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Center for Computational Systems Medicine level1
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Fusion Gene Summary

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Fusion Gene Sample Information

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Fusion ORF Analysis

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Fusion Amino Acid Sequences

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Fusion Protein Functional Features

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Fusion Protein-Protein Interaction

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Related drugs with this fusion protein

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Related disease with this fusion protein

Fusion Protein:NOTCH3-C3

Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: NOTCH3-C3
FusionPDB ID: 59777
FusionGDB2.0 ID: 59777
HgeneTgene
Gene symbol

NOTCH3

C3

Gene ID

4854

718

Gene namenotch receptor 3complement C3
SynonymsCADASIL|CADASIL1|CASIL|IMF2|LMNSAHUS5|ARMD9|ASP|C3a|C3b|CPAMD1|HEL-S-62p
Cytomap

19p13.12

19p13.3

Type of geneprotein-codingprotein-coding
Descriptionneurogenic locus notch homolog protein 3Notch homolog 3notch 3complement C3C3 and PZP-like alpha-2-macroglobulin domain-containing protein 1C3a anaphylatoxinacylation-stimulating protein cleavage productcomplement component 3complement component C3acomplement component C3bepididymis secretory sperm binding pr
Modification date2020032920200327
UniProtAcc

Q9UM47

A6NLC5

Ensembl transtripts involved in fusion geneENST idsENST00000263388, ENST00000599668, 
ENST00000245907, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score15 X 17 X 11=280522 X 20 X 8=3520
# samples 1822
** MAII scorelog2(18/2805*10)=-3.96193195916648
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(22/3520*10)=-4
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Context (manual curation of fusion genes in FusionPDB)

PubMed: NOTCH3 [Title/Abstract] AND C3 [Title/Abstract] AND fusion [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)NOTCH3(15270445)-C3(6720693), # samples:1
Anticipated loss of major functional domain due to fusion event.NOTCH3-C3 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.
NOTCH3-C3 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
TgeneC3

GO:0001934

positive regulation of protein phosphorylation

15833747

TgeneC3

GO:0010575

positive regulation of vascular endothelial growth factor production

16452172

TgeneC3

GO:0010828

positive regulation of glucose transmembrane transport

9059512|15833747

TgeneC3

GO:0010866

regulation of triglyceride biosynthetic process

10432298

TgeneC3

GO:0010884

positive regulation of lipid storage

9555951

TgeneC3

GO:0045745

positive regulation of G protein-coupled receptor signaling pathway

15833747


check buttonFusion gene breakpoints across NOTCH3 (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 C3 (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 Gene Sample Information

check buttonFusion gene information from FusionGDB2.0.
check button Fusion gene information from two resources (ChiTars 5.0 and ChimerDB 4.0)
* All genome coordinats were lifted-over on hg19.
* Click on the break point to see the gene structure around the break point region using the UCSC Genome Browser.
SourceDiseaseSampleHgeneHchrHbpHstrandTgeneTchrTbpTstrand
ChimerDB4BRCATCGA-B6-A402-01ANOTCH3chr19

15270445

-C3chr19

6720693

-


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Fusion ORF Analysis


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)
ENST00000263388NOTCH3chr1915270445-ENST00000245907C3chr196720693-1333480717670412321

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
ENST00000263388ENST00000245907NOTCH3chr1915270445-C3chr196720693-0.0036667230.99633324

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Fusion Amino Acid Sequences


check button For individual full-length fusion transcript sequence from FusionPDB, we ran ORFfinder and chose the longest ORF among the all predicted ones.
>FusionGDB ID_FusionGDB isoform ID_FGname_Hgene_Hchr_Hbp_Henst_Tgene_Tchr_Tbp_Tenst_length(fusion AA) seq_BP

>59777_59777_1_NOTCH3-C3_NOTCH3_chr19_15270445_ENST00000263388_C3_chr19_6720693_ENST00000245907_length(amino acids)=2321AA_BP=
MGPGARGRRRRRRPMSPPPPPPPVRALPLLLLLAGPGAAAPPCLDGSPCANGGRCTQLPSREAACLCPPGWVGERCQLEDPCHSGPCAGR
GVCQSSVVAGTARFSCRCPRGFRGPDCSLPDPCLSSPCAHGARCSVGPDGRFLCSCPPGYQGRSCRSDVDECRVGEPCRHGGTCLNTPGS
FRCQCPAGYTGPLCENPAVPCAPSPCRNGGTCRQSGDLTYDCACLPGFEGQNCEVNVDDCPGHRCLNGGTCVDGVNTYNCQCPPEWTGQF
CTEDVDECQLQPNACHNGGTCFNTLGGHSCVCVNGWTGESCSQNIDDCATAVCFHGATCHDRVASFYCACPMGKTGLLCHLDDACVSNPC
HEDAICDTNPVNGRAICTCPPGFTGGACDQDVDECSIGANPCEHLGRCVNTQGSFLCQCGRGYTGPRCETDVNECLSGPCRNQATCLDRI
GQFTCICMAGFTGTYCEVDIDECQSSPCVNGGVCKDRVNGFSCTCPSGFSGSTCQLDVDECASTPCRNGAKCVDQPDGYECRCAEGFEGT
LCDRNVDDCSPDPCHHGRCVDGIASFSCACAPGYTGTRCESQVDECRSQPCRHGGKCLDLVDKYLCRCPSGTTGVNCEVNIDDCASNPCT
FGVCRDGINRYDCVCQPGFTGPLCNVEINECASSPCGEGGSCVDGENGFRCLCPPGSLPPLCLPPSHPCAHEPCSHGICYDAPGGFRCVC
EPGWSGPRCSQSLARDACESQPCRAGGTCSSDGMGFHCTCPPGVQGRQCELLSPCTPNPCEHGGRCESAPGQLPVCSCPQGWQGPRCQQD
VDECAGPAPCGPHGICTNLAGSFSCTCHGGYTGPSCDQDINDCDPNPCLNGGSCQDGVGSFSCSCLPGFAGPRCARDVDECLSNPCGPGT
CTDHVASFTCTCPPGYGGFHCEQDLPDCSPSSCFNGGTCVDGVNSFSCLCRPGYTGAHCQHEADPCLSRPCLHGGVCSAAHPGFRCTCLE
SFTGPQCQTLVDWCSRQPCQNGGRCVQTGAYCLCPPGWSGRLCDIRSLPCREAAAQIGVRLEQLCQAGGQCVDEDSSHYCVCPEGRTGSH
CEQEVDPCLAQPCQHGGTCRGYMGGYMCECLPGYNGDNCEDDVDECASQPCQHGGSCIDLVARYLCSCPPGTLGVLCEINEDDCGPGPPL
DSGPRCLHNGTCVDLVGGFRCTCPPGYTGLRCEADINECRSGACHAAHTRDCLQDPGGGFRCLCHAGFSGPRCQTVLSPCESQPCQHGGQ
CRPSPGPGGGLTFTCHCAQPFWGPRCERVARSCRELQCPVGVPCQQTPRGPRCACPPGLSGPSCRSFPGSPPGASNASCAAAPCLHGGSC
RPAPLAPFFRCACAQGWTGPRCEAPAAAPEVSEEPRCPRAACQAKRGDQRCDRECNSPGCGWDGGDCSLSVGDPWRQCEALQCWRLFNNS
RCDPACSSPACLYDNFDCHAGGRERTCNPVYEKYCADHFADGRCDQGCNTEECGWDGLDCASEVPALLARGVLVLTVLLPPEELLRSSAD
FLQRLSAILRTSLRFRLDAHGQAMVFPYHRPSPGSEPRARRELAPEVIGSVVMLEIDNRLCLQSPENDHCFPDAQSAADYLGALSAVERL
DFPYPLRDVRGEPLEPPEPSVPLLPLLVAGAVLLLVILVLGVMVARRKREHSTLWFPEGFSLHKDVASGHKGRREPVGQDALGMKNMAKG
ESLMGEVATDWMDTECPEAKRLKVEEPGMGAEEAVDCRQWTQHHLVAADIRVAPAMALTPPQGDADADGMDVNVRGPDGFTPLMLASFCG
GALEPMPTEEDEADDTSASIISDLICQGAQLGARTDRTGETALHLAARYARADAAKRLLDAGADTNAQDHSGRTPLHTAVTADAQGVFQI
LIRNRSTDLDARMADGSTALILAARLAVEGMVEELIASHADVNAVDELGKSALHWAAAVNNVEATLALLKNGANKDMQDSKEETPLFLAA
REGSYEAAKLLLDHFANREITDHLDRLPRDVAQERLHQDIVRLLDQPSGPRSPPGPHGLGPLLCPPGAFLPGLKAAQSGSKKSRRPPGKA
GLGPQGPRGRGKKLTLACPGPLADSSVTLSPVDSLDSPRPFGGPPASPGGFPLEGPYAAATATAVSLAQLGGPGRAGLGRQPPGGCVLSL
GLLNPVAVPLDWARLPPPAPPGPSFLLPLAPGPQLLNPGTPVSPQERPPPYLAVPGHGEEYPAAGAHSSPPKARFLRVPSEHPYLTPSPE

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Fusion Protein Functional Features


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/chr19:15270445/chr19:6720693)
- 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 buttonMain function of each fusion partner protein. (from UniProt)
HgeneTgene
NOTCH3

Q9UM47

C3

A6NLC5

FUNCTION: Functions as a receptor for membrane-bound ligands Jagged1, Jagged2 and Delta1 to regulate cell-fate determination (PubMed:15350543). Upon ligand activation through the released notch intracellular domain (NICD) it forms a transcriptional activator complex with RBPJ/RBPSUH and activates genes of the enhancer of split locus. Affects the implementation of differentiation, proliferation and apoptotic programs (By similarity). {ECO:0000250|UniProtKB:Q9R172, ECO:0000269|PubMed:15350543}.FUNCTION: May play a role in neuronal and neurobehavioral development. {ECO:0000250|UniProtKB:Q1LY84}.

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, because of limited space for viewing, we only show the protein feature retention information belong to the 13 regional features. All retention annotation result can be downloaded at

download page

* Minus value of BPloci means that the break pointn is located before the CDS.
- Retained protein feature among the 13 regional features.
PartnerGeneHbpTbpENSTStrandBPexonTotalExonProtein feature loci*BPlociTotalLenProtein featureProtein feature note
HgeneNOTCH3chr19:15270445chr19:6720693ENST00000263388-33331000_10342665.02322.0DomainEGF-like 26
HgeneNOTCH3chr19:15270445chr19:6720693ENST00000263388-33331036_10822665.02322.0DomainEGF-like 27
HgeneNOTCH3chr19:15270445chr19:6720693ENST00000263388-33331084_11202665.02322.0DomainEGF-like 28
HgeneNOTCH3chr19:15270445chr19:6720693ENST00000263388-33331122_11582665.02322.0DomainEGF-like 29%3B calcium-binding
HgeneNOTCH3chr19:15270445chr19:6720693ENST00000263388-33331160_12032665.02322.0DomainEGF-like 30%3B calcium-binding
HgeneNOTCH3chr19:15270445chr19:6720693ENST00000263388-3333119_1562665.02322.0DomainEGF-like 3
HgeneNOTCH3chr19:15270445chr19:6720693ENST00000263388-33331205_12442665.02322.0DomainEGF-like 31
HgeneNOTCH3chr19:15270445chr19:6720693ENST00000263388-33331246_12872665.02322.0DomainEGF-like 32
HgeneNOTCH3chr19:15270445chr19:6720693ENST00000263388-33331289_13252665.02322.0DomainEGF-like 33
HgeneNOTCH3chr19:15270445chr19:6720693ENST00000263388-33331335_13732665.02322.0DomainEGF-like 34
HgeneNOTCH3chr19:15270445chr19:6720693ENST00000263388-3333158_1952665.02322.0DomainEGF-like 4%3B calcium-binding
HgeneNOTCH3chr19:15270445chr19:6720693ENST00000263388-3333197_2342665.02322.0DomainEGF-like 5
HgeneNOTCH3chr19:15270445chr19:6720693ENST00000263388-3333236_2722665.02322.0DomainEGF-like 6%3B calcium-binding
HgeneNOTCH3chr19:15270445chr19:6720693ENST00000263388-3333274_3122665.02322.0DomainEGF-like 7
HgeneNOTCH3chr19:15270445chr19:6720693ENST00000263388-3333314_3502665.02322.0DomainEGF-like 8%3B calcium-binding
HgeneNOTCH3chr19:15270445chr19:6720693ENST00000263388-3333351_3892665.02322.0DomainEGF-like 9
HgeneNOTCH3chr19:15270445chr19:6720693ENST00000263388-3333391_4292665.02322.0DomainEGF-like 10%3B calcium-binding
HgeneNOTCH3chr19:15270445chr19:6720693ENST00000263388-333340_772665.02322.0DomainEGF-like 1
HgeneNOTCH3chr19:15270445chr19:6720693ENST00000263388-3333431_4672665.02322.0DomainEGF-like 11%3B calcium-binding
HgeneNOTCH3chr19:15270445chr19:6720693ENST00000263388-3333469_5052665.02322.0DomainEGF-like 12%3B calcium-binding
HgeneNOTCH3chr19:15270445chr19:6720693ENST00000263388-3333507_5432665.02322.0DomainEGF-like 13%3B calcium-binding
HgeneNOTCH3chr19:15270445chr19:6720693ENST00000263388-3333545_5802665.02322.0DomainEGF-like 14%3B calcium-binding
HgeneNOTCH3chr19:15270445chr19:6720693ENST00000263388-3333582_6182665.02322.0DomainEGF-like 15%3B calcium-binding
HgeneNOTCH3chr19:15270445chr19:6720693ENST00000263388-3333620_6552665.02322.0DomainEGF-like 16%3B calcium-binding
HgeneNOTCH3chr19:15270445chr19:6720693ENST00000263388-3333657_6932665.02322.0DomainEGF-like 17%3B calcium-binding
HgeneNOTCH3chr19:15270445chr19:6720693ENST00000263388-3333695_7302665.02322.0DomainEGF-like 18
HgeneNOTCH3chr19:15270445chr19:6720693ENST00000263388-3333734_7702665.02322.0DomainEGF-like 19
HgeneNOTCH3chr19:15270445chr19:6720693ENST00000263388-3333771_8082665.02322.0DomainEGF-like 20
HgeneNOTCH3chr19:15270445chr19:6720693ENST00000263388-333378_1182665.02322.0DomainEGF-like 2
HgeneNOTCH3chr19:15270445chr19:6720693ENST00000263388-3333810_8472665.02322.0DomainEGF-like 21%3B calcium-binding
HgeneNOTCH3chr19:15270445chr19:6720693ENST00000263388-3333849_8852665.02322.0DomainEGF-like 22%3B calcium-binding
HgeneNOTCH3chr19:15270445chr19:6720693ENST00000263388-3333887_9222665.02322.0DomainEGF-like 23%3B calcium-binding
HgeneNOTCH3chr19:15270445chr19:6720693ENST00000263388-3333924_9602665.02322.0DomainEGF-like 24
HgeneNOTCH3chr19:15270445chr19:6720693ENST00000263388-3333962_9982665.02322.0DomainEGF-like 25
HgeneNOTCH3chr19:15270445chr19:6720693ENST00000263388-33331387_14272665.02322.0RepeatNote=LNR 1
HgeneNOTCH3chr19:15270445chr19:6720693ENST00000263388-33331428_14582665.02322.0RepeatNote=LNR 2
HgeneNOTCH3chr19:15270445chr19:6720693ENST00000263388-33331467_15052665.02322.0RepeatNote=LNR 3
HgeneNOTCH3chr19:15270445chr19:6720693ENST00000263388-33331838_18672665.02322.0RepeatNote=ANK 1
HgeneNOTCH3chr19:15270445chr19:6720693ENST00000263388-33331871_19012665.02322.0RepeatNote=ANK 2
HgeneNOTCH3chr19:15270445chr19:6720693ENST00000263388-33331905_19342665.02322.0RepeatNote=ANK 3
HgeneNOTCH3chr19:15270445chr19:6720693ENST00000263388-33331938_19672665.02322.0RepeatNote=ANK 4
HgeneNOTCH3chr19:15270445chr19:6720693ENST00000263388-33331971_20002665.02322.0RepeatNote=ANK 5
HgeneNOTCH3chr19:15270445chr19:6720693ENST00000263388-33331665_23212665.02322.0Topological domainCytoplasmic
HgeneNOTCH3chr19:15270445chr19:6720693ENST00000263388-333340_16432665.02322.0Topological domainExtracellular
HgeneNOTCH3chr19:15270445chr19:6720693ENST00000263388-33331644_16642665.02322.0TransmembraneHelical
TgeneC3chr19:15270445chr19:6720693ENST00000245907-1411518_166124.6666666666666681664.0DomainNTR
TgeneC3chr19:15270445chr19:6720693ENST00000245907-141693_72824.6666666666666681664.0DomainAnaphylatoxin-like

- Not-retained protein feature among the 13 regional features.
PartnerGeneHbpTbpENSTStrandBPexonTotalExonProtein feature loci*BPlociTotalLenProtein featureProtein feature note


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Fusion Protein-Protein Interaction


check button Go to ChiPPI (Chimeric Protein-Protein interactions) to see the chimeric PPI interaction in

ChiPPI page.


check button Protein-protein interactors with each fusion partner protein in wild-type from validated records (BIOGRID-3.4.160)
GenePPI interactors


check button Protein-protein interactors based on sequence similarity (STRING)
GeneSTRING network
NOTCH3
C3


check button - Retained interactions in fusion protein (protein functional feature from UniProt).
PartnerGeneHbpTbpENSTStrandBPexonTotalExonProtein feature loci*BPlociTotalLenStill interaction with


check button - Lost interactions due to fusion (protein functional feature from UniProt).
PartnerGeneHbpTbpENSTStrandBPexonTotalExonProtein feature loci*BPlociTotalLenInteraction lost with


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Related Drugs to NOTCH3-C3


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 NOTCH3-C3


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