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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:RHBDD1-AMACR

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: RHBDD1-AMACR
FusionPDB ID: 73864
FusionGDB2.0 ID: 73864
HgeneTgene
Gene symbol

RHBDD1

AMACR

Gene ID

84236

23600

Gene namerhomboid domain containing 1alpha-methylacyl-CoA racemase
SynonymsRHBDL4|RRP4AMACRD|CBAS4|P504S|RACE|RM
Cytomap

2q36.3

5p13.2

Type of geneprotein-codingprotein-coding
Descriptionrhomboid-related protein 4rhomboid domain-containing protein 1rhomboid-like protein 4alpha-methylacyl-CoA racemase2-methylacyl-CoA racemase
Modification date2020031320200313
UniProtAcc.

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 idsENST00000493526, ENST00000341329, 
ENST00000392062, ENST00000409053, 
ENST00000335606, ENST00000382072, 
ENST00000382068, ENST00000382085, 
ENST00000426255, ENST00000441713, 
ENST00000502637, ENST00000512079, 
ENST00000514195, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score3 X 1 X 2=628 X 3 X 4=336
# samples 323
** MAII scorelog2(3/6*10)=2.32192809488736log2(23/336*10)=-0.546827371834385
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: RHBDD1 [Title/Abstract] AND AMACR [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: RHBDD1 [Title/Abstract] AND AMACR [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)RHBDD1(227779067)-AMACR(34006004), # samples:2
Anticipated loss of major functional domain due to fusion event.RHBDD1-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.
RHBDD1-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.
RHBDD1-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.
RHBDD1-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
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/chr2:227779067/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 RHBDD1 (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)
ENST00000341329RHBDD1chr2227779067+ENST00000335606AMACRchr534006004-491510982361999587
ENST00000341329RHBDD1chr2227779067+ENST00000382072AMACRchr534006004-375810982361447403
ENST00000392062RHBDD1chr2227779067+ENST00000335606AMACRchr534006004-519713805182281587
ENST00000392062RHBDD1chr2227779067+ENST00000382072AMACRchr534006004-404013805181729403
ENST00000409053RHBDD1chr2227779067+ENST00000335606AMACRchr534006004-4188371131272419
ENST00000409053RHBDD1chr2227779067+ENST00000382072AMACRchr534006004-303137113720235

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
ENST00000341329ENST00000335606RHBDD1chr2227779067+AMACRchr534006004-0.00065690.9993431
ENST00000341329ENST00000382072RHBDD1chr2227779067+AMACRchr534006004-0.0034827030.9965173
ENST00000392062ENST00000335606RHBDD1chr2227779067+AMACRchr534006004-0.0006100280.99939
ENST00000392062ENST00000382072RHBDD1chr2227779067+AMACRchr534006004-0.0033983480.9966016
ENST00000409053ENST00000335606RHBDD1chr2227779067+AMACRchr534006004-0.0004254080.9995746
ENST00000409053ENST00000382072RHBDD1chr2227779067+AMACRchr534006004-0.0060780210.993922

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 RHBDD1-AMACR

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
RHBDD1chr2227779067AMACRchr5340060041098287QLERALQASLWDRGVMEKLQLGPEIL
RHBDD1chr2227779067AMACRchr5340060041380287QLERALQASLWDRGVMEKLQLGPEIL
RHBDD1chr2227779067AMACRchr534006004371119QLERALQASLWDRGVMEKLQLGPEIL

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Potential FusionNeoAntigen Information of RHBDD1-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.
RHBDD1-AMACR_227779067_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)
RHBDD1-AMACRchr2227779067chr5340060041098HLA-A03:12SLWDRGVMEK0.99910.5187818
RHBDD1-AMACRchr2227779067chr5340060041098HLA-A11:03SLWDRGVMEK0.99880.5768818
RHBDD1-AMACRchr2227779067chr5340060041098HLA-A11:04SLWDRGVMEK0.99830.5307818
RHBDD1-AMACRchr2227779067chr5340060041098HLA-A34:02SLWDRGVMEK0.99660.5105818
RHBDD1-AMACRchr2227779067chr5340060041098HLA-A74:09SLWDRGVMEK0.93940.7204818
RHBDD1-AMACRchr2227779067chr5340060041098HLA-A74:11SLWDRGVMEK0.93940.7204818
RHBDD1-AMACRchr2227779067chr5340060041098HLA-A74:03SLWDRGVMEK0.93940.7204818
RHBDD1-AMACRchr2227779067chr5340060041098HLA-A11:03ASLWDRGVMEK0.99950.6157718
RHBDD1-AMACRchr2227779067chr5340060041098HLA-A11:04ASLWDRGVMEK0.99860.5987718
RHBDD1-AMACRchr2227779067chr5340060041098HLA-A02:27SLWDRGVMEKL0.99720.6501819
RHBDD1-AMACRchr2227779067chr5340060041098HLA-A02:22SLWDRGVMEKL0.99710.5291819
RHBDD1-AMACRchr2227779067chr5340060041098HLA-A02:17SLWDRGVMEKL0.9960.68819
RHBDD1-AMACRchr2227779067chr5340060041098HLA-A02:04SLWDRGVMEKL0.9960.6453819
RHBDD1-AMACRchr2227779067chr5340060041098HLA-A02:11SLWDRGVMEKL0.99570.5981819
RHBDD1-AMACRchr2227779067chr5340060041098HLA-A02:67SLWDRGVMEKL0.99530.5788819
RHBDD1-AMACRchr2227779067chr5340060041098HLA-A02:24SLWDRGVMEKL0.99530.5788819
RHBDD1-AMACRchr2227779067chr5340060041098HLA-A02:30SLWDRGVMEKL0.99530.5788819
RHBDD1-AMACRchr2227779067chr5340060041098HLA-A02:60SLWDRGVMEKL0.9950.5519819
RHBDD1-AMACRchr2227779067chr5340060041098HLA-A02:16SLWDRGVMEKL0.98850.5473819
RHBDD1-AMACRchr2227779067chr5340060041098HLA-A02:35SLWDRGVMEKL0.96290.5924819
RHBDD1-AMACRchr2227779067chr5340060041098HLA-A02:19SLWDRGVMEKL0.95860.5287819
RHBDD1-AMACRchr2227779067chr5340060041098HLA-A02:20SLWDRGVMEKL0.91230.5838819
RHBDD1-AMACRchr2227779067chr5340060041098HLA-A02:29SLWDRGVMEKL0.90880.5796819
RHBDD1-AMACRchr2227779067chr5340060041098HLA-C04:10LWDRGVMEKL0.99930.9424919
RHBDD1-AMACRchr2227779067chr5340060041098HLA-C04:07LWDRGVMEKL0.99920.944919
RHBDD1-AMACRchr2227779067chr5340060041098HLA-A11:01SLWDRGVMEK0.99860.5566818
RHBDD1-AMACRchr2227779067chr5340060041098HLA-A11:01ASLWDRGVMEK0.99950.6295718
RHBDD1-AMACRchr2227779067chr5340060041098HLA-A02:01SLWDRGVMEKL0.99530.5788819
RHBDD1-AMACRchr2227779067chr5340060041098HLA-C04:01LWDRGVMEKL0.99920.944919
RHBDD1-AMACRchr2227779067chr5340060041098HLA-C18:01LWDRGVMEKL0.99870.9451919
RHBDD1-AMACRchr2227779067chr5340060041098HLA-A11:02SLWDRGVMEK0.99860.5566818
RHBDD1-AMACRchr2227779067chr5340060041098HLA-A74:01SLWDRGVMEK0.93940.7204818
RHBDD1-AMACRchr2227779067chr5340060041098HLA-A11:02ASLWDRGVMEK0.99950.6295718

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Potential FusionNeoAntigen Information of RHBDD1-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 RHBDD1-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
7155QASLWDRGVMEKLQRHBDD1AMACRchr2227779067chr5340060041098

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of RHBDD1-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-B14:023BVN7155QASLWDRGVMEKLQ-7.93863-8.05203
HLA-B14:023BVN7155QASLWDRGVMEKLQ-6.18626-7.22156
HLA-B52:013W397155QASLWDRGVMEKLQ-6.77739-6.89079
HLA-B52:013W397155QASLWDRGVMEKLQ-4.36659-5.40189
HLA-A24:025HGA7155QASLWDRGVMEKLQ-6.78109-6.89449
HLA-A24:025HGA7155QASLWDRGVMEKLQ-5.77386-6.80916
HLA-B44:053DX87155QASLWDRGVMEKLQ-5.9032-6.0166
HLA-B44:053DX87155QASLWDRGVMEKLQ-5.04949-6.08479

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Vaccine Design for the FusionNeoAntigens of RHBDD1-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
RHBDD1-AMACRchr2227779067chr534006004718ASLWDRGVMEKCCAGCCTCTGGGACCGAGGTGTCATGGAGAAAC
RHBDD1-AMACRchr2227779067chr534006004818SLWDRGVMEKGCCTCTGGGACCGAGGTGTCATGGAGAAAC
RHBDD1-AMACRchr2227779067chr534006004819SLWDRGVMEKLGCCTCTGGGACCGAGGTGTCATGGAGAAACTCC
RHBDD1-AMACRchr2227779067chr534006004919LWDRGVMEKLTCTGGGACCGAGGTGTCATGGAGAAACTCC

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 RHBDD1-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
PRADRHBDD1-AMACRchr2227779067ENST00000341329chr534006004ENST00000335606TCGA-HC-7749

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Potential target of CAR-T therapy development for RHBDD1-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
HgeneRHBDD1chr2:227779067chr5:34006004ENST00000341329+67107_127285316.0TransmembraneHelical
HgeneRHBDD1chr2:227779067chr5:34006004ENST00000341329+67139_157285316.0TransmembraneHelical
HgeneRHBDD1chr2:227779067chr5:34006004ENST00000341329+67181_201285316.0TransmembraneHelical
HgeneRHBDD1chr2:227779067chr5:34006004ENST00000341329+6722_42285316.0TransmembraneHelical
HgeneRHBDD1chr2:227779067chr5:34006004ENST00000392062+89107_127285316.0TransmembraneHelical
HgeneRHBDD1chr2:227779067chr5:34006004ENST00000392062+89139_157285316.0TransmembraneHelical
HgeneRHBDD1chr2:227779067chr5:34006004ENST00000392062+89181_201285316.0TransmembraneHelical
HgeneRHBDD1chr2:227779067chr5:34006004ENST00000392062+8922_42285316.0TransmembraneHelical

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 RHBDD1-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 RHBDD1-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