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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:TCF12-RGMA

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: TCF12-RGMA
FusionPDB ID: 89719
FusionGDB2.0 ID: 89719
HgeneTgene
Gene symbol

TCF12

RGMA

Gene ID

6938

56963

Gene nametranscription factor 12repulsive guidance molecule BMP co-receptor a
SynonymsCRS3|HEB|HTF4|HsT17266|TCF-12|bHLHb20|p64RGM
Cytomap

15q21.3

15q26.1

Type of geneprotein-codingprotein-coding
Descriptiontranscription factor 12DNA-binding protein HTF4E-box-binding proteinclass B basic helix-loop-helix protein 20helix-loop-helix transcription factor 4transcription factor HTF-4repulsive guidance molecule ARGM domain family, member Arepulsive guidance molecule family member a
Modification date2020031320200313
UniProtAcc..
Ensembl transtripts involved in fusion geneENST idsENST00000267811, ENST00000333725, 
ENST00000438423, ENST00000452095, 
ENST00000557843, ENST00000343827, 
ENST00000537840, ENST00000543579, 
ENST00000559703, ENST00000559710, 
ENST00000560764, 
ENST00000538818, 
ENST00000555584, ENST00000556087, 
ENST00000556658, ENST00000557301, 
ENST00000557420, ENST00000329082, 
ENST00000425933, ENST00000542321, 
ENST00000543599, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score29 X 19 X 12=66126 X 4 X 3=72
# samples 327
** MAII scorelog2(32/6612*10)=-4.36894291440495
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(7/72*10)=-0.0406419844973459
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: TCF12 [Title/Abstract] AND RGMA [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: TCF12 [Title/Abstract] AND RGMA [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)TCF12(57384089)-RGMA(93595737), # samples:1
Anticipated loss of major functional domain due to fusion event.TCF12-RGMA 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.
TCF12-RGMA 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.
TCF12-RGMA 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.
TCF12-RGMA 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
HgeneTCF12

GO:0045944

positive regulation of transcription by RNA polymerase II

11802795

TgeneRGMA

GO:0045944

positive regulation of transcription by RNA polymerase II

22728873



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/chr15:57384089/chr15:93595737)
- 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 TCF12 (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 RGMA (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)
ENST00000438423TCF12chr1557384089-ENST00000425933RGMAchr1593595737-34366212601843527
ENST00000438423TCF12chr1557384089-ENST00000543599RGMAchr1593595737-34366212601843527
ENST00000438423TCF12chr1557384089-ENST00000329082RGMAchr1593595737-34356212601843527
ENST00000438423TCF12chr1557384089-ENST00000542321RGMAchr1593595737-34266212601843527
ENST00000267811TCF12chr1557384089-ENST00000425933RGMAchr1593595737-34446293041851515
ENST00000267811TCF12chr1557384089-ENST00000543599RGMAchr1593595737-34446293041851515
ENST00000267811TCF12chr1557384089-ENST00000329082RGMAchr1593595737-34436293041851515
ENST00000267811TCF12chr1557384089-ENST00000542321RGMAchr1593595737-34346293041851515
ENST00000452095TCF12chr1557384089-ENST00000425933RGMAchr1593595737-34226072941829511
ENST00000452095TCF12chr1557384089-ENST00000543599RGMAchr1593595737-34226072941829511
ENST00000452095TCF12chr1557384089-ENST00000329082RGMAchr1593595737-34216072941829511
ENST00000452095TCF12chr1557384089-ENST00000542321RGMAchr1593595737-34126072941829511
ENST00000333725TCF12chr1557384089-ENST00000425933RGMAchr1593595737-33755602351782515
ENST00000333725TCF12chr1557384089-ENST00000543599RGMAchr1593595737-33755602351782515
ENST00000333725TCF12chr1557384089-ENST00000329082RGMAchr1593595737-33745602351782515
ENST00000333725TCF12chr1557384089-ENST00000542321RGMAchr1593595737-33655602351782515
ENST00000557843TCF12chr1557384089-ENST00000425933RGMAchr1593595737-3227412511634527
ENST00000557843TCF12chr1557384089-ENST00000543599RGMAchr1593595737-3227412511634527
ENST00000557843TCF12chr1557384089-ENST00000329082RGMAchr1593595737-3226412511634527
ENST00000557843TCF12chr1557384089-ENST00000542321RGMAchr1593595737-3217412511634527

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
ENST00000438423ENST00000425933TCF12chr1557384089-RGMAchr1593595737-0.0116059360.988394
ENST00000438423ENST00000543599TCF12chr1557384089-RGMAchr1593595737-0.0116059360.988394
ENST00000438423ENST00000329082TCF12chr1557384089-RGMAchr1593595737-0.0117883760.9882116
ENST00000438423ENST00000542321TCF12chr1557384089-RGMAchr1593595737-0.0118805420.98811954
ENST00000267811ENST00000425933TCF12chr1557384089-RGMAchr1593595737-0.0118264880.98817354
ENST00000267811ENST00000543599TCF12chr1557384089-RGMAchr1593595737-0.0118264880.98817354
ENST00000267811ENST00000329082TCF12chr1557384089-RGMAchr1593595737-0.0120167330.9879832
ENST00000267811ENST00000542321TCF12chr1557384089-RGMAchr1593595737-0.0121074040.98789257
ENST00000452095ENST00000425933TCF12chr1557384089-RGMAchr1593595737-0.0128872390.9871128
ENST00000452095ENST00000543599TCF12chr1557384089-RGMAchr1593595737-0.0128872390.9871128
ENST00000452095ENST00000329082TCF12chr1557384089-RGMAchr1593595737-0.0130788710.9869212
ENST00000452095ENST00000542321TCF12chr1557384089-RGMAchr1593595737-0.0132205580.98677945
ENST00000333725ENST00000425933TCF12chr1557384089-RGMAchr1593595737-0.0124140720.9875859
ENST00000333725ENST00000543599TCF12chr1557384089-RGMAchr1593595737-0.0124140720.9875859
ENST00000333725ENST00000329082TCF12chr1557384089-RGMAchr1593595737-0.0126176770.98738235
ENST00000333725ENST00000542321TCF12chr1557384089-RGMAchr1593595737-0.0126941410.9873059
ENST00000557843ENST00000425933TCF12chr1557384089-RGMAchr1593595737-0.0118759630.9881241
ENST00000557843ENST00000543599TCF12chr1557384089-RGMAchr1593595737-0.0118759630.9881241
ENST00000557843ENST00000329082TCF12chr1557384089-RGMAchr1593595737-0.0120761050.9879239
ENST00000557843ENST00000542321TCF12chr1557384089-RGMAchr1593595737-0.0121474630.9878526

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 TCF12-RGMA

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
TCF12chr1557384089RGMAchr1593595737412120GLSPTPFMNSNLMATSPCKILKCNSE
TCF12chr1557384089RGMAchr1593595737560108GLSPTPFMNSNLMATSPCKILKCNSE
TCF12chr1557384089RGMAchr1593595737607104GLSPTPFMNSNLMATSPCKILKCNSE
TCF12chr1557384089RGMAchr1593595737621120GLSPTPFMNSNLMATSPCKILKCNSE
TCF12chr1557384089RGMAchr1593595737629108GLSPTPFMNSNLMATSPCKILKCNSE

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Potential FusionNeoAntigen Information of TCF12-RGMA 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.
TCF12-RGMA_57384089_93595737.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)
TCF12-RGMAchr1557384089chr1593595737629HLA-A02:13FMNSNLMAT0.97770.5532615
TCF12-RGMAchr1557384089chr1593595737629HLA-A02:38FMNSNLMAT0.95250.5346615
TCF12-RGMAchr1557384089chr1593595737629HLA-C03:08MATSPCKIL0.99680.91741221
TCF12-RGMAchr1557384089chr1593595737629HLA-C03:19MATSPCKIL0.99670.98411221
TCF12-RGMAchr1557384089chr1593595737629HLA-C03:07MATSPCKIL0.9960.98191221
TCF12-RGMAchr1557384089chr1593595737629HLA-C12:12MATSPCKIL0.88410.94011221
TCF12-RGMAchr1557384089chr1593595737629HLA-C03:04MATSPCKIL0.99750.98641221
TCF12-RGMAchr1557384089chr1593595737629HLA-C03:03MATSPCKIL0.99750.98641221
TCF12-RGMAchr1557384089chr1593595737629HLA-C03:05MATSPCKIL0.99680.9351221
TCF12-RGMAchr1557384089chr1593595737629HLA-C03:17MATSPCKIL0.99630.97241221
TCF12-RGMAchr1557384089chr1593595737629HLA-A02:03FMNSNLMAT0.98980.6297615
TCF12-RGMAchr1557384089chr1593595737629HLA-C16:04MATSPCKIL0.94680.98311221
TCF12-RGMAchr1557384089chr1593595737629HLA-C03:06MATSPCKIL0.86450.9861221
TCF12-RGMAchr1557384089chr1593595737629HLA-B07:13MATSPCKIL0.72990.86041221
TCF12-RGMAchr1557384089chr1593595737629HLA-C16:01MATSPCKIL0.71270.98071221

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Potential FusionNeoAntigen Information of TCF12-RGMA 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 TCF12-RGMA

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
2472FMNSNLMATSPCKITCF12RGMAchr1557384089chr1593595737629

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of TCF12-RGMA

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-B14:023BVN2472FMNSNLMATSPCKI-5.49577-5.60917
HLA-B14:023BVN2472FMNSNLMATSPCKI-4.37152-5.40682
HLA-B52:013W392472FMNSNLMATSPCKI-6.90336-7.01676
HLA-B52:013W392472FMNSNLMATSPCKI-4.80833-5.84363
HLA-A11:014UQ22472FMNSNLMATSPCKI-9.82261-9.93601
HLA-A24:025HGA2472FMNSNLMATSPCKI-9.78612-9.89952
HLA-A24:025HGA2472FMNSNLMATSPCKI-4.98992-6.02522
HLA-B27:056PYJ2472FMNSNLMATSPCKI-5.31553-6.35083
HLA-B44:053DX82472FMNSNLMATSPCKI-5.70582-5.81922
HLA-B44:053DX82472FMNSNLMATSPCKI-4.32241-5.35771

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Vaccine Design for the FusionNeoAntigens of TCF12-RGMA

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
TCF12-RGMAchr1557384089chr15935957371221MATSPCKILTGGCCACCTCCCCGTGCAAGATCCTCA
TCF12-RGMAchr1557384089chr1593595737615FMNSNLMATTCATGAACTCAAATCTGATGGCCACCT

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 TCF12-RGMA

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
STADTCF12-RGMAchr1557384089ENST00000267811chr1593595737ENST00000329082TCGA-CG-4304-01A

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Potential target of CAR-T therapy development for TCF12-RGMA

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 TCF12-RGMA

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 TCF12-RGMA

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