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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:MDM2-SYK

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: MDM2-SYK
FusionPDB ID: 52422
FusionGDB2.0 ID: 52422
HgeneTgene
Gene symbol

MDM2

SYK

Gene ID

4193

6850

Gene nameMDM2 proto-oncogenespleen associated tyrosine kinase
SynonymsACTFS|HDMX|LSKB|hdm2p72-Syk
Cytomap

12q15

9q22.2

Type of geneprotein-codingprotein-coding
DescriptionE3 ubiquitin-protein ligase Mdm2MDM2 oncogene, E3 ubiquitin protein ligaseMDM2 proto-oncogene, E3 ubiquitin protein ligaseMdm2, p53 E3 ubiquitin protein ligase homologMdm2, transformed 3T3 cell double minute 2, p53 binding proteindouble minute 2, humtyrosine-protein kinase SYKspleen tyrosine kinase
Modification date2020032920200329
UniProtAcc

Q00987

Main function of 5'-partner protein: FUNCTION: E3 ubiquitin-protein ligase that mediates ubiquitination of p53/TP53, leading to its degradation by the proteasome. Inhibits p53/TP53- and p73/TP73-mediated cell cycle arrest and apoptosis by binding its transcriptional activation domain. Also acts as a ubiquitin ligase E3 toward itself and ARRB1. Permits the nuclear export of p53/TP53. Promotes proteasome-dependent ubiquitin-independent degradation of retinoblastoma RB1 protein. Inhibits DAXX-mediated apoptosis by inducing its ubiquitination and degradation. Component of the TRIM28/KAP1-MDM2-p53/TP53 complex involved in stabilizing p53/TP53. Also component of the TRIM28/KAP1-ERBB4-MDM2 complex which links growth factor and DNA damage response pathways. Mediates ubiquitination and subsequent proteasome degradation of DYRK2 in nucleus. Ubiquitinates IGF1R and SNAI1 and promotes them to proteasomal degradation (PubMed:12821780, PubMed:15053880, PubMed:15195100, PubMed:15632057, PubMed:16337594, PubMed:17290220, PubMed:19098711, PubMed:19219073, PubMed:19837670, PubMed:19965871, PubMed:20173098, PubMed:20385133, PubMed:20858735, PubMed:22128911). Ubiquitinates DCX, leading to DCX degradation and reduction of the dendritic spine density of olfactory bulb granule cells (By similarity). Ubiquitinates DLG4, leading to proteasomal degradation of DLG4 which is required for AMPA receptor endocytosis (By similarity). Negatively regulates NDUFS1, leading to decreased mitochondrial respiration, marked oxidative stress, and commitment to the mitochondrial pathway of apoptosis (PubMed:30879903). Binds NDUFS1 leading to its cytosolic retention rather than mitochondrial localization resulting in decreased supercomplex assembly (interactions between complex I and complex III), decreased complex I activity, ROS production, and apoptosis (PubMed:30879903). {ECO:0000250|UniProtKB:P23804, ECO:0000269|PubMed:12821780, ECO:0000269|PubMed:15053880, ECO:0000269|PubMed:15195100, ECO:0000269|PubMed:15632057, ECO:0000269|PubMed:16337594, ECO:0000269|PubMed:17290220, ECO:0000269|PubMed:19098711, ECO:0000269|PubMed:19219073, ECO:0000269|PubMed:19837670, ECO:0000269|PubMed:19965871, ECO:0000269|PubMed:20173098, ECO:0000269|PubMed:20385133, ECO:0000269|PubMed:20858735, ECO:0000269|PubMed:22128911, ECO:0000269|PubMed:30879903}.

P43405

Main function of 5'-partner protein: FUNCTION: Non-receptor tyrosine kinase which mediates signal transduction downstream of a variety of transmembrane receptors including classical immunoreceptors like the B-cell receptor (BCR). Regulates several biological processes including innate and adaptive immunity, cell adhesion, osteoclast maturation, platelet activation and vascular development. Assembles into signaling complexes with activated receptors at the plasma membrane via interaction between its SH2 domains and the receptor tyrosine-phosphorylated ITAM domains. The association with the receptor can also be indirect and mediated by adapter proteins containing ITAM or partial hemITAM domains. The phosphorylation of the ITAM domains is generally mediated by SRC subfamily kinases upon engagement of the receptor. More rarely signal transduction via SYK could be ITAM-independent. Direct downstream effectors phosphorylated by SYK include VAV1, PLCG1, PI-3-kinase, LCP2 and BLNK. Initially identified as essential in B-cell receptor (BCR) signaling, it is necessary for the maturation of B-cells most probably at the pro-B to pre-B transition. Activated upon BCR engagement, it phosphorylates and activates BLNK an adapter linking the activated BCR to downstream signaling adapters and effectors. It also phosphorylates and activates PLCG1 and the PKC signaling pathway. It also phosphorylates BTK and regulates its activity in B-cell antigen receptor (BCR)-coupled signaling. In addition to its function downstream of BCR plays also a role in T-cell receptor signaling. Plays also a crucial role in the innate immune response to fungal, bacterial and viral pathogens. It is for instance activated by the membrane lectin CLEC7A. Upon stimulation by fungal proteins, CLEC7A together with SYK activates immune cells inducing the production of ROS. Also activates the inflammasome and NF-kappa-B-mediated transcription of chemokines and cytokines in presence of pathogens. Regulates neutrophil degranulation and phagocytosis through activation of the MAPK signaling cascade (By similarity). Required for the stimulation of neutrophil phagocytosis by IL15 (PubMed:15123770). Also mediates the activation of dendritic cells by cell necrosis stimuli. Also involved in mast cells activation. Involved in interleukin-3/IL3-mediated signaling pathway in basophils (By similarity). Also functions downstream of receptors mediating cell adhesion. Relays for instance, integrin-mediated neutrophils and macrophages activation and P-selectin receptor/SELPG-mediated recruitment of leukocytes to inflammatory loci. Plays also a role in non-immune processes. It is for instance involved in vascular development where it may regulate blood and lymphatic vascular separation. It is also required for osteoclast development and function. Functions in the activation of platelets by collagen, mediating PLCG2 phosphorylation and activation. May be coupled to the collagen receptor by the ITAM domain-containing FCER1G. Also activated by the membrane lectin CLEC1B that is required for activation of platelets by PDPN/podoplanin. Involved in platelet adhesion being activated by ITGB3 engaged by fibrinogen. Together with CEACAM20, enhances production of the cytokine CXCL8/IL-8 via the NFKB pathway and may thus have a role in the intestinal immune response (By similarity). {ECO:0000250|UniProtKB:P48025, ECO:0000269|PubMed:12387735, ECO:0000269|PubMed:12456653, ECO:0000269|PubMed:15123770, ECO:0000269|PubMed:15388330, ECO:0000269|PubMed:19909739, ECO:0000269|PubMed:8657103, ECO:0000269|PubMed:9535867}.
Ensembl transtripts involved in fusion geneENST idsENST00000258148, ENST00000258149, 
ENST00000299252, ENST00000348801, 
ENST00000350057, ENST00000356290, 
ENST00000360430, ENST00000393410, 
ENST00000393412, ENST00000393413, 
ENST00000428863, ENST00000462284, 
ENST00000478070, ENST00000517852, 
ENST00000540827, ENST00000544561, 
ENST00000545204, ENST00000544125, 
ENST00000375746, ENST00000476708, 
ENST00000375747, ENST00000375751, 
ENST00000375754, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score39 X 20 X 11=85809 X 9 X 6=486
# samples 479
** MAII scorelog2(47/8580*10)=-4.19024498582191
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0		log2(9/486*10)=-2.43295940727611
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: MDM2 [Title/Abstract] AND SYK [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: MDM2 [Title/Abstract] AND SYK [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)MDM2(69203072)-SYK(93657810), # samples:2
Anticipated loss of major functional domain due to fusion event.MDM2-SYK 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.
MDM2-SYK 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
HgeneMDM2

GO:0000122

negative regulation of transcription by RNA polymerase II

9271120|17310983

HgeneMDM2

GO:0006511

ubiquitin-dependent protein catabolic process

11278372|15314173|16173922|17310983

HgeneMDM2

GO:0016567

protein ubiquitination

9450543|15878855|19656744|20153724

HgeneMDM2

GO:0031648

protein destabilization

9529249|10360174|15314173

HgeneMDM2

GO:0032436

positive regulation of proteasomal ubiquitin-dependent protein catabolic process

11278372

HgeneMDM2

GO:0034504

protein localization to nucleus

10360174

HgeneMDM2

GO:0042176

regulation of protein catabolic process

9153395

HgeneMDM2

GO:0043518

negative regulation of DNA damage response, signal transduction by p53 class mediator

9529249|10360174

HgeneMDM2

GO:0045184

establishment of protein localization

10360174

HgeneMDM2

GO:0045892

negative regulation of transcription, DNA-templated

9271120

HgeneMDM2

GO:0065003

protein-containing complex assembly

10608892|12915590

HgeneMDM2

GO:0071157

negative regulation of cell cycle arrest

9529249

HgeneMDM2

GO:0071480

cellular response to gamma radiation

16213212

HgeneMDM2

GO:0072717

cellular response to actinomycin D

15314173

HgeneMDM2

GO:1901797

negative regulation of signal transduction by p53 class mediator

16173922

TgeneSYK

GO:0006468

protein phosphorylation

17681949

TgeneSYK

GO:0007159

leukocyte cell-cell adhesion

12885943

TgeneSYK

GO:0030593

neutrophil chemotaxis

12885943



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/chr12:69203072/chr9:93657810)
- 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 MDM2 (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 SYK (3'-gene)
* Click on the image to open the UCSC genome browser with custom track showing this image in a new window.
all structure


Top

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)
ENST00000462284MDM2chr1269203072+ENST00000375751SYKchr993657810+342340124291989146
ENST00000462284MDM2chr1269203072+ENST00000375754SYKchr993657810+342340124291989146
ENST00000462284MDM2chr1269203072+ENST00000375747SYKchr993657810+342340124291989146
ENST00000356290MDM2chr1269203072+ENST00000375751SYKchr993657810+340838624141974146
ENST00000356290MDM2chr1269203072+ENST00000375754SYKchr993657810+340838624141974146
ENST00000356290MDM2chr1269203072+ENST00000375747SYKchr993657810+340838624141974146
ENST00000540827MDM2chr1269203072+ENST00000375751SYKchr993657810+340838624141974146
ENST00000540827MDM2chr1269203072+ENST00000375754SYKchr993657810+340838624141974146
ENST00000540827MDM2chr1269203072+ENST00000375747SYKchr993657810+340838624141974146
ENST00000258149MDM2chr1269203072+ENST00000375751SYKchr993657810+340838624141974146
ENST00000258149MDM2chr1269203072+ENST00000375754SYKchr993657810+340838624141974146
ENST00000258149MDM2chr1269203072+ENST00000375747SYKchr993657810+340838624141974146
ENST00000428863MDM2chr1269203072+ENST00000375751SYKchr993657810+340838624141974146
ENST00000428863MDM2chr1269203072+ENST00000375754SYKchr993657810+340838624141974146
ENST00000428863MDM2chr1269203072+ENST00000375747SYKchr993657810+340838624141974146
ENST00000393412MDM2chr1269203072+ENST00000375751SYKchr993657810+337735523831943146
ENST00000393412MDM2chr1269203072+ENST00000375754SYKchr993657810+337735523831943146
ENST00000393412MDM2chr1269203072+ENST00000375747SYKchr993657810+337735523831943146
ENST00000258148MDM2chr1269203072+ENST00000375751SYKchr993657810+313511321411701146
ENST00000258148MDM2chr1269203072+ENST00000375754SYKchr993657810+313511321411701146
ENST00000258148MDM2chr1269203072+ENST00000375747SYKchr993657810+313511321411701146
ENST00000544561MDM2chr1269203072+ENST00000375751SYKchr993657810+31038121091669146
ENST00000544561MDM2chr1269203072+ENST00000375754SYKchr993657810+31038121091669146
ENST00000544561MDM2chr1269203072+ENST00000375747SYKchr993657810+31038121091669146
ENST00000393410MDM2chr1269203072+ENST00000375751SYKchr993657810+31038121091669146
ENST00000393410MDM2chr1269203072+ENST00000375754SYKchr993657810+31038121091669146
ENST00000393410MDM2chr1269203072+ENST00000375747SYKchr993657810+31038121091669146
ENST00000393413MDM2chr1269203072+ENST00000375751SYKchr993657810+31038121091669146
ENST00000393413MDM2chr1269203072+ENST00000375754SYKchr993657810+31038121091669146
ENST00000393413MDM2chr1269203072+ENST00000375747SYKchr993657810+31038121091669146
ENST00000517852MDM2chr1269203072+ENST00000375751SYKchr993657810+31038121091669146
ENST00000517852MDM2chr1269203072+ENST00000375754SYKchr993657810+31038121091669146
ENST00000517852MDM2chr1269203072+ENST00000375747SYKchr993657810+31038121091669146
ENST00000545204MDM2chr1269203072+ENST00000375751SYKchr993657810+31098721151675146
ENST00000545204MDM2chr1269203072+ENST00000375754SYKchr993657810+31098721151675146
ENST00000545204MDM2chr1269203072+ENST00000375747SYKchr993657810+31098721151675146
ENST00000350057MDM2chr1269203072+ENST00000375751SYKchr993657810+31038121091669146
ENST00000350057MDM2chr1269203072+ENST00000375754SYKchr993657810+31038121091669146
ENST00000350057MDM2chr1269203072+ENST00000375747SYKchr993657810+31038121091669146
ENST00000360430MDM2chr1269203072+ENST00000375751SYKchr993657810+31038121091669146
ENST00000360430MDM2chr1269203072+ENST00000375754SYKchr993657810+31038121091669146
ENST00000360430MDM2chr1269203072+ENST00000375747SYKchr993657810+31038121091669146
ENST00000299252MDM2chr1269203072+ENST00000375751SYKchr993657810+31038121091669146
ENST00000299252MDM2chr1269203072+ENST00000375754SYKchr993657810+31038121091669146
ENST00000299252MDM2chr1269203072+ENST00000375747SYKchr993657810+31038121091669146
ENST00000348801MDM2chr1269203072+ENST00000375751SYKchr993657810+30886620941654146
ENST00000348801MDM2chr1269203072+ENST00000375754SYKchr993657810+30886620941654146
ENST00000348801MDM2chr1269203072+ENST00000375747SYKchr993657810+30886620941654146
ENST00000478070MDM2chr1269203072+ENST00000375751SYKchr993657810+30886620941654146
ENST00000478070MDM2chr1269203072+ENST00000375754SYKchr993657810+30886620941654146
ENST00000478070MDM2chr1269203072+ENST00000375747SYKchr993657810+30886620941654146
ENST00000462284MDM2chr1269203072+ENST00000375751SYKchr993657809+342340124291989146
ENST00000462284MDM2chr1269203072+ENST00000375754SYKchr993657809+342340124291989146
ENST00000462284MDM2chr1269203072+ENST00000375747SYKchr993657809+342340124291989146
ENST00000356290MDM2chr1269203072+ENST00000375751SYKchr993657809+340838624141974146
ENST00000356290MDM2chr1269203072+ENST00000375754SYKchr993657809+340838624141974146
ENST00000356290MDM2chr1269203072+ENST00000375747SYKchr993657809+340838624141974146
ENST00000540827MDM2chr1269203072+ENST00000375751SYKchr993657809+340838624141974146
ENST00000540827MDM2chr1269203072+ENST00000375754SYKchr993657809+340838624141974146
ENST00000540827MDM2chr1269203072+ENST00000375747SYKchr993657809+340838624141974146
ENST00000258149MDM2chr1269203072+ENST00000375751SYKchr993657809+340838624141974146
ENST00000258149MDM2chr1269203072+ENST00000375754SYKchr993657809+340838624141974146
ENST00000258149MDM2chr1269203072+ENST00000375747SYKchr993657809+340838624141974146
ENST00000428863MDM2chr1269203072+ENST00000375751SYKchr993657809+340838624141974146
ENST00000428863MDM2chr1269203072+ENST00000375754SYKchr993657809+340838624141974146
ENST00000428863MDM2chr1269203072+ENST00000375747SYKchr993657809+340838624141974146
ENST00000393412MDM2chr1269203072+ENST00000375751SYKchr993657809+337735523831943146
ENST00000393412MDM2chr1269203072+ENST00000375754SYKchr993657809+337735523831943146
ENST00000393412MDM2chr1269203072+ENST00000375747SYKchr993657809+337735523831943146
ENST00000258148MDM2chr1269203072+ENST00000375751SYKchr993657809+313511321411701146
ENST00000258148MDM2chr1269203072+ENST00000375754SYKchr993657809+313511321411701146
ENST00000258148MDM2chr1269203072+ENST00000375747SYKchr993657809+313511321411701146
ENST00000544561MDM2chr1269203072+ENST00000375751SYKchr993657809+31038121091669146
ENST00000544561MDM2chr1269203072+ENST00000375754SYKchr993657809+31038121091669146
ENST00000544561MDM2chr1269203072+ENST00000375747SYKchr993657809+31038121091669146
ENST00000393410MDM2chr1269203072+ENST00000375751SYKchr993657809+31038121091669146
ENST00000393410MDM2chr1269203072+ENST00000375754SYKchr993657809+31038121091669146
ENST00000393410MDM2chr1269203072+ENST00000375747SYKchr993657809+31038121091669146
ENST00000393413MDM2chr1269203072+ENST00000375751SYKchr993657809+31038121091669146
ENST00000393413MDM2chr1269203072+ENST00000375754SYKchr993657809+31038121091669146
ENST00000393413MDM2chr1269203072+ENST00000375747SYKchr993657809+31038121091669146
ENST00000517852MDM2chr1269203072+ENST00000375751SYKchr993657809+31038121091669146
ENST00000517852MDM2chr1269203072+ENST00000375754SYKchr993657809+31038121091669146
ENST00000517852MDM2chr1269203072+ENST00000375747SYKchr993657809+31038121091669146
ENST00000545204MDM2chr1269203072+ENST00000375751SYKchr993657809+31098721151675146
ENST00000545204MDM2chr1269203072+ENST00000375754SYKchr993657809+31098721151675146
ENST00000545204MDM2chr1269203072+ENST00000375747SYKchr993657809+31098721151675146
ENST00000350057MDM2chr1269203072+ENST00000375751SYKchr993657809+31038121091669146
ENST00000350057MDM2chr1269203072+ENST00000375754SYKchr993657809+31038121091669146
ENST00000350057MDM2chr1269203072+ENST00000375747SYKchr993657809+31038121091669146
ENST00000360430MDM2chr1269203072+ENST00000375751SYKchr993657809+31038121091669146
ENST00000360430MDM2chr1269203072+ENST00000375754SYKchr993657809+31038121091669146
ENST00000360430MDM2chr1269203072+ENST00000375747SYKchr993657809+31038121091669146
ENST00000299252MDM2chr1269203072+ENST00000375751SYKchr993657809+31038121091669146
ENST00000299252MDM2chr1269203072+ENST00000375754SYKchr993657809+31038121091669146
ENST00000299252MDM2chr1269203072+ENST00000375747SYKchr993657809+31038121091669146
ENST00000348801MDM2chr1269203072+ENST00000375751SYKchr993657809+30886620941654146
ENST00000348801MDM2chr1269203072+ENST00000375754SYKchr993657809+30886620941654146
ENST00000348801MDM2chr1269203072+ENST00000375747SYKchr993657809+30886620941654146
ENST00000478070MDM2chr1269203072+ENST00000375751SYKchr993657809+30886620941654146
ENST00000478070MDM2chr1269203072+ENST00000375754SYKchr993657809+30886620941654146
ENST00000478070MDM2chr1269203072+ENST00000375747SYKchr993657809+30886620941654146

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
ENST00000462284ENST00000375751MDM2chr1269203072+SYKchr993657810+0.633348460.36665154
ENST00000462284ENST00000375754MDM2chr1269203072+SYKchr993657810+0.633348460.36665154
ENST00000462284ENST00000375747MDM2chr1269203072+SYKchr993657810+0.633348460.36665154
ENST00000356290ENST00000375751MDM2chr1269203072+SYKchr993657810+0.62493850.3750615
ENST00000356290ENST00000375754MDM2chr1269203072+SYKchr993657810+0.62493850.3750615
ENST00000356290ENST00000375747MDM2chr1269203072+SYKchr993657810+0.62493850.3750615
ENST00000540827ENST00000375751MDM2chr1269203072+SYKchr993657810+0.62493850.3750615
ENST00000540827ENST00000375754MDM2chr1269203072+SYKchr993657810+0.62493850.3750615
ENST00000540827ENST00000375747MDM2chr1269203072+SYKchr993657810+0.62493850.3750615
ENST00000258149ENST00000375751MDM2chr1269203072+SYKchr993657810+0.62493850.3750615
ENST00000258149ENST00000375754MDM2chr1269203072+SYKchr993657810+0.62493850.3750615
ENST00000258149ENST00000375747MDM2chr1269203072+SYKchr993657810+0.62493850.3750615
ENST00000428863ENST00000375751MDM2chr1269203072+SYKchr993657810+0.62493850.3750615
ENST00000428863ENST00000375754MDM2chr1269203072+SYKchr993657810+0.62493850.3750615
ENST00000428863ENST00000375747MDM2chr1269203072+SYKchr993657810+0.62493850.3750615
ENST00000393412ENST00000375751MDM2chr1269203072+SYKchr993657810+0.61328360.38671643
ENST00000393412ENST00000375754MDM2chr1269203072+SYKchr993657810+0.61328360.38671643
ENST00000393412ENST00000375747MDM2chr1269203072+SYKchr993657810+0.61328360.38671643
ENST00000258148ENST00000375751MDM2chr1269203072+SYKchr993657810+0.54022760.4597724
ENST00000258148ENST00000375754MDM2chr1269203072+SYKchr993657810+0.54022760.4597724
ENST00000258148ENST00000375747MDM2chr1269203072+SYKchr993657810+0.54022760.4597724
ENST00000544561ENST00000375751MDM2chr1269203072+SYKchr993657810+0.54359760.45640236
ENST00000544561ENST00000375754MDM2chr1269203072+SYKchr993657810+0.54359760.45640236
ENST00000544561ENST00000375747MDM2chr1269203072+SYKchr993657810+0.54359760.45640236
ENST00000393410ENST00000375751MDM2chr1269203072+SYKchr993657810+0.54359760.45640236
ENST00000393410ENST00000375754MDM2chr1269203072+SYKchr993657810+0.54359760.45640236
ENST00000393410ENST00000375747MDM2chr1269203072+SYKchr993657810+0.54359760.45640236
ENST00000393413ENST00000375751MDM2chr1269203072+SYKchr993657810+0.54359760.45640236
ENST00000393413ENST00000375754MDM2chr1269203072+SYKchr993657810+0.54359760.45640236
ENST00000393413ENST00000375747MDM2chr1269203072+SYKchr993657810+0.54359760.45640236
ENST00000517852ENST00000375751MDM2chr1269203072+SYKchr993657810+0.54359760.45640236
ENST00000517852ENST00000375754MDM2chr1269203072+SYKchr993657810+0.54359760.45640236
ENST00000517852ENST00000375747MDM2chr1269203072+SYKchr993657810+0.54359760.45640236
ENST00000545204ENST00000375751MDM2chr1269203072+SYKchr993657810+0.53098870.46901137
ENST00000545204ENST00000375754MDM2chr1269203072+SYKchr993657810+0.53098870.46901137
ENST00000545204ENST00000375747MDM2chr1269203072+SYKchr993657810+0.53098870.46901137
ENST00000350057ENST00000375751MDM2chr1269203072+SYKchr993657810+0.54359760.45640236
ENST00000350057ENST00000375754MDM2chr1269203072+SYKchr993657810+0.54359760.45640236
ENST00000350057ENST00000375747MDM2chr1269203072+SYKchr993657810+0.54359760.45640236
ENST00000360430ENST00000375751MDM2chr1269203072+SYKchr993657810+0.54359760.45640236
ENST00000360430ENST00000375754MDM2chr1269203072+SYKchr993657810+0.54359760.45640236
ENST00000360430ENST00000375747MDM2chr1269203072+SYKchr993657810+0.54359760.45640236
ENST00000299252ENST00000375751MDM2chr1269203072+SYKchr993657810+0.54359760.45640236
ENST00000299252ENST00000375754MDM2chr1269203072+SYKchr993657810+0.54359760.45640236
ENST00000299252ENST00000375747MDM2chr1269203072+SYKchr993657810+0.54359760.45640236
ENST00000348801ENST00000375751MDM2chr1269203072+SYKchr993657810+0.5492850.450715
ENST00000348801ENST00000375754MDM2chr1269203072+SYKchr993657810+0.5492850.450715
ENST00000348801ENST00000375747MDM2chr1269203072+SYKchr993657810+0.5492850.450715
ENST00000478070ENST00000375751MDM2chr1269203072+SYKchr993657810+0.5492850.450715
ENST00000478070ENST00000375754MDM2chr1269203072+SYKchr993657810+0.5492850.450715
ENST00000478070ENST00000375747MDM2chr1269203072+SYKchr993657810+0.5492850.450715
ENST00000462284ENST00000375751MDM2chr1269203072+SYKchr993657809+0.633348460.36665154
ENST00000462284ENST00000375754MDM2chr1269203072+SYKchr993657809+0.633348460.36665154
ENST00000462284ENST00000375747MDM2chr1269203072+SYKchr993657809+0.633348460.36665154
ENST00000356290ENST00000375751MDM2chr1269203072+SYKchr993657809+0.62493850.3750615
ENST00000356290ENST00000375754MDM2chr1269203072+SYKchr993657809+0.62493850.3750615
ENST00000356290ENST00000375747MDM2chr1269203072+SYKchr993657809+0.62493850.3750615
ENST00000540827ENST00000375751MDM2chr1269203072+SYKchr993657809+0.62493850.3750615
ENST00000540827ENST00000375754MDM2chr1269203072+SYKchr993657809+0.62493850.3750615
ENST00000540827ENST00000375747MDM2chr1269203072+SYKchr993657809+0.62493850.3750615
ENST00000258149ENST00000375751MDM2chr1269203072+SYKchr993657809+0.62493850.3750615
ENST00000258149ENST00000375754MDM2chr1269203072+SYKchr993657809+0.62493850.3750615
ENST00000258149ENST00000375747MDM2chr1269203072+SYKchr993657809+0.62493850.3750615
ENST00000428863ENST00000375751MDM2chr1269203072+SYKchr993657809+0.62493850.3750615
ENST00000428863ENST00000375754MDM2chr1269203072+SYKchr993657809+0.62493850.3750615
ENST00000428863ENST00000375747MDM2chr1269203072+SYKchr993657809+0.62493850.3750615
ENST00000393412ENST00000375751MDM2chr1269203072+SYKchr993657809+0.61328360.38671643
ENST00000393412ENST00000375754MDM2chr1269203072+SYKchr993657809+0.61328360.38671643
ENST00000393412ENST00000375747MDM2chr1269203072+SYKchr993657809+0.61328360.38671643
ENST00000258148ENST00000375751MDM2chr1269203072+SYKchr993657809+0.54022760.4597724
ENST00000258148ENST00000375754MDM2chr1269203072+SYKchr993657809+0.54022760.4597724
ENST00000258148ENST00000375747MDM2chr1269203072+SYKchr993657809+0.54022760.4597724
ENST00000544561ENST00000375751MDM2chr1269203072+SYKchr993657809+0.54359760.45640236
ENST00000544561ENST00000375754MDM2chr1269203072+SYKchr993657809+0.54359760.45640236
ENST00000544561ENST00000375747MDM2chr1269203072+SYKchr993657809+0.54359760.45640236
ENST00000393410ENST00000375751MDM2chr1269203072+SYKchr993657809+0.54359760.45640236
ENST00000393410ENST00000375754MDM2chr1269203072+SYKchr993657809+0.54359760.45640236
ENST00000393410ENST00000375747MDM2chr1269203072+SYKchr993657809+0.54359760.45640236
ENST00000393413ENST00000375751MDM2chr1269203072+SYKchr993657809+0.54359760.45640236
ENST00000393413ENST00000375754MDM2chr1269203072+SYKchr993657809+0.54359760.45640236
ENST00000393413ENST00000375747MDM2chr1269203072+SYKchr993657809+0.54359760.45640236
ENST00000517852ENST00000375751MDM2chr1269203072+SYKchr993657809+0.54359760.45640236
ENST00000517852ENST00000375754MDM2chr1269203072+SYKchr993657809+0.54359760.45640236
ENST00000517852ENST00000375747MDM2chr1269203072+SYKchr993657809+0.54359760.45640236
ENST00000545204ENST00000375751MDM2chr1269203072+SYKchr993657809+0.53098870.46901137
ENST00000545204ENST00000375754MDM2chr1269203072+SYKchr993657809+0.53098870.46901137
ENST00000545204ENST00000375747MDM2chr1269203072+SYKchr993657809+0.53098870.46901137
ENST00000350057ENST00000375751MDM2chr1269203072+SYKchr993657809+0.54359760.45640236
ENST00000350057ENST00000375754MDM2chr1269203072+SYKchr993657809+0.54359760.45640236
ENST00000350057ENST00000375747MDM2chr1269203072+SYKchr993657809+0.54359760.45640236
ENST00000360430ENST00000375751MDM2chr1269203072+SYKchr993657809+0.54359760.45640236
ENST00000360430ENST00000375754MDM2chr1269203072+SYKchr993657809+0.54359760.45640236
ENST00000360430ENST00000375747MDM2chr1269203072+SYKchr993657809+0.54359760.45640236
ENST00000299252ENST00000375751MDM2chr1269203072+SYKchr993657809+0.54359760.45640236
ENST00000299252ENST00000375754MDM2chr1269203072+SYKchr993657809+0.54359760.45640236
ENST00000299252ENST00000375747MDM2chr1269203072+SYKchr993657809+0.54359760.45640236
ENST00000348801ENST00000375751MDM2chr1269203072+SYKchr993657809+0.5492850.450715
ENST00000348801ENST00000375754MDM2chr1269203072+SYKchr993657809+0.5492850.450715
ENST00000348801ENST00000375747MDM2chr1269203072+SYKchr993657809+0.5492850.450715
ENST00000478070ENST00000375751MDM2chr1269203072+SYKchr993657809+0.5492850.450715
ENST00000478070ENST00000375754MDM2chr1269203072+SYKchr993657809+0.5492850.450715
ENST00000478070ENST00000375747MDM2chr1269203072+SYKchr993657809+0.5492850.450715

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 MDM2-SYK

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

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Potential FusionNeoAntigen Information of MDM2-SYK 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.

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)

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Potential FusionNeoAntigen Information of MDM2-SYK 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 MDM2-SYK

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.

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of MDM2-SYK

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

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Vaccine Design for the FusionNeoAntigens of MDM2-SYK

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

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 MDM2-SYK

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

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Potential target of CAR-T therapy development for MDM2-SYK

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 MDM2-SYK

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 MDM2-SYK

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
TgeneSYKC0025202melanoma1CTD_human
TgeneSYKC0025500Mesothelioma1CTD_human