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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:RND3-B2M

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: RND3-B2M
FusionPDB ID: 74663
FusionGDB2.0 ID: 74663
HgeneTgene
Gene symbol

RND3

B2M

Gene ID

390

567

Gene nameRho family GTPase 3beta-2-microglobulin
SynonymsARHE|Rho8|RhoE|memBIMD43
Cytomap

2q23.3

15q21.1

Type of geneprotein-codingprotein-coding
Descriptionrho-related GTP-binding protein RhoEprotein MemBras homolog gene family, member Erho-related GTP-binding protein Rho8small GTP binding protein Rho8beta-2-microglobulinbeta chain of MHC class I moleculesbeta-2-microglobin
Modification date2020031320200329
UniProtAcc.

P61769

Main function of 5'-partner protein: FUNCTION: Component of the class I major histocompatibility complex (MHC). Involved in the presentation of peptide antigens to the immune system. Exogenously applied M.tuberculosis EsxA or EsxA-EsxB (or EsxA expressed in host) binds B2M and decreases its export to the cell surface (total protein levels do not change), probably leading to defects in class I antigen presentation (PubMed:25356553). {ECO:0000269|PubMed:25356553}.
Ensembl transtripts involved in fusion geneENST idsENST00000263895, ENST00000375734, 
ENST00000472416, ENST00000409557, 
ENST00000559220, ENST00000544417, 
ENST00000558401, ENST00000559916, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score6 X 6 X 2=7264 X 31 X 17=33728
# samples 671
** MAII scorelog2(6/72*10)=-0.263034405833794
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(71/33728*10)=-5.56998393724517
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: RND3 [Title/Abstract] AND B2M [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: RND3 [Title/Abstract] AND B2M [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)RND3(151343208)-B2M(45007621), # samples:1
Anticipated loss of major functional domain due to fusion event.RND3-B2M 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.
RND3-B2M 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.
RND3-B2M seems lost the major protein functional domain in Hgene partner, which is a essential gene due to the frame-shifted ORF.
RND3-B2M seems lost the major protein functional domain in Hgene partner, which is a tumor suppressor due to the frame-shifted ORF.
RND3-B2M seems lost the major protein functional domain in Tgene partner, which is a CGC 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
TgeneB2M

GO:0002726

positive regulation of T cell cytokine production

24643698

TgeneB2M

GO:0007611

learning or memory

26147761

TgeneB2M

GO:0050680

negative regulation of epithelial cell proliferation

28213472

TgeneB2M

GO:0050768

negative regulation of neurogenesis

26147761

TgeneB2M

GO:0090647

modulation of age-related behavioral decline

26147761

TgeneB2M

GO:1900121

negative regulation of receptor binding

9465039

TgeneB2M

GO:1990000

amyloid fibril formation

28468825

TgeneB2M

GO:2000774

positive regulation of cellular senescence

28213472

TgeneB2M

GO:2000978

negative regulation of forebrain neuron differentiation

26147761



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/chr2:151343208/chr15:45007621)
- 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 RND3 (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 B2M (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)
ENST00000375734RND3chr2151343208-ENST00000558401B2Mchr1545007621+2066488250780176
ENST00000375734RND3chr2151343208-ENST00000559916B2Mchr1545007621+1468488250780176
ENST00000263895RND3chr2151343208-ENST00000558401B2Mchr1545007621+2000422103714203
ENST00000263895RND3chr2151343208-ENST00000559916B2Mchr1545007621+1402422103714203

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
ENST00000375734ENST00000558401RND3chr2151343208-B2Mchr1545007621+0.0006243670.99937564
ENST00000375734ENST00000559916RND3chr2151343208-B2Mchr1545007621+0.0010186260.9989813
ENST00000263895ENST00000558401RND3chr2151343208-B2Mchr1545007621+0.0010105230.9989895
ENST00000263895ENST00000559916RND3chr2151343208-B2Mchr1545007621+0.0013034550.9986966

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 RND3-B2M

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
RND3chr2151343208B2Mchr1545007621422105IDTQRIELSLWDTSGTPKIQVYSRHP
RND3chr2151343208B2Mchr154500762148878IDTQRIELSLWDTSGTPKIQVYSRHP

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Potential FusionNeoAntigen Information of RND3-B2M 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.
RND3-B2M_151343208_45007621.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)
RND3-B2Mchr2151343208chr1545007621422HLA-A02:27SLWDTSGTPKI0.99690.6011819
RND3-B2Mchr2151343208chr1545007621422HLA-A02:11SLWDTSGTPKI0.99670.6157819
RND3-B2Mchr2151343208chr1545007621422HLA-A02:67SLWDTSGTPKI0.99660.5755819
RND3-B2Mchr2151343208chr1545007621422HLA-A02:24SLWDTSGTPKI0.99660.5755819
RND3-B2Mchr2151343208chr1545007621422HLA-A02:30SLWDTSGTPKI0.99660.5755819
RND3-B2Mchr2151343208chr1545007621422HLA-A02:60SLWDTSGTPKI0.99660.5948819
RND3-B2Mchr2151343208chr1545007621422HLA-A02:04SLWDTSGTPKI0.9960.6574819
RND3-B2Mchr2151343208chr1545007621422HLA-A02:13SLWDTSGTPKI0.99580.7872819
RND3-B2Mchr2151343208chr1545007621422HLA-A02:21SLWDTSGTPKI0.99440.6917819
RND3-B2Mchr2151343208chr1545007621422HLA-A02:16SLWDTSGTPKI0.99370.5934819
RND3-B2Mchr2151343208chr1545007621422HLA-A02:35SLWDTSGTPKI0.98120.6083819
RND3-B2Mchr2151343208chr1545007621422HLA-A02:38SLWDTSGTPKI0.97590.7323819
RND3-B2Mchr2151343208chr1545007621422HLA-A02:19SLWDTSGTPKI0.96090.519819
RND3-B2Mchr2151343208chr1545007621422HLA-A02:20SLWDTSGTPKI0.88720.5853819
RND3-B2Mchr2151343208chr1545007621422HLA-A02:29SLWDTSGTPKI0.88570.5798819
RND3-B2Mchr2151343208chr1545007621422HLA-C15:06TSGTPKIQV0.99850.83641221
RND3-B2Mchr2151343208chr1545007621422HLA-C04:10LWDTSGTPKI0.99920.8652919
RND3-B2Mchr2151343208chr1545007621422HLA-C04:07LWDTSGTPKI0.99910.8861919
RND3-B2Mchr2151343208chr1545007621422HLA-A02:07SLWDTSGTPKI0.99720.712819
RND3-B2Mchr2151343208chr1545007621422HLA-A02:01SLWDTSGTPKI0.99660.5755819
RND3-B2Mchr2151343208chr1545007621422HLA-C15:05TSGTPKIQV0.99880.84761221
RND3-B2Mchr2151343208chr1545007621422HLA-C15:02TSGTPKIQV0.99880.82491221
RND3-B2Mchr2151343208chr1545007621422HLA-C04:01LWDTSGTPKI0.99910.8861919
RND3-B2Mchr2151343208chr1545007621422HLA-A69:01DTSGTPKIQV0.9530.55231121
RND3-B2Mchr2151343208chr1545007621422HLA-C16:02TSGTPKIQVY0.85780.98871222
RND3-B2Mchr2151343208chr1545007621422HLA-A25:01DTSGTPKIQVY0.99540.81671122
RND3-B2Mchr2151343208chr1545007621422HLA-A02:14SLWDTSGTPKI0.99470.5853819
RND3-B2Mchr2151343208chr1545007621422HLA-A02:06SLWDTSGTPKI0.99440.6917819
RND3-B2Mchr2151343208chr1545007621422HLA-A02:03SLWDTSGTPKI0.99320.7174819

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Potential FusionNeoAntigen Information of RND3-B2M 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 RND3-B2M

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
1927ELSLWDTSGTPKIQRND3B2Mchr2151343208chr1545007621422

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of RND3-B2M

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-B14:023BVN1927ELSLWDTSGTPKIQ-7.15543-7.26883
HLA-B14:023BVN1927ELSLWDTSGTPKIQ-4.77435-5.80965
HLA-B52:013W391927ELSLWDTSGTPKIQ-6.80875-6.92215
HLA-B52:013W391927ELSLWDTSGTPKIQ-4.20386-5.23916
HLA-A11:014UQ21927ELSLWDTSGTPKIQ-7.5194-8.5547
HLA-A11:014UQ21927ELSLWDTSGTPKIQ-6.9601-7.0735
HLA-A24:025HGA1927ELSLWDTSGTPKIQ-7.52403-7.63743
HLA-A24:025HGA1927ELSLWDTSGTPKIQ-5.82433-6.85963
HLA-B27:056PYJ1927ELSLWDTSGTPKIQ-3.28285-4.31815
HLA-B44:053DX81927ELSLWDTSGTPKIQ-5.91172-6.94702
HLA-B44:053DX81927ELSLWDTSGTPKIQ-4.24346-4.35686

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Vaccine Design for the FusionNeoAntigens of RND3-B2M

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
RND3-B2Mchr2151343208chr15450076211121DTSGTPKIQVCTTCGGGTACTCCAAAGATTCAGGTTTACT
RND3-B2Mchr2151343208chr15450076211122DTSGTPKIQVYCTTCGGGTACTCCAAAGATTCAGGTTTACTCAC
RND3-B2Mchr2151343208chr15450076211221TSGTPKIQVCGGGTACTCCAAAGATTCAGGTTTACT
RND3-B2Mchr2151343208chr15450076211222TSGTPKIQVYCGGGTACTCCAAAGATTCAGGTTTACTCAC
RND3-B2Mchr2151343208chr1545007621819SLWDTSGTPKITGTGGGACACTTCGGGTACTCCAAAGATTCAGG
RND3-B2Mchr2151343208chr1545007621919LWDTSGTPKIGGGACACTTCGGGTACTCCAAAGATTCAGG

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 RND3-B2M

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
STADRND3-B2Mchr2151343208ENST00000263895chr1545007621ENST00000558401TCGA-HU-8238-01A

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Potential target of CAR-T therapy development for RND3-B2M

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 RND3-B2M

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 RND3-B2M

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