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Center for Computational Systems Medicine
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Fusion Gene and Fusion Protein Summary

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Fusion Amino Acid Sequences (multiple BPs and multiple gene isoforms)

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Fusion Protein Breakpoint Sequences - (for the Screening of the FusionNeoAntigens)

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Potential FusionNeoAntigens in HLA I - (netMHCpan v4.1 + deepHLApan v1.1)

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Potential FusionNeoAntigens in HLA II - (netMHCIIpan v4.1)

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Fusion Breakpoint 14 AA Peptide Structure - (RoseTTAFold)

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D - (Glide)

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Vaccine Design for the FusionNeoAntigens (RNA/protein sequences)

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Potential target of CAR-T therapy development

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Information on the samples that have these potential fusion neoantigens

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Fusion Protein Targeting Drugs - (Manual Curation)

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Fusion Protein Related diseases - (Manual Curation)

Fusion Protein:SRD5A1-GRK4

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: SRD5A1-GRK4
FusionPDB ID: 86271
FusionGDB2.0 ID: 86271
HgeneTgene
Gene symbol

SRD5A1

GRK4

Gene ID

6715

2868

Gene namesteroid 5 alpha-reductase 1G protein-coupled receptor kinase 4
SynonymsS5AR 1GPRK2L|GPRK4|GRK4a|IT11
Cytomap

5p15.31

4p16.3

Type of geneprotein-codingprotein-coding
Description3-oxo-5-alpha-steroid 4-dehydrogenase 1SR type 1steroid 5-alpha-reductase type Isteroid-5-alpha-reductase, alpha polypeptide 1 (3-oxo-5 alpha-steroid delta 4-dehydrogenase alpha 1)G protein-coupled receptor kinase 4G protein-coupled receptor kinase 2-like
Modification date2020031320200313
UniProtAcc.

P32298

Main function of 5'-partner protein: FUNCTION: Specifically phosphorylates the activated forms of G protein-coupled receptors. GRK4-alpha can phosphorylate rhodopsin and its activity is inhibited by calmodulin; the other three isoforms do not phosphorylate rhodopsin and do not interact with calmodulin. GRK4-alpha and GRK4-gamma phosphorylate DRD3. Phosphorylates ADRB2. {ECO:0000269|PubMed:19520868, ECO:0000269|PubMed:8626439}.
Ensembl transtripts involved in fusion geneENST idsENST00000537411, ENST00000274192, 
ENST00000538824, ENST00000504286, 
ENST00000345167, ENST00000398051, 
ENST00000398052, ENST00000504933, 
ENST00000442472, ENST00000503518, 
ENST00000509545, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score6 X 2 X 5=607 X 7 X 4=196
# samples 67
** MAII scorelog2(6/60*10)=0log2(7/196*10)=-1.48542682717024
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: SRD5A1 [Title/Abstract] AND GRK4 [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: SRD5A1 [Title/Abstract] AND GRK4 [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)SRD5A1(6663079)-GRK4(3024140), # samples:2
Anticipated loss of major functional domain due to fusion event.SRD5A1-GRK4 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.
SRD5A1-GRK4 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.
SRD5A1-GRK4 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.
SRD5A1-GRK4 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
TgeneGRK4

GO:0031623

receptor internalization

20074556



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/chr5:6663079/chr4:3024140)
- 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 buttonRetention analysis results 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, are available here.

check buttonFusion gene breakpoints across SRD5A1 (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 GRK4 (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 Amino Acid Sequences


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)
ENST00000274192SRD5A1chr56663079+ENST00000398051GRK4chr43024140+17169471591613484
ENST00000274192SRD5A1chr56663079+ENST00000398052GRK4chr43024140+18749471591751530
ENST00000274192SRD5A1chr56663079+ENST00000504933GRK4chr43024140+17369471591613484
ENST00000274192SRD5A1chr56663079+ENST00000345167GRK4chr43024140+18749471591751530
ENST00000538824SRD5A1chr56663079+ENST00000398051GRK4chr43024140+1424655831321412
ENST00000538824SRD5A1chr56663079+ENST00000398052GRK4chr43024140+1582655831459458
ENST00000538824SRD5A1chr56663079+ENST00000504933GRK4chr43024140+1444655831321412
ENST00000538824SRD5A1chr56663079+ENST00000345167GRK4chr43024140+1582655831459458

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
ENST00000274192ENST00000398051SRD5A1chr56663079+GRK4chr43024140+0.0059175310.9940825
ENST00000274192ENST00000398052SRD5A1chr56663079+GRK4chr43024140+0.0044243230.99557567
ENST00000274192ENST00000504933SRD5A1chr56663079+GRK4chr43024140+0.0054611780.99453884
ENST00000274192ENST00000345167SRD5A1chr56663079+GRK4chr43024140+0.0044243230.99557567
ENST00000538824ENST00000398051SRD5A1chr56663079+GRK4chr43024140+0.0608000680.9391999
ENST00000538824ENST00000398052SRD5A1chr56663079+GRK4chr43024140+0.0349465760.9650534
ENST00000538824ENST00000504933SRD5A1chr56663079+GRK4chr43024140+0.0587765760.94122344
ENST00000538824ENST00000345167SRD5A1chr56663079+GRK4chr43024140+0.0349465760.9650534

check button Predicted full-length fusion amino acid sequences. For individual full-length fusion transcript sequence from FusionPDB, we ran ORFfinder and chose the longest ORF among all the predicted ones.

Get the fusion protein sequences from here.

Fusion protein sequence information is available in the fasta format.
>FusionGDB ID_FusionGDB isoform ID_FGname_Hgene_Hchr_Hbp_Henst_Tgene_Tchr_Tbp_Tenst_length(fusion AA) seq_BP

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Fusion Protein Breakpoint Sequences for SRD5A1-GRK4

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
SRD5A1chr56663079GRK4chr43024140655191FCFLSGRAKEHHEDLKPENILLDDRG
SRD5A1chr56663079GRK4chr43024140947263FCFLSGRAKEHHEDLKPENILLDDRG

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Potential FusionNeoAntigen Information of SRD5A1-GRK4 in HLA I

check button Multiple sequence alignments of the potential FusionNeoAntigens per fusion breakpoints. If the MSA is empty, then it means that there were predicted fusion neoantigens in this fusion breakpoint, but those predicted fusion neoantigens were not across the breakpoint, which is not fusion-specific.
SRD5A1-GRK4_6663079_3024140.msa

check button Potential FusionNeoAntigen Information
* We used NetMHCpan v4.1 (%rank<0.5) and deepHLApan v1.1 (immunogenic score>0.5)
Fusion geneHchrHbpTgeneTchrTbpHLA IFusionNeoAntigen peptideBinding scoreImmunogenic scoreNeoantigen start (at BP 13)Neoantigen end (at BP 13)
SRD5A1-GRK4chr56663079chr43024140947HLA-B45:01KEHHEDLKP0.9850.6486817
SRD5A1-GRK4chr56663079chr43024140947HLA-B08:01RAKEHHEDL0.75050.5683615
SRD5A1-GRK4chr56663079chr43024140947HLA-B41:01HEDLKPENI0.6050.86281120
SRD5A1-GRK4chr56663079chr43024140947HLA-B39:13HEDLKPENI0.54390.93781120
SRD5A1-GRK4chr56663079chr43024140947HLA-B41:01KEHHEDLKP0.40640.6836817
SRD5A1-GRK4chr56663079chr43024140947HLA-B50:01KEHHEDLKP0.18110.5188817
SRD5A1-GRK4chr56663079chr43024140947HLA-A30:08RAKEHHEDLK0.99180.8044616
SRD5A1-GRK4chr56663079chr43024140947HLA-B39:01HHEDLKPENI0.98940.90391020
SRD5A1-GRK4chr56663079chr43024140947HLA-B38:01HHEDLKPENI0.9860.97481020
SRD5A1-GRK4chr56663079chr43024140947HLA-B38:02HHEDLKPENI0.98570.97461020
SRD5A1-GRK4chr56663079chr43024140947HLA-B39:13HEDLKPENIL0.88790.86741121
SRD5A1-GRK4chr56663079chr43024140947HLA-B39:01HHEDLKPENIL0.99970.85371021
SRD5A1-GRK4chr56663079chr43024140947HLA-B38:02HHEDLKPENIL0.99940.9511021
SRD5A1-GRK4chr56663079chr43024140947HLA-B38:01HHEDLKPENIL0.99930.95181021
SRD5A1-GRK4chr56663079chr43024140947HLA-B15:10HHEDLKPENIL0.99910.5761021
SRD5A1-GRK4chr56663079chr43024140947HLA-B38:01EHHEDLKPENI0.9980.8622920
SRD5A1-GRK4chr56663079chr43024140947HLA-B15:37HHEDLKPENIL0.99310.57391021
SRD5A1-GRK4chr56663079chr43024140947HLA-B39:13HEDLKPENILL0.99030.8721122
SRD5A1-GRK4chr56663079chr43024140947HLA-C15:06RAKEHHEDL0.98460.9621615
SRD5A1-GRK4chr56663079chr43024140947HLA-C03:08RAKEHHEDL0.9730.9551615
SRD5A1-GRK4chr56663079chr43024140947HLA-C03:19RAKEHHEDL0.94390.9917615
SRD5A1-GRK4chr56663079chr43024140947HLA-C12:12RAKEHHEDL0.93720.936615
SRD5A1-GRK4chr56663079chr43024140947HLA-B42:02RAKEHHEDL0.90640.5621615
SRD5A1-GRK4chr56663079chr43024140947HLA-C06:03RAKEHHEDL0.90550.9908615
SRD5A1-GRK4chr56663079chr43024140947HLA-C12:04RAKEHHEDL0.88490.9903615
SRD5A1-GRK4chr56663079chr43024140947HLA-C02:06RAKEHHEDL0.75790.9669615
SRD5A1-GRK4chr56663079chr43024140947HLA-B39:08HEDLKPENI0.63690.87791120
SRD5A1-GRK4chr56663079chr43024140947HLA-B39:05HHEDLKPENI0.98380.89531020
SRD5A1-GRK4chr56663079chr43024140947HLA-B39:08HEDLKPENIL0.94950.83591121
SRD5A1-GRK4chr56663079chr43024140947HLA-B39:12HHEDLKPENIL0.99970.86351021
SRD5A1-GRK4chr56663079chr43024140947HLA-B39:09HHEDLKPENIL0.99970.50991021
SRD5A1-GRK4chr56663079chr43024140947HLA-B39:05HHEDLKPENIL0.99920.85391021
SRD5A1-GRK4chr56663079chr43024140947HLA-B39:08HEDLKPENILL0.99640.8311122
SRD5A1-GRK4chr56663079chr43024140947HLA-B40:04HEDLKPENI0.99760.63651120
SRD5A1-GRK4chr56663079chr43024140947HLA-C03:05RAKEHHEDL0.93870.957615
SRD5A1-GRK4chr56663079chr43024140947HLA-C03:17RAKEHHEDL0.92810.9815615
SRD5A1-GRK4chr56663079chr43024140947HLA-C03:03RAKEHHEDL0.92420.9909615
SRD5A1-GRK4chr56663079chr43024140947HLA-C03:04RAKEHHEDL0.92420.9909615
SRD5A1-GRK4chr56663079chr43024140947HLA-C16:04RAKEHHEDL0.88290.9668615
SRD5A1-GRK4chr56663079chr43024140947HLA-C03:67RAKEHHEDL0.88160.9863615
SRD5A1-GRK4chr56663079chr43024140947HLA-C12:03RAKEHHEDL0.85920.9743615
SRD5A1-GRK4chr56663079chr43024140947HLA-C07:04RAKEHHEDL0.83350.9177615
SRD5A1-GRK4chr56663079chr43024140947HLA-B07:13RAKEHHEDL0.80720.8835615
SRD5A1-GRK4chr56663079chr43024140947HLA-B41:03HEDLKPENI0.75660.55081120
SRD5A1-GRK4chr56663079chr43024140947HLA-B08:18RAKEHHEDL0.75050.5683615
SRD5A1-GRK4chr56663079chr43024140947HLA-B08:12RAKEHHEDL0.72670.6633615
SRD5A1-GRK4chr56663079chr43024140947HLA-C12:02RAKEHHEDL0.69390.9584615
SRD5A1-GRK4chr56663079chr43024140947HLA-B39:11HEDLKPENI0.63020.80621120
SRD5A1-GRK4chr56663079chr43024140947HLA-C16:02RAKEHHEDL0.60120.9917615
SRD5A1-GRK4chr56663079chr43024140947HLA-C16:01RAKEHHEDL0.55030.9762615
SRD5A1-GRK4chr56663079chr43024140947HLA-B39:02HEDLKPENI0.53270.93811120
SRD5A1-GRK4chr56663079chr43024140947HLA-B50:04KEHHEDLKP0.18110.5188817
SRD5A1-GRK4chr56663079chr43024140947HLA-B50:05KEHHEDLKP0.18110.5188817
SRD5A1-GRK4chr56663079chr43024140947HLA-A30:01RAKEHHEDLK0.99230.8688616
SRD5A1-GRK4chr56663079chr43024140947HLA-B38:05HHEDLKPENI0.9860.97481020
SRD5A1-GRK4chr56663079chr43024140947HLA-B39:11HEDLKPENIL0.95870.76991121
SRD5A1-GRK4chr56663079chr43024140947HLA-B39:02HEDLKPENIL0.92120.86281121
SRD5A1-GRK4chr56663079chr43024140947HLA-B39:11HHEDLKPENI0.90740.83531020
SRD5A1-GRK4chr56663079chr43024140947HLA-B39:31HHEDLKPENIL0.99970.85521021
SRD5A1-GRK4chr56663079chr43024140947HLA-B38:05HHEDLKPENIL0.99930.95181021
SRD5A1-GRK4chr56663079chr43024140947HLA-B38:05EHHEDLKPENI0.9980.8622920
SRD5A1-GRK4chr56663079chr43024140947HLA-B15:09HHEDLKPENIL0.99780.6081021
SRD5A1-GRK4chr56663079chr43024140947HLA-B39:11HEDLKPENILL0.99650.76731122
SRD5A1-GRK4chr56663079chr43024140947HLA-B39:11HHEDLKPENIL0.99640.80041021
SRD5A1-GRK4chr56663079chr43024140947HLA-B39:02HEDLKPENILL0.99380.86791122

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Potential FusionNeoAntigen Information of SRD5A1-GRK4 in HLA II

check button Multiple sequence alignments of the potential FusionNeoAntigens per fusion breakpoints. If the MSA is empty, then it means that there were predicted fusion neoantigens in this fusion breakpoint, but those predicted fusion neoantigens were not across the breakpoint, which is not fusion-specific.
SRD5A1-GRK4_6663079_3024140.msa

check button Potential FusionNeoAntigen Information
* We used NetMHCIIpan v4.1 (%rank<0.5).
Fusion geneHchrHbpTgeneTchrTbpHLA IIFusionNeoAntigen peptideNeoantigen start (at BP 13)Neoantigen end (at BP 13)
SRD5A1-GRK4chr56663079chr43024140947DRB1-0467HEDLKPENILLDDRG1126
SRD5A1-GRK4chr56663079chr43024140947DRB1-0467HHEDLKPENILLDDR1025

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Fusion breakpoint peptide structures of SRD5A1-GRK4

check button3D structures of the fusion breakpoint peptide of 14AA sequence that have potential fusion neoantigens
* The minimum length of the amino acid sequence in RoseTTAFold is 14AA. Here, we predicted the 14AA fusion protein breakpoint sequence not the fusion neoantigen peptide, which is shorter than 14 AA.
File nameBPseqHgeneTgeneHchrHbpTchrTbpAAlen
7687RAKEHHEDLKPENISRD5A1GRK4chr56663079chr43024140947

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of SRD5A1-GRK4

check buttonVirtual screening between 25 HLAs (from PDB) and FusionNeoAntigens
* We used Glide to predict the interaction between HLAs and neoantigens.
HLA allelePDB IDFile nameBPseqDocking scoreGlide score
HLA-B14:023BVN7687RAKEHHEDLKPENI-6.07233-6.07953
HLA-B52:013W397687RAKEHHEDLKPENI-5.45645-5.46365
HLA-A24:025HGA7687RAKEHHEDLKPENI-3.85827-3.86547
HLA-B44:053DX87687RAKEHHEDLKPENI-4.76301-4.77021

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Vaccine Design for the FusionNeoAntigens of SRD5A1-GRK4

check button mRNA and peptide sequences of FusionNeoAntigens that have potential interaction with HLA-Is.
Fusion geneHchrHbpTchrTbpStart in +/-13AAEnd in +/-13AAFusionNeoAntigen peptide sequenceFusionNeoAntigen RNA sequence
SRD5A1-GRK4chr56663079chr430241401020HHEDLKPENIGCATCATGAAGACTTGAAGCCTGAGAATAT
SRD5A1-GRK4chr56663079chr430241401021HHEDLKPENILGCATCATGAAGACTTGAAGCCTGAGAATATTCT
SRD5A1-GRK4chr56663079chr430241401120HEDLKPENITCATGAAGACTTGAAGCCTGAGAATAT
SRD5A1-GRK4chr56663079chr430241401121HEDLKPENILTCATGAAGACTTGAAGCCTGAGAATATTCT
SRD5A1-GRK4chr56663079chr430241401122HEDLKPENILLTCATGAAGACTTGAAGCCTGAGAATATTCTCCT
SRD5A1-GRK4chr56663079chr43024140615RAKEHHEDLTAGAGCAAAAGAGCATCATGAAGACTT
SRD5A1-GRK4chr56663079chr43024140616RAKEHHEDLKTAGAGCAAAAGAGCATCATGAAGACTTGAA
SRD5A1-GRK4chr56663079chr43024140817KEHHEDLKPAAAAGAGCATCATGAAGACTTGAAGCC
SRD5A1-GRK4chr56663079chr43024140920EHHEDLKPENIAGAGCATCATGAAGACTTGAAGCCTGAGAATAT

check button mRNA and peptide sequences of FusionNeoAntigens that have potential interaction with HLA-IIs.
Fusion geneHchrHbpTchrTbpStart in +/-13AAEnd in +/-13AAFusionNeoAntigen peptideFusionNEoAntigen RNA sequence
SRD5A1-GRK4chr56663079chr430241401025HHEDLKPENILLDDRGCATCATGAAGACTTGAAGCCTGAGAATATTCTCCTTGATGATCG
SRD5A1-GRK4chr56663079chr430241401126HEDLKPENILLDDRGTCATGAAGACTTGAAGCCTGAGAATATTCTCCTTGATGATCGTGG

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Information of the samples that have these potential fusion neoantigens of SRD5A1-GRK4

check button These samples were reported as having these fusion breakpoints. For individual breakpoints, we checked the open reading frames considering multiple gene isoforms and chose the in-frame fusion genes only. Then, we made fusion protein sequences and predicted the fusion neoantigens. These fusion-positive samples may have these potential fusion neoantigens.
Cancer typeFusion geneHchrHbpHenstTchrTbpTenstSample
ESCASRD5A1-GRK4chr56663079ENST00000274192chr43024140ENST00000345167TCGA-L5-A8NW

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Potential target of CAR-T therapy development for SRD5A1-GRK4

check button Predicted 3D structure. We used RoseTTAFold.

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, to provide the retention of the transmembrane domain, we only show the protein feature retention information of those transmembrane features


* Minus value of BPloci means that the break point is located before the CDS.
- In-frame and retained 'Transmembrane'.
PartnerGeneHbpTbpENSTStrandBPexonTotalExonProtein feature loci*BPlociTotalLenProtein featureProtein feature note
HgeneSRD5A1chr5:6663079chr4:3024140ENST00000274192+45111_131237260.0TransmembraneHelical
HgeneSRD5A1chr5:6663079chr4:3024140ENST00000274192+4512_29237260.0TransmembraneHelical
HgeneSRD5A1chr5:6663079chr4:3024140ENST00000274192+45151_171237260.0TransmembraneHelical
HgeneSRD5A1chr5:6663079chr4:3024140ENST00000274192+45209_229237260.0TransmembraneHelical
HgeneSRD5A1chr5:6663079chr4:3024140ENST00000274192+4586_106237260.0TransmembraneHelical

check button Subcellular localization prediction of the transmembrane domain retained fusion proteins
* We used DeepLoc 1.0. The order of the X-axis of the barplot is as follows: Entry_ID, Localization, Type, Nucleus, Cytoplasm, Extracellular, Mitochondrion, Cell_membrane, Endoplasmic_reticulum, Plastid, Golgi.apparatus, Lysosome.Vacuole, Peroxisome. Y-axis is the output score of DeepLoc. Clicking the image will open a new tab with a large image.
HgeneHchrHbpHenstTgeneTchrTbpTenstDeepLoc result

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Related Drugs to SRD5A1-GRK4

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 SRD5A1-GRK4

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