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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:FCHSD2-ARHGEF17

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: FCHSD2-ARHGEF17
FusionPDB ID: 29981
FusionGDB2.0 ID: 29981
HgeneTgene
Gene symbol

FCHSD2

ARHGEF17

Gene ID

9873

9828

Gene nameFCH and double SH3 domains 2Rho guanine nucleotide exchange factor 17
SynonymsNWK|NWK1|SH3MD3P164RHOGEF|RHOGEF17|TEM4|p164-RhoGEF
Cytomap

11q13.4

11q13.4

Type of geneprotein-codingprotein-coding
DescriptionF-BAR and double SH3 domains protein 2FCH and double SH3 domains protein 2SH3 multiple domains 3SH3 multiple domains protein 3caromnervous wreck homologprotein nervous wreck 1rho guanine nucleotide exchange factor 17164 kDa Rho-specific guanine-nucleotide exchange factorRho guanine nucleotide exchange factor (GEF) 17Rho-specific guanine-nucleotide exchange factor 164 kDatumor endothelial marker 4
Modification date2020031320200313
UniProtAcc

O94868

Main function of 5'-partner protein: FUNCTION: Adapter protein that plays a role in endocytosis via clathrin-coated pits. Contributes to the internalization of cell surface receptors, such as integrin ITGB1 and transferrin receptor (PubMed:29887380). Promotes endocytosis of EGFR in cancer cells, and thereby contributes to the down-regulation of EGFR signaling (PubMed:30249660). Recruited to clathrin-coated pits during a mid-to-late stage of assembly, where it is required for normal progress from U-shaped intermediate stage pits to terminal, omega-shaped pits (PubMed:29887380). Binds to membranes enriched in phosphatidylinositol 3,4-bisphosphate or phosphatidylinositol 3,4,5-trisphosphate (PubMed:29887380). When bound to membranes, promotes actin polymerization via its interaction with WAS and/or WASL which leads to the activation of the Arp2/3 complex. Does not promote actin polymerisation in the absence of membranes (PubMed:29887380). {ECO:0000269|PubMed:29887380, ECO:0000269|PubMed:30249660}.

Q96PE2

Main function of 5'-partner protein: FUNCTION: Acts as guanine nucleotide exchange factor (GEF) for RhoA GTPases. {ECO:0000269|PubMed:12071859}.
Ensembl transtripts involved in fusion geneENST idsENST00000311172, ENST00000409314, 
ENST00000409418, ENST00000409853, 
ENST00000458644, ENST00000409263, 
ENST00000536170, ENST00000263674, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score43 X 26 X 16=178885 X 3 X 5=75
# samples 595
** MAII scorelog2(59/17888*10)=-4.92213332859399
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(5/75*10)=-0.584962500721156
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: FCHSD2 [Title/Abstract] AND ARHGEF17 [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: FCHSD2 [Title/Abstract] AND ARHGEF17 [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)FCHSD2(72578910)-ARHGEF17(73057928), # samples:3
Anticipated loss of major functional domain due to fusion event.FCHSD2-ARHGEF17 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.
FCHSD2-ARHGEF17 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.
FCHSD2-ARHGEF17 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.
FCHSD2-ARHGEF17 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.
FCHSD2-ARHGEF17 seems lost the major protein functional domain in Hgene partner, which is a essential gene due to the frame-shifted ORF.
FCHSD2-ARHGEF17 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
TgeneARHGEF17

GO:0030036

actin cytoskeleton organization

12071859



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/chr11:72578910/chr11:73057928)
- 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 FCHSD2 (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 ARHGEF17 (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)
ENST00000311172FCHSD2chr1172578910-ENST00000263674ARHGEF17chr1173057928+5690137912543781417
ENST00000409314FCHSD2chr1172578910-ENST00000263674ARHGEF17chr1173057928+5860154916945481459
ENST00000409418FCHSD2chr1172578910-ENST00000263674ARHGEF17chr1173057928+6003169238446911435
ENST00000458644FCHSD2chr1172578910-ENST00000263674ARHGEF17chr1173057928+5582127129042701326

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
ENST00000311172ENST00000263674FCHSD2chr1172578910-ARHGEF17chr1173057928+0.0030912650.9969087
ENST00000409314ENST00000263674FCHSD2chr1172578910-ARHGEF17chr1173057928+0.0029351250.9970649
ENST00000409418ENST00000263674FCHSD2chr1172578910-ARHGEF17chr1173057928+0.0039000520.99609995
ENST00000458644ENST00000263674FCHSD2chr1172578910-ARHGEF17chr1173057928+0.0040016380.9959984

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 FCHSD2-ARHGEF17

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
FCHSD2chr1172578910ARHGEF17chr11730579281271322NERWARPPAVTSNGTLHSDMRKHVAM
FCHSD2chr1172578910ARHGEF17chr11730579281379413NERWARPPAVTSNGTLHSDMRKHVAM
FCHSD2chr1172578910ARHGEF17chr11730579281549455NERWARPPAVTSNGTLHSDMRKHVAM
FCHSD2chr1172578910ARHGEF17chr11730579281692431NERWARPPAVTSNGTLHSDMRKHVAM

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Potential FusionNeoAntigen Information of FCHSD2-ARHGEF17 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 FCHSD2-ARHGEF17 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.
FCHSD2-ARHGEF17_72578910_73057928.msa

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)
FCHSD2-ARHGEF17chr1172578910chr11730579281379DRB1-0307SNGTLHSDMRKHVAM1126
FCHSD2-ARHGEF17chr1172578910chr11730579281379DRB1-0324SNGTLHSDMRKHVAM1126
FCHSD2-ARHGEF17chr1172578910chr11730579281379DRB1-1107SNGTLHSDMRKHVAM1126
FCHSD2-ARHGEF17chr1172578910chr11730579281379DRB3-0201PPAVTSNGTLHSDMR621
FCHSD2-ARHGEF17chr1172578910chr11730579281379DRB3-0201RPPAVTSNGTLHSDM520
FCHSD2-ARHGEF17chr1172578910chr11730579281379DRB3-0201ARPPAVTSNGTLHSD419
FCHSD2-ARHGEF17chr1172578910chr11730579281379DRB3-0204PPAVTSNGTLHSDMR621
FCHSD2-ARHGEF17chr1172578910chr11730579281379DRB3-0204RPPAVTSNGTLHSDM520
FCHSD2-ARHGEF17chr1172578910chr11730579281379DRB3-0204ARPPAVTSNGTLHSD419
FCHSD2-ARHGEF17chr1172578910chr11730579281379DRB3-0205PPAVTSNGTLHSDMR621
FCHSD2-ARHGEF17chr1172578910chr11730579281379DRB3-0214PPAVTSNGTLHSDMR621
FCHSD2-ARHGEF17chr1172578910chr11730579281379DRB3-0224PPAVTSNGTLHSDMR621
FCHSD2-ARHGEF17chr1172578910chr11730579281379DRB3-0224RPPAVTSNGTLHSDM520
FCHSD2-ARHGEF17chr1172578910chr11730579281379DRB3-0224ARPPAVTSNGTLHSD419

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Fusion breakpoint peptide structures of FCHSD2-ARHGEF17

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 FCHSD2-ARHGEF17

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 FCHSD2-ARHGEF17

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
FCHSD2-ARHGEF17chr1172578910chr11730579281126SNGTLHSDMRKHVAMCACTCGGACATGCGGAAGCACGTGGCCATGACCCTGCTGGACACA
FCHSD2-ARHGEF17chr1172578910chr1173057928419ARPPAVTSNGTLHSDGTGACCAGTAATGGCACTTTACACTCGGACATGCGGAAGCACGTG
FCHSD2-ARHGEF17chr1172578910chr1173057928520RPPAVTSNGTLHSDMACCAGTAATGGCACTTTACACTCGGACATGCGGAAGCACGTGGCC
FCHSD2-ARHGEF17chr1172578910chr1173057928621PPAVTSNGTLHSDMRAGTAATGGCACTTTACACTCGGACATGCGGAAGCACGTGGCCATG

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Information of the samples that have these potential fusion neoantigens of FCHSD2-ARHGEF17

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 FCHSD2-ARHGEF17

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 FCHSD2-ARHGEF17

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 FCHSD2-ARHGEF17

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