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Center for Computational Systems Medicine level2
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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 Structure

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pLDDT scores

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Ramachandran Plot of Fusion Protein Structure

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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:NOV-ENPP2

Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: NOV-ENPP2
FusionPDB ID: 59804
FusionGDB2.0 ID: 59804
HgeneTgene
Gene symbol

NOV

ENPP2

Gene ID

6134

5168

Gene nameribosomal protein L10ectonucleotide pyrophosphatase/phosphodiesterase 2
SynonymsAUTSX5|DXS648|DXS648E|L10|MRXS35|NOV|QMATX|ATX-X|AUTOTAXIN|LysoPLD|NPP2|PD-IALPHA|PDNP2
Cytomap

Xq28

8q24.12

Type of geneprotein-codingprotein-coding
Description60S ribosomal protein L10Wilms tumor-related proteinlaminin receptor homologlarge ribosomal subunit protein uL16tumor suppressor QMectonucleotide pyrophosphatase/phosphodiesterase family member 2E-NPP 2autotaxin-textracellular lysophospholipase Dphosphodiesterase I/nucleotide pyrophosphatase 2plasma lysophospholipase D
Modification date2020031320200313
UniProtAcc

Q9UNW9

Q13822

Ensembl transtripts involved in fusion geneENST idsENST00000259526, ENST00000075322, 
ENST00000518109, ENST00000522167, 
ENST00000522826, ENST00000259486, 
ENST00000427067, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score2 X 2 X 2=810 X 9 X 6=540
# samples 211
** MAII scorelog2(2/8*10)=1.32192809488736log2(11/540*10)=-2.29545588352617
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Context (manual curation of fusion genes in FusionPDB)

PubMed: NOV [Title/Abstract] AND ENPP2 [Title/Abstract] AND fusion [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)NOV(120431585)-ENPP2(120606100), # samples:5
Anticipated loss of major functional domain due to fusion event.NOV-ENPP2 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.
NOV-ENPP2 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.
NOV-ENPP2 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.
NOV-ENPP2 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
TgeneENPP2

GO:0009395

phospholipid catabolic process

15280042|26371182

TgeneENPP2

GO:0030149

sphingolipid catabolic process

14500380

TgeneENPP2

GO:0030334

regulation of cell migration

1733949

TgeneENPP2

GO:0034638

phosphatidylcholine catabolic process

21240271

TgeneENPP2

GO:0050731

positive regulation of peptidyl-tyrosine phosphorylation

18054784


check buttonFusion gene breakpoints across NOV (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 ENPP2 (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
ChimerDB4ESCATCGA-JY-A6FD-01ANOVchr8

120431585

-ENPP2chr8

120606100

-
ChimerDB4ESCATCGA-JY-A6FD-01ANOVchr8

120431585

+ENPP2chr8

120606100

-
ChimerDB4ESCATCGA-JY-A6FDNOVchr8

120431585

+ENPP2chr8

120606100

-


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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)
ENST00000259526NOVchr8120431585+ENST00000259486ENPP2chr8120606100-3059100482623871
ENST00000259526NOVchr8120431585+ENST00000427067ENPP2chr8120606100-3134100482698896

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
ENST00000259526ENST00000259486NOVchr8120431585+ENPP2chr8120606100-0.0019197710.99808025
ENST00000259526ENST00000427067NOVchr8120431585+ENPP2chr8120606100-0.0018631730.99813676

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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

>59804_59804_1_NOV-ENPP2_NOV_chr8_120431585_ENST00000259526_ENPP2_chr8_120606100_ENST00000259486_length(amino acids)=871AA_BP=332
MPWQPRGSFHFPTQPISPLLPALQPTGLCASQERAIKPVLGVIGKHRTRGKASSANLQRRKSRLVKARGESLSMQSVQSTSFCLRKQCLC
LTFLLLHLLGQVAATQRCPPQCPGRCPATPPTCAPGVRAVLDGCSCCLVCARQRGESCSDLEPCDESSGLYCDRSADPSNQTGICTAVEG
DNCVFDGVIYRSGEKFQPSCKFQCTCRDGQIGCVPRCQLDVLLPEPNCPAPRKVEVPGECCEKWICGPDEEDSLGGLTLAAYRPEATLGV
EVSDSSVNCIEQTTEWTACSKSCGMGFSTRVTNRNRQCEMLKQTRLCMVRPCEQEPEQPTDKMTNPLREIDKIVGQLMDGLKQLKLHRCV
NVIFVGDHGMEDVTCDRTEFLSNYLTNVDDITLVPGTLGRIRSKFSNNAKYDPKAIIANLTCKKPDQHFKPYLKQHLPKRLHYANNRRIE
DIHLLVERRWHVARKPLDVYKKPSGKCFFQGDHGFDNKVNSMQTVFVGYGSTFKYKTKVPPFENIELYNVMCDLLGLKPAPNNGTHGSLN
HLLRTNTFRPTMPEEVTRPNYPGIMYLQSDFDLGCTCDDKVEPKNKLDELNKRLHTKGSTEERHLLYGRPAVLYRTRYDILYHTDFESGY
SEIFLMPLWTSYTVSKQAEVSSVPDHLTSCVRPDVRVSPSFSQNCLAYKNDKQMSYGFLFPPYLSSSPEAKYDAFLVTNMVPMYPAFKRV
WNYFQRVLVKKYASERNGVNVISGPIFDYDYDGLHDTEDKIKQYVEGSSIPVPTHYYSIITSCLDFTQPADKCDGPLSVSSFILPHRPDN

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>59804_59804_2_NOV-ENPP2_NOV_chr8_120431585_ENST00000259526_ENPP2_chr8_120606100_ENST00000427067_length(amino acids)=896AA_BP=332
MPWQPRGSFHFPTQPISPLLPALQPTGLCASQERAIKPVLGVIGKHRTRGKASSANLQRRKSRLVKARGESLSMQSVQSTSFCLRKQCLC
LTFLLLHLLGQVAATQRCPPQCPGRCPATPPTCAPGVRAVLDGCSCCLVCARQRGESCSDLEPCDESSGLYCDRSADPSNQTGICTAVEG
DNCVFDGVIYRSGEKFQPSCKFQCTCRDGQIGCVPRCQLDVLLPEPNCPAPRKVEVPGECCEKWICGPDEEDSLGGLTLAAYRPEATLGV
EVSDSSVNCIEQTTEWTACSKSCGMGFSTRVTNRNRQCEMLKQTRLCMVRPCEQEPEQPTDKMTNPLREIDKIVGQLMDGLKQLKLHRCV
NVIFVGDHGMEDVTCDRTEFLSNYLTNVDDITLVPGTLGRIRSKFSNNAKYDPKAIIANLTCKKPDQHFKPYLKQHLPKRLHYANNRRIE
DIHLLVERRWHVARKPLDVYKKPSGKCFFQGDHGFDNKVNSMQTVFVGYGSTFKYKTKVPPFENIELYNVMCDLLGLKPAPNNGTHGSLN
HLLRTNTFRPTMPEEVTRPNYPGIMYLQSDFDLGCTCDDKVEPKNKLDELNKRLHTKGSTEAETRKFRGSRNENKENINGNFEPRKERHL
LYGRPAVLYRTRYDILYHTDFESGYSEIFLMPLWTSYTVSKQAEVSSVPDHLTSCVRPDVRVSPSFSQNCLAYKNDKQMSYGFLFPPYLS
SSPEAKYDAFLVTNMVPMYPAFKRVWNYFQRVLVKKYASERNGVNVISGPIFDYDYDGLHDTEDKIKQYVEGSSIPVPTHYYSIITSCLD

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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/chr8:120431585/chr8:120606100)
- 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
NOV

Q9UNW9

ENPP2

Q13822

FUNCTION: May regulate RNA splicing or metabolism in a specific subset of developing neurons (By similarity). Binds single strand RNA. {ECO:0000250}.FUNCTION: Hydrolyzes lysophospholipids to produce the signaling molecule lysophosphatidic acid (LPA) in extracellular fluids (PubMed:15769751, PubMed:26371182, PubMed:27754931, PubMed:14500380, PubMed:12354767,). Major substrate is lysophosphatidylcholine (PubMed:12176993, PubMed:27754931, PubMed:14500380). Also can act on sphingosylphosphorylcholine producing sphingosine-1-phosphate, a modulator of cell motility (PubMed:14500380). Can hydrolyze, in vitro, bis-pNPP, to some extent pNP-TMP, and barely ATP (PubMed:15769751, PubMed:12176993). Involved in several motility-related processes such as angiogenesis and neurite outgrowth. Acts as an angiogenic factor by stimulating migration of smooth muscle cells and microtubule formation (PubMed:11559573). Stimulates migration of melanoma cells, probably via a pertussis toxin-sensitive G protein (PubMed:1733949). May have a role in induction of parturition (PubMed:12176993). Possible involvement in cell proliferation and adipose tissue development (Probable). Tumor cell motility-stimulating factor (PubMed:1733949, PubMed:11559573). Required for LPA production in activated platelets, cleaves the sn-1 lysophospholipids to generate sn-1 lysophosphatidic acids containing predominantly 18:2 and 20:4 fatty acids (PubMed:21393252). Shows a preference for the sn-1 to the sn-2 isomer of 1-O-alkyl-sn-glycero-3-phosphocholine (lyso-PAF) (PubMed:21393252). {ECO:0000269|PubMed:11559573, ECO:0000269|PubMed:12176993, ECO:0000269|PubMed:12354767, ECO:0000269|PubMed:14500380, ECO:0000269|PubMed:15769751, ECO:0000269|PubMed:1733949, ECO:0000269|PubMed:21240271, ECO:0000269|PubMed:21393252, ECO:0000269|PubMed:26371182, ECO:0000269|PubMed:27754931, ECO:0000305|PubMed:15700135}.

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
HgeneNOVchr8:120431585chr8:120606100ENST00000259526+45108_174259.0358.0DomainVWFC
HgeneNOVchr8:120431585chr8:120606100ENST00000259526+45205_250259.0358.0DomainTSP type-1
HgeneNOVchr8:120431585chr8:120606100ENST00000259526+4532_105259.0358.0DomainIGFBP N-terminal
TgeneENPP2chr8:120431585chr8:120606100ENST000000753221025830_851324.0864.0RegionRequired for secretion
TgeneENPP2chr8:120431585chr8:120606100ENST000002594861126830_851376.0916.0RegionRequired for secretion
TgeneENPP2chr8:120431585chr8:120606100ENST000005228261026830_851324.0889.0RegionRequired for secretion

- Not-retained protein feature among the 13 regional features.
PartnerGeneHbpTbpENSTStrandBPexonTotalExonProtein feature loci*BPlociTotalLenProtein featureProtein feature note
HgeneNOVchr8:120431585chr8:120606100ENST00000259526+45264_338259.0358.0DomainCTCK
TgeneENPP2chr8:120431585chr8:120606100ENST00000075322102555_98324.0864.0DomainSMB 1
TgeneENPP2chr8:120431585chr8:120606100ENST00000075322102599_143324.0864.0DomainSMB 2
TgeneENPP2chr8:120431585chr8:120606100ENST00000259486112655_98376.0916.0DomainSMB 1
TgeneENPP2chr8:120431585chr8:120606100ENST00000259486112699_143376.0916.0DomainSMB 2
TgeneENPP2chr8:120431585chr8:120606100ENST00000522826102655_98324.0889.0DomainSMB 1
TgeneENPP2chr8:120431585chr8:120606100ENST00000522826102699_143324.0889.0DomainSMB 2
TgeneENPP2chr8:120431585chr8:120606100ENST000000753221025127_129324.0864.0MotifCell attachment site
TgeneENPP2chr8:120431585chr8:120606100ENST000002594861126127_129376.0916.0MotifCell attachment site
TgeneENPP2chr8:120431585chr8:120606100ENST000005228261026127_129324.0889.0MotifCell attachment site
TgeneENPP2chr8:120431585chr8:120606100ENST000000753221025211_214324.0864.0RegionSubstrate binding
TgeneENPP2chr8:120431585chr8:120606100ENST000000753221025244_255324.0864.0RegionSubstrate binding
TgeneENPP2chr8:120431585chr8:120606100ENST000002594861126211_214376.0916.0RegionSubstrate binding
TgeneENPP2chr8:120431585chr8:120606100ENST000002594861126244_255376.0916.0RegionSubstrate binding
TgeneENPP2chr8:120431585chr8:120606100ENST000005228261026211_214324.0889.0RegionSubstrate binding
TgeneENPP2chr8:120431585chr8:120606100ENST000005228261026244_255324.0889.0RegionSubstrate binding


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Fusion Protein Structures

check button PDB and CIF files of the predicted fusion proteins
* Here we show the 3D structure of the fusion proteins using Mol*. AlphaFold produces a per-residue confidence score (pLDDT) between 0 and 100. Model confidence is shown from the pLDDT values per residue. pLDDT corresponds to the model’s prediction of its score on the local Distance Difference Test. It is a measure of local accuracy (from AlphfaFold website). To color code individual residues, we transformed individual PDB files into CIF format.
Fusion protein PDB link (fusion AA seq ID in FusionPDB)HgeneHchrHbpHstrandTgeneTchrTbpTstrandAA seqLen(AA seq)
PDB file >>>1689_NOV_120431585_ENPP2_120606100_ranked_0.pdbNOV120431585120431585ENST00000427067ENPP2chr8120606100-
MPWQPRGSFHFPTQPISPLLPALQPTGLCASQERAIKPVLGVIGKHRTRGKASSANLQRRKSRLVKARGESLSMQSVQSTSFCLRKQCLC
LTFLLLHLLGQVAATQRCPPQCPGRCPATPPTCAPGVRAVLDGCSCCLVCARQRGESCSDLEPCDESSGLYCDRSADPSNQTGICTAVEG
DNCVFDGVIYRSGEKFQPSCKFQCTCRDGQIGCVPRCQLDVLLPEPNCPAPRKVEVPGECCEKWICGPDEEDSLGGLTLAAYRPEATLGV
EVSDSSVNCIEQTTEWTACSKSCGMGFSTRVTNRNRQCEMLKQTRLCMVRPCEQEPEQPTDKMTNPLREIDKIVGQLMDGLKQLKLHRCV
NVIFVGDHGMEDVTCDRTEFLSNYLTNVDDITLVPGTLGRIRSKFSNNAKYDPKAIIANLTCKKPDQHFKPYLKQHLPKRLHYANNRRIE
DIHLLVERRWHVARKPLDVYKKPSGKCFFQGDHGFDNKVNSMQTVFVGYGSTFKYKTKVPPFENIELYNVMCDLLGLKPAPNNGTHGSLN
HLLRTNTFRPTMPEEVTRPNYPGIMYLQSDFDLGCTCDDKVEPKNKLDELNKRLHTKGSTEAETRKFRGSRNENKENINGNFEPRKERHL
LYGRPAVLYRTRYDILYHTDFESGYSEIFLMPLWTSYTVSKQAEVSSVPDHLTSCVRPDVRVSPSFSQNCLAYKNDKQMSYGFLFPPYLS
SSPEAKYDAFLVTNMVPMYPAFKRVWNYFQRVLVKKYASERNGVNVISGPIFDYDYDGLHDTEDKIKQYVEGSSIPVPTHYYSIITSCLD
896


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pLDDT score distribution

check button pLDDT score distribution of the predicted wild-type structures of two partner proteins from AlphaFold2
* AlphaFold produces a per-residue confidence score (pLDDT) between 0 and 100.

all structure
ENPP2_pLDDT.png
all structure
all structure

check button pLDDT score distribution of the predicted fusion protein structures from AlphaFold2
* AlphaFold produces a per-residue confidence score (pLDDT) between 0 and 100.
all structure


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Ramachandran Plot of Fusion Protein Structure


check button Ramachandran plot of the torsional angles - phi (φ)and psi (ψ) - of the residues (amino acids) contained in this fusion protein peptide.
Fusion AA seq ID in FusionPDB and their Ramachandran plots

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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
NOV
ENPP2


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 NOV-ENPP2


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 NOV-ENPP2


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