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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:HKR1-CHMP2A

Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: HKR1-CHMP2A
FusionPDB ID: 36597
FusionGDB2.0 ID: 36597
HgeneTgene
Gene symbol

HKR1

CHMP2A

Gene ID

284459

27243

Gene namezinc finger protein 875charged multivesicular body protein 2A
SynonymsHKR1BC-2|BC2|CHMP2|VPS2|VPS2A
Cytomap

19q13.12

19q13.43

Type of geneprotein-codingprotein-coding
Descriptionzinc finger protein 875HKR1, GLI-Kruppel zinc finger family memberKrueppel-related zinc finger protein 1oncogene HKR1charged multivesicular body protein 2aVPS2 homolog Achromatin modifying protein 2Aputative breast adenocarcinoma marker (32kD)putative breast adenocarcinoma marker BC-2vacuolar protein sorting-associated protein 2-1vps2-1
Modification date2020031320200313
UniProtAcc.

O43633

Ensembl transtripts involved in fusion geneENST idsENST00000324411, ENST00000392153, 
ENST00000589392, ENST00000591259, 
ENST00000541583, ENST00000544914, 
ENST00000586897, ENST00000589218, 
ENST00000591134, ENST00000591417, 
ENST00000591471, ENST00000592168, 
ENST00000312547, ENST00000600118, 
ENST00000601220, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score10 X 6 X 7=4205 X 4 X 3=60
# samples 115
** MAII scorelog2(11/420*10)=-1.93288580414146
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: HKR1 [Title/Abstract] AND CHMP2A [Title/Abstract] AND fusion [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)HKR1(37826159)-CHMP2A(59063552), # samples:2
Anticipated loss of major functional domain due to fusion event.HKR1-CHMP2A 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.
HKR1-CHMP2A 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.
HKR1-CHMP2A 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.
HKR1-CHMP2A 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
TgeneCHMP2A

GO:0039702

viral budding via host ESCRT complex

24878737


check buttonFusion gene breakpoints across HKR1 (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 CHMP2A (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-KK-A8IA-01AHKR1chr19

37826159

+CHMP2Achr19

59063552

-
ChimerDB4PRADTCGA-KK-A8IAHKR1chr19

37826159

+CHMP2Achr19

59063552

-


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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)
ENST00000392153HKR1chr1937826159+ENST00000600118CHMP2Achr1959063552-61020617526169
ENST00000392153HKR1chr1937826159+ENST00000601220CHMP2Achr1959063552-61020617526169
ENST00000392153HKR1chr1937826159+ENST00000312547CHMP2Achr1959063552-61020617526169
ENST00000589392HKR1chr1937826159+ENST00000600118CHMP2Achr1959063552-574170528121135
ENST00000589392HKR1chr1937826159+ENST00000601220CHMP2Achr1959063552-574170528121135
ENST00000589392HKR1chr1937826159+ENST00000312547CHMP2Achr1959063552-574170528121135
ENST00000591259HKR1chr1937826159+ENST00000600118CHMP2Achr1959063552-56416022480152
ENST00000591259HKR1chr1937826159+ENST00000601220CHMP2Achr1959063552-56416022480152
ENST00000591259HKR1chr1937826159+ENST00000312547CHMP2Achr1959063552-56416022480152

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
ENST00000392153ENST00000600118HKR1chr1937826159+CHMP2Achr1959063552-0.0045053110.9954947
ENST00000392153ENST00000601220HKR1chr1937826159+CHMP2Achr1959063552-0.0045053110.9954947
ENST00000392153ENST00000312547HKR1chr1937826159+CHMP2Achr1959063552-0.0045053110.9954947
ENST00000589392ENST00000600118HKR1chr1937826159+CHMP2Achr1959063552-0.0044353940.9955646
ENST00000589392ENST00000601220HKR1chr1937826159+CHMP2Achr1959063552-0.0044353940.9955646
ENST00000589392ENST00000312547HKR1chr1937826159+CHMP2Achr1959063552-0.0044353940.9955646
ENST00000591259ENST00000600118HKR1chr1937826159+CHMP2Achr1959063552-0.00386680.9961332
ENST00000591259ENST00000601220HKR1chr1937826159+CHMP2Achr1959063552-0.00386680.9961332
ENST00000591259ENST00000312547HKR1chr1937826159+CHMP2Achr1959063552-0.00386680.9961332

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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

>36597_36597_1_HKR1-CHMP2A_HKR1_chr19_37826159_ENST00000392153_CHMP2A_chr19_59063552_ENST00000312547_length(amino acids)=169AA_BP=63
MGPGKASLLRSFPHLCTLLPDFRLQDPQRAPAFHLSSETLPFSRKSTQETRKMATGLLRAKKELKLPQIQKIMMEFERQAEIMDMKEEMM

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

>36597_36597_2_HKR1-CHMP2A_HKR1_chr19_37826159_ENST00000392153_CHMP2A_chr19_59063552_ENST00000600118_length(amino acids)=169AA_BP=63
MGPGKASLLRSFPHLCTLLPDFRLQDPQRAPAFHLSSETLPFSRKSTQETRKMATGLLRAKKELKLPQIQKIMMEFERQAEIMDMKEEMM

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

>36597_36597_3_HKR1-CHMP2A_HKR1_chr19_37826159_ENST00000392153_CHMP2A_chr19_59063552_ENST00000601220_length(amino acids)=169AA_BP=63
MGPGKASLLRSFPHLCTLLPDFRLQDPQRAPAFHLSSETLPFSRKSTQETRKMATGLLRAKKELKLPQIQKIMMEFERQAEIMDMKEEMM

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

>36597_36597_4_HKR1-CHMP2A_HKR1_chr19_37826159_ENST00000589392_CHMP2A_chr19_59063552_ENST00000312547_length(amino acids)=135AA_BP=1
MGIHWLSRSGRGTQSLRRFLSRSSRSASASARAEAAASAFFPPAATLSEPPVEGRFDSSSVRLSPSSSRTWDTTASLSSSSSSSPMASSM

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

>36597_36597_5_HKR1-CHMP2A_HKR1_chr19_37826159_ENST00000589392_CHMP2A_chr19_59063552_ENST00000600118_length(amino acids)=135AA_BP=1
MGIHWLSRSGRGTQSLRRFLSRSSRSASASARAEAAASAFFPPAATLSEPPVEGRFDSSSVRLSPSSSRTWDTTASLSSSSSSSPMASSM

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

>36597_36597_6_HKR1-CHMP2A_HKR1_chr19_37826159_ENST00000589392_CHMP2A_chr19_59063552_ENST00000601220_length(amino acids)=135AA_BP=1
MGIHWLSRSGRGTQSLRRFLSRSSRSASASARAEAAASAFFPPAATLSEPPVEGRFDSSSVRLSPSSSRTWDTTASLSSSSSSSPMASSM

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

>36597_36597_7_HKR1-CHMP2A_HKR1_chr19_37826159_ENST00000591259_CHMP2A_chr19_59063552_ENST00000312547_length(amino acids)=152AA_BP=46
MLPDFRLQDPQRAPAFHLSSETLPFSRKSTQETRKMATGLLRAKKELKLPQIQKIMMEFERQAEIMDMKEEMMNDAIDDAMGDEEDEEES

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

>36597_36597_8_HKR1-CHMP2A_HKR1_chr19_37826159_ENST00000591259_CHMP2A_chr19_59063552_ENST00000600118_length(amino acids)=152AA_BP=46
MLPDFRLQDPQRAPAFHLSSETLPFSRKSTQETRKMATGLLRAKKELKLPQIQKIMMEFERQAEIMDMKEEMMNDAIDDAMGDEEDEEES

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

>36597_36597_9_HKR1-CHMP2A_HKR1_chr19_37826159_ENST00000591259_CHMP2A_chr19_59063552_ENST00000601220_length(amino acids)=152AA_BP=46
MLPDFRLQDPQRAPAFHLSSETLPFSRKSTQETRKMATGLLRAKKELKLPQIQKIMMEFERQAEIMDMKEEMMNDAIDDAMGDEEDEEES

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

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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/chr19:37826159/chr19:59063552)
- 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
.CHMP2A

O43633

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.FUNCTION: Probable core component of the endosomal sorting required for transport complex III (ESCRT-III) which is involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs. MVBs contain intraluminal vesicles (ILVs) that are generated by invagination and scission from the limiting membrane of the endosome and mostly are delivered to lysosomes enabling degradation of membrane proteins, such as stimulated growth factor receptors, lysosomal enzymes and lipids. The MVB pathway appears to require the sequential function of ESCRT-O, -I,-II and -III complexes. ESCRT-III proteins mostly dissociate from the invaginating membrane before the ILV is released. The ESCRT machinery also functions in topologically equivalent membrane fission events, such as the terminal stages of cytokinesis (PubMed:21310966). Together with SPAST, the ESCRT-III complex promotes nuclear envelope sealing and mitotic spindle disassembly during late anaphase (PubMed:26040712). ESCRT-III proteins are believed to mediate the necessary vesicle extrusion and/or membrane fission activities, possibly in conjunction with the AAA ATPase VPS4. {ECO:0000269|PubMed:21310966, ECO:0000269|PubMed:26040712, ECO:0000305}.; FUNCTION: (Microbial infection) The ESCRT machinery functions in topologically equivalent membrane fission events, such as the budding of enveloped viruses (HIV-1 and other lentiviruses). Involved in HIV-1 p6- and p9-dependent virus release. {ECO:0000269|PubMed:14505570, ECO:0000269|PubMed:14519844}.

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
TgeneCHMP2Achr19:37826159chr19:59063552ENST0000031254726195_222116.0223.0Coiled coilOntology_term=ECO:0000255
TgeneCHMP2Achr19:37826159chr19:59063552ENST0000060011815195_222116.0223.0Coiled coilOntology_term=ECO:0000255
TgeneCHMP2Achr19:37826159chr19:59063552ENST0000060122026195_222116.0223.0Coiled coilOntology_term=ECO:0000255
TgeneCHMP2Achr19:37826159chr19:59063552ENST0000031254726210_220116.0223.0MotifNote=MIT-interacting motif
TgeneCHMP2Achr19:37826159chr19:59063552ENST0000060011815210_220116.0223.0MotifNote=MIT-interacting motif
TgeneCHMP2Achr19:37826159chr19:59063552ENST0000060122026210_220116.0223.0MotifNote=MIT-interacting motif

- Not-retained protein feature among the 13 regional features.
PartnerGeneHbpTbpENSTStrandBPexonTotalExonProtein feature loci*BPlociTotalLenProtein featureProtein feature note
HgeneHKR1chr19:37826159chr19:59063552ENST00000324411+2633_1040660.0DomainKRAB
HgeneHKR1chr19:37826159chr19:59063552ENST00000392153+2533_10411.0641.0DomainKRAB
HgeneHKR1chr19:37826159chr19:59063552ENST00000324411+26301_3230660.0Zinc fingerC2H2-type 1
HgeneHKR1chr19:37826159chr19:59063552ENST00000324411+26329_3510660.0Zinc fingerC2H2-type 2
HgeneHKR1chr19:37826159chr19:59063552ENST00000324411+26357_3790660.0Zinc fingerC2H2-type 3
HgeneHKR1chr19:37826159chr19:59063552ENST00000324411+26385_4070660.0Zinc fingerC2H2-type 4
HgeneHKR1chr19:37826159chr19:59063552ENST00000324411+26413_4350660.0Zinc fingerC2H2-type 5
HgeneHKR1chr19:37826159chr19:59063552ENST00000324411+26441_4630660.0Zinc fingerC2H2-type 6
HgeneHKR1chr19:37826159chr19:59063552ENST00000324411+26469_4910660.0Zinc fingerC2H2-type 7
HgeneHKR1chr19:37826159chr19:59063552ENST00000324411+26497_5190660.0Zinc fingerC2H2-type 8
HgeneHKR1chr19:37826159chr19:59063552ENST00000324411+26525_5470660.0Zinc fingerC2H2-type 9
HgeneHKR1chr19:37826159chr19:59063552ENST00000324411+26553_5750660.0Zinc fingerC2H2-type 10
HgeneHKR1chr19:37826159chr19:59063552ENST00000324411+26579_6010660.0Zinc fingerC2H2-type 11
HgeneHKR1chr19:37826159chr19:59063552ENST00000324411+26607_6290660.0Zinc fingerC2H2-type 12
HgeneHKR1chr19:37826159chr19:59063552ENST00000324411+26635_6570660.0Zinc fingerC2H2-type 13
HgeneHKR1chr19:37826159chr19:59063552ENST00000392153+25301_32311.0641.0Zinc fingerC2H2-type 1
HgeneHKR1chr19:37826159chr19:59063552ENST00000392153+25329_35111.0641.0Zinc fingerC2H2-type 2
HgeneHKR1chr19:37826159chr19:59063552ENST00000392153+25357_37911.0641.0Zinc fingerC2H2-type 3
HgeneHKR1chr19:37826159chr19:59063552ENST00000392153+25385_40711.0641.0Zinc fingerC2H2-type 4
HgeneHKR1chr19:37826159chr19:59063552ENST00000392153+25413_43511.0641.0Zinc fingerC2H2-type 5
HgeneHKR1chr19:37826159chr19:59063552ENST00000392153+25441_46311.0641.0Zinc fingerC2H2-type 6
HgeneHKR1chr19:37826159chr19:59063552ENST00000392153+25469_49111.0641.0Zinc fingerC2H2-type 7
HgeneHKR1chr19:37826159chr19:59063552ENST00000392153+25497_51911.0641.0Zinc fingerC2H2-type 8
HgeneHKR1chr19:37826159chr19:59063552ENST00000392153+25525_54711.0641.0Zinc fingerC2H2-type 9
HgeneHKR1chr19:37826159chr19:59063552ENST00000392153+25553_57511.0641.0Zinc fingerC2H2-type 10
HgeneHKR1chr19:37826159chr19:59063552ENST00000392153+25579_60111.0641.0Zinc fingerC2H2-type 11
HgeneHKR1chr19:37826159chr19:59063552ENST00000392153+25607_62911.0641.0Zinc fingerC2H2-type 12
HgeneHKR1chr19:37826159chr19:59063552ENST00000392153+25635_65711.0641.0Zinc fingerC2H2-type 13
TgeneCHMP2Achr19:37826159chr19:59063552ENST000003125472612_53116.0223.0Coiled coilOntology_term=ECO:0000255
TgeneCHMP2Achr19:37826159chr19:59063552ENST000006001181512_53116.0223.0Coiled coilOntology_term=ECO:0000255
TgeneCHMP2Achr19:37826159chr19:59063552ENST000006012202612_53116.0223.0Coiled coilOntology_term=ECO:0000255


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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 >>>179_HKR1_37826159_CHMP2A_59063552_ranked_0.pdbHKR13782615937826159ENST00000312547CHMP2Achr1959063552-
MGPGKASLLRSFPHLCTLLPDFRLQDPQRAPAFHLSSETLPFSRKSTQETRKMATGLLRAKKELKLPQIQKIMMEFERQAEIMDMKEEMM
169


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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
CHMP2A_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
HKR1
CHMP2A


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
TgeneCHMP2Achr19:37826159chr19:59063552ENST000003125472656_222116.0223.0VPS4B
TgeneCHMP2Achr19:37826159chr19:59063552ENST000006001181556_222116.0223.0VPS4B
TgeneCHMP2Achr19:37826159chr19:59063552ENST000006012202656_222116.0223.0VPS4B


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Related Drugs to HKR1-CHMP2A


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 HKR1-CHMP2A


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