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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:CRCP-ADAM22

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: CRCP-ADAM22
FusionPDB ID: 19294
FusionGDB2.0 ID: 19294
HgeneTgene
Gene symbol

CRCP

ADAM22

Gene ID

27297

53616

Gene nameCGRP receptor componentADAM metallopeptidase domain 22
SynonymsC17|CGRP-RCP|CGRPRCP|POLR3I|POLR3J|RCP|RCP9|RPC9ADAM 22|EIEE61|MDC2
Cytomap

7q11.21

7q21.12

Type of geneprotein-codingprotein-coding
DescriptionDNA-directed RNA polymerase III subunit RPC9CGRP-receptor component proteinRNA polymerase III subunit C9calcitonin gene-related peptide-receptor component proteindisintegrin and metalloproteinase domain-containing protein 22a disintegrin and metalloproteinase domain 22metalloproteinase-disintegrin ADAM22-3metalloproteinase-like, disintegrin-like, and cysteine-rich protein 2
Modification date2020032220200313
UniProtAcc

O75575

Main function of 5'-partner protein: FUNCTION: DNA-dependent RNA polymerase catalyzes the transcription of DNA into RNA using the four ribonucleoside triphosphates as substrates. Specific peripheric component of RNA polymerase III which synthesizes small RNAs, such as 5S rRNA and tRNAs. Plays a key role in sensing and limiting infection by intracellular bacteria and DNA viruses. Acts as nuclear and cytosolic DNA sensor involved in innate immune response. Can sense non-self dsDNA that serves as template for transcription into dsRNA. The non-self RNA polymerase III transcripts induce type I interferon and NF- Kappa-B through the RIG-I pathway (By similarity). {ECO:0000250}.; FUNCTION: Accessory protein for the calcitonin gene-related peptide (CGRP) receptor. It modulates CGRP responsiveness in a variety of tissues.

Q9P0K1

Main function of 5'-partner protein: FUNCTION: Probable ligand for integrin in the brain. This is a non catalytic metalloprotease-like protein (PubMed:19692335). Involved in regulation of cell adhesion and spreading and in inhibition of cell proliferation. Neuronal receptor for LGI1. {ECO:0000269|PubMed:12589811, ECO:0000269|PubMed:15882968, ECO:0000269|PubMed:16385342, ECO:0000269|PubMed:19692335}.
Ensembl transtripts involved in fusion geneENST idsENST00000338592, ENST00000395326, 
ENST00000398684, ENST00000415001, 
ENST00000431089, ENST00000492264, 
ENST00000476330, ENST00000265727, 
ENST00000315984, ENST00000398201, 
ENST00000398204, ENST00000398209, 
ENST00000439864, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score4 X 3 X 3=365 X 5 X 4=100
# samples 46
** MAII scorelog2(4/36*10)=0.15200309344505
effective Gene in Pan-Cancer Fusion Genes (eGinPCFGs).
DoF>8 and MAII>0
log2(6/100*10)=-0.736965594166206
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: CRCP [Title/Abstract] AND ADAM22 [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: CRCP [Title/Abstract] AND ADAM22 [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)CRCP(65579957)-ADAM22(87704941), # samples:3
Anticipated loss of major functional domain due to fusion event.CRCP-ADAM22 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.
CRCP-ADAM22 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
HgeneCRCP

GO:0006383

transcription by RNA polymerase III

12482973



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/chr7:65579957/chr7:87704941)
- 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 CRCP (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 ADAM22 (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)
ENST00000395326CRCPchr765579957+ENST00000398204ADAM22chr787704941+90543663582655765
ENST00000395326CRCPchr765579957+ENST00000439864ADAM22chr787704941+24043663581071237
ENST00000395326CRCPchr765579957+ENST00000398201ADAM22chr787704941+27083663582622754
ENST00000395326CRCPchr765579957+ENST00000265727ADAM22chr787704941+28553663582763801
ENST00000395326CRCPchr765579957+ENST00000315984ADAM22chr787704941+33843663582742794
ENST00000395326CRCPchr765579957+ENST00000398209ADAM22chr787704941+91413663582742794
ENST00000398684CRCPchr765579957+ENST00000398204ADAM22chr787704941+88181301222419765
ENST00000398684CRCPchr765579957+ENST00000439864ADAM22chr787704941+2168130122835237
ENST00000398684CRCPchr765579957+ENST00000398201ADAM22chr787704941+24721301222386754
ENST00000398684CRCPchr765579957+ENST00000265727ADAM22chr787704941+26191301222527801
ENST00000398684CRCPchr765579957+ENST00000315984ADAM22chr787704941+31481301222506794
ENST00000398684CRCPchr765579957+ENST00000398209ADAM22chr787704941+89051301222506794
ENST00000338592CRCPchr765579957+ENST00000398204ADAM22chr787704941+88091211132410765
ENST00000338592CRCPchr765579957+ENST00000439864ADAM22chr787704941+2159121113826237
ENST00000338592CRCPchr765579957+ENST00000398201ADAM22chr787704941+24631211132377754
ENST00000338592CRCPchr765579957+ENST00000265727ADAM22chr787704941+26101211132518801
ENST00000338592CRCPchr765579957+ENST00000315984ADAM22chr787704941+31391211132497794
ENST00000338592CRCPchr765579957+ENST00000398209ADAM22chr787704941+88961211132497794

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
ENST00000395326ENST00000398204CRCPchr765579957+ADAM22chr787704941+0.0003262690.9996737
ENST00000395326ENST00000439864CRCPchr765579957+ADAM22chr787704941+0.0008003580.9991997
ENST00000395326ENST00000398201CRCPchr765579957+ADAM22chr787704941+0.0006016810.99939835
ENST00000395326ENST00000265727CRCPchr765579957+ADAM22chr787704941+0.0005838260.99941623
ENST00000395326ENST00000315984CRCPchr765579957+ADAM22chr787704941+0.0004381090.99956185
ENST00000395326ENST00000398209CRCPchr765579957+ADAM22chr787704941+0.0002671750.9997328
ENST00000398684ENST00000398204CRCPchr765579957+ADAM22chr787704941+0.0003215140.9996785
ENST00000398684ENST00000439864CRCPchr765579957+ADAM22chr787704941+0.0007165820.9992835
ENST00000398684ENST00000398201CRCPchr765579957+ADAM22chr787704941+0.0005643430.9994356
ENST00000398684ENST00000265727CRCPchr765579957+ADAM22chr787704941+0.000598870.9994011
ENST00000398684ENST00000315984CRCPchr765579957+ADAM22chr787704941+0.0004635510.9995365
ENST00000398684ENST00000398209CRCPchr765579957+ADAM22chr787704941+0.0002625890.99973744
ENST00000338592ENST00000398204CRCPchr765579957+ADAM22chr787704941+0.0003205890.99967945
ENST00000338592ENST00000439864CRCPchr765579957+ADAM22chr787704941+0.0006071110.99939287
ENST00000338592ENST00000398201CRCPchr765579957+ADAM22chr787704941+0.0005603430.99943966
ENST00000338592ENST00000265727CRCPchr765579957+ADAM22chr787704941+0.0005990470.999401
ENST00000338592ENST00000315984CRCPchr765579957+ADAM22chr787704941+0.0004648690.9995352
ENST00000338592ENST00000398209CRCPchr765579957+ADAM22chr787704941+0.0002618010.99973816

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 CRCP-ADAM22

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

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Potential FusionNeoAntigen Information of CRCP-ADAM22 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 CRCP-ADAM22 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 CRCP-ADAM22

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 CRCP-ADAM22

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 CRCP-ADAM22

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 CRCP-ADAM22

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 CRCP-ADAM22

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
TgeneADAM22chr7:65579957chr7:87704941ENST00000265727231737_7570907.0TransmembraneHelical
TgeneADAM22chr7:65579957chr7:87704941ENST00000398201229737_7570860.0TransmembraneHelical
TgeneADAM22chr7:65579957chr7:87704941ENST00000398204230737_7570871.0TransmembraneHelical
TgeneADAM22chr7:65579957chr7:87704941ENST00000398209231737_7570900.0TransmembraneHelical

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 CRCP-ADAM22

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 CRCP-ADAM22

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