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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:FOXP1-SH3RF2

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: FOXP1-SH3RF2
FusionPDB ID: 31217
FusionGDB2.0 ID: 31217
HgeneTgene
Gene symbol

FOXP1

SH3RF2

Gene ID

27086

153769

Gene nameforkhead box P1SH3 domain containing ring finger 2
Synonyms12CC4|HSPC215|MFH|QRF1|hFKH1BHEPP1|POSHER|PPP1R39|RNF158
Cytomap

3p13

5q32

Type of geneprotein-codingprotein-coding
Descriptionforkhead box protein P1fork head-related protein like Bglutamine-rich factor 1mac-1-regulated forkheadE3 ubiquitin-protein ligase SH3RF2POSH-eliminating RING proteinRING finger protein 158RING-type E3 ubiquitin transferase SH3RF2SH3 domain-containing RING finger protein 2heart protein phosphatase 1-binding proteinphosphatase 1 binding proteinprotei
Modification date2020032920200313
UniProtAcc

Q9H334

Main function of 5'-partner protein: FUNCTION: Transcriptional repressor (PubMed:18347093, PubMed:26647308). Can act with CTBP1 to synergistically repress transcription but CTPBP1 is not essential (By similarity). Plays an important role in the specification and differentiation of lung epithelium. Acts cooperatively with FOXP4 to regulate lung secretory epithelial cell fate and regeneration by restricting the goblet cell lineage program; the function may involve regulation of AGR2. Essential transcriptional regulator of B-cell development. Involved in regulation of cardiac muscle cell proliferation. Involved in the columnar organization of spinal motor neurons. Promotes the formation of the lateral motor neuron column (LMC) and the preganglionic motor column (PGC) and is required for respective appropriate motor axon projections. The segment-appropriate generation of spinal chord motor columns requires cooperation with other Hox proteins. Can regulate PITX3 promoter activity; may promote midbrain identity in embryonic stem cell-derived dopamine neurons by regulating PITX3. Negatively regulates the differentiation of T follicular helper cells T(FH)s. Involved in maintenance of hair follicle stem cell quiescence; the function probably involves regulation of FGF18 (By similarity). Represses transcription of various pro-apoptotic genes and cooperates with NF-kappa B-signaling in promoting B-cell expansion by inhibition of caspase-dependent apoptosis (PubMed:25267198). Binds to CSF1R promoter elements and is involved in regulation of monocyte differentiation and macrophage functions; repression of CSF1R in monocytes seems to involve NCOR2 as corepressor (PubMed:15286807, PubMed:18799727, PubMed:18347093). Involved in endothelial cell proliferation, tube formation and migration indicative for a role in angiogenesis; the role in neovascularization seems to implicate suppression of SEMA5B (PubMed:24023716). Can negatively regulate androgen receptor signaling (PubMed:18640093). Acts as a transcriptional activator of the FBXL7 promoter; this activity is regulated by AURKA (PubMed:28218735). {ECO:0000250|UniProtKB:P58462, ECO:0000269|PubMed:15286807, ECO:0000269|PubMed:18640093, ECO:0000269|PubMed:18799727, ECO:0000269|PubMed:24023716, ECO:0000269|PubMed:25267198, ECO:0000269|PubMed:26647308, ECO:0000269|PubMed:28218735, ECO:0000305|PubMed:18347093, ECO:0000305|PubMed:24023716}.; FUNCTION: [Isoform 8]: Involved in transcriptional regulation in embryonic stem cells (ESCs). Stimulates expression of transcription factors that are required for pluripotency and decreases expression of differentiation-associated genes. Has distinct DNA-binding specifities as compared to the canonical form and preferentially binds DNA with the sequence 5'-CGATACAA-3' (or closely related sequences) (PubMed:21924763). Promotes ESC self-renewal and pluripotency (By similarity). {ECO:0000250|UniProtKB:P58462, ECO:0000269|PubMed:21924763}.
.
Ensembl transtripts involved in fusion geneENST idsENST00000318789, ENST00000468577, 
ENST00000475937, ENST00000484350, 
ENST00000491238, ENST00000493089, 
ENST00000498215, ENST00000472382, 
ENST00000318779, 
ENST00000511705, 
ENST00000359120, ENST00000511217, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score34 X 30 X 13=132603 X 2 X 3=18
# samples 383
** MAII scorelog2(38/13260*10)=-5.124937546669
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(3/18*10)=0.736965594166206
effective Gene in Pan-Cancer Fusion Genes (eGinPCFGs).
DoF>8 and MAII>0
Fusion gene context

PubMed: FOXP1 [Title/Abstract] AND SH3RF2 [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: FOXP1 [Title/Abstract] AND SH3RF2 [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)FOXP1(71090479)-SH3RF2(145379621), # samples:3
Anticipated loss of major functional domain due to fusion event.FOXP1-SH3RF2 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.
FOXP1-SH3RF2 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.
FOXP1-SH3RF2 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.
FOXP1-SH3RF2 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.
FOXP1-SH3RF2 seems lost the major protein functional domain in Hgene partner, which is a CGC due to the frame-shifted ORF.
FOXP1-SH3RF2 seems lost the major protein functional domain in Hgene partner, which is a epigenetic factor due to the frame-shifted ORF.
FOXP1-SH3RF2 seems lost the major protein functional domain in Hgene partner, which is a transcription factor due to the frame-shifted ORF.
FOXP1-SH3RF2 seems lost the major protein functional domain in Hgene partner, which is a tumor suppressor due to the frame-shifted ORF.
FOXP1-SH3RF2 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
HgeneFOXP1

GO:0002903

negative regulation of B cell apoptotic process

25267198

HgeneFOXP1

GO:0010629

negative regulation of gene expression

30111844

HgeneFOXP1

GO:0030316

osteoclast differentiation

18799727

HgeneFOXP1

GO:0032496

response to lipopolysaccharide

18799727

HgeneFOXP1

GO:0032680

regulation of tumor necrosis factor production

18799727

HgeneFOXP1

GO:0035926

chemokine (C-C motif) ligand 2 secretion

18799727

HgeneFOXP1

GO:0036035

osteoclast development

18799727

HgeneFOXP1

GO:0042116

macrophage activation

18799727

HgeneFOXP1

GO:0042117

monocyte activation

18799727

HgeneFOXP1

GO:0045655

regulation of monocyte differentiation

15286807

HgeneFOXP1

GO:0045892

negative regulation of transcription, DNA-templated

20950788

HgeneFOXP1

GO:0050706

regulation of interleukin-1 beta secretion

18799727

HgeneFOXP1

GO:0050727

regulation of inflammatory response

18799727

HgeneFOXP1

GO:0060766

negative regulation of androgen receptor signaling pathway

18640093

HgeneFOXP1

GO:1900424

regulation of defense response to bacterium

18799727

HgeneFOXP1

GO:1901256

regulation of macrophage colony-stimulating factor production

18799727

HgeneFOXP1

GO:2001182

regulation of interleukin-12 secretion

18799727

TgeneSH3RF2

GO:0010923

negative regulation of phosphatase activity

19389623



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/chr3:71090479/chr5:145379621)
- 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 FOXP1 (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 SH3RF2 (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)
ENST00000318789FOXP1chr371090479-ENST00000359120SH3RF2chr5145379621+3822139512183206662
ENST00000318789FOXP1chr371090479-ENST00000511217SH3RF2chr5145379621+6572139512183206662
ENST00000493089FOXP1chr371090479-ENST00000359120SH3RF2chr5145379621+3925149813213309662
ENST00000493089FOXP1chr371090479-ENST00000511217SH3RF2chr5145379621+6675149813213309662

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
ENST00000318789ENST00000359120FOXP1chr371090479-SH3RF2chr5145379621+0.043149310.9568507
ENST00000318789ENST00000511217FOXP1chr371090479-SH3RF2chr5145379621+0.0073812450.99261874
ENST00000493089ENST00000359120FOXP1chr371090479-SH3RF2chr5145379621+0.0437480430.9562519
ENST00000493089ENST00000511217FOXP1chr371090479-SH3RF2chr5145379621+0.0066286360.99337137

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 FOXP1-SH3RF2

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
FOXP1chr371090479SH3RF2chr5145379621139559QWTALSPHSQKGKVPRAKALCNYRGQ
FOXP1chr371090479SH3RF2chr5145379621149859QWTALSPHSQKGKVPRAKALCNYRGQ

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Potential FusionNeoAntigen Information of FOXP1-SH3RF2 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.
FOXP1-SH3RF2_71090479_145379621.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)
FOXP1-SH3RF2chr371090479chr51453796211395HLA-A31:02HSQKGKVPR0.93670.5335716
FOXP1-SH3RF2chr371090479chr51453796211395HLA-B14:02GKVPRAKAL0.910.82331120
FOXP1-SH3RF2chr371090479chr51453796211395HLA-B14:01GKVPRAKAL0.910.82331120
FOXP1-SH3RF2chr371090479chr51453796211395HLA-B07:10GKVPRAKAL0.01220.65721120
FOXP1-SH3RF2chr371090479chr51453796211395HLA-A02:13ALSPHSQKGKV0.94240.5695314
FOXP1-SH3RF2chr371090479chr51453796211395HLA-C01:17KVPRAKAL0.94390.95261220
FOXP1-SH3RF2chr371090479chr51453796211395HLA-C01:30KVPRAKAL0.91470.95881220
FOXP1-SH3RF2chr371090479chr51453796211395HLA-B15:04SQKGKVPRA0.83820.902817
FOXP1-SH3RF2chr371090479chr51453796211395HLA-B14:03GKVPRAKAL0.40440.8021120
FOXP1-SH3RF2chr371090479chr51453796211395HLA-C01:02KVPRAKAL0.92180.9531220
FOXP1-SH3RF2chr371090479chr51453796211395HLA-C01:03KVPRAKAL0.86650.95361220
FOXP1-SH3RF2chr371090479chr51453796211395HLA-A30:01KGKVPRAKA0.96280.86331019
FOXP1-SH3RF2chr371090479chr51453796211395HLA-A30:01SQKGKVPRA0.93840.7867817
FOXP1-SH3RF2chr371090479chr51453796211395HLA-B67:01SPHSQKGKV0.17570.6098514
FOXP1-SH3RF2chr371090479chr51453796211395HLA-B15:68GKVPRAKAL0.12280.62741120
FOXP1-SH3RF2chr371090479chr51453796211395HLA-A30:01SQKGKVPRAK0.98520.7774818

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Potential FusionNeoAntigen Information of FOXP1-SH3RF2 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 FOXP1-SH3RF2

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
6691PHSQKGKVPRAKALFOXP1SH3RF2chr371090479chr51453796211395

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of FOXP1-SH3RF2

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-B14:023BVN6691PHSQKGKVPRAKAL-6.77781-6.89121
HLA-B14:023BVN6691PHSQKGKVPRAKAL-3.08719-4.12249
HLA-B52:013W396691PHSQKGKVPRAKAL-6.66315-6.77655
HLA-B52:013W396691PHSQKGKVPRAKAL-2.65785-3.69315
HLA-A24:025HGA6691PHSQKGKVPRAKAL-7.20627-7.31967
HLA-A24:025HGA6691PHSQKGKVPRAKAL-6.50211-7.53741
HLA-B44:053DX86691PHSQKGKVPRAKAL-7.75024-7.86364
HLA-B44:053DX86691PHSQKGKVPRAKAL-6.53073-7.56603
HLA-A02:016TDR6691PHSQKGKVPRAKAL-4.4528-5.4881

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Vaccine Design for the FusionNeoAntigens of FOXP1-SH3RF2

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
FOXP1-SH3RF2chr371090479chr51453796211019KGKVPRAKAAAGGGAAAGGTGCCTCGAGCAAAGGCC
FOXP1-SH3RF2chr371090479chr51453796211120GKVPRAKALGGAAAGGTGCCTCGAGCAAAGGCCTTA
FOXP1-SH3RF2chr371090479chr51453796211220KVPRAKALAAGGTGCCTCGAGCAAAGGCCTTA
FOXP1-SH3RF2chr371090479chr5145379621314ALSPHSQKGKVGCTCTCAGTCCACACTCCCAAAAGGGAAAGGTG
FOXP1-SH3RF2chr371090479chr5145379621514SPHSQKGKVAGTCCACACTCCCAAAAGGGAAAGGTG
FOXP1-SH3RF2chr371090479chr5145379621716HSQKGKVPRCACTCCCAAAAGGGAAAGGTGCCTCGA
FOXP1-SH3RF2chr371090479chr5145379621817SQKGKVPRATCCCAAAAGGGAAAGGTGCCTCGAGCA
FOXP1-SH3RF2chr371090479chr5145379621818SQKGKVPRAKTCCCAAAAGGGAAAGGTGCCTCGAGCAAAG

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 FOXP1-SH3RF2

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
CHOLFOXP1-SH3RF2chr371090479ENST00000318789chr5145379621ENST00000359120TCGA-WD-A7RX-01A

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Potential target of CAR-T therapy development for FOXP1-SH3RF2

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 FOXP1-SH3RF2

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 FOXP1-SH3RF2

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