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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:HSP90B1-S100A4

Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: HSP90B1-S100A4
FusionPDB ID: 37828
FusionGDB2.0 ID: 37828
HgeneTgene
Gene symbol

HSP90B1

S100A4

Gene ID

7184

6275

Gene nameheat shock protein 90 beta family member 1S100 calcium binding protein A4
SynonymsECGP|GP96|GRP94|HEL-S-125m|HEL35|TRA118A2|42A|CAPL|FSP1|MTS1|P9KA|PEL98
Cytomap

12q23.3

1q21.3

Type of geneprotein-codingprotein-coding
Descriptionendoplasmin94 kDa glucose-regulated proteinendothelial cell (HBMEC) glycoproteinepididymis luminal protein 35epididymis secretory sperm binding protein Li 125mheat shock protein 90 kDa beta member 1heat shock protein 90kDa beta (Grp94), member 1heaprotein S100-A4S100 calcium-binding protein A4 (calcium protein, calvasculin, metastasin, murine placental homolog)calcium placental proteinfibroblast-specific protein-1leukemia multidrug resistance associated proteinmalignant transformation suppress
Modification date2020032020200327
UniProtAcc

P14625

.
Ensembl transtripts involved in fusion geneENST idsENST00000299767, ENST00000354332, 
ENST00000368714, ENST00000368716, 
ENST00000481009, ENST00000368715, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score19 X 19 X 10=36105 X 3 X 4=60
# samples 255
** MAII scorelog2(25/3610*10)=-3.85199883711245
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(5/60*10)=-0.263034405833794
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Context (manual curation of fusion genes in FusionPDB)

PubMed: HSP90B1 [Title/Abstract] AND S100A4 [Title/Abstract] AND fusion [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)HSP90B1(104340474)-S100A4(153516399), # samples:1
Anticipated loss of major functional domain due to fusion event.HSP90B1-S100A4 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.
HSP90B1-S100A4 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.
HSP90B1-S100A4 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.
HSP90B1-S100A4 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
HgeneHSP90B1

GO:0001666

response to hypoxia

15620698

HgeneHSP90B1

GO:0031247

actin rod assembly

19000834

HgeneHSP90B1

GO:0043666

regulation of phosphoprotein phosphatase activity

19000834

HgeneHSP90B1

GO:0071318

cellular response to ATP

19000834

TgeneS100A4

GO:0043123

positive regulation of I-kappaB kinase/NF-kappaB signaling

15033494


check buttonFusion gene breakpoints across HSP90B1 (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 S100A4 (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
ChimerDB4Non-Cancer215NHSP90B1chr12

104340474

+S100A4chr1

153516399

-


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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)
ENST00000299767HSP90B1chr12104340474+ENST00000368715S100A4chr1153516399-259922881822452756

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
ENST00000299767ENST00000368715HSP90B1chr12104340474+S100A4chr1153516399-0.0005291480.9994709

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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

>37828_37828_1_HSP90B1-S100A4_HSP90B1_chr12_104340474_ENST00000299767_S100A4_chr1_153516399_ENST00000368715_length(amino acids)=756AA_BP=702
MRALWVLGLCCVLLTFGSVRADDEVDVDGTVEEDLGKSREGSRTDDEVVQREEEAIQLDGLNASQIRELREKSEKFAFQAEVNRMMKLII
NSLYKNKEIFLRELISNASDALDKIRLISLTDENALSGNEELTVKIKCDKEKNLLHVTDTGVGMTREELVKNLGTIAKSGTSEFLNKMTE
AQEDGQSTSELIGQFGVGFYSAFLVADKVIVTSKHNNDTQHIWESDSNEFSVIADPRGNTLGRGTTITLVLKEEASDYLELDTIKNLVKK
YSQFINFPIYVWSSKTETVEEPMEEEEAAKEEKEESDDEAAVEEEEEEKKPKTKKVEKTVWDWELMNDIKPIWQRPSKEVEEDEYKAFYK
SFSKESDDPMAYIHFTAEGEVTFKSILFVPTSAPRGLFDEYGSKKSDYIKLYVRRVFITDDFHDMMPKYLNFVKGVVDSDDLPLNVSRET
LQQHKLLKVIRKKLVRKTLDMIKKIADDKYNDTFWKEFGTNIKLGVIEDHSNRTRLAKLLRFQSSHHPTDITSLDQYVERMKEKQDKIYF
MAGSSRKEAESSPFVERLLKKGYEVIYLTEPVDEYCIQALPEFDGKRFQNVAKEGVKFDESEKTKESREAVEKEFEPLLNWMKDKALKDK
IEKAVVSQRLTESPCALVASQYGWSGNMERIMKAQAYQTGKDISTNYYASQKKTFEINPRHPLIRDMLRRIKKRTDEAAFQKLMSNLDSN

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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/chr12:104340474/chr1:153516399)
- 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
HSP90B1

P14625

.
FUNCTION: Molecular chaperone that functions in the processing and transport of secreted proteins (By similarity). When associated with CNPY3, required for proper folding of Toll-like receptors (By similarity). Functions in endoplasmic reticulum associated degradation (ERAD) (PubMed:18264092). Has ATPase activity (By similarity). May participate in the unfolding of cytosolic leaderless cargos (lacking the secretion signal sequence) such as the interleukin 1/IL-1 to facilitate their translocation into the ERGIC (endoplasmic reticulum-Golgi intermediate compartment) and secretion; the translocation process is mediated by the cargo receptor TMED10 (PubMed:32272059). {ECO:0000250|UniProtKB:P08113, ECO:0000269|PubMed:18264092, ECO:0000269|PubMed:32272059}.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
TgeneS100A4chr12:104340474chr1:153516399ENST000003543322463_7447.0102.0Calcium binding2%3B high affinity
TgeneS100A4chr12:104340474chr1:153516399ENST000003687141363_7447.0102.0Calcium binding2%3B high affinity
TgeneS100A4chr12:104340474chr1:153516399ENST000003687151363_7447.0102.0Calcium binding2%3B high affinity
TgeneS100A4chr12:104340474chr1:153516399ENST000003687161363_7447.0102.0Calcium binding2%3B high affinity
TgeneS100A4chr12:104340474chr1:153516399ENST000003543322450_8547.0102.0DomainEF-hand 2
TgeneS100A4chr12:104340474chr1:153516399ENST000003687141350_8547.0102.0DomainEF-hand 2
TgeneS100A4chr12:104340474chr1:153516399ENST000003687151350_8547.0102.0DomainEF-hand 2
TgeneS100A4chr12:104340474chr1:153516399ENST000003687161350_8547.0102.0DomainEF-hand 2

- Not-retained protein feature among the 13 regional features.
PartnerGeneHbpTbpENSTStrandBPexonTotalExonProtein feature loci*BPlociTotalLenProtein featureProtein feature note
HgeneHSP90B1chr12:104340474chr1:153516399ENST00000299767+1518800_803702.0804.0MotifNote=Prevents secretion from ER
TgeneS100A4chr12:104340474chr1:153516399ENST000003543322420_3347.0102.0Calcium binding1%3B low affinity
TgeneS100A4chr12:104340474chr1:153516399ENST000003687141320_3347.0102.0Calcium binding1%3B low affinity
TgeneS100A4chr12:104340474chr1:153516399ENST000003687151320_3347.0102.0Calcium binding1%3B low affinity
TgeneS100A4chr12:104340474chr1:153516399ENST000003687161320_3347.0102.0Calcium binding1%3B low affinity
TgeneS100A4chr12:104340474chr1:153516399ENST000003543322412_4747.0102.0DomainEF-hand 1
TgeneS100A4chr12:104340474chr1:153516399ENST000003687141312_4747.0102.0DomainEF-hand 1
TgeneS100A4chr12:104340474chr1:153516399ENST000003687151312_4747.0102.0DomainEF-hand 1
TgeneS100A4chr12:104340474chr1:153516399ENST000003687161312_4747.0102.0DomainEF-hand 1


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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
HSP90B1
S100A4


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 HSP90B1-S100A4


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 HSP90B1-S100A4


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