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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:TPM3-GPR37L1

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: TPM3-GPR37L1
FusionPDB ID: 93380
FusionGDB2.0 ID: 93380
HgeneTgene
Gene symbol

TPM3

GPR37L1

Gene ID

7170

9283

Gene nametropomyosin 3G protein-coupled receptor 37 like 1
SynonymsCAPM1|CFTD|HEL-189|HEL-S-82p|NEM1|OK/SW-cl.5|TM-5|TM3|TM30|TM30nm|TM5|TPM3nu|TPMsk3|TRK|hscp30ET(B)R-LP-2|ETBR-LP-2|ETBRLP2
Cytomap

1q21.3

1q32.1

Type of geneprotein-codingprotein-coding
Descriptiontropomyosin alpha-3 chainalpha-tropomyosin, slow skeletalcytoskeletal tropomyosin TM30epididymis luminal protein 189epididymis secretory sperm binding protein Li 82pheat-stable cytoskeletal protein 30 kDatropomyosin 3 nutropomyosin gammatropomyosiG-protein coupled receptor 37-like 1endothelin B receptor-like protein 2endothelin type b receptor-like protein 2prosaposin receptor GPR37L1
Modification date2020032820200313
UniProtAcc

P06753

Main function of 5'-partner protein: FUNCTION: Binds to actin filaments in muscle and non-muscle cells. Plays a central role, in association with the troponin complex, in the calcium dependent regulation of vertebrate striated muscle contraction. Smooth muscle contraction is regulated by interaction with caldesmon. In non-muscle cells is implicated in stabilizing cytoskeleton actin filaments. {ECO:0000250|UniProtKB:P09493}.

O60883

Main function of 5'-partner protein: FUNCTION: G-protein coupled receptor (PubMed:27072655). Has been shown to bind the neuroprotective and glioprotective factor prosaposin (PSAP), leading to endocytosis followed by an ERK phosphorylation cascade (PubMed:23690594). However, other studies have shown that prosaposin does not increase activity (PubMed:27072655, PubMed:28688853). It has been suggested that GPR37L1 is a constitutively active receptor which signals through the guanine nucleotide-binding protein G(s) subunit alpha (PubMed:27072655). Participates in the regulation of postnatal cerebellar development by modulating the Shh pathway (By similarity). Regulates baseline blood pressure in females and protects against cardiovascular stress in males (By similarity). Mediates inhibition of astrocyte glutamate transporters and reduction in neuronal N-methyl-D-aspartate receptor activity (By similarity). {ECO:0000250|UniProtKB:Q99JG2, ECO:0000269|PubMed:23690594, ECO:0000269|PubMed:27072655, ECO:0000269|PubMed:28688853}.
Ensembl transtripts involved in fusion geneENST idsENST00000469717, ENST00000302206, 
ENST00000271850, ENST00000323144, 
ENST00000328159, ENST00000330188, 
ENST00000341372, ENST00000341485, 
ENST00000368530, ENST00000368531, 
ENST00000368533, 
ENST00000367282, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score15 X 22 X 8=264012 X 6 X 7=504
# samples 2416
** MAII scorelog2(24/2640*10)=-3.4594316186373
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(16/504*10)=-1.65535182861255
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: TPM3 [Title/Abstract] AND GPR37L1 [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: TPM3 [Title/Abstract] AND GPR37L1 [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)TPM3(154142876)-GPR37L1(202096869), # samples:2
Anticipated loss of major functional domain due to fusion event.TPM3-GPR37L1 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.
TPM3-GPR37L1 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.
TPM3-GPR37L1 seems lost the major protein functional domain in Hgene partner, which is a CGC due to the frame-shifted ORF.
TPM3-GPR37L1 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
TgeneGPR37L1

GO:0007193

adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway

23690594

TgeneGPR37L1

GO:0043410

positive regulation of MAPK cascade

23690594



check button Four levels of functional features of fusion genes
Go to FGviewer search page for the most frequent breakpoint (https://ccsmweb.uth.edu/FGviewer/chr1:154142876/chr1:202096869)
- 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 TPM3 (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 GPR37L1 (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)
ENST00000368533TPM3chr1154142876-ENST00000367282GPR37L1chr1202096869+65697177021532276
ENST00000330188TPM3chr1154142876-ENST00000367282GPR37L1chr1202096869+66027507351565276
ENST00000341485TPM3chr1154142876-ENST00000367282GPR37L1chr1202096869+65577059522317
ENST00000341372TPM3chr1154142876-ENST00000367282GPR37L1chr1202096869+65036516361466276
ENST00000328159TPM3chr1154142876-ENST00000367282GPR37L1chr1202096869+65166646491479276
ENST00000271850TPM3chr1154142876-ENST00000367282GPR37L1chr1202096869+666781534864276
ENST00000368531TPM3chr1154142876-ENST00000367282GPR37L1chr1202096869+65276756601490276
ENST00000323144TPM3chr1154142876-ENST00000367282GPR37L1chr1202096869+65617096941524276
ENST00000368530TPM3chr1154142876-ENST00000367282GPR37L1chr1202096869+68209681871017276
ENST00000368533TPM3chr1154142875-ENST00000367282GPR37L1chr1202096868+65697177021532276
ENST00000330188TPM3chr1154142875-ENST00000367282GPR37L1chr1202096868+66027507351565276
ENST00000341485TPM3chr1154142875-ENST00000367282GPR37L1chr1202096868+65577059522317
ENST00000341372TPM3chr1154142875-ENST00000367282GPR37L1chr1202096868+65036516361466276
ENST00000328159TPM3chr1154142875-ENST00000367282GPR37L1chr1202096868+65166646491479276
ENST00000271850TPM3chr1154142875-ENST00000367282GPR37L1chr1202096868+666781534864276
ENST00000368531TPM3chr1154142875-ENST00000367282GPR37L1chr1202096868+65276756601490276
ENST00000323144TPM3chr1154142875-ENST00000367282GPR37L1chr1202096868+65617096941524276
ENST00000368530TPM3chr1154142875-ENST00000367282GPR37L1chr1202096868+68209681871017276

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
ENST00000368533ENST00000367282TPM3chr1154142876-GPR37L1chr1202096869+0.180987310.8190127
ENST00000330188ENST00000367282TPM3chr1154142876-GPR37L1chr1202096869+0.187202260.8127977
ENST00000341485ENST00000367282TPM3chr1154142876-GPR37L1chr1202096869+0.177081110.8229189
ENST00000341372ENST00000367282TPM3chr1154142876-GPR37L1chr1202096869+0.18350470.8164953
ENST00000328159ENST00000367282TPM3chr1154142876-GPR37L1chr1202096869+0.183638840.8163611
ENST00000271850ENST00000367282TPM3chr1154142876-GPR37L1chr1202096869+0.170286880.8297131
ENST00000368531ENST00000367282TPM3chr1154142876-GPR37L1chr1202096869+0.183507190.8164928
ENST00000323144ENST00000367282TPM3chr1154142876-GPR37L1chr1202096869+0.18893480.8110652
ENST00000368530ENST00000367282TPM3chr1154142876-GPR37L1chr1202096869+0.177950650.8220493
ENST00000368533ENST00000367282TPM3chr1154142875-GPR37L1chr1202096868+0.180987310.8190127
ENST00000330188ENST00000367282TPM3chr1154142875-GPR37L1chr1202096868+0.187202260.8127977
ENST00000341485ENST00000367282TPM3chr1154142875-GPR37L1chr1202096868+0.177081110.8229189
ENST00000341372ENST00000367282TPM3chr1154142875-GPR37L1chr1202096868+0.18350470.8164953
ENST00000328159ENST00000367282TPM3chr1154142875-GPR37L1chr1202096868+0.183638840.8163611
ENST00000271850ENST00000367282TPM3chr1154142875-GPR37L1chr1202096868+0.170286880.8297131
ENST00000368531ENST00000367282TPM3chr1154142875-GPR37L1chr1202096868+0.183507190.8164928
ENST00000323144ENST00000367282TPM3chr1154142875-GPR37L1chr1202096868+0.18893480.8110652
ENST00000368530ENST00000367282TPM3chr1154142875-GPR37L1chr1202096868+0.177950650.8220493

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 TPM3-GPR37L1

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
TPM3chr1154142875GPR37L1chr1202096868815260SVAKLEKTIDDLEGLLSGSHDFQPLC
TPM3chr1154142875GPR37L1chr1202096868968260SVAKLEKTIDDLEGLLSGSHDFQPLC
TPM3chr1154142876GPR37L1chr1202096869815260SVAKLEKTIDDLEGLLSGSHDFQPLC
TPM3chr1154142876GPR37L1chr1202096869968260SVAKLEKTIDDLEGLLSGSHDFQPLC

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Potential FusionNeoAntigen Information of TPM3-GPR37L1 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 TPM3-GPR37L1 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 TPM3-GPR37L1

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 TPM3-GPR37L1

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 TPM3-GPR37L1

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 TPM3-GPR37L1

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 TPM3-GPR37L1

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
TgeneGPR37L1chr1:154142875chr1:202096868ENST0000036728202252_2720482.0TransmembraneHelical%3B Name%3D4
TgeneGPR37L1chr1:154142875chr1:202096868ENST0000036728202311_3310482.0TransmembraneHelical%3B Name%3D5
TgeneGPR37L1chr1:154142875chr1:202096868ENST0000036728202362_3820482.0TransmembraneHelical%3B Name%3D6
TgeneGPR37L1chr1:154142875chr1:202096868ENST0000036728202399_4190482.0TransmembraneHelical%3B Name%3D7
TgeneGPR37L1chr1:154142876chr1:202096869ENST0000036728202252_2720482.0TransmembraneHelical%3B Name%3D4
TgeneGPR37L1chr1:154142876chr1:202096869ENST0000036728202311_3310482.0TransmembraneHelical%3B Name%3D5
TgeneGPR37L1chr1:154142876chr1:202096869ENST0000036728202362_3820482.0TransmembraneHelical%3B Name%3D6
TgeneGPR37L1chr1:154142876chr1:202096869ENST0000036728202399_4190482.0TransmembraneHelical%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 TPM3-GPR37L1

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 TPM3-GPR37L1

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
HgeneTPM3C1836448Nemaline myopathy 19CTD_human;GENOMICS_ENGLAND;UNIPROT
HgeneTPM3C0546264Congenital Fiber Type Disproportion4CTD_human;GENOMICS_ENGLAND;UNIPROT
HgeneTPM3C0007097Carcinoma2CTD_human
HgeneTPM3C0024667Animal Mammary Neoplasms2CTD_human
HgeneTPM3C0024668Mammary Neoplasms, Experimental2CTD_human
HgeneTPM3C0205696Anaplastic carcinoma2CTD_human
HgeneTPM3C0205697Carcinoma, Spindle-Cell2CTD_human
HgeneTPM3C0205698Undifferentiated carcinoma2CTD_human
HgeneTPM3C0205699Carcinomatosis2CTD_human
HgeneTPM3C0206157Myopathies, Nemaline2GENOMICS_ENGLAND
HgeneTPM3C1257925Mammary Carcinoma, Animal2CTD_human
HgeneTPM3C0001418Adenocarcinoma1CTD_human
HgeneTPM3C0007102Malignant tumor of colon1CTD_human
HgeneTPM3C0009375Colonic Neoplasms1CTD_human
HgeneTPM3C0023893Liver Cirrhosis, Experimental1CTD_human
HgeneTPM3C0024623Malignant neoplasm of stomach1CTD_human
HgeneTPM3C0038356Stomach Neoplasms1CTD_human
HgeneTPM3C0040136Thyroid Neoplasm1CTD_human
HgeneTPM3C0151468Thyroid Gland Follicular Adenoma1CTD_human
HgeneTPM3C0205641Adenocarcinoma, Basal Cell1CTD_human
HgeneTPM3C0205642Adenocarcinoma, Oxyphilic1CTD_human
HgeneTPM3C0205643Carcinoma, Cribriform1CTD_human
HgeneTPM3C0205644Carcinoma, Granular Cell1CTD_human
HgeneTPM3C0205645Adenocarcinoma, Tubular1CTD_human
HgeneTPM3C0270960Congenital myopathy (disorder)1GENOMICS_ENGLAND
HgeneTPM3C0334121Inflammatory Myofibroblastic Tumor1ORPHANET
HgeneTPM3C0546125Nemaline Myopathy, Childhood Onset1ORPHANET
HgeneTPM3C0549473Thyroid carcinoma1CTD_human
HgeneTPM3C1708349Hereditary Diffuse Gastric Cancer1CTD_human
HgeneTPM3C3710589Cap Myopathy1ORPHANET