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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:RARB-FAM19A4

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: RARB-FAM19A4
FusionPDB ID: 72331
FusionGDB2.0 ID: 72331
HgeneTgene
Gene symbol

RARB

FAM19A4

Gene ID

5915

151647

Gene nameretinoic acid receptor betaTAFA chemokine like family member 4
SynonymsHAP|MCOPS12|NR1B2|RARbeta1|RRB2FAM19A4|TAFA-4
Cytomap

3p24.2

3p14.1

Type of geneprotein-codingprotein-coding
Descriptionretinoic acid receptor betaHBV-activated proteinRAR-betaRAR-epsilonhepatitis B virus activated proteinnuclear receptor subfamily 1 group B member 2retinoic acid receptor, beta polypeptidechemokine-like protein TAFA-4family with sequence similarity 19 (chemokine (C-C motif)-like), member A4family with sequence similarity 19 member A4, C-C motif chemokine likeprotein FAM19A4
Modification date2020032820200313
UniProtAcc..
Ensembl transtripts involved in fusion geneENST idsENST00000462272, ENST00000330688, 
ENST00000404969, ENST00000437042, 
ENST00000458646, 
ENST00000295569, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score12 X 11 X 5=6604 X 5 X 4=80
# samples 124
** MAII scorelog2(12/660*10)=-2.4594316186373
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(4/80*10)=-1
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: RARB [Title/Abstract] AND FAM19A4 [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: RARB [Title/Abstract] AND FAM19A4 [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)RARB(25542814)-FAM19A4(68802169), # samples:2
Anticipated loss of major functional domain due to fusion event.RARB-FAM19A4 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.
RARB-FAM19A4 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.
RARB-FAM19A4 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.
RARB-FAM19A4 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/chr3:25542814/chr3:68802169)
- 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 RARB (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 FAM19A4 (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)
ENST00000404969RARBchr325542814+ENST00000295569FAM19A4chr368802169-21384690761253
ENST00000437042RARBchr325542814+ENST00000295569FAM19A4chr368802169-222956097852251
ENST00000330688RARBchr325542814+ENST00000295569FAM19A4chr368802169-25388693941161255
ENST00000458646RARBchr325542814+ENST00000295569FAM19A4chr368802169-204437565667200

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
ENST00000404969ENST00000295569RARBchr325542814+FAM19A4chr368802169-0.0024892790.9975107
ENST00000437042ENST00000295569RARBchr325542814+FAM19A4chr368802169-0.0095359820.990464
ENST00000330688ENST00000295569RARBchr325542814+FAM19A4chr368802169-0.0017605160.9982395
ENST00000458646ENST00000295569RARBchr325542814+FAM19A4chr368802169-0.023187590.9768124

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 RARB-FAM19A4

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
RARBchr325542814FAM19A4chr368802169375104LQKCFEVGMSKECHHQIKQGTCEVVA
RARBchr325542814FAM19A4chr368802169469157LQKCFEVGMSKECHHQIKQGTCEVVA
RARBchr325542814FAM19A4chr368802169560155LQKCFEVGMSKECHHQIKQGTCEVVA
RARBchr325542814FAM19A4chr368802169869159LQKCFEVGMSKECHHQIKQGTCEVVA

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Potential FusionNeoAntigen Information of RARB-FAM19A4 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.
RARB-FAM19A4_25542814_68802169.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)
RARB-FAM19A4chr325542814chr368802169869HLA-B15:16MSKECHHQI0.98360.6254817
RARB-FAM19A4chr325542814chr368802169869HLA-C15:06MSKECHHQI0.99880.798817
RARB-FAM19A4chr325542814chr368802169869HLA-C12:12MSKECHHQI0.93490.8001817
RARB-FAM19A4chr325542814chr368802169869HLA-C12:04MSKECHHQI0.9240.971817
RARB-FAM19A4chr325542814chr368802169869HLA-C06:03MSKECHHQI0.92090.9723817
RARB-FAM19A4chr325542814chr368802169869HLA-C15:02MSKECHHQI0.99880.7531817
RARB-FAM19A4chr325542814chr368802169869HLA-C16:04MSKECHHQI0.95130.9235817
RARB-FAM19A4chr325542814chr368802169869HLA-C12:03MSKECHHQI0.92330.9245817
RARB-FAM19A4chr325542814chr368802169869HLA-C16:02MSKECHHQI0.90250.976817
RARB-FAM19A4chr325542814chr368802169869HLA-A30:01MSKECHHQIK0.98130.5337818

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Potential FusionNeoAntigen Information of RARB-FAM19A4 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 RARB-FAM19A4

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
9952VGMSKECHHQIKQGRARBFAM19A4chr325542814chr368802169869

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of RARB-FAM19A4

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-B14:023BVN9952VGMSKECHHQIKQG-6.62904-6.74084
HLA-B14:023BVN9952VGMSKECHHQIKQG-4.47112-5.51422
HLA-B52:013W399952VGMSKECHHQIKQG-6.67729-6.78909
HLA-B52:013W399952VGMSKECHHQIKQG-3.57043-4.61353
HLA-A11:014UQ29952VGMSKECHHQIKQG-8.27675-8.38855
HLA-A24:025HGA9952VGMSKECHHQIKQG-6.47973-6.59153
HLA-A24:025HGA9952VGMSKECHHQIKQG-5.29795-6.34105
HLA-B44:053DX89952VGMSKECHHQIKQG-6.59186-7.63496
HLA-B44:053DX89952VGMSKECHHQIKQG-4.74709-4.85889
HLA-A02:016TDR9952VGMSKECHHQIKQG-4.32034-5.36344

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Vaccine Design for the FusionNeoAntigens of RARB-FAM19A4

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
RARB-FAM19A4chr325542814chr368802169817MSKECHHQIGAATGTCCAAAGAATGTCACCACCAAA
RARB-FAM19A4chr325542814chr368802169818MSKECHHQIKGAATGTCCAAAGAATGTCACCACCAAATCA

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 RARB-FAM19A4

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
PRADRARB-FAM19A4chr325542814ENST00000330688chr368802169ENST00000295569TCGA-EJ-5501-01A

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Potential target of CAR-T therapy development for RARB-FAM19A4

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 RARB-FAM19A4

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 RARB-FAM19A4

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