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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:FKBP4-GNB2L1

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: FKBP4-GNB2L1
FusionPDB ID: 30500
FusionGDB2.0 ID: 30500
HgeneTgene
Gene symbol

FKBP4

GNB2L1

Gene ID

63943

10399

Gene nameFKBP prolyl isomerase likereceptor for activated C kinase 1
SynonymsDIR1|FKBP4|NG7|WISP39GNB2L1|Gnb2-rs1|H12.3|HLC-7|PIG21
Cytomap

6p21.32

5q35.3

Type of geneprotein-codingprotein-coding
DescriptionFK506-binding protein-likeFK506 binding protein likeWAF-1/CIP1 stabilizing protein 39peptidyl-prolyl cis-trans isomerasereceptor of activated protein C kinase 1cell proliferation-inducing gene 21 proteinguanine nucleotide binding protein (G protein), beta polypeptide 2-like 1guanine nucleotide binding protein beta polypeptide 2-like 1guanine nucleotide-binding protein
Modification date2020031320200313
UniProtAcc

Q02790

Main function of 5'-partner protein: FUNCTION: Immunophilin protein with PPIase and co-chaperone activities. Component of steroid receptors heterocomplexes through interaction with heat-shock protein 90 (HSP90). May play a role in the intracellular trafficking of heterooligomeric forms of steroid hormone receptors between cytoplasm and nuclear compartments. The isomerase activity controls neuronal growth cones via regulation of TRPC1 channel opening. Acts also as a regulator of microtubule dynamics by inhibiting MAPT/TAU ability to promote microtubule assembly. May have a protective role against oxidative stress in mitochondria. {ECO:0000269|PubMed:1279700, ECO:0000269|PubMed:1376003, ECO:0000269|PubMed:19945390, ECO:0000269|PubMed:21730050, ECO:0000269|PubMed:2378870}.
.
Ensembl transtripts involved in fusion geneENST idsENST00000001008, ENST00000540260, 
ENST00000456394, ENST00000505461, 
ENST00000511566, ENST00000511900, 
ENST00000514455, ENST00000376817, 
ENST00000504726, ENST00000512805, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score7 X 7 X 5=24511 X 10 X 7=770
# samples 812
** MAII scorelog2(8/245*10)=-1.61470984411521
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(12/770*10)=-2.68182403997375
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: FKBP4 [Title/Abstract] AND GNB2L1 [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: FKBP4 [Title/Abstract] AND GNB2L1 [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)FKBP4(2904410)-GNB2L1(180664042), # samples:1
Anticipated loss of major functional domain due to fusion event.FKBP4-GNB2L1 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.
FKBP4-GNB2L1 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.
FKBP4-GNB2L1 seems lost the major protein functional domain in Tgene partner, which is a essential gene due to the frame-shifted ORF.
FKBP4-GNB2L1 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
TgeneGNB2L1

GO:0001934

positive regulation of protein phosphorylation

11312657|17108144

TgeneGNB2L1

GO:0030308

negative regulation of cell growth

9584165

TgeneGNB2L1

GO:0030335

positive regulation of cell migration

20499158

TgeneGNB2L1

GO:0031334

positive regulation of protein complex assembly

20541605

TgeneGNB2L1

GO:0032091

negative regulation of protein binding

20541605

TgeneGNB2L1

GO:0032436

positive regulation of proteasomal ubiquitin-dependent protein catabolic process

19785988

TgeneGNB2L1

GO:0043065

positive regulation of apoptotic process

20541605

TgeneGNB2L1

GO:0043547

positive regulation of GTPase activity

20499158

TgeneGNB2L1

GO:0051726

regulation of cell cycle

9584165

TgeneGNB2L1

GO:0071333

cellular response to glucose stimulus

20103773

TgeneGNB2L1

GO:0071363

cellular response to growth factor stimulus

20010870



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/chr12:2904410/chr5:180664042)
- 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 FKBP4 (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 GNB2L1 (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)
ENST00000001008FKBP4chr122904410+ENST00000376817GNB2L1chr5180664042-3982929395129
ENST00000001008FKBP4chr122904410+ENST00000512805GNB2L1chr5180664042-3982929395129
ENST00000001008FKBP4chr122904410+ENST00000504726GNB2L1chr5180664042-3942929392128

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
ENST00000001008ENST00000376817FKBP4chr122904410+GNB2L1chr5180664042-0.424930960.57506907
ENST00000001008ENST00000512805FKBP4chr122904410+GNB2L1chr5180664042-0.424930960.57506907
ENST00000001008ENST00000504726FKBP4chr122904410+GNB2L1chr5180664042-0.415022280.58497775

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 FKBP4-GNB2L1

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
FKBP4chr122904410GNB2L1chr518066404229294SGHQPQTGRRRAEDSVCWLHGQPGAS

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Potential FusionNeoAntigen Information of FKBP4-GNB2L1 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.
FKBP4-GNB2L1_2904410_180664042.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)
FKBP4-GNB2L1chr122904410chr5180664042292HLA-B27:05RRAEDSVCW0.97860.641918
FKBP4-GNB2L1chr122904410chr5180664042292HLA-B27:07RRAEDSVCWL0.99710.6032919
FKBP4-GNB2L1chr122904410chr5180664042292HLA-C05:09RAEDSVCWL0.9970.9391019
FKBP4-GNB2L1chr122904410chr5180664042292HLA-C08:15RAEDSVCWL0.99530.9771019
FKBP4-GNB2L1chr122904410chr5180664042292HLA-B27:03RRAEDSVCW0.88510.6527918
FKBP4-GNB2L1chr122904410chr5180664042292HLA-C07:95RRAEDSVCW0.84520.7816918
FKBP4-GNB2L1chr122904410chr5180664042292HLA-C08:03RAEDSVCWL0.38550.99031019
FKBP4-GNB2L1chr122904410chr5180664042292HLA-C05:01RAEDSVCWL0.9970.9391019
FKBP4-GNB2L1chr122904410chr5180664042292HLA-C08:02RAEDSVCWL0.99530.9771019
FKBP4-GNB2L1chr122904410chr5180664042292HLA-B27:08RRAEDSVCW0.97750.5461918
FKBP4-GNB2L1chr122904410chr5180664042292HLA-C07:01RRAEDSVCW0.85780.776918
FKBP4-GNB2L1chr122904410chr5180664042292HLA-C07:22RRAEDSVCW0.40520.7769918
FKBP4-GNB2L1chr122904410chr5180664042292HLA-C08:01RAEDSVCWL0.38550.99031019
FKBP4-GNB2L1chr122904410chr5180664042292HLA-B07:13RAEDSVCWL0.01430.83531019
FKBP4-GNB2L1chr122904410chr5180664042292HLA-B27:06RRAEDSVCWL0.99770.8584919
FKBP4-GNB2L1chr122904410chr5180664042292HLA-B27:09RRAEDSVCWL0.99710.722919

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Potential FusionNeoAntigen Information of FKBP4-GNB2L1 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 FKBP4-GNB2L1

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
9369TGRRRAEDSVCWLHFKBP4GNB2L1chr122904410chr5180664042292

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of FKBP4-GNB2L1

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-B14:023BVN9369TGRRRAEDSVCWLH-5.49577-5.60917
HLA-B14:023BVN9369TGRRRAEDSVCWLH-4.37152-5.40682
HLA-B52:013W399369TGRRRAEDSVCWLH-6.90336-7.01676
HLA-B52:013W399369TGRRRAEDSVCWLH-4.80833-5.84363
HLA-A11:014UQ29369TGRRRAEDSVCWLH-9.82261-9.93601
HLA-A24:025HGA9369TGRRRAEDSVCWLH-9.78612-9.89952
HLA-A24:025HGA9369TGRRRAEDSVCWLH-4.98992-6.02522
HLA-B27:056PYJ9369TGRRRAEDSVCWLH-5.31553-6.35083
HLA-B44:053DX89369TGRRRAEDSVCWLH-5.70582-5.81922
HLA-B44:053DX89369TGRRRAEDSVCWLH-4.32241-5.35771

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Vaccine Design for the FusionNeoAntigens of FKBP4-GNB2L1

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
FKBP4-GNB2L1chr122904410chr51806640421019RAEDSVCWLGTGCTGAAGACTCTGTTTGCTGGCTAC
FKBP4-GNB2L1chr122904410chr5180664042918RRAEDSVCWGGCGTGCTGAAGACTCTGTTTGCTGGC
FKBP4-GNB2L1chr122904410chr5180664042919RRAEDSVCWLGGCGTGCTGAAGACTCTGTTTGCTGGCTAC

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 FKBP4-GNB2L1

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
OVFKBP4-GNB2L1chr122904410ENST00000001008chr5180664042ENST00000376817TCGA-36-1578

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Potential target of CAR-T therapy development for FKBP4-GNB2L1

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 FKBP4-GNB2L1

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 FKBP4-GNB2L1

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