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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:SRGAP2-KCNJ10

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: SRGAP2-KCNJ10
FusionPDB ID: 86368
FusionGDB2.0 ID: 86368
HgeneTgene
Gene symbol

SRGAP2

KCNJ10

Gene ID

23380

3766

Gene nameSLIT-ROBO Rho GTPase activating protein 2potassium inwardly rectifying channel subfamily J member 10
SynonymsARHGAP34|FNBP2|SRGAP2A|SRGAP3BIRK-10|KCNJ13-PEN|KIR1.2|KIR4.1|SESAME
Cytomap

1q32.1

1q23.2

Type of geneprotein-codingprotein-coding
DescriptionSLIT-ROBO Rho GTPase-activating protein 2SLIT-ROBO GAP2formin-binding protein 2rho GTPase-activating protein 34ATP-sensitive inward rectifier potassium channel 10ATP-dependent inwardly rectifying potassium channel Kir4.1glial ATP-dependent inwardly rectifying potassium channel KIR4.1inward rectifier K(+) channel Kir1.2inward rectifier K+ channel KIR1.2potassi
Modification date2020031320200322
UniProtAcc.

P78508

Main function of 5'-partner protein: FUNCTION: May be responsible for potassium buffering action of glial cells in the brain. Inward rectifier potassium channels are characterized by a greater tendency to allow potassium to flow into the cell rather than out of it. Their voltage dependence is regulated by the concentration of extracellular potassium; as external potassium is raised, the voltage range of the channel opening shifts to more positive voltages. The inward rectification is mainly due to the blockage of outward current by internal magnesium. Can be blocked by extracellular barium and cesium (By similarity). In the kidney, together with KCNJ16, mediates basolateral K(+) recycling in distal tubules; this process is critical for Na(+) reabsorption at the tubules. {ECO:0000250, ECO:0000305|PubMed:24561201}.
Ensembl transtripts involved in fusion geneENST idsENST00000414007, ENST00000419187, 
ENST00000471256, 
ENST00000509700, 
ENST00000368089, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score11 X 7 X 7=5393 X 3 X 2=18
# samples 113
** MAII scorelog2(11/539*10)=-2.29278174922785
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(3/18*10)=0.736965594166206
effective Gene in Pan-Cancer Fusion Genes (eGinPCFGs).
DoF>8 and MAII>0
Fusion gene context

PubMed: SRGAP2 [Title/Abstract] AND KCNJ10 [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: SRGAP2 [Title/Abstract] AND KCNJ10 [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)SRGAP2(206610392)-KCNJ10(160012322), # samples:2
Anticipated loss of major functional domain due to fusion event.SRGAP2-KCNJ10 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.
SRGAP2-KCNJ10 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
HgeneSRGAP2

GO:0043547

positive regulation of GTPase activity

21148482

HgeneSRGAP2

GO:0046847

filopodium assembly

22559944

HgeneSRGAP2

GO:0051014

actin filament severing

21148482

HgeneSRGAP2

GO:0060996

dendritic spine development

22559944

HgeneSRGAP2

GO:2001223

negative regulation of neuron migration

22559944



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/chr1:206610392/chr1:160012322)
- 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 SRGAP2 (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 KCNJ10 (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)
ENST00000414007SRGAP2chr1206610392+ENST00000368089KCNJ10chr1160012322-62791213361394452

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
ENST00000414007ENST00000368089SRGAP2chr1206610392+KCNJ10chr1160012322-0.000529360.99947065

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 SRGAP2-KCNJ10

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
SRGAP2chr1206610392KCNJ10chr11600123221213392QVEVNDIKNAFERDDVSCQGVLQSDH

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Potential FusionNeoAntigen Information of SRGAP2-KCNJ10 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.
SRGAP2-KCNJ10_206610392_160012322.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)
SRGAP2-KCNJ10chr1206610392chr11600123221213HLA-B39:01ERDDVSCQGVL0.99870.88721122
SRGAP2-KCNJ10chr1206610392chr11600123221213HLA-B38:01ERDDVSCQGVL0.99790.94841122
SRGAP2-KCNJ10chr1206610392chr11600123221213HLA-B38:02ERDDVSCQGVL0.99790.95311122
SRGAP2-KCNJ10chr1206610392chr11600123221213HLA-B39:09ERDDVSCQGVL0.99840.75461122
SRGAP2-KCNJ10chr1206610392chr11600123221213HLA-B39:05ERDDVSCQGVL0.99810.8761122
SRGAP2-KCNJ10chr1206610392chr11600123221213HLA-B39:11ERDDVSCQGVL0.99890.80381122
SRGAP2-KCNJ10chr1206610392chr11600123221213HLA-B39:31ERDDVSCQGVL0.99890.88821122
SRGAP2-KCNJ10chr1206610392chr11600123221213HLA-B38:05ERDDVSCQGVL0.99790.94841122

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Potential FusionNeoAntigen Information of SRGAP2-KCNJ10 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.
SRGAP2-KCNJ10_206610392_160012322.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)
SRGAP2-KCNJ10chr1206610392chr11600123221213DRB1-0411QVEVNDIKNAFERDD015
SRGAP2-KCNJ10chr1206610392chr11600123221213DRB1-0450QVEVNDIKNAFERDD015
SRGAP2-KCNJ10chr1206610392chr11600123221213DRB1-0459QVEVNDIKNAFERDD015
SRGAP2-KCNJ10chr1206610392chr11600123221213DRB1-0467QVEVNDIKNAFERDD015
SRGAP2-KCNJ10chr1206610392chr11600123221213DRB1-0491QVEVNDIKNAFERDD015

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Fusion breakpoint peptide structures of SRGAP2-KCNJ10

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
3766IKNAFERDDVSCQGSRGAP2KCNJ10chr1206610392chr11600123221213

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of SRGAP2-KCNJ10

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-B14:023BVN3766IKNAFERDDVSCQG-7.15543-7.26883
HLA-B14:023BVN3766IKNAFERDDVSCQG-4.77435-5.80965
HLA-B52:013W393766IKNAFERDDVSCQG-6.80875-6.92215
HLA-B52:013W393766IKNAFERDDVSCQG-4.20386-5.23916
HLA-A11:014UQ23766IKNAFERDDVSCQG-7.5194-8.5547
HLA-A11:014UQ23766IKNAFERDDVSCQG-6.9601-7.0735
HLA-A24:025HGA3766IKNAFERDDVSCQG-7.52403-7.63743
HLA-A24:025HGA3766IKNAFERDDVSCQG-5.82433-6.85963
HLA-B27:056PYJ3766IKNAFERDDVSCQG-3.28285-4.31815
HLA-B44:053DX83766IKNAFERDDVSCQG-5.91172-6.94702
HLA-B44:053DX83766IKNAFERDDVSCQG-4.24346-4.35686

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Vaccine Design for the FusionNeoAntigens of SRGAP2-KCNJ10

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
SRGAP2-KCNJ10chr1206610392chr11600123221122ERDDVSCQGVLAGAGAGATGACGTCAGTTGCCAAGGTGTATTAC

check button mRNA and peptide sequences of FusionNeoAntigens that have potential interaction with HLA-IIs.
Fusion geneHchrHbpTchrTbpStart in +/-13AAEnd in +/-13AAFusionNeoAntigen peptideFusionNEoAntigen RNA sequence
SRGAP2-KCNJ10chr1206610392chr1160012322015QVEVNDIKNAFERDDAGGTGGAAGTGAATGACATCAAAAATGCCTTTGAGAGAGATGACG

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Information of the samples that have these potential fusion neoantigens of SRGAP2-KCNJ10

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
CESCSRGAP2-KCNJ10chr1206610392ENST00000414007chr1160012322ENST00000368089TCGA-VS-A957-01A

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Potential target of CAR-T therapy development for SRGAP2-KCNJ10

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
TgeneKCNJ10chr1:206610392chr1:160012322ENST0000036808902115_1260380.0IntramembraneHelical%3B Pore-forming%3B Name%3DH5
TgeneKCNJ10chr1:206610392chr1:160012322ENST0000036808902127_1330380.0IntramembranePore-forming
TgeneKCNJ10chr1:206610392chr1:160012322ENST0000036808902143_1640380.0TransmembraneHelical%3B Name%3DM2
TgeneKCNJ10chr1:206610392chr1:160012322ENST000003680890265_890380.0TransmembraneHelical%3B Name%3DM1

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 SRGAP2-KCNJ10

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 SRGAP2-KCNJ10

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