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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:SOX13-MERTK

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: SOX13-MERTK
FusionPDB ID: 85295
FusionGDB2.0 ID: 85295
HgeneTgene
Gene symbol

SOX13

MERTK

Gene ID

9580

10461

Gene nameSRY-box transcription factor 13MER proto-oncogene, tyrosine kinase
SynonymsICA12|Sox-13MER|RP38|Tyro12|c-Eyk|c-mer
Cytomap

1q32.1

2q13

Type of geneprotein-codingprotein-coding
Descriptiontranscription factor SOX-13SRY (sex determining region Y)-box 13SRY-box 13SRY-related HMG-box gene 13islet cell antibody 12islet cell antigen 12type 1 diabetes autoantigen ICA12tyrosine-protein kinase MerMER receptor tyrosine kinaseSTK kinasec-mer proto-oncogene tyrosine kinaseproto-oncogene c-Merreceptor tyrosine kinase MerTK
Modification date2020031320200329
UniProtAcc.

Q12866

Main function of 5'-partner protein: FUNCTION: Receptor tyrosine kinase that transduces signals from the extracellular matrix into the cytoplasm by binding to several ligands including LGALS3, TUB, TULP1 or GAS6. Regulates many physiological processes including cell survival, migration, differentiation, and phagocytosis of apoptotic cells (efferocytosis). Ligand binding at the cell surface induces autophosphorylation of MERTK on its intracellular domain that provides docking sites for downstream signaling molecules. Following activation by ligand, interacts with GRB2 or PLCG2 and induces phosphorylation of MAPK1, MAPK2, FAK/PTK2 or RAC1. MERTK signaling plays a role in various processes such as macrophage clearance of apoptotic cells, platelet aggregation, cytoskeleton reorganization and engulfment. Functions in the retinal pigment epithelium (RPE) as a regulator of rod outer segments fragments phagocytosis. Plays also an important role in inhibition of Toll-like receptors (TLRs)-mediated innate immune response by activating STAT1, which selectively induces production of suppressors of cytokine signaling SOCS1 and SOCS3. {ECO:0000269|PubMed:17005688}.
Ensembl transtripts involved in fusion geneENST idsENST00000367203, ENST00000367204, 
ENST00000295408, ENST00000409780, 
ENST00000421804, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score6 X 4 X 5=1207 X 10 X 8=560
# samples 613
** MAII scorelog2(6/120*10)=-1
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(13/560*10)=-2.10691520391651
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: SOX13 [Title/Abstract] AND MERTK [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: SOX13 [Title/Abstract] AND MERTK [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)SOX13(204083733)-MERTK(112725714), # samples:2
Anticipated loss of major functional domain due to fusion event.SOX13-MERTK 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.
SOX13-MERTK 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.
SOX13-MERTK 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.
SOX13-MERTK 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
TgeneMERTK

GO:0050766

positive regulation of phagocytosis

18395422



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/chr1:204083733/chr2:112725714)
- 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 SOX13 (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 MERTK (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)
ENST00000367204SOX13chr1204083733+ENST00000295408MERTKchr2112725714+33805271092682857
ENST00000367204SOX13chr1204083733+ENST00000421804MERTKchr2112725714+31555271092682857
ENST00000367204SOX13chr1204083733+ENST00000409780MERTKchr2112725714+31865271092682857

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
ENST00000367204ENST00000295408SOX13chr1204083733+MERTKchr2112725714+0.001263460.99873656
ENST00000367204ENST00000421804SOX13chr1204083733+MERTKchr2112725714+0.001586340.9984137
ENST00000367204ENST00000409780SOX13chr1204083733+MERTKchr2112725714+0.001457010.998543

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 SOX13-MERTK

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
SOX13chr1204083733MERTKchr2112725714527139FLGRNSMEAKDVKAIPSPPTEVSIRN

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Potential FusionNeoAntigen Information of SOX13-MERTK 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.
SOX13-MERTK_204083733_112725714.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)
SOX13-MERTKchr1204083733chr2112725714527HLA-B41:01MEAKDVKA0.99550.9104614
SOX13-MERTKchr1204083733chr2112725714527HLA-B44:03MEAKDVKAI0.9810.9026615
SOX13-MERTKchr1204083733chr2112725714527HLA-B45:01MEAKDVKAI0.96410.646615
SOX13-MERTKchr1204083733chr2112725714527HLA-B41:01MEAKDVKAI0.58980.8901615
SOX13-MERTKchr1204083733chr2112725714527HLA-B50:01MEAKDVKAI0.43080.5402615
SOX13-MERTKchr1204083733chr2112725714527HLA-B39:13MEAKDVKAI0.32980.6244615
SOX13-MERTKchr1204083733chr2112725714527HLA-B45:01MEAKDVKAIP0.99050.8741616
SOX13-MERTKchr1204083733chr2112725714527HLA-B15:16KAIPSPPTEV0.97030.88841222
SOX13-MERTKchr1204083733chr2112725714527HLA-A02:21KAIPSPPTEV0.87920.50331222
SOX13-MERTKchr1204083733chr2112725714527HLA-B52:01KAIPSPPTEV0.87590.98931222
SOX13-MERTKchr1204083733chr2112725714527HLA-B39:08MEAKDVKAI0.59270.779615
SOX13-MERTKchr1204083733chr2112725714527HLA-C15:06KAIPSPPTEV0.99950.86251222
SOX13-MERTKchr1204083733chr2112725714527HLA-C03:07KAIPSPPTEV0.99940.95941222
SOX13-MERTKchr1204083733chr2112725714527HLA-C12:04KAIPSPPTEV0.99910.99451222
SOX13-MERTKchr1204083733chr2112725714527HLA-C06:03KAIPSPPTEV0.99910.99461222
SOX13-MERTKchr1204083733chr2112725714527HLA-C12:12KAIPSPPTEV0.99840.95781222
SOX13-MERTKchr1204083733chr2112725714527HLA-C02:06KAIPSPPTEV0.99730.96291222
SOX13-MERTKchr1204083733chr2112725714527HLA-C03:08KAIPSPPTEV0.98860.79311222
SOX13-MERTKchr1204083733chr2112725714527HLA-C03:19KAIPSPPTEV0.98470.98621222
SOX13-MERTKchr1204083733chr2112725714527HLA-C01:17KAIPSPPTEV0.97580.94021222
SOX13-MERTKchr1204083733chr2112725714527HLA-C08:04KAIPSPPTEV0.97340.99081222
SOX13-MERTKchr1204083733chr2112725714527HLA-C08:13KAIPSPPTEV0.97340.99081222
SOX13-MERTKchr1204083733chr2112725714527HLA-B40:04MEAKDVKAI0.99840.5476615
SOX13-MERTKchr1204083733chr2112725714527HLA-B44:13MEAKDVKAI0.9810.9026615
SOX13-MERTKchr1204083733chr2112725714527HLA-B44:07MEAKDVKAI0.9810.9026615
SOX13-MERTKchr1204083733chr2112725714527HLA-B44:26MEAKDVKAI0.9810.9026615
SOX13-MERTKchr1204083733chr2112725714527HLA-B41:03MEAKDVKAI0.67790.5446615
SOX13-MERTKchr1204083733chr2112725714527HLA-B50:05MEAKDVKAI0.43080.5402615
SOX13-MERTKchr1204083733chr2112725714527HLA-B50:04MEAKDVKAI0.43080.5402615
SOX13-MERTKchr1204083733chr2112725714527HLA-B39:02MEAKDVKAI0.31370.6331615
SOX13-MERTKchr1204083733chr2112725714527HLA-C15:02KAIPSPPTEV0.99970.88871222
SOX13-MERTKchr1204083733chr2112725714527HLA-C15:05KAIPSPPTEV0.99950.89981222
SOX13-MERTKchr1204083733chr2112725714527HLA-C16:02KAIPSPPTEV0.99790.99221222
SOX13-MERTKchr1204083733chr2112725714527HLA-C02:02KAIPSPPTEV0.99710.97131222
SOX13-MERTKchr1204083733chr2112725714527HLA-C02:10KAIPSPPTEV0.99710.97131222
SOX13-MERTKchr1204083733chr2112725714527HLA-C12:03KAIPSPPTEV0.99550.98711222
SOX13-MERTKchr1204083733chr2112725714527HLA-C01:03KAIPSPPTEV0.98140.95791222
SOX13-MERTKchr1204083733chr2112725714527HLA-C17:01KAIPSPPTEV0.9810.98261222
SOX13-MERTKchr1204083733chr2112725714527HLA-C01:02KAIPSPPTEV0.97220.93831222
SOX13-MERTKchr1204083733chr2112725714527HLA-C03:06KAIPSPPTEV0.94030.98361222
SOX13-MERTKchr1204083733chr2112725714527HLA-A02:06KAIPSPPTEV0.87920.50331222
SOX13-MERTKchr1204083733chr2112725714527HLA-B07:13KAIPSPPTEV0.85860.82571222

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Potential FusionNeoAntigen Information of SOX13-MERTK 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.
SOX13-MERTK_204083733_112725714.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)
SOX13-MERTKchr1204083733chr2112725714527DRB1-0413AKDVKAIPSPPTEVS823
SOX13-MERTKchr1204083733chr2112725714527DRB1-0427AKDVKAIPSPPTEVS823
SOX13-MERTKchr1204083733chr2112725714527DRB1-0440AKDVKAIPSPPTEVS823
SOX13-MERTKchr1204083733chr2112725714527DRB1-0440EAKDVKAIPSPPTEV722
SOX13-MERTKchr1204083733chr2112725714527DRB1-0442AKDVKAIPSPPTEVS823
SOX13-MERTKchr1204083733chr2112725714527DRB1-0444AKDVKAIPSPPTEVS823
SOX13-MERTKchr1204083733chr2112725714527DRB1-0444EAKDVKAIPSPPTEV722
SOX13-MERTKchr1204083733chr2112725714527DRB1-0449AKDVKAIPSPPTEVS823
SOX13-MERTKchr1204083733chr2112725714527DRB1-0455AKDVKAIPSPPTEVS823
SOX13-MERTKchr1204083733chr2112725714527DRB1-0456AKDVKAIPSPPTEVS823
SOX13-MERTKchr1204083733chr2112725714527DRB1-0465AKDVKAIPSPPTEVS823
SOX13-MERTKchr1204083733chr2112725714527DRB1-0465EAKDVKAIPSPPTEV722
SOX13-MERTKchr1204083733chr2112725714527DRB1-0468AKDVKAIPSPPTEVS823
SOX13-MERTKchr1204083733chr2112725714527DRB1-0468EAKDVKAIPSPPTEV722
SOX13-MERTKchr1204083733chr2112725714527DRB1-0470AKDVKAIPSPPTEVS823
SOX13-MERTKchr1204083733chr2112725714527DRB1-0473AKDVKAIPSPPTEVS823
SOX13-MERTKchr1204083733chr2112725714527DRB1-0479AKDVKAIPSPPTEVS823
SOX13-MERTKchr1204083733chr2112725714527DRB1-0479EAKDVKAIPSPPTEV722
SOX13-MERTKchr1204083733chr2112725714527DRB1-1615AKDVKAIPSPPTEVS823
SOX13-MERTKchr1204083733chr2112725714527DRB1-1615EAKDVKAIPSPPTEV722

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Fusion breakpoint peptide structures of SOX13-MERTK

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
5880MEAKDVKAIPSPPTSOX13MERTKchr1204083733chr2112725714527

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of SOX13-MERTK

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-B14:023BVN5880MEAKDVKAIPSPPT-7.15543-7.26883
HLA-B14:023BVN5880MEAKDVKAIPSPPT-4.77435-5.80965
HLA-B52:013W395880MEAKDVKAIPSPPT-6.80875-6.92215
HLA-B52:013W395880MEAKDVKAIPSPPT-4.20386-5.23916
HLA-A11:014UQ25880MEAKDVKAIPSPPT-7.5194-8.5547
HLA-A11:014UQ25880MEAKDVKAIPSPPT-6.9601-7.0735
HLA-A24:025HGA5880MEAKDVKAIPSPPT-7.52403-7.63743
HLA-A24:025HGA5880MEAKDVKAIPSPPT-5.82433-6.85963
HLA-B27:056PYJ5880MEAKDVKAIPSPPT-3.28285-4.31815
HLA-B44:053DX85880MEAKDVKAIPSPPT-5.91172-6.94702
HLA-B44:053DX85880MEAKDVKAIPSPPT-4.24346-4.35686

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Vaccine Design for the FusionNeoAntigens of SOX13-MERTK

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
SOX13-MERTKchr1204083733chr21127257141222KAIPSPPTEVAAGCAATTCCCTCCCCACCAACTGAAGTCA
SOX13-MERTKchr1204083733chr2112725714614MEAKDVKATGGAAGCCAAAGATGTCAAAGCAA
SOX13-MERTKchr1204083733chr2112725714615MEAKDVKAITGGAAGCCAAAGATGTCAAAGCAATTC
SOX13-MERTKchr1204083733chr2112725714616MEAKDVKAIPTGGAAGCCAAAGATGTCAAAGCAATTCCCT

check button mRNA and peptide sequences of FusionNeoAntigens that have potential interaction with HLA-IIs.
Fusion geneHchrHbpTchrTbpStart in +/-13AAEnd in +/-13AAFusionNeoAntigen peptideFusionNEoAntigen RNA sequence
SOX13-MERTKchr1204083733chr2112725714722EAKDVKAIPSPPTEVAAGCCAAAGATGTCAAAGCAATTCCCTCCCCACCAACTGAAGTCA
SOX13-MERTKchr1204083733chr2112725714823AKDVKAIPSPPTEVSCCAAAGATGTCAAAGCAATTCCCTCCCCACCAACTGAAGTCAGCA

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Information of the samples that have these potential fusion neoantigens of SOX13-MERTK

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
BRCASOX13-MERTKchr1204083733ENST00000367204chr2112725714ENST00000295408TCGA-AN-A0FT-01A

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Potential target of CAR-T therapy development for SOX13-MERTK

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
TgeneMERTKchr1:204083733chr2:112725714ENST00000295408419506_52601000.0TransmembraneHelical
TgeneMERTKchr1:204083733chr2:112725714ENST00000421804420506_5260951.3333333333334TransmembraneHelical

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 SOX13-MERTK

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 SOX13-MERTK

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