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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:MARCH3-HTR4

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: MARCH3-HTR4
FusionPDB ID: 51686
FusionGDB2.0 ID: 51686
HgeneTgene
Gene symbol

MARCH3

HTR4

Gene ID

115123

3360

Gene namemembrane associated ring-CH-type finger 35-hydroxytryptamine receptor 4
SynonymsMARCH-III|MARCH3|RNF1735-HT4|5-HT4R
Cytomap

5q23.2

5q32

Type of geneprotein-codingprotein-coding
DescriptionE3 ubiquitin-protein ligase MARCH3RING finger protein 173RING-type E3 ubiquitin transferase MARCH3membrane associated ring finger 3membrane-associated RING-CH protein IIImembrane-associated ring finger (C3HC4) 3, E3 ubiquitin protein ligase5-hydroxytryptamine receptor 45-hydroxytryptamine (serotonin) receptor 4, G protein-coupled5-hydroxytryptamine receptor 4 transcript variant b25-hydroxytryptamine receptor 4 transcript variant b3cardiac 5-HT4 receptor
Modification date2020031320200313
UniProtAcc..
Ensembl transtripts involved in fusion geneENST idsENST00000308660, ENST00000502289, 
ENST00000515241, 
ENST00000519495, 
ENST00000520086, ENST00000314512, 
ENST00000354217, ENST00000360693, 
ENST00000362016, ENST00000377888, 
ENST00000517929, ENST00000520514, 
ENST00000521530, ENST00000521735, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score5 X 4 X 4=804 X 4 X 3=48
# samples 54
** MAII scorelog2(5/80*10)=-0.678071905112638
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(4/48*10)=-0.263034405833794
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: MARCH3 [Title/Abstract] AND HTR4 [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: MARCH3 [Title/Abstract] AND HTR4 [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)MARCH3(126250622)-HTR4(147929825), # samples:1
Anticipated loss of major functional domain due to fusion event.MARCH3-HTR4 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.
MARCH3-HTR4 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.
MARCH3-HTR4 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/chr5:126250622/chr5:147929825)
- 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 MARCH3 (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 HTR4 (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)
ENST00000308660MARCH3chr5126250622-ENST00000521735HTR4chr5147929825-21229089452018357
ENST00000502289MARCH3chr5126250622-ENST00000521530HTR4chr5147929825-20557643571901514
ENST00000502289MARCH3chr5126250622-ENST00000354217HTR4chr5147929825-20557643571901514
ENST00000502289MARCH3chr5126250622-ENST00000314512HTR4chr5147929825-21317643571874505
ENST00000502289MARCH3chr5126250622-ENST00000517929HTR4chr5147929825-19247643571820487
ENST00000502289MARCH3chr5126250622-ENST00000520514HTR4chr5147929825-19747643571973538
ENST00000502289MARCH3chr5126250622-ENST00000377888HTR4chr5147929825-35617643571904515
ENST00000502289MARCH3chr5126250622-ENST00000360693HTR4chr5147929825-36817643572024555
ENST00000502289MARCH3chr5126250622-ENST00000362016HTR4chr5147929825-35927643571946529

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
ENST00000308660ENST00000521735MARCH3chr5126250622-HTR4chr5147929825-0.0082867370.9917133
ENST00000502289ENST00000521530MARCH3chr5126250622-HTR4chr5147929825-0.0158734410.9841265
ENST00000502289ENST00000354217MARCH3chr5126250622-HTR4chr5147929825-0.0158734410.9841265
ENST00000502289ENST00000314512MARCH3chr5126250622-HTR4chr5147929825-0.0206599050.9793401
ENST00000502289ENST00000517929MARCH3chr5126250622-HTR4chr5147929825-0.015260950.98473907
ENST00000502289ENST00000520514MARCH3chr5126250622-HTR4chr5147929825-0.0118833620.9881166
ENST00000502289ENST00000377888MARCH3chr5126250622-HTR4chr5147929825-0.0104995880.98950034
ENST00000502289ENST00000360693MARCH3chr5126250622-HTR4chr5147929825-0.0116579510.9883421
ENST00000502289ENST00000362016MARCH3chr5126250622-HTR4chr5147929825-0.0111587050.98884135

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 MARCH3-HTR4

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
MARCH3chr5126250622HTR4chr5147929825764136RFAVERKPRPLVDSEEGFGSVEKVVL

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Potential FusionNeoAntigen Information of MARCH3-HTR4 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 MARCH3-HTR4 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.
MARCH3-HTR4_126250622_147929825.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)
MARCH3-HTR4chr5126250622chr5147929825764DRB1-1148RFAVERKPRPLVDSE015
MARCH3-HTR4chr5126250622chr5147929825764DRB1-1155RFAVERKPRPLVDSE015
MARCH3-HTR4chr5126250622chr5147929825764DRB1-1308RFAVERKPRPLVDSE015
MARCH3-HTR4chr5126250622chr5147929825764DRB1-1343RFAVERKPRPLVDSE015
MARCH3-HTR4chr5126250622chr5147929825764DRB1-1354RFAVERKPRPLVDSE015
MARCH3-HTR4chr5126250622chr5147929825764DRB1-1370RFAVERKPRPLVDSE015
MARCH3-HTR4chr5126250622chr5147929825764DRB1-1372RFAVERKPRPLVDSE015
MARCH3-HTR4chr5126250622chr5147929825764DRB1-1375RFAVERKPRPLVDSE015
MARCH3-HTR4chr5126250622chr5147929825764DRB1-1376RFAVERKPRPLVDSE015
MARCH3-HTR4chr5126250622chr5147929825764DRB1-1384RFAVERKPRPLVDSE015
MARCH3-HTR4chr5126250622chr5147929825764DRB1-1416RFAVERKPRPLVDSE015

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Fusion breakpoint peptide structures of MARCH3-HTR4

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 MARCH3-HTR4

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 MARCH3-HTR4

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
MARCH3-HTR4chr5126250622chr5147929825015RFAVERKPRPLVDSECAGGTTTGCAGTCGAGCGCAAACCCAGGCCGTTAGTGGATTCTGA

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Information of the samples that have these potential fusion neoantigens of MARCH3-HTR4

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 MARCH3-HTR4

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
TgeneHTR4chr5:126250622chr5:147929825ENST0000031451218138_1580421.3333333333333TransmembraneHelical%3B Name%3D4
TgeneHTR4chr5:126250622chr5:147929825ENST0000031451218193_2130421.3333333333333TransmembraneHelical%3B Name%3D5
TgeneHTR4chr5:126250622chr5:147929825ENST000003145121820_400421.3333333333333TransmembraneHelical%3B Name%3D1
TgeneHTR4chr5:126250622chr5:147929825ENST0000031451218261_2810421.3333333333333TransmembraneHelical%3B Name%3D6
TgeneHTR4chr5:126250622chr5:147929825ENST0000031451218295_3150421.3333333333333TransmembraneHelical%3B Name%3D7
TgeneHTR4chr5:126250622chr5:147929825ENST000003145121859_790421.3333333333333TransmembraneHelical%3B Name%3D2
TgeneHTR4chr5:126250622chr5:147929825ENST000003145121894_1160421.3333333333333TransmembraneHelical%3B Name%3D3
TgeneHTR4chr5:126250622chr5:147929825ENST0000035421717138_1580388.0TransmembraneHelical%3B Name%3D4
TgeneHTR4chr5:126250622chr5:147929825ENST0000035421717193_2130388.0TransmembraneHelical%3B Name%3D5
TgeneHTR4chr5:126250622chr5:147929825ENST000003542171720_400388.0TransmembraneHelical%3B Name%3D1
TgeneHTR4chr5:126250622chr5:147929825ENST0000035421717261_2810388.0TransmembraneHelical%3B Name%3D6
TgeneHTR4chr5:126250622chr5:147929825ENST0000035421717295_3150388.0TransmembraneHelical%3B Name%3D7
TgeneHTR4chr5:126250622chr5:147929825ENST000003542171759_790388.0TransmembraneHelical%3B Name%3D2
TgeneHTR4chr5:126250622chr5:147929825ENST000003542171794_1160388.0TransmembraneHelical%3B Name%3D3
TgeneHTR4chr5:126250622chr5:147929825ENST0000036069318138_1580429.0TransmembraneHelical%3B Name%3D4
TgeneHTR4chr5:126250622chr5:147929825ENST0000036069318193_2130429.0TransmembraneHelical%3B Name%3D5
TgeneHTR4chr5:126250622chr5:147929825ENST000003606931820_400429.0TransmembraneHelical%3B Name%3D1
TgeneHTR4chr5:126250622chr5:147929825ENST0000036069318261_2810429.0TransmembraneHelical%3B Name%3D6
TgeneHTR4chr5:126250622chr5:147929825ENST0000036069318295_3150429.0TransmembraneHelical%3B Name%3D7
TgeneHTR4chr5:126250622chr5:147929825ENST000003606931859_790429.0TransmembraneHelical%3B Name%3D2
TgeneHTR4chr5:126250622chr5:147929825ENST000003606931894_1160429.0TransmembraneHelical%3B Name%3D3
TgeneHTR4chr5:126250622chr5:147929825ENST0000036201618138_1580403.0TransmembraneHelical%3B Name%3D4
TgeneHTR4chr5:126250622chr5:147929825ENST0000036201618193_2130403.0TransmembraneHelical%3B Name%3D5
TgeneHTR4chr5:126250622chr5:147929825ENST000003620161820_400403.0TransmembraneHelical%3B Name%3D1
TgeneHTR4chr5:126250622chr5:147929825ENST0000036201618261_2810403.0TransmembraneHelical%3B Name%3D6
TgeneHTR4chr5:126250622chr5:147929825ENST0000036201618295_3150403.0TransmembraneHelical%3B Name%3D7
TgeneHTR4chr5:126250622chr5:147929825ENST000003620161859_790403.0TransmembraneHelical%3B Name%3D2
TgeneHTR4chr5:126250622chr5:147929825ENST000003620161894_1160403.0TransmembraneHelical%3B Name%3D3
TgeneHTR4chr5:126250622chr5:147929825ENST0000037788817138_1580389.0TransmembraneHelical%3B Name%3D4
TgeneHTR4chr5:126250622chr5:147929825ENST0000037788817193_2130389.0TransmembraneHelical%3B Name%3D5
TgeneHTR4chr5:126250622chr5:147929825ENST000003778881720_400389.0TransmembraneHelical%3B Name%3D1
TgeneHTR4chr5:126250622chr5:147929825ENST0000037788817261_2810389.0TransmembraneHelical%3B Name%3D6
TgeneHTR4chr5:126250622chr5:147929825ENST0000037788817295_3150389.0TransmembraneHelical%3B Name%3D7
TgeneHTR4chr5:126250622chr5:147929825ENST000003778881759_790389.0TransmembraneHelical%3B Name%3D2
TgeneHTR4chr5:126250622chr5:147929825ENST000003778881794_1160389.0TransmembraneHelical%3B Name%3D3
TgeneHTR4chr5:126250622chr5:147929825ENST0000051792906138_1580361.0TransmembraneHelical%3B Name%3D4
TgeneHTR4chr5:126250622chr5:147929825ENST0000051792906193_2130361.0TransmembraneHelical%3B Name%3D5
TgeneHTR4chr5:126250622chr5:147929825ENST000005179290620_400361.0TransmembraneHelical%3B Name%3D1
TgeneHTR4chr5:126250622chr5:147929825ENST0000051792906261_2810361.0TransmembraneHelical%3B Name%3D6
TgeneHTR4chr5:126250622chr5:147929825ENST0000051792906295_3150361.0TransmembraneHelical%3B Name%3D7
TgeneHTR4chr5:126250622chr5:147929825ENST000005179290659_790361.0TransmembraneHelical%3B Name%3D2
TgeneHTR4chr5:126250622chr5:147929825ENST000005179290694_1160361.0TransmembraneHelical%3B Name%3D3
TgeneHTR4chr5:126250622chr5:147929825ENST0000052051406138_1580412.0TransmembraneHelical%3B Name%3D4
TgeneHTR4chr5:126250622chr5:147929825ENST0000052051406193_2130412.0TransmembraneHelical%3B Name%3D5
TgeneHTR4chr5:126250622chr5:147929825ENST000005205140620_400412.0TransmembraneHelical%3B Name%3D1
TgeneHTR4chr5:126250622chr5:147929825ENST0000052051406261_2810412.0TransmembraneHelical%3B Name%3D6
TgeneHTR4chr5:126250622chr5:147929825ENST0000052051406295_3150412.0TransmembraneHelical%3B Name%3D7
TgeneHTR4chr5:126250622chr5:147929825ENST000005205140659_790412.0TransmembraneHelical%3B Name%3D2
TgeneHTR4chr5:126250622chr5:147929825ENST000005205140694_1160412.0TransmembraneHelical%3B Name%3D3
TgeneHTR4chr5:126250622chr5:147929825ENST0000052153006138_1580388.0TransmembraneHelical%3B Name%3D4
TgeneHTR4chr5:126250622chr5:147929825ENST0000052153006193_2130388.0TransmembraneHelical%3B Name%3D5
TgeneHTR4chr5:126250622chr5:147929825ENST000005215300620_400388.0TransmembraneHelical%3B Name%3D1
TgeneHTR4chr5:126250622chr5:147929825ENST0000052153006261_2810388.0TransmembraneHelical%3B Name%3D6
TgeneHTR4chr5:126250622chr5:147929825ENST0000052153006295_3150388.0TransmembraneHelical%3B Name%3D7
TgeneHTR4chr5:126250622chr5:147929825ENST000005215300659_790388.0TransmembraneHelical%3B Name%3D2
TgeneHTR4chr5:126250622chr5:147929825ENST000005215300694_1160388.0TransmembraneHelical%3B Name%3D3
TgeneHTR4chr5:126250622chr5:147929825ENST0000052173507138_1580382.3333333333333TransmembraneHelical%3B Name%3D4
TgeneHTR4chr5:126250622chr5:147929825ENST0000052173507193_2130382.3333333333333TransmembraneHelical%3B Name%3D5
TgeneHTR4chr5:126250622chr5:147929825ENST000005217350720_400382.3333333333333TransmembraneHelical%3B Name%3D1
TgeneHTR4chr5:126250622chr5:147929825ENST0000052173507261_2810382.3333333333333TransmembraneHelical%3B Name%3D6
TgeneHTR4chr5:126250622chr5:147929825ENST0000052173507295_3150382.3333333333333TransmembraneHelical%3B Name%3D7
TgeneHTR4chr5:126250622chr5:147929825ENST000005217350759_790382.3333333333333TransmembraneHelical%3B Name%3D2
TgeneHTR4chr5:126250622chr5:147929825ENST000005217350794_1160382.3333333333333TransmembraneHelical%3B Name%3D3

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 MARCH3-HTR4

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 MARCH3-HTR4

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