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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:PRPF8-LDHA

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: PRPF8-LDHA
FusionPDB ID: 69069
FusionGDB2.0 ID: 69069
HgeneTgene
Gene symbol

PRPF8

LDHA

Gene ID

10594

3939

Gene namepre-mRNA processing factor 8lactate dehydrogenase A
SynonymsHPRP8|PRP8|PRPC8|RP13|SNRNP220GSD11|HEL-S-133P|LDHM|PIG19
Cytomap

17p13.3

11p15.1

Type of geneprotein-codingprotein-coding
Descriptionpre-mRNA-processing-splicing factor 8220 kDa U5 snRNP-specific proteinPRP8 homologPRP8 pre-mRNA processing factor 8 homologU5 snRNP-specific protein (220 kD), ortholog of S. cerevisiae Prp8papoptosis-regulated protein 1apoptosis-regulated protein 2L-lactate dehydrogenase A chainLDH muscle subunitLDH-ALDH-Mcell proliferation-inducing gene 19 proteinepididymis secretory sperm binding protein Li 133Plactate dehydrogenase Mproliferation-inducing gene 19renal carcinoma antigen NY-REN-59
Modification date2020031320200313
UniProtAcc.

Q6ZMR3

Main function of 5'-partner protein: FUNCTION: Displays an lactate dehydrogenase activity. Significantly increases the transcriptional activity of JUN, when overexpressed. {ECO:0000269|PubMed:18351441}.
Ensembl transtripts involved in fusion geneENST idsENST00000304992, ENST00000572621, 
ENST00000575116, 
ENST00000227157, 
ENST00000379412, ENST00000396222, 
ENST00000540430, ENST00000542179, 
ENST00000422447, ENST00000430553, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score13 X 16 X 7=14567 X 7 X 1=49
# samples 167
** MAII scorelog2(16/1456*10)=-3.18586654531133
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(7/49*10)=0.514573172829758
effective Gene in Pan-Cancer Fusion Genes (eGinPCFGs).
DoF>8 and MAII>0
Fusion gene context

PubMed: PRPF8 [Title/Abstract] AND LDHA [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: PRPF8 [Title/Abstract] AND LDHA [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)PRPF8(1579226)-LDHA(18428658), # samples:1
Anticipated loss of major functional domain due to fusion event.PRPF8-LDHA 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.
PRPF8-LDHA 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.
PRPF8-LDHA seems lost the major protein functional domain in Hgene partner, which is a essential gene due to the frame-shifted ORF.
PRPF8-LDHA seems lost the major protein functional domain in Tgene partner, which is a cell metabolism gene due to the frame-shifted ORF.
PRPF8-LDHA seems lost the major protein functional domain in Tgene partner, which is a essential gene 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
HgenePRPF8

GO:0000244

spliceosomal tri-snRNP complex assembly

20595234

HgenePRPF8

GO:0000398

mRNA splicing, via spliceosome

28781166|29301961



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/chr17:1579226/chr11:18428658)
- 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 PRPF8 (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 LDHA (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)
ENST00000304992PRPF8chr171579226-ENST00000430553LDHAchr1118428658+3344279392957982

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
ENST00000304992ENST00000430553PRPF8chr171579226-LDHAchr1118428658+0.0010803780.9989196

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 PRPF8-LDHA

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
PRPF8chr171579226LDHAchr11184286582793928IKRHLLTQRAFKEGLYGIKDDVFLSV

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Potential FusionNeoAntigen Information of PRPF8-LDHA 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.
PRPF8-LDHA_1579226_18428658.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)
PRPF8-LDHAchr171579226chr11184286582793HLA-B48:01TQRAFKEGL0.98160.696615
PRPF8-LDHAchr171579226chr11184286582793HLA-B15:18QRAFKEGLY0.35460.713716
PRPF8-LDHAchr171579226chr11184286582793HLA-B07:10TQRAFKEGL0.20930.6324615
PRPF8-LDHAchr171579226chr11184286582793HLA-B15:01TQRAFKEGLY0.99990.8027616
PRPF8-LDHAchr171579226chr11184286582793HLA-A30:08RAFKEGLYGIK0.99650.6254819
PRPF8-LDHAchr171579226chr11184286582793HLA-B15:04TQRAFKEGL0.93910.937615
PRPF8-LDHAchr171579226chr11184286582793HLA-B48:03TQRAFKEGL0.83990.5381615
PRPF8-LDHAchr171579226chr11184286582793HLA-B15:07TQRAFKEGLY0.99930.6416616
PRPF8-LDHAchr171579226chr11184286582793HLA-B15:73TQRAFKEGL0.91330.9571615
PRPF8-LDHAchr171579226chr11184286582793HLA-B39:02TQRAFKEGL0.85610.9581615
PRPF8-LDHAchr171579226chr11184286582793HLA-B40:12TQRAFKEGL0.83990.5381615
PRPF8-LDHAchr171579226chr11184286582793HLA-B15:30TQRAFKEGL0.81760.9509615
PRPF8-LDHAchr171579226chr11184286582793HLA-B15:68TQRAFKEGL0.70350.7522615
PRPF8-LDHAchr171579226chr11184286582793HLA-B48:05TQRAFKEGL0.25530.5014615
PRPF8-LDHAchr171579226chr11184286582793HLA-B15:34TQRAFKEGLY0.99990.8027616
PRPF8-LDHAchr171579226chr11184286582793HLA-B15:125TQRAFKEGLY0.99990.8027616
PRPF8-LDHAchr171579226chr11184286582793HLA-B15:135TQRAFKEGLY0.99990.8259616
PRPF8-LDHAchr171579226chr11184286582793HLA-B15:33TQRAFKEGLY0.99990.8027616
PRPF8-LDHAchr171579226chr11184286582793HLA-B15:50TQRAFKEGLY0.99980.7805616
PRPF8-LDHAchr171579226chr11184286582793HLA-B15:35TQRAFKEGLY0.99930.817616
PRPF8-LDHAchr171579226chr11184286582793HLA-B15:53TQRAFKEGLY0.99880.773616
PRPF8-LDHAchr171579226chr11184286582793HLA-B15:12TQRAFKEGLY0.99860.7487616
PRPF8-LDHAchr171579226chr11184286582793HLA-B15:54TQRAFKEGLY0.9910.7386616
PRPF8-LDHAchr171579226chr11184286582793HLA-B15:68TQRAFKEGLY0.97570.5116616
PRPF8-LDHAchr171579226chr11184286582793HLA-A30:01RAFKEGLYGIK0.99720.759819

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Potential FusionNeoAntigen Information of PRPF8-LDHA 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 PRPF8-LDHA

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
9584TQRAFKEGLYGIKDPRPF8LDHAchr171579226chr11184286582793

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of PRPF8-LDHA

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-B14:023BVN9584TQRAFKEGLYGIKD-5.47913-5.67113
HLA-B14:023BVN9584TQRAFKEGLYGIKD-3.84443-4.60543
HLA-B52:013W399584TQRAFKEGLYGIKD-6.76995-6.96195
HLA-B52:013W399584TQRAFKEGLYGIKD-5.58751-6.34851
HLA-A11:014UQ29584TQRAFKEGLYGIKD-5.74663-6.50763
HLA-A11:014UQ29584TQRAFKEGLYGIKD-5.69582-5.88782
HLA-A24:025HGA9584TQRAFKEGLYGIKD-8.42283-9.18383
HLA-A24:025HGA9584TQRAFKEGLYGIKD-7.2103-7.4023
HLA-B27:056PYJ9584TQRAFKEGLYGIKD-7.69112-7.88312
HLA-B44:053DX89584TQRAFKEGLYGIKD-5.89348-6.08548
HLA-B44:053DX89584TQRAFKEGLYGIKD-3.81554-4.57654
HLA-A02:016TDR9584TQRAFKEGLYGIKD-3.68024-4.44124

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Vaccine Design for the FusionNeoAntigens of PRPF8-LDHA

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
PRPF8-LDHAchr171579226chr1118428658615TQRAFKEGLACACAGAGAGCCTTCAAAGAGGGTCTT
PRPF8-LDHAchr171579226chr1118428658616TQRAFKEGLYACACAGAGAGCCTTCAAAGAGGGTCTTTAC
PRPF8-LDHAchr171579226chr1118428658716QRAFKEGLYCAGAGAGCCTTCAAAGAGGGTCTTTAC
PRPF8-LDHAchr171579226chr1118428658819RAFKEGLYGIKAGAGCCTTCAAAGAGGGTCTTTACGGAATAAAG

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 PRPF8-LDHA

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
N/APRPF8-LDHAchr171579226ENST00000304992chr1118428658ENST00000430553BG122659

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Potential target of CAR-T therapy development for PRPF8-LDHA

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 PRPF8-LDHA

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 PRPF8-LDHA

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