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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:NRP1-PTEN

Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: NRP1-PTEN
FusionPDB ID: 60345
FusionGDB2.0 ID: 60345
HgeneTgene
Gene symbol

NRP1

PTEN

Gene ID

8829

5728

Gene nameneuropilin 1phosphatase and tensin homolog
SynonymsBDCA4|CD304|NP1|NRP|VEGF165R10q23del|BZS|CWS1|DEC|GLM2|MHAM|MMAC1|PTEN1|PTENbeta|TEP1
Cytomap

10p11.22

10q23.31

Type of geneprotein-codingprotein-coding
Descriptionneuropilin-1transmembrane receptorvascular endothelial cell growth factor 165 receptorphosphatidylinositol 3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTENMMAC1 phosphatase and tensin homolog deleted on chromosome 10PTENepsilonmitochondrial PTENalphamitochondrial phosphatase and tensin protein alphamutat
Modification date2020032220200329
UniProtAcc

O14786

.
Ensembl transtripts involved in fusion geneENST idsENST00000265371, ENST00000374816, 
ENST00000374821, ENST00000374822, 
ENST00000374823, ENST00000374867, 
ENST00000395995, ENST00000432372, 
ENST00000374875, 
ENST00000472832, 
ENST00000371953, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score13 X 9 X 6=70230 X 21 X 10=6300
# samples 1436
** MAII scorelog2(14/702*10)=-2.32604420335959
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(36/6300*10)=-4.12928301694497
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Context (manual curation of fusion genes in FusionPDB)

PubMed: NRP1 [Title/Abstract] AND PTEN [Title/Abstract] AND fusion [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)NRP1(33619636)-PTEN(89717610), # samples:3
PTEN(89693008)-NRP1(33559784), # samples:2
Anticipated loss of major functional domain due to fusion event.NRP1-PTEN 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.
NRP1-PTEN 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.
NRP1-PTEN 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.
NRP1-PTEN 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.
NRP1-PTEN seems lost the major protein functional domain in Hgene partner, which is a IUPHAR drug target due to the frame-shifted ORF.
NRP1-PTEN seems lost the major protein functional domain in Tgene partner, which is a cell metabolism gene due to the frame-shifted ORF.
NRP1-PTEN seems lost the major protein functional domain in Tgene partner, which is a CGC due to the frame-shifted ORF.
NRP1-PTEN seems lost the major protein functional domain in Tgene partner, which is a IUPHAR drug target due to the frame-shifted ORF.
NRP1-PTEN seems lost the major protein functional domain in Tgene partner, which is a tumor suppressor due to the frame-shifted 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
HgeneNRP1

GO:0051894

positive regulation of focal adhesion assembly

24863063

TgenePTEN

GO:0001933

negative regulation of protein phosphorylation

20123964

TgenePTEN

GO:0006470

protein dephosphorylation

9256433

TgenePTEN

GO:0008285

negative regulation of cell proliferation

19057511

TgenePTEN

GO:0045736

negative regulation of cyclin-dependent protein serine/threonine kinase activity

21241890

TgenePTEN

GO:0046855

inositol phosphate dephosphorylation

9593664

TgenePTEN

GO:0046856

phosphatidylinositol dephosphorylation

9593664|9811831

TgenePTEN

GO:0050821

protein stabilization

20123964

TgenePTEN

GO:0060070

canonical Wnt signaling pathway

20123964

TgenePTEN

GO:1902807

negative regulation of cell cycle G1/S phase transition

10918569

TgenePTEN

GO:1904668

positive regulation of ubiquitin protein ligase activity

21241890

TgenePTEN

GO:2000060

positive regulation of ubiquitin-dependent protein catabolic process

21241890

TgenePTEN

GO:2000134

negative regulation of G1/S transition of mitotic cell cycle

21241890


check buttonFusion gene breakpoints across NRP1 (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 PTEN (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
ChimerDB4PRADTCGA-HC-A48F-01ANRP1chr10

33619636

-PTENchr10

89717610

+
ChimerDB4PRADTCGA-HC-A48FNRP1chr10

33619635

-PTENchr10

89717609

+
ChimerDB4PRADTCGA-HC-A48FNRP1chr10

33619636

-PTENchr10

89717610

+


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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)
ENST00000265371NRP1chr1033619636-ENST00000371953PTENchr1089717610+78107748541351165
ENST00000265371NRP1chr1033619635-ENST00000371953PTENchr1089717609+78107748541351165

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
ENST00000265371ENST00000371953NRP1chr1033619636-PTENchr1089717610+0.0007062480.9992937
ENST00000265371ENST00000371953NRP1chr1033619635-PTENchr1089717609+0.0007062480.9992937

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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

>60345_60345_1_NRP1-PTEN_NRP1_chr10_33619635_ENST00000265371_PTEN_chr10_89717609_ENST00000371953_length(amino acids)=165AA_BP=
MYFEFPQPLPVCGDIKVEFFHKQNKMLKKDKMFHFWVNTFFIPGPEETSEKVENGSLCDQEIDSICSIERADNDKEYLVLTLTKNDLDKA

--------------------------------------------------------------

>60345_60345_2_NRP1-PTEN_NRP1_chr10_33619636_ENST00000265371_PTEN_chr10_89717610_ENST00000371953_length(amino acids)=165AA_BP=
MYFEFPQPLPVCGDIKVEFFHKQNKMLKKDKMFHFWVNTFFIPGPEETSEKVENGSLCDQEIDSICSIERADNDKEYLVLTLTKNDLDKA

--------------------------------------------------------------

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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/chr10:33619636/chr10:89717610)
- 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
NRP1

O14786

.
FUNCTION: Cell-surface receptor involved in the development of the cardiovascular system, in angiogenesis, in the formation of certain neuronal circuits and in organogenesis outside the nervous system. Mediates the chemorepulsant activity of semaphorins (PubMed:9288753, PubMed:9529250, PubMed:10688880). Recognizes a C-end rule (CendR) motif R/KXXR/K on its ligands which causes cellular internalization and vascular leakage (PubMed:19805273). It binds to semaphorin 3A, the PLGF-2 isoform of PGF, the VEGF165 isoform of VEGFA and VEGFB (PubMed:9288753, PubMed:9529250, PubMed:10688880, PubMed:19805273). Coexpression with KDR results in increased VEGF165 binding to KDR as well as increased chemotaxis. Regulates VEGF-induced angiogenesis. Binding to VEGFA initiates a signaling pathway needed for motor neuron axon guidance and cell body migration, including for the caudal migration of facial motor neurons from rhombomere 4 to rhombomere 6 during embryonic development (By similarity). Regulates mitochondrial iron transport via interaction with ABCB8/MITOSUR (PubMed:30623799). {ECO:0000250|UniProtKB:P97333, ECO:0000269|PubMed:10688880, ECO:0000269|PubMed:19805273, ECO:0000269|PubMed:30623799, ECO:0000269|PubMed:9288753, ECO:0000269|PubMed:9529250}.; FUNCTION: [Isoform 2]: Binds VEGF-165 and may inhibit its binding to cells (PubMed:10748121, PubMed:26503042). May induce apoptosis by sequestering VEGF-165 (PubMed:10748121). May bind as well various members of the semaphorin family. Its expression has an averse effect on blood vessel number and integrity. {ECO:0000269|PubMed:10748121, ECO:0000269|PubMed:26503042}.; FUNCTION: (Microbial infection) Acts as a host factor for human coronavirus SARS-CoV-2 infection. Recognizes and binds to CendR motif RRAR on SARS-CoV-2 spike protein S1 which enhances SARS-CoV-2 infection. {ECO:0000269|PubMed:33082293, ECO:0000269|PubMed:33082294}.FUNCTION: Might normally function as a transcriptional repressor. EWS-fusion-proteins (EFPS) may play a role in the tumorigenic process. They may disturb gene expression by mimicking, or interfering with the normal function of CTD-POLII within the transcription initiation complex. They may also contribute to an aberrant activation of the fusion protein target genes.

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
TgenePTENchr10:33619635chr10:89717609ENST0000037195359401_403211.33333333333334404.0RegionNote=PDZ domain-binding
TgenePTENchr10:33619636chr10:89717610ENST0000037195359401_403211.33333333333334404.0RegionNote=PDZ domain-binding

- Not-retained protein feature among the 13 regional features.
PartnerGeneHbpTbpENSTStrandBPexonTotalExonProtein feature loci*BPlociTotalLenProtein featureProtein feature note
HgeneNRP1chr10:33619635chr10:89717609ENST00000265371-318147_26582.66666666666667924.0DomainCUB 2
HgeneNRP1chr10:33619635chr10:89717609ENST00000265371-31827_14182.66666666666667924.0DomainCUB 1
HgeneNRP1chr10:33619635chr10:89717609ENST00000265371-318645_81182.66666666666667924.0DomainMAM
HgeneNRP1chr10:33619635chr10:89717609ENST00000374821-211147_26582.66666666666667610.0DomainCUB 2
HgeneNRP1chr10:33619635chr10:89717609ENST00000374821-21127_14182.66666666666667610.0DomainCUB 1
HgeneNRP1chr10:33619635chr10:89717609ENST00000374821-211645_81182.66666666666667610.0DomainMAM
HgeneNRP1chr10:33619635chr10:89717609ENST00000374822-212147_26582.66666666666667645.0DomainCUB 2
HgeneNRP1chr10:33619635chr10:89717609ENST00000374822-21227_14182.66666666666667645.0DomainCUB 1
HgeneNRP1chr10:33619635chr10:89717609ENST00000374822-212645_81182.66666666666667645.0DomainMAM
HgeneNRP1chr10:33619635chr10:89717609ENST00000374867-217147_26582.66666666666667924.0DomainCUB 2
HgeneNRP1chr10:33619635chr10:89717609ENST00000374867-21727_14182.66666666666667924.0DomainCUB 1
HgeneNRP1chr10:33619635chr10:89717609ENST00000374867-217645_81182.66666666666667924.0DomainMAM
HgeneNRP1chr10:33619636chr10:89717610ENST00000265371-318147_26582.66666666666667924.0DomainCUB 2
HgeneNRP1chr10:33619636chr10:89717610ENST00000265371-31827_14182.66666666666667924.0DomainCUB 1
HgeneNRP1chr10:33619636chr10:89717610ENST00000265371-318645_81182.66666666666667924.0DomainMAM
HgeneNRP1chr10:33619636chr10:89717610ENST00000374821-211147_26582.66666666666667610.0DomainCUB 2
HgeneNRP1chr10:33619636chr10:89717610ENST00000374821-21127_14182.66666666666667610.0DomainCUB 1
HgeneNRP1chr10:33619636chr10:89717610ENST00000374821-211645_81182.66666666666667610.0DomainMAM
HgeneNRP1chr10:33619636chr10:89717610ENST00000374822-212147_26582.66666666666667645.0DomainCUB 2
HgeneNRP1chr10:33619636chr10:89717610ENST00000374822-21227_14182.66666666666667645.0DomainCUB 1
HgeneNRP1chr10:33619636chr10:89717610ENST00000374822-212645_81182.66666666666667645.0DomainMAM
HgeneNRP1chr10:33619636chr10:89717610ENST00000374867-217147_26582.66666666666667924.0DomainCUB 2
HgeneNRP1chr10:33619636chr10:89717610ENST00000374867-21727_14182.66666666666667924.0DomainCUB 1
HgeneNRP1chr10:33619636chr10:89717610ENST00000374867-217645_81182.66666666666667924.0DomainMAM
HgeneNRP1chr10:33619635chr10:89717609ENST00000265371-31822_85682.66666666666667924.0Topological domainExtracellular
HgeneNRP1chr10:33619635chr10:89717609ENST00000265371-318880_92382.66666666666667924.0Topological domainCytoplasmic
HgeneNRP1chr10:33619635chr10:89717609ENST00000374821-21122_85682.66666666666667610.0Topological domainExtracellular
HgeneNRP1chr10:33619635chr10:89717609ENST00000374821-211880_92382.66666666666667610.0Topological domainCytoplasmic
HgeneNRP1chr10:33619635chr10:89717609ENST00000374822-21222_85682.66666666666667645.0Topological domainExtracellular
HgeneNRP1chr10:33619635chr10:89717609ENST00000374822-212880_92382.66666666666667645.0Topological domainCytoplasmic
HgeneNRP1chr10:33619635chr10:89717609ENST00000374867-21722_85682.66666666666667924.0Topological domainExtracellular
HgeneNRP1chr10:33619635chr10:89717609ENST00000374867-217880_92382.66666666666667924.0Topological domainCytoplasmic
HgeneNRP1chr10:33619636chr10:89717610ENST00000265371-31822_85682.66666666666667924.0Topological domainExtracellular
HgeneNRP1chr10:33619636chr10:89717610ENST00000265371-318880_92382.66666666666667924.0Topological domainCytoplasmic
HgeneNRP1chr10:33619636chr10:89717610ENST00000374821-21122_85682.66666666666667610.0Topological domainExtracellular
HgeneNRP1chr10:33619636chr10:89717610ENST00000374821-211880_92382.66666666666667610.0Topological domainCytoplasmic
HgeneNRP1chr10:33619636chr10:89717610ENST00000374822-21222_85682.66666666666667645.0Topological domainExtracellular
HgeneNRP1chr10:33619636chr10:89717610ENST00000374822-212880_92382.66666666666667645.0Topological domainCytoplasmic
HgeneNRP1chr10:33619636chr10:89717610ENST00000374867-21722_85682.66666666666667924.0Topological domainExtracellular
HgeneNRP1chr10:33619636chr10:89717610ENST00000374867-217880_92382.66666666666667924.0Topological domainCytoplasmic
HgeneNRP1chr10:33619635chr10:89717609ENST00000265371-318857_87982.66666666666667924.0TransmembraneHelical
HgeneNRP1chr10:33619635chr10:89717609ENST00000374821-211857_87982.66666666666667610.0TransmembraneHelical
HgeneNRP1chr10:33619635chr10:89717609ENST00000374822-212857_87982.66666666666667645.0TransmembraneHelical
HgeneNRP1chr10:33619635chr10:89717609ENST00000374867-217857_87982.66666666666667924.0TransmembraneHelical
HgeneNRP1chr10:33619636chr10:89717610ENST00000265371-318857_87982.66666666666667924.0TransmembraneHelical
HgeneNRP1chr10:33619636chr10:89717610ENST00000374821-211857_87982.66666666666667610.0TransmembraneHelical
HgeneNRP1chr10:33619636chr10:89717610ENST00000374822-212857_87982.66666666666667645.0TransmembraneHelical
HgeneNRP1chr10:33619636chr10:89717610ENST00000374867-217857_87982.66666666666667924.0TransmembraneHelical
TgenePTENchr10:33619635chr10:89717609ENST000003719535914_185211.33333333333334404.0DomainPhosphatase tensin-type
TgenePTENchr10:33619635chr10:89717609ENST0000037195359190_350211.33333333333334404.0DomainC2 tensin-type
TgenePTENchr10:33619636chr10:89717610ENST000003719535914_185211.33333333333334404.0DomainPhosphatase tensin-type
TgenePTENchr10:33619636chr10:89717610ENST0000037195359190_350211.33333333333334404.0DomainC2 tensin-type


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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 >>>167_NRP1_33619636_PTEN_89717610_ranked_0.pdbNRP13361963533619636ENST00000371953PTENchr1089717610+
MYFEFPQPLPVCGDIKVEFFHKQNKMLKKDKMFHFWVNTFFIPGPEETSEKVENGSLCDQEIDSICSIERADNDKEYLVLTLTKNDLDKA
165


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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.
NRP1_pLDDT.png
all structure
all structure
PTEN_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
NRP1
PTEN


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 NRP1-PTEN


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 NRP1-PTEN


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