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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-OGT

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: MAP4K4-OGT
FusionPDB ID: 51410
FusionGDB2.0 ID: 51410
HgeneTgene
Gene symbol

MAP4K4

OGT

Gene ID

9448

8473

Gene namemitogen-activated protein kinase kinase kinase kinase 4O-linked N-acetylglucosamine (GlcNAc) transferase
SynonymsFLH21957|HEL-S-31|HGK|MEKKK4|NIKHINCUT-1|HRNT1|MRX106|O-GLCNAC|OGT1
Cytomap

2q11.2

Xq13.1

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-UDP-N-acetylglucosamine--peptide N-acetylglucosaminyltransferase 110 kDa subunitO-GlcNAc transferase p110 subunitO-GlcNAc transferase subunit p110O-linked N-acetylglucosamine (GlcNAc) transferase (UDP-N-acetylglucosamine:polypeptide-N-acetylglucosaminy
Modification date2020031520200327
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, 
ENST00000498566, 
ENST00000373701, ENST00000373719, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score16 X 11 X 9=15847 X 7 X 5=245
# samples 168
** MAII scorelog2(16/1584*10)=-3.30742852519225
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(8/245*10)=-1.61470984411521
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

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

Fusion neoantigen context

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

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)MAP4K4(102315000)-OGT(70764416), # samples:1
Anticipated loss of major functional domain due to fusion event.MAP4K4-OGT 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-OGT 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-OGT 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.
MAP4K4-OGT 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

TgeneOGT

GO:0006110

regulation of glycolytic process

22923583

TgeneOGT

GO:0006493

protein O-linked glycosylation

21240259|21285374|22923583|23222540|23352454|24474760

TgeneOGT

GO:0006915

apoptotic process

20824293

TgeneOGT

GO:0032868

response to insulin

18288188

TgeneOGT

GO:0035020

regulation of Rac protein signal transduction

18288188

TgeneOGT

GO:0043981

histone H4-K5 acetylation

20018852

TgeneOGT

GO:0043982

histone H4-K8 acetylation

20018852

TgeneOGT

GO:0043984

histone H4-K16 acetylation

20018852

TgeneOGT

GO:0045862

positive regulation of proteolysis

21285374

TgeneOGT

GO:0045944

positive regulation of transcription by RNA polymerase II

23222540|23353889

TgeneOGT

GO:0046626

regulation of insulin receptor signaling pathway

18288188

TgeneOGT

GO:0048015

phosphatidylinositol-mediated signaling

18288188



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/chr2:102315000/chrX:70764416)
- 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 OGT (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)
ENST00000425019MAP4K4chr2102315000+ENST00000373719OGTchrX70764416+52424602353138967
ENST00000425019MAP4K4chr2102315000+ENST00000373701OGTchrX70764416+31614602353138967
ENST00000324219MAP4K4chr2102315000+ENST00000373719OGTchrX70764416+497919752875956
ENST00000324219MAP4K4chr2102315000+ENST00000373701OGTchrX70764416+289819752875956
ENST00000350198MAP4K4chr2102315000+ENST00000373719OGTchrX70764416+497919752875956
ENST00000350198MAP4K4chr2102315000+ENST00000373701OGTchrX70764416+289819752875956
ENST00000302217MAP4K4chr2102315000+ENST00000373719OGTchrX70764416+497919752875956
ENST00000302217MAP4K4chr2102315000+ENST00000373701OGTchrX70764416+289819752875956
ENST00000413150MAP4K4chr2102315000+ENST00000373719OGTchrX70764416+4960178222856944
ENST00000413150MAP4K4chr2102315000+ENST00000373701OGTchrX70764416+2879178222856944
ENST00000347699MAP4K4chr2102315000+ENST00000373719OGTchrX70764416+490512302801933
ENST00000347699MAP4K4chr2102315000+ENST00000373701OGTchrX70764416+282412302801933
ENST00000456652MAP4K4chr2102315000+ENST00000373719OGTchrX70764416+490512302801933
ENST00000456652MAP4K4chr2102315000+ENST00000373701OGTchrX70764416+282412302801933

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
ENST00000425019ENST00000373719MAP4K4chr2102315000+OGTchrX70764416+0.0001772590.9998228
ENST00000425019ENST00000373701MAP4K4chr2102315000+OGTchrX70764416+0.0015319360.998468
ENST00000324219ENST00000373719MAP4K4chr2102315000+OGTchrX70764416+0.0001695360.9998305
ENST00000324219ENST00000373701MAP4K4chr2102315000+OGTchrX70764416+0.0014714270.9985286
ENST00000350198ENST00000373719MAP4K4chr2102315000+OGTchrX70764416+0.0001695360.9998305
ENST00000350198ENST00000373701MAP4K4chr2102315000+OGTchrX70764416+0.0014714270.9985286
ENST00000302217ENST00000373719MAP4K4chr2102315000+OGTchrX70764416+0.0001695360.9998305
ENST00000302217ENST00000373701MAP4K4chr2102315000+OGTchrX70764416+0.0014714270.9985286
ENST00000413150ENST00000373719MAP4K4chr2102315000+OGTchrX70764416+0.00016950.9998305
ENST00000413150ENST00000373701MAP4K4chr2102315000+OGTchrX70764416+0.0015210510.99847895
ENST00000347699ENST00000373719MAP4K4chr2102315000+OGTchrX70764416+0.0001872250.9998128
ENST00000347699ENST00000373701MAP4K4chr2102315000+OGTchrX70764416+0.0018522870.9981477
ENST00000456652ENST00000373719MAP4K4chr2102315000+OGTchrX70764416+0.0001872250.9998128
ENST00000456652ENST00000373701MAP4K4chr2102315000+OGTchrX70764416+0.0018522870.9981477

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-OGT

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
MAP4K4chr2102315000OGTchrX7076441612341EVVGNGTYGQVYKDLYCVRSDLGNLL
MAP4K4chr2102315000OGTchrX7076441617852EVVGNGTYGQVYKDLYCVRSDLGNLL
MAP4K4chr2102315000OGTchrX7076441619764EVVGNGTYGQVYKDLYCVRSDLGNLL
MAP4K4chr2102315000OGTchrX7076441646075EVVGNGTYGQVYKDLYCVRSDLGNLL

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Potential FusionNeoAntigen Information of MAP4K4-OGT 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-OGT_102315000_70764416.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-OGTchr2102315000chrX70764416197HLA-A02:21QVYKDLYCV0.9840.6185918
MAP4K4-OGTchr2102315000chrX70764416197HLA-A02:35QVYKDLYCV0.98310.5034918
MAP4K4-OGTchr2102315000chrX70764416197HLA-A02:06QVYKDLYCV0.9840.6185918
MAP4K4-OGTchr2102315000chrX70764416197HLA-A69:01QVYKDLYCV0.97050.6733918

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Potential FusionNeoAntigen Information of MAP4K4-OGT 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-OGT

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
9760TYGQVYKDLYCVRSMAP4K4OGTchr2102315000chrX70764416197

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

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-B14:023BVN9760TYGQVYKDLYCVRS-7.9962-8.1096
HLA-B14:023BVN9760TYGQVYKDLYCVRS-5.70842-6.74372
HLA-B52:013W399760TYGQVYKDLYCVRS-6.83737-6.95077
HLA-B52:013W399760TYGQVYKDLYCVRS-4.4836-5.5189
HLA-A11:014UQ29760TYGQVYKDLYCVRS-10.0067-10.1201
HLA-A11:014UQ29760TYGQVYKDLYCVRS-9.03915-10.0745
HLA-A24:025HGA9760TYGQVYKDLYCVRS-6.56204-6.67544
HLA-A24:025HGA9760TYGQVYKDLYCVRS-5.42271-6.45801
HLA-B44:053DX89760TYGQVYKDLYCVRS-7.85648-8.89178
HLA-B44:053DX89760TYGQVYKDLYCVRS-5.3978-5.5112
HLA-A02:016TDR9760TYGQVYKDLYCVRS-3.37154-4.40684

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Vaccine Design for the FusionNeoAntigens of MAP4K4-OGT

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-OGTchr2102315000chrX70764416918QVYKDLYCVCAAGTCTATAAGGATTTGTACTGTGTT

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-OGT

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
ESCAMAP4K4-OGTchr2102315000ENST00000302217chrX70764416ENST00000373701TCGA-L5-A8NU

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

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-OGT

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-OGT

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