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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:MINK1-PELP1

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: MINK1-PELP1
FusionPDB ID: 53690
FusionGDB2.0 ID: 53690
HgeneTgene
Gene symbol

MINK1

PELP1

Gene ID

50488

27043

Gene namemisshapen like kinase 1proline, glutamate and leucine rich protein 1
SynonymsB55|MAP4K6|MINK|YSK2|ZC3MNAR|P160
Cytomap

17p13.2

17p13.2

Type of geneprotein-codingprotein-coding
Descriptionmisshapen-like kinase 1GCK family kinase MINKMAPK/ERK kinase kinase kinase 6MEK kinase kinase 6MEKKK 6misshapen/NIK-related kinasemitogen-activated protein kinase kinase kinase kinase 6proline-, glutamic acid- and leucine-rich protein 1modulator of non-genomic activity of estrogen receptorproline and glutamic acid rich nuclear proteintranscription factor HMX3
Modification date2020032020200329
UniProtAcc

Q8N4C8

Main function of 5'-partner protein: FUNCTION: Serine/threonine kinase which acts as a negative regulator of Ras-related Rap2-mediated signal transduction to control neuronal structure and AMPA receptor trafficking. Required for normal synaptic density, dendrite complexity, as well as surface AMPA receptor expression in hippocampal neurons. Can activate the JNK and MAPK14/p38 pathways and mediates stimulation of the stress-activated protein kinase MAPK14/p38 MAPK downstream of the Raf/ERK pathway. Phosphorylates: TANC1 upon stimulation by RAP2A, MBP and SMAD1. Has an essential function in negative selection of thymocytes, perhaps by coupling NCK1 to activation of JNK1.; FUNCTION: Isoform 4 can activate the JNK pathway. Involved in the regulation of actin cytoskeleton reorganization, cell-matrix adhesion, cell-cell adhesion and cell migration.
.
Ensembl transtripts involved in fusion geneENST idsENST00000347992, ENST00000355280, 
ENST00000453408, 
ENST00000436683, 
ENST00000570823, ENST00000269230, 
ENST00000301396, ENST00000572293, 
ENST00000574876, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score13 X 8 X 5=5207 X 5 X 7=245
# samples 1713
** MAII scorelog2(17/520*10)=-1.61297687689075
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(13/245*10)=-0.914270125974116
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: MINK1 [Title/Abstract] AND PELP1 [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: MINK1 [Title/Abstract] AND PELP1 [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)MINK1(4736935)-PELP1(4586247), # samples:1
Anticipated loss of major functional domain due to fusion event.MINK1-PELP1 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.
MINK1-PELP1 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.
MINK1-PELP1 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.
MINK1-PELP1 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
HgeneMINK1

GO:0046777

protein autophosphorylation

15469942

TgenePELP1

GO:0045944

positive regulation of transcription by RNA polymerase II

17505058

TgenePELP1

GO:0071391

cellular response to estrogen stimulus

17505058



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/chr17:4736935/chr17:4586247)
- 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 MINK1 (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 PELP1 (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)
ENST00000355280MINK1chr174736935+ENST00000574876PELP1chr174586247-328125319632251009
ENST00000355280MINK1chr174736935+ENST00000572293PELP1chr174586247-328025319632251009
ENST00000355280MINK1chr174736935+ENST00000269230PELP1chr174586247-30102531962955919
ENST00000355280MINK1chr174736935+ENST00000301396PELP1chr174586247-371225319636571153
ENST00000347992MINK1chr174736935+ENST00000574876PELP1chr174586247-326924118432131009
ENST00000347992MINK1chr174736935+ENST00000572293PELP1chr174586247-326824118432131009
ENST00000347992MINK1chr174736935+ENST00000269230PELP1chr174586247-29982411842943919
ENST00000347992MINK1chr174736935+ENST00000301396PELP1chr174586247-370024118436451153
ENST00000453408MINK1chr174736935+ENST00000574876PELP1chr174586247-308557030291009
ENST00000453408MINK1chr174736935+ENST00000572293PELP1chr174586247-308457030291009
ENST00000453408MINK1chr174736935+ENST00000269230PELP1chr174586247-28145702759919
ENST00000453408MINK1chr174736935+ENST00000301396PELP1chr174586247-351657034611153

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
ENST00000355280ENST00000574876MINK1chr174736935+PELP1chr174586247-0.0069090510.99309087
ENST00000355280ENST00000572293MINK1chr174736935+PELP1chr174586247-0.0068730510.993127
ENST00000355280ENST00000269230MINK1chr174736935+PELP1chr174586247-0.0080340050.991966
ENST00000355280ENST00000301396MINK1chr174736935+PELP1chr174586247-0.0038336150.99616647
ENST00000347992ENST00000574876MINK1chr174736935+PELP1chr174586247-0.0066870460.9933129
ENST00000347992ENST00000572293MINK1chr174736935+PELP1chr174586247-0.006651590.9933484
ENST00000347992ENST00000269230MINK1chr174736935+PELP1chr174586247-0.0078954270.99210453
ENST00000347992ENST00000301396MINK1chr174736935+PELP1chr174586247-0.0037304890.99626946
ENST00000453408ENST00000574876MINK1chr174736935+PELP1chr174586247-0.0060282690.99397177
ENST00000453408ENST00000572293MINK1chr174736935+PELP1chr174586247-0.005999730.9940003
ENST00000453408ENST00000269230MINK1chr174736935+PELP1chr174586247-0.0082096010.9917904
ENST00000453408ENST00000301396MINK1chr174736935+PELP1chr174586247-0.0031901790.9968098

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 MINK1-PELP1

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
MINK1chr174736935PELP1chr17458624724117APARSLDDIDLSALRTQDPPATMELA
MINK1chr174736935PELP1chr174586247241548PSPFRAPPFHPPGPMPSVGSMPSAGP
MINK1chr174736935PELP1chr174586247241692PSPFRAPPFHPPGPMPSVGSMPSAGP
MINK1chr174736935PELP1chr17458624725317APARSLDDIDLSALRTQDPPATMELA
MINK1chr174736935PELP1chr174586247253548PSPFRAPPFHPPGPMPSVGSMPSAGP
MINK1chr174736935PELP1chr174586247253692PSPFRAPPFHPPGPMPSVGSMPSAGP
MINK1chr174736935PELP1chr1745862475717APARSLDDIDLSALRTQDPPATMELA
MINK1chr174736935PELP1chr17458624757548PSPFRAPPFHPPGPMPSVGSMPSAGP
MINK1chr174736935PELP1chr17458624757692PSPFRAPPFHPPGPMPSVGSMPSAGP

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Potential FusionNeoAntigen Information of MINK1-PELP1 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.
MINK1-PELP1_4736935_4586247.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)
MINK1-PELP1chr174736935chr174586247241HLA-B15:73ALRTQDPPATM0.99710.99621223
MINK1-PELP1chr174736935chr174586247241HLA-B15:30ALRTQDPPATM0.99480.99531223

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Potential FusionNeoAntigen Information of MINK1-PELP1 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 MINK1-PELP1

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
1029DDIDLSALRTQDPPMINK1PELP1chr174736935chr174586247241

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of MINK1-PELP1

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-B14:023BVN1029DDIDLSALRTQDPP-7.9962-8.1096
HLA-B14:023BVN1029DDIDLSALRTQDPP-5.70842-6.74372
HLA-B52:013W391029DDIDLSALRTQDPP-6.83737-6.95077
HLA-B52:013W391029DDIDLSALRTQDPP-4.4836-5.5189
HLA-A11:014UQ21029DDIDLSALRTQDPP-10.0067-10.1201
HLA-A11:014UQ21029DDIDLSALRTQDPP-9.03915-10.0745
HLA-A24:025HGA1029DDIDLSALRTQDPP-6.56204-6.67544
HLA-A24:025HGA1029DDIDLSALRTQDPP-5.42271-6.45801
HLA-B44:053DX81029DDIDLSALRTQDPP-7.85648-8.89178
HLA-B44:053DX81029DDIDLSALRTQDPP-5.3978-5.5112
HLA-B35:011A1N1029DDIDLSALRTQDPP-6.27422-6.38762
HLA-B35:011A1N1029DDIDLSALRTQDPP-5.27424-6.30954
HLA-A02:016TDR1029DDIDLSALRTQDPP-3.37154-4.40684

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Vaccine Design for the FusionNeoAntigens of MINK1-PELP1

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
MINK1-PELP1chr174736935chr1745862471223ALRTQDPPATMCGGACCCAGGACCCGCCTGCCACAATGGAGCTG

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 MINK1-PELP1

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
STADMINK1-PELP1chr174736935ENST00000347992chr174586247ENST00000269230TCGA-HU-A4GN-01A

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Potential target of CAR-T therapy development for MINK1-PELP1

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 MINK1-PELP1

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 MINK1-PELP1

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