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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:TMEM135-GRM5

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: TMEM135-GRM5
FusionPDB ID: 91678
FusionGDB2.0 ID: 91678
HgeneTgene
Gene symbol

TMEM135

GRM5

Gene ID

65084

2915

Gene nametransmembrane protein 135glutamate metabotropic receptor 5
SynonymsPMP52GPRC1E|MGLUR5|PPP1R86|mGlu5
Cytomap

11q14.2

11q14.2-q14.3

Type of geneprotein-codingprotein-coding
Descriptiontransmembrane protein 135peroxisomal membrane protein 52metabotropic glutamate receptor 5glutamate receptor, metabotropic 5protein phosphatase 1, regulatory subunit 86
Modification date2020031320200329
UniProtAcc.

P41594

Main function of 5'-partner protein: FUNCTION: G-protein coupled receptor for glutamate. Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of down-stream effectors. Signaling activates a phosphatidylinositol-calcium second messenger system and generates a calcium-activated chloride current. Plays an important role in the regulation of synaptic plasticity and the modulation of the neural network activity. {ECO:0000269|PubMed:25042998, ECO:0000269|PubMed:7908515}.
Ensembl transtripts involved in fusion geneENST idsENST00000305494, ENST00000340353, 
ENST00000532959, ENST00000535167, 
ENST00000355734, 
ENST00000393294, 
ENST00000393297, ENST00000418177, 
ENST00000455756, ENST00000305432, 
ENST00000305447, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score17 X 12 X 8=16327 X 5 X 4=140
# samples 207
** MAII scorelog2(20/1632*10)=-3.02856915219677
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(7/140*10)=-1
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: TMEM135 [Title/Abstract] AND GRM5 [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: TMEM135 [Title/Abstract] AND GRM5 [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)TMEM135(87006865)-GRM5(88242672), # samples:1
Anticipated loss of major functional domain due to fusion event.TMEM135-GRM5 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.
TMEM135-GRM5 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.
TMEM135-GRM5 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.
TMEM135-GRM5 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.
TMEM135-GRM5 seems lost the major protein functional domain in Tgene partner, which is a essential gene due to the frame-shifted ORF.
TMEM135-GRM5 seems lost the major protein functional domain in Tgene partner, which is a IUPHAR drug target due to the frame-shifted 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


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/chr11:87006865/chr11:88242672)
- 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 TMEM135 (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 GRM5 (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)
ENST00000340353TMEM135chr1187006865-ENST00000305447GRM5chr1188242672-23826871241599491
ENST00000340353TMEM135chr1187006865-ENST00000305432GRM5chr1188242672-23826871241599491
ENST00000532959TMEM135chr1187006865-ENST00000305447GRM5chr1188242672-1992297251209394
ENST00000532959TMEM135chr1187006865-ENST00000305432GRM5chr1188242672-1992297251209394
ENST00000305494TMEM135chr1187006865-ENST00000305447GRM5chr1188242672-2285590271502491
ENST00000305494TMEM135chr1187006865-ENST00000305432GRM5chr1188242672-2285590271502491
ENST00000535167TMEM135chr1187006865-ENST00000305447GRM5chr1188242672-22185233891435348
ENST00000535167TMEM135chr1187006865-ENST00000305432GRM5chr1188242672-22185233891435348

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
ENST00000340353ENST00000305447TMEM135chr1187006865-GRM5chr1188242672-0.0519536060.9480463
ENST00000340353ENST00000305432TMEM135chr1187006865-GRM5chr1188242672-0.0519536060.9480463
ENST00000532959ENST00000305447TMEM135chr1187006865-GRM5chr1188242672-0.0523847860.9476152
ENST00000532959ENST00000305432TMEM135chr1187006865-GRM5chr1188242672-0.0523847860.9476152
ENST00000305494ENST00000305447TMEM135chr1187006865-GRM5chr1188242672-0.046635410.95336455
ENST00000305494ENST00000305432TMEM135chr1187006865-GRM5chr1188242672-0.046635410.95336455
ENST00000535167ENST00000305447TMEM135chr1187006865-GRM5chr1188242672-0.0261431670.9738568
ENST00000535167ENST00000305432TMEM135chr1187006865-GRM5chr1188242672-0.0261431670.9738568

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 TMEM135-GRM5

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
TMEM135chr1187006865GRM5chr118824267229787FFRCKDGLKGFTFSALSSNGKSVTWA
TMEM135chr1187006865GRM5chr118824267252341FFRCKDGLKGFTFSALSSNGKSVTWA
TMEM135chr1187006865GRM5chr1188242672590184FFRCKDGLKGFTFSALSSNGKSVTWA
TMEM135chr1187006865GRM5chr1188242672687184FFRCKDGLKGFTFSALSSNGKSVTWA

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Potential FusionNeoAntigen Information of TMEM135-GRM5 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.
TMEM135-GRM5_87006865_88242672.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)
TMEM135-GRM5chr1187006865chr1188242672590HLA-A02:22GLKGFTFSA0.99520.5766615
TMEM135-GRM5chr1187006865chr1188242672590HLA-A02:13GLKGFTFSA0.99240.7729615
TMEM135-GRM5chr1187006865chr1188242672590HLA-A02:27GLKGFTFSA0.9870.6764615
TMEM135-GRM5chr1187006865chr1188242672590HLA-A02:11GLKGFTFSA0.96140.5769615
TMEM135-GRM5chr1187006865chr1188242672590HLA-A02:67GLKGFTFSA0.96030.5433615
TMEM135-GRM5chr1187006865chr1188242672590HLA-A02:24GLKGFTFSA0.96030.5433615
TMEM135-GRM5chr1187006865chr1188242672590HLA-A02:30GLKGFTFSA0.96030.5433615
TMEM135-GRM5chr1187006865chr1188242672590HLA-A02:16GLKGFTFSA0.95830.5836615
TMEM135-GRM5chr1187006865chr1188242672590HLA-A02:38GLKGFTFSA0.95720.7846615
TMEM135-GRM5chr1187006865chr1188242672590HLA-A02:29GLKGFTFSA0.81830.5504615
TMEM135-GRM5chr1187006865chr1188242672590HLA-A02:20GLKGFTFSA0.80480.553615
TMEM135-GRM5chr1187006865chr1188242672590HLA-A02:01GLKGFTFSA0.96030.5433615
TMEM135-GRM5chr1187006865chr1188242672590HLA-A02:03GLKGFTFSA0.99830.7655615

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Potential FusionNeoAntigen Information of TMEM135-GRM5 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.
TMEM135-GRM5_87006865_88242672.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)
TMEM135-GRM5chr1187006865chr1188242672590DRB5-0101GFTFSALSSNGKSVT924
TMEM135-GRM5chr1187006865chr1188242672590DRB5-0101KGFTFSALSSNGKSV823
TMEM135-GRM5chr1187006865chr1188242672590DRB5-0101LKGFTFSALSSNGKS722
TMEM135-GRM5chr1187006865chr1188242672590DRB5-0102GFTFSALSSNGKSVT924
TMEM135-GRM5chr1187006865chr1188242672590DRB5-0102KGFTFSALSSNGKSV823
TMEM135-GRM5chr1187006865chr1188242672590DRB5-0103GFTFSALSSNGKSVT924
TMEM135-GRM5chr1187006865chr1188242672590DRB5-0104GFTFSALSSNGKSVT924
TMEM135-GRM5chr1187006865chr1188242672590DRB5-0104KGFTFSALSSNGKSV823
TMEM135-GRM5chr1187006865chr1188242672590DRB5-0105GFTFSALSSNGKSVT924
TMEM135-GRM5chr1187006865chr1188242672590DRB5-0105KGFTFSALSSNGKSV823
TMEM135-GRM5chr1187006865chr1188242672590DRB5-0105LKGFTFSALSSNGKS722
TMEM135-GRM5chr1187006865chr1188242672590DRB5-0108NGFTFSALSSNGKSVT924
TMEM135-GRM5chr1187006865chr1188242672590DRB5-0108NKGFTFSALSSNGKSV823
TMEM135-GRM5chr1187006865chr1188242672590DRB5-0113GFTFSALSSNGKSVT924
TMEM135-GRM5chr1187006865chr1188242672590DRB5-0113KGFTFSALSSNGKSV823
TMEM135-GRM5chr1187006865chr1188242672590DRB5-0113LKGFTFSALSSNGKS722
TMEM135-GRM5chr1187006865chr1188242672590DRB5-0114GFTFSALSSNGKSVT924
TMEM135-GRM5chr1187006865chr1188242672590DRB5-0114KGFTFSALSSNGKSV823
TMEM135-GRM5chr1187006865chr1188242672590DRB5-0114LKGFTFSALSSNGKS722

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Fusion breakpoint peptide structures of TMEM135-GRM5

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
2939GLKGFTFSALSSNGTMEM135GRM5chr1187006865chr1188242672590

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of TMEM135-GRM5

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-B14:023BVN2939GLKGFTFSALSSNG-7.9962-8.1096
HLA-B14:023BVN2939GLKGFTFSALSSNG-5.70842-6.74372
HLA-B52:013W392939GLKGFTFSALSSNG-6.83737-6.95077
HLA-B52:013W392939GLKGFTFSALSSNG-4.4836-5.5189
HLA-A11:014UQ22939GLKGFTFSALSSNG-10.0067-10.1201
HLA-A11:014UQ22939GLKGFTFSALSSNG-9.03915-10.0745
HLA-A24:025HGA2939GLKGFTFSALSSNG-6.56204-6.67544
HLA-A24:025HGA2939GLKGFTFSALSSNG-5.42271-6.45801
HLA-B44:053DX82939GLKGFTFSALSSNG-7.85648-8.89178
HLA-B44:053DX82939GLKGFTFSALSSNG-5.3978-5.5112
HLA-A02:016TDR2939GLKGFTFSALSSNG-3.37154-4.40684

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Vaccine Design for the FusionNeoAntigens of TMEM135-GRM5

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
TMEM135-GRM5chr1187006865chr1188242672615GLKGFTFSAATTTACATTTTCTGCACTTAGTTCCAA

check button mRNA and peptide sequences of FusionNeoAntigens that have potential interaction with HLA-IIs.
Fusion geneHchrHbpTchrTbpStart in +/-13AAEnd in +/-13AAFusionNeoAntigen peptideFusionNEoAntigen RNA sequence
TMEM135-GRM5chr1187006865chr1188242672722LKGFTFSALSSNGKSTACATTTTCTGCACTTAGTTCCAATGGAAAATCCGTCACGTGGGC
TMEM135-GRM5chr1187006865chr1188242672823KGFTFSALSSNGKSVATTTTCTGCACTTAGTTCCAATGGAAAATCCGTCACGTGGGCCCA
TMEM135-GRM5chr1187006865chr1188242672924GFTFSALSSNGKSVTTTCTGCACTTAGTTCCAATGGAAAATCCGTCACGTGGGCCCAGAA

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Information of the samples that have these potential fusion neoantigens of TMEM135-GRM5

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
PRADTMEM135-GRM5chr1187006865ENST00000305494chr1188242672ENST00000305432TCGA-EJ-7115-01A

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Potential target of CAR-T therapy development for TMEM135-GRM5

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
HgeneTMEM135chr11:87006865chr11:88242672ENST00000305494-715149_169183459.0TransmembraneHelical
HgeneTMEM135chr11:87006865chr11:88242672ENST00000305494-71568_88183459.0TransmembraneHelical
HgeneTMEM135chr11:87006865chr11:88242672ENST00000305494-71596_116183459.0TransmembraneHelical
HgeneTMEM135chr11:87006865chr11:88242672ENST00000340353-61468_88161437.0TransmembraneHelical
HgeneTMEM135chr11:87006865chr11:88242672ENST00000340353-61496_116161437.0TransmembraneHelical
TgeneGRM5chr11:87006865chr11:88242672ENST0000039329709581_6030943.0TransmembraneNote=Helical%3B Name%3D1
TgeneGRM5chr11:87006865chr11:88242672ENST0000039329709614_6360943.0TransmembraneNote=Helical%3B Name%3D2
TgeneGRM5chr11:87006865chr11:88242672ENST0000039329709645_6670943.0TransmembraneNote=Helical%3B Name%3D3
TgeneGRM5chr11:87006865chr11:88242672ENST0000039329709694_7140943.0TransmembraneNote=Helical%3B Name%3D4
TgeneGRM5chr11:87006865chr11:88242672ENST0000039329709738_7590943.0TransmembraneNote=Helical%3B Name%3D5
TgeneGRM5chr11:87006865chr11:88242672ENST0000039329709773_7950943.0TransmembraneNote=Helical%3B Name%3D6
TgeneGRM5chr11:87006865chr11:88242672ENST0000039329709799_8200943.0TransmembraneNote=Helical%3B Name%3D7

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 TMEM135-GRM5

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 TMEM135-GRM5

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