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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:BSG-PMEL

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: BSG-PMEL
FusionPDB ID: 10394
FusionGDB2.0 ID: 10394
HgeneTgene
Gene symbol

BSG

PMEL

Gene ID

682

6490

Gene namebasigin (Ok blood group)premelanosome protein
Synonyms5F7|CD147|EMMPRIN|EMPRIN|OK|SLC7A11|TCSFD12S53E|ME20|ME20-M|ME20M|P1|P100|PMEL17|SI|SIL|SILV|gp100
Cytomap

19p13.3

12q13.2

Type of geneprotein-codingprotein-coding
DescriptionbasiginOK blood group antigencollagenase stimulatory factorextracellular matrix metalloproteinase inducerleukocyte activation antigen M6tumor cell-derived collagenase stimulatory factormelanocyte protein PMELmelanocyte protein Pmel 17melanocyte protein mel 17melanocytes lineage-specific antigen GP100melanoma-associated ME20 antigenmelanosomal matrix protein17silver locus protein homologsilver, mouse, homolog of
Modification date2020031520200313
UniProtAcc

P35613

Main function of 5'-partner protein: FUNCTION: [Isoform 1]: Essential for normal retinal maturation and development (By similarity). Acts as a retinal cell surface receptor for NXNL1 and plays an important role in NXNL1-mediated survival of retinal cone photoreceptors (PubMed:25957687). In association with glucose transporter SLC16A1/GLUT1 and NXNL1, promotes retinal cone survival by enhancing aerobic glycolysis and accelerating the entry of glucose into photoreceptors (PubMed:25957687). May act as a potent stimulator of IL6 secretion in multiple cell lines that include monocytes (PubMed:21620857). {ECO:0000250|UniProtKB:P18572, ECO:0000269|PubMed:21620857, ECO:0000269|PubMed:25957687}.; FUNCTION: [Isoform 2]: Signaling receptor for cyclophilins, essential for PPIA/CYPA and PPIB/CYPB-dependent signaling related to chemotaxis and adhesion of immune cells (PubMed:11943775, PubMed:11688976). Plays an important role in targeting monocarboxylate transporters SLC16A1/GLUT1, SLC16A11 and SLC16A12 to the plasma membrane (PubMed:17127621, PubMed:21778275, PubMed:28666119). Acts as a coreceptor for vascular endothelial growth factor receptor 2 (KDR/VEGFR2) in endothelial cells enhancing its VEGFA-mediated activation and downstream signaling (PubMed:25825981). Promotes angiogenesis through EPAS1/HIF2A-mediated up-regulation of VEGFA (isoform VEGF-165 and VEGF-121) and KDR/VEGFR2 in endothelial cells (PubMed:19837976). Plays a key role in regulating tumor growth, invasion, metastasis and neoangiogenesis by stimulating the production and release of extracellular matrix metalloproteinases and KDR/VEGFR2 by both tumor cells and stromal cells (fibroblasts and endothelial cells) (PubMed:12553375, PubMed:11992541, PubMed:15833850). {ECO:0000269|PubMed:11688976, ECO:0000269|PubMed:11943775, ECO:0000269|PubMed:11992541, ECO:0000269|PubMed:12553375, ECO:0000269|PubMed:15833850, ECO:0000269|PubMed:17127621, ECO:0000269|PubMed:19837976, ECO:0000269|PubMed:21778275, ECO:0000269|PubMed:25825981, ECO:0000269|PubMed:28666119}.; FUNCTION: [Isoform 1]: (Microbial infection) Erythrocyte receptor for P.falciparum RH5 which is essential for erythrocyte invasion by the merozoite stage of P.falciparum isolates 3D7 and Dd2. {ECO:0000269|PubMed:22080952}.; FUNCTION: [Isoform 2]: (Microbial infection) Erythrocyte receptor for P.falciparum RH5 which is essential for erythrocyte invasion by the merozoite stage of P.falciparum isolates 3D7, Dd2, 7G8 and HB3 (PubMed:22080952, PubMed:26195724). Binding of P.falciparum RH5 results in BSG dimerization which triggers an increase in intracellular Ca(2+) in the erythrocyte (PubMed:28409866). This essential step leads to a rearrangement of the erythrocyte cytoskeleton required for the merozoite invasion (PubMed:28409866). {ECO:0000269|PubMed:22080952, ECO:0000269|PubMed:26195724, ECO:0000269|PubMed:28409866}.; FUNCTION: [Isoform 2]: (Microbial infection) Can facilitate human SARS coronavirus (SARS-CoV-1) infection via its interaction with virus-associated PPIA/CYPA. {ECO:0000269|PubMed:15688292}.; FUNCTION: [Isoform 2]: (Microbial infection) Can facilitate HIV-1 infection via its interaction with virus-associated PPIA/CYPA. {ECO:0000269|PubMed:11353871}.; FUNCTION: [Isoform 2]: (Microbial infection) First described as a receptor for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), it is not required for SARS-CoV-2 infection. {ECO:0000269|PubMed:33432067, ECO:0000303|PubMed:32307653}.; FUNCTION: [Isoform 2]: (Microbial infection) Acts as a receptor for measles virus. {ECO:0000269|PubMed:20147391}.; FUNCTION: [Isoform 2]: (Microbial infection) Promotes entry of pentamer-expressing human cytomegalovirus (HCMV) into epithelial and endothelial cells. {ECO:0000269|PubMed:29739904}.
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Ensembl transtripts involved in fusion geneENST idsENST00000333511, ENST00000353555, 
ENST00000346916, ENST00000545507, 
ENST00000574970, 
ENST00000548689, 
ENST00000360714, ENST00000449260, 
ENST00000536427, ENST00000539511, 
ENST00000548493, ENST00000548747, 
ENST00000550447, ENST00000550464, 
ENST00000552882, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score26 X 17 X 12=53044 X 3 X 1=12
# samples 294
** MAII scorelog2(29/5304*10)=-4.19295597009765
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(4/12*10)=1.73696559416621
effective Gene in Pan-Cancer Fusion Genes (eGinPCFGs).
DoF>8 and MAII>0
Fusion gene context

PubMed: BSG [Title/Abstract] AND PMEL [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: BSG [Title/Abstract] AND PMEL [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)BSG(572701)-PMEL(56349647), # samples:1
Anticipated loss of major functional domain due to fusion event.BSG-PMEL 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.
BSG-PMEL 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
TgenePMEL

GO:0032438

melanosome organization

11694580



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/chr19:572701/chr12:56349647)
- 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 BSG (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 PMEL (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)
ENST00000333511BSGchr19572701+ENST00000449260PMELchr1256349647-78213770672200
ENST00000333511BSGchr19572701+ENST00000552882PMELchr1256349647-76113770651193
ENST00000333511BSGchr19572701+ENST00000550464PMELchr1256349647-76013770651193
ENST00000333511BSGchr19572701+ENST00000548747PMELchr1256349647-76013770651193
ENST00000333511BSGchr19572701+ENST00000536427PMELchr1256349647-78113770672200
ENST00000333511BSGchr19572701+ENST00000539511PMELchr1256349647-76013770651193
ENST00000333511BSGchr19572701+ENST00000360714PMELchr1256349647-78113770672200
ENST00000333511BSGchr19572701+ENST00000548493PMELchr1256349647-76013770651193
ENST00000333511BSGchr19572701+ENST00000550447PMELchr1256349647-66613770651193
ENST00000353555BSGchr19572701+ENST00000449260PMELchr1256349647-76912457659200
ENST00000353555BSGchr19572701+ENST00000552882PMELchr1256349647-74812457638193
ENST00000353555BSGchr19572701+ENST00000550464PMELchr1256349647-74712457638193
ENST00000353555BSGchr19572701+ENST00000548747PMELchr1256349647-74712457638193
ENST00000353555BSGchr19572701+ENST00000536427PMELchr1256349647-76812457659200
ENST00000353555BSGchr19572701+ENST00000539511PMELchr1256349647-74712457638193
ENST00000353555BSGchr19572701+ENST00000360714PMELchr1256349647-76812457659200
ENST00000353555BSGchr19572701+ENST00000548493PMELchr1256349647-74712457638193
ENST00000353555BSGchr19572701+ENST00000550447PMELchr1256349647-65312457638193

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
ENST00000333511ENST00000449260BSGchr19572701+PMELchr1256349647-0.091893890.9081061
ENST00000333511ENST00000552882BSGchr19572701+PMELchr1256349647-0.0597358420.94026417
ENST00000333511ENST00000550464BSGchr19572701+PMELchr1256349647-0.0608278660.9391722
ENST00000333511ENST00000548747BSGchr19572701+PMELchr1256349647-0.0608278660.9391722
ENST00000333511ENST00000536427BSGchr19572701+PMELchr1256349647-0.093530060.90646994
ENST00000333511ENST00000539511BSGchr19572701+PMELchr1256349647-0.0608278660.9391722
ENST00000333511ENST00000360714BSGchr19572701+PMELchr1256349647-0.093530060.90646994
ENST00000333511ENST00000548493BSGchr19572701+PMELchr1256349647-0.0608278660.9391722
ENST00000333511ENST00000550447BSGchr19572701+PMELchr1256349647-0.0364195850.96358037
ENST00000353555ENST00000449260BSGchr19572701+PMELchr1256349647-0.097712640.90228736
ENST00000353555ENST00000552882BSGchr19572701+PMELchr1256349647-0.063627040.936373
ENST00000353555ENST00000550464BSGchr19572701+PMELchr1256349647-0.064794120.9352059
ENST00000353555ENST00000548747BSGchr19572701+PMELchr1256349647-0.064794120.9352059
ENST00000353555ENST00000536427BSGchr19572701+PMELchr1256349647-0.099283370.9007166
ENST00000353555ENST00000539511BSGchr19572701+PMELchr1256349647-0.064794120.9352059
ENST00000353555ENST00000360714BSGchr19572701+PMELchr1256349647-0.099283370.9007166
ENST00000353555ENST00000548493BSGchr19572701+PMELchr1256349647-0.064794120.9352059
ENST00000353555ENST00000550447BSGchr19572701+PMELchr1256349647-0.0352449270.96475506

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 BSG-PMEL

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
BSGchr19572701PMELchr125634964712421LGFALLGTHGASGAEGIESAEILQAV
BSGchr19572701PMELchr125634964713721LGFALLGTHGASGAEGIESAEILQAV

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Potential FusionNeoAntigen Information of BSG-PMEL 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.
BSG-PMEL_572701_56349647.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)
BSG-PMELchr19572701chr1256349647137HLA-B38:01THGASGAEGI0.96730.9647717
BSG-PMELchr19572701chr1256349647137HLA-B38:05THGASGAEGI0.96730.9647717

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Potential FusionNeoAntigen Information of BSG-PMEL 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.
BSG-PMEL_572701_56349647.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)
BSG-PMELchr19572701chr1256349647137DRB1-0454LGFALLGTHGASGAE015

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Fusion breakpoint peptide structures of BSG-PMEL

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
3170GTHGASGAEGIESABSGPMELchr19572701chr1256349647137

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of BSG-PMEL

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-B14:023BVN3170GTHGASGAEGIESA-7.15543-7.26883
HLA-B14:023BVN3170GTHGASGAEGIESA-4.77435-5.80965
HLA-B52:013W393170GTHGASGAEGIESA-6.80875-6.92215
HLA-B52:013W393170GTHGASGAEGIESA-4.20386-5.23916
HLA-A11:014UQ23170GTHGASGAEGIESA-7.5194-8.5547
HLA-A11:014UQ23170GTHGASGAEGIESA-6.9601-7.0735
HLA-A24:025HGA3170GTHGASGAEGIESA-7.52403-7.63743
HLA-A24:025HGA3170GTHGASGAEGIESA-5.82433-6.85963
HLA-B27:056PYJ3170GTHGASGAEGIESA-3.28285-4.31815
HLA-B44:053DX83170GTHGASGAEGIESA-5.91172-6.94702
HLA-B44:053DX83170GTHGASGAEGIESA-4.24346-4.35686

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Vaccine Design for the FusionNeoAntigens of BSG-PMEL

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
BSG-PMELchr19572701chr1256349647717THGASGAEGIACGGAGCCTCCGGGGCTGAGGGTATTGAAA

check button mRNA and peptide sequences of FusionNeoAntigens that have potential interaction with HLA-IIs.
Fusion geneHchrHbpTchrTbpStart in +/-13AAEnd in +/-13AAFusionNeoAntigen peptideFusionNEoAntigen RNA sequence
BSG-PMELchr19572701chr1256349647015LGFALLGTHGASGAEGATTCGCGCTGCTGGGCACCCACGGAGCCTCCGGGGCTGAGGGTA

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Information of the samples that have these potential fusion neoantigens of BSG-PMEL

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
SKCMBSG-PMELchr19572701ENST00000333511chr1256349647ENST00000360714TCGA-D3-A1Q9-06A

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Potential target of CAR-T therapy development for BSG-PMEL

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
TgenePMELchr19:572701chr12:56349647ENST00000449260611596_6160669.0TransmembraneHelical
TgenePMELchr19:572701chr12:56349647ENST00000539511510596_6160576.0TransmembraneHelical
TgenePMELchr19:572701chr12:56349647ENST00000548493712596_6160662.0TransmembraneHelical
TgenePMELchr19:572701chr12:56349647ENST00000548747611596_6160662.0TransmembraneHelical
TgenePMELchr19:572701chr12:56349647ENST0000055046449596_6160576.0TransmembraneHelical
TgenePMELchr19:572701chr12:56349647ENST00000552882712596_6160662.0TransmembraneHelical

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

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Related Drugs to BSG-PMEL

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 BSG-PMEL

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