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Center for Computational Systems Medicine level2
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Fusion Gene Summary

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Fusion Gene Sample Information

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Fusion ORF Analysis

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Fusion Amino Acid Sequences

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Fusion Protein Functional Features

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Fusion Protein Structure

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pLDDT scores

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Ramachandran Plot of Fusion Protein Structure

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Fusion Protein-Protein Interaction

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Related drugs with this fusion protein

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Related disease with this fusion protein

Fusion Protein:MSN-HTR3D

Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: MSN-HTR3D
FusionPDB ID: 55396
FusionGDB2.0 ID: 55396
HgeneTgene
Gene symbol

MSN

HTR3D

Gene ID

4478

200909

Gene namemoesin5-hydroxytryptamine receptor 3D
SynonymsHEL70|IMD505HT3D
Cytomap

Xq12

3q27.1

Type of geneprotein-codingprotein-coding
Descriptionmoesinepididymis luminal protein 70membrane-organizing extension spike protein5-hydroxytryptamine receptor 3D5-hydroxytryptamine (serotonin) receptor 3 family member D5-hydroxytryptamine (serotonin) receptor 3D, ionotropic5-hydroxytryptamine receptor 3 subunit Dserotonin 5-HT-3D receptorserotonin receptor 3D
Modification date2020032720200313
UniProtAcc

P26038

.
Ensembl transtripts involved in fusion geneENST idsENST00000360270, ENST00000609205, 
ENST00000334128, ENST00000382489, 
ENST00000428798, ENST00000453435, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score10 X 11 X 5=5503 X 3 X 2=18
# samples 123
** MAII scorelog2(12/550*10)=-2.1963972128035
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(3/18*10)=0.736965594166206
effective Gene in Pan-Cancer Fusion Genes (eGinPCFGs).
DoF>8 and MAII>0
Context (manual curation of fusion genes in FusionPDB)

PubMed: MSN [Title/Abstract] AND HTR3D [Title/Abstract] AND fusion [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)MSN(64887720)-HTR3D(183755809), # samples:3
Anticipated loss of major functional domain due to fusion event.MSN-HTR3D 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.
MSN-HTR3D 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
HgeneMSN

GO:0001771

immunological synapse formation

27405666

HgeneMSN

GO:0042098

T cell proliferation

27405666

HgeneMSN

GO:0070489

T cell aggregation

27405666

HgeneMSN

GO:0071394

cellular response to testosterone stimulus

24065547

HgeneMSN

GO:0072678

T cell migration

27405666


check buttonFusion gene breakpoints across MSN (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 HTR3D (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 Gene Sample Information

check buttonFusion gene information from FusionGDB2.0.
check button Fusion gene information from two resources (ChiTars 5.0 and ChimerDB 4.0)
* All genome coordinats were lifted-over on hg19.
* Click on the break point to see the gene structure around the break point region using the UCSC Genome Browser.
SourceDiseaseSampleHgeneHchrHbpHstrandTgeneTchrTbpTstrand
ChimerDB4LUSCTCGA-56-5898-01AMSNchrX

64887720

-HTR3Dchr3

183755809

+
ChimerDB4LUSCTCGA-56-5898-01AMSNchrX

64887720

+HTR3Dchr3

183755809

+
ChimerDB4LUSCTCGA-56-5898MSNchrX

64887720

+HTR3Dchr3

183755809

+


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Fusion ORF Analysis


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)
ENST00000360270MSNchrX64887720+ENST00000334128HTR3Dchr3183755809+1277184172882236
ENST00000360270MSNchrX64887720+ENST00000428798HTR3Dchr3183755809+883184172882237
ENST00000360270MSNchrX64887720+ENST00000382489HTR3Dchr3183755809+1198184172888238
ENST00000360270MSNchrX64887720+ENST00000453435HTR3Dchr3183755809+1108184172882236

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
ENST00000360270ENST00000334128MSNchrX64887720+HTR3Dchr3183755809+0.132768360.86723167
ENST00000360270ENST00000428798MSNchrX64887720+HTR3Dchr3183755809+0.111074610.8889253
ENST00000360270ENST00000382489MSNchrX64887720+HTR3Dchr3183755809+0.0583992670.94160074
ENST00000360270ENST00000453435MSNchrX64887720+HTR3Dchr3183755809+0.087918770.91208124

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Fusion Amino Acid Sequences


check button For individual full-length fusion transcript sequence from FusionPDB, we ran ORFfinder and chose the longest ORF among the all predicted ones.
>FusionGDB ID_FusionGDB isoform ID_FGname_Hgene_Hchr_Hbp_Henst_Tgene_Tchr_Tbp_Tenst_length(fusion AA) seq_BP

>55396_55396_1_MSN-HTR3D_MSN_chrX_64887720_ENST00000360270_HTR3D_chr3_183755809_ENST00000334128_length(amino acids)=236AA_BP=4
MPKTVAIRRRCRPSPYVVNFLVPSGILIAIDALSFYLPLESGNCAPFKMTVLLGYSVFLLMMNDLLPATSTSSHASLVRPHPSRDQKRGV
YFALCLSLMVGSLLETIFITHLLHVATTQPLPLPRWLHSLLLHCTGQGRCCPTAPQKGNKGPGLTPTHLPGVKEPEVSAGQMPGPGEAEL

--------------------------------------------------------------

>55396_55396_2_MSN-HTR3D_MSN_chrX_64887720_ENST00000360270_HTR3D_chr3_183755809_ENST00000382489_length(amino acids)=238AA_BP=4
MPKTVAIRRRCRPSPYVVNFLVPSGILIAIDALSFYLPLESGNCAPFKMTVLLGYSVFLLMMNDLLPATSTSSHASLVAPLALMQTPLPA
GVYFALCLSLMVGSLLETIFITHLLHVATTQPLPLPRWLHSLLLHCTGQGRCCPTAPQKGNKGPGLTPTHLPGVKEPEVSAGQMPGPGEA

--------------------------------------------------------------

>55396_55396_3_MSN-HTR3D_MSN_chrX_64887720_ENST00000360270_HTR3D_chr3_183755809_ENST00000428798_length(amino acids)=237AA_BP=4
MPKTVAIRRRCRPSPYVVNFLVPSGILIAIDALSFYLPLESGNCAPFKMTVLLGYSVFLLMMNDLLPATSTSSHASLVRPHPSRDQKRGV
YFALCLSLMVGSLLETIFITHLLHVATTQPLPLPRWLHSLLLHCTGQGRCCPTAPQKGNKGPGLTPTHLPGVKEPEVSAGQMPGPGEAEL

--------------------------------------------------------------

>55396_55396_4_MSN-HTR3D_MSN_chrX_64887720_ENST00000360270_HTR3D_chr3_183755809_ENST00000453435_length(amino acids)=236AA_BP=4
MPKTVAIRRRCRPSPYVVNFLVPSGILIAIDALSFYLPLESGNCAPFKMTVLLGYSVFLLMMNDLLPATSTSSHASLVRPHPSRDQKRGV
YFALCLSLMVGSLLETIFITHLLHVATTQPLPLPRWLHSLLLHCTGQGRCCPTAPQKGNKGPGLTPTHLPGVKEPEVSAGQMPGPGEAEL

--------------------------------------------------------------

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Fusion Protein Functional Features


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/chrX:64887720/chr3:183755809)
- 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 buttonMain function of each fusion partner protein. (from UniProt)
HgeneTgene
MSN

P26038

.
FUNCTION: Ezrin-radixin-moesin (ERM) family protein that connects the actin cytoskeleton to the plasma membrane and thereby regulates the structure and function of specific domains of the cell cortex. Tethers actin filaments by oscillating between a resting and an activated state providing transient interactions between moesin and the actin cytoskeleton (PubMed:10212266). Once phosphorylated on its C-terminal threonine, moesin is activated leading to interaction with F-actin and cytoskeletal rearrangement (PubMed:10212266). These rearrangements regulate many cellular processes, including cell shape determination, membrane transport, and signal transduction (PubMed:12387735, PubMed:15039356). The role of moesin is particularly important in immunity acting on both T and B-cells homeostasis and self-tolerance, regulating lymphocyte egress from lymphoid organs (PubMed:9298994, PubMed:9616160). Modulates phagolysosomal biogenesis in macrophages (By similarity). Participates also in immunologic synapse formation (PubMed:27405666). {ECO:0000250|UniProtKB:P26041, ECO:0000269|PubMed:10212266, ECO:0000269|PubMed:12387735, ECO:0000269|PubMed:15039356, ECO:0000269|PubMed:27405666, ECO:0000269|PubMed:9298994, ECO:0000269|PubMed:9616160}.FUNCTION: Might normally function as a transcriptional repressor. EWS-fusion-proteins (EFPS) may play a role in the tumorigenic process. They may disturb gene expression by mimicking, or interfering with the normal function of CTD-POLII within the transcription initiation complex. They may also contribute to an aberrant activation of the fusion protein target genes.

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, because of limited space for viewing, we only show the protein feature retention information belong to the 13 regional features. All retention annotation result can be downloaded at

download page

* Minus value of BPloci means that the break pointn is located before the CDS.
- Retained protein feature among the 13 regional features.
PartnerGeneHbpTbpENSTStrandBPexonTotalExonProtein feature loci*BPlociTotalLenProtein featureProtein feature note
TgeneHTR3DchrX:64887720chr3:183755809ENST0000038248948254_264220.0455.0Topological domainCytoplasmic
TgeneHTR3DchrX:64887720chr3:183755809ENST0000038248948286_306220.0455.0Topological domainExtracellular
TgeneHTR3DchrX:64887720chr3:183755809ENST0000038248948328_431220.0455.0Topological domainCytoplasmic
TgeneHTR3DchrX:64887720chr3:183755809ENST0000038248948453_454220.0455.0Topological domainExtracellular
TgeneHTR3DchrX:64887720chr3:183755809ENST0000042879848254_264172.0405.0Topological domainCytoplasmic
TgeneHTR3DchrX:64887720chr3:183755809ENST0000042879848286_306172.0405.0Topological domainExtracellular
TgeneHTR3DchrX:64887720chr3:183755809ENST0000042879848328_431172.0405.0Topological domainCytoplasmic
TgeneHTR3DchrX:64887720chr3:183755809ENST0000042879848453_454172.0405.0Topological domainExtracellular
TgeneHTR3DchrX:64887720chr3:183755809ENST0000045343504254_2641.0234.0Topological domainCytoplasmic
TgeneHTR3DchrX:64887720chr3:183755809ENST000004534350425_2321.0234.0Topological domainExtracellular
TgeneHTR3DchrX:64887720chr3:183755809ENST0000045343504286_3061.0234.0Topological domainExtracellular
TgeneHTR3DchrX:64887720chr3:183755809ENST0000045343504328_4311.0234.0Topological domainCytoplasmic
TgeneHTR3DchrX:64887720chr3:183755809ENST0000045343504453_4541.0234.0Topological domainExtracellular
TgeneHTR3DchrX:64887720chr3:183755809ENST0000038248948233_253220.0455.0TransmembraneHelical%3B Name%3D1
TgeneHTR3DchrX:64887720chr3:183755809ENST0000038248948265_285220.0455.0TransmembraneHelical%3B Name%3D2
TgeneHTR3DchrX:64887720chr3:183755809ENST0000038248948307_327220.0455.0TransmembraneHelical%3B Name%3D3
TgeneHTR3DchrX:64887720chr3:183755809ENST0000038248948432_452220.0455.0TransmembraneHelical%3B Name%3D4
TgeneHTR3DchrX:64887720chr3:183755809ENST0000042879848233_253172.0405.0TransmembraneHelical%3B Name%3D1
TgeneHTR3DchrX:64887720chr3:183755809ENST0000042879848265_285172.0405.0TransmembraneHelical%3B Name%3D2
TgeneHTR3DchrX:64887720chr3:183755809ENST0000042879848307_327172.0405.0TransmembraneHelical%3B Name%3D3
TgeneHTR3DchrX:64887720chr3:183755809ENST0000042879848432_452172.0405.0TransmembraneHelical%3B Name%3D4
TgeneHTR3DchrX:64887720chr3:183755809ENST0000045343504233_2531.0234.0TransmembraneHelical%3B Name%3D1
TgeneHTR3DchrX:64887720chr3:183755809ENST0000045343504265_2851.0234.0TransmembraneHelical%3B Name%3D2
TgeneHTR3DchrX:64887720chr3:183755809ENST0000045343504307_3271.0234.0TransmembraneHelical%3B Name%3D3
TgeneHTR3DchrX:64887720chr3:183755809ENST0000045343504432_4521.0234.0TransmembraneHelical%3B Name%3D4

- Not-retained protein feature among the 13 regional features.
PartnerGeneHbpTbpENSTStrandBPexonTotalExonProtein feature loci*BPlociTotalLenProtein featureProtein feature note
HgeneMSNchrX:64887720chr3:183755809ENST00000360270+1132_2954.0578.0DomainFERM
HgeneMSNchrX:64887720chr3:183755809ENST00000360270+113115_1204.0578.0Motif[IL]-x-C-x-x-[DE] motif
TgeneHTR3DchrX:64887720chr3:183755809ENST000003824894825_232220.0455.0Topological domainExtracellular
TgeneHTR3DchrX:64887720chr3:183755809ENST000004287984825_232172.0405.0Topological domainExtracellular


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Fusion Protein Structures

check button PDB and CIF files of the predicted fusion proteins
* Here we show the 3D structure of the fusion proteins using Mol*. AlphaFold produces a per-residue confidence score (pLDDT) between 0 and 100. Model confidence is shown from the pLDDT values per residue. pLDDT corresponds to the model’s prediction of its score on the local Distance Difference Test. It is a measure of local accuracy (from AlphfaFold website). To color code individual residues, we transformed individual PDB files into CIF format.
Fusion protein PDB link (fusion AA seq ID in FusionPDB)HgeneHchrHbpHstrandTgeneTchrTbpTstrandAA seqLen(AA seq)
PDB file >>>374_MSN_64887720_HTR3D_183755809_ranked_0.pdbMSN6488772064887720ENST00000453435HTR3Dchr3183755809+
MPKTVAIRRRCRPSPYVVNFLVPSGILIAIDALSFYLPLESGNCAPFKMTVLLGYSVFLLMMNDLLPATSTSSHASLVAPLALMQTPLPA
GVYFALCLSLMVGSLLETIFITHLLHVATTQPLPLPRWLHSLLLHCTGQGRCCPTAPQKGNKGPGLTPTHLPGVKEPEVSAGQMPGPGEA
238


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pLDDT score distribution

check button pLDDT score distribution of the predicted wild-type structures of two partner proteins from AlphaFold2
* AlphaFold produces a per-residue confidence score (pLDDT) between 0 and 100.
MSN_pLDDT.png
all structure
all structure
HTR3D_pLDDT.png
all structure
all structure

check button pLDDT score distribution of the predicted fusion protein structures from AlphaFold2
* AlphaFold produces a per-residue confidence score (pLDDT) between 0 and 100.
all structure


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Ramachandran Plot of Fusion Protein Structure


check button Ramachandran plot of the torsional angles - phi (φ)and psi (ψ) - of the residues (amino acids) contained in this fusion protein peptide.
Fusion AA seq ID in FusionPDB and their Ramachandran plots

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Fusion Protein-Protein Interaction


check button Go to ChiPPI (Chimeric Protein-Protein interactions) to see the chimeric PPI interaction in

ChiPPI page.


check button Protein-protein interactors with each fusion partner protein in wild-type from validated records (BIOGRID-3.4.160)
GenePPI interactors


check button Protein-protein interactors based on sequence similarity (STRING)
GeneSTRING network
MSN
HTR3D


check button - Retained interactions in fusion protein (protein functional feature from UniProt).
PartnerGeneHbpTbpENSTStrandBPexonTotalExonProtein feature loci*BPlociTotalLenStill interaction with


check button - Lost interactions due to fusion (protein functional feature from UniProt).
PartnerGeneHbpTbpENSTStrandBPexonTotalExonProtein feature loci*BPlociTotalLenInteraction lost with


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Related Drugs to MSN-HTR3D


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 MSN-HTR3D


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