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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:ITGA3-LRWD1

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: ITGA3-LRWD1
FusionPDB ID: 40423
FusionGDB2.0 ID: 40423
HgeneTgene
Gene symbol

ITGA3

LRWD1

Gene ID

3675

222229

Gene nameintegrin subunit alpha 3leucine rich repeats and WD repeat domain containing 1
SynonymsCD49C|FRP-2|GAP-B3|GAPB3|ILNEB|MSK18|VCA-2|VL3A|VLA3aCENP-33|ORCA
Cytomap

17q21.33

7q22.1

Type of geneprotein-codingprotein-coding
Descriptionintegrin alpha-3CD49 antigen-like family member Calpha 3 subunit of VLA-3 receptorantigen CD49Cantigen identified by monoclonal antibody J143galactoprotein B3integrin alpha 3integrin, alpha 3 (antigen CD49C, alpha 3 subunit of VLA-3 receptor)testileucine-rich repeat and WD repeat-containing protein 1ORC-associated proteincentromere protein 33origin recognition complex-associated proteintesticular tissue protein Li 4
Modification date2020032020200313
UniProtAcc

P26006

Main function of 5'-partner protein: FUNCTION: Integrin alpha-3/beta-1 is a receptor for fibronectin, laminin, collagen, epiligrin, thrombospondin and CSPG4. Integrin alpha-3/beta-1 provides a docking site for FAP (seprase) at invadopodia plasma membranes in a collagen-dependent manner and hence may participate in the adhesion, formation of invadopodia and matrix degradation processes, promoting cell invasion. Alpha-3/beta-1 may mediate with LGALS3 the stimulation by CSPG4 of endothelial cells migration. {ECO:0000269|PubMed:10455171, ECO:0000269|PubMed:15181153}.

Q9UFC0

Main function of 5'-partner protein: FUNCTION: Required for G1/S transition. Recruits and stabilizes the origin recognition complex (ORC) onto chromatin during G1 to establish pre-replication complex (preRC) and to heterochromatic sites in post-replicated cells. Binds a combination of DNA and histone methylation repressive marks on heterochromatin. Binds histone H3 and H4 trimethylation marks H3K9me3, H3K27me3 and H4K20me3 in a cooperative manner with DNA methylation. Required for silencing of major satellite repeats. May be important ORC2, ORC3 and ORC4 stability. {ECO:0000269|PubMed:20850016, ECO:0000269|PubMed:20932478, ECO:0000269|PubMed:21029866, ECO:0000269|PubMed:22427655, ECO:0000269|PubMed:22645314}.
Ensembl transtripts involved in fusion geneENST idsENST00000007722, ENST00000320031, 
ENST00000544892, 
ENST00000292616, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score9 X 10 X 7=6302 X 2 X 2=8
# samples 92
** MAII scorelog2(9/630*10)=-2.8073549220576
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(2/8*10)=1.32192809488736
Fusion gene context

PubMed: ITGA3 [Title/Abstract] AND LRWD1 [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: ITGA3 [Title/Abstract] AND LRWD1 [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)ITGA3(48157739)-LRWD1(102107786), # samples:1
Anticipated loss of major functional domain due to fusion event.ITGA3-LRWD1 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.
ITGA3-LRWD1 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.
* 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
HgeneITGA3

GO:1903078

positive regulation of protein localization to plasma membrane

10455171

TgeneLRWD1

GO:0071169

establishment of protein localization to chromatin

20932478



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/chr17:48157739/chr7:102107786)
- 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 ITGA3 (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 LRWD1 (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)
ENST00000320031ITGA3chr1748157739+ENST00000292616LRWD1chr7102107786+4781315017446611495
ENST00000007722ITGA3chr1748157739+ENST00000292616LRWD1chr7102107786+44512820043311443

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
ENST00000320031ENST00000292616ITGA3chr1748157739+LRWD1chr7102107786+0.0031374820.99686253
ENST00000007722ENST00000292616ITGA3chr1748157739+LRWD1chr7102107786+0.0022432950.9977568

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 ITGA3-LRWD1

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
ITGA3chr1748157739LRWD1chr71021077862820935VVTNVTVKARVWNSTFIEVTAHWEKF
ITGA3chr1748157739LRWD1chr71021077863150987VVTNVTVKARVWNSTFIEVTAHWEKF

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Potential FusionNeoAntigen Information of ITGA3-LRWD1 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.
ITGA3-LRWD1_48157739_102107786.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)
ITGA3-LRWD1chr1748157739chr71021077862820HLA-B27:07ARVWNSTFI0.99810.6169817
ITGA3-LRWD1chr1748157739chr71021077862820HLA-B57:01KARVWNSTF0.99430.9914716
ITGA3-LRWD1chr1748157739chr71021077862820HLA-B15:25KARVWNSTF0.9910.9763716
ITGA3-LRWD1chr1748157739chr71021077862820HLA-B15:17KARVWNSTF0.99040.9741716
ITGA3-LRWD1chr1748157739chr71021077862820HLA-B58:02KARVWNSTF0.98710.9221716
ITGA3-LRWD1chr1748157739chr71021077862820HLA-B15:16KARVWNSTF0.9860.9721716
ITGA3-LRWD1chr1748157739chr71021077862820HLA-B57:03KARVWNSTF0.96670.9876716
ITGA3-LRWD1chr1748157739chr71021077862820HLA-B46:01KARVWNSTF0.86060.5626716
ITGA3-LRWD1chr1748157739chr71021077862820HLA-A32:13KARVWNSTF0.57990.9547716
ITGA3-LRWD1chr1748157739chr71021077862820HLA-A02:21RVWNSTFIEV0.99520.7225919
ITGA3-LRWD1chr1748157739chr71021077862820HLA-A02:20RVWNSTFIEV0.9890.6182919
ITGA3-LRWD1chr1748157739chr71021077862820HLA-B57:01NSTFIEVTAHW0.99990.98841223
ITGA3-LRWD1chr1748157739chr71021077862820HLA-B58:02NSTFIEVTAHW0.99970.97651223
ITGA3-LRWD1chr1748157739chr71021077862820HLA-B58:01NSTFIEVTAHW0.99950.96541223
ITGA3-LRWD1chr1748157739chr71021077862820HLA-B57:03NSTFIEVTAHW0.99910.98971223
ITGA3-LRWD1chr1748157739chr71021077862820HLA-B15:07KARVWNSTF0.9940.8463716
ITGA3-LRWD1chr1748157739chr71021077862820HLA-C12:12KARVWNSTF0.82850.9638716
ITGA3-LRWD1chr1748157739chr71021077862820HLA-C15:04KARVWNSTF0.82240.9606716
ITGA3-LRWD1chr1748157739chr71021077862820HLA-C03:14KARVWNSTF0.64740.9856716
ITGA3-LRWD1chr1748157739chr71021077862820HLA-C04:14VWNSTFIEV0.43290.91691019
ITGA3-LRWD1chr1748157739chr71021077862820HLA-B27:06ARVWNSTFI0.99880.8791817
ITGA3-LRWD1chr1748157739chr71021077862820HLA-B27:09ARVWNSTFI0.99780.8634817
ITGA3-LRWD1chr1748157739chr71021077862820HLA-B57:10KARVWNSTF0.99430.9914716
ITGA3-LRWD1chr1748157739chr71021077862820HLA-B15:35KARVWNSTF0.99410.9412716
ITGA3-LRWD1chr1748157739chr71021077862820HLA-B58:06KARVWNSTF0.99340.9253716
ITGA3-LRWD1chr1748157739chr71021077862820HLA-B15:24KARVWNSTF0.99260.9776716
ITGA3-LRWD1chr1748157739chr71021077862820HLA-B15:39KARVWNSTF0.99140.9538716
ITGA3-LRWD1chr1748157739chr71021077862820HLA-B57:04KARVWNSTF0.98640.7915716
ITGA3-LRWD1chr1748157739chr71021077862820HLA-B07:09KARVWNSTF0.9560.5494716
ITGA3-LRWD1chr1748157739chr71021077862820HLA-A32:01KARVWNSTF0.95490.9404716
ITGA3-LRWD1chr1748157739chr71021077862820HLA-B57:02KARVWNSTF0.8660.9285716
ITGA3-LRWD1chr1748157739chr71021077862820HLA-C03:02KARVWNSTF0.85120.9849716
ITGA3-LRWD1chr1748157739chr71021077862820HLA-C15:09KARVWNSTF0.82240.9606716
ITGA3-LRWD1chr1748157739chr71021077862820HLA-C06:08ARVWNSTFI0.81010.9819817
ITGA3-LRWD1chr1748157739chr71021077862820HLA-C16:04KARVWNSTF0.78970.9814716
ITGA3-LRWD1chr1748157739chr71021077862820HLA-C12:03KARVWNSTF0.77610.9881716
ITGA3-LRWD1chr1748157739chr71021077862820HLA-C12:02KARVWNSTF0.74160.9752716
ITGA3-LRWD1chr1748157739chr71021077862820HLA-C03:05KARVWNSTF0.63290.9575716
ITGA3-LRWD1chr1748157739chr71021077862820HLA-C04:04VWNSTFIEV0.49290.96771019
ITGA3-LRWD1chr1748157739chr71021077862820HLA-C02:02KARVWNSTF0.48110.9828716
ITGA3-LRWD1chr1748157739chr71021077862820HLA-C02:10KARVWNSTF0.48110.9828716
ITGA3-LRWD1chr1748157739chr71021077862820HLA-C16:01KARVWNSTF0.38450.9884716
ITGA3-LRWD1chr1748157739chr71021077862820HLA-C16:02KARVWNSTF0.26030.9952716
ITGA3-LRWD1chr1748157739chr71021077862820HLA-C06:02ARVWNSTFI0.02340.9939817
ITGA3-LRWD1chr1748157739chr71021077862820HLA-C06:17ARVWNSTFI0.02340.9939817
ITGA3-LRWD1chr1748157739chr71021077862820HLA-A02:06RVWNSTFIEV0.99520.7225919
ITGA3-LRWD1chr1748157739chr71021077862820HLA-B57:10NSTFIEVTAHW0.99990.98841223
ITGA3-LRWD1chr1748157739chr71021077862820HLA-B57:04NSTFIEVTAHW0.99980.76161223
ITGA3-LRWD1chr1748157739chr71021077862820HLA-B57:02NSTFIEVTAHW0.99920.9321223

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Potential FusionNeoAntigen Information of ITGA3-LRWD1 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 ITGA3-LRWD1

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
10027VKARVWNSTFIEVTITGA3LRWD1chr1748157739chr71021077862820

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of ITGA3-LRWD1

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-B14:023BVN10027VKARVWNSTFIEVT-7.9953-8.11
HLA-B14:023BVN10027VKARVWNSTFIEVT-6.76387-7.80047
HLA-B52:013W3910027VKARVWNSTFIEVT-6.72115-6.83585
HLA-B52:013W3910027VKARVWNSTFIEVT-4.59437-5.63097
HLA-A24:025HGA10027VKARVWNSTFIEVT-8.73414-8.84884
HLA-A24:025HGA10027VKARVWNSTFIEVT-6.32039-7.35699
HLA-B44:053DX810027VKARVWNSTFIEVT-5.20472-5.31942
HLA-B44:053DX810027VKARVWNSTFIEVT-4.80907-5.84567
HLA-B35:011A1N10027VKARVWNSTFIEVT-5.66114-6.69774
HLA-B35:011A1N10027VKARVWNSTFIEVT-5.12233-5.23703
HLA-A02:016TDR10027VKARVWNSTFIEVT0.647201-0.389399

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Vaccine Design for the FusionNeoAntigens of ITGA3-LRWD1

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
ITGA3-LRWD1chr1748157739chr71021077861019VWNSTFIEVTTCATCGAGGTCACAGCTCACTGGGAG
ITGA3-LRWD1chr1748157739chr71021077861223NSTFIEVTAHWGAGGTCACAGCTCACTGGGAGAAGTTCATGGCC
ITGA3-LRWD1chr1748157739chr7102107786716KARVWNSTFAACAGCACCTTCATCGAGGTCACAGCT
ITGA3-LRWD1chr1748157739chr7102107786817ARVWNSTFIAGCACCTTCATCGAGGTCACAGCTCAC
ITGA3-LRWD1chr1748157739chr7102107786919RVWNSTFIEVACCTTCATCGAGGTCACAGCTCACTGGGAG

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 ITGA3-LRWD1

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
STADITGA3-LRWD1chr1748157739ENST00000007722chr7102107786ENST00000292616TCGA-CD-A4MH-01A

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Potential target of CAR-T therapy development for ITGA3-LRWD1

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 ITGA3-LRWD1

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 ITGA3-LRWD1

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