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	Kinase Fusion Gene Summary
	Kinase Fusion Gene Sample Information
	Kinase Fusion ORF Analysis
	Kinase Fusion Amino Acid Sequences
	Multiple Sequence Alignment of All Fusion Protein Isoforms
	Kinase Fusion Protein Functional Features
	Kinase Fusion Protein Structures
	Comparison of Fusion Protein Isoforms
	Comparison of Fusion Protein Sequences/Structures with Known Sequences/Structures from PDB
	pLDDT Scores and Difference Analysis of pLDDT Scores Between the Active Sites (Best) and Non-Active Sites.
	Ramachandran Plot of Kinase Fusion Protein Structure
	Potential Active Site Information
	Virtual Screening Results
	Kinase-Substrate Information
	Related Drugs with This Kinase Fusion Protein
	Related Disease with This Kinase Fusion Protein
	Clinical Trials of the Found Drugs/Small Molecules

Kinase Fusion Gene:LIMK2_ATXN10

Kinase Fusion Protein Summary

Kinase Fusion gene summary

Kinase Fusion partner gene information	Kinase Fusion gene name: LIMK2_ATXN10
	KinaseFusionDB ID: KFG3157
	FusionGDB2.0 ID: KFG3157
		Hgene	Tgene
	Gene symbol	LIMK2	ATXN10
	Gene ID	3985	25814
	Gene name	LIM domain kinase 2	ataxin 10
	Synonyms	-	ATX10\|E46L\|HUMEEP\|SCA10
	Cytomap	22q12.2	22q13.31
	Type of gene	protein-coding	protein-coding
	Description	LIM domain kinase 2	ataxin-10brain protein E46 homologspinocerebellar ataxia type 10 protein
	Modification date	20240305	20240411
	UniProtAcc	P53671	Q9UBB4
Ensembl transtripts involved in fusion gene	ENST ids	ENST00000331728, ENST00000333611, ENST00000340552, ENST00000406516, ENST00000444929, ENST00000467301,	ENST00000402380, ENST00000498009, ENST00000252934, ENST00000381061,
Context (manual curation of fusion genes in KinaseFusionDB)	PubMed: LIMK2 [Title/Abstract] AND ATXN10 [Title/Abstract] AND fusion [Title/Abstract]
Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)	LIMK2(31654412)-ATXN10(46202839), # samples:3

Gene ontology of each fusion partner gene with evidence of Inferred from Direct Assay (IDA) from Entrez

Partner	Gene	GO ID	GO term	PubMed ID
Hgene	LIMK2	GO:0006468	protein phosphorylation	22328514
Hgene	LIMK2	GO:0030953	astral microtubule organization	22328514
Tgene	ATXN10	GO:0031175	neuron projection development	16498633

Kinase Fusion 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.

Kinase Fusion gene breakpoints across ATXN10 (3'-gene)
* Click on the image to open the UCSC genome browser with custom track showing this image in a new window.

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Kinase Fusion Gene Sample Information

Kinase Fusion gene information.

Kinase Fusion gene information from four resources (ChiTars 5.0, ChimerDB 4.0, COSMIC, and CCLE)
* 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.

Source	Sample	Hgene	Hchr	Hbp	Tgene	Tchr	Tbp
ChimerDB4	TCGA-CV-6941-01A	LIMK2	chr22	31654412	ATXN10	chr22	46202839

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Kinase Fusion ORF Analysis

Kinase Fusion information from ORFfinder translation from full-length transcript sequence from KinaseFusionDB.

Henst	Tenst	Hgene	Hchr	Hbp	Tgene	Tchr	Tbp	Seq length (transcript)	Seq length (amino acids)
ENST00000406516	ENST00000381061	LIMK2	chr22	31654412	ATXN10	chr22	46202839	2175	154

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Kinase Fusion Amino Acid Sequences

For individual full-length fusion transcript sequence from KinaseFusionDB, we ran ORFfinder and chose the longest ORF among the all predicted ones.

>Henst_Tenst_Hgene_Hchr_Hbp_Tgene_Tchr_Tbp_length(fusion AA)_AAseq

>ENST00000406516_ENST00000381061_LIMK2_chr22_31654412_ATXN10_chr22_46202839_length(amino acids)=154
MRGAAVSPASSSPFPRSRDHVRAGGCSECQDSLTNWYYEKDGKLYCPKDYWGKFGEFCHGCSLLMTGPFMVNELDGIPLILDNCNISDSN

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

Multiple Sequence Alignment of All Fusion Protein Isoforms

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Kinase Fusion Protein Functional Features

Four levels of functional features of fusion genes
Go to FGviewer search page for the most frequent breakpoint (https://ccsmweb.uth.edu/FGviewer/chr22:31654412/chr22:46202839)
- 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.

Main function of each fusion partner protein. (from UniProt)

Hgene	Tgene
LIMK2 P53671	ATXN10 Q9UBB4
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}.	FUNCTION: Necessary for the survival of cerebellar neurons. Induces neuritogenesis by activating the Ras-MAP kinase pathway. May play a role in the maintenance of a critical intracellular glycosylation level and homeostasis. {ECO:0000250}.

Retention 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 domain in the 5'-partner of fusion protein (protein functional feature from UniProt).

636384

Partner

Hgeneene

Hbp

Tgeneene

Tbp

ENST

BPexon

TotalExon

Protein feature loci

BPloci

TotalLen

Feature

Note

Hgene

LIMK2

31654412

ATXN10

46202839

ENST00000406516

12_63

618

Domain

Note=LIM zinc-binding 1;Ontology_term=ECO:0000255;evidence=ECO:0000255|PROSITE-ProRule:PRU00125

Hgene

LIMK2

31654412

ATXN10

46202839

ENST00000406516

12_63

687

Domain

Note=LIM zinc-binding 1;Ontology_term=ECO:0000255;evidence=ECO:0000255|PROSITE-ProRule:PRU00125

Hgene

LIMK2

31654412

ATXN10

46202839

ENST00000406516

12_63

639

Domain

Note=LIM zinc-binding 1;Ontology_term=ECO:0000255;evidence=ECO:0000255|PROSITE-ProRule:PRU00125

- Retained domain in the 3'-partner of fusion protein (protein functional feature from UniProt).

Partner

Hgeneene

Hbp

Tgeneene

Tbp

ENST

BPexon

TotalExon

Protein feature loci

BPloci

TotalLen

Feature

Note

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Kinase Fusion Protein Structures

CIF files of the predicted kinase 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.

Kinase Fusion protein CIF link (fusion AA seq ID in KinaseFusionDB)	Henst	Tenst	Hgene	Hchr	Hbp	Tgene	Tchr	Tbp	AA seq	Len(AA seq)
PDB file >>>144_LIMK2_ATXN10	ENST00000406516	ENST00000381061	LIMK2	chr22	31654412	ATXN10	chr22	46202839	MRGAAVSPASSSPFPRSRDHVRAGGCSECQDSLTNWYYEKDGKLYCPKDYWGKFGEFCHGCSLLMTGPFMVNELDGIPLILDNCNISDSN	154
3D view using mol* of 144_LIMK2_ATXN10

PDB file >>>HKFP_214_LIMK2_ATXN10	ENST00000406516	ENST00000381061	LIMK2	chr22	31654412	ATXN10	chr22	46202839	MRGAAVSPASSSPFPRSRDHVRAGGCSECQDSLTNWYYEKDGKLYCPKDYWGKFGEFCHGCSLLMTGPFMVNELDGIPLILDNCNISDSN	154_LIMK2_ATXN10

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Comparison of Fusion Protein Isoforms

Superimpose the 3D Structures Among All Fusion Protein Isoforms
* Download the pdb file and open it from the molstar online viewer.

Comparison of the Secondary Structures of Fusion Protein Isoforms

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Comparison of Fusion Protein Sequences/Structures with Known Sequences/Structures from PDB

LIMK2_ATXN10 does not have any known PDB structures.

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pLDDT score distribution

pLDDT score distribution of the predicted fusion protein structures from AlphaFold2
* AlphaFold produces a per-residue confidence score (pLDDT) between 0 and 100.
* The blue color at the bottom marks the best active site residues.

144_LIMK2_ATXN10.png

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Potential Active Site Information

The potential binding sites of these fusion proteins were identified using SiteMap, a module of the Schrodinger suite.

Kinase Fusion AA seq ID in KinaseFusionDB

Site score

Size

Dscore

Volume

Exposure

Enclosure

Contact

Phobic

Philic

Balance

Don/Acc

Residues

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Ramachandran Plot of Kinase Fusion Protein Structure

Ramachandran plot of the torsional angles - phi (φ)and psi (ψ) - of the residues (amino acids) contained in this fusion protein peptide.

144_LIMK2_ATXN10_ramachandran.png

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Virtual Screening Results

Distribution of the average docking score across all approved kinase inhibitors.
Distribution of the number of occurrence across all approved kinase inhibitors.

5'-kinase fusion protein case

3'-kinase fusion protein case

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Drug information from DrugBank of the top 20 interacting small molecules.
* The detailed information of individual kinase inhibitors are available in the download page.

Fusion gene name info	Drug	Docking score	Glide g score	Glide energy
144_LIMK2_ATXN10-DOCK_HTVS_1-001	Nilotinib	-6.962860000000001	-7.102460000000001	-56.7253
144_LIMK2_ATXN10-DOCK_HTVS_1-001	Nilotinib	-6.962860000000001	-7.102460000000001	-56.7253
144_LIMK2_ATXN10-DOCK_HTVS_1-001	Belumosudil	-6.86262	-6.8703199999999995	-49.5436
144_LIMK2_ATXN10-DOCK_HTVS_1-001	Avapritinib	-6.64525	-6.97655	-48.2981
144_LIMK2_ATXN10-DOCK_HTVS_1-001	Avapritinib	-6.64525	-6.97655	-48.2981
144_LIMK2_ATXN10-DOCK_HTVS_1-001	Avapritinib	-6.64525	-6.97655	-48.2981
144_LIMK2_ATXN10-DOCK_HTVS_1-001	Avapritinib	-6.64525	-6.97655	-48.2981
144_LIMK2_ATXN10-DOCK_HTVS_1-001	Acalabrutinib	-6.3708800000000005	-6.3849800000000005	-53.677
144_LIMK2_ATXN10-DOCK_HTVS_1-001	Acalabrutinib	-6.3708800000000005	-6.3849800000000005	-53.677
144_LIMK2_ATXN10-DOCK_HTVS_1-001	Tivozanib	-6.2479	-6.2479	-58.5038
144_LIMK2_ATXN10-DOCK_HTVS_1-001	Zanubrutinib	-6.19451	-6.19451	-53.7961
144_LIMK2_ATXN10-DOCK_HTVS_1-001	Belumosudil	-6.14682	-6.15452	-49.4304
144_LIMK2_ATXN10-DOCK_HTVS_1-001	Selpercatinib	-6.047280000000001	-6.077780000000001	-55.0779
144_LIMK2_ATXN10-DOCK_HTVS_1-001	Selpercatinib	-6.047280000000001	-6.077780000000001	-55.0779
144_LIMK2_ATXN10-DOCK_HTVS_1-001	Larotrectinib	-6.02113	-6.02113	-41.3689
144_LIMK2_ATXN10-DOCK_HTVS_1-001	Asciminib	-5.90594	-6.37094	-52.5717
144_LIMK2_ATXN10-DOCK_HTVS_1-001	Netarsudil	-5.89692	-5.90802	-52.7111
144_LIMK2_ATXN10-DOCK_HTVS_1-001	Netarsudil	-5.89692	-5.90802	-52.7111
144_LIMK2_ATXN10-DOCK_HTVS_1-001	Asciminib	-5.86659	-6.33159	-52.1846
144_LIMK2_ATXN10-DOCK_HTVS_1-001	Trametinib	-5.750859999999999	-5.750859999999999	-49.989

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Kinase-Substrate Information of LIMK2_ATXN10

Phosphorylation target of the kinase
(phosphosite, 03-17-2024)

Kinase	Kinase UniProt Acc	Kinase species	Substrate	Substrate UniProt Acc	Substrate phosphorylated residues	Substrate phosphorylated sites (+/-7AA)	Domain
LIMK2	P53671	human	DSTN	P60981	S3	_____MAsGVQVADE
LIMK2	P53671	human	CFL1	P23528	S3	_____MAsGVAVsDG
LIMK2	P53671	human	G3BP1	Q13283	S149	VtEPQEEsEEEVEEP

Biological Network Integration of This Kinase and Substrates
(GeneMANIA website)

Enriched GO biological processes of the phosphorylation target genes of the kinase

Kinase	GOID	GO term	P.adjust
LIMK2	ID	Description	0.00e+00
LIMK2	GO:0051014	actin filament severing	1.50e-04
LIMK2	GO:0030042	actin filament depolymerization	1.03e-03
LIMK2	GO:0051261	protein depolymerization	2.71e-03
LIMK2	GO:0008154	actin polymerization or depolymerization	5.92e-03
LIMK2	GO:0032984	protein-containing complex disassembly	7.39e-03
LIMK2	GO:0007265	Ras protein signal transduction	1.19e-02
LIMK2	GO:0009615	response to virus	1.39e-02
LIMK2	GO:0007015	actin filament organization	1.39e-02
LIMK2	GO:0007264	small GTPase mediated signal transduction	1.39e-02
LIMK2	GO:0022411	cellular component disassembly	1.39e-02
LIMK2	GO:0030836	positive regulation of actin filament depolymerization	1.39e-02
LIMK2	GO:1901881	positive regulation of protein depolymerization	1.86e-02
LIMK2	GO:0044794	positive regulation by host of viral process	1.90e-02
LIMK2	GO:0040019	positive regulation of embryonic development	1.93e-02
LIMK2	GO:0034063	stress granule assembly	2.43e-02
LIMK2	GO:0043243	positive regulation of protein-containing complex disassembly	2.72e-02
LIMK2	GO:0061001	regulation of dendritic spine morphogenesis	2.90e-02
LIMK2	GO:0044788	modulation by host of viral process	3.18e-02
LIMK2	GO:0030834	regulation of actin filament depolymerization	3.18e-02
LIMK2	GO:0060997	dendritic spine morphogenesis	3.18e-02
LIMK2	GO:0051293	establishment of spindle localization	3.18e-02
LIMK2	GO:0051653	spindle localization	3.27e-02
LIMK2	GO:0032481	positive regulation of type I interferon production	3.27e-02
LIMK2	GO:0032508	DNA duplex unwinding	3.27e-02
LIMK2	GO:0097061	dendritic spine organization	3.27e-02
LIMK2	GO:1902117	positive regulation of organelle assembly	3.27e-02
LIMK2	GO:0032392	DNA geometric change	3.27e-02
LIMK2	GO:1901879	regulation of protein depolymerization	3.27e-02
LIMK2	GO:0051851	modulation by host of symbiont process	3.27e-02
LIMK2	GO:0000281	mitotic cytokinesis	3.27e-02
LIMK2	GO:0106027	neuron projection organization	3.27e-02
LIMK2	GO:0071103	DNA conformation change	3.27e-02
LIMK2	GO:0045995	regulation of embryonic development	3.27e-02
LIMK2	GO:0060996	dendritic spine development	3.27e-02
LIMK2	GO:0099175	regulation of postsynapse organization	3.44e-02
LIMK2	GO:0061640	cytoskeleton-dependent cytokinesis	3.59e-02
LIMK2	GO:0051702	biological process involved in interaction with symbiont	3.59e-02
LIMK2	GO:0032479	regulation of type I interferon production	3.59e-02
LIMK2	GO:0032606	type I interferon production	3.59e-02
LIMK2	GO:0043244	regulation of protein-containing complex disassembly	3.59e-02
LIMK2	GO:0007266	Rho protein signal transduction	3.80e-02
LIMK2	GO:0048813	dendrite morphogenesis	3.80e-02
LIMK2	GO:0090090	negative regulation of canonical Wnt signaling pathway	3.80e-02
LIMK2	GO:0008064	regulation of actin polymerization or depolymerization	4.07e-02
LIMK2	GO:0030832	regulation of actin filament length	4.07e-02
LIMK2	GO:0030178	negative regulation of Wnt signaling pathway	4.34e-02
LIMK2	GO:1902905	positive regulation of supramolecular fiber organization	4.34e-02
LIMK2	GO:0051495	positive regulation of cytoskeleton organization	4.47e-02
LIMK2	GO:0000910	cytokinesis	4.47e-02

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Related Drugs to LIMK2_ATXN10

Drugs used for this fusion-positive patient.
(Manual curation of PubMed, 04-30-2022 + MyCancerGenome)

Hgene

Tgene

Drug

Source

PMID

Distribution of the number of studies mentioning LIMK2-ATXN10 and kinase inhibitors the PubMed Abstract (04-01-2024)

Fusion gene - drug pair 1

Fusion gene - drug pair 2

PMID

Publication date

DOI

Study title

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Related Diseases to LIMK2_ATXN10

Diseases that have this fusion gene.
(Manual curation of PubMed, 04-30-2022 + MyCancerGenome)

Hgene

Tgene

Disease

Source

PMID

Related diseases from the literature mentioned this fusion gene and drug.
(PubMed, 04-01-2024)

MeSH ID

MeSH term

Diseases associated with fusion partners.
(DisGeNet 4.0)

Partner

Gene

Disease ID

Disease name

# pubmeds

Source

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Clinical Trials of the Found Drugs/Small Molecules

Statistics of the Clinical Trials of the Found Kinase Inibitors from clinicaltrials.gov (06-17-2024)

Clinical Trials from clinicaltrials.gov (06-17-2024)

Fusion Gene

Kinase Inhibitor

NCT ID

Study Status

Phases

Disease

# Enrolment

Date