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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:RGPD5-NBEA

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: RGPD5-NBEA
FusionPDB ID: 73786
FusionGDB2.0 ID: 73786
HgeneTgene
Gene symbol

RGPD5

NBEA

Gene ID

84220

26960

Gene nameRANBP2 like and GRIP domain containing 5neurobeachin
SynonymsBS-63|BS63|HEL161|RGP5BCL8B|LYST2
Cytomap

2q13

13q13.3

Type of geneprotein-codingprotein-coding
DescriptionRANBP2-like and GRIP domain-containing protein 5/6RANBP2-like and GRIP domain-containing protein 5epididymis luminal protein 161ran-binding protein 2-like 1ran-binding protein 2-like 1/2ranBP2-like 1ranBP2-like 1/2ranBP2L1sperm membrane protein BSneurobeachinlysosomal-trafficking regulator 2
Modification date2020031320200328
UniProtAcc.

Q6ZNJ1

Main function of 5'-partner protein: FUNCTION: Probably involved in thrombopoiesis. Plays a role in the development or secretion of alpha-granules, that contain several growth factors important for platelet biogenesis. {ECO:0000269|PubMed:21765411, ECO:0000269|PubMed:21765412}.
Ensembl transtripts involved in fusion geneENST idsENST00000016946, ENST00000272454, 
ENST00000393283, ENST00000495582, 
ENST00000379922, ENST00000461581, 
ENST00000310336, ENST00000379939, 
ENST00000400445, ENST00000537702, 
ENST00000540320, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score5 X 4 X 5=10017 X 16 X 6=1632
# samples 518
** MAII scorelog2(5/100*10)=-1
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0		log2(18/1632*10)=-3.18057224564182
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: RGPD5 [Title/Abstract] AND NBEA [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: RGPD5 [Title/Abstract] AND NBEA [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)RGPD5(110565981)-NBEA(36158035), # samples:1
Anticipated loss of major functional domain due to fusion event.RGPD5-NBEA 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.
RGPD5-NBEA 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.
RGPD5-NBEA 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.
RGPD5-NBEA 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


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/chr2:110565981/chr13:36158035)
- 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 RGPD5 (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 NBEA (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)
ENST00000393283RGPD5chr2110565981+ENST00000540320NBEAchr1336158035+471911694342974846
ENST00000393283RGPD5chr2110565981+ENST00000400445NBEAchr1336158035+471911694342974846
ENST00000393283RGPD5chr2110565981+ENST00000310336NBEAchr1336158035+471911694342974846
ENST00000393283RGPD5chr2110565981+ENST00000379939NBEAchr1336158035+472011694342974846
ENST00000393283RGPD5chr2110565981+ENST00000537702NBEAchr1336158035+351811694342974846
ENST00000272454RGPD5chr2110565981+ENST00000540320NBEAchr1336158035+4378828932633846
ENST00000272454RGPD5chr2110565981+ENST00000400445NBEAchr1336158035+4378828932633846
ENST00000272454RGPD5chr2110565981+ENST00000310336NBEAchr1336158035+4378828932633846
ENST00000272454RGPD5chr2110565981+ENST00000379939NBEAchr1336158035+4379828932633846
ENST00000272454RGPD5chr2110565981+ENST00000537702NBEAchr1336158035+3177828932633846
ENST00000016946RGPD5chr2110565981+ENST00000540320NBEAchr1336158035+4344794592599846
ENST00000016946RGPD5chr2110565981+ENST00000400445NBEAchr1336158035+4344794592599846
ENST00000016946RGPD5chr2110565981+ENST00000310336NBEAchr1336158035+4344794592599846
ENST00000016946RGPD5chr2110565981+ENST00000379939NBEAchr1336158035+4345794592599846
ENST00000016946RGPD5chr2110565981+ENST00000537702NBEAchr1336158035+3143794592599846

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
ENST00000393283ENST00000540320RGPD5chr2110565981+NBEAchr1336158035+0.0003750880.99962485
ENST00000393283ENST00000400445RGPD5chr2110565981+NBEAchr1336158035+0.0003750880.99962485
ENST00000393283ENST00000310336RGPD5chr2110565981+NBEAchr1336158035+0.0003750880.99962485
ENST00000393283ENST00000379939RGPD5chr2110565981+NBEAchr1336158035+0.000375980.999624
ENST00000393283ENST00000537702RGPD5chr2110565981+NBEAchr1336158035+0.0007612750.9992387
ENST00000272454ENST00000540320RGPD5chr2110565981+NBEAchr1336158035+0.0003177160.9996823
ENST00000272454ENST00000400445RGPD5chr2110565981+NBEAchr1336158035+0.0003177160.9996823
ENST00000272454ENST00000310336RGPD5chr2110565981+NBEAchr1336158035+0.0003177160.9996823
ENST00000272454ENST00000379939RGPD5chr2110565981+NBEAchr1336158035+0.0003183440.9996817
ENST00000272454ENST00000537702RGPD5chr2110565981+NBEAchr1336158035+0.0006167920.9993832
ENST00000016946ENST00000540320RGPD5chr2110565981+NBEAchr1336158035+0.0003114870.9996885
ENST00000016946ENST00000400445RGPD5chr2110565981+NBEAchr1336158035+0.0003114870.9996885
ENST00000016946ENST00000310336RGPD5chr2110565981+NBEAchr1336158035+0.0003114870.9996885
ENST00000016946ENST00000379939RGPD5chr2110565981+NBEAchr1336158035+0.0003120930.9996879
ENST00000016946ENST00000537702RGPD5chr2110565981+NBEAchr1336158035+0.0006028770.99939716

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 RGPD5-NBEA

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
RGPD5chr2110565981NBEAchr13361580351169245SLEWNSCVVQTLKPIGALNPKRAVFY
RGPD5chr2110565981NBEAchr1336158035794245SLEWNSCVVQTLKPIGALNPKRAVFY
RGPD5chr2110565981NBEAchr1336158035828245SLEWNSCVVQTLKPIGALNPKRAVFY

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Potential FusionNeoAntigen Information of RGPD5-NBEA 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 RGPD5-NBEA 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 RGPD5-NBEA

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 RGPD5-NBEA

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 RGPD5-NBEA

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 RGPD5-NBEA

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 RGPD5-NBEA

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 RGPD5-NBEA

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 RGPD5-NBEA

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