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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:FKBP1A-ACSL1

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: FKBP1A-ACSL1
FusionPDB ID: 30460
FusionGDB2.0 ID: 30460
HgeneTgene
Gene symbol

FKBP1A

ACSL1

Gene ID

2280

2180

Gene nameFKBP prolyl isomerase 1Aacyl-CoA synthetase long chain family member 1
SynonymsFKBP-12|FKBP-1A|FKBP1|FKBP12|PKC12|PKCI2|PPIASEACS1|FACL1|FACL2|LACS|LACS1|LACS2
Cytomap

20p13

4q35.1

Type of geneprotein-codingprotein-coding
Descriptionpeptidyl-prolyl cis-trans isomerase FKBP1A12 kDa FK506-binding protein12 kDa FKBPFK506 binding protein 1A, 12kDaFK506 binding protein12FK506-binding protein 1FK506-binding protein 12FK506-binding protein 1AFK506-binding protein, T-cell, 12-kDFKBPlong-chain-fatty-acid--CoA ligase 1LACS 1LACS 2acyl-CoA synthetase 1arachidonate--CoA ligasefatty-acid-Coenzyme A ligase, long-chain 1fatty-acid-Coenzyme A ligase, long-chain 2lignoceroyl-CoA synthaselong-chain acyl-CoA synthetase 1long-chain acy
Modification date2020031320200313
UniProtAcc

P62942

Main function of 5'-partner protein: FUNCTION: Keeps in an inactive conformation TGFBR1, the TGF-beta type I serine/threonine kinase receptor, preventing TGF-beta receptor activation in absence of ligand. Recruits SMAD7 to ACVR1B which prevents the association of SMAD2 and SMAD3 with the activin receptor complex, thereby blocking the activin signal. May modulate the RYR1 calcium channel activity. PPIases accelerate the folding of proteins. It catalyzes the cis-trans isomerization of proline imidic peptide bonds in oligopeptides. {ECO:0000269|PubMed:16720724, ECO:0000269|PubMed:1696686, ECO:0000269|PubMed:1701173, ECO:0000269|PubMed:9233797}.

P33121

Main function of 5'-partner protein: FUNCTION: Catalyzes the conversion of long-chain fatty acids to their active form acyl-CoAs for both synthesis of cellular lipids, and degradation via beta-oxidation (PubMed:24269233, PubMed:22633490, PubMed:21242590). Preferentially uses palmitoleate, oleate and linoleate (PubMed:24269233). Preferentially activates arachidonate than epoxyeicosatrienoic acids (EETs) or hydroxyeicosatrienoic acids (HETEs) (By similarity). {ECO:0000250|UniProtKB:P18163, ECO:0000269|PubMed:21242590, ECO:0000269|PubMed:22633490, ECO:0000269|PubMed:24269233}.
Ensembl transtripts involved in fusion geneENST idsENST00000381715, ENST00000381719, 
ENST00000381724, ENST00000400137, 
ENST00000439640, ENST00000460490, 
ENST00000504900, ENST00000281455, 
ENST00000437665, ENST00000454703, 
ENST00000504342, ENST00000507295, 
ENST00000513317, ENST00000515030, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score6 X 6 X 5=1803 X 3 X 3=27
# samples 73
** MAII scorelog2(7/180*10)=-1.36257007938471
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(3/27*10)=0.15200309344505
effective Gene in Pan-Cancer Fusion Genes (eGinPCFGs).
DoF>8 and MAII>0
Fusion gene context

PubMed: FKBP1A [Title/Abstract] AND ACSL1 [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: FKBP1A [Title/Abstract] AND ACSL1 [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)FKBP1A(1356134)-ACSL1(185689604), # samples:1
Anticipated loss of major functional domain due to fusion event.FKBP1A-ACSL1 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.
FKBP1A-ACSL1 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.
FKBP1A-ACSL1 seems lost the major protein functional domain in Hgene partner, which is a IUPHAR drug target due to the frame-shifted ORF.
FKBP1A-ACSL1 seems lost the major protein functional domain in Tgene partner, which is a cell metabolism gene due to the frame-shifted ORF.
FKBP1A-ACSL1 seems lost the major protein functional domain in Tgene 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
HgeneFKBP1A

GO:0000413

protein peptidyl-prolyl isomerization

1696686

HgeneFKBP1A

GO:0007183

SMAD protein complex assembly

16720724

HgeneFKBP1A

GO:0031398

positive regulation of protein ubiquitination

16720724

HgeneFKBP1A

GO:0032092

positive regulation of protein binding

18346205

HgeneFKBP1A

GO:0032515

negative regulation of phosphoprotein phosphatase activity

7592869

HgeneFKBP1A

GO:0032925

regulation of activin receptor signaling pathway

16720724

HgeneFKBP1A

GO:0051280

negative regulation of release of sequestered calcium ion into cytosol

12443530

HgeneFKBP1A

GO:0060314

regulation of ryanodine-sensitive calcium-release channel activity

7592869

HgeneFKBP1A

GO:0060315

negative regulation of ryanodine-sensitive calcium-release channel activity

12443530

HgeneFKBP1A

GO:0097435

supramolecular fiber organization

18346205

HgeneFKBP1A

GO:1990000

amyloid fibril formation

18346205

TgeneACSL1

GO:0001676

long-chain fatty acid metabolic process

22022213|24269233

TgeneACSL1

GO:0008610

lipid biosynthetic process

21242590

TgeneACSL1

GO:0044539

long-chain fatty acid import

22022213



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/chr20:1356134/chr4:185689604)
- 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 FKBP1A (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 ACSL1 (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)
ENST00000400137FKBP1Achr201356134-ENST00000504900ACSL1chr4185689604-783362164535123
ENST00000381724FKBP1Achr201356134-ENST00000454703ACSL1chr4185689604-29523181351421428
ENST00000381724FKBP1Achr201356134-ENST00000515030ACSL1chr4185689604-29473181351421428
ENST00000381724FKBP1Achr201356134-ENST00000281455ACSL1chr4185689604-29463181351421428
ENST00000381724FKBP1Achr201356134-ENST00000507295ACSL1chr4185689604-17663181351421428
ENST00000381724FKBP1Achr201356134-ENST00000437665ACSL1chr4185689604-16443181351421428
ENST00000381724FKBP1Achr201356134-ENST00000504342ACSL1chr4185689604-15263181351421428
ENST00000381724FKBP1Achr201356134-ENST00000513317ACSL1chr4185689604-15003181351421428
ENST00000381719FKBP1Achr201356134-ENST00000454703ACSL1chr4185689604-2862228301331433
ENST00000381719FKBP1Achr201356134-ENST00000515030ACSL1chr4185689604-2857228301331433
ENST00000381719FKBP1Achr201356134-ENST00000281455ACSL1chr4185689604-2856228301331433
ENST00000381719FKBP1Achr201356134-ENST00000507295ACSL1chr4185689604-1676228301331433
ENST00000381719FKBP1Achr201356134-ENST00000437665ACSL1chr4185689604-1554228301331433
ENST00000381719FKBP1Achr201356134-ENST00000504342ACSL1chr4185689604-1436228301331433
ENST00000381719FKBP1Achr201356134-ENST00000513317ACSL1chr4185689604-1410228301331433
ENST00000381715FKBP1Achr201356134-ENST00000454703ACSL1chr4185689604-2876242591345428
ENST00000381715FKBP1Achr201356134-ENST00000515030ACSL1chr4185689604-2871242591345428
ENST00000381715FKBP1Achr201356134-ENST00000281455ACSL1chr4185689604-2870242591345428
ENST00000381715FKBP1Achr201356134-ENST00000507295ACSL1chr4185689604-1690242591345428
ENST00000381715FKBP1Achr201356134-ENST00000437665ACSL1chr4185689604-1568242591345428
ENST00000381715FKBP1Achr201356134-ENST00000504342ACSL1chr4185689604-1450242591345428
ENST00000381715FKBP1Achr201356134-ENST00000513317ACSL1chr4185689604-1424242591345428
ENST00000439640FKBP1Achr201356134-ENST00000454703ACSL1chr4185689604-278415001253417
ENST00000439640FKBP1Achr201356134-ENST00000515030ACSL1chr4185689604-277915001253417
ENST00000439640FKBP1Achr201356134-ENST00000281455ACSL1chr4185689604-277815001253417
ENST00000439640FKBP1Achr201356134-ENST00000507295ACSL1chr4185689604-159815001253417
ENST00000439640FKBP1Achr201356134-ENST00000437665ACSL1chr4185689604-147615001253417
ENST00000439640FKBP1Achr201356134-ENST00000504342ACSL1chr4185689604-135815001253417
ENST00000439640FKBP1Achr201356134-ENST00000513317ACSL1chr4185689604-133215001253417

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
ENST00000400137ENST00000504900FKBP1Achr201356134-ACSL1chr4185689604-0.160511330.8394886
ENST00000381724ENST00000454703FKBP1Achr201356134-ACSL1chr4185689604-0.0004764350.9995235
ENST00000381724ENST00000515030FKBP1Achr201356134-ACSL1chr4185689604-0.0004751310.99952483
ENST00000381724ENST00000281455FKBP1Achr201356134-ACSL1chr4185689604-0.0004741860.9995258
ENST00000381724ENST00000507295FKBP1Achr201356134-ACSL1chr4185689604-0.0009454860.9990545
ENST00000381724ENST00000437665FKBP1Achr201356134-ACSL1chr4185689604-0.0018583710.99814165
ENST00000381724ENST00000504342FKBP1Achr201356134-ACSL1chr4185689604-0.0028989270.997101
ENST00000381724ENST00000513317FKBP1Achr201356134-ACSL1chr4185689604-0.0030030140.996997
ENST00000381719ENST00000454703FKBP1Achr201356134-ACSL1chr4185689604-0.000782230.99921775
ENST00000381719ENST00000515030FKBP1Achr201356134-ACSL1chr4185689604-0.000777020.999223
ENST00000381719ENST00000281455FKBP1Achr201356134-ACSL1chr4185689604-0.0007761970.9992238
ENST00000381719ENST00000507295FKBP1Achr201356134-ACSL1chr4185689604-0.0012882440.9987117
ENST00000381719ENST00000437665FKBP1Achr201356134-ACSL1chr4185689604-0.002457030.997543
ENST00000381719ENST00000504342FKBP1Achr201356134-ACSL1chr4185689604-0.0039829980.99601704
ENST00000381719ENST00000513317FKBP1Achr201356134-ACSL1chr4185689604-0.0040570610.9959429
ENST00000381715ENST00000454703FKBP1Achr201356134-ACSL1chr4185689604-0.0004358940.9995641
ENST00000381715ENST00000515030FKBP1Achr201356134-ACSL1chr4185689604-0.0004329220.9995671
ENST00000381715ENST00000281455FKBP1Achr201356134-ACSL1chr4185689604-0.0004331790.99956685
ENST00000381715ENST00000507295FKBP1Achr201356134-ACSL1chr4185689604-0.0007760090.99922395
ENST00000381715ENST00000437665FKBP1Achr201356134-ACSL1chr4185689604-0.0014897210.9985103
ENST00000381715ENST00000504342FKBP1Achr201356134-ACSL1chr4185689604-0.0024418970.9975581
ENST00000381715ENST00000513317FKBP1Achr201356134-ACSL1chr4185689604-0.0025070420.997493
ENST00000439640ENST00000454703FKBP1Achr201356134-ACSL1chr4185689604-0.0002958320.9997042
ENST00000439640ENST00000515030FKBP1Achr201356134-ACSL1chr4185689604-0.0002933780.99970657
ENST00000439640ENST00000281455FKBP1Achr201356134-ACSL1chr4185689604-0.000293780.9997062
ENST00000439640ENST00000507295FKBP1Achr201356134-ACSL1chr4185689604-0.0004314190.9995685
ENST00000439640ENST00000437665FKBP1Achr201356134-ACSL1chr4185689604-0.0008571340.9991429
ENST00000439640ENST00000504342FKBP1Achr201356134-ACSL1chr4185689604-0.0013886740.99861133
ENST00000439640ENST00000513317FKBP1Achr201356134-ACSL1chr4185689604-0.0014158750.99858415

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 FKBP1A-ACSL1

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
FKBP1Achr201356134ACSL1chr418568960415050QEVIRGWEEGVAQCVMLCHGAKIGFF
FKBP1Achr201356134ACSL1chr418568960422866QEVIRGWEEGVAQCVMLCHGAKIGFF
FKBP1Achr201356134ACSL1chr418568960424261QEVIRGWEEGVAQCVMLCHGAKIGFF
FKBP1Achr201356134ACSL1chr418568960431861QEVIRGWEEGVAQCVMLCHGAKIGFF
FKBP1Achr201356134ACSL1chr418568960436266QEVIRGWEEGVAQCVMLCHGAKIGFF

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Potential FusionNeoAntigen Information of FKBP1A-ACSL1 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.
FKBP1A-ACSL1_1356134_185689604.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)
FKBP1A-ACSL1chr201356134chr4185689604242HLA-B18:01EEGVAQCVM0.72970.8732716
FKBP1A-ACSL1chr201356134chr4185689604242HLA-B18:05EEGVAQCVM0.72970.8732716
FKBP1A-ACSL1chr201356134chr4185689604242HLA-B18:03EEGVAQCVM0.64930.8661716
FKBP1A-ACSL1chr201356134chr4185689604242HLA-B18:11EEGVAQCVM0.63480.8361716

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Potential FusionNeoAntigen Information of FKBP1A-ACSL1 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.

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)

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Fusion breakpoint peptide structures of FKBP1A-ACSL1

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
10440WEEGVAQCVMLCHGFKBP1AACSL1chr201356134chr4185689604242

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of FKBP1A-ACSL1

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-B14:023BVN10440WEEGVAQCVMLCHG-7.15543-7.26883
HLA-B14:023BVN10440WEEGVAQCVMLCHG-4.77435-5.80965
HLA-B52:013W3910440WEEGVAQCVMLCHG-6.80875-6.92215
HLA-B52:013W3910440WEEGVAQCVMLCHG-4.20386-5.23916
HLA-A11:014UQ210440WEEGVAQCVMLCHG-7.5194-8.5547
HLA-A11:014UQ210440WEEGVAQCVMLCHG-6.9601-7.0735
HLA-A24:025HGA10440WEEGVAQCVMLCHG-7.52403-7.63743
HLA-A24:025HGA10440WEEGVAQCVMLCHG-5.82433-6.85963
HLA-B27:056PYJ10440WEEGVAQCVMLCHG-3.28285-4.31815
HLA-B44:053DX810440WEEGVAQCVMLCHG-5.91172-6.94702
HLA-B44:053DX810440WEEGVAQCVMLCHG-4.24346-4.35686
HLA-B35:011A1N10440WEEGVAQCVMLCHG-5.9251-6.0385
HLA-B35:011A1N10440WEEGVAQCVMLCHG-4.80237-5.83767

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Vaccine Design for the FusionNeoAntigens of FKBP1A-ACSL1

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
FKBP1A-ACSL1chr201356134chr4185689604716EEGVAQCVMGAAGAAGGGGTTGCCCAGTGTGTAATG

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

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Information of the samples that have these potential fusion neoantigens of FKBP1A-ACSL1

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
LUSCFKBP1A-ACSL1chr201356134ENST00000381715chr4185689604ENST00000281455TCGA-51-4081

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Potential target of CAR-T therapy development for FKBP1A-ACSL1

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

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 FKBP1A-ACSL1

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 FKBP1A-ACSL1

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