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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:NFYA-TREML2

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: NFYA-TREML2
FusionPDB ID: 59028
FusionGDB2.0 ID: 59028
HgeneTgene
Gene symbol

NFYA

TREML2

Gene ID

4800

79865

Gene namenuclear transcription factor Y subunit alphatriggering receptor expressed on myeloid cells like 2
SynonymsCBF-A|CBF-B|HAP2|NF-YAC6orf76|TLT-2|TLT2|dJ238O23.1
Cytomap

6p21.1

6p21.1

Type of geneprotein-codingprotein-coding
Descriptionnuclear transcription factor Y subunit alphaCAAT-box DNA binding protein subunit ACCAAT-binding transcription factor subunit BHAP2 CCAAT-binding proteinTranscription factor NF-Y, A subunitnuclear transcription factor Y subunit Anuclear transcriptiontrem-like transcript 2 proteintriggering receptor expressed on myeloid cells-like protein 2
Modification date2020032720200313
UniProtAcc

P23511

Main function of 5'-partner protein: FUNCTION: Component of the sequence-specific heterotrimeric transcription factor (NF-Y) which specifically recognizes a 5'-CCAAT-3' box motif found in the promoters of its target genes. NF-Y can function as both an activator and a repressor, depending on its interacting cofactors. NF-YA positively regulates the transcription of the core clock component ARNTL/BMAL1. {ECO:0000269|PubMed:12741956}.
.
Ensembl transtripts involved in fusion geneENST idsENST00000341376, ENST00000353205, 
ENST00000483722, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score4 X 4 X 4=641 X 1 X 1=1
# samples 41
** MAII scorelog2(4/64*10)=-0.678071905112638
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(1/1*10)=3.32192809488736
Fusion gene context

PubMed: NFYA [Title/Abstract] AND TREML2 [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: NFYA [Title/Abstract] AND TREML2 [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)NFYA(41058048)-TREML2(41162571), # samples:3
Anticipated loss of major functional domain due to fusion event.NFYA-TREML2 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.
NFYA-TREML2 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.
NFYA-TREML2 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.
NFYA-TREML2 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
HgeneNFYA

GO:0006355

regulation of transcription, DNA-templated

15243141

TgeneTREML2

GO:0042110

T cell activation

18650384



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/chr6:41058048/chr6:41162571)
- 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 NFYA (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 TREML2 (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)
ENST00000341376NFYAchr641058048+ENST00000483722TREML2chr641162571-3488748751337420
ENST00000353205NFYAchr641058048+ENST00000483722TREML2chr641162571-3363623371212391

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
ENST00000341376ENST00000483722NFYAchr641058048+TREML2chr641162571-0.0173075480.9826925
ENST00000353205ENST00000483722NFYAchr641058048+TREML2chr641162571-0.0062324640.9937675

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 NFYA-TREML2

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
NFYAchr641058048TREML2chr641162571623195YQPVNADGTILQQAPQTERNIPFTHL
NFYAchr641058048TREML2chr641162571748224YQPVNADGTILQQAPQTERNIPFTHL

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Potential FusionNeoAntigen Information of NFYA-TREML2 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.
NFYA-TREML2_41058048_41162571.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)
NFYA-TREML2chr641058048chr641162571748HLA-A31:02LQQAPQTER0.81580.81941019
NFYA-TREML2chr641058048chr641162571748HLA-A31:06LQQAPQTER0.70950.6751019
NFYA-TREML2chr641058048chr641162571748HLA-A31:06ILQQAPQTER0.80630.6136919
NFYA-TREML2chr641058048chr641162571748HLA-B13:02QQAPQTERNI0.62880.93361121
NFYA-TREML2chr641058048chr641162571748HLA-A31:01LQQAPQTER0.81470.81041019
NFYA-TREML2chr641058048chr641162571748HLA-C01:17QAPQTERNI0.6640.96861221
NFYA-TREML2chr641058048chr641162571748HLA-C01:30QAPQTERNI0.5160.96881221
NFYA-TREML2chr641058048chr641162571748HLA-C01:03QAPQTERNI0.88390.97711221
NFYA-TREML2chr641058048chr641162571748HLA-C01:02QAPQTERNI0.70480.96821221

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Potential FusionNeoAntigen Information of NFYA-TREML2 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.
NFYA-TREML2_41058048_41162571.msa

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)
NFYA-TREML2chr641058048chr641162571748DRB1-0301YQPVNADGTILQQAP015
NFYA-TREML2chr641058048chr641162571748DRB1-0307YQPVNADGTILQQAP015
NFYA-TREML2chr641058048chr641162571748DRB1-0310YQPVNADGTILQQAP015
NFYA-TREML2chr641058048chr641162571748DRB1-0313YQPVNADGTILQQAP015
NFYA-TREML2chr641058048chr641162571748DRB1-0315YQPVNADGTILQQAP015
NFYA-TREML2chr641058048chr641162571748DRB1-0318YQPVNADGTILQQAP015
NFYA-TREML2chr641058048chr641162571748DRB1-0320YQPVNADGTILQQAP015
NFYA-TREML2chr641058048chr641162571748DRB1-0322YQPVNADGTILQQAP015
NFYA-TREML2chr641058048chr641162571748DRB1-0326YQPVNADGTILQQAP015
NFYA-TREML2chr641058048chr641162571748DRB1-0328YQPVNADGTILQQAP015
NFYA-TREML2chr641058048chr641162571748DRB1-0330YQPVNADGTILQQAP015
NFYA-TREML2chr641058048chr641162571748DRB1-0332YQPVNADGTILQQAP015
NFYA-TREML2chr641058048chr641162571748DRB1-0334YQPVNADGTILQQAP015
NFYA-TREML2chr641058048chr641162571748DRB1-0336YQPVNADGTILQQAP015
NFYA-TREML2chr641058048chr641162571748DRB1-0342YQPVNADGTILQQAP015
NFYA-TREML2chr641058048chr641162571748DRB1-0344YQPVNADGTILQQAP015
NFYA-TREML2chr641058048chr641162571748DRB1-0346YQPVNADGTILQQAP015
NFYA-TREML2chr641058048chr641162571748DRB1-0348YQPVNADGTILQQAP015
NFYA-TREML2chr641058048chr641162571748DRB1-0350YQPVNADGTILQQAP015
NFYA-TREML2chr641058048chr641162571748DRB1-0352YQPVNADGTILQQAP015
NFYA-TREML2chr641058048chr641162571748DRB1-0354YQPVNADGTILQQAP015
NFYA-TREML2chr641058048chr641162571748DRB1-0401YQPVNADGTILQQAP015
NFYA-TREML2chr641058048chr641162571748DRB1-0413YQPVNADGTILQQAP015
NFYA-TREML2chr641058048chr641162571748DRB1-0413QPVNADGTILQQAPQ116
NFYA-TREML2chr641058048chr641162571748DRB1-0422YQPVNADGTILQQAP015
NFYA-TREML2chr641058048chr641162571748DRB1-0422QPVNADGTILQQAPQ116
NFYA-TREML2chr641058048chr641162571748DRB1-0433YQPVNADGTILQQAP015
NFYA-TREML2chr641058048chr641162571748DRB1-0434YQPVNADGTILQQAP015
NFYA-TREML2chr641058048chr641162571748DRB1-0435YQPVNADGTILQQAP015
NFYA-TREML2chr641058048chr641162571748DRB1-0438YQPVNADGTILQQAP015
NFYA-TREML2chr641058048chr641162571748DRB1-0444YQPVNADGTILQQAP015
NFYA-TREML2chr641058048chr641162571748DRB1-0463YQPVNADGTILQQAP015
NFYA-TREML2chr641058048chr641162571748DRB1-0464YQPVNADGTILQQAP015
NFYA-TREML2chr641058048chr641162571748DRB1-0466YQPVNADGTILQQAP015
NFYA-TREML2chr641058048chr641162571748DRB1-0472YQPVNADGTILQQAP015
NFYA-TREML2chr641058048chr641162571748DRB1-0476YQPVNADGTILQQAP015
NFYA-TREML2chr641058048chr641162571748DRB1-1107YQPVNADGTILQQAP015
NFYA-TREML2chr641058048chr641162571748DRB1-1476YQPVNADGTILQQAP015
NFYA-TREML2chr641058048chr641162571748DRB1-1479YQPVNADGTILQQAP015

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Fusion breakpoint peptide structures of NFYA-TREML2

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
1129DGTILQQAPQTERNNFYATREML2chr641058048chr641162571748

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of NFYA-TREML2

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-B14:023BVN1129DGTILQQAPQTERN-7.15543-7.26883
HLA-B14:023BVN1129DGTILQQAPQTERN-4.77435-5.80965
HLA-B52:013W391129DGTILQQAPQTERN-6.80875-6.92215
HLA-B52:013W391129DGTILQQAPQTERN-4.20386-5.23916
HLA-A11:014UQ21129DGTILQQAPQTERN-7.5194-8.5547
HLA-A11:014UQ21129DGTILQQAPQTERN-6.9601-7.0735
HLA-A24:025HGA1129DGTILQQAPQTERN-7.52403-7.63743
HLA-A24:025HGA1129DGTILQQAPQTERN-5.82433-6.85963
HLA-B27:056PYJ1129DGTILQQAPQTERN-3.28285-4.31815
HLA-B44:053DX81129DGTILQQAPQTERN-5.91172-6.94702
HLA-B44:053DX81129DGTILQQAPQTERN-4.24346-4.35686

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Vaccine Design for the FusionNeoAntigens of NFYA-TREML2

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
NFYA-TREML2chr641058048chr6411625711019LQQAPQTERTCCAGCAAGCTCCCCAAACTGAGAGGA
NFYA-TREML2chr641058048chr6411625711121QQAPQTERNIAGCAAGCTCCCCAAACTGAGAGGAACATTC
NFYA-TREML2chr641058048chr6411625711221QAPQTERNIAAGCTCCCCAAACTGAGAGGAACATTC
NFYA-TREML2chr641058048chr641162571919ILQQAPQTERTTCTCCAGCAAGCTCCCCAAACTGAGAGGA

check button mRNA and peptide sequences of FusionNeoAntigens that have potential interaction with HLA-IIs.
Fusion geneHchrHbpTchrTbpStart in +/-13AAEnd in +/-13AAFusionNeoAntigen peptideFusionNEoAntigen RNA sequence
NFYA-TREML2chr641058048chr641162571015YQPVNADGTILQQAPATCAACCAGTTAATGCAGATGGCACCATTCTCCAGCAAGCTCCCC
NFYA-TREML2chr641058048chr641162571116QPVNADGTILQQAPQAACCAGTTAATGCAGATGGCACCATTCTCCAGCAAGCTCCCCAAA

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Information of the samples that have these potential fusion neoantigens of NFYA-TREML2

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
COADNFYA-TREML2chr641058048ENST00000341376chr641162571ENST00000483722TCGA-DM-A1D7-01A

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Potential target of CAR-T therapy development for NFYA-TREML2

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
TgeneTREML2chr6:41058048chr6:41162571ENST0000048372215269_2890322.0TransmembraneHelical

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

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Related Drugs to NFYA-TREML2

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 NFYA-TREML2

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