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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:MAP4K4-TXNL4A

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: MAP4K4-TXNL4A
FusionPDB ID: 51416
FusionGDB2.0 ID: 51416
HgeneTgene
Gene symbol

MAP4K4

TXNL4A

Gene ID

9448

10907

Gene namemitogen-activated protein kinase kinase kinase kinase 4thioredoxin like 4A
SynonymsFLH21957|HEL-S-31|HGK|MEKKK4|NIKBMKS|DIB1|DIM1|SNRNP15|TXNL4|U5-15kD
Cytomap

2q11.2

18q23

Type of geneprotein-codingprotein-coding
Descriptionmitogen-activated protein kinase kinase kinase kinase 4HPK/GCK-like kinase HGKMAPK/ERK kinase kinase kinase 4MEK kinase kinase 4Ste20 group protein kinase HGKepididymis secretory protein Li 31hepatocyte progenitor kinase-like/germinal center kinase-thioredoxin-like protein 4ADIM1 protein homologspliceosomal U5 snRNP-specific 15 kDa proteinthioredoxin-like 4thioredoxin-like U5 snRNP protein U5-15kD
Modification date2020031520200313
UniProtAcc

O95819

Main function of 5'-partner protein: FUNCTION: Serine/threonine kinase that may play a role in the response to environmental stress and cytokines such as TNF-alpha. Appears to act upstream of the JUN N-terminal pathway. Phosphorylates SMAD1 on Thr-322. {ECO:0000269|PubMed:21690388, ECO:0000269|PubMed:9890973}.
.
Ensembl transtripts involved in fusion geneENST idsENST00000302217, ENST00000324219, 
ENST00000347699, ENST00000350198, 
ENST00000413150, ENST00000425019, 
ENST00000456652, ENST00000350878, 
ENST00000498066, 
ENST00000585474, 
ENST00000591711, ENST00000592837, 
ENST00000592957, ENST00000588162, 
ENST00000589926, ENST00000269601, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score16 X 11 X 9=15847 X 3 X 6=126
# samples 169
** MAII scorelog2(16/1584*10)=-3.30742852519225
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(9/126*10)=-0.485426827170242
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: MAP4K4 [Title/Abstract] AND TXNL4A [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: MAP4K4 [Title/Abstract] AND TXNL4A [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)MAP4K4(102407238)-TXNL4A(77737701), # samples:1
Anticipated loss of major functional domain due to fusion event.MAP4K4-TXNL4A 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.
MAP4K4-TXNL4A 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
HgeneMAP4K4

GO:0006468

protein phosphorylation

9890973

HgeneMAP4K4

GO:0035556

intracellular signal transduction

9890973

HgeneMAP4K4

GO:0046328

regulation of JNK cascade

14966141

TgeneTXNL4A

GO:0000398

mRNA splicing, via spliceosome

28781166



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/chr2:102407238/chr18:77737701)
- 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 MAP4K4 (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 TXNL4A (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)
ENST00000425019MAP4K4chr2102407238+ENST00000269601TXNL4Achr1877737701-1611517235792185
ENST00000324219MAP4K4chr2102407238+ENST00000269601TXNL4Achr1877737701-13482545529174
ENST00000350198MAP4K4chr2102407238+ENST00000269601TXNL4Achr1877737701-13482545529174
ENST00000302217MAP4K4chr2102407238+ENST00000269601TXNL4Achr1877737701-13482545529174
ENST00000413150MAP4K4chr2102407238+ENST00000269601TXNL4Achr1877737701-132923522510162
ENST00000347699MAP4K4chr2102407238+ENST00000269601TXNL4Achr1877737701-12741800455151
ENST00000456652MAP4K4chr2102407238+ENST00000269601TXNL4Achr1877737701-12741800455151

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
ENST00000425019ENST00000269601MAP4K4chr2102407238+TXNL4Achr1877737701-0.001253830.99874616
ENST00000324219ENST00000269601MAP4K4chr2102407238+TXNL4Achr1877737701-0.0026689870.997331
ENST00000350198ENST00000269601MAP4K4chr2102407238+TXNL4Achr1877737701-0.0026689870.997331
ENST00000302217ENST00000269601MAP4K4chr2102407238+TXNL4Achr1877737701-0.0026689870.997331
ENST00000413150ENST00000269601MAP4K4chr2102407238+TXNL4Achr1877737701-0.001672470.99832755
ENST00000347699ENST00000269601MAP4K4chr2102407238+TXNL4Achr1877737701-0.0019973660.9980026
ENST00000456652ENST00000269601MAP4K4chr2102407238+TXNL4Achr1877737701-0.0019973660.9980026

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 MAP4K4-TXNL4A

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
MAP4K4chr2102407238TXNL4Achr187773770118060GQLAAIKVMDVTEVKNFAVIYLVDIT
MAP4K4chr2102407238TXNL4Achr187773770123571GQLAAIKVMDVTEVKNFAVIYLVDIT
MAP4K4chr2102407238TXNL4Achr187773770125483GQLAAIKVMDVTEVKNFAVIYLVDIT
MAP4K4chr2102407238TXNL4Achr187773770151794GQLAAIKVMDVTEVKNFAVIYLVDIT

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Potential FusionNeoAntigen Information of MAP4K4-TXNL4A 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.
MAP4K4-TXNL4A_102407238_77737701.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)
MAP4K4-TXNL4Achr2102407238chr1877737701254HLA-A30:08KVMDVTEVK0.99670.5713615
MAP4K4-TXNL4Achr2102407238chr1877737701254HLA-B15:02EVKNFAVIY0.91420.91041221
MAP4K4-TXNL4Achr2102407238chr1877737701254HLA-B39:13TEVKNFAVI0.35020.87431120
MAP4K4-TXNL4Achr2102407238chr1877737701254HLA-B50:01TEVKNFAVI0.26440.59741120
MAP4K4-TXNL4Achr2102407238chr1877737701254HLA-B44:03TEVKNFAVIY0.99910.93241121
MAP4K4-TXNL4Achr2102407238chr1877737701254HLA-B18:01TEVKNFAVIY0.96880.91911121
MAP4K4-TXNL4Achr2102407238chr1877737701254HLA-B57:03KVMDVTEVKNF0.99990.9718617
MAP4K4-TXNL4Achr2102407238chr1877737701254HLA-A32:13KVMDVTEVKNF0.99920.8858617
MAP4K4-TXNL4Achr2102407238chr1877737701254HLA-B40:06TEVKNFAV0.99990.65871119
MAP4K4-TXNL4Achr2102407238chr1877737701254HLA-B40:06TEVKNFAVI0.99960.60051120
MAP4K4-TXNL4Achr2102407238chr1877737701254HLA-B15:21EVKNFAVIY0.91980.87521221
MAP4K4-TXNL4Achr2102407238chr1877737701254HLA-B15:31EVKNFAVIY0.86460.82961221
MAP4K4-TXNL4Achr2102407238chr1877737701254HLA-B40:04TEVKNFAVI0.99840.74941120
MAP4K4-TXNL4Achr2102407238chr1877737701254HLA-A30:01KVMDVTEVK0.99590.7748615
MAP4K4-TXNL4Achr2102407238chr1877737701254HLA-A25:01EVKNFAVIY0.99380.78651221
MAP4K4-TXNL4Achr2102407238chr1877737701254HLA-B18:08TEVKNFAVI0.92850.9411120
MAP4K4-TXNL4Achr2102407238chr1877737701254HLA-B35:11EVKNFAVIY0.89880.86321221
MAP4K4-TXNL4Achr2102407238chr1877737701254HLA-B35:20EVKNFAVIY0.84370.88141221
MAP4K4-TXNL4Achr2102407238chr1877737701254HLA-B15:11EVKNFAVIY0.82330.83031221
MAP4K4-TXNL4Achr2102407238chr1877737701254HLA-B15:08EVKNFAVIY0.82040.8271221
MAP4K4-TXNL4Achr2102407238chr1877737701254HLA-B35:43EVKNFAVIY0.78430.83621221
MAP4K4-TXNL4Achr2102407238chr1877737701254HLA-B35:24EVKNFAVIY0.7470.89471221
MAP4K4-TXNL4Achr2102407238chr1877737701254HLA-B15:12EVKNFAVIY0.63510.90051221
MAP4K4-TXNL4Achr2102407238chr1877737701254HLA-B18:04EVKNFAVIY0.36790.90651221
MAP4K4-TXNL4Achr2102407238chr1877737701254HLA-B39:02TEVKNFAVI0.32170.88651120
MAP4K4-TXNL4Achr2102407238chr1877737701254HLA-B50:04TEVKNFAVI0.26440.59741120
MAP4K4-TXNL4Achr2102407238chr1877737701254HLA-B50:05TEVKNFAVI0.26440.59741120
MAP4K4-TXNL4Achr2102407238chr1877737701254HLA-B18:07EVKNFAVIY0.13240.86971221
MAP4K4-TXNL4Achr2102407238chr1877737701254HLA-B44:07TEVKNFAVIY0.99910.93241121
MAP4K4-TXNL4Achr2102407238chr1877737701254HLA-B44:26TEVKNFAVIY0.99910.93241121
MAP4K4-TXNL4Achr2102407238chr1877737701254HLA-B44:13TEVKNFAVIY0.99910.93241121
MAP4K4-TXNL4Achr2102407238chr1877737701254HLA-A69:01DVTEVKNFAV0.98910.7154919
MAP4K4-TXNL4Achr2102407238chr1877737701254HLA-B18:08TEVKNFAVIY0.97660.90441121
MAP4K4-TXNL4Achr2102407238chr1877737701254HLA-B18:04TEVKNFAVIY0.96910.92751121
MAP4K4-TXNL4Achr2102407238chr1877737701254HLA-B18:05TEVKNFAVIY0.96880.91911121
MAP4K4-TXNL4Achr2102407238chr1877737701254HLA-B18:06TEVKNFAVIY0.96640.91521121
MAP4K4-TXNL4Achr2102407238chr1877737701254HLA-B18:03TEVKNFAVIY0.93720.91191121
MAP4K4-TXNL4Achr2102407238chr1877737701254HLA-B15:53TEVKNFAVIY0.93390.87541121
MAP4K4-TXNL4Achr2102407238chr1877737701254HLA-B18:11TEVKNFAVIY0.88510.88121121
MAP4K4-TXNL4Achr2102407238chr1877737701254HLA-B57:02KVMDVTEVKNF0.99990.826617
MAP4K4-TXNL4Achr2102407238chr1877737701254HLA-B15:24KVMDVTEVKNF0.99990.8814617
MAP4K4-TXNL4Achr2102407238chr1877737701254HLA-A32:01KVMDVTEVKNF0.99960.8706617

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Potential FusionNeoAntigen Information of MAP4K4-TXNL4A 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 MAP4K4-TXNL4A

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
4685KVMDVTEVKNFAVIMAP4K4TXNL4Achr2102407238chr1877737701254

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of MAP4K4-TXNL4A

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-B14:023BVN4685KVMDVTEVKNFAVI-7.15543-7.26883
HLA-B14:023BVN4685KVMDVTEVKNFAVI-4.77435-5.80965
HLA-B52:013W394685KVMDVTEVKNFAVI-6.80875-6.92215
HLA-B52:013W394685KVMDVTEVKNFAVI-4.20386-5.23916
HLA-A11:014UQ24685KVMDVTEVKNFAVI-7.5194-8.5547
HLA-A11:014UQ24685KVMDVTEVKNFAVI-6.9601-7.0735
HLA-A24:025HGA4685KVMDVTEVKNFAVI-7.52403-7.63743
HLA-A24:025HGA4685KVMDVTEVKNFAVI-5.82433-6.85963
HLA-B27:056PYJ4685KVMDVTEVKNFAVI-3.28285-4.31815
HLA-B44:053DX84685KVMDVTEVKNFAVI-5.91172-6.94702
HLA-B44:053DX84685KVMDVTEVKNFAVI-4.24346-4.35686

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Vaccine Design for the FusionNeoAntigens of MAP4K4-TXNL4A

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
MAP4K4-TXNL4Achr2102407238chr18777377011119TEVKNFAVACTGAGGTTAAAAATTTTGCAGTT
MAP4K4-TXNL4Achr2102407238chr18777377011120TEVKNFAVIACTGAGGTTAAAAATTTTGCAGTTATT
MAP4K4-TXNL4Achr2102407238chr18777377011121TEVKNFAVIYACTGAGGTTAAAAATTTTGCAGTTATTTAT
MAP4K4-TXNL4Achr2102407238chr18777377011221EVKNFAVIYGAGGTTAAAAATTTTGCAGTTATTTAT
MAP4K4-TXNL4Achr2102407238chr1877737701615KVMDVTEVKAAAGTTATGGATGTCACTGAGGTTAAA
MAP4K4-TXNL4Achr2102407238chr1877737701617KVMDVTEVKNFAAAGTTATGGATGTCACTGAGGTTAAAAATTTT
MAP4K4-TXNL4Achr2102407238chr1877737701919DVTEVKNFAVGATGTCACTGAGGTTAAAAATTTTGCAGTT

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 MAP4K4-TXNL4A

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
STADMAP4K4-TXNL4Achr2102407238ENST00000302217chr1877737701ENST00000269601TCGA-BR-8366

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Potential target of CAR-T therapy development for MAP4K4-TXNL4A

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 MAP4K4-TXNL4A

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 MAP4K4-TXNL4A

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