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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:CPE-AMACR

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: CPE-AMACR
FusionPDB ID: 18945
FusionGDB2.0 ID: 18945
HgeneTgene
Gene symbol

CPE

AMACR

Gene ID

1363

23600

Gene namecarboxypeptidase Ealpha-methylacyl-CoA racemase
SynonymsCPHAMACRD|CBAS4|P504S|RACE|RM
Cytomap

4q32.3

5p13.2

Type of geneprotein-codingprotein-coding
Descriptioncarboxypeptidase Ecarboxypeptidase Hcobalt-stimulated chromaffin granule carboxypeptidaseenkephalin convertaseepididymis secretory sperm binding proteininsulin granule-associated carboxypeptidaseprohormone-processing carboxypeptidasealpha-methylacyl-CoA racemase2-methylacyl-CoA racemase
Modification date2020031320200313
UniProtAcc

A4D0V7

Main function of 5'-partner protein:

Q9UHK6

Main function of 5'-partner protein: FUNCTION: Catalyzes the interconversion of (R)- and (S)-stereoisomers of alpha-methyl-branched-chain fatty acyl-CoA esters (PubMed:7649182, PubMed:10655068, PubMed:11060359). Acts only on coenzyme A thioesters, not on free fatty acids, and accepts as substrates a wide range of alpha-methylacyl-CoAs, including pristanoyl-CoA, trihydroxycoprostanoyl-CoA (an intermediate in bile acid synthesis), and arylpropionic acids like the anti-inflammatory drug ibuprofen (2-(4-isobutylphenyl)propionic acid) but neither 3-methyl-branched nor linear-chain acyl-CoAs (PubMed:7649182, PubMed:10655068, PubMed:11060359). {ECO:0000269|PubMed:10655068, ECO:0000269|PubMed:11060359, ECO:0000269|PubMed:7649182}.
Ensembl transtripts involved in fusion geneENST idsENST00000402744, ENST00000382068, 
ENST00000382085, ENST00000426255, 
ENST00000441713, ENST00000502637, 
ENST00000512079, ENST00000514195, 
ENST00000335606, ENST00000382072, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score8 X 5 X 5=20028 X 3 X 4=336
# samples 823
** MAII scorelog2(8/200*10)=-1.32192809488736
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(23/336*10)=-0.546827371834385
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: CPE [Title/Abstract] AND AMACR [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: CPE [Title/Abstract] AND AMACR [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)CPE(166300680)-AMACR(34006004), # samples:2
Anticipated loss of major functional domain due to fusion event.CPE-AMACR 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.
CPE-AMACR 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.
CPE-AMACR 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.
CPE-AMACR 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
HgeneCPE

GO:0016055

Wnt signaling pathway

22824791

HgeneCPE

GO:0072657

protein localization to membrane

19166515

TgeneAMACR

GO:0008206

bile acid metabolic process

10655068



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/chr4:166300680/chr5:34006004)
- 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 CPE (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 AMACR (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)
ENST00000402744CPEchr4166300680+ENST00000335606AMACRchr534006004-4404587401488482
ENST00000402744CPEchr4166300680+ENST00000382072AMACRchr534006004-324758740936298

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
ENST00000402744ENST00000335606CPEchr4166300680+AMACRchr534006004-0.0003472350.99965274
ENST00000402744ENST00000382072CPEchr4166300680+AMACRchr534006004-0.0957126540.90428734

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 CPE-AMACR

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
CPEchr4166300680AMACRchr534006004587182VIELSDNPGVHEPGVMEKLQLGPEIL

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Potential FusionNeoAntigen Information of CPE-AMACR 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.
CPE-AMACR_166300680_34006004.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)
CPE-AMACRchr4166300680chr534006004587HLA-B47:01HEPGVMEKL0.90170.64581019
CPE-AMACRchr4166300680chr534006004587HLA-B18:01HEPGVMEKL0.84090.96941019
CPE-AMACRchr4166300680chr534006004587HLA-B39:13HEPGVMEKL0.6130.96231019
CPE-AMACRchr4166300680chr534006004587HLA-A30:08GVHEPGVMEK0.99370.735818
CPE-AMACRchr4166300680chr534006004587HLA-B39:01VHEPGVMEKL0.99330.9184919
CPE-AMACRchr4166300680chr534006004587HLA-B38:01VHEPGVMEKL0.9820.9659919
CPE-AMACRchr4166300680chr534006004587HLA-B38:02VHEPGVMEKL0.98150.9698919
CPE-AMACRchr4166300680chr534006004587HLA-B15:10VHEPGVMEKL0.97530.8288919
CPE-AMACRchr4166300680chr534006004587HLA-B15:37VHEPGVMEKL0.89870.8369919
CPE-AMACRchr4166300680chr534006004587HLA-B39:09HEPGVMEKL0.68210.6431019
CPE-AMACRchr4166300680chr534006004587HLA-B39:08HEPGVMEKL0.64970.83041019
CPE-AMACRchr4166300680chr534006004587HLA-B39:09VHEPGVMEKL0.99280.6123919
CPE-AMACRchr4166300680chr534006004587HLA-B39:05VHEPGVMEKL0.98350.9167919
CPE-AMACRchr4166300680chr534006004587HLA-B40:04HEPGVMEKL0.99760.72171019
CPE-AMACRchr4166300680chr534006004587HLA-B18:05HEPGVMEKL0.84090.96941019
CPE-AMACRchr4166300680chr534006004587HLA-B18:08HEPGVMEKL0.83860.93911019
CPE-AMACRchr4166300680chr534006004587HLA-B18:06HEPGVMEKL0.79740.97561019
CPE-AMACRchr4166300680chr534006004587HLA-B18:03HEPGVMEKL0.75050.96721019
CPE-AMACRchr4166300680chr534006004587HLA-B18:11HEPGVMEKL0.71160.95241019
CPE-AMACRchr4166300680chr534006004587HLA-B41:03HEPGVMEKL0.64090.57411019
CPE-AMACRchr4166300680chr534006004587HLA-B39:31HEPGVMEKL0.64010.96171019
CPE-AMACRchr4166300680chr534006004587HLA-B39:02HEPGVMEKL0.60670.96121019
CPE-AMACRchr4166300680chr534006004587HLA-B59:01NPGVHEPGV0.47140.591615
CPE-AMACRchr4166300680chr534006004587HLA-B39:31VHEPGVMEKL0.99320.9242919
CPE-AMACRchr4166300680chr534006004587HLA-A30:01GVHEPGVMEK0.99160.842818
CPE-AMACRchr4166300680chr534006004587HLA-B38:05VHEPGVMEKL0.9820.9659919
CPE-AMACRchr4166300680chr534006004587HLA-B15:09VHEPGVMEKL0.92570.6427919
CPE-AMACRchr4166300680chr534006004587HLA-B39:11VHEPGVMEKL0.88580.7631919

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Potential FusionNeoAntigen Information of CPE-AMACR 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 CPE-AMACR

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
6311NPGVHEPGVMEKLQCPEAMACRchr4166300680chr534006004587

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of CPE-AMACR

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-B14:023BVN6311NPGVHEPGVMEKLQ-8.85616-8.96956
HLA-B14:023BVN6311NPGVHEPGVMEKLQ-5.66423-6.69953
HLA-B52:013W396311NPGVHEPGVMEKLQ-6.49489-6.60829
HLA-B52:013W396311NPGVHEPGVMEKLQ-3.99785-5.03315
HLA-A11:014UQ26311NPGVHEPGVMEKLQ-4.90759-5.94289
HLA-A24:025HGA6311NPGVHEPGVMEKLQ-7.27887-7.39227
HLA-A24:025HGA6311NPGVHEPGVMEKLQ-7.11524-8.15054
HLA-B27:056PYJ6311NPGVHEPGVMEKLQ-6.11615-6.22955
HLA-B27:056PYJ6311NPGVHEPGVMEKLQ-4.78818-5.82348
HLA-B44:053DX86311NPGVHEPGVMEKLQ-7.22602-7.33942
HLA-B44:053DX86311NPGVHEPGVMEKLQ-4.86671-5.90201

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Vaccine Design for the FusionNeoAntigens of CPE-AMACR

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
CPE-AMACRchr4166300680chr5340060041019HEPGVMEKLATGAGCCTGGTGTCATGGAGAAACTCC
CPE-AMACRchr4166300680chr534006004615NPGVHEPGVACCCTGGCGTCCATGAGCCTGGTGTCA
CPE-AMACRchr4166300680chr534006004818GVHEPGVMEKGCGTCCATGAGCCTGGTGTCATGGAGAAAC
CPE-AMACRchr4166300680chr534006004919VHEPGVMEKLTCCATGAGCCTGGTGTCATGGAGAAACTCC

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 CPE-AMACR

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
PRADCPE-AMACRchr4166300680ENST00000402744chr534006004ENST00000335606TCGA-KC-A7FD

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Potential target of CAR-T therapy development for CPE-AMACR

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 CPE-AMACR

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 CPE-AMACR

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