchr1134999729chr11344775581107DRB1-0115VNDFIIKAAAVTLKT116
PDHX-CATchr1134999729chr11344775581107DRB1-0117NDFIIKAAAVTLKTD217
PDHX-CATchr1134999729chr11344775581107DRB1-0119NDFIIKAAAVTLKTD217
PDHX-CATchr1134999729chr11344775581107DRB1-0121NDFIIKAAAVTLKTD217
PDHX-CATchr1134999729chr11344775581107DRB1-0123NDFIIKAAAVTLKTD217
PDHX-CATchr1134999729chr11344775581107DRB1-0123VNDFIIKAAAVTLKT116
PDHX-CATchr1134999729chr11344775581107DRB1-0125NDFIIKAAAVTLKTD217
PDHX-CATchr1134999729chr11344775581107DRB1-0127NDFIIKAAAVTLKTD217
PDHX-CATchr1134999729chr11344775581107DRB1-0129NDFIIKAAAVTLKTD217
PDHX-CATchr1134999729chr11344775581107DRB1-0129VNDFIIKAAAVTLKT116
PDHX-CATchr1134999729chr11344775581107DRB1-0131NDFIIKAAAVTLKTD217
PDHX-CATchr1134999729chr11344775581107DRB1-0704NDFIIKAAAVTLKTD217
PDHX-CATchr1134999729chr11344775581107DRB1-0704VNDFIIKAAAVTLKT116
PDHX-CATchr1134999729chr11344775581107DRB1-0709NDFIIKAAAVTLKTD217
PDHX-CATchr1134999729chr11344775581107DRB1-0711NDFIIKAAAVTLKTD217
PDHX-CATchr1134999729chr11344775581107DRB1-0712NDFIIKAAAVTLKTD217
PDHX-CATchr1134999729chr11344775581107DRB1-0813VNDFIIKAAAVTLKT116
PDHX-CATchr1134999729chr11344775581107DRB1-0815VNDFIIKAAAVTLKT116
PDHX-CATchr1134999729chr11344775581107DRB1-0830VNDFIIKAAAVTLKT116
PDHX-CATchr1134999729chr11344775581107DRB1-0904NDFIIKAAAVTLKTD217
PDHX-CATchr1134999729chr11344775581107DRB1-0905NDFIIKAAAVTLKTD217
PDHX-CATchr1134999729chr11344775581107DRB1-0906NDFIIKAAAVTLKTD217
PDHX-CATchr1134999729chr11344775581107DRB1-0907NDFIIKAAAVTLKTD217
PDHX-CATchr1134999729chr11344775581107DRB1-1367VNDFIIKAAAVTLKT116
PDHX-CATchr1134999729chr11344775581107DRB1-1467VNDFIIKAAAVTLKT116
PDHX-CATchr1134999729chr11344775581107DRB1-1467SVNDFIIKAAAVTLK015
PDHX-CATchr1134999729chr11344775581107DRB1-1489VNDFIIKAAAVTLKT116
PDHX-CATchr1134999729chr11344775581107DRB1-1498VNDFIIKAAAVTLKT116

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Fusion breakpoint peptide structures of PDHX-CAT

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
3748IKAAAVTLKTDQGIPDHXCATchr1134999729chr11344775581107

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of PDHX-CAT

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-B14:023BVN3748IKAAAVTLKTDQGI-7.23508-7.34688
HLA-B14:023BVN3748IKAAAVTLKTDQGI-6.00169-7.04479
HLA-B52:013W393748IKAAAVTLKTDQGI-6.26147-6.37327
HLA-B52:013W393748IKAAAVTLKTDQGI-5.36318-6.40628
HLA-A24:025HGA3748IKAAAVTLKTDQGI-8.09402-9.13712
HLA-A24:025HGA3748IKAAAVTLKTDQGI-7.44127-7.55307
HLA-B27:056PYJ3748IKAAAVTLKTDQGI-8.61781-8.72961
HLA-B44:053DX83748IKAAAVTLKTDQGI-5.30146-5.41326
HLA-B44:053DX83748IKAAAVTLKTDQGI-3.83212-4.87522
HLA-A02:016TDR3748IKAAAVTLKTDQGI-5.03872-5.15052

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Vaccine Design for the FusionNeoAntigens of PDHX-CAT

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
PDHX-CATchr1134999729chr1134477558514IIKAAAVTLAAGGCAGCAGCTGTTACCCTTAAAACT

check button mRNA and peptide sequences of FusionNeoAntigens that have potential interaction with HLA-IIs.
Fusion geneHchrHbpTchrTbpStart in +/-13AAEnd in +/-13AAFusionNeoAntigen peptideFusionNEoAntigen RNA sequence
PDHX-CATchr1134999729chr1134477558015SVNDFIIKAAAVTLKAATGATTTTATCATCAAGGCAGCAGCTGTTACCCTTAAAACTGAC
PDHX-CATchr1134999729chr1134477558116VNDFIIKAAAVTLKTGATTTTATCATCAAGGCAGCAGCTGTTACCCTTAAAACTGACCAG
PDHX-CATchr1134999729chr1134477558217NDFIIKAAAVTLKTDTTTATCATCAAGGCAGCAGCTGTTACCCTTAAAACTGACCAGGGC

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Information of the samples that have these potential fusion neoantigens of PDHX-CAT

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
BRCAPDHX-CATchr1134999729ENST00000227868chr1134477558ENST00000241052TCGA-E9-A1RB-01A

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Potential target of CAR-T therapy development for PDHX-CAT

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 PDHX-CAT

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 PDHX-CAT

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