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Center for Computational Systems Medicine
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Kinase Fusion Gene Summary

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Kinase Fusion Gene Sample Information

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Kinase Fusion ORF Analysis

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Kinase Fusion Amino Acid Sequences

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Multiple Sequence Alignment of All Fusion Protein Isoforms

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Kinase Fusion Protein Functional Features

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Kinase Fusion Protein Structures

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Comparison of Fusion Protein Isoforms

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

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pLDDT Scores and Difference Analysis of pLDDT Scores Between the Active Sites (Best) and Non-Active Sites.

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Ramachandran Plot of Kinase Fusion Protein Structure

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Potential Active Site Information

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Virtual Screening Results

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Kinase-Substrate Information

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Related Drugs with This Kinase Fusion Protein

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Related Disease with This Kinase Fusion Protein

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Clinical Trials of the Found Drugs/Small Molecules

Kinase Fusion Gene:STK3_SPAG1

Kinase Fusion Protein Summary

check button Kinase Fusion gene summary
Kinase Fusion partner gene informationKinase Fusion gene name: STK3_SPAG1
KinaseFusionDB ID: KFG6260
FusionGDB2.0 ID: KFG6260
HgeneTgene
Gene symbol

STK3

SPAG1

Gene ID

8428

6674

Gene nameserine/threonine kinase 24sperm associated antigen 1
SynonymsHEL-S-95|MST3|MST3B|STE20|STK3CILD28|CT140|DNAAF13|HEL-S-268|HSD-3.8|SP75|TPIS
Cytomap

13q32.2

8q22.2

Type of geneprotein-codingprotein-coding
Descriptionserine/threonine-protein kinase 24STE20-like kinase 3STE20-like kinase MST3epididymis secretory protein Li 95mammalian STE20-like protein kinase 3serine/threonine kinase 24 (STE20 homolog, yeast)sterile 20-like kinase 3sperm-associated antigen 1TPR-containing protein involved in spermatogenesisdynein axonemal assembly factor 13epididymis secretory protein Li 268infertility-related sperm protein Spag-1tetratricopeptide repeat-containing protein
Modification date2024041120240407
UniProtAcc

Q9UEW8

Q6Q759

Ensembl transtripts involved in fusion geneENST idsENST00000419617, ENST00000523601, 
ENST00000521768, 		ENST00000523302, 
ENST00000251809, ENST00000388798, 
ENST00000520508, ENST00000520643, 
Context (manual curation of fusion genes in KinaseFusionDB)

PubMed: STK3 [Title/Abstract] AND SPAG1 [Title/Abstract] AND fusion [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)SPAG1(101245765)-STK3(99719539), # samples:2
STK3(99718694)-SPAG1(101190043), # samples:1
check button Gene ontology of each fusion partner gene with evidence of Inferred from Direct Assay (IDA) from Entrez
PartnerGeneGO IDGO termPubMed ID
HgeneSTK3

GO:0006468

protein phosphorylation

19604147

HgeneSTK3

GO:0034599

cellular response to oxidative stress

22291017

HgeneSTK3

GO:0046777

protein autophosphorylation

17046825|17657516


check buttonKinase Fusion gene breakpoints across STK3 (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 buttonKinase Fusion gene breakpoints across SPAG1 (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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Kinase Fusion Gene Sample Information

check buttonKinase Fusion gene information.
check button 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.
SourceSampleHgeneHchrHbpTgeneTchrTbp
ChimerDB4TCGA-ZQ-A9CRSTK3chr8

99718694

SPAG1chr8

101190043



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Kinase Fusion ORF Analysis


check buttonKinase Fusion information from ORFfinder translation from full-length transcript sequence from KinaseFusionDB.
HenstTenstHgeneHchrHbpTgeneTchrTbpSeq length
(transcript)		Seq length
(amino acids)

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Kinase Fusion Amino Acid Sequences


check button 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

Multiple Sequence Alignment of All Fusion Protein Isoforms



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Kinase 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/chr8:101245765/chr8:99719539)
- 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
STK3

Q9UEW8

SPAG1

Q6Q759

FUNCTION: Effector serine/threonine-protein kinase component of the WNK-SPAK/OSR1 kinase cascade, which is involved in various processes, such as ion transport, response to hypertonic stress and blood pressure (PubMed:16669787, PubMed:18270262, PubMed:21321328, PubMed:34289367). Specifically recognizes and binds proteins with a RFXV motif (PubMed:16669787, PubMed:21321328). Acts downstream of WNK kinases (WNK1, WNK2, WNK3 or WNK4): following activation by WNK kinases, catalyzes phosphorylation of ion cotransporters, such as SLC12A1/NKCC2, SLC12A2/NKCC1, SLC12A3/NCC, SLC12A5/KCC2 or SLC12A6/KCC3, regulating their activity (PubMed:21321328). Mediates regulatory volume increase in response to hyperosmotic stress by catalyzing phosphorylation of ion cotransporters SLC12A1/NKCC2, SLC12A2/NKCC1 and SLC12A6/KCC3 downstream of WNK1 and WNK3 kinases (PubMed:12740379, PubMed:16669787, PubMed:21321328). Phosphorylation of Na-K-Cl cotransporters SLC12A2/NKCC1 and SLC12A2/NKCC1 promote their activation and ion influx; simultaneously, phosphorylation of K-Cl cotransporters SLC12A5/KCC2 and SLC12A6/KCC3 inhibit their activity, blocking ion efflux (PubMed:16669787, PubMed:19665974, PubMed:21321328). Acts as a regulator of NaCl reabsorption in the distal nephron by mediating phosphorylation and activation of the thiazide-sensitive Na-Cl cotransporter SLC12A3/NCC in distal convoluted tubule cells of kidney downstream of WNK4 (PubMed:18270262). Mediates the inhibition of SLC4A4, SLC26A6 as well as CFTR activities (By similarity). Phosphorylates RELT (By similarity). {ECO:0000250|UniProtKB:Q9Z1W9, ECO:0000269|PubMed:12740379, ECO:0000269|PubMed:16669787, ECO:0000269|PubMed:18270262, ECO:0000269|PubMed:19665974, ECO:0000269|PubMed:21321328, ECO:0000269|PubMed:34289367}.FUNCTION: Component of the central pair apparatus of ciliary axonemes. Plays a critical role in the function and structure of motile cilia. May play a role in endochondral bone formation, most likely because of a function in primary cilia of chondrocytes and osteoblasts (By similarity). Essential for normal spermatogenesis and male fertility (By similarity). Required for normal manchette structure, transport of proteins along the manchette microtubules and formation of the sperm head and flagellum (By similarity). Essential for sperm flagellum development and proper assembly of the respiratory motile cilia central pair apparatus, but not the brain ependymal cilia (By similarity). {ECO:0000250|UniProtKB:Q5S003}.

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.

check button - Retained domain in the 5'-partner of fusion protein (protein functional feature from UniProt).
PartnerHgeneeneHbpTgeneeneTbpENSTBPexonTotalExonProtein feature lociBPlociTotalLenFeatureNote


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


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Kinase-Substrate Information of STK3_SPAG1


check button Phosphorylation target of the kinase
(phosphosite, 03-17-2024)
KinaseKinase UniProt AccKinase speciesSubstrateSubstrate UniProt AccSubstrate phosphorylated residuesSubstrate phosphorylated sites (+/-7AA)Domain
STK3Q13188humanNR3C1P04150S682VPkDGLksQELFDEIHormone_recep
STK3Q13188humanPRKCAP17252S226LNPQWNEsFtFkLKPC2
STK3Q13188humanABL1P00519T735DTEWRSVtLPRDLQS
STK3Q13188humanMOB1BQ7L9L4T74QINMLYGtITDFCTEMob1_phocein
STK3Q13188humanSAV1Q9H4B6S36LLRNLMPsFIRHGPT
STK3Q13188humanNR3C1P04150T562StWRIMTtLNMLGGRHormone_recep
STK3Q13188humanMOB1AQ9H8S9T35LLkHAEAtLGsGNLRMob1_phocein
STK3Q13188humanOBSCNQ5VST9T5798AESVVVStAIQEFYK
STK3Q13188humanNEK2P51955S406NsEsQLtsksKCKDL
STK3Q13188humanMOB1AQ9H8S9T12FsSRssktFKPkkNI
STK3Q13188humanLATS1O95835S909HQRCLAHsLVGTPNYPkinase
STK3Q13188humanPRKAA1Q13131T183sDGEFLRtsCGsPNyPkinase
STK3Q13188humanPRKCAP17252T228PQWNEsFtFkLKPsDC2
STK3Q13188humanSAV1Q9H4B6S269YRHPCAPsVPRyDQP
STK3Q13188humanSTK3Q13188T378DEEEEDGtMKRNAts
STK3Q13188humanSAV1Q9H4B6T26GKYVKKEtsPLLRNL
STK3Q13188humanNR3C1P04150T668EEYLCMKtLLLLSSVHormone_recep
STK3Q13188humanLATS1O95835T967MKVINWQtSLHIPPQPkinase
STK3Q13188humanYAP1P46937S127PQHVRAHssPAsLQL
STK3Q13188humanSAV1Q9H4B6S27KYVKKEtsPLLRNLM
STK3Q13188humanLATS1O95835T1079EHAFyEFtFRRFFDD
STK3Q13188humanNEK2P51955S365LkERkFLsLASNPEL
STK3Q13188humanSTAT3P40763T622kEGGVTFtWVEkDISSH2
STK3Q13188humanLATS1O95835T1060EEENVNDtLNGWYKN
STK3Q13188humanMOB1AQ9H8S9T74QINMLYGtITEFCTEMob1_phocein
STK3Q13188humanNEK2P51955S356ENLLkNYsLLkERkF
STK3Q13188humanNR3C1P04150S746TFLDKTMsIEFPEML
STK3Q13188humanMAP1LC3BQ9GZQ8T50QLPVLDktkFLVPDHATG8
STK3Q13188humanMOB1BQ7L9L4T35LLkHAEAtLGsGNLRMob1_phocein
STK3Q13188humanSTK3Q13188T180DtMAkRNtVIGTPFWPkinase
STK3Q13188humanSIK3Q9Y2K2T221TPGQLLKtWCGSPPYPkinase
STK3Q13188humanLATS1O95835T1012kAHPFFKtIDFSSDL
STK3Q13188humanLATS1O95835S872GDHPRQDsMDFSNEWPkinase
STK3Q13188humanNEK2P51955S438EkNYQLksRQILGMR
STK3Q13188humanMOB1BQ7L9L4T12FGsRssktFKPkkNI


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

check button Enriched GO biological processes of the phosphorylation target genes of the kinase
KinaseGOIDGO termP.adjust
STK3IDDescription0.00e+00
STK3GO:0035329hippo signaling6.70e-10
STK3GO:1904019epithelial cell apoptotic process4.11e-05
STK3GO:0048638regulation of developmental growth4.65e-05
STK3GO:0035265organ growth5.76e-05
STK3GO:0046620regulation of organ growth2.25e-04
STK3GO:1904035regulation of epithelial cell apoptotic process3.18e-04
STK3GO:0050678regulation of epithelial cell proliferation1.94e-03
STK3GO:0060038cardiac muscle cell proliferation1.94e-03
STK3GO:1904036negative regulation of epithelial cell apoptotic process2.21e-03
STK3GO:0016055Wnt signaling pathway2.29e-03
STK3GO:0198738cell-cell signaling by wnt2.29e-03
STK3GO:0050673epithelial cell proliferation2.55e-03
STK3GO:2000736regulation of stem cell differentiation2.77e-03
STK3GO:0014855striated muscle cell proliferation3.10e-03
STK3GO:0048708astrocyte differentiation3.33e-03
STK3GO:0055017cardiac muscle tissue growth3.34e-03
STK3GO:0060419heart growth4.07e-03
STK3GO:0071560cellular response to transforming growth factor beta stimulus4.20e-03
STK3GO:0071559response to transforming growth factor beta4.31e-03
STK3GO:0034504protein localization to nucleus5.10e-03
STK3GO:0001824blastocyst development5.61e-03
STK3GO:0060562epithelial tube morphogenesis5.70e-03
STK3GO:0030518intracellular steroid hormone receptor signaling pathway5.70e-03
STK3GO:0002065columnar/cuboidal epithelial cell differentiation5.70e-03
STK3GO:0030111regulation of Wnt signaling pathway5.70e-03
STK3GO:0097284hepatocyte apoptotic process5.70e-03
STK3GO:0030522intracellular receptor signaling pathway6.24e-03
STK3GO:0061744motor behavior6.37e-03
STK3GO:0043401steroid hormone mediated signaling pathway6.80e-03
STK3GO:0070102interleukin-6-mediated signaling pathway7.27e-03
STK3GO:2000737negative regulation of stem cell differentiation7.27e-03
STK3GO:0045598regulation of fat cell differentiation7.27e-03
STK3GO:0001701in utero embryonic development7.39e-03
STK3GO:0060479lung cell differentiation7.39e-03
STK3GO:0060487lung epithelial cell differentiation7.39e-03
STK3GO:0060575intestinal epithelial cell differentiation7.39e-03
STK3GO:0060537muscle tissue development9.96e-03
STK3GO:0030216keratinocyte differentiation1.07e-02
STK3GO:0033146regulation of intracellular estrogen receptor signaling pathway1.07e-02
STK3GO:0019827stem cell population maintenance1.09e-02
STK3GO:0046621negative regulation of organ growth1.09e-02
STK3GO:0045766positive regulation of angiogenesis1.09e-02
STK3GO:1904018positive regulation of vasculature development1.09e-02
STK3GO:0098727maintenance of cell number1.09e-02
STK3GO:0006109regulation of carbohydrate metabolic process1.09e-02
STK3GO:0009755hormone-mediated signaling pathway1.15e-02
STK3GO:0071354cellular response to interleukin-61.16e-02
STK3GO:0046777protein autophosphorylation1.20e-02
STK3GO:0071383cellular response to steroid hormone stimulus1.27e-02

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Related Drugs to STK3_SPAG1


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

check button Distribution of the number of studies mentioning STK3-SPAG1 and kinase inhibitors the PubMed Abstract (04-01-2024)

Fusion gene - drug pair 1Fusion gene - drug pair 2PMIDPublication dateDOIStudy title

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Related Diseases to STK3_SPAG1


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

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

check button Diseases associated with fusion partners.
(DisGeNet 4.0)
PartnerGeneDisease IDDisease name# pubmedsSource


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Clinical Trials of the Found Drugs/Small Molecules


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

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

Fusion GeneKinase InhibitorNCT IDStudy StatusPhasesDisease# EnrolmentDate