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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:PPP1R12C-DRD4

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: PPP1R12C-DRD4
FusionPDB ID: 67783
FusionGDB2.0 ID: 67783
HgeneTgene
Gene symbol

PPP1R12C

DRD4

Gene ID

54776

1815

Gene nameprotein phosphatase 1 regulatory subunit 12Cdopamine receptor D4
SynonymsAAVS1|LENG3|MBS85|p84|p85D4DR
Cytomap

19q13.42

11p15.5

Type of geneprotein-codingprotein-coding
Descriptionprotein phosphatase 1 regulatory subunit 12Cleukocyte receptor cluster (LRC) encoded novel gene 3leukocyte receptor cluster (LRC) member 3myosin-binding subunit 85protein phosphatase 1 myosin-binding subunit of 85 kDaprotein phosphatase 1 myosin-bindD(4) dopamine receptorD(2C) dopamine receptordopamine D4 receptorseven transmembrane helix receptor
Modification date2020031320200329
UniProtAcc..
Ensembl transtripts involved in fusion geneENST idsENST00000263433, ENST00000376393, 
ENST00000435544, 
ENST00000528733, 
ENST00000176183, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score23 X 6 X 11=15184 X 5 X 3=60
# samples 247
** MAII scorelog2(24/1518*10)=-2.66106547980695
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(7/60*10)=0.222392421336448
effective Gene in Pan-Cancer Fusion Genes (eGinPCFGs).
DoF>8 and MAII>0
Fusion gene context

PubMed: PPP1R12C [Title/Abstract] AND DRD4 [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: PPP1R12C [Title/Abstract] AND DRD4 [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)PPP1R12C(55610151)-DRD4(639432), # samples:1
Anticipated loss of major functional domain due to fusion event.PPP1R12C-DRD4 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.
PPP1R12C-DRD4 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.
PPP1R12C-DRD4 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.
PPP1R12C-DRD4 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
TgeneDRD4

GO:0000187

activation of MAPK activity

9843378|15755724

TgeneDRD4

GO:0007195

adenylate cyclase-inhibiting dopamine receptor signaling pathway

7512953|9003072|9843378

TgeneDRD4

GO:0007212

dopamine receptor signaling pathway

1840645

TgeneDRD4

GO:0032417

positive regulation of sodium:proton antiporter activity

7512953

TgeneDRD4

GO:0033674

positive regulation of kinase activity

15755724

TgeneDRD4

GO:0034776

response to histamine

16839358

TgeneDRD4

GO:0050482

arachidonic acid secretion

7512953

TgeneDRD4

GO:0050709

negative regulation of protein secretion

16839358

TgeneDRD4

GO:1901386

negative regulation of voltage-gated calcium channel activity

7921596



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/chr19:55610151/chr11:639432)
- 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 PPP1R12C (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 DRD4 (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)
ENST00000263433PPP1R12Cchr1955610151-ENST00000176183DRD4chr11639432+2045967161941641
ENST00000376393PPP1R12Cchr1955610151-ENST00000176183DRD4chr11639432+2045967161941641
ENST00000435544PPP1R12Cchr1955610151-ENST00000176183DRD4chr11639432+1935857801831583

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
ENST00000263433ENST00000176183PPP1R12Cchr1955610151-DRD4chr11639432+0.029876120.9701239
ENST00000376393ENST00000176183PPP1R12Cchr1955610151-DRD4chr11639432+0.029876120.9701239
ENST00000435544ENST00000176183PPP1R12Cchr1955610151-DRD4chr11639432+0.0634266360.9365734

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 PPP1R12C-DRD4

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
PPP1R12Cchr1955610151DRD4chr11639432857252DLADEEVLSLLEELARKQEDVQGGAW
PPP1R12Cchr1955610151DRD4chr11639432857377FFLPCPLMLLLYWATFRGLQRWEVAR
PPP1R12Cchr1955610151DRD4chr11639432857426APRLPQDPCGPDCAPPAPGLPRGPCG
PPP1R12Cchr1955610151DRD4chr11639432967435FFLPCPLMLLLYWATFRGLQRWEVAR
PPP1R12Cchr1955610151DRD4chr11639432967484APRLPQDPCGPDCAPPAPGLPRGPCG

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Potential FusionNeoAntigen Information of PPP1R12C-DRD4 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 PPP1R12C-DRD4 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 PPP1R12C-DRD4

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 PPP1R12C-DRD4

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 PPP1R12C-DRD4

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 PPP1R12C-DRD4

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 PPP1R12C-DRD4

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
TgeneDRD4chr19:55610151chr11:639432ENST0000017618304111_1310420.0TransmembraneHelical%3B Name%3D3
TgeneDRD4chr19:55610151chr11:639432ENST0000017618304153_1730420.0TransmembraneHelical%3B Name%3D4
TgeneDRD4chr19:55610151chr11:639432ENST0000017618304193_2130420.0TransmembraneHelical%3B Name%3D5
TgeneDRD4chr19:55610151chr11:639432ENST0000017618304347_3670420.0TransmembraneHelical%3B Name%3D6
TgeneDRD4chr19:55610151chr11:639432ENST0000017618304383_4030420.0TransmembraneHelical%3B Name%3D7

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 PPP1R12C-DRD4

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 PPP1R12C-DRD4

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