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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:BLNK-EPRS

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: BLNK-EPRS
FusionPDB ID: 9809
FusionGDB2.0 ID: 9809
HgeneTgene
Gene symbol

BLNK

EPRS

Gene ID

29760

2058

Gene nameB cell linkerglutamyl-prolyl-tRNA synthetase 1
SynonymsAGM4|BASH|BLNK-S|LY57|SLP-65|SLP65|bcaEARS|EPRS|GLUPRORS|HLD15|PARS|PIG32|QARS|QPRS
Cytomap

10q24.1

1q41

Type of geneprotein-codingprotein-coding
DescriptionB-cell linker proteinB cell adaptor containing SH2 domainB-cell activationB-cell adapter containing a SH2 domain proteinB-cell adapter containing a Src homology 2 domain proteinSrc homology 2 domain-containing leukocyte protein of 65 kDaSrc homologybifunctional glutamate/proline--tRNA ligasebifunctional aminoacyl-tRNA synthetasecell proliferation-inducing gene 32 proteinglutamate tRNA ligaseglutamatyl-prolyl-tRNA synthetaseglutaminyl-tRNA synthetaseproliferation-inducing gene 32 proteinprolif
Modification date2020031320200313
UniProtAcc

Q8WV28

Main function of 5'-partner protein: FUNCTION: Functions as a central linker protein, downstream of the B-cell receptor (BCR), bridging the SYK kinase to a multitude of signaling pathways and regulating biological outcomes of B-cell function and development. Plays a role in the activation of ERK/EPHB2, MAP kinase p38 and JNK. Modulates AP1 activation. Important for the activation of NF-kappa-B and NFAT. Plays an important role in BCR-mediated PLCG1 and PLCG2 activation and Ca(2+) mobilization and is required for trafficking of the BCR to late endosomes. However, does not seem to be required for pre-BCR-mediated activation of MAP kinase and phosphatidyl-inositol 3 (PI3) kinase signaling. May be required for the RAC1-JNK pathway. Plays a critical role in orchestrating the pro-B cell to pre-B cell transition. May play an important role in BCR-induced B-cell apoptosis. {ECO:0000269|PubMed:10583958, ECO:0000269|PubMed:15270728, ECO:0000269|PubMed:16912232, ECO:0000269|PubMed:9697839}.

P07814

Main function of 5'-partner protein: FUNCTION: Multifunctional protein which is primarily part of the aminoacyl-tRNA synthetase multienzyme complex, also know as multisynthetase complex, that catalyzes the attachment of the cognate amino acid to the corresponding tRNA in a two-step reaction: the amino acid is first activated by ATP to form a covalent intermediate with AMP and is then transferred to the acceptor end of the cognate tRNA (PubMed:1756734, PubMed:24100331, PubMed:23263184). The phosphorylation of EPRS1, induced by interferon-gamma, dissociates the protein from the aminoacyl-tRNA synthetase multienzyme complex and recruits it to the GAIT complex that binds to stem loop-containing GAIT elements in the 3'-UTR of diverse inflammatory mRNAs (such as ceruplasmin), suppressing their translation. Interferon-gamma can therefore redirect, in specific cells, the EPRS1 function from protein synthesis to translation inhibition (PubMed:15479637, PubMed:23071094). Also functions as an effector of the mTORC1 signaling pathway by promoting, through SLC27A1, the uptake of long-chain fatty acid by adipocytes. Thereby, it also plays a role in fat metabolism and more indirectly influences lifespan (PubMed:28178239). {ECO:0000269|PubMed:15479637, ECO:0000269|PubMed:1756734, ECO:0000269|PubMed:23071094, ECO:0000269|PubMed:23263184, ECO:0000269|PubMed:24100331, ECO:0000269|PubMed:28178239}.
Ensembl transtripts involved in fusion geneENST idsENST00000224337, ENST00000371176, 
ENST00000413476, ENST00000427367, 
ENST00000495266, 
ENST00000468487, 
ENST00000366923, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score7 X 6 X 6=2529 X 9 X 4=324
# samples 79
** MAII scorelog2(7/252*10)=-1.84799690655495
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(9/324*10)=-1.84799690655495
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: BLNK [Title/Abstract] AND EPRS [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: BLNK [Title/Abstract] AND EPRS [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)BLNK(97987166)-EPRS(220195860), # samples:1
Anticipated loss of major functional domain due to fusion event.BLNK-EPRS 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.
BLNK-EPRS 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.
BLNK-EPRS 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.
BLNK-EPRS 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
HgeneBLNK

GO:0035556

intracellular signal transduction

9341187

TgeneEPRS

GO:0006433

prolyl-tRNA aminoacylation

24100331

TgeneEPRS

GO:0017148

negative regulation of translation

23071094

TgeneEPRS

GO:0071346

cellular response to interferon-gamma

15479637



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/chr10:97987166/chr1:220195860)
- 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 BLNK (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 EPRS (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)
ENST00000224337BLNKchr1097987166-ENST00000366923EPRSchr1220195860-430450310340981331
ENST00000371176BLNKchr1097987166-ENST00000366923EPRSchr1220195860-430450310340981331
ENST00000427367BLNKchr1097987166-ENST00000366923EPRSchr1220195860-434053913941341331
ENST00000413476BLNKchr1097987166-ENST00000366923EPRSchr1220195860-434053913941341331

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
ENST00000224337ENST00000366923BLNKchr1097987166-EPRSchr1220195860-0.0005390630.999461
ENST00000371176ENST00000366923BLNKchr1097987166-EPRSchr1220195860-0.0005390630.999461
ENST00000427367ENST00000366923BLNKchr1097987166-EPRSchr1220195860-0.0005704050.9994295
ENST00000413476ENST00000366923BLNKchr1097987166-EPRSchr1220195860-0.0005704050.9994295

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 BLNK-EPRS

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
BLNKchr1097987166EPRSchr1220195860503132PVHPALPFARGEYIAIEKNLQMWEEM
BLNKchr1097987166EPRSchr1220195860503631KPGNPPAEIGQNISSNSSASILESKS
BLNKchr1097987166EPRSchr1220195860539132PVHPALPFARGEYIAIEKNLQMWEEM
BLNKchr1097987166EPRSchr1220195860539631KPGNPPAEIGQNISSNSSASILESKS

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Potential FusionNeoAntigen Information of BLNK-EPRS 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.
BLNK-EPRS_97987166_220195860.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)
BLNK-EPRSchr1097987166chr1220195860503HLA-B45:01AEIGQNISS0.98760.7437615
BLNK-EPRSchr1097987166chr1220195860503HLA-B41:01AEIGQNISS0.30830.7213615
BLNK-EPRSchr1097987166chr1220195860503HLA-C15:05ISSNSSASI0.99880.86731221

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Potential FusionNeoAntigen Information of BLNK-EPRS 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.
BLNK-EPRS_97987166_220195860.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)
BLNK-EPRSchr1097987166chr1220195860503DRB1-0338GQNISSNSSASILES924
BLNK-EPRSchr1097987166chr1220195860503DRB1-0338IGQNISSNSSASILE823
BLNK-EPRSchr1097987166chr1220195860503DRB1-1493GQNISSNSSASILES924
BLNK-EPRSchr1097987166chr1220195860503DRB1-1525GQNISSNSSASILES924
BLNK-EPRSchr1097987166chr1220195860503DRB3-0109GQNISSNSSASILES924
BLNK-EPRSchr1097987166chr1220195860503DRB3-0201GQNISSNSSASILES924
BLNK-EPRSchr1097987166chr1220195860503DRB3-0201IGQNISSNSSASILE823
BLNK-EPRSchr1097987166chr1220195860503DRB3-0201PAEIGQNISSNSSAS520
BLNK-EPRSchr1097987166chr1220195860503DRB3-0201QNISSNSSASILESK1025
BLNK-EPRSchr1097987166chr1220195860503DRB3-0201EIGQNISSNSSASIL722
BLNK-EPRSchr1097987166chr1220195860503DRB3-0202GQNISSNSSASILES924
BLNK-EPRSchr1097987166chr1220195860503DRB3-0202IGQNISSNSSASILE823
BLNK-EPRSchr1097987166chr1220195860503DRB3-0204GQNISSNSSASILES924
BLNK-EPRSchr1097987166chr1220195860503DRB3-0204IGQNISSNSSASILE823
BLNK-EPRSchr1097987166chr1220195860503DRB3-0205GQNISSNSSASILES924
BLNK-EPRSchr1097987166chr1220195860503DRB3-0209GQNISSNSSASILES924
BLNK-EPRSchr1097987166chr1220195860503DRB3-0209IGQNISSNSSASILE823
BLNK-EPRSchr1097987166chr1220195860503DRB3-0209EIGQNISSNSSASIL722
BLNK-EPRSchr1097987166chr1220195860503DRB3-0209QNISSNSSASILESK1025
BLNK-EPRSchr1097987166chr1220195860503DRB3-0210GQNISSNSSASILES924
BLNK-EPRSchr1097987166chr1220195860503DRB3-0210IGQNISSNSSASILE823
BLNK-EPRSchr1097987166chr1220195860503DRB3-0211GQNISSNSSASILES924
BLNK-EPRSchr1097987166chr1220195860503DRB3-0211IGQNISSNSSASILE823
BLNK-EPRSchr1097987166chr1220195860503DRB3-0212GQNISSNSSASILES924
BLNK-EPRSchr1097987166chr1220195860503DRB3-0212IGQNISSNSSASILE823
BLNK-EPRSchr1097987166chr1220195860503DRB3-0213GQNISSNSSASILES924
BLNK-EPRSchr1097987166chr1220195860503DRB3-0214GQNISSNSSASILES924
BLNK-EPRSchr1097987166chr1220195860503DRB3-0214IGQNISSNSSASILE823
BLNK-EPRSchr1097987166chr1220195860503DRB3-0215GQNISSNSSASILES924
BLNK-EPRSchr1097987166chr1220195860503DRB3-0215IGQNISSNSSASILE823
BLNK-EPRSchr1097987166chr1220195860503DRB3-0216GQNISSNSSASILES924
BLNK-EPRSchr1097987166chr1220195860503DRB3-0216IGQNISSNSSASILE823
BLNK-EPRSchr1097987166chr1220195860503DRB3-0216EIGQNISSNSSASIL722
BLNK-EPRSchr1097987166chr1220195860503DRB3-0217GQNISSNSSASILES924
BLNK-EPRSchr1097987166chr1220195860503DRB3-0218GQNISSNSSASILES924
BLNK-EPRSchr1097987166chr1220195860503DRB3-0218IGQNISSNSSASILE823
BLNK-EPRSchr1097987166chr1220195860503DRB3-0219GQNISSNSSASILES924
BLNK-EPRSchr1097987166chr1220195860503DRB3-0219IGQNISSNSSASILE823
BLNK-EPRSchr1097987166chr1220195860503DRB3-0220GQNISSNSSASILES924
BLNK-EPRSchr1097987166chr1220195860503DRB3-0220IGQNISSNSSASILE823
BLNK-EPRSchr1097987166chr1220195860503DRB3-0221GQNISSNSSASILES924
BLNK-EPRSchr1097987166chr1220195860503DRB3-0221IGQNISSNSSASILE823
BLNK-EPRSchr1097987166chr1220195860503DRB3-0221EIGQNISSNSSASIL722
BLNK-EPRSchr1097987166chr1220195860503DRB3-0221QNISSNSSASILESK1025
BLNK-EPRSchr1097987166chr1220195860503DRB3-0222GQNISSNSSASILES924
BLNK-EPRSchr1097987166chr1220195860503DRB3-0222IGQNISSNSSASILE823
BLNK-EPRSchr1097987166chr1220195860503DRB3-0223GQNISSNSSASILES924
BLNK-EPRSchr1097987166chr1220195860503DRB3-0223IGQNISSNSSASILE823
BLNK-EPRSchr1097987166chr1220195860503DRB3-0224GQNISSNSSASILES924
BLNK-EPRSchr1097987166chr1220195860503DRB3-0224IGQNISSNSSASILE823
BLNK-EPRSchr1097987166chr1220195860503DRB3-0224PAEIGQNISSNSSAS520
BLNK-EPRSchr1097987166chr1220195860503DRB3-0224QNISSNSSASILESK1025
BLNK-EPRSchr1097987166chr1220195860503DRB3-0224EIGQNISSNSSASIL722
BLNK-EPRSchr1097987166chr1220195860503DRB3-0225GQNISSNSSASILES924
BLNK-EPRSchr1097987166chr1220195860503DRB3-0225IGQNISSNSSASILE823
BLNK-EPRSchr1097987166chr1220195860503DRB3-0301GQNISSNSSASILES924
BLNK-EPRSchr1097987166chr1220195860503DRB3-0301IGQNISSNSSASILE823
BLNK-EPRSchr1097987166chr1220195860503DRB3-0301EIGQNISSNSSASIL722
BLNK-EPRSchr1097987166chr1220195860503DRB3-0301QNISSNSSASILESK1025
BLNK-EPRSchr1097987166chr1220195860503DRB3-0303GQNISSNSSASILES924
BLNK-EPRSchr1097987166chr1220195860503DRB3-0303IGQNISSNSSASILE823
BLNK-EPRSchr1097987166chr1220195860503DRB3-0303EIGQNISSNSSASIL722
BLNK-EPRSchr1097987166chr1220195860503DRB3-0303QNISSNSSASILESK1025

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Fusion breakpoint peptide structures of BLNK-EPRS

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
156AEIGQNISSNSSASBLNKEPRSchr1097987166chr1220195860503

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of BLNK-EPRS

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-B52:013W39156AEIGQNISSNSSAS-6.65674-6.65674
HLA-B44:053DX8156AEIGQNISSNSSAS-6.36866-6.36866

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Vaccine Design for the FusionNeoAntigens of BLNK-EPRS

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
BLNK-EPRSchr1097987166chr12201958601221ISSNSSASITAGCTATTGAGAAGAATCTACAAATGT
BLNK-EPRSchr1097987166chr1220195860615AEIGQNISSTCGCCAGAGGCGAGTATATAGCTATTG

check button mRNA and peptide sequences of FusionNeoAntigens that have potential interaction with HLA-IIs.
Fusion geneHchrHbpTchrTbpStart in +/-13AAEnd in +/-13AAFusionNeoAntigen peptideFusionNEoAntigen RNA sequence
BLNK-EPRSchr1097987166chr12201958601025QNISSNSSASILESKAGTATATAGCTATTGAGAAGAATCTACAAATGTGGGAAGAAATGA
BLNK-EPRSchr1097987166chr1220195860520PAEIGQNISSNSSASCCTTCGCCAGAGGCGAGTATATAGCTATTGAGAAGAATCTACAAA
BLNK-EPRSchr1097987166chr1220195860722EIGQNISSNSSASILCCAGAGGCGAGTATATAGCTATTGAGAAGAATCTACAAATGTGGG
BLNK-EPRSchr1097987166chr1220195860823IGQNISSNSSASILEGAGGCGAGTATATAGCTATTGAGAAGAATCTACAAATGTGGGAAG
BLNK-EPRSchr1097987166chr1220195860924GQNISSNSSASILESGCGAGTATATAGCTATTGAGAAGAATCTACAAATGTGGGAAGAAA

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Information of the samples that have these potential fusion neoantigens of BLNK-EPRS

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
STADBLNK-EPRSchr1097987166ENST00000224337chr1220195860ENST00000366923TCGA-BR-8372-01A

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Potential target of CAR-T therapy development for BLNK-EPRS

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 BLNK-EPRS

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 BLNK-EPRS

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