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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:ACACB-MARCH9

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: ACACB-MARCH9
FusionPDB ID: 1185
FusionGDB2.0 ID: 1185
HgeneTgene
Gene symbol

ACACB

MARCH9

Gene ID

32

92979

Gene nameacetyl-CoA carboxylase betamembrane associated ring-CH-type finger 9
SynonymsACC2|ACCB|HACC275MARCH-IX|MARCH9|RNF179
Cytomap

12q24.11

12q14.1

Type of geneprotein-codingprotein-coding
Descriptionacetyl-CoA carboxylase 2ACC-betaacetyl-Coenzyme A carboxylase betaE3 ubiquitin-protein ligase MARCH9RING finger protein 179RING-type E3 ubiquitin transferase MARCH9membrane associated ring finger 9membrane-associated RING finger protein 9membrane-associated RING-CH protein IXmembrane-associated ring finger (C3HC4)
Modification date2020031320200313
UniProtAcc

O00763

Main function of 5'-partner protein: FUNCTION: Mitochondrial enzyme that catalyzes the carboxylation of acetyl-CoA to malonyl-CoA and plays a central role in fatty acid metabolism (PubMed:16854592, PubMed:19236960, PubMed:20457939, PubMed:20952656, PubMed:19900410, PubMed:26976583). Catalyzes 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:19236960, PubMed:20457939, PubMed:20952656, PubMed:26976583). Through the production of malonyl-CoA that allosterically inhibits carnitine palmitoyltransferase 1 at the mitochondria, negatively regulates fatty acid oxidation (By similarity). Together with its cytosolic isozyme ACACA, which is involved in de novo fatty acid biosynthesis, promotes lipid storage (By similarity). {ECO:0000250|UniProtKB:E9Q4Z2, ECO:0000269|PubMed:16854592, ECO:0000269|PubMed:19236960, ECO:0000269|PubMed:19900410, ECO:0000269|PubMed:20457939, ECO:0000269|PubMed:20952656, ECO:0000269|PubMed:26976583}.
.
Ensembl transtripts involved in fusion geneENST idsENST00000338432, ENST00000377848, 
ENST00000377854, ENST00000543201, 
ENST00000543080, 
ENST00000548358, 
ENST00000266643, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score4 X 5 X 5=1005 X 5 X 4=100
# samples 65
** MAII scorelog2(6/100*10)=-0.736965594166206
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(5/100*10)=-1
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: ACACB [Title/Abstract] AND MARCH9 [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: ACACB [Title/Abstract] AND MARCH9 [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)ACACB(109675185)-MARCH9(58150712), # samples:2
Anticipated loss of major functional domain due to fusion event.ACACB-MARCH9 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.
ACACB-MARCH9 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.
ACACB-MARCH9 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.
ACACB-MARCH9 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
HgeneACACB

GO:0006084

acetyl-CoA metabolic process

20952656

HgeneACACB

GO:0051289

protein homotetramerization

20952656



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/chr12:109675185/chr12:58150712)
- 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 ACACB (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 MARCH9 (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)
ENST00000338432ACACBchr12109675185+ENST00000266643MARCH9chr1258150712+6975478111954641781
ENST00000377854ACACBchr12109675185+ENST00000266643MARCH9chr1258150712+66554461951441711
ENST00000377848ACACBchr12109675185+ENST00000266643MARCH9chr1258150712+68654671953541781
ENST00000543201ACACBchr12109675185+ENST00000266643MARCH9chr1258150712+285566111344447

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
ENST00000338432ENST00000266643ACACBchr12109675185+MARCH9chr1258150712+0.0028288420.9971712
ENST00000377854ENST00000266643ACACBchr12109675185+MARCH9chr1258150712+0.0019072170.99809283
ENST00000377848ENST00000266643ACACBchr12109675185+MARCH9chr1258150712+0.0024456350.99755436
ENST00000543201ENST00000266643ACACBchr12109675185+MARCH9chr1258150712+0.028522640.9714774

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 ACACB-MARCH9

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
ACACBchr12109675185MARCH9chr125815071244611484IRAIIRHSDLITKGELLSPCRCDGSV
ACACBchr12109675185MARCH9chr125815071246711554IRAIIRHSDLITKGELLSPCRCDGSV
ACACBchr12109675185MARCH9chr125815071247811554IRAIIRHSDLITKGELLSPCRCDGSV
ACACBchr12109675185MARCH9chr1258150712661220IRAIIRHSDLITKGELLSPCRCDGSV

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Potential FusionNeoAntigen Information of ACACB-MARCH9 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.
ACACB-MARCH9_109675185_58150712.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)
ACACB-MARCH9chr12109675185chr12581507124781HLA-B08:01DLITKGEL0.99410.8633816
ACACB-MARCH9chr12109675185chr12581507124781HLA-B08:01DLITKGELL0.61370.8563817
ACACB-MARCH9chr12109675185chr12581507124781HLA-B39:01RHSDLITKGEL0.99910.8775516
ACACB-MARCH9chr12109675185chr12581507124781HLA-B38:02RHSDLITKGEL0.99810.9596516
ACACB-MARCH9chr12109675185chr12581507124781HLA-B38:01RHSDLITKGEL0.9980.9651516
ACACB-MARCH9chr12109675185chr12581507124781HLA-B07:10RHSDLITKGEL0.98730.6472516
ACACB-MARCH9chr12109675185chr12581507124781HLA-B15:10RHSDLITKGEL0.98220.5294516
ACACB-MARCH9chr12109675185chr12581507124781HLA-C08:15HSDLITKGEL0.99990.981616
ACACB-MARCH9chr12109675185chr12581507124781HLA-B39:05RHSDLITKGEL0.99780.8581516
ACACB-MARCH9chr12109675185chr12581507124781HLA-B08:18DLITKGEL0.99410.8633816
ACACB-MARCH9chr12109675185chr12581507124781HLA-B08:12DLITKGEL0.89550.8949816
ACACB-MARCH9chr12109675185chr12581507124781HLA-B08:18DLITKGELL0.61370.8563817
ACACB-MARCH9chr12109675185chr12581507124781HLA-B08:12DLITKGELL0.54680.8891817
ACACB-MARCH9chr12109675185chr12581507124781HLA-C08:02HSDLITKGEL0.99990.981616
ACACB-MARCH9chr12109675185chr12581507124781HLA-B38:05RHSDLITKGEL0.9980.9651516
ACACB-MARCH9chr12109675185chr12581507124781HLA-B39:11RHSDLITKGEL0.99660.8747516

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Potential FusionNeoAntigen Information of ACACB-MARCH9 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.
ACACB-MARCH9_109675185_58150712.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)
ACACB-MARCH9chr12109675185chr12581507124781DRB1-0437IRAIIRHSDLITKGE015
ACACB-MARCH9chr12109675185chr12581507124781DRB1-1457IRAIIRHSDLITKGE015

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Fusion breakpoint peptide structures of ACACB-MARCH9

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
3497HSDLITKGELLSPCACACBMARCH9chr12109675185chr12581507124781

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of ACACB-MARCH9

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-B14:023BVN3497HSDLITKGELLSPC-7.15543-7.26883
HLA-B14:023BVN3497HSDLITKGELLSPC-4.77435-5.80965
HLA-B52:013W393497HSDLITKGELLSPC-6.80875-6.92215
HLA-B52:013W393497HSDLITKGELLSPC-4.20386-5.23916
HLA-A11:014UQ23497HSDLITKGELLSPC-7.5194-8.5547
HLA-A11:014UQ23497HSDLITKGELLSPC-6.9601-7.0735
HLA-A24:025HGA3497HSDLITKGELLSPC-7.52403-7.63743
HLA-A24:025HGA3497HSDLITKGELLSPC-5.82433-6.85963
HLA-B27:056PYJ3497HSDLITKGELLSPC-3.28285-4.31815
HLA-B44:053DX83497HSDLITKGELLSPC-5.91172-6.94702
HLA-B44:053DX83497HSDLITKGELLSPC-4.24346-4.35686

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Vaccine Design for the FusionNeoAntigens of ACACB-MARCH9

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
ACACB-MARCH9chr12109675185chr1258150712516RHSDLITKGELAGGCACTCTGACCTGATCACAAAGGGGGAGCTC
ACACB-MARCH9chr12109675185chr1258150712616HSDLITKGELCACTCTGACCTGATCACAAAGGGGGAGCTC
ACACB-MARCH9chr12109675185chr1258150712816DLITKGELGACCTGATCACAAAGGGGGAGCTC
ACACB-MARCH9chr12109675185chr1258150712817DLITKGELLGACCTGATCACAAAGGGGGAGCTCTTA

check button mRNA and peptide sequences of FusionNeoAntigens that have potential interaction with HLA-IIs.
Fusion geneHchrHbpTchrTbpStart in +/-13AAEnd in +/-13AAFusionNeoAntigen peptideFusionNEoAntigen RNA sequence
ACACB-MARCH9chr12109675185chr1258150712015IRAIIRHSDLITKGEATCCGCGCCATCATCAGGCACTCTGACCTGATCACAAAGGGGGAG

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Information of the samples that have these potential fusion neoantigens of ACACB-MARCH9

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
SARCACACB-MARCH9chr12109675185ENST00000338432chr1258150712ENST00000266643TCGA-3B-A9HS-01A

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Potential target of CAR-T therapy development for ACACB-MARCH9

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
TgeneMARCH9chr12:109675185chr12:58150712ENST0000026664304185_2050347.0TransmembraneHelical
TgeneMARCH9chr12:109675185chr12:58150712ENST0000026664304219_2390347.0TransmembraneHelical
TgeneMARCH9chr12:109675185chr12:58150712ENST0000054835802185_2050234.0TransmembraneHelical
TgeneMARCH9chr12:109675185chr12:58150712ENST0000054835802219_2390234.0TransmembraneHelical

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 ACACB-MARCH9

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 ACACB-MARCH9

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