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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:LIMK2-CDC45

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: LIMK2-CDC45
FusionPDB ID: 44720
FusionGDB2.0 ID: 44720
HgeneTgene
Gene symbol

LIMK2

CDC45

Gene ID

3985

8318

Gene nameLIM domain kinase 2cell division cycle 45
Synonyms-CDC45L|CDC45L2|MGORS7|PORC-PI-1
Cytomap

22q12.2

22q11.21

Type of geneprotein-codingprotein-coding
DescriptionLIM domain kinase 2cell division control protein 45 homologCDC45 cell division cycle 45 homologCDC45 cell division cycle 45-likeCDC45-related proteincell division cycle 45 homologcell division cycle 45-like 2human CDC45
Modification date2020031320200313
UniProtAcc

P53671

Main function of 5'-partner protein: FUNCTION: Serine/threonine-protein kinase that plays an essential role in the regulation of actin filament dynamics (PubMed:10436159, PubMed:11018042). Acts downstream of several Rho family GTPase signal transduction pathways (PubMed:10436159, PubMed:11018042). Involved in astral microtubule organization and mitotic spindle orientation during early stages of mitosis by mediating phosphorylation of TPPP (PubMed:22328514). Displays serine/threonine-specific phosphorylation of myelin basic protein and histone (MBP) in vitro (PubMed:8537403). Suppresses ciliogenesis via multiple pathways; phosphorylation of CFL1, suppression of directional trafficking of ciliary vesicles to the ciliary base, and by facilitating YAP1 nuclear localization where it acts as a transcriptional corepressor of the TEAD4 target genes AURKA and PLK1 (PubMed:25849865). {ECO:0000269|PubMed:10436159, ECO:0000269|PubMed:11018042, ECO:0000269|PubMed:22328514, ECO:0000269|PubMed:25849865, ECO:0000269|PubMed:8537403}.

O75419

Main function of 5'-partner protein: FUNCTION: Required for initiation of chromosomal DNA replication.
Ensembl transtripts involved in fusion geneENST idsENST00000331728, ENST00000333611, 
ENST00000340552, ENST00000406516, 
ENST00000444929, ENST00000467301, 
ENST00000404724, ENST00000483431, 
ENST00000263201, ENST00000407835, 
ENST00000437685, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score11 X 7 X 7=5393 X 4 X 3=36
# samples 135
** MAII scorelog2(13/539*10)=-2.05177364972405
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0		log2(5/36*10)=0.473931188332412
effective Gene in Pan-Cancer Fusion Genes (eGinPCFGs).
DoF>8 and MAII>0
Fusion gene context

PubMed: LIMK2 [Title/Abstract] AND CDC45 [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: LIMK2 [Title/Abstract] AND CDC45 [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)LIMK2(31664186)-CDC45(19504050), # samples:3
Anticipated loss of major functional domain due to fusion event.LIMK2-CDC45 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.
LIMK2-CDC45 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.
LIMK2-CDC45 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.
LIMK2-CDC45 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
HgeneLIMK2

GO:0006468

protein phosphorylation

22328514

HgeneLIMK2

GO:0030953

astral microtubule organization

22328514



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/chr22:31664186/chr22:19504050)
- 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 LIMK2 (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 CDC45 (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)
ENST00000406516LIMK2chr2231664186+ENST00000407835CDC45chr2219504050+17461352771612511
ENST00000406516LIMK2chr2231664186+ENST00000437685CDC45chr2219504050+17451352771612511
ENST00000406516LIMK2chr2231664186+ENST00000263201CDC45chr2219504050+17451352771612511
ENST00000444929LIMK2chr2231664186+ENST00000407835CDC45chr2219504050+110370982969295
ENST00000444929LIMK2chr2231664186+ENST00000437685CDC45chr2219504050+110270982969295
ENST00000444929LIMK2chr2231664186+ENST00000263201CDC45chr2219504050+110270982969295
ENST00000331728LIMK2chr2231664186+ENST00000407835CDC45chr2219504050+18251431661691541
ENST00000331728LIMK2chr2231664186+ENST00000437685CDC45chr2219504050+18241431661691541
ENST00000331728LIMK2chr2231664186+ENST00000263201CDC45chr2219504050+18241431661691541
ENST00000333611LIMK2chr2231664186+ENST00000407835CDC45chr2219504050+196315691411829562
ENST00000333611LIMK2chr2231664186+ENST00000437685CDC45chr2219504050+196215691411829562
ENST00000333611LIMK2chr2231664186+ENST00000263201CDC45chr2219504050+196215691411829562
ENST00000340552LIMK2chr2231664186+ENST00000407835CDC45chr2219504050+18781484561744562
ENST00000340552LIMK2chr2231664186+ENST00000437685CDC45chr2219504050+18771484561744562
ENST00000340552LIMK2chr2231664186+ENST00000263201CDC45chr2219504050+18771484561744562
ENST00000406516LIMK2chr2231664186+ENST00000407835CDC45chr2219504049+17461352771612511
ENST00000406516LIMK2chr2231664186+ENST00000437685CDC45chr2219504049+17451352771612511
ENST00000406516LIMK2chr2231664186+ENST00000263201CDC45chr2219504049+17451352771612511
ENST00000444929LIMK2chr2231664186+ENST00000407835CDC45chr2219504049+110370982969295
ENST00000444929LIMK2chr2231664186+ENST00000437685CDC45chr2219504049+110270982969295
ENST00000444929LIMK2chr2231664186+ENST00000263201CDC45chr2219504049+110270982969295
ENST00000331728LIMK2chr2231664186+ENST00000407835CDC45chr2219504049+18251431661691541
ENST00000331728LIMK2chr2231664186+ENST00000437685CDC45chr2219504049+18241431661691541
ENST00000331728LIMK2chr2231664186+ENST00000263201CDC45chr2219504049+18241431661691541
ENST00000333611LIMK2chr2231664186+ENST00000407835CDC45chr2219504049+196315691411829562
ENST00000333611LIMK2chr2231664186+ENST00000437685CDC45chr2219504049+196215691411829562
ENST00000333611LIMK2chr2231664186+ENST00000263201CDC45chr2219504049+196215691411829562
ENST00000340552LIMK2chr2231664186+ENST00000407835CDC45chr2219504049+18781484561744562
ENST00000340552LIMK2chr2231664186+ENST00000437685CDC45chr2219504049+18771484561744562
ENST00000340552LIMK2chr2231664186+ENST00000263201CDC45chr2219504049+18771484561744562

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
ENST00000406516ENST00000407835LIMK2chr2231664186+CDC45chr2219504050+0.0101634810.9898365
ENST00000406516ENST00000437685LIMK2chr2231664186+CDC45chr2219504050+0.0103579360.9896421
ENST00000406516ENST00000263201LIMK2chr2231664186+CDC45chr2219504050+0.0103579360.9896421
ENST00000444929ENST00000407835LIMK2chr2231664186+CDC45chr2219504050+0.029879630.97012043
ENST00000444929ENST00000437685LIMK2chr2231664186+CDC45chr2219504050+0.0304418450.9695581
ENST00000444929ENST00000263201LIMK2chr2231664186+CDC45chr2219504050+0.0304418450.9695581
ENST00000331728ENST00000407835LIMK2chr2231664186+CDC45chr2219504050+0.0103591050.9896409
ENST00000331728ENST00000437685LIMK2chr2231664186+CDC45chr2219504050+0.0105710820.98942894
ENST00000331728ENST00000263201LIMK2chr2231664186+CDC45chr2219504050+0.0105710820.98942894
ENST00000333611ENST00000407835LIMK2chr2231664186+CDC45chr2219504050+0.013666860.9863332
ENST00000333611ENST00000437685LIMK2chr2231664186+CDC45chr2219504050+0.0139072510.98609275
ENST00000333611ENST00000263201LIMK2chr2231664186+CDC45chr2219504050+0.0139072510.98609275
ENST00000340552ENST00000407835LIMK2chr2231664186+CDC45chr2219504050+0.0137790790.98622096
ENST00000340552ENST00000437685LIMK2chr2231664186+CDC45chr2219504050+0.0140221990.98597777
ENST00000340552ENST00000263201LIMK2chr2231664186+CDC45chr2219504050+0.0140221990.98597777
ENST00000406516ENST00000407835LIMK2chr2231664186+CDC45chr2219504049+0.0101634810.9898365
ENST00000406516ENST00000437685LIMK2chr2231664186+CDC45chr2219504049+0.0103579360.9896421
ENST00000406516ENST00000263201LIMK2chr2231664186+CDC45chr2219504049+0.0103579360.9896421
ENST00000444929ENST00000407835LIMK2chr2231664186+CDC45chr2219504049+0.029879630.97012043
ENST00000444929ENST00000437685LIMK2chr2231664186+CDC45chr2219504049+0.0304418450.9695581
ENST00000444929ENST00000263201LIMK2chr2231664186+CDC45chr2219504049+0.0304418450.9695581
ENST00000331728ENST00000407835LIMK2chr2231664186+CDC45chr2219504049+0.0103591050.9896409
ENST00000331728ENST00000437685LIMK2chr2231664186+CDC45chr2219504049+0.0105710820.98942894
ENST00000331728ENST00000263201LIMK2chr2231664186+CDC45chr2219504049+0.0105710820.98942894
ENST00000333611ENST00000407835LIMK2chr2231664186+CDC45chr2219504049+0.013666860.9863332
ENST00000333611ENST00000437685LIMK2chr2231664186+CDC45chr2219504049+0.0139072510.98609275
ENST00000333611ENST00000263201LIMK2chr2231664186+CDC45chr2219504049+0.0139072510.98609275
ENST00000340552ENST00000407835LIMK2chr2231664186+CDC45chr2219504049+0.0137790790.98622096
ENST00000340552ENST00000437685LIMK2chr2231664186+CDC45chr2219504049+0.0140221990.98597777
ENST00000340552ENST00000263201LIMK2chr2231664186+CDC45chr2219504049+0.0140221990.98597777

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 LIMK2-CDC45

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
LIMK2chr2231664186CDC45chr22195040491352425QKVRFAKGIASGMTKNRRCKLLPLVM
LIMK2chr2231664186CDC45chr22195040491431455QKVRFAKGIASGMTKNRRCKLLPLVM
LIMK2chr2231664186CDC45chr22195040491484476QKVRFAKGIASGMTKNRRCKLLPLVM
LIMK2chr2231664186CDC45chr22195040491569476QKVRFAKGIASGMTKNRRCKLLPLVM
LIMK2chr2231664186CDC45chr2219504049709209QKVRFAKGIASGMTKNRRCKLLPLVM
LIMK2chr2231664186CDC45chr22195040501352425QKVRFAKGIASGMTKNRRCKLLPLVM
LIMK2chr2231664186CDC45chr22195040501431455QKVRFAKGIASGMTKNRRCKLLPLVM
LIMK2chr2231664186CDC45chr22195040501484476QKVRFAKGIASGMTKNRRCKLLPLVM
LIMK2chr2231664186CDC45chr22195040501569476QKVRFAKGIASGMTKNRRCKLLPLVM
LIMK2chr2231664186CDC45chr2219504050709209QKVRFAKGIASGMTKNRRCKLLPLVM

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Potential FusionNeoAntigen Information of LIMK2-CDC45 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.
LIMK2-CDC45_31664186_19504049.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)
LIMK2-CDC45chr2231664186chr22195040491431HLA-B08:01MTKNRRCKL0.99390.54731221
LIMK2-CDC45chr2231664186chr22195040491431HLA-A30:08KGIASGMTK0.98560.9549615
LIMK2-CDC45chr2231664186chr22195040491431HLA-A03:25KGIASGMTK0.97720.7763615
LIMK2-CDC45chr2231664186chr22195040491431HLA-A03:12KGIASGMTK0.9770.7984615
LIMK2-CDC45chr2231664186chr22195040491431HLA-A11:04KGIASGMTK0.96580.7296615
LIMK2-CDC45chr2231664186chr22195040491431HLA-A03:01KGIASGMTK0.97720.7763615
LIMK2-CDC45chr2231664186chr22195040491431HLA-B08:18MTKNRRCKL0.99390.54731221
LIMK2-CDC45chr2231664186chr22195040491431HLA-A30:01KGIASGMTK0.98540.9822615
LIMK2-CDC45chr2231664186chr22195040491431HLA-B08:12MTKNRRCKL0.7560.7571221

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Potential FusionNeoAntigen Information of LIMK2-CDC45 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 LIMK2-CDC45

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
4253KGIASGMTKNRRCKLIMK2CDC45chr2231664186chr22195040491431

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of LIMK2-CDC45

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-B14:023BVN4253KGIASGMTKNRRCK-7.88652-7.99992
HLA-B14:023BVN4253KGIASGMTKNRRCK-4.29833-5.33363
HLA-B52:013W394253KGIASGMTKNRRCK-6.2261-6.3395
HLA-B52:013W394253KGIASGMTKNRRCK-5.09871-6.13401
HLA-A11:014UQ24253KGIASGMTKNRRCK-6.21923-6.33263
HLA-A24:025HGA4253KGIASGMTKNRRCK-7.43578-7.54918
HLA-A24:025HGA4253KGIASGMTKNRRCK-5.56562-6.60092
HLA-B27:056PYJ4253KGIASGMTKNRRCK-8.68547-8.79887
HLA-B44:053DX84253KGIASGMTKNRRCK-5.68979-5.80319
HLA-B44:053DX84253KGIASGMTKNRRCK-2.56245-3.59775
HLA-A02:016TDR4253KGIASGMTKNRRCK-5.13852-5.25192

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Vaccine Design for the FusionNeoAntigens of LIMK2-CDC45

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
LIMK2-CDC45chr2231664186chr22195040491221MTKNRRCKLATGACAAAGAACCGGCGCTGCAAACTG
LIMK2-CDC45chr2231664186chr2219504049615KGIASGMTKAAAGGAATCGCCTCCGGAATGACAAAG

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 LIMK2-CDC45

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
BLCALIMK2-CDC45chr2231664186ENST00000331728chr2219504049ENST00000263201TCGA-DK-A3IN

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Potential target of CAR-T therapy development for LIMK2-CDC45

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 LIMK2-CDC45

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 LIMK2-CDC45

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