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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:PLP1_SGK1

Kinase Fusion Protein Summary

check button Kinase Fusion gene summary
Kinase Fusion partner gene informationKinase Fusion gene name: PLP1_SGK1
KinaseFusionDB ID: KFG4753
FusionGDB2.0 ID: KFG4753
HgeneTgene
Gene symbol

PLP1

SGK1

Gene ID

5354

6446

Gene nameproteolipid protein 1serum/glucocorticoid regulated kinase 1
SynonymsGPM6C|HLD1|MMPL|PLP|PLP/DM20|PMD|SPG2SGK
Cytomap

Xq22.2

6q23.2

Type of geneprotein-codingprotein-coding
Descriptionmyelin proteolipid proteinlipophilinmajor myelin proteolipid proteinserine/threonine-protein kinase Sgk1serine/threonine protein kinase SGK
Modification date2024040720240305
UniProtAcc

P60201

O00141

Ensembl transtripts involved in fusion geneENST idsENST00000303958, ENST00000361621, 
ENST00000418604, ENST00000466486, 
ENST00000367858, ENST00000237305, 
ENST00000367857, ENST00000413996, 
ENST00000475719, ENST00000489458, 
ENST00000524929, ENST00000528577, 
Context (manual curation of fusion genes in KinaseFusionDB)

PubMed: PLP1 [Title/Abstract] AND SGK1 [Title/Abstract] AND fusion [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)PLP1(103047545)-SGK1(134639049), # 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

check buttonKinase Fusion gene breakpoints across PLP1 (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 SGK1 (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
ChimerDB4TCGA-HT-7902-01APLP1chrX

103047545

SGK1chr6

134639049



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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/:103047545/:134639049)
- 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
PLP1

P60201

SGK1

O00141

FUNCTION: This is the major myelin protein from the central nervous system. It plays an important role in the formation or maintenance of the multilamellar structure of myelin.FUNCTION: Serine/threonine-protein kinase which is involved in the regulation of a wide variety of ion channels, membrane transporters, cellular enzymes, transcription factors, neuronal excitability, cell growth, proliferation, survival, migration and apoptosis. Plays an important role in cellular stress response. Contributes to regulation of renal Na(+) retention, renal K(+) elimination, salt appetite, gastric acid secretion, intestinal Na(+)/H(+) exchange and nutrient transport, insulin-dependent salt sensitivity of blood pressure, salt sensitivity of peripheral glucose uptake, cardiac repolarization and memory consolidation. Up-regulates Na(+) channels: SCNN1A/ENAC, SCN5A and ASIC1/ACCN2, K(+) channels: KCNJ1/ROMK1, KCNA1-5, KCNQ1-5 and KCNE1, epithelial Ca(2+) channels: TRPV5 and TRPV6, chloride channels: BSND, CLCN2 and CFTR, glutamate transporters: SLC1A3/EAAT1, SLC1A2 /EAAT2, SLC1A1/EAAT3, SLC1A6/EAAT4 and SLC1A7/EAAT5, amino acid transporters: SLC1A5/ASCT2, SLC38A1/SN1 and SLC6A19, creatine transporter: SLC6A8, Na(+)/dicarboxylate cotransporter: SLC13A2/NADC1, Na(+)-dependent phosphate cotransporter: SLC34A2/NAPI-2B, glutamate receptor: GRIK2/GLUR6. Up-regulates carriers: SLC9A3/NHE3, SLC12A1/NKCC2, SLC12A3/NCC, SLC5A3/SMIT, SLC2A1/GLUT1, SLC5A1/SGLT1 and SLC15A2/PEPT2. Regulates enzymes: GSK3A/B, PMM2 and Na(+)/K(+) ATPase, and transcription factors: CTNNB1 and nuclear factor NF-kappa-B. Stimulates sodium transport into epithelial cells by enhancing the stability and expression of SCNN1A/ENAC. This is achieved by phosphorylating the NEDD4L ubiquitin E3 ligase, promoting its interaction with 14-3-3 proteins, thereby preventing it from binding to SCNN1A/ENAC and targeting it for degradation. Regulates store-operated Ca(+2) entry (SOCE) by stimulating ORAI1 and STIM1. Regulates KCNJ1/ROMK1 directly via its phosphorylation or indirectly via increased interaction with SLC9A3R2/NHERF2. Phosphorylates MDM2 and activates MDM2-dependent ubiquitination of p53/TP53. Phosphorylates MAPT/TAU and mediates microtubule depolymerization and neurite formation in hippocampal neurons. Phosphorylates SLC2A4/GLUT4 and up-regulates its activity. Phosphorylates APBB1/FE65 and promotes its localization to the nucleus. Phosphorylates MAPK1/ERK2 and activates it by enhancing its interaction with MAP2K1/MEK1 and MAP2K2/MEK2. Phosphorylates FBXW7 and plays an inhibitory role in the NOTCH1 signaling. Phosphorylates FOXO1 resulting in its relocalization from the nucleus to the cytoplasm. Phosphorylates FOXO3, promoting its exit from the nucleus and interference with FOXO3-dependent transcription. Phosphorylates BRAF and MAP3K3/MEKK3 and inhibits their activity. Phosphorylates SLC9A3/NHE3 in response to dexamethasone, resulting in its activation and increased localization at the cell membrane. Phosphorylates CREB1. Necessary for vascular remodeling during angiogenesis. Sustained high levels and activity may contribute to conditions such as hypertension and diabetic nephropathy. Isoform 2 exhibited a greater effect on cell plasma membrane expression of SCNN1A/ENAC and Na(+) transport than isoform 1. {ECO:0000269|PubMed:11154281, ECO:0000269|PubMed:11410590, ECO:0000269|PubMed:11696533, ECO:0000269|PubMed:12397388, ECO:0000269|PubMed:12590200, ECO:0000269|PubMed:12634932, ECO:0000269|PubMed:12650886, ECO:0000269|PubMed:12761204, ECO:0000269|PubMed:12911626, ECO:0000269|PubMed:14623317, ECO:0000269|PubMed:14706641, ECO:0000269|PubMed:15040001, ECO:0000269|PubMed:15044175, ECO:0000269|PubMed:15234985, ECO:0000269|PubMed:15319523, ECO:0000269|PubMed:15496163, ECO:0000269|PubMed:15733869, ECO:0000269|PubMed:15737648, ECO:0000269|PubMed:15845389, ECO:0000269|PubMed:15888551, ECO:0000269|PubMed:16036218, ECO:0000269|PubMed:16443776, ECO:0000269|PubMed:16982696, ECO:0000269|PubMed:17382906, ECO:0000269|PubMed:18005662, ECO:0000269|PubMed:18304449, ECO:0000269|PubMed:18753299, ECO:0000269|PubMed:19447520, ECO:0000269|PubMed:19756449, ECO:0000269|PubMed:20511718, ECO:0000269|PubMed:20730100, ECO:0000269|PubMed:21865597}.

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 PLP1_SGK1


check button Phosphorylation target of the kinase
(phosphosite, 03-17-2024)
KinaseKinase UniProt AccKinase speciesSubstrateSubstrate UniProt AccSubstrate phosphorylated residuesSubstrate phosphorylated sites (+/-7AA)Domain
SGK1O00141humanNEDD4LQ96PU5S342ssRLRsCsVtDAVAE
SGK1O00141humanTBC1D4O60343S318EFRsRCssVtGVQRRPID
SGK1O00141humanNDRG2Q9UN36T330tRLsRsRtAsLtsAA
SGK1O00141humanNCSTNQ92542S437FLRArNIsGVVLADHNicastrin
SGK1O00141humanNDRG2Q9UN36S346VDGNRsRsRtLsQss
SGK1O00141humanCDKN1BP46527T157GIRkrPAtDDSSTQN
SGK1O00141humanKMT2DO14686-3S1331RGRARLKsTASSIET
SGK1O00141humanMKNK1Q9BUB5-2S353QVLQRNSsTMDLTLF
SGK1O00141humanGSK3BP49841Y216RGEPNVsyICsRyyRPkinase
SGK1O00141humanFOXO3O43524S315DFRsRTNsNAstVsG
SGK1O00141humanNEDD4LQ96PU5S448IRRPRsLssPtVtLS
SGK1O00141humanMAPK1P28482S29GPRyTNLsYIGEGAyPkinase
SGK1O00141humanTSC2P49815S981AFRCRSIsVSEHVVR
SGK1O00141humanTBC1D4O60343S570AKRsLtssLENIFsr
SGK1O00141humanMAP2K4P45985S80IERLRtHsIESSGkL
SGK1O00141humanTSC2P49815S1130GARDRVRsMsGGHGL
SGK1O00141humanWNK4Q96J92S1190SSRQRRLsKGSFPTS
SGK1O00141humanNDRG1Q92597T366GtRsRsHtsEGAHLD
SGK1O00141humanHTTP42858S419GGRsRsGsIVELIAG
SGK1O00141humanFBXW7Q969H0S227QQRRRITsVQPPTGL
SGK1O00141humanNFKBIAP25963S32LLDDRHDsGLDsMkD
SGK1O00141humanAPBB1O00213S610ECRVRFLsFLAVGRDPID
SGK1O00141humanNDRG1Q92597T346GtRsRsHtsEGtRsR
SGK1O00141humanNDRG1Q92597T356GtRsRsHtsEGtRsR
SGK1O00141humanTSC2P49815T1462GLrPrGytISDsAPs
SGK1O00141humanNDRG2Q9UN36T348GNRsRsRtLsQssEs
SGK1O00141humanCREB1P16220S119EILsRRPsyRkILNDpKID
SGK1O00141humanNEDD4LQ96PU5T367AGRARsstVtGGEEP
SGK1O00141humanTSC2P49815S939sFRARstsLNERPKs
SGK1O00141humanGSK3BP49841S9SGRPRttsFAEsCkP
SGK1O00141humanZBTB33Q86T24T606yLSDRSStIPAMkDD
SGK1O00141humanNDRG2Q9UN36S332LsRsRtAsLtsAAsV
SGK1O00141humanTBC1D4O60343S751EGRKRtsstCsNEsL
SGK1O00141humanMDM2Q00987S166SsRRRAIsEtEENsD
SGK1O00141humanMAPTP10636-8S214GsRsRtPsLPtPPtR
SGK1O00141humanTBC1D4O60343S341QPRRRHAsAPsHVQPPID
SGK1O00141humanCDKN1BP46527T198PGLRRRQt_______
SGK1O00141humanTSC2P49815S1798GQRKRLIssVEDFTE
SGK1O00141humanSGK1O00141S422AEAFLGFsYAPPTDSPkinase_C
SGK1O00141humanCARHSP1Q9Y2V2S52tRRtrtFsAtVRAsQ
SGK1O00141humanWNK1Q9H4A3T60EYRRRRHtMDKDSrG
SGK1O00141humanTBC1D4O60343T642QFRRRAHtFsHPPss
SGK1O00141humanSLC2A4P14672S274LERERPLsLLQLLGsSugar_tr
SGK1O00141humanNDRG1Q92597S330LMRsRtAsGssVtsL
SGK1O00141humanTBC1D4O60343T568NKAKRsLtssLENIF
SGK1O00141humanTBC1D4O60343S588RMRGRLGsVDsFERs
SGK1O00141humanTSC2P49815S1132RDRVRsMsGGHGLRV
SGK1O00141humanTBC1D4O60343S666GRAQGVRsPLLRQSS
SGK1O00141humanWNK4Q96J92S1201FPTSRRNsLQRSEPP
SGK1O00141humanPIKFYVEQ9Y2I7S318LsLDRsGsPMVPSyE
SGK1O00141humanRICTORQ6R327T1135NRRIRtLtEPsVDFNRICTOR_phospho
SGK1O00141humanIKBKBO14920S181DQGsLCtsFVGTLQyPkinase
SGK1O00141humanNDRG1Q92597T328TRLMRsRtAsGssVt
SGK1O00141humanWNK4Q96J92S1217PGIMRRNsLSGSStG


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
SGK1IDDescription0.00e+00
SGK1GO:0018105peptidyl-serine phosphorylation1.12e-05
SGK1GO:0018209peptidyl-serine modification1.12e-05
SGK1GO:0007611learning or memory7.35e-05
SGK1GO:0043434response to peptide hormone7.35e-05
SGK1GO:0050890cognition1.02e-04
SGK1GO:0062197cellular response to chemical stress1.02e-04
SGK1GO:0016049cell growth1.26e-04
SGK1GO:0010506regulation of autophagy1.57e-04
SGK1GO:0010038response to metal ion1.57e-04
SGK1GO:0010821regulation of mitochondrion organization4.93e-04
SGK1GO:0071375cellular response to peptide hormone stimulus9.00e-04
SGK1GO:0031647regulation of protein stability1.01e-03
SGK1GO:0006913nucleocytoplasmic transport1.01e-03
SGK1GO:0051169nuclear transport1.01e-03
SGK1GO:0071496cellular response to external stimulus1.23e-03
SGK1GO:0032869cellular response to insulin stimulus1.36e-03
SGK1GO:0045732positive regulation of protein catabolic process1.40e-03
SGK1GO:1903828negative regulation of protein localization1.51e-03
SGK1GO:1901653cellular response to peptide1.51e-03
SGK1GO:0044058regulation of digestive system process1.87e-03
SGK1GO:0071356cellular response to tumor necrosis factor2.01e-03
SGK1GO:0048588developmental cell growth2.01e-03
SGK1GO:1903146regulation of autophagy of mitochondrion2.06e-03
SGK1GO:0001558regulation of cell growth2.15e-03
SGK1GO:0007613memory2.15e-03
SGK1GO:0031669cellular response to nutrient levels2.15e-03
SGK1GO:0034599cellular response to oxidative stress2.24e-03
SGK1GO:0034612response to tumor necrosis factor2.32e-03
SGK1GO:0031400negative regulation of protein modification process2.38e-03
SGK1GO:0043666regulation of phosphoprotein phosphatase activity2.51e-03
SGK1GO:0032868response to insulin2.51e-03
SGK1GO:0031648protein destabilization2.74e-03
SGK1GO:0031668cellular response to extracellular stimulus2.90e-03
SGK1GO:0071456cellular response to hypoxia3.25e-03
SGK1GO:0043086negative regulation of catalytic activity3.31e-03
SGK1GO:0010508positive regulation of autophagy3.32e-03
SGK1GO:0043525positive regulation of neuron apoptotic process3.48e-03
SGK1GO:0034614cellular response to reactive oxygen species3.48e-03
SGK1GO:0031667response to nutrient levels3.52e-03
SGK1GO:0036294cellular response to decreased oxygen levels3.62e-03
SGK1GO:0034504protein localization to nucleus3.62e-03
SGK1GO:0030002intracellular monoatomic anion homeostasis3.62e-03
SGK1GO:0030644intracellular chloride ion homeostasis3.62e-03
SGK1GO:0010921regulation of phosphatase activity3.85e-03
SGK1GO:0051168nuclear export4.05e-03
SGK1GO:0030157pancreatic juice secretion4.05e-03
SGK1GO:0072584caveolin-mediated endocytosis4.05e-03
SGK1GO:0048638regulation of developmental growth4.13e-03
SGK1GO:0071453cellular response to oxygen levels4.33e-03

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Related Drugs to PLP1_SGK1


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 PLP1-SGK1 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 PLP1_SGK1


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