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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:MCAT-ACSS2

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: MCAT-ACSS2
FusionPDB ID: 52132
FusionGDB2.0 ID: 52132
HgeneTgene
Gene symbol

MCAT

ACSS2

Gene ID

27349

55902

Gene namemalonyl-CoA-acyl carrier protein transacylaseacyl-CoA synthetase short chain family member 2
SynonymsFASN2C|MCT|MCT1|MT|NET62|fabDACAS2|ACECS|ACS|ACSA|AceCS1|dJ1161H23.1
Cytomap

22q13.2

20q11.22

Type of geneprotein-codingprotein-coding
Descriptionmalonyl-CoA-acyl carrier protein transacylase, mitochondrial[Acyl-carrier-protein] malonyltransferase[acyl-carrier-protein] S-malonyltransferasemalonyl CoA:ACP acyltransferase (mitochondrial)mitochondrial malonyl CoA:ACP acyltransferasemitochondrial acetyl-coenzyme A synthetase, cytoplasmicacetate thiokinaseacetate-CoA ligaseacetyl-CoA synthetase 1acetyl-Coenzyme A synthetase 2 (ADP forming)acyl-activating enzymecytoplasmic acetyl-coenzyme A synthetasepropionate--CoA ligase
Modification date2020031320200313
UniProtAcc

Q8IVS2

Main function of 5'-partner protein: FUNCTION: Catalyzes the transfer of a malonyl moiety from malonyl-CoA to the free thiol group of the phosphopantetheine arm of the mitochondrial ACP protein (NDUFAB1). This suggests the existence of the biosynthesis of fatty acids in mitochondria. {ECO:0000269|PubMed:12882974}.

Q9NR19

Main function of 5'-partner protein: FUNCTION: Catalyzes the synthesis of acetyl-CoA from short-chain fatty acids (PubMed:10843999, PubMed:28003429). Acetate is the preferred substrate (PubMed:10843999, PubMed:28003429). Can also utilize propionate with a much lower affinity (By similarity). {ECO:0000250|UniProtKB:Q9QXG4, ECO:0000269|PubMed:10843999, ECO:0000269|PubMed:28003429}.
Ensembl transtripts involved in fusion geneENST idsENST00000290429, ENST00000327555, 
ENST00000464244, 
ENST00000476922, 
ENST00000253382, ENST00000336325, 
ENST00000360596, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score2 X 3 X 2=1211 X 8 X 6=528
# samples 212
** MAII scorelog2(2/12*10)=0.736965594166206
effective Gene in Pan-Cancer Fusion Genes (eGinPCFGs).
DoF>8 and MAII>0
log2(12/528*10)=-2.13750352374993
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: MCAT [Title/Abstract] AND ACSS2 [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: MCAT [Title/Abstract] AND ACSS2 [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)MCAT(43537167)-ACSS2(33513500), # samples:1
Anticipated loss of major functional domain due to fusion event.MCAT-ACSS2 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.
MCAT-ACSS2 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
HgeneMCAT

GO:0006633

fatty acid biosynthetic process

12882974



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/chr22:43537167/chr20:33513500)
- 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 MCAT (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 ACSS2 (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)
ENST00000290429MCATchr2243537167-ENST00000336325ACSS2chr2033513500+1758557461005319
ENST00000290429MCATchr2243537167-ENST00000360596ACSS2chr2033513500+1754557461005319
ENST00000290429MCATchr2243537167-ENST00000253382ACSS2chr2033513500+1754557461005319
ENST00000327555MCATchr2243537167-ENST00000336325ACSS2chr2033513500+172852716975319
ENST00000327555MCATchr2243537167-ENST00000360596ACSS2chr2033513500+172452716975319
ENST00000327555MCATchr2243537167-ENST00000253382ACSS2chr2033513500+172452716975319

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
ENST00000290429ENST00000336325MCATchr2243537167-ACSS2chr2033513500+0.0112953340.9887046
ENST00000290429ENST00000360596MCATchr2243537167-ACSS2chr2033513500+0.0113904490.98860955
ENST00000290429ENST00000253382MCATchr2243537167-ACSS2chr2033513500+0.0113904490.98860955
ENST00000327555ENST00000336325MCATchr2243537167-ACSS2chr2033513500+0.0115161370.98848385
ENST00000327555ENST00000360596MCATchr2243537167-ACSS2chr2033513500+0.01158340.9884166
ENST00000327555ENST00000253382MCATchr2243537167-ACSS2chr2033513500+0.01158340.9884166

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 MCAT-ACSS2

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
MCATchr2243537167ACSS2chr2033513500527170AALVFAGAMEFAEGCQRDQDGYYWIT
MCATchr2243537167ACSS2chr2033513500557170AALVFAGAMEFAEGCQRDQDGYYWIT

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Potential FusionNeoAntigen Information of MCAT-ACSS2 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 MCAT-ACSS2 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 MCAT-ACSS2

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 MCAT-ACSS2

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 MCAT-ACSS2

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

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Information of the samples that have these potential fusion neoantigens of MCAT-ACSS2

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 MCAT-ACSS2

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 MCAT-ACSS2

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 MCAT-ACSS2

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