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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:NAP1L1-OSTF1

Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: NAP1L1-OSTF1
FusionPDB ID: 57187
FusionGDB2.0 ID: 57187
HgeneTgene
Gene symbol

NAP1L1

OSTF1

Gene ID

4673

26578

Gene namenucleosome assembly protein 1 like 1osteoclast stimulating factor 1
SynonymsNAP1|NAP1L|NRPOSF|SH3P2|bA235O14.1
Cytomap

12q21.2

9q21.13

Type of geneprotein-codingprotein-coding
Descriptionnucleosome assembly protein 1-like 1HSP22-like protein interacting proteinNAP-1-related proteinosteoclast-stimulating factor 1
Modification date2020032220200313
UniProtAcc

P55209

.
Ensembl transtripts involved in fusion geneENST idsENST00000261182, ENST00000393263, 
ENST00000431879, ENST00000535020, 
ENST00000542344, ENST00000544816, 
ENST00000547773, ENST00000548044, 
ENST00000549596, ENST00000552342, 
ENST00000547993, 
ENST00000346234, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score17 X 16 X 4=10885 X 5 X 3=75
# samples 247
** MAII scorelog2(24/1088*10)=-2.18057224564182
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(7/75*10)=-0.0995356735509144
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Context (manual curation of fusion genes in FusionPDB)

PubMed: NAP1L1 [Title/Abstract] AND OSTF1 [Title/Abstract] AND fusion [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)NAP1L1(76467983)-OSTF1(77752454), # samples:3
Anticipated loss of major functional domain due to fusion event.NAP1L1-OSTF1 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.
NAP1L1-OSTF1 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.
NAP1L1-OSTF1 seems lost the major protein functional domain in Hgene partner, which is a epigenetic factor due to the frame-shifted ORF.
NAP1L1-OSTF1 seems lost the major protein functional domain in Hgene partner, which is a essential gene 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

check buttonFusion gene breakpoints across NAP1L1 (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 OSTF1 (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
ChimerDB4SARCTCGA-DX-A6BE-01ANAP1L1chr12

76467983

-OSTF1chr9

77752454

+
ChimerDB4SARCTCGA-WK-A8Y0-01ANAP1L1chr12

76467983

-OSTF1chr9

77752454

+
ChimerDB4SARCTCGA-WK-A8Y0-01ANAP1L1chr12

76478347

-OSTF1chr9

77752454

+


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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)
ENST00000393263NAP1L1chr1276467983-ENST00000346234OSTF1chr977752454+89813714337376

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
ENST00000393263ENST00000346234NAP1L1chr1276467983-OSTF1chr977752454+0.575384740.4246152

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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

>57187_57187_1_NAP1L1-OSTF1_NAP1L1_chr12_76467983_ENST00000393263_OSTF1_chr9_77752454_ENST00000346234_length(amino acids)=76AA_BP=

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

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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/chr12:76467983/chr9:77752454)
- 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
NAP1L1

P55209

.
FUNCTION: Histone chaperone that plays a role in the nuclear import of H2A-H2B and nucleosome assembly (PubMed:20002496, PubMed:26841755). Participates also in several important DNA repair mechanisms: greatly enhances ERCC6-mediated chromatin remodeling which is essential for transcription-coupled nucleotide excision DNA repair (PubMed:28369616). Stimulates also homologous recombination (HR) by RAD51 and RAD54 which is essential in mitotic DNA double strand break (DSB) repair (PubMed:24798879). Plays a key role in the regulation of embryonic neurogenesis (By similarity). Promotes the proliferation of neural progenitors and inhibits neuronal differentiation during cortical development (By similarity). Regulates neurogenesis via the modulation of RASSF10; regulates RASSF10 expression by promoting SETD1A-mediated H3K4 methylation at the RASSF10 promoter (By similarity). {ECO:0000250|UniProtKB:P28656, ECO:0000269|PubMed:20002496, ECO:0000269|PubMed:24798879, ECO:0000269|PubMed:26841755, ECO:0000269|PubMed:28369616}.; FUNCTION: (Microbial infection) Positively regulates Epstein-Barr virus reactivation in epithelial cells through the induction of viral BZLF1 expression. {ECO:0000269|PubMed:23691099}.; FUNCTION: (Microbial infection) Together with human herpesvirus 8 protein LANA1, assists the proper assembly of the nucleosome on the replicated viral DNA. {ECO:0000269|PubMed:27599637}.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
TgeneOSTF1chr12:76467983chr9:77752454ENST00000346234610139_168136.0215.0RepeatNote=ANK 3

- Not-retained protein feature among the 13 regional features.
PartnerGeneHbpTbpENSTStrandBPexonTotalExonProtein feature loci*BPlociTotalLenProtein featureProtein feature note
HgeneNAP1L1chr12:76467983chr9:77752454ENST00000261182-21510_305.666666666666667392.0Compositional biasNote=Asp/Glu-rich (acidic)
HgeneNAP1L1chr12:76467983chr9:77752454ENST00000261182-215129_1455.666666666666667392.0Compositional biasNote=Asp/Glu-rich (acidic)
HgeneNAP1L1chr12:76467983chr9:77752454ENST00000261182-215348_3785.666666666666667392.0Compositional biasNote=Asp/Glu-rich (acidic)
HgeneNAP1L1chr12:76467983chr9:77752454ENST00000393263-21610_305.666666666666667558.3333333333334Compositional biasNote=Asp/Glu-rich (acidic)
HgeneNAP1L1chr12:76467983chr9:77752454ENST00000393263-216129_1455.666666666666667558.3333333333334Compositional biasNote=Asp/Glu-rich (acidic)
HgeneNAP1L1chr12:76467983chr9:77752454ENST00000393263-216348_3785.666666666666667558.3333333333334Compositional biasNote=Asp/Glu-rich (acidic)
HgeneNAP1L1chr12:76467983chr9:77752454ENST00000261182-215273_2795.666666666666667392.0MotifNuclear localization signal
HgeneNAP1L1chr12:76467983chr9:77752454ENST00000393263-216273_2795.666666666666667558.3333333333334MotifNuclear localization signal
TgeneOSTF1chr12:76467983chr9:77752454ENST000003462346104_11136.0215.0Compositional biasNote=Pro-rich
TgeneOSTF1chr12:76467983chr9:77752454ENST0000034623461012_71136.0215.0DomainSH3
TgeneOSTF1chr12:76467983chr9:77752454ENST00000346234610105_135136.0215.0RepeatNote=ANK 2
TgeneOSTF1chr12:76467983chr9:77752454ENST0000034623461072_101136.0215.0RepeatNote=ANK 1


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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)


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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
OSTF1_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.


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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
NAP1L1
OSTF1


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 NAP1L1-OSTF1


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 NAP1L1-OSTF1


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