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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:MAPK1-ARHGEF7

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: MAPK1-ARHGEF7
FusionPDB ID: 51523
FusionGDB2.0 ID: 51523
HgeneTgene
Gene symbol

MAPK1

ARHGEF7

Gene ID

5594

8874

Gene namemitogen-activated protein kinase 1Rho guanine nucleotide exchange factor 7
SynonymsERK|ERK-2|ERK2|ERT1|MAPK2|P42MAPK|PRKM1|PRKM2|p38|p40|p41|p41mapk|p42-MAPKBETA-PIX|COOL-1|COOL1|Nbla10314|P50|P50BP|P85|P85COOL1|P85SPR|PAK3|PIXB
Cytomap

22q11.22

13q34

Type of geneprotein-codingprotein-coding
Descriptionmitogen-activated protein kinase 1MAP kinase 1MAP kinase 2MAP kinase isoform p42MAPK 2extracellular signal-regulated kinase 2mitogen-activated protein kinase 2protein tyrosine kinase ERK2rho guanine nucleotide exchange factor 7PAK-interacting exchange factor betaRho guanine nucleotide exchange factor (GEF) 7SH3 domain-containing proline-rich protein
Modification date2020032720200327
UniProtAcc

Q8NDC0

Main function of 5'-partner protein:

Q14155

Main function of 5'-partner protein: FUNCTION: Acts as a RAC1 guanine nucleotide exchange factor (GEF) and can induce membrane ruffling. Functions in cell migration, attachment and cell spreading. Promotes targeting of RAC1 to focal adhesions (By similarity). May function as a positive regulator of apoptosis. Downstream of NMDA receptors and CaMKK-CaMK1 signaling cascade, promotes the formation of spines and synapses in hippocampal neurons. {ECO:0000250, ECO:0000269|PubMed:18184567, ECO:0000269|PubMed:18716323, ECO:0000269|PubMed:19041750}.
Ensembl transtripts involved in fusion geneENST idsENST00000215832, ENST00000398822, 
ENST00000544786, ENST00000491588, 
ENST00000218789, ENST00000375723, 
ENST00000375736, ENST00000375737, 
ENST00000426073, ENST00000544132, 
ENST00000370623, ENST00000375739, 
ENST00000478679, ENST00000483189, 
ENST00000317133, ENST00000375741, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score20 X 16 X 10=320013 X 13 X 5=845
# samples 2413
** MAII scorelog2(24/3200*10)=-3.73696559416621
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(13/845*10)=-2.70043971814109
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: MAPK1 [Title/Abstract] AND ARHGEF7 [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: MAPK1 [Title/Abstract] AND ARHGEF7 [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)MAPK1(22221612)-ARHGEF7(111870026), # samples:2
Anticipated loss of major functional domain due to fusion event.MAPK1-ARHGEF7 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.
MAPK1-ARHGEF7 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.
MAPK1-ARHGEF7 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.
MAPK1-ARHGEF7 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
HgeneMAPK1

GO:0006468

protein phosphorylation

23184662

HgeneMAPK1

GO:0010800

positive regulation of peptidyl-threonine phosphorylation

16314496

HgeneMAPK1

GO:0018105

peptidyl-serine phosphorylation

15850461

HgeneMAPK1

GO:0034198

cellular response to amino acid starvation

11096076

HgeneMAPK1

GO:0038127

ERBB signaling pathway

15133037

HgeneMAPK1

GO:0051403

stress-activated MAPK cascade

11096076

HgeneMAPK1

GO:0070371

ERK1 and ERK2 cascade

16314496

HgeneMAPK1

GO:0070849

response to epidermal growth factor

18794356

TgeneARHGEF7

GO:0043547

positive regulation of GTPase activity

21048939



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/chr22:22221612/chr13:111870026)
- 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 MAPK1 (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 ARHGEF7 (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)
ENST00000215832MAPK1chr2222221612-ENST00000317133ARHGEF7chr13111870026+32933081042188694
ENST00000215832MAPK1chr2222221612-ENST00000375741ARHGEF7chr13111870026+50523081042188694
ENST00000215832MAPK1chr2222221612-ENST00000375739ARHGEF7chr13111870026+50523081042188694
ENST00000215832MAPK1chr2222221612-ENST00000370623ARHGEF7chr13111870026+48703081042251715
ENST00000398822MAPK1chr2222221612-ENST00000317133ARHGEF7chr13111870026+3344359382239733
ENST00000398822MAPK1chr2222221612-ENST00000375741ARHGEF7chr13111870026+5103359382239733
ENST00000398822MAPK1chr2222221612-ENST00000375739ARHGEF7chr13111870026+5103359382239733
ENST00000398822MAPK1chr2222221612-ENST00000370623ARHGEF7chr13111870026+4921359382302754
ENST00000544786MAPK1chr2222221612-ENST00000317133ARHGEF7chr13111870026+31041191221999625
ENST00000544786MAPK1chr2222221612-ENST00000375741ARHGEF7chr13111870026+48631191221999625
ENST00000544786MAPK1chr2222221612-ENST00000375739ARHGEF7chr13111870026+48631191221999625
ENST00000544786MAPK1chr2222221612-ENST00000370623ARHGEF7chr13111870026+46811191222062646
ENST00000215832MAPK1chr2222221612-ENST00000317133ARHGEF7chr13111806252+35963081042491795
ENST00000215832MAPK1chr2222221612-ENST00000375741ARHGEF7chr13111806252+54183081042554816
ENST00000398822MAPK1chr2222221612-ENST00000317133ARHGEF7chr13111806252+3647359382542834
ENST00000398822MAPK1chr2222221612-ENST00000375741ARHGEF7chr13111806252+5469359382605855
ENST00000544786MAPK1chr2222221612-ENST00000317133ARHGEF7chr13111806252+34071191522302716
ENST00000544786MAPK1chr2222221612-ENST00000375741ARHGEF7chr13111806252+52291191522365737

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
ENST00000215832ENST00000317133MAPK1chr2222221612-ARHGEF7chr13111870026+0.0044282250.99557173
ENST00000215832ENST00000375741MAPK1chr2222221612-ARHGEF7chr13111870026+0.0015134860.9984865
ENST00000215832ENST00000375739MAPK1chr2222221612-ARHGEF7chr13111870026+0.0015134860.9984865
ENST00000215832ENST00000370623MAPK1chr2222221612-ARHGEF7chr13111870026+0.0011352110.99886477
ENST00000398822ENST00000317133MAPK1chr2222221612-ARHGEF7chr13111870026+0.0052227690.9947772
ENST00000398822ENST00000375741MAPK1chr2222221612-ARHGEF7chr13111870026+0.0016969930.99830294
ENST00000398822ENST00000375739MAPK1chr2222221612-ARHGEF7chr13111870026+0.0016969930.99830294
ENST00000398822ENST00000370623MAPK1chr2222221612-ARHGEF7chr13111870026+0.0012654810.99873453
ENST00000544786ENST00000317133MAPK1chr2222221612-ARHGEF7chr13111870026+0.00292320.99707687
ENST00000544786ENST00000375741MAPK1chr2222221612-ARHGEF7chr13111870026+0.0011540390.99884593
ENST00000544786ENST00000375739MAPK1chr2222221612-ARHGEF7chr13111870026+0.0011540390.99884593
ENST00000544786ENST00000370623MAPK1chr2222221612-ARHGEF7chr13111870026+0.0008857970.9991142
ENST00000215832ENST00000317133MAPK1chr2222221612-ARHGEF7chr13111806252+0.0041806550.99581933
ENST00000215832ENST00000375741MAPK1chr2222221612-ARHGEF7chr13111806252+0.001512480.9984875
ENST00000398822ENST00000317133MAPK1chr2222221612-ARHGEF7chr13111806252+0.0049437460.9950563
ENST00000398822ENST00000375741MAPK1chr2222221612-ARHGEF7chr13111806252+0.0016929560.998307
ENST00000544786ENST00000317133MAPK1chr2222221612-ARHGEF7chr13111806252+0.002839960.9971601
ENST00000544786ENST00000375741MAPK1chr2222221612-ARHGEF7chr13111806252+0.001162870.9988372

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 MAPK1-ARHGEF7

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
MAPK1chr2222221612ARHGEF7chr1311180625235949AQSLREGRQELSGGRRASSSARRRRR
MAPK1chr2222221612ARHGEF7chr1311187002635949AQSLREGRQELSGGRRASSSARRRRR

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Potential FusionNeoAntigen Information of MAPK1-ARHGEF7 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.
MAPK1-ARHGEF7_22221612_111806252.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)
MAPK1-ARHGEF7chr2222221612chr13111806252359HLA-B45:01QELSGGRRA0.99480.9461817
MAPK1-ARHGEF7chr2222221612chr13111806252359HLA-B50:02QELSGGRRA0.98530.7706817
MAPK1-ARHGEF7chr2222221612chr13111806252359HLA-B41:01QELSGGRRA0.56190.8847817
MAPK1-ARHGEF7chr2222221612chr13111806252359HLA-B50:01QELSGGRRA0.21270.8703817
MAPK1-ARHGEF7chr2222221612chr13111806252359HLA-B50:02RQELSGGRRA0.66140.7664717
MAPK1-ARHGEF7chr2222221612chr13111806252359HLA-B45:01RQELSGGRRA0.65250.9387717
MAPK1-ARHGEF7chr2222221612chr13111806252359HLA-B50:01RQELSGGRRA0.47910.9013717
MAPK1-ARHGEF7chr2222221612chr13111806252359HLA-B41:01RQELSGGRRA0.46540.908717
MAPK1-ARHGEF7chr2222221612chr13111806252359HLA-B40:06QELSGGRRA0.97570.762817
MAPK1-ARHGEF7chr2222221612chr13111806252359HLA-B44:09QELSGGRRA0.79710.5514817
MAPK1-ARHGEF7chr2222221612chr13111806252359HLA-B40:06RQELSGGRRA0.9410.7553717
MAPK1-ARHGEF7chr2222221612chr13111806252359HLA-B50:04QELSGGRRA0.21270.8703817
MAPK1-ARHGEF7chr2222221612chr13111806252359HLA-B50:05QELSGGRRA0.21270.8703817
MAPK1-ARHGEF7chr2222221612chr13111806252359HLA-B50:05RQELSGGRRA0.47910.9013717
MAPK1-ARHGEF7chr2222221612chr13111806252359HLA-B50:04RQELSGGRRA0.47910.9013717

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Potential FusionNeoAntigen Information of MAPK1-ARHGEF7 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 MAPK1-ARHGEF7

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
3090GRQELSGGRRASSSMAPK1ARHGEF7chr2222221612chr13111806252359

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of MAPK1-ARHGEF7

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-B14:023BVN3090GRQELSGGRRASSS-7.5588-7.6706
HLA-B14:023BVN3090GRQELSGGRRASSS-4.42712-5.47022
HLA-B52:013W393090GRQELSGGRRASSS-5.79336-5.90516
HLA-B52:013W393090GRQELSGGRRASSS-4.82735-5.87045
HLA-A11:014UQ23090GRQELSGGRRASSS-10.3742-10.486
HLA-A24:025HGA3090GRQELSGGRRASSS-7.36249-8.40559
HLA-A24:025HGA3090GRQELSGGRRASSS-7.07591-7.18771
HLA-B27:056PYJ3090GRQELSGGRRASSS-8.75018-8.86198
HLA-B44:053DX83090GRQELSGGRRASSS-5.28726-5.39906
HLA-B44:053DX83090GRQELSGGRRASSS-4.30205-5.34515
HLA-A02:016TDR3090GRQELSGGRRASSS-4.2167-4.3285

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Vaccine Design for the FusionNeoAntigens of MAPK1-ARHGEF7

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
MAPK1-ARHGEF7chr2222221612chr13111806252717RQELSGGRRACGCCTACGGCATGGTGTGGTCTACCCCGAG
MAPK1-ARHGEF7chr2222221612chr13111806252817QELSGGRRACTACGGCATGGTGTGGTCTACCCCGAG

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 MAPK1-ARHGEF7

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
LUADMAPK1-ARHGEF7chr2222221612ENST00000398822chr13111806252ENST00000317133TCGA-69-7979-01A

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Potential target of CAR-T therapy development for MAPK1-ARHGEF7

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 MAPK1-ARHGEF7

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 MAPK1-ARHGEF7

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