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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:ZMYM4-ACACA

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: ZMYM4-ACACA
FusionPDB ID: 101356
FusionGDB2.0 ID: 101356
HgeneTgene
Gene symbol

ZMYM4

ACACA

Gene ID

9202

31

Gene namezinc finger MYM-type containing 4acetyl-CoA carboxylase alpha
SynonymsCDIR|MYM|ZNF198L3|ZNF262ACAC|ACACAD|ACC|ACC1|ACCA
Cytomap

1p34.3

17q12

Type of geneprotein-codingprotein-coding
Descriptionzinc finger MYM-type protein 4cell death inhibiting RNAzinc finger protein 262zinc finger, MYM-type 4acetyl-CoA carboxylase 1ACC-alphaacetyl-Coenzyme A carboxylase alpha
Modification date2020031320200313
UniProtAcc.

Q13085

Main function of 5'-partner protein: FUNCTION: Cytosolic enzyme that catalyzes the carboxylation of acetyl-CoA to malonyl-CoA, the first and rate-limiting step of de novo fatty acid biosynthesis (PubMed:20952656, PubMed:20457939, PubMed:29899443). This is a 2 steps reaction starting with the ATP-dependent carboxylation of the biotin carried by the biotin carboxyl carrier (BCC) domain followed by the transfer of the carboxyl group from carboxylated biotin to acetyl-CoA (PubMed:20952656, PubMed:20457939, PubMed:29899443). {ECO:0000269|PubMed:20457939, ECO:0000269|PubMed:20952656, ECO:0000269|PubMed:29899443}.
Ensembl transtripts involved in fusion geneENST idsENST00000314607, ENST00000373297, 
ENST00000482131, 
ENST00000361253, 
ENST00000416895, ENST00000588142, 
ENST00000589665, ENST00000335166, 
ENST00000353139, ENST00000360679, 
ENST00000394406, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score14 X 8 X 10=112020 X 22 X 7=3080
# samples 1521
** MAII scorelog2(15/1120*10)=-2.90046432644909
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(21/3080*10)=-3.87446911791614
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: ZMYM4 [Title/Abstract] AND ACACA [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: ZMYM4 [Title/Abstract] AND ACACA [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)ZMYM4(35734686)-ACACA(35538297), # samples:1
Anticipated loss of major functional domain due to fusion event.ZMYM4-ACACA 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.
ZMYM4-ACACA 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.
ZMYM4-ACACA 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.
ZMYM4-ACACA 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


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/chr1:35734686/chr17:35538297)
- 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 ZMYM4 (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 ACACA (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)
ENST00000373297ZMYM4chr135734686+ENST00000353139ACACAchr1735538297-4823119802494804
ENST00000373297ZMYM4chr135734686+ENST00000360679ACACAchr1735538297-4817119802494804
ENST00000373297ZMYM4chr135734686+ENST00000394406ACACAchr1735538297-4817119802494804
ENST00000373297ZMYM4chr135734686+ENST00000335166ACACAchr1735538297-2994119802494804
ENST00000314607ZMYM4chr135734686+ENST00000353139ACACAchr1735538297-4823119802494804
ENST00000314607ZMYM4chr135734686+ENST00000360679ACACAchr1735538297-4817119802494804
ENST00000314607ZMYM4chr135734686+ENST00000394406ACACAchr1735538297-4817119802494804
ENST00000314607ZMYM4chr135734686+ENST00000335166ACACAchr1735538297-2994119802494804

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
ENST00000373297ENST00000353139ZMYM4chr135734686+ACACAchr1735538297-0.0020218890.99797815
ENST00000373297ENST00000360679ZMYM4chr135734686+ACACAchr1735538297-0.0020363210.99796367
ENST00000373297ENST00000394406ZMYM4chr135734686+ACACAchr1735538297-0.0020363210.99796367
ENST00000373297ENST00000335166ZMYM4chr135734686+ACACAchr1735538297-0.0024062810.9975937
ENST00000314607ENST00000353139ZMYM4chr135734686+ACACAchr1735538297-0.0020218890.99797815
ENST00000314607ENST00000360679ZMYM4chr135734686+ACACAchr1735538297-0.0020363210.99796367
ENST00000314607ENST00000394406ZMYM4chr135734686+ACACAchr1735538297-0.0020363210.99796367
ENST00000314607ENST00000335166ZMYM4chr135734686+ACACAchr1735538297-0.0024062810.9975937

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 ZMYM4-ACACA

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
ZMYM4chr135734686ACACAchr173553829711913MAEREVESGPRKRIMFQAYGDKQGPL

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Potential FusionNeoAntigen Information of ZMYM4-ACACA 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.
ZMYM4-ACACA_35734686_35538297.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)
ZMYM4-ACACAchr135734686chr1735538297119HLA-B27:04KRIMFQAY0.99980.7851119
ZMYM4-ACACAchr135734686chr1735538297119HLA-B44:03VESGPRKRI0.85730.896514
ZMYM4-ACACAchr135734686chr1735538297119HLA-B15:03RKRIMFQAY0.21590.8981019
ZMYM4-ACACAchr135734686chr1735538297119HLA-B44:03VESGPRKRIMF0.98810.811516
ZMYM4-ACACAchr135734686chr1735538297119HLA-C07:46KRIMFQAY0.99710.90971119
ZMYM4-ACACAchr135734686chr1735538297119HLA-B15:07RKRIMFQAY0.55880.87441019
ZMYM4-ACACAchr135734686chr1735538297119HLA-C01:30SGPRKRIMF0.14870.971716
ZMYM4-ACACAchr135734686chr1735538297119HLA-C01:17SGPRKRIMF0.07650.9742716
ZMYM4-ACACAchr135734686chr1735538297119HLA-B15:68KRIMFQAY0.81020.72511119
ZMYM4-ACACAchr135734686chr1735538297119HLA-B44:26VESGPRKRI0.85730.896514
ZMYM4-ACACAchr135734686chr1735538297119HLA-B44:13VESGPRKRI0.85730.896514
ZMYM4-ACACAchr135734686chr1735538297119HLA-B44:07VESGPRKRI0.85730.896514
ZMYM4-ACACAchr135734686chr1735538297119HLA-B15:35RKRIMFQAY0.62780.97111019
ZMYM4-ACACAchr135734686chr1735538297119HLA-B15:53RKRIMFQAY0.23140.96351019
ZMYM4-ACACAchr135734686chr1735538297119HLA-B48:02RKRIMFQAY0.18020.96381019
ZMYM4-ACACAchr135734686chr1735538297119HLA-B15:54RKRIMFQAY0.12450.95591019
ZMYM4-ACACAchr135734686chr1735538297119HLA-B15:68RKRIMFQAY0.10020.80781019
ZMYM4-ACACAchr135734686chr1735538297119HLA-C01:02SGPRKRIMF0.05470.9745716
ZMYM4-ACACAchr135734686chr1735538297119HLA-B07:09GPRKRIMFQAY0.99550.5503819
ZMYM4-ACACAchr135734686chr1735538297119HLA-B44:13VESGPRKRIMF0.98810.811516
ZMYM4-ACACAchr135734686chr1735538297119HLA-B44:07VESGPRKRIMF0.98810.811516
ZMYM4-ACACAchr135734686chr1735538297119HLA-B44:26VESGPRKRIMF0.98810.811516

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Potential FusionNeoAntigen Information of ZMYM4-ACACA 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.
ZMYM4-ACACA_35734686_35538297.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)
ZMYM4-ACACAchr135734686chr1735538297119DRB1-1502KRIMFQAYGDKQGPL1126
ZMYM4-ACACAchr135734686chr1735538297119DRB1-1502RKRIMFQAYGDKQGP1025
ZMYM4-ACACAchr135734686chr1735538297119DRB1-1508KRIMFQAYGDKQGPL1126
ZMYM4-ACACAchr135734686chr1735538297119DRB1-1508RKRIMFQAYGDKQGP1025
ZMYM4-ACACAchr135734686chr1735538297119DRB1-1511KRIMFQAYGDKQGPL1126
ZMYM4-ACACAchr135734686chr1735538297119DRB1-1514KRIMFQAYGDKQGPL1126
ZMYM4-ACACAchr135734686chr1735538297119DRB1-1514RKRIMFQAYGDKQGP1025
ZMYM4-ACACAchr135734686chr1735538297119DRB1-1515KRIMFQAYGDKQGPL1126
ZMYM4-ACACAchr135734686chr1735538297119DRB1-1519KRIMFQAYGDKQGPL1126
ZMYM4-ACACAchr135734686chr1735538297119DRB1-1519RKRIMFQAYGDKQGP1025
ZMYM4-ACACAchr135734686chr1735538297119DRB1-1526KRIMFQAYGDKQGPL1126
ZMYM4-ACACAchr135734686chr1735538297119DRB1-1526RKRIMFQAYGDKQGP1025
ZMYM4-ACACAchr135734686chr1735538297119DRB1-1530KRIMFQAYGDKQGPL1126
ZMYM4-ACACAchr135734686chr1735538297119DRB1-1531KRIMFQAYGDKQGPL1126
ZMYM4-ACACAchr135734686chr1735538297119DRB1-1538KRIMFQAYGDKQGPL1126
ZMYM4-ACACAchr135734686chr1735538297119DRB1-1538RKRIMFQAYGDKQGP1025
ZMYM4-ACACAchr135734686chr1735538297119DRB1-1539KRIMFQAYGDKQGPL1126
ZMYM4-ACACAchr135734686chr1735538297119DRB1-1539RKRIMFQAYGDKQGP1025
ZMYM4-ACACAchr135734686chr1735538297119DRB1-1544KRIMFQAYGDKQGPL1126
ZMYM4-ACACAchr135734686chr1735538297119DRB1-1544RKRIMFQAYGDKQGP1025
ZMYM4-ACACAchr135734686chr1735538297119DRB1-1547KRIMFQAYGDKQGPL1126
ZMYM4-ACACAchr135734686chr1735538297119DRB1-1547RKRIMFQAYGDKQGP1025

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Fusion breakpoint peptide structures of ZMYM4-ACACA

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
2127ESGPRKRIMFQAYGZMYM4ACACAchr135734686chr1735538297119

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of ZMYM4-ACACA

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-B14:023BVN2127ESGPRKRIMFQAYG-6.15238-6.26578
HLA-B14:023BVN2127ESGPRKRIMFQAYG-5.35203-6.38733
HLA-B52:013W392127ESGPRKRIMFQAYG-5.804-6.8393
HLA-B52:013W392127ESGPRKRIMFQAYG-5.45277-5.56617
HLA-A11:014UQ22127ESGPRKRIMFQAYG-8.28119-9.31649
HLA-A24:025HGA2127ESGPRKRIMFQAYG-9.93626-10.0497
HLA-A24:025HGA2127ESGPRKRIMFQAYG-5.67154-6.70684
HLA-B27:056PYJ2127ESGPRKRIMFQAYG-4.30966-5.34496
HLA-B44:053DX82127ESGPRKRIMFQAYG-7.17842-7.29182
HLA-B44:053DX82127ESGPRKRIMFQAYG-4.14208-5.17738
HLA-A02:016TDR2127ESGPRKRIMFQAYG-5.17192-5.28532

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Vaccine Design for the FusionNeoAntigens of ZMYM4-ACACA

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
ZMYM4-ACACAchr135734686chr17355382971019RKRIMFQAYCGAAAGAGGATCATGTTTCAGGCATAT
ZMYM4-ACACAchr135734686chr17355382971119KRIMFQAYAAGAGGATCATGTTTCAGGCATAT
ZMYM4-ACACAchr135734686chr1735538297514VESGPRKRIGTGGAGTCCGGCCCCCGAAAGAGGATC
ZMYM4-ACACAchr135734686chr1735538297516VESGPRKRIMFGTGGAGTCCGGCCCCCGAAAGAGGATCATGTTT
ZMYM4-ACACAchr135734686chr1735538297716SGPRKRIMFTCCGGCCCCCGAAAGAGGATCATGTTT
ZMYM4-ACACAchr135734686chr1735538297819GPRKRIMFQAYGGCCCCCGAAAGAGGATCATGTTTCAGGCATAT

check button mRNA and peptide sequences of FusionNeoAntigens that have potential interaction with HLA-IIs.
Fusion geneHchrHbpTchrTbpStart in +/-13AAEnd in +/-13AAFusionNeoAntigen peptideFusionNEoAntigen RNA sequence
ZMYM4-ACACAchr135734686chr17355382971025RKRIMFQAYGDKQGPCGAAAGAGGATCATGTTTCAGGCATATGGAGACAAACAGGGACCA
ZMYM4-ACACAchr135734686chr17355382971126KRIMFQAYGDKQGPLAAGAGGATCATGTTTCAGGCATATGGAGACAAACAGGGACCACTG

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Information of the samples that have these potential fusion neoantigens of ZMYM4-ACACA

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
STADZMYM4-ACACAchr135734686ENST00000314607chr1735538297ENST00000335166TCGA-CG-5721-01A

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Potential target of CAR-T therapy development for ZMYM4-ACACA

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 ZMYM4-ACACA

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 ZMYM4-ACACA

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