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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:GNAS-ITGAV

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: GNAS-ITGAV
FusionPDB ID: 33630
FusionGDB2.0 ID: 33630
HgeneTgene
Gene symbol

GNAS

ITGAV

Gene ID

2778

3685

Gene nameGNAS complex locusintegrin subunit alpha V
SynonymsAHO|C20orf45|GNAS1|GPSA|GSA|GSP|NESP|PITA3|POH|SCG6|SgVICD51|MSK8|VNRA|VTNR
Cytomap

20q13.32

2q32.1

Type of geneprotein-codingprotein-coding
Descriptionprotein ALEXprotein GNASprotein SCG6 (secretogranin VI)G protein subunit alpha Sadenylate cyclase-stimulating G alpha proteinalternative gene product encoded by XL-exonextra large alphas proteinguanine nucleotide binding protein (G protein), alpha integrin alpha-Vantigen identified by monoclonal antibody L230integrin alphaVbeta3integrin, alpha V (vitronectin receptor, alpha polypeptide, antigen CD51)vitronectin receptor subunit alpha
Modification date2020032920200313
UniProtAcc

P63092

Main function of 5'-partner protein: FUNCTION: Guanine nucleotide-binding proteins (G proteins) function as transducers in numerous signaling pathways controlled by G protein-coupled receptors (GPCRs) (PubMed:17110384). Signaling involves the activation of adenylyl cyclases, resulting in increased levels of the signaling molecule cAMP (PubMed:26206488, PubMed:8702665). GNAS functions downstream of several GPCRs, including beta-adrenergic receptors (PubMed:21488135). Stimulates the Ras signaling pathway via RAPGEF2 (PubMed:12391161). {ECO:0000269|PubMed:12391161, ECO:0000269|PubMed:17110384, ECO:0000269|PubMed:21488135, ECO:0000269|PubMed:26206488, ECO:0000269|PubMed:8702665}.

P06756

Main function of 5'-partner protein: FUNCTION: The alpha-V (ITGAV) integrins are receptors for vitronectin, cytotactin, fibronectin, fibrinogen, laminin, matrix metalloproteinase-2, osteopontin, osteomodulin, prothrombin, thrombospondin and vWF. They recognize the sequence R-G-D in a wide array of ligands. ITGAV:ITGB3 binds to fractalkine (CX3CL1) and may act as its coreceptor in CX3CR1-dependent fractalkine signaling (PubMed:23125415). ITGAV:ITGB3 binds to NRG1 (via EGF domain) and this binding is essential for NRG1-ERBB signaling (PubMed:20682778). ITGAV:ITGB3 binds to FGF1 and this binding is essential for FGF1 signaling (PubMed:18441324). ITGAV:ITGB3 binds to FGF2 and this binding is essential for FGF2 signaling (PubMed:28302677). ITGAV:ITGB3 binds to IGF1 and this binding is essential for IGF1 signaling (PubMed:19578119). ITGAV:ITGB3 binds to IGF2 and this binding is essential for IGF2 signaling (PubMed:28873464). ITGAV:ITGB3 binds to IL1B and this binding is essential for IL1B signaling (PubMed:29030430). ITGAV:ITGB3 binds to PLA2G2A via a site (site 2) which is distinct from the classical ligand-binding site (site 1) and this induces integrin conformational changes and enhanced ligand binding to site 1 (PubMed:18635536, PubMed:25398877). ITGAV:ITGB3 and ITGAV:ITGB6 act as a receptor for fibrillin-1 (FBN1) and mediate R-G-D-dependent cell adhesion to FBN1 (PubMed:12807887, PubMed:17158881). Integrin alpha-V/beta-6 or alpha-V/beta-8 (ITGAV:ITGB6 or ITGAV:ITGB8) mediates R-G-D-dependent release of transforming growth factor beta-1 (TGF-beta-1) from regulatory Latency-associated peptide (LAP), thereby playing a key role in TGF-beta-1 activation (PubMed:15184403, PubMed:22278742, PubMed:28117447). ITGAV:ITGB3 act as a receptor for CD40LG (PubMed:31331973). {ECO:0000269|PubMed:12807887, ECO:0000269|PubMed:15184403, ECO:0000269|PubMed:17158881, ECO:0000269|PubMed:18441324, ECO:0000269|PubMed:18635536, ECO:0000269|PubMed:19578119, ECO:0000269|PubMed:20682778, ECO:0000269|PubMed:22278742, ECO:0000269|PubMed:23125415, ECO:0000269|PubMed:25398877, ECO:0000269|PubMed:28117447, ECO:0000269|PubMed:28302677, ECO:0000269|PubMed:28873464, ECO:0000269|PubMed:29030430, ECO:0000269|PubMed:31331973}.; FUNCTION: (Microbial infection) Integrin ITGAV:ITGB5 acts as a receptor for Adenovirus type C. {ECO:0000269|PubMed:20615244}.; FUNCTION: (Microbial infection) Integrin ITGAV:ITGB5 and ITGAV:ITGB3 act as receptors for Coxsackievirus A9 and B1. {ECO:0000269|PubMed:15194773, ECO:0000269|PubMed:7519807, ECO:0000269|PubMed:9426447}.; FUNCTION: (Microbial infection) Integrin ITGAV:ITGB3 acts as a receptor for Herpes virus 8/HHV-8. {ECO:0000269|PubMed:18045938}.; FUNCTION: (Microbial infection) Integrin ITGAV:ITGB6 acts as a receptor for herpes simplex 1/HHV-1. {ECO:0000269|PubMed:24367260}.; FUNCTION: (Microbial infection) Integrin ITGAV:ITGB3 acts as a receptor for Human parechovirus 1. {ECO:0000269|PubMed:11160695}.; FUNCTION: (Microbial infection) Integrin ITGAV:ITGB3 acts as a receptor for West nile virus. {ECO:0000269|PubMed:23658209}.; FUNCTION: (Microbial infection) In case of HIV-1 infection, the interaction with extracellular viral Tat protein seems to enhance angiogenesis in Kaposi's sarcoma lesions. {ECO:0000269|PubMed:10397733}.
Ensembl transtripts involved in fusion geneENST idsENST00000265620, ENST00000306090, 
ENST00000313949, ENST00000354359, 
ENST00000371075, ENST00000371085, 
ENST00000371095, ENST00000371100, 
ENST00000371102, ENST00000464624, 
ENST00000306120, ENST00000371081, 
ENST00000371098, ENST00000371099, 
ENST00000474571, ENST00000261023, 
ENST00000374907, ENST00000433736, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score44 X 25 X 16=176009 X 8 X 6=432
# samples 519
** MAII scorelog2(51/17600*10)=-5.10893437155316
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(9/432*10)=-2.26303440583379
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: GNAS [Title/Abstract] AND ITGAV [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: GNAS [Title/Abstract] AND ITGAV [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)GNAS(57486241)-ITGAV(187540547), # samples:1
Anticipated loss of major functional domain due to fusion event.GNAS-ITGAV 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.
GNAS-ITGAV 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.
GNAS-ITGAV 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.
GNAS-ITGAV 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.
GNAS-ITGAV seems lost the major protein functional domain in Hgene partner, which is a cell metabolism gene due to the frame-shifted ORF.
GNAS-ITGAV seems lost the major protein functional domain in Hgene partner, which is a CGC due to the frame-shifted ORF.
GNAS-ITGAV seems lost the major protein functional domain in Tgene partner, which is a CGC due to the frame-shifted ORF.
GNAS-ITGAV seems lost the major protein functional domain in Tgene partner, which is a IUPHAR drug target due to the frame-shifted ORF.
GNAS-ITGAV 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
TgeneITGAV

GO:0007155

cell adhesion

10218736

TgeneITGAV

GO:0008284

positive regulation of cell proliferation

19578119

TgeneITGAV

GO:0033627

cell adhesion mediated by integrin

12807887|17158881

TgeneITGAV

GO:0034446

substrate adhesion-dependent cell spreading

24658351

TgeneITGAV

GO:0045785

positive regulation of cell adhesion

10708943

TgeneITGAV

GO:0050764

regulation of phagocytosis

10570297

TgeneITGAV

GO:0070588

calcium ion transmembrane transport

18395422

TgeneITGAV

GO:1901388

regulation of transforming growth factor beta activation

22278742

TgeneITGAV

GO:2000536

negative regulation of entry of bacterium into host cell

10570297



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/chr20:57486241/chr2:187540547)
- 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 GNAS (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 ITGAV (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)
ENST00000371100GNASchr2057486241-ENST00000261023ITGAVchr2187540547+7965402953136651044
ENST00000371100GNASchr2057486241-ENST00000374907ITGAVchr2187540547+7961402953136651044
ENST00000371100GNASchr2057486241-ENST00000433736ITGAVchr2187540547+4505402953136651044
ENST00000371102GNASchr2057486241-ENST00000261023ITGAVchr2187540547+73743438330741023
ENST00000371102GNASchr2057486241-ENST00000374907ITGAVchr2187540547+73703438330741023
ENST00000371102GNASchr2057486241-ENST00000433736ITGAVchr2187540547+39143438330741023
ENST00000371095GNASchr2057486241-ENST00000261023ITGAVchr2187540547+5867193115822527
ENST00000371095GNASchr2057486241-ENST00000374907ITGAVchr2187540547+586319314251567380
ENST00000371095GNASchr2057486241-ENST00000433736ITGAVchr2187540547+240719314251567380
ENST00000371085GNASchr2057486241-ENST00000261023ITGAVchr2187540547+5908197216231541
ENST00000371085GNASchr2057486241-ENST00000374907ITGAVchr2187540547+590419724241608394
ENST00000371085GNASchr2057486241-ENST00000433736ITGAVchr2187540547+244819724241608394
ENST00000354359GNASchr2057486241-ENST00000261023ITGAVchr2187540547+5911197516261542
ENST00000354359GNASchr2057486241-ENST00000374907ITGAVchr2187540547+590719754241611395
ENST00000354359GNASchr2057486241-ENST00000433736ITGAVchr2187540547+245119754241611395
ENST00000265620GNASchr2057486241-ENST00000261023ITGAVchr2187540547+5802186615170506
ENST00000265620GNASchr2057486241-ENST00000374907ITGAVchr2187540547+579818663631502379
ENST00000265620GNASchr2057486241-ENST00000433736ITGAVchr2187540547+234218663631502379
ENST00000306090GNASchr2057486241-ENST00000261023ITGAVchr2187540547+5578164212991433
ENST00000306090GNASchr2057486241-ENST00000374907ITGAVchr2187540547+557416421421284380
ENST00000306090GNASchr2057486241-ENST00000433736ITGAVchr2187540547+211816421421284380

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
ENST00000371100ENST00000261023GNASchr2057486241-ITGAVchr2187540547+0.0006243830.99937564
ENST00000371100ENST00000374907GNASchr2057486241-ITGAVchr2187540547+0.0006242260.99937576
ENST00000371100ENST00000433736GNASchr2057486241-ITGAVchr2187540547+0.0052110320.994789
ENST00000371102ENST00000261023GNASchr2057486241-ITGAVchr2187540547+0.0002554580.9997446
ENST00000371102ENST00000374907GNASchr2057486241-ITGAVchr2187540547+0.0002554880.9997445
ENST00000371102ENST00000433736GNASchr2057486241-ITGAVchr2187540547+0.0032753260.99672467
ENST00000371095ENST00000261023GNASchr2057486241-ITGAVchr2187540547+0.0002261620.9997738
ENST00000371095ENST00000374907GNASchr2057486241-ITGAVchr2187540547+0.0002214090.99977857
ENST00000371095ENST00000433736GNASchr2057486241-ITGAVchr2187540547+0.0035418740.9964581
ENST00000371085ENST00000261023GNASchr2057486241-ITGAVchr2187540547+0.0002298990.9997701
ENST00000371085ENST00000374907GNASchr2057486241-ITGAVchr2187540547+0.0002260840.9997739
ENST00000371085ENST00000433736GNASchr2057486241-ITGAVchr2187540547+0.0036014380.99639857
ENST00000354359ENST00000261023GNASchr2057486241-ITGAVchr2187540547+0.000186480.9998135
ENST00000354359ENST00000374907GNASchr2057486241-ITGAVchr2187540547+0.0001834630.9998166
ENST00000354359ENST00000433736GNASchr2057486241-ITGAVchr2187540547+0.0027453620.99725467
ENST00000265620ENST00000261023GNASchr2057486241-ITGAVchr2187540547+0.0001323080.9998677
ENST00000265620ENST00000374907GNASchr2057486241-ITGAVchr2187540547+0.0001294530.99987054
ENST00000265620ENST00000433736GNASchr2057486241-ITGAVchr2187540547+0.002216310.9977837
ENST00000306090ENST00000261023GNASchr2057486241-ITGAVchr2187540547+0.0002143710.9997856
ENST00000306090ENST00000374907GNASchr2057486241-ITGAVchr2187540547+0.0002094720.9997905
ENST00000306090ENST00000433736GNASchr2057486241-ITGAVchr2187540547+0.0032844330.99671555

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 GNAS-ITGAV

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

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Potential FusionNeoAntigen Information of GNAS-ITGAV 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 GNAS-ITGAV 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 GNAS-ITGAV

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 GNAS-ITGAV

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 GNAS-ITGAV

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 GNAS-ITGAV

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 GNAS-ITGAV

check button Predicted 3D structure. We used RoseTTAFold.
202_GNAS-ITGAV_df54b_pred.pdb


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
TgeneITGAVchr20:57486241chr2:187540547ENST000002610232630993_101601049.0TransmembraneHelical
TgeneITGAVchr20:57486241chr2:187540547ENST000003749072428993_101601013.0TransmembraneHelical
TgeneITGAVchr20:57486241chr2:187540547ENST000004337362630993_101601003.0TransmembraneHelical

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
GNASchr2057486241ENST00000265620ITGAVchr2187540547ENST00000261023
GNASchr2057486241ENST00000265620ITGAVchr2187540547ENST00000374907
GNASchr2057486241ENST00000306090ITGAVchr2187540547ENST00000261023
GNASchr2057486241ENST00000306090ITGAVchr2187540547ENST00000374907
GNASchr2057486241ENST00000354359ITGAVchr2187540547ENST00000261023
GNASchr2057486241ENST00000354359ITGAVchr2187540547ENST00000374907
GNASchr2057486241ENST00000371085ITGAVchr2187540547ENST00000261023
GNASchr2057486241ENST00000371085ITGAVchr2187540547ENST00000374907
GNASchr2057486241ENST00000371095ITGAVchr2187540547ENST00000261023

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Related Drugs to GNAS-ITGAV

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 GNAS-ITGAV

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