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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:RPRD1A-MAP4K4

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: RPRD1A-MAP4K4
FusionPDB ID: 77238
FusionGDB2.0 ID: 77238
HgeneTgene
Gene symbol

RPRD1A

MAP4K4

Gene ID

55197

9448

Gene nameregulation of nuclear pre-mRNA domain containing 1Amitogen-activated protein kinase kinase kinase kinase 4
SynonymsHsT3101|P15RSFLH21957|HEL-S-31|HGK|MEKKK4|NIK
Cytomap

18q12.2

2q11.2

Type of geneprotein-codingprotein-coding
Descriptionregulation of nuclear pre-mRNA domain-containing protein 1ACDKN2B-related proteinCyclin-dependent kinase inhibitor 2B-related protein (p15INK4B-related protein)cyclin-dependent kinase 2B-inhibitor-related proteinp15INK4B-related proteinmitogen-activated protein kinase kinase kinase kinase 4HPK/GCK-like kinase HGKMAPK/ERK kinase kinase kinase 4MEK kinase kinase 4Ste20 group protein kinase HGKepididymis secretory protein Li 31hepatocyte progenitor kinase-like/germinal center kinase-
Modification date2020031320200315
UniProtAcc.

O95819

Main function of 5'-partner protein: FUNCTION: Serine/threonine kinase that may play a role in the response to environmental stress and cytokines such as TNF-alpha. Appears to act upstream of the JUN N-terminal pathway. Phosphorylates SMAD1 on Thr-322. {ECO:0000269|PubMed:21690388, ECO:0000269|PubMed:9890973}.
Ensembl transtripts involved in fusion geneENST idsENST00000319040, ENST00000357384, 
ENST00000399022, ENST00000588737, 
ENST00000590898, ENST00000337059, 
ENST00000588459, 		ENST00000498066, 
ENST00000302217, ENST00000324219, 
ENST00000347699, ENST00000350198, 
ENST00000350878, ENST00000413150, 
ENST00000425019, ENST00000456652, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score13 X 14 X 7=127413 X 14 X 8=1456
# samples 1714
** MAII scorelog2(17/1274*10)=-2.9057586261186
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0		log2(14/1456*10)=-3.37851162325373
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: RPRD1A [Title/Abstract] AND MAP4K4 [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: RPRD1A [Title/Abstract] AND MAP4K4 [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)RPRD1A(33647216)-MAP4K4(102472438), # samples:1
Anticipated loss of major functional domain due to fusion event.RPRD1A-MAP4K4 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.
RPRD1A-MAP4K4 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.
RPRD1A-MAP4K4 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.
RPRD1A-MAP4K4 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
TgeneMAP4K4

GO:0006468

protein phosphorylation

9890973

TgeneMAP4K4

GO:0035556

intracellular signal transduction

9890973

TgeneMAP4K4

GO:0046328

regulation of JNK cascade

14966141



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/chr18:33647216/chr2:102472438)
- 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 RPRD1A (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 MAP4K4 (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)
ENST00000399022RPRD1Achr1833647216-ENST00000425019MAP4K4chr2102472438+31563234102908832
ENST00000399022RPRD1Achr1833647216-ENST00000324219MAP4K4chr2102472438+31323234103052880
ENST00000399022RPRD1Achr1833647216-ENST00000350198MAP4K4chr2102472438+26703234102590726
ENST00000399022RPRD1Achr1833647216-ENST00000302217MAP4K4chr2102472438+27393234102659749
ENST00000399022RPRD1Achr1833647216-ENST00000413150MAP4K4chr2102472438+59933234102554714
ENST00000399022RPRD1Achr1833647216-ENST00000347699MAP4K4chr2102472438+28823234102809799
ENST00000399022RPRD1Achr1833647216-ENST00000456652MAP4K4chr2102472438+33863234102647745
ENST00000399022RPRD1Achr1833647216-ENST00000350878MAP4K4chr2102472438+30693234102989859
ENST00000357384RPRD1Achr1833647216-ENST00000425019MAP4K4chr2102472438+31363033902888832
ENST00000357384RPRD1Achr1833647216-ENST00000324219MAP4K4chr2102472438+31123033903032880
ENST00000357384RPRD1Achr1833647216-ENST00000350198MAP4K4chr2102472438+26503033902570726
ENST00000357384RPRD1Achr1833647216-ENST00000302217MAP4K4chr2102472438+27193033902639749
ENST00000357384RPRD1Achr1833647216-ENST00000413150MAP4K4chr2102472438+59733033902534714
ENST00000357384RPRD1Achr1833647216-ENST00000347699MAP4K4chr2102472438+28623033902789799
ENST00000357384RPRD1Achr1833647216-ENST00000456652MAP4K4chr2102472438+33663033902627745
ENST00000357384RPRD1Achr1833647216-ENST00000350878MAP4K4chr2102472438+30493033902969859
ENST00000319040RPRD1Achr1833647216-ENST00000425019MAP4K4chr2102472438+31363033902888832
ENST00000319040RPRD1Achr1833647216-ENST00000324219MAP4K4chr2102472438+31123033903032880
ENST00000319040RPRD1Achr1833647216-ENST00000350198MAP4K4chr2102472438+26503033902570726
ENST00000319040RPRD1Achr1833647216-ENST00000302217MAP4K4chr2102472438+27193033902639749
ENST00000319040RPRD1Achr1833647216-ENST00000413150MAP4K4chr2102472438+59733033902534714
ENST00000319040RPRD1Achr1833647216-ENST00000347699MAP4K4chr2102472438+28623033902789799
ENST00000319040RPRD1Achr1833647216-ENST00000456652MAP4K4chr2102472438+33663033902627745
ENST00000319040RPRD1Achr1833647216-ENST00000350878MAP4K4chr2102472438+30493033902969859

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
ENST00000399022ENST00000425019RPRD1Achr1833647216-MAP4K4chr2102472438+0.0074580030.992542
ENST00000399022ENST00000324219RPRD1Achr1833647216-MAP4K4chr2102472438+0.0047148860.9952851
ENST00000399022ENST00000350198RPRD1Achr1833647216-MAP4K4chr2102472438+0.0121373790.9878626
ENST00000399022ENST00000302217RPRD1Achr1833647216-MAP4K4chr2102472438+0.0079838650.9920161
ENST00000399022ENST00000413150RPRD1Achr1833647216-MAP4K4chr2102472438+0.0005533270.9994467
ENST00000399022ENST00000347699RPRD1Achr1833647216-MAP4K4chr2102472438+0.0113871370.9886129
ENST00000399022ENST00000456652RPRD1Achr1833647216-MAP4K4chr2102472438+0.0020787090.9979213
ENST00000399022ENST00000350878RPRD1Achr1833647216-MAP4K4chr2102472438+0.0035519570.99644804
ENST00000357384ENST00000425019RPRD1Achr1833647216-MAP4K4chr2102472438+0.0071656580.9928343
ENST00000357384ENST00000324219RPRD1Achr1833647216-MAP4K4chr2102472438+0.0045107480.9954893
ENST00000357384ENST00000350198RPRD1Achr1833647216-MAP4K4chr2102472438+0.0117625580.98823744
ENST00000357384ENST00000302217RPRD1Achr1833647216-MAP4K4chr2102472438+0.007773240.9922267
ENST00000357384ENST00000413150RPRD1Achr1833647216-MAP4K4chr2102472438+0.000551610.99944836
ENST00000357384ENST00000347699RPRD1Achr1833647216-MAP4K4chr2102472438+0.0111174830.9888825
ENST00000357384ENST00000456652RPRD1Achr1833647216-MAP4K4chr2102472438+0.0020174070.9979826
ENST00000357384ENST00000350878RPRD1Achr1833647216-MAP4K4chr2102472438+0.0034334460.99656653
ENST00000319040ENST00000425019RPRD1Achr1833647216-MAP4K4chr2102472438+0.0071656580.9928343
ENST00000319040ENST00000324219RPRD1Achr1833647216-MAP4K4chr2102472438+0.0045107480.9954893
ENST00000319040ENST00000350198RPRD1Achr1833647216-MAP4K4chr2102472438+0.0117625580.98823744
ENST00000319040ENST00000302217RPRD1Achr1833647216-MAP4K4chr2102472438+0.007773240.9922267
ENST00000319040ENST00000413150RPRD1Achr1833647216-MAP4K4chr2102472438+0.000551610.99944836
ENST00000319040ENST00000347699RPRD1Achr1833647216-MAP4K4chr2102472438+0.0111174830.9888825
ENST00000319040ENST00000456652RPRD1Achr1833647216-MAP4K4chr2102472438+0.0020174070.9979826
ENST00000319040ENST00000350878RPRD1Achr1833647216-MAP4K4chr2102472438+0.0034334460.99656653

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 RPRD1A-MAP4K4

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

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Potential FusionNeoAntigen Information of RPRD1A-MAP4K4 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.

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)

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Potential FusionNeoAntigen Information of RPRD1A-MAP4K4 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 RPRD1A-MAP4K4

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.

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of RPRD1A-MAP4K4

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

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Vaccine Design for the FusionNeoAntigens of RPRD1A-MAP4K4

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

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 RPRD1A-MAP4K4

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

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Potential target of CAR-T therapy development for RPRD1A-MAP4K4

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 RPRD1A-MAP4K4

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 RPRD1A-MAP4K4

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