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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:SCAF1-MAP4K1

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: SCAF1-MAP4K1
FusionPDB ID: 79407
FusionGDB2.0 ID: 79407
HgeneTgene
Gene symbol

SCAF1

MAP4K1

Gene ID

58506

11184

Gene nameSR-related CTD associated factor 1mitogen-activated protein kinase kinase kinase kinase 1
SynonymsSRA1HPK1
Cytomap

19q13.33

19q13.2

Type of geneprotein-codingprotein-coding
Descriptionsplicing factor, arginine/serine-rich 19SCAFSR-related C-terminal domain-associated factor 1SR-related and CTD-associated factor 1SR-related-CTD-associated factorserine arginine-rich pre-mRNA splicing factor SR-A1mitogen-activated protein kinase kinase kinase kinase 1MAPK/ERK kinase kinase kinase 1MEK kinase kinase 1MEKKK 1hematopoietic progenitor kinase 1
Modification date2020031320200327
UniProtAcc.

Q92918

Main function of 5'-partner protein: FUNCTION: Serine/threonine-protein kinase, which may play a role in the response to environmental stress (PubMed:24362026). Appears to act upstream of the JUN N-terminal pathway (PubMed:8824585). May play a role in hematopoietic lineage decisions and growth regulation (PubMed:8824585, PubMed:24362026). Able to autophosphorylate (PubMed:8824585). Together with CLNK, it enhances CD3-triggered activation of T-cells and subsequent IL2 production (By similarity). {ECO:0000250|UniProtKB:P70218, ECO:0000269|PubMed:24362026, ECO:0000269|PubMed:8824585}.
Ensembl transtripts involved in fusion geneENST idsENST00000360565, ENST00000423454, 
ENST00000589002, ENST00000396857, 
ENST00000589130, ENST00000591517, 
ENST00000586296, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score9 X 8 X 9=6486 X 6 X 5=180
# samples 136
** MAII scorelog2(13/648*10)=-2.31748218985617
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(6/180*10)=-1.58496250072116
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: SCAF1 [Title/Abstract] AND MAP4K1 [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: SCAF1 [Title/Abstract] AND MAP4K1 [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)SCAF1(50161146)-MAP4K1(39078457), # samples:3
Anticipated loss of major functional domain due to fusion event.SCAF1-MAP4K1 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.
SCAF1-MAP4K1 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.
SCAF1-MAP4K1 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.
SCAF1-MAP4K1 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.
SCAF1-MAP4K1 seems lost the major protein functional domain in Hgene partner, which is a essential gene due to the frame-shifted ORF.
SCAF1-MAP4K1 seems lost the major protein functional domain in Tgene partner, which is a essential gene due to the frame-shifted ORF.
SCAF1-MAP4K1 seems lost the major protein functional domain in Tgene partner, which is a IUPHAR drug target due to the frame-shifted ORF.
SCAF1-MAP4K1 seems lost the major protein functional domain in Tgene partner, which is a kinase due to the frame-shifted ORF.
SCAF1-MAP4K1 seems lost the major protein functional domain in Tgene partner, which is a tumor suppressor due to the frame-shifted 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
TgeneMAP4K1

GO:0006468

protein phosphorylation

8824585

TgeneMAP4K1

GO:0007257

activation of JUN kinase activity

8824585

TgeneMAP4K1

GO:0018105

peptidyl-serine phosphorylation

11053428|24362026

TgeneMAP4K1

GO:0046777

protein autophosphorylation

8824585|24362026

TgeneMAP4K1

GO:1904628

cellular response to phorbol 13-acetate 12-myristate

8824585



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/chr19:50161146/chr19:39078457)
- 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 SCAF1 (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 MAP4K1 (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)
ENST00000360565SCAF1chr1950161146+ENST00000586296MAP4K1chr1939078457-404538714939031284

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
ENST00000360565ENST00000586296SCAF1chr1950161146+MAP4K1chr1939078457-0.0074766270.9925234

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 SCAF1-MAP4K1

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
SCAF1chr1950161146MAP4K1chr19390784573871211HLTLGTGDGGPAPPPAPSSASSSPSP
SCAF1chr1950161146MAP4K1chr19390784573871223PPPAPSSASSSPSPSPSSSSPSPPPP

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Potential FusionNeoAntigen Information of SCAF1-MAP4K1 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.
SCAF1-MAP4K1_50161146_39078457.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)
SCAF1-MAP4K1chr1950161146chr19390784573871HLA-B07:02APPPAPSSA0.99830.57641120
SCAF1-MAP4K1chr1950161146chr19390784573871HLA-B07:05GPAPPPAPS0.99830.7146918
SCAF1-MAP4K1chr1950161146chr19390784573871HLA-B07:05APPPAPSSA0.99820.58671120
SCAF1-MAP4K1chr1950161146chr19390784573871HLA-B56:01GPAPPPAPS0.98150.5187918
SCAF1-MAP4K1chr1950161146chr19390784573871HLA-B82:01APPPAPSSA0.28710.65421120
SCAF1-MAP4K1chr1950161146chr19390784573871HLA-B08:09APPPAPSSA0.17240.83151120
SCAF1-MAP4K1chr1950161146chr19390784573871HLA-B07:02GPAPPPAPSSA0.99990.6631920
SCAF1-MAP4K1chr1950161146chr19390784573871HLA-B07:05GPAPPPAPSSA0.99990.7153920
SCAF1-MAP4K1chr1950161146chr19390784573871HLA-B56:01GPAPPPAPSSA0.9980.5377920
SCAF1-MAP4K1chr1950161146chr19390784573871HLA-B54:01GPAPPPAPS0.99120.76918
SCAF1-MAP4K1chr1950161146chr19390784573871HLA-B07:12APPPAPSSA0.98120.64741120
SCAF1-MAP4K1chr1950161146chr19390784573871HLA-B54:01APPPAPSSA0.97710.61461120
SCAF1-MAP4K1chr1950161146chr19390784573871HLA-B07:04APPPAPSSA0.80050.57481120
SCAF1-MAP4K1chr1950161146chr19390784573871HLA-B78:01APPPAPSSA0.58730.65161120
SCAF1-MAP4K1chr1950161146chr19390784573871HLA-B42:02APPPAPSSA0.35770.63861120
SCAF1-MAP4K1chr1950161146chr19390784573871HLA-B42:01APPPAPSSA0.31170.63371120
SCAF1-MAP4K1chr1950161146chr19390784573871HLA-B39:10APPPAPSSA0.27040.89841120
SCAF1-MAP4K1chr1950161146chr19390784573871HLA-B07:12GPAPPPAPSSA0.99990.7455920
SCAF1-MAP4K1chr1950161146chr19390784573871HLA-B54:01GPAPPPAPSSA0.99890.7857920
SCAF1-MAP4K1chr1950161146chr19390784573871HLA-B07:22APPPAPSSA0.99830.57641120
SCAF1-MAP4K1chr1950161146chr19390784573871HLA-B07:09APPPAPSSA0.99770.58621120
SCAF1-MAP4K1chr1950161146chr19390784573871HLA-B55:02GPAPPPAPS0.9750.5251918
SCAF1-MAP4K1chr1950161146chr19390784573871HLA-B55:04APPPAPSSA0.89580.55851120
SCAF1-MAP4K1chr1950161146chr19390784573871HLA-B56:05GPAPPPAPS0.72540.6895918
SCAF1-MAP4K1chr1950161146chr19390784573871HLA-B78:02APPPAPSSA0.53580.67051120
SCAF1-MAP4K1chr1950161146chr19390784573871HLA-B67:01APPPAPSSA0.43270.90051120
SCAF1-MAP4K1chr1950161146chr19390784573871HLA-B82:02APPPAPSSA0.28710.65421120
SCAF1-MAP4K1chr1950161146chr19390784573871HLA-B07:22GPAPPPAPSSA0.99990.6631920
SCAF1-MAP4K1chr1950161146chr19390784573871HLA-B55:02GPAPPPAPSSA0.99860.5768920
SCAF1-MAP4K1chr1950161146chr19390784573871HLA-B56:05GPAPPPAPSSA0.99250.5401920

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Potential FusionNeoAntigen Information of SCAF1-MAP4K1 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 SCAF1-MAP4K1

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
2703GDGGPAPPPAPSSASCAF1MAP4K1chr1950161146chr19390784573871

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of SCAF1-MAP4K1

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-B14:023BVN2703GDGGPAPPPAPSSA-7.9962-8.1096
HLA-B14:023BVN2703GDGGPAPPPAPSSA-5.70842-6.74372
HLA-B52:013W392703GDGGPAPPPAPSSA-6.83737-6.95077
HLA-B52:013W392703GDGGPAPPPAPSSA-4.4836-5.5189
HLA-A11:014UQ22703GDGGPAPPPAPSSA-10.0067-10.1201
HLA-A11:014UQ22703GDGGPAPPPAPSSA-9.03915-10.0745
HLA-A24:025HGA2703GDGGPAPPPAPSSA-6.56204-6.67544
HLA-A24:025HGA2703GDGGPAPPPAPSSA-5.42271-6.45801
HLA-B44:053DX82703GDGGPAPPPAPSSA-7.85648-8.89178
HLA-B44:053DX82703GDGGPAPPPAPSSA-5.3978-5.5112
HLA-A02:016TDR2703GDGGPAPPPAPSSA-3.37154-4.40684

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Vaccine Design for the FusionNeoAntigens of SCAF1-MAP4K1

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
SCAF1-MAP4K1chr1950161146chr19390784571120APPPAPSSACACAAGGCCTGTAGTGGTGGAGACACG
SCAF1-MAP4K1chr1950161146chr1939078457918GPAPPPAPSGCCGTCCACAAGGCCTGTAGTGGTGGA
SCAF1-MAP4K1chr1950161146chr1939078457920GPAPPPAPSSAGCCGTCCACAAGGCCTGTAGTGGTGGAGACACG

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 SCAF1-MAP4K1

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
BRCASCAF1-MAP4K1chr1950161146ENST00000360565chr1939078457ENST00000586296TCGA-A2-A0EV-01A

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Potential target of CAR-T therapy development for SCAF1-MAP4K1

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 SCAF1-MAP4K1

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 SCAF1-MAP4K1

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