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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:CRK-STX8

Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: CRK-STX8
FusionPDB ID: 19504
FusionGDB2.0 ID: 19504
HgeneTgene
Gene symbol

CRK

STX8

Gene ID

1398

9482

Gene nameCRK proto-oncogene, adaptor proteinsyntaxin 8
SynonymsCRKII|p38CARB
Cytomap

17p13.3

17p13.1

Type of geneprotein-codingprotein-coding
Descriptionadapter molecule crkproto-oncogene c-Crkv-crk avian sarcoma virus CT10 oncogene homologv-crk sarcoma virus CT10 oncogene-like proteinsyntaxin-8CIP-1-associated regulator of cyclin B
Modification date2020032720200313
UniProtAcc

P46109

.
Ensembl transtripts involved in fusion geneENST idsENST00000300574, ENST00000398970, 
ENST00000574295, ENST00000572145, 
ENST00000573373, ENST00000306357, 
ENST00000574431, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score15 X 11 X 7=115524 X 16 X 8=3072
# samples 1829
** MAII scorelog2(18/1155*10)=-2.68182403997375
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(29/3072*10)=-3.40505341070622
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Context (manual curation of fusion genes in FusionPDB)

PubMed: CRK [Title/Abstract] AND STX8 [Title/Abstract] AND fusion [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)CRK(1359171)-STX8(9153962), # samples:3
Anticipated loss of major functional domain due to fusion event.CRK-STX8 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.
CRK-STX8 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
HgeneCRK

GO:0009966

regulation of signal transduction

17515907

HgeneCRK

GO:0032956

regulation of actin cytoskeleton organization

11870224

HgeneCRK

GO:0043087

regulation of GTPase activity

11870224

HgeneCRK

GO:0048013

ephrin receptor signaling pathway

11870224

HgeneCRK

GO:0061045

negative regulation of wound healing

17515907

HgeneCRK

GO:2000146

negative regulation of cell motility

17515907

TgeneSTX8

GO:0045022

early endosome to late endosome transport

10564279

TgeneSTX8

GO:1903076

regulation of protein localization to plasma membrane

18570918


check buttonFusion gene breakpoints across CRK (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 STX8 (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
ChimerDB4LUSCTCGA-85-A4CN-01ACRKchr17

1359171

-STX8chr17

9153962

-
ChimerDB4LUSCTCGA-85-A4CNCRKchr17

1359170

-STX8chr17

9153962

-
ChimerDB4LUSCTCGA-85-A4CNCRKchr17

1359171

-STX8chr17

9153962

-


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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)
ENST00000398970CRKchr171359171-ENST00000306357STX8chr179153962-522347141503120
ENST00000398970CRKchr171359171-ENST00000574431STX8chr179153962-506347141503120
ENST00000300574CRKchr171359171-ENST00000306357STX8chr179153962-557382176538120
ENST00000300574CRKchr171359171-ENST00000574431STX8chr179153962-541382176538120
ENST00000574295CRKchr171359171-ENST00000306357STX8chr179153962-44827367429120
ENST00000574295CRKchr171359171-ENST00000574431STX8chr179153962-43227367429120
ENST00000398970CRKchr171359170-ENST00000306357STX8chr179153962-522347141503120
ENST00000398970CRKchr171359170-ENST00000574431STX8chr179153962-506347141503120
ENST00000300574CRKchr171359170-ENST00000306357STX8chr179153962-557382176538120
ENST00000300574CRKchr171359170-ENST00000574431STX8chr179153962-541382176538120
ENST00000574295CRKchr171359170-ENST00000306357STX8chr179153962-44827367429120
ENST00000574295CRKchr171359170-ENST00000574431STX8chr179153962-43227367429120

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
ENST00000398970ENST00000306357CRKchr171359171-STX8chr179153962-0.073846530.9261534
ENST00000398970ENST00000574431CRKchr171359171-STX8chr179153962-0.067895880.9321041
ENST00000300574ENST00000306357CRKchr171359171-STX8chr179153962-0.054759930.9452401
ENST00000300574ENST00000574431CRKchr171359171-STX8chr179153962-0.0517239460.94827604
ENST00000574295ENST00000306357CRKchr171359171-STX8chr179153962-0.062835750.93716425
ENST00000574295ENST00000574431CRKchr171359171-STX8chr179153962-0.0534751340.94652486
ENST00000398970ENST00000306357CRKchr171359170-STX8chr179153962-0.073846530.9261534
ENST00000398970ENST00000574431CRKchr171359170-STX8chr179153962-0.067895880.9321041
ENST00000300574ENST00000306357CRKchr171359170-STX8chr179153962-0.054759930.9452401
ENST00000300574ENST00000574431CRKchr171359170-STX8chr179153962-0.0517239460.94827604
ENST00000574295ENST00000306357CRKchr171359170-STX8chr179153962-0.062835750.93716425
ENST00000574295ENST00000574431CRKchr171359170-STX8chr179153962-0.0534751340.94652486

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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

>19504_19504_1_CRK-STX8_CRK_chr17_1359170_ENST00000300574_STX8_chr17_9153962_ENST00000306357_length(amino acids)=120AA_BP=68
MVLGEVESAGGGGAAAGPAARGVPGAGLEHQPRGLCAQRLRELARLPLHHQQQRPAPAGATVARPASARDDHGDFTAACGYRGCCSLADQ

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

>19504_19504_2_CRK-STX8_CRK_chr17_1359170_ENST00000300574_STX8_chr17_9153962_ENST00000574431_length(amino acids)=120AA_BP=68
MVLGEVESAGGGGAAAGPAARGVPGAGLEHQPRGLCAQRLRELARLPLHHQQQRPAPAGATVARPASARDDHGDFTAACGYRGCCSLADQ

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

>19504_19504_3_CRK-STX8_CRK_chr17_1359170_ENST00000398970_STX8_chr17_9153962_ENST00000306357_length(amino acids)=120AA_BP=68
MVLGEVESAGGGGAAAGPAARGVPGAGLEHQPRGLCAQRLRELARLPLHHQQQRPAPAGATVARPASARDDHGDFTAACGYRGCCSLADQ

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

>19504_19504_4_CRK-STX8_CRK_chr17_1359170_ENST00000398970_STX8_chr17_9153962_ENST00000574431_length(amino acids)=120AA_BP=68
MVLGEVESAGGGGAAAGPAARGVPGAGLEHQPRGLCAQRLRELARLPLHHQQQRPAPAGATVARPASARDDHGDFTAACGYRGCCSLADQ

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

>19504_19504_5_CRK-STX8_CRK_chr17_1359170_ENST00000574295_STX8_chr17_9153962_ENST00000306357_length(amino acids)=120AA_BP=68
MVLGEVESAGGGGAAAGPAARGVPGAGLEHQPRGLCAQRLRELARLPLHHQQQRPAPAGATVARPASARDDHGDFTAACGYRGCCSLADQ

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

>19504_19504_6_CRK-STX8_CRK_chr17_1359170_ENST00000574295_STX8_chr17_9153962_ENST00000574431_length(amino acids)=120AA_BP=68
MVLGEVESAGGGGAAAGPAARGVPGAGLEHQPRGLCAQRLRELARLPLHHQQQRPAPAGATVARPASARDDHGDFTAACGYRGCCSLADQ

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

>19504_19504_7_CRK-STX8_CRK_chr17_1359171_ENST00000300574_STX8_chr17_9153962_ENST00000306357_length(amino acids)=120AA_BP=68
MVLGEVESAGGGGAAAGPAARGVPGAGLEHQPRGLCAQRLRELARLPLHHQQQRPAPAGATVARPASARDDHGDFTAACGYRGCCSLADQ

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

>19504_19504_8_CRK-STX8_CRK_chr17_1359171_ENST00000300574_STX8_chr17_9153962_ENST00000574431_length(amino acids)=120AA_BP=68
MVLGEVESAGGGGAAAGPAARGVPGAGLEHQPRGLCAQRLRELARLPLHHQQQRPAPAGATVARPASARDDHGDFTAACGYRGCCSLADQ

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

>19504_19504_9_CRK-STX8_CRK_chr17_1359171_ENST00000398970_STX8_chr17_9153962_ENST00000306357_length(amino acids)=120AA_BP=68
MVLGEVESAGGGGAAAGPAARGVPGAGLEHQPRGLCAQRLRELARLPLHHQQQRPAPAGATVARPASARDDHGDFTAACGYRGCCSLADQ

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

>19504_19504_10_CRK-STX8_CRK_chr17_1359171_ENST00000398970_STX8_chr17_9153962_ENST00000574431_length(amino acids)=120AA_BP=68
MVLGEVESAGGGGAAAGPAARGVPGAGLEHQPRGLCAQRLRELARLPLHHQQQRPAPAGATVARPASARDDHGDFTAACGYRGCCSLADQ

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

>19504_19504_11_CRK-STX8_CRK_chr17_1359171_ENST00000574295_STX8_chr17_9153962_ENST00000306357_length(amino acids)=120AA_BP=68
MVLGEVESAGGGGAAAGPAARGVPGAGLEHQPRGLCAQRLRELARLPLHHQQQRPAPAGATVARPASARDDHGDFTAACGYRGCCSLADQ

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

>19504_19504_12_CRK-STX8_CRK_chr17_1359171_ENST00000574295_STX8_chr17_9153962_ENST00000574431_length(amino acids)=120AA_BP=68
MVLGEVESAGGGGAAAGPAARGVPGAGLEHQPRGLCAQRLRELARLPLHHQQQRPAPAGATVARPASARDDHGDFTAACGYRGCCSLADQ

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

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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/chr17:1359171/chr17:9153962)
- 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
CRK

P46109

.
FUNCTION: May mediate the transduction of intracellular signals.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
TgeneSTX8chr17:1359170chr17:9153962ENST0000030635768233_236214.33333333333334237.0Topological domainVesicular
TgeneSTX8chr17:1359171chr17:9153962ENST0000030635768233_236214.33333333333334237.0Topological domainVesicular
TgeneSTX8chr17:1359170chr17:9153962ENST0000030635768216_232214.33333333333334237.0TransmembraneHelical%3B Anchor for type IV membrane protein
TgeneSTX8chr17:1359171chr17:9153962ENST0000030635768216_232214.33333333333334237.0TransmembraneHelical%3B Anchor for type IV membrane protein

- Not-retained protein feature among the 13 regional features.
PartnerGeneHbpTbpENSTStrandBPexonTotalExonProtein feature loci*BPlociTotalLenProtein featureProtein feature note
HgeneCRKchr17:1359170chr17:9153962ENST00000300574-13132_19280.33333333333333305.0DomainSH3 1
HgeneCRKchr17:1359170chr17:9153962ENST00000300574-1313_11880.33333333333333305.0DomainSH2
HgeneCRKchr17:1359170chr17:9153962ENST00000300574-13235_29680.33333333333333305.0DomainSH3 2
HgeneCRKchr17:1359170chr17:9153962ENST00000398970-13132_19280.33333333333333205.0DomainSH3 1
HgeneCRKchr17:1359170chr17:9153962ENST00000398970-1313_11880.33333333333333205.0DomainSH2
HgeneCRKchr17:1359170chr17:9153962ENST00000398970-13235_29680.33333333333333205.0DomainSH3 2
HgeneCRKchr17:1359171chr17:9153962ENST00000300574-13132_19280.33333333333333305.0DomainSH3 1
HgeneCRKchr17:1359171chr17:9153962ENST00000300574-1313_11880.33333333333333305.0DomainSH2
HgeneCRKchr17:1359171chr17:9153962ENST00000300574-13235_29680.33333333333333305.0DomainSH3 2
HgeneCRKchr17:1359171chr17:9153962ENST00000398970-13132_19280.33333333333333205.0DomainSH3 1
HgeneCRKchr17:1359171chr17:9153962ENST00000398970-1313_11880.33333333333333205.0DomainSH2
HgeneCRKchr17:1359171chr17:9153962ENST00000398970-13235_29680.33333333333333205.0DomainSH3 2
TgeneSTX8chr17:1359170chr17:9153962ENST000003063576842_65214.33333333333334237.0Coiled coilOntology_term=ECO:0000255
TgeneSTX8chr17:1359171chr17:9153962ENST000003063576842_65214.33333333333334237.0Coiled coilOntology_term=ECO:0000255
TgeneSTX8chr17:1359170chr17:9153962ENST0000030635768145_207214.33333333333334237.0Domaint-SNARE coiled-coil homology
TgeneSTX8chr17:1359171chr17:9153962ENST0000030635768145_207214.33333333333334237.0Domaint-SNARE coiled-coil homology
TgeneSTX8chr17:1359170chr17:9153962ENST00000306357681_215214.33333333333334237.0Topological domainCytoplasmic
TgeneSTX8chr17:1359171chr17:9153962ENST00000306357681_215214.33333333333334237.0Topological domainCytoplasmic


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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 >>>48_CRK_1359171_STX8_9153962_ranked_0.pdbCRK13591701359171ENST00000574431STX8chr179153962-
MVLGEVESAGGGGAAAGPAARGVPGAGLEHQPRGLCAQRLRELARLPLHHQQQRPAPAGATVARPASARDDHGDFTAACGYRGCCSLADQ
120


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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.
CRK_pLDDT.png
all structure
all structure
STX8_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
CRK
STX8


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 CRK-STX8


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 CRK-STX8


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