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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:RPS6KA3_C12orf57

Kinase Fusion Protein Summary

check button Kinase Fusion gene summary
Kinase Fusion partner gene informationKinase Fusion gene name: RPS6KA3_C12orf57
KinaseFusionDB ID: KFG5557
FusionGDB2.0 ID: KFG5557
HgeneTgene
Gene symbol

RPS6KA3

C12orf57

Gene ID

6197

113246

Gene nameribosomal protein S6 kinase A3chromosome 12 open reading frame 57
SynonymsCLS|HU-3|ISPK-1|MAPKAPK1B|MRX19|RSK|RSK2|S6K-alpha3|XLID19|p90-RSK2|pp90RSK2C10|GRCC10
Cytomap

Xp22.12

12p13.31

Type of geneprotein-codingprotein-coding
Descriptionribosomal protein S6 kinase alpha-3MAP kinase-activated protein kinase 1bMAPK-activated protein kinase 1bMAPKAP kinase 1bMAPKAPK-1bRSK-2S6K-alpha-3epididymis secretory sperm binding proteininsulin-stimulated protein kinase 1p90-RSK 3ribosomal S6protein C10gene rich cluster C10likely ortholog of mouse gene rich cluster, C10
Modification date2024040320240305
UniProtAcc

P51812

Q99622

Ensembl transtripts involved in fusion geneENST idsENST00000379548, ENST00000379565, 
ENST00000479809, ENST00000540702, 
ENST00000544447, 		ENST00000229281, 
ENST00000537087, ENST00000544681, 
ENST00000540506, ENST00000542222, 
Context (manual curation of fusion genes in KinaseFusionDB)

PubMed: RPS6KA3 [Title/Abstract] AND C12orf57 [Title/Abstract] AND fusion [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)RPS6KA3(20202495)-C12orf57(7053240), # 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
HgeneRPS6KA3

GO:0043154

negative regulation of cysteine-type endopeptidase activity involved in apoptotic process

18402937


check buttonKinase Fusion gene breakpoints across RPS6KA3 (5'-gene)
* Click on the image to open the UCSC genome browser with custom track showing this image in a new window.

check buttonKinase Fusion gene breakpoints across C12orf57 (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

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
ChiTaRS5.0EC561147RPS6KA3chrX

20202495

C12orf57chr12

7053240



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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/:20202495/:7053240)
- 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
RPS6KA3

P51812

C12orf57

Q99622

FUNCTION: Serine/threonine-protein kinase that acts downstream of ERK (MAPK1/ERK2 and MAPK3/ERK1) signaling and mediates mitogenic and stress-induced activation of the transcription factors CREB1, ETV1/ER81 and NR4A1/NUR77, regulates translation through RPS6 and EIF4B phosphorylation, and mediates cellular proliferation, survival, and differentiation by modulating mTOR signaling and repressing pro-apoptotic function of BAD and DAPK1 (PubMed:9770464, PubMed:16223362, PubMed:17360704, PubMed:16213824). In fibroblast, is required for EGF-stimulated phosphorylation of CREB1 and histone H3 at 'Ser-10', which results in the subsequent transcriptional activation of several immediate-early genes (PubMed:9770464, PubMed:10436156). In response to mitogenic stimulation (EGF and PMA), phosphorylates and activates NR4A1/NUR77 and ETV1/ER81 transcription factors and the cofactor CREBBP (PubMed:16223362). Upon insulin-derived signal, acts indirectly on the transcription regulation of several genes by phosphorylating GSK3B at 'Ser-9' and inhibiting its activity (PubMed:8250835). Phosphorylates RPS6 in response to serum or EGF via an mTOR-independent mechanism and promotes translation initiation by facilitating assembly of the preinitiation complex (PubMed:17360704). In response to insulin, phosphorylates EIF4B, enhancing EIF4B affinity for the EIF3 complex and stimulating cap-dependent translation (PubMed:18508509, PubMed:18813292). Is involved in the mTOR nutrient-sensing pathway by directly phosphorylating TSC2 at 'Ser-1798', which potently inhibits TSC2 ability to suppress mTOR signaling, and mediates phosphorylation of RPTOR, which regulates mTORC1 activity and may promote rapamycin-sensitive signaling independently of the PI3K/AKT pathway (PubMed:18722121). Mediates cell survival by phosphorylating the pro-apoptotic proteins BAD and DAPK1 and suppressing their pro-apoptotic function (PubMed:16213824). Promotes the survival of hepatic stellate cells by phosphorylating CEBPB in response to the hepatotoxin carbon tetrachloride (CCl4) (PubMed:18508509, PubMed:18813292). Is involved in cell cycle regulation by phosphorylating the CDK inhibitor CDKN1B, which promotes CDKN1B association with 14-3-3 proteins and prevents its translocation to the nucleus and inhibition of G1 progression (By similarity). In LPS-stimulated dendritic cells, is involved in TLR4-induced macropinocytosis, and in myeloma cells, acts as effector of FGFR3-mediated transformation signaling, after direct phosphorylation at Tyr-529 by FGFR3 (By similarity). Negatively regulates EGF-induced MAPK1/3 phosphorylation via phosphorylation of SOS1 (By similarity). Phosphorylates SOS1 at 'Ser-1134' and 'Ser-1161' that create YWHAB and YWHAE binding sites and which contribute to the negative regulation of MAPK1/3 phosphorylation (By similarity). Phosphorylates EPHA2 at 'Ser-897', the RPS6KA-EPHA2 signaling pathway controls cell migration (PubMed:26158630). Acts as a regulator of osteoblast differentiation by mediating phosphorylation of ATF4, thereby promoting ATF4 transactivation activity (By similarity). {ECO:0000250|UniProtKB:P18654, ECO:0000269|PubMed:10436156, ECO:0000269|PubMed:16213824, ECO:0000269|PubMed:16223362, ECO:0000269|PubMed:17360704, ECO:0000269|PubMed:18722121, ECO:0000269|PubMed:26158630, ECO:0000269|PubMed:8250835, ECO:0000269|PubMed:9770464, ECO:0000303|PubMed:18508509, ECO:0000303|PubMed:18813292}.FUNCTION: In brain, may be required for corpus callosum development. {ECO:0000269|PubMed:23453666}.

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 RPS6KA3_C12orf57


check button Phosphorylation target of the kinase
(phosphosite, 03-17-2024)
KinaseKinase UniProt AccKinase speciesSubstrateSubstrate UniProt AccSubstrate phosphorylated residuesSubstrate phosphorylated sites (+/-7AA)Domain
RPS6KA3P51812humanNFATC4Q14934S289PALsRRGsLGEEGsE
RPS6KA3P51812humanWWC1Q8IX03S947CRLNRsDsDSSTLSK
RPS6KA3P51812humanNFATC4Q14934S281SGTPSSAsPALsRRG
RPS6KA3P51812humanTHP07101-4S44RFIGRRQsLIEDARKTOH_N
RPS6KA3P51812humanRIOK2Q9BVS4S483QYRTRtLsItssGsA
RPS6KA3P51812humanEIF2AK2P19525T451kRtRSKGtLRyMsPEPkinase
RPS6KA3P51812humanYBX1P67809S102NPRKyLrsVGDGEtVCSD
RPS6KA3P51812humanTINF2Q9BSI4S295FPFRNLGsPtQVISk
RPS6KA3P51812humanH3C1P68431S10tkQtArkstGGkAPrHistone
RPS6KA3P51812humanRRN3Q9NYV6S649PVLYMQPsPL_____
RPS6KA3P51812humanLCP1P13796S5___MARGsVsDEEMM
RPS6KA3P51812humanMYL12AP19105S19KRPQRAtsNVFAMFD
RPS6KA3P51812humanTBX21Q9UL17S503DSKRRRVsPYPsSGD
RPS6KA3P51812humanTBX21Q9UL17S507RRVsPYPsSGDSsSP
RPS6KA3P51812humanMAP3K5Q99683T1109DRKIIATtLSKLkLEHisK-N-like
RPS6KA3P51812humanDAPK1P53355S289QALSRKAsAVNMEkF
RPS6KA3P51812humanSTAT3P40763S727NtIDLPMsPrTLDSL
RPS6KA3P51812humanSTMN1P16949S16kELEKrAsGQAFELIStathmin
RPS6KA3P51812humanEPHA2P29317S897RVsIRLPstsGsEGV
RPS6KA3P51812humanBADQ92934S99PFrGrsRsAPPNLWABcl-2_BAD
RPS6KA3P51812humanNFATC4Q14934S344QAVALPRsEEPASCN
RPS6KA3P51812humanWWC1Q8IX03T929stIIRsKtFsPGPQS
RPS6KA3P51812humanNFKBIAP25963S32LLDDRHDsGLDsMkD
RPS6KA3P51812humanGSK3AP49840S21sGrARtssFAEPGGG
RPS6KA3P51812humanPPP1R3AQ16821S65SSGTRRVsFADSFGF
RPS6KA3P51812humanNFATC4Q14934S676SNGRRKRsPTQSFRFRHD_dimer
RPS6KA3P51812humanNFATC4Q14934S285SSAsPALsRRGsLGE
RPS6KA3P51812humanSPRED2Q7Z698S168QPTRTIssPTSCEHR
RPS6KA3P51812humanMAP3K5Q99683S83ATRGRGssVGGGSrR
RPS6KA3P51812humanBADQ92934S75EIRsRHssyPAGtEDBcl-2_BAD
RPS6KA3P51812humanCASP8Q14790T263SIRDRNGtHLDAGALPeptidase_C14
RPS6KA3P51812humanCREB1P16220S119EILsRRPsyRkILNDpKID
RPS6KA3P51812humanGSK3BP49841S9SGRPRttsFAEsCkP
RPS6KA3P51812humanRANBP3Q9H6Z4S126VKRERtssLtQFPPs
RPS6KA3P51812humanESR1P03372S167GGRERLAsTNDkGSMOest_recep
RPS6KA3P51812humanH2AXP16104S16kARAkAksRSsrAGLHistone
RPS6KA3P51812humanRPS6P62753S236AKRRRLssLRAstsK
RPS6KA3P51812humanVGLL1Q99990S84PNQWRYSsPWTKPQP
RPS6KA3P51812humanRELAQ04206S276sMQLRRPsDRELsEPRHD_dimer
RPS6KA3P51812humanTINF2Q9BSI4S330ASTGKSKsPCQTLGG
RPS6KA3P51812humanTHP07101-2S67RFIGRRQsLIEDARKTOH_N
RPS6KA3P51812humanMAP3K5Q99683T1326VNGADEDtISRFLAE
RPS6KA3P51812humanTHP07101S71RFIGRRQsLIEDARKTOH_N
RPS6KA3P51812humanPPP1R3AQ16821S46PQPSRRGsDssEDIY
RPS6KA3P51812humanATF4P18848S245TrGSPNRsLPsPGVL
RPS6KA3P51812humanFOXN2P32314S369LGDsGYAsQPCAKIS
RPS6KA3P51812humanFOXN2P32314S365EDDPLGDsGYAsQPC
RPS6KA3P51812humanSPRED2Q7Z698S167EQPTRTIssPTSCEH
RPS6KA3P51812humanH2BC3P33778S32DGKkRKRsRkEsysIHistone
RPS6KA3P51812humanFGFR1P11362S789DTRSSTCsSGEDSVF
RPS6KA3P51812humanRPS6P62753S235IAKRRRLssLRAsts
RPS6KA3P51812humanSLC9A3P48764S663TMRKRLEsFKSTKLG
RPS6KA3P51812humanTHP07101-3S40RFIGRRQsLIEDARKTOH_N
RPS6KA3P51812humanCICQ96RK0S173PGKRRtQsLsALPKE
RPS6KA3P51812humanEIF2S1P05198S52MILLsELsRRRIRsIS1
RPS6KA3P51812humanKCNK3O14649S393GLMKRRssV______


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
RPS6KA3IDDescription0.00e+00
RPS6KA3GO:0071248cellular response to metal ion2.28e-04
RPS6KA3GO:0071241cellular response to inorganic substance2.28e-04
RPS6KA3GO:0097191extrinsic apoptotic signaling pathway2.28e-04
RPS6KA3GO:0010038response to metal ion2.56e-04
RPS6KA3GO:0071287cellular response to manganese ion3.40e-04
RPS6KA3GO:0034198cellular response to amino acid starvation1.04e-03
RPS6KA3GO:1990928response to amino acid starvation1.04e-03
RPS6KA3GO:0002064epithelial cell development1.04e-03
RPS6KA3GO:0010042response to manganese ion1.15e-03
RPS6KA3GO:0045862positive regulation of proteolysis1.15e-03
RPS6KA3GO:0038034signal transduction in absence of ligand1.59e-03
RPS6KA3GO:0097192extrinsic apoptotic signaling pathway in absence of ligand1.59e-03
RPS6KA3GO:1902893regulation of miRNA transcription1.71e-03
RPS6KA3GO:0061614miRNA transcription1.71e-03
RPS6KA3GO:2001233regulation of apoptotic signaling pathway1.71e-03
RPS6KA3GO:0003323type B pancreatic cell development1.71e-03
RPS6KA3GO:0010950positive regulation of endopeptidase activity1.71e-03
RPS6KA3GO:1902894negative regulation of miRNA transcription1.77e-03
RPS6KA3GO:2000629negative regulation of miRNA metabolic process1.89e-03
RPS6KA3GO:0010952positive regulation of peptidase activity2.20e-03
RPS6KA3GO:0008625extrinsic apoptotic signaling pathway via death domain receptors2.33e-03
RPS6KA3GO:2000628regulation of miRNA metabolic process2.33e-03
RPS6KA3GO:0003309type B pancreatic cell differentiation2.43e-03
RPS6KA3GO:0005979regulation of glycogen biosynthetic process2.47e-03
RPS6KA3GO:0010962regulation of glucan biosynthetic process2.47e-03
RPS6KA3GO:0140747regulation of ncRNA transcription2.57e-03
RPS6KA3GO:0006109regulation of carbohydrate metabolic process2.64e-03
RPS6KA3GO:0062197cellular response to chemical stress2.74e-03
RPS6KA3GO:0097193intrinsic apoptotic signaling pathway2.74e-03
RPS6KA3GO:0046777protein autophosphorylation3.02e-03
RPS6KA3GO:0002068glandular epithelial cell development3.02e-03
RPS6KA3GO:0071214cellular response to abiotic stimulus3.02e-03
RPS6KA3GO:0104004cellular response to environmental stimulus3.02e-03
RPS6KA3GO:0035883enteroendocrine cell differentiation3.02e-03
RPS6KA3GO:0070306lens fiber cell differentiation3.02e-03
RPS6KA3GO:0001819positive regulation of cytokine production3.02e-03
RPS6KA3GO:0010586miRNA metabolic process3.02e-03
RPS6KA3GO:0070873regulation of glycogen metabolic process3.02e-03
RPS6KA3GO:0032885regulation of polysaccharide biosynthetic process3.12e-03
RPS6KA3GO:0071496cellular response to external stimulus3.12e-03
RPS6KA3GO:0043280positive regulation of cysteine-type endopeptidase activity involved in apoptotic process3.40e-03
RPS6KA3GO:0032355response to estradiol3.56e-03
RPS6KA3GO:0005978glycogen biosynthetic process4.15e-03
RPS6KA3GO:0006984ER-nucleus signaling pathway4.15e-03
RPS6KA3GO:0009250glucan biosynthetic process4.15e-03
RPS6KA3GO:0031018endocrine pancreas development4.15e-03
RPS6KA3GO:0032881regulation of polysaccharide metabolic process4.15e-03
RPS6KA3GO:0042789mRNA transcription by RNA polymerase II4.15e-03
RPS6KA3GO:0002286T cell activation involved in immune response4.15e-03

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Related Drugs to RPS6KA3_C12orf57


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 RPS6KA3-C12orf57 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 RPS6KA3_C12orf57


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