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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:RLF-MFSD2A

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: RLF-MFSD2A
FusionPDB ID: 74217
FusionGDB2.0 ID: 74217
HgeneTgene
Gene symbol

RLF

MFSD2A

Gene ID

6018

84879

Gene nameRLF zinc fingermajor facilitator superfamily domain containing 2A
SynonymsZN-15L|ZNF292LMCPH15|MFSD2|NLS1
Cytomap

1p34.2

1p34.2

Type of geneprotein-codingprotein-coding
Descriptionzinc finger protein RlfZn-15 relatedrearranged L-myc fusion gene proteinrearranged L-myc fusion sequencezn-15-related proteinsodium-dependent lysophosphatidylcholine symporter 1major facilitator superfamily domain-containing protein 2Asodium-dependent LPC symporter 1
Modification date2020031320200313
UniProtAcc.

Q8NA29

Main function of 5'-partner protein: FUNCTION: Sodium-dependent lysophosphatidylcholine (LPC) symporter, which plays an essential role for blood-brain barrier formation and function (PubMed:24828040). Specifically expressed in endothelium of the blood-brain barrier of micro-vessels and transports LPC into the brain (By similarity). Transport of LPC is essential because it constitutes the major mechanism by which docosahexaenoic acid (DHA), an omega-3 fatty acid that is essential for normal brain growth and cognitive function, enters the brain (PubMed:26005868). Transports LPC carrying long-chain fatty acids such LPC oleate and LPC palmitate with a minimum acyl chain length of 14 carbons (By similarity). Does not transport docosahexaenoic acid in unesterified fatty acid (By similarity). Specifically required for blood-brain barrier formation and function, probably by mediating lipid transport (By similarity). Not required for central nervous system vascular morphogenesis (By similarity). Acts as a transporter for tunicamycin, an inhibitor of asparagine-linked glycosylation (PubMed:21677192). In placenta, acts as a receptor for ERVFRD-1/syncytin-2 and is required for trophoblast fusion (PubMed:18988732, PubMed:23177091). {ECO:0000250|UniProtKB:Q9DA75, ECO:0000269|PubMed:18988732, ECO:0000269|PubMed:21677192, ECO:0000269|PubMed:23177091, ECO:0000269|PubMed:24828040, ECO:0000269|PubMed:26005868}.
Ensembl transtripts involved in fusion geneENST idsENST00000372771, ENST00000372809, 
ENST00000420632, ENST00000480630, 
ENST00000372811, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score13 X 7 X 7=6378 X 8 X 3=192
# samples 138
** MAII scorelog2(13/637*10)=-2.29278174922785
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(8/192*10)=-1.26303440583379
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: RLF [Title/Abstract] AND MFSD2A [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: RLF [Title/Abstract] AND MFSD2A [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)RLF(40627308)-MFSD2A(40422759), # samples:2
RLF(40627308)-MFSD2A(40424373), # samples:2
Anticipated loss of major functional domain due to fusion event.RLF-MFSD2A 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.
RLF-MFSD2A 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.
RLF-MFSD2A 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.
RLF-MFSD2A 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
HgeneRLF

GO:0015074

DNA integration

1851085

HgeneRLF

GO:0051276

chromosome organization

1649386

TgeneMFSD2A

GO:0051977

lysophospholipid transport

24828044



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/chr1:40627308/chr1:40422759)
- 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 RLF (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 MFSD2A (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)
ENST00000372771RLFchr140627308+ENST00000372811MFSD2Achr140422759+216226491763584
ENST00000372771RLFchr140627308+ENST00000372811MFSD2Achr140424373+202726491628539

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
ENST00000372771ENST00000372811RLFchr140627308+MFSD2Achr140422759+0.0115305250.98846954
ENST00000372771ENST00000372811RLFchr140627308+MFSD2Achr140424373+0.0099840370.9900159

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 RLF-MFSD2A

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
RLFchr140627308MFSD2Achr14042275926484SEVSSLNYCRSFCQKEPKKKKQQLSV
RLFchr140627308MFSD2Achr14042437326479REQEVSEVSSLNYCRSFCQVGPFSAS

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Potential FusionNeoAntigen Information of RLF-MFSD2A 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.
RLF-MFSD2A_40627308_40422759.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)
RLF-MFSD2Achr140627308chr140422759264HLA-A30:08RSFCQKEPK0.99710.632918
RLF-MFSD2Achr140627308chr140422759264HLA-A30:08RSFCQKEPKK0.99710.6612919
RLF-MFSD2Achr140627308chr140422759264HLA-A30:01RSFCQKEPK0.99720.7607918
RLF-MFSD2Achr140627308chr140422759264HLA-A30:01RSFCQKEPKK0.99690.7603919

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Potential FusionNeoAntigen Information of RLF-MFSD2A 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 RLF-MFSD2A

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
6461NYCRSFCQKEPKKKRLFMFSD2Achr140627308chr140422759264

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of RLF-MFSD2A

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-B14:023BVN6461NYCRSFCQKEPKKK-7.9962-8.1096
HLA-B14:023BVN6461NYCRSFCQKEPKKK-5.70842-6.74372
HLA-B52:013W396461NYCRSFCQKEPKKK-6.83737-6.95077
HLA-B52:013W396461NYCRSFCQKEPKKK-4.4836-5.5189
HLA-A11:014UQ26461NYCRSFCQKEPKKK-10.0067-10.1201
HLA-A11:014UQ26461NYCRSFCQKEPKKK-9.03915-10.0745
HLA-A24:025HGA6461NYCRSFCQKEPKKK-6.56204-6.67544
HLA-A24:025HGA6461NYCRSFCQKEPKKK-5.42271-6.45801
HLA-B44:053DX86461NYCRSFCQKEPKKK-7.85648-8.89178
HLA-B44:053DX86461NYCRSFCQKEPKKK-5.3978-5.5112
HLA-A02:016TDR6461NYCRSFCQKEPKKK-3.37154-4.40684

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Vaccine Design for the FusionNeoAntigens of RLF-MFSD2A

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
RLF-MFSD2Achr140627308chr140422759918RSFCQKEPKAGCTTCTGCCAGAAAGAACCGAAAAAG
RLF-MFSD2Achr140627308chr140422759919RSFCQKEPKKAGCTTCTGCCAGAAAGAACCGAAAAAGAAG

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 RLF-MFSD2A

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
OVRLF-MFSD2Achr140627308ENST00000372771chr140422759ENST00000372811TCGA-24-1557-01A

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Potential target of CAR-T therapy development for RLF-MFSD2A

check button Predicted 3D structure. We used RoseTTAFold.
379_RLF-MFSD2A_cc6a8_pred.pdb


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
TgeneMFSD2Achr1:40627308chr1:40422759ENST00000372809014129_1490544.0TransmembraneHelical
TgeneMFSD2Achr1:40627308chr1:40422759ENST00000372809014161_1810544.0TransmembraneHelical
TgeneMFSD2Achr1:40627308chr1:40422759ENST00000372809014257_2770544.0TransmembraneHelical
TgeneMFSD2Achr1:40627308chr1:40422759ENST00000372809014311_3310544.0TransmembraneHelical
TgeneMFSD2Achr1:40627308chr1:40422759ENST00000372809014345_3650544.0TransmembraneHelical
TgeneMFSD2Achr1:40627308chr1:40422759ENST00000372809014371_3910544.0TransmembraneHelical
TgeneMFSD2Achr1:40627308chr1:40422759ENST00000372809014394_4140544.0TransmembraneHelical
TgeneMFSD2Achr1:40627308chr1:40422759ENST00000372809014438_4580544.0TransmembraneHelical
TgeneMFSD2Achr1:40627308chr1:40422759ENST0000037280901447_670544.0TransmembraneHelical
TgeneMFSD2Achr1:40627308chr1:40422759ENST00000372809014481_5010544.0TransmembraneHelical
TgeneMFSD2Achr1:40627308chr1:40422759ENST0000037280901481_1010544.0TransmembraneHelical
TgeneMFSD2Achr1:40627308chr1:40422759ENST00000372811014129_1490531.0TransmembraneHelical
TgeneMFSD2Achr1:40627308chr1:40422759ENST00000372811014161_1810531.0TransmembraneHelical
TgeneMFSD2Achr1:40627308chr1:40422759ENST00000372811014257_2770531.0TransmembraneHelical
TgeneMFSD2Achr1:40627308chr1:40422759ENST00000372811014311_3310531.0TransmembraneHelical
TgeneMFSD2Achr1:40627308chr1:40422759ENST00000372811014345_3650531.0TransmembraneHelical
TgeneMFSD2Achr1:40627308chr1:40422759ENST00000372811014371_3910531.0TransmembraneHelical
TgeneMFSD2Achr1:40627308chr1:40422759ENST00000372811014394_4140531.0TransmembraneHelical
TgeneMFSD2Achr1:40627308chr1:40422759ENST00000372811014438_4580531.0TransmembraneHelical
TgeneMFSD2Achr1:40627308chr1:40422759ENST0000037281101447_670531.0TransmembraneHelical
TgeneMFSD2Achr1:40627308chr1:40422759ENST00000372811014481_5010531.0TransmembraneHelical
TgeneMFSD2Achr1:40627308chr1:40422759ENST0000037281101481_1010531.0TransmembraneHelical
TgeneMFSD2Achr1:40627308chr1:40424373ENST00000372809014129_1490544.0TransmembraneHelical
TgeneMFSD2Achr1:40627308chr1:40424373ENST00000372809014161_1810544.0TransmembraneHelical
TgeneMFSD2Achr1:40627308chr1:40424373ENST00000372809014257_2770544.0TransmembraneHelical
TgeneMFSD2Achr1:40627308chr1:40424373ENST00000372809014311_3310544.0TransmembraneHelical
TgeneMFSD2Achr1:40627308chr1:40424373ENST00000372809014345_3650544.0TransmembraneHelical
TgeneMFSD2Achr1:40627308chr1:40424373ENST00000372809014371_3910544.0TransmembraneHelical
TgeneMFSD2Achr1:40627308chr1:40424373ENST00000372809014394_4140544.0TransmembraneHelical
TgeneMFSD2Achr1:40627308chr1:40424373ENST00000372809014438_4580544.0TransmembraneHelical
TgeneMFSD2Achr1:40627308chr1:40424373ENST0000037280901447_670544.0TransmembraneHelical
TgeneMFSD2Achr1:40627308chr1:40424373ENST00000372809014481_5010544.0TransmembraneHelical
TgeneMFSD2Achr1:40627308chr1:40424373ENST0000037280901481_1010544.0TransmembraneHelical
TgeneMFSD2Achr1:40627308chr1:40424373ENST00000372811114129_1490531.0TransmembraneHelical
TgeneMFSD2Achr1:40627308chr1:40424373ENST00000372811114161_1810531.0TransmembraneHelical
TgeneMFSD2Achr1:40627308chr1:40424373ENST00000372811114257_2770531.0TransmembraneHelical
TgeneMFSD2Achr1:40627308chr1:40424373ENST00000372811114311_3310531.0TransmembraneHelical
TgeneMFSD2Achr1:40627308chr1:40424373ENST00000372811114345_3650531.0TransmembraneHelical
TgeneMFSD2Achr1:40627308chr1:40424373ENST00000372811114371_3910531.0TransmembraneHelical
TgeneMFSD2Achr1:40627308chr1:40424373ENST00000372811114394_4140531.0TransmembraneHelical
TgeneMFSD2Achr1:40627308chr1:40424373ENST00000372811114438_4580531.0TransmembraneHelical
TgeneMFSD2Achr1:40627308chr1:40424373ENST00000372811114481_5010531.0TransmembraneHelical
TgeneMFSD2Achr1:40627308chr1:40424373ENST0000037281111481_1010531.0TransmembraneHelical

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
RLFchr140627308ENST00000372771MFSD2Achr140422759ENST00000372811
RLFchr140627308ENST00000372771MFSD2Achr140424373ENST00000372811

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Related Drugs to RLF-MFSD2A

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 RLF-MFSD2A

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