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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:PRR14L-CC2D1A

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: PRR14L-CC2D1A
FusionPDB ID: 69136
FusionGDB2.0 ID: 69136
HgeneTgene
Gene symbol

PRR14L

CC2D1A

Gene ID

253143

54862

Gene nameproline rich 14 likecoiled-coil and C2 domain containing 1A
SynonymsC22orf30FREUD-1|Freud-1/Aki1|MRT3
Cytomap

22q12.2

19p13.12

Type of geneprotein-codingprotein-coding
Descriptionprotein PRR14Lproline rich 14-like proteincoiled-coil and C2 domain-containing protein 1AAkt kinase-interacting protein 1FRE under dual repression-binding protein 1five prime repressor element under dual repression-binding protein 1five repressor element under dual repression-binding protein
Modification date2020031320200313
UniProtAcc.

Q6P1N0

Main function of 5'-partner protein: FUNCTION: Transcription factor that binds specifically to the DRE (dual repressor element) and represses HTR1A gene transcription in neuronal cells. The combination of calcium and ATP specifically inactivates the binding with FRE. May play a role in the altered regulation of HTR1A associated with anxiety and major depression. Mediates HDAC-independent repression of HTR1A promoter in neuronal cell. Performs essential function in controlling functional maturation of synapses (By similarity). Plays distinct roles depending on its localization. When cytoplasmic, acts as a scaffold protein in the PI3K/PDK1/AKT pathway. Repressor of HTR1A when nuclear. In the centrosome, regulates spindle pole localization of the cohesin subunit SCC1/RAD21, thereby mediating centriole cohesion during mitosis. {ECO:0000250, ECO:0000269|PubMed:20171170}.
Ensembl transtripts involved in fusion geneENST idsENST00000327423, ENST00000397493, 
ENST00000434485, ENST00000461722, 
ENST00000318003, ENST00000589606, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score7 X 7 X 5=2456 X 6 X 5=180
# samples 86
** MAII scorelog2(8/245*10)=-1.61470984411521
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(6/180*10)=-1.58496250072116
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: PRR14L [Title/Abstract] AND CC2D1A [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: PRR14L [Title/Abstract] AND CC2D1A [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)PRR14L(32134373)-CC2D1A(14034146), # samples:2
Anticipated loss of major functional domain due to fusion event.PRR14L-CC2D1A 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.
PRR14L-CC2D1A 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.
PRR14L-CC2D1A 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.
PRR14L-CC2D1A 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.
PRR14L-CC2D1A seems lost the major protein functional domain in Hgene partner, which is a essential gene due to the frame-shifted ORF.
PRR14L-CC2D1A seems lost the major protein functional domain in Tgene partner, which is a essential gene due to the frame-shifted ORF.
PRR14L-CC2D1A seems lost the major protein functional domain in Tgene partner, which is a transcription factor 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


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/chr22:32134373/chr19:14034146)
- 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 PRR14L (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 CC2D1A (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)
ENST00000434485PRR14Lchr2232134373-ENST00000318003CC2D1Achr1914034146+23666671931881562
ENST00000434485PRR14Lchr2232134373-ENST00000589606CC2D1Achr1914034146+21436671931878561

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
ENST00000434485ENST00000318003PRR14Lchr2232134373-CC2D1Achr1914034146+0.0168064220.98319364
ENST00000434485ENST00000589606PRR14Lchr2232134373-CC2D1Achr1914034146+0.0184631720.9815368

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 PRR14L-CC2D1A

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
PRR14Lchr2232134373CC2D1Achr1914034146667151AKEDPHQHSTAAEEKTSPSQVPPAPV

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Potential FusionNeoAntigen Information of PRR14L-CC2D1A 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.
PRR14L-CC2D1A_32134373_14034146.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)
PRR14L-CC2D1Achr2232134373chr1914034146667HLA-B45:01EEKTSPSQV0.99730.86051221
PRR14L-CC2D1Achr2232134373chr1914034146667HLA-B50:02EEKTSPSQV0.99040.73751221
PRR14L-CC2D1Achr2232134373chr1914034146667HLA-B41:01EEKTSPSQV0.87160.95151221
PRR14L-CC2D1Achr2232134373chr1914034146667HLA-B45:01AEEKTSPSQV0.99710.90641121
PRR14L-CC2D1Achr2232134373chr1914034146667HLA-B45:01EEKTSPSQVP0.98620.85441222
PRR14L-CC2D1Achr2232134373chr1914034146667HLA-B50:02EEKTSPSQVP0.94640.76021222
PRR14L-CC2D1Achr2232134373chr1914034146667HLA-B41:01AEEKTSPSQV0.85770.92521121
PRR14L-CC2D1Achr2232134373chr1914034146667HLA-B45:01AEEKTSPSQVP0.99960.93391122
PRR14L-CC2D1Achr2232134373chr1914034146667HLA-B50:02AEEKTSPSQVP0.99910.78811122
PRR14L-CC2D1Achr2232134373chr1914034146667HLA-B41:01AEEKTSPSQVP0.99710.94241122
PRR14L-CC2D1Achr2232134373chr1914034146667HLA-B44:09EEKTSPSQV0.78630.52841221
PRR14L-CC2D1Achr2232134373chr1914034146667HLA-B41:03EEKTSPSQV0.83570.82011221
PRR14L-CC2D1Achr2232134373chr1914034146667HLA-B18:03EEKTSPSQV0.54320.84481221
PRR14L-CC2D1Achr2232134373chr1914034146667HLA-B41:03AEEKTSPSQV0.72230.80361121

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Potential FusionNeoAntigen Information of PRR14L-CC2D1A 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 PRR14L-CC2D1A

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
7309QHSTAAEEKTSPSQPRR14LCC2D1Achr2232134373chr1914034146667

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of PRR14L-CC2D1A

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-B14:023BVN7309QHSTAAEEKTSPSQ-7.9962-8.1096
HLA-B14:023BVN7309QHSTAAEEKTSPSQ-5.70842-6.74372
HLA-B52:013W397309QHSTAAEEKTSPSQ-6.83737-6.95077
HLA-B52:013W397309QHSTAAEEKTSPSQ-4.4836-5.5189
HLA-A11:014UQ27309QHSTAAEEKTSPSQ-10.0067-10.1201
HLA-A11:014UQ27309QHSTAAEEKTSPSQ-9.03915-10.0745
HLA-A24:025HGA7309QHSTAAEEKTSPSQ-6.56204-6.67544
HLA-A24:025HGA7309QHSTAAEEKTSPSQ-5.42271-6.45801
HLA-B44:053DX87309QHSTAAEEKTSPSQ-7.85648-8.89178
HLA-B44:053DX87309QHSTAAEEKTSPSQ-5.3978-5.5112
HLA-A02:016TDR7309QHSTAAEEKTSPSQ-3.37154-4.40684

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Vaccine Design for the FusionNeoAntigens of PRR14L-CC2D1A

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
PRR14L-CC2D1Achr2232134373chr19140341461121AEEKTSPSQVAGTCAGGTGCCGCCTGCCCCTGTCAACAAG
PRR14L-CC2D1Achr2232134373chr19140341461122AEEKTSPSQVPAGTCAGGTGCCGCCTGCCCCTGTCAACAAGGAC
PRR14L-CC2D1Achr2232134373chr19140341461221EEKTSPSQVCAGGTGCCGCCTGCCCCTGTCAACAAG
PRR14L-CC2D1Achr2232134373chr19140341461222EEKTSPSQVPCAGGTGCCGCCTGCCCCTGTCAACAAGGAC

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 PRR14L-CC2D1A

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
UCECPRR14L-CC2D1Achr2232134373ENST00000434485chr1914034146ENST00000318003TCGA-PG-A7D5-01A

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Potential target of CAR-T therapy development for PRR14L-CC2D1A

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 PRR14L-CC2D1A

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 PRR14L-CC2D1A

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