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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:BCR-ARVCF

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: BCR-ARVCF
FusionPDB ID: 9503
FusionGDB2.0 ID: 9503
HgeneTgene
Gene symbol

BCR

ARVCF

Gene ID

613

421

Gene nameBCR activator of RhoGEF and GTPaseARVCF delta catenin family member
SynonymsALL|BCR1|CML|D22S11|D22S662|PHL-
Cytomap

22q11.23

22q11.21

Type of geneprotein-codingprotein-coding
Descriptionbreakpoint cluster region proteinBCR, RhoGEF and GTPase activating proteinBCR/FGFR1 chimera proteinFGFR1/BCR chimera proteinbreakpoint cluster regionrenal carcinoma antigen NY-REN-26armadillo repeat protein deleted in velo-cardio-facial syndromearmadillo repeat gene deleted in velocardiofacial syndrome
Modification date2020031320200320
UniProtAcc

P11274

Main function of 5'-partner protein: FUNCTION: Protein with a unique structure having two opposing regulatory activities toward small GTP-binding proteins. The C-terminus is a GTPase-activating protein (GAP) domain which stimulates GTP hydrolysis by RAC1, RAC2 and CDC42. Accelerates the intrinsic rate of GTP hydrolysis of RAC1 or CDC42, leading to down-regulation of the active GTP-bound form (PubMed:7479768, PubMed:1903516, PubMed:17116687). The central Dbl homology (DH) domain functions as guanine nucleotide exchange factor (GEF) that modulates the GTPases CDC42, RHOA and RAC1. Promotes the conversion of CDC42, RHOA and RAC1 from the GDP-bound to the GTP-bound form (PubMed:7479768, PubMed:23940119). The amino terminus contains an intrinsic kinase activity (PubMed:1657398). Functions as an important negative regulator of neuronal RAC1 activity (By similarity). Regulates macrophage functions such as CSF1-directed motility and phagocytosis through the modulation of RAC1 activity (PubMed:17116687). Plays a major role as a RHOA GEF in keratinocytes being involved in focal adhesion formation and keratinocyte differentiation (PubMed:23940119). {ECO:0000250|UniProtKB:Q6PAJ1, ECO:0000269|PubMed:1657398, ECO:0000269|PubMed:17116687, ECO:0000269|PubMed:1903516, ECO:0000269|PubMed:23940119, ECO:0000269|PubMed:7479768}.

O00192

Main function of 5'-partner protein: FUNCTION: Involved in protein-protein interactions at adherens junctions.
Ensembl transtripts involved in fusion geneENST idsENST00000305877, ENST00000359540, 
ENST00000398512, ENST00000436990, 
ENST00000487793, ENST00000263207, 
ENST00000344269, ENST00000401994, 
ENST00000406259, ENST00000406522, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score22 X 142 X 16=499843 X 3 X 2=18
# samples 1633
** MAII scorelog2(163/49984*10)=-4.93852248902354
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: BCR [Title/Abstract] AND ARVCF [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: BCR [Title/Abstract] AND ARVCF [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)BCR(23615961)-ARVCF(19969614), # samples:2
Anticipated loss of major functional domain due to fusion event.BCR-ARVCF 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.
BCR-ARVCF 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.
BCR-ARVCF 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.
BCR-ARVCF 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
HgeneBCR

GO:0090630

activation of GTPase activity

7479768



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/chr22:23615961/chr22:19969614)
- 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 BCR (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 ARVCF (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)
ENST00000305877BCRchr2223615961+ENST00000263207ARVCFchr2219969614-6405286675155441597
ENST00000305877BCRchr2223615961+ENST00000344269ARVCFchr2219969614-6403286675155441597
ENST00000305877BCRchr2223615961+ENST00000406522ARVCFchr2219969614-5527286675155261592
ENST00000305877BCRchr2223615961+ENST00000401994ARVCFchr2219969614-5545286675155441598
ENST00000305877BCRchr2223615961+ENST00000406259ARVCFchr2219969614-5527286675155261592
ENST00000359540BCRchr2223615961+ENST00000263207ARVCFchr2219969614-6250271159653891597
ENST00000359540BCRchr2223615961+ENST00000344269ARVCFchr2219969614-6248271159653891597
ENST00000359540BCRchr2223615961+ENST00000406522ARVCFchr2219969614-5372271159653711592
ENST00000359540BCRchr2223615961+ENST00000401994ARVCFchr2219969614-5390271159653891598
ENST00000359540BCRchr2223615961+ENST00000406259ARVCFchr2219969614-5372271159653711592

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
ENST00000305877ENST00000263207BCRchr2223615961+ARVCFchr2219969614-0.0094778230.9905222
ENST00000305877ENST00000344269BCRchr2223615961+ARVCFchr2219969614-0.0094632120.99053675
ENST00000305877ENST00000406522BCRchr2223615961+ARVCFchr2219969614-0.0091929040.9908071
ENST00000305877ENST00000401994BCRchr2223615961+ARVCFchr2219969614-0.0118574720.98814255
ENST00000305877ENST00000406259BCRchr2223615961+ARVCFchr2219969614-0.0091929040.9908071
ENST00000359540ENST00000263207BCRchr2223615961+ARVCFchr2219969614-0.0090061730.9909938
ENST00000359540ENST00000344269BCRchr2223615961+ARVCFchr2219969614-0.0089939550.9910061
ENST00000359540ENST00000406522BCRchr2223615961+ARVCFchr2219969614-0.0089611990.99103874
ENST00000359540ENST00000401994BCRchr2223615961+ARVCFchr2219969614-0.0115243140.9884757
ENST00000359540ENST00000406259BCRchr2223615961+ARVCFchr2219969614-0.0089611990.99103874

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 BCR-ARVCF

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
BCRchr2223615961ARVCFchr22199696142711346SNENLTSSEEDFSSGQSSRVSPSPTT
BCRchr2223615961ARVCFchr22199696142866346SNENLTSSEEDFSSGQSSRVSPSPTT

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Potential FusionNeoAntigen Information of BCR-ARVCF 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.
BCR-ARVCF_23615961_19969614.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)
BCR-ARVCFchr2223615961chr22199696142866HLA-A33:01EDFSSGQSSR0.95450.6413919
BCR-ARVCFchr2223615961chr22199696142866HLA-A33:05EDFSSGQSSR0.95450.6413919
BCR-ARVCFchr2223615961chr22199696142866HLA-C15:06FSSGQSSRV0.99920.92321120
BCR-ARVCFchr2223615961chr22199696142866HLA-C04:06FSSGQSSRV0.99910.95761120
BCR-ARVCFchr2223615961chr22199696142866HLA-C03:07FSSGQSSRV0.99870.9671120
BCR-ARVCFchr2223615961chr22199696142866HLA-C06:03FSSGQSSRV0.99060.99311120
BCR-ARVCFchr2223615961chr22199696142866HLA-C12:04FSSGQSSRV0.99020.99131120
BCR-ARVCFchr2223615961chr22199696142866HLA-C12:12FSSGQSSRV0.95410.95231120
BCR-ARVCFchr2223615961chr22199696142866HLA-C02:06FSSGQSSRV0.55860.96441120
BCR-ARVCFchr2223615961chr22199696142866HLA-C15:02FSSGQSSRV0.99950.90621120
BCR-ARVCFchr2223615961chr22199696142866HLA-C15:05FSSGQSSRV0.99940.91511120
BCR-ARVCFchr2223615961chr22199696142866HLA-C03:06FSSGQSSRV0.9870.97571120
BCR-ARVCFchr2223615961chr22199696142866HLA-A68:02FSSGQSSRV0.97260.50761120
BCR-ARVCFchr2223615961chr22199696142866HLA-C16:02FSSGQSSRV0.95910.98921120
BCR-ARVCFchr2223615961chr22199696142866HLA-C12:03FSSGQSSRV0.95630.97651120
BCR-ARVCFchr2223615961chr22199696142866HLA-C16:04FSSGQSSRV0.95320.96361120

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Potential FusionNeoAntigen Information of BCR-ARVCF 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.
BCR-ARVCF_23615961_19969614.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)
BCR-ARVCFchr2223615961chr22199696142866DRB1-0901EEDFSSGQSSRVSPS823
BCR-ARVCFchr2223615961chr22199696142866DRB1-0901SEEDFSSGQSSRVSP722
BCR-ARVCFchr2223615961chr22199696142866DRB1-0902EEDFSSGQSSRVSPS823
BCR-ARVCFchr2223615961chr22199696142866DRB1-0903EEDFSSGQSSRVSPS823
BCR-ARVCFchr2223615961chr22199696142866DRB1-0903SEEDFSSGQSSRVSP722
BCR-ARVCFchr2223615961chr22199696142866DRB1-0904EEDFSSGQSSRVSPS823
BCR-ARVCFchr2223615961chr22199696142866DRB1-0904SEEDFSSGQSSRVSP722
BCR-ARVCFchr2223615961chr22199696142866DRB1-0904SSEEDFSSGQSSRVS621
BCR-ARVCFchr2223615961chr22199696142866DRB1-0905EEDFSSGQSSRVSPS823
BCR-ARVCFchr2223615961chr22199696142866DRB1-0905SEEDFSSGQSSRVSP722
BCR-ARVCFchr2223615961chr22199696142866DRB1-0907EEDFSSGQSSRVSPS823
BCR-ARVCFchr2223615961chr22199696142866DRB1-0907SEEDFSSGQSSRVSP722
BCR-ARVCFchr2223615961chr22199696142866DRB1-0907SSEEDFSSGQSSRVS621
BCR-ARVCFchr2223615961chr22199696142866DRB1-0908EEDFSSGQSSRVSPS823
BCR-ARVCFchr2223615961chr22199696142866DRB1-0909EEDFSSGQSSRVSPS823
BCR-ARVCFchr2223615961chr22199696142866DRB1-0909SEEDFSSGQSSRVSP722
BCR-ARVCFchr2223615961chr22199696142866DRB5-0112EEDFSSGQSSRVSPS823

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Fusion breakpoint peptide structures of BCR-ARVCF

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
8999SSEEDFSSGQSSRVBCRARVCFchr2223615961chr22199696142866

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of BCR-ARVCF

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-B14:023BVN8999SSEEDFSSGQSSRV-8.13059-8.24239
HLA-B14:023BVN8999SSEEDFSSGQSSRV-1.44825-2.49135
HLA-B52:013W398999SSEEDFSSGQSSRV-7.36487-7.47667
HLA-B52:013W398999SSEEDFSSGQSSRV-5.18523-6.22833
HLA-A11:014UQ28999SSEEDFSSGQSSRV-9.7297-10.7728
HLA-A11:014UQ28999SSEEDFSSGQSSRV-7.68161-7.79341
HLA-A24:025HGA8999SSEEDFSSGQSSRV-6.90089-7.01269
HLA-A24:025HGA8999SSEEDFSSGQSSRV-5.47721-6.52031
HLA-B44:053DX88999SSEEDFSSGQSSRV-6.49821-7.54131
HLA-B44:053DX88999SSEEDFSSGQSSRV-6.27125-6.38305

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Vaccine Design for the FusionNeoAntigens of BCR-ARVCF

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
BCR-ARVCFchr2223615961chr22199696141120FSSGQSSRVGGAGAGGAGCAGAGCCCAGGCAGCCAG
BCR-ARVCFchr2223615961chr2219969614919EDFSSGQSSRAAGAAGGGAGAGGAGCAGAGCCCAGGCAGC

check button mRNA and peptide sequences of FusionNeoAntigens that have potential interaction with HLA-IIs.
Fusion geneHchrHbpTchrTbpStart in +/-13AAEnd in +/-13AAFusionNeoAntigen peptideFusionNEoAntigen RNA sequence
BCR-ARVCFchr2223615961chr2219969614621SSEEDFSSGQSSRVSATGACGGTGAAGAAGGGAGAGGAGCAGAGCCCAGGCAGCCAGGCC
BCR-ARVCFchr2223615961chr2219969614722SEEDFSSGQSSRVSPACGGTGAAGAAGGGAGAGGAGCAGAGCCCAGGCAGCCAGGCCTCA
BCR-ARVCFchr2223615961chr2219969614823EEDFSSGQSSRVSPSGTGAAGAAGGGAGAGGAGCAGAGCCCAGGCAGCCAGGCCTCACTG

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Information of the samples that have these potential fusion neoantigens of BCR-ARVCF

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
COADBCR-ARVCFchr2223615961ENST00000305877chr2219969614ENST00000263207TCGA-A6-5657-01A

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Potential target of CAR-T therapy development for BCR-ARVCF

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 BCR-ARVCF

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 BCR-ARVCF

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
HgeneBCRC0005586Bipolar Disorder4PSYGENET
HgeneBCRC0023473Myeloid Leukemia, Chronic3CTD_human;ORPHANET
HgeneBCRC0005699Blast Phase1CTD_human
HgeneBCRC0006413Burkitt Lymphoma1ORPHANET
HgeneBCRC0023893Liver Cirrhosis, Experimental1CTD_human
HgeneBCRC0027022Myeloproliferative disease1CTD_human
HgeneBCRC0027540Necrosis1CTD_human
HgeneBCRC0027659Neoplasms, Experimental1CTD_human
HgeneBCRC0041696Unipolar Depression1PSYGENET
HgeneBCRC1269683Major Depressive Disorder1PSYGENET
HgeneBCRC1292769Precursor B-cell lymphoblastic leukemia1ORPHANET