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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:CHMP4B-ZNF341

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: CHMP4B-ZNF341
FusionPDB ID: 16562
FusionGDB2.0 ID: 16562
HgeneTgene
Gene symbol

CHMP4B

ZNF341

Gene ID

128866

84905

Gene namecharged multivesicular body protein 4Bzinc finger protein 341
SynonymsC20orf178|CHMP4A|CTPP3|CTRCT31|SNF7|SNF7-2|Shax1|VPS32B|Vps32-2|dJ553F4.4HIES3
Cytomap

20q11.22

20q11.22

Type of geneprotein-codingprotein-coding
Descriptioncharged multivesicular body protein 4bSNF7 homolog associated with Alix 1Snf7 homologue associated with Alix 1chromatin modifying protein 4Bchromatin-modifying protein 4bhSnf7-2hVps32-2vacuolar protein-sorting-associated protein 32-2zinc finger protein 341
Modification date2020031320200313
UniProtAcc

Q9H444

Main function of 5'-partner protein: FUNCTION: Probable core component of the endosomal sorting required for transport complex III (ESCRT-III) which is involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs. MVBs contain intraluminal vesicles (ILVs) that are generated by invagination and scission from the limiting membrane of the endosome and mostly are delivered to lysosomes enabling degradation of membrane proteins, such as stimulated growth factor receptors, lysosomal enzymes and lipids. The MVB pathway appears to require the sequential function of ESCRT-O, -I,-II and -III complexes. ESCRT-III proteins mostly dissociate from the invaginating membrane before the ILV is released (PubMed:12860994, PubMed:18209100). The ESCRT machinery also functions in topologically equivalent membrane fission events, such as the terminal stages of cytokinesis (PubMed:21310966). Together with SPAST, the ESCRT-III complex promotes nuclear envelope sealing and mitotic spindle disassembly during late anaphase (PubMed:26040712). Plays a role in the endosomal sorting pathway. ESCRT-III proteins are believed to mediate the necessary vesicle extrusion and/or membrane fission activities, possibly in conjunction with the AAA ATPase VPS4. When overexpressed, membrane-assembled circular arrays of CHMP4B filaments can promote or stabilize negative curvature and outward budding. CHMP4A/B/C are required for the exosomal release of SDCBP, CD63 and syndecan (PubMed:22660413). {ECO:0000269|PubMed:12860994, ECO:0000269|PubMed:18209100, ECO:0000269|PubMed:21310966, ECO:0000269|PubMed:22660413, ECO:0000269|PubMed:26040712}.; FUNCTION: (Microbial infection) The ESCRT machinery also functions in topologically equivalent membrane fission events, such as the budding of enveloped viruses (HIV-1 and other lentiviruses). Via its interaction with PDCD6IP involved in HIV-1 p6- and p9-dependent virus release. {ECO:0000269|PubMed:14505569, ECO:0000269|PubMed:14505570, ECO:0000269|PubMed:14519844, ECO:0000269|PubMed:22422861}.
.
Ensembl transtripts involved in fusion geneENST idsENST00000217402, ENST00000342427, 
ENST00000375200, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score13 X 7 X 7=6375 X 6 X 2=60
# samples 196
** MAII scorelog2(19/637*10)=-1.74529395392535
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(6/60*10)=0
Fusion gene context

PubMed: CHMP4B [Title/Abstract] AND ZNF341 [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: CHMP4B [Title/Abstract] AND ZNF341 [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)CHMP4B(32440009)-ZNF341(32328708), # samples:2
Anticipated loss of major functional domain due to fusion event.CHMP4B-ZNF341 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.
CHMP4B-ZNF341 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
HgeneCHMP4B

GO:0039702

viral budding via host ESCRT complex

24878737

HgeneCHMP4B

GO:0051258

protein polymerization

18209100



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/chr20:32440009/chr20:32328708)
- 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 CHMP4B (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 ZNF341 (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)
ENST00000217402CHMP4Bchr2032440009+ENST00000375200ZNF341chr2032328708+406177516533081047
ENST00000217402CHMP4Bchr2032440009+ENST00000342427ZNF341chr2032328708+404077516532871040

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
ENST00000217402ENST00000375200CHMP4Bchr2032440009+ZNF341chr2032328708+0.0027368010.9972632
ENST00000217402ENST00000342427CHMP4Bchr2032440009+ZNF341chr2032328708+0.0028552170.99714476

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 CHMP4B-ZNF341

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
CHMP4Bchr2032440009ZNF341chr2032328708775203LPNVPSIALPSKPGMDNQTVLAVQSL

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Potential FusionNeoAntigen Information of CHMP4B-ZNF341 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.
CHMP4B-ZNF341_32440009_32328708.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)
CHMP4B-ZNF341chr2032440009chr2032328708775HLA-B35:03KPGMDNQTVL0.69060.80541121
CHMP4B-ZNF341chr2032440009chr2032328708775HLA-B35:04KPGMDNQTVL0.4660.88641121
CHMP4B-ZNF341chr2032440009chr2032328708775HLA-B35:02KPGMDNQTVL0.4660.88641121
CHMP4B-ZNF341chr2032440009chr2032328708775HLA-C03:19IALPSKPGM0.99840.9777615
CHMP4B-ZNF341chr2032440009chr2032328708775HLA-C03:08IALPSKPGM0.99790.8521615
CHMP4B-ZNF341chr2032440009chr2032328708775HLA-C03:07IALPSKPGM0.99750.9711615
CHMP4B-ZNF341chr2032440009chr2032328708775HLA-C15:04IALPSKPGM0.99750.8454615
CHMP4B-ZNF341chr2032440009chr2032328708775HLA-C15:06IALPSKPGM0.98980.9098615
CHMP4B-ZNF341chr2032440009chr2032328708775HLA-C04:06IALPSKPGM0.96960.9552615
CHMP4B-ZNF341chr2032440009chr2032328708775HLA-C12:12IALPSKPGM0.95960.9463615
CHMP4B-ZNF341chr2032440009chr2032328708775HLA-C06:03IALPSKPGM0.86740.9958615
CHMP4B-ZNF341chr2032440009chr2032328708775HLA-C08:13IALPSKPGM0.85520.9882615
CHMP4B-ZNF341chr2032440009chr2032328708775HLA-C08:04IALPSKPGM0.85520.9882615
CHMP4B-ZNF341chr2032440009chr2032328708775HLA-C12:04IALPSKPGM0.84930.9963615
CHMP4B-ZNF341chr2032440009chr2032328708775HLA-C03:14IALPSKPGM0.80480.9809615
CHMP4B-ZNF341chr2032440009chr2032328708775HLA-B42:02KPGMDNQTVL0.66530.53881121
CHMP4B-ZNF341chr2032440009chr2032328708775HLA-B42:01KPGMDNQTVL0.56860.52951121
CHMP4B-ZNF341chr2032440009chr2032328708775HLA-B39:10KPGMDNQTVL0.51010.8581121
CHMP4B-ZNF341chr2032440009chr2032328708775HLA-B35:12KPGMDNQTVL0.4660.88641121
CHMP4B-ZNF341chr2032440009chr2032328708775HLA-C01:02ALPSKPGM0.94010.9653715
CHMP4B-ZNF341chr2032440009chr2032328708775HLA-C03:03IALPSKPGM0.99870.9738615
CHMP4B-ZNF341chr2032440009chr2032328708775HLA-C03:04IALPSKPGM0.99870.9738615
CHMP4B-ZNF341chr2032440009chr2032328708775HLA-C03:67IALPSKPGM0.99840.9578615
CHMP4B-ZNF341chr2032440009chr2032328708775HLA-C03:02IALPSKPGM0.99760.9585615
CHMP4B-ZNF341chr2032440009chr2032328708775HLA-C15:09IALPSKPGM0.99750.8454615
CHMP4B-ZNF341chr2032440009chr2032328708775HLA-C03:17IALPSKPGM0.99720.9611615
CHMP4B-ZNF341chr2032440009chr2032328708775HLA-C03:05IALPSKPGM0.99710.9087615
CHMP4B-ZNF341chr2032440009chr2032328708775HLA-C12:03IALPSKPGM0.96740.9882615
CHMP4B-ZNF341chr2032440009chr2032328708775HLA-C03:06IALPSKPGM0.95150.9735615
CHMP4B-ZNF341chr2032440009chr2032328708775HLA-C16:04IALPSKPGM0.9450.986615
CHMP4B-ZNF341chr2032440009chr2032328708775HLA-C12:02IALPSKPGM0.91060.983615
CHMP4B-ZNF341chr2032440009chr2032328708775HLA-B35:13IALPSKPGM0.88350.8813615
CHMP4B-ZNF341chr2032440009chr2032328708775HLA-C16:01IALPSKPGM0.85480.9827615
CHMP4B-ZNF341chr2032440009chr2032328708775HLA-C16:02IALPSKPGM0.75050.9926615
CHMP4B-ZNF341chr2032440009chr2032328708775HLA-B07:13IALPSKPGM0.73050.7552615
CHMP4B-ZNF341chr2032440009chr2032328708775HLA-B51:05KPGMDNQTV0.42620.55271120
CHMP4B-ZNF341chr2032440009chr2032328708775HLA-B59:01KPGMDNQTV0.3440.64611120
CHMP4B-ZNF341chr2032440009chr2032328708775HLA-C17:01IALPSKPGM0.29640.9555615
CHMP4B-ZNF341chr2032440009chr2032328708775HLA-B35:13KPGMDNQTVL0.62660.81331121
CHMP4B-ZNF341chr2032440009chr2032328708775HLA-B67:01KPGMDNQTVL0.49570.69971121
CHMP4B-ZNF341chr2032440009chr2032328708775HLA-B35:09KPGMDNQTVL0.4660.88641121

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Potential FusionNeoAntigen Information of CHMP4B-ZNF341 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 CHMP4B-ZNF341

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
3589IALPSKPGMDNQTVCHMP4BZNF341chr2032440009chr2032328708775

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of CHMP4B-ZNF341

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-B14:023BVN3589IALPSKPGMDNQTV-6.11479-7.15009
HLA-B14:023BVN3589IALPSKPGMDNQTV-4.76706-4.88046
HLA-B52:013W393589IALPSKPGMDNQTV-6.87405-6.98745
HLA-B52:013W393589IALPSKPGMDNQTV-5.3619-6.3972
HLA-A11:014UQ23589IALPSKPGMDNQTV-9.79836-9.91176
HLA-A24:025HGA3589IALPSKPGMDNQTV-8.83847-8.95187
HLA-A24:025HGA3589IALPSKPGMDNQTV-8.05027-9.08557
HLA-B44:053DX83589IALPSKPGMDNQTV-7.51915-7.63255
HLA-B44:053DX83589IALPSKPGMDNQTV-4.45384-5.48914
HLA-A02:016TDR3589IALPSKPGMDNQTV-2.8902-3.9255

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Vaccine Design for the FusionNeoAntigens of CHMP4B-ZNF341

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
CHMP4B-ZNF341chr2032440009chr20323287081120KPGMDNQTVAACCCGGAATGGACAATCAGACCGTTC
CHMP4B-ZNF341chr2032440009chr20323287081121KPGMDNQTVLAACCCGGAATGGACAATCAGACCGTTCTGG
CHMP4B-ZNF341chr2032440009chr2032328708615IALPSKPGMTAGCCCTACCATCAAAACCCGGAATGG
CHMP4B-ZNF341chr2032440009chr2032328708715ALPSKPGMCCCTACCATCAAAACCCGGAATGG

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 CHMP4B-ZNF341

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
BRCACHMP4B-ZNF341chr2032440009ENST00000217402chr2032328708ENST00000342427TCGA-B6-A3ZX-01A

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Potential target of CAR-T therapy development for CHMP4B-ZNF341

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 CHMP4B-ZNF341

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 CHMP4B-ZNF341

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