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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:RAF1_PPARG

Kinase Fusion Protein Summary

check button Kinase Fusion gene summary
Kinase Fusion partner gene informationKinase Fusion gene name: RAF1_PPARG
KinaseFusionDB ID: KFG5257
FusionGDB2.0 ID: KFG5257
HgeneTgene
Gene symbol

RAF1

PPARG

Gene ID

6037

5468

Gene nameperoxisome proliferator activated receptor gamma
SynonymsCIMT1|GLM1|NR1C3|PPARG1|PPARG2|PPARG5|PPARgamma
Cytomap

3p25.2

Type of geneprotein-coding
Descriptionperoxisome proliferator-activated receptor gammaPPAR-gammanuclear receptor subfamily 1 group C member 3peroxisome proliferator-activated receptor-gamma 5peroxisome proliferator-activated receptor-gamma splicing
Modification date20240416
UniProtAcc

P04049

Q86YN6

Ensembl transtripts involved in fusion geneENST idsENST00000251849, ENST00000442415, 
ENST00000542177, ENST00000534997, 
ENST00000309576, ENST00000397010, 
ENST00000397012, ENST00000397026, 
ENST00000287820, ENST00000397000, 
ENST00000397015, ENST00000539812, 
Context (manual curation of fusion genes in KinaseFusionDB)

PubMed: RAF1 [Title/Abstract] AND PPARG [Title/Abstract] AND fusion [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)RAF1(12705312)-PPARG(12353879), # 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
TgenePPARG

GO:0000122

negative regulation of transcription by RNA polymerase II

12700342

TgenePPARG

GO:0006919

activation of cysteine-type endopeptidase activity involved in apoptotic process

18293083

TgenePPARG

GO:0007165

signal transduction

9568716

TgenePPARG

GO:0010628

positive regulation of gene expression

18382765

TgenePPARG

GO:0010629

negative regulation of gene expression

28467929

TgenePPARG

GO:0010742

macrophage derived foam cell differentiation

-

TgenePPARG

GO:0010745

negative regulation of macrophage derived foam cell differentiation

19114110

TgenePPARG

GO:0010875

positive regulation of cholesterol efflux

24751522

TgenePPARG

GO:0010887

negative regulation of cholesterol storage

19114110

TgenePPARG

GO:0010891

negative regulation of sequestering of triglyceride

12700342

TgenePPARG

GO:0016525

negative regulation of angiogenesis

28566713

TgenePPARG

GO:0030224

monocyte differentiation

9568716

TgenePPARG

GO:0030512

negative regulation of transforming growth factor beta receptor signaling pathway

31023188

TgenePPARG

GO:0035357

peroxisome proliferator activated receptor signaling pathway

25704091

TgenePPARG

GO:0042789

mRNA transcription by RNA polymerase II

16373399

TgenePPARG

GO:0042953

lipoprotein transport

9568716

TgenePPARG

GO:0043407

negative regulation of MAP kinase activity

18382765

TgenePPARG

GO:0043537

negative regulation of blood vessel endothelial cell migration

28566713

TgenePPARG

GO:0045944

positive regulation of transcription by RNA polymerase II

9568715|12700342|16239304|16373399|17611579|24751522

TgenePPARG

GO:0048384

retinoic acid receptor signaling pathway

16239304

TgenePPARG

GO:0048469

cell maturation

9568716

TgenePPARG

GO:0048662

negative regulation of smooth muscle cell proliferation

18382765|20622039|31023188

TgenePPARG

GO:0051091

positive regulation of DNA-binding transcription factor activity

18293083

TgenePPARG

GO:0071404

cellular response to low-density lipoprotein particle stimulus

9568716

TgenePPARG

GO:1901202

negative regulation of extracellular matrix assembly

25704091

TgenePPARG

GO:1902894

negative regulation of miRNA transcription

24751522

TgenePPARG

GO:1902895

positive regulation of miRNA transcription

25704091|28566713

TgenePPARG

GO:1904706

negative regulation of vascular associated smooth muscle cell proliferation

28522568

TgenePPARG

GO:1904893

negative regulation of receptor signaling pathway via STAT

28467929

TgenePPARG

GO:1905599

positive regulation of low-density lipoprotein receptor activity

9568716

TgenePPARG

GO:2000272

negative regulation of signaling receptor activity

12700342


check buttonKinase Fusion gene breakpoints across RAF1 (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 PPARG (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-IN-8462-11ARAF1chr3

12705312

PPARGchr3

12353879



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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/:12705312/:12353879)
- 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
RAF1

P04049

PPARG

Q86YN6

FUNCTION: Serine/threonine-protein kinase that acts as a regulatory link between the membrane-associated Ras GTPases and the MAPK/ERK cascade, and this critical regulatory link functions as a switch determining cell fate decisions including proliferation, differentiation, apoptosis, survival and oncogenic transformation. RAF1 activation initiates a mitogen-activated protein kinase (MAPK) cascade that comprises a sequential phosphorylation of the dual-specific MAPK kinases (MAP2K1/MEK1 and MAP2K2/MEK2) and the extracellular signal-regulated kinases (MAPK3/ERK1 and MAPK1/ERK2). The phosphorylated form of RAF1 (on residues Ser-338 and Ser-339, by PAK1) phosphorylates BAD/Bcl2-antagonist of cell death at 'Ser-75'. Phosphorylates adenylyl cyclases: ADCY2, ADCY5 and ADCY6, resulting in their activation. Phosphorylates PPP1R12A resulting in inhibition of the phosphatase activity. Phosphorylates TNNT2/cardiac muscle troponin T. Can promote NF-kB activation and inhibit signal transducers involved in motility (ROCK2), apoptosis (MAP3K5/ASK1 and STK3/MST2), proliferation and angiogenesis (RB1). Can protect cells from apoptosis also by translocating to the mitochondria where it binds BCL2 and displaces BAD/Bcl2-antagonist of cell death. Regulates Rho signaling and migration, and is required for normal wound healing. Plays a role in the oncogenic transformation of epithelial cells via repression of the TJ protein, occludin (OCLN) by inducing the up-regulation of a transcriptional repressor SNAI2/SLUG, which induces down-regulation of OCLN. Restricts caspase activation in response to selected stimuli, notably Fas stimulation, pathogen-mediated macrophage apoptosis, and erythroid differentiation. {ECO:0000269|PubMed:11427728, ECO:0000269|PubMed:11719507, ECO:0000269|PubMed:15385642, ECO:0000269|PubMed:15618521, ECO:0000269|PubMed:15849194, ECO:0000269|PubMed:16892053, ECO:0000269|PubMed:16924233, ECO:0000269|PubMed:9360956}.FUNCTION: Plays a role of stimulator of transcription factors and nuclear receptors activities. Activates transcriptional activity of estrogen receptor alpha, nuclear respiratory factor 1 (NRF1) and glucocorticoid receptor in the presence of glucocorticoids. May play a role in constitutive non-adrenergic-mediated mitochondrial biogenesis as suggested by increased basal oxygen consumption and mitochondrial number when overexpressed. May be involved in fat oxidation and non-oxidative glucose metabolism and in the regulation of energy expenditure. Induces the expression of PERM1 in the skeletal muscle in an ESRRA-dependent manner. {ECO:0000269|PubMed:11854298, ECO:0000269|PubMed:12678921, ECO:0000269|PubMed:15546003, ECO:0000269|PubMed:23836911}.

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 RAF1_PPARG


check button Phosphorylation target of the kinase
(phosphosite, 03-17-2024)
KinaseKinase UniProt AccKinase speciesSubstrateSubstrate UniProt AccSubstrate phosphorylated residuesSubstrate phosphorylated sites (+/-7AA)Domain
RAF1P04049humanRAF1P04049S621PKINRsAsEPsLHRA
RAF1P04049humanKLF10Q13118T93TIPAFCLtPPYsPSD
RAF1P04049humanBADQ92934S75EIRsRHssyPAGtEDBcl-2_BAD
RAF1P04049humanBADQ92934S118GRELRRMsDEFVDsFBcl-2_BAD
RAF1P04049humanMAP2K1Q02750S222LIDsMANsFVGtRSYPkinase
RAF1P04049humanRAF1P04049S359StRIGsGsFGtVYkGPK_Tyr_Ser-Thr
RAF1P04049humanEEF1A2Q05639S21GHVDSGkstttGHLIGTP_EFTU
RAF1P04049humanMAP2K1Q02750S218VsGQLIDsMANsFVGPkinase
RAF1P04049humanRAF1P04049S259sQRQRststPNVHMV
RAF1P04049humanMYCP01106T23MPLNVsFtNRNyDLDMyc_N
RAF1P04049humanRAF1P04049S338RPRGQRDssyyWEIE
RAF1P04049humanBADQ92934S99PFrGrsRsAPPNLWABcl-2_BAD
RAF1P04049humanPPP1R12AO14974T696ARQsRRstQGVtLtD


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
RAF1IDDescription0.00e+00
RAF1GO:0044342type B pancreatic cell proliferation4.58e-05
RAF1GO:0035019somatic stem cell population maintenance3.64e-04
RAF1GO:0051347positive regulation of transferase activity1.14e-03
RAF1GO:0035270endocrine system development1.22e-03
RAF1GO:0050673epithelial cell proliferation1.22e-03
RAF1GO:0043281regulation of cysteine-type endopeptidase activity involved in apoptotic process1.62e-03
RAF1GO:0019827stem cell population maintenance1.83e-03
RAF1GO:0098727maintenance of cell number1.83e-03
RAF1GO:2000116regulation of cysteine-type endopeptidase activity1.84e-03
RAF1GO:0030878thyroid gland development2.45e-03
RAF1GO:0052548regulation of endopeptidase activity4.55e-03
RAF1GO:0048538thymus development4.55e-03
RAF1GO:0052547regulation of peptidase activity4.55e-03
RAF1GO:0048009insulin-like growth factor receptor signaling pathway4.55e-03
RAF1GO:0060324face development4.55e-03
RAF1GO:1902105regulation of leukocyte differentiation4.55e-03
RAF1GO:0033674positive regulation of kinase activity4.95e-03
RAF1GO:0035773insulin secretion involved in cellular response to glucose stimulus5.56e-03
RAF1GO:2001244positive regulation of intrinsic apoptotic signaling pathway5.56e-03
RAF1GO:2001233regulation of apoptotic signaling pathway6.87e-03
RAF1GO:1903706regulation of hemopoiesis7.50e-03
RAF1GO:0010720positive regulation of cell development8.29e-03
RAF1GO:0008625extrinsic apoptotic signaling pathway via death domain receptors8.29e-03
RAF1GO:0048534hematopoietic or lymphoid organ development1.03e-02
RAF1GO:0043280positive regulation of cysteine-type endopeptidase activity involved in apoptotic process1.27e-02
RAF1GO:0002761regulation of myeloid leukocyte differentiation1.52e-02
RAF1GO:2001056positive regulation of cysteine-type endopeptidase activity1.58e-02
RAF1GO:0071333cellular response to glucose stimulus1.68e-02
RAF1GO:0071331cellular response to hexose stimulus1.68e-02
RAF1GO:0071326cellular response to monosaccharide stimulus1.68e-02
RAF1GO:2001235positive regulation of apoptotic signaling pathway1.73e-02
RAF1GO:0071456cellular response to hypoxia1.73e-02
RAF1GO:0071322cellular response to carbohydrate stimulus1.77e-02
RAF1GO:0010950positive regulation of endopeptidase activity1.78e-02
RAF1GO:0001678intracellular glucose homeostasis1.78e-02
RAF1GO:0036294cellular response to decreased oxygen levels1.78e-02
RAF1GO:0010952positive regulation of peptidase activity2.00e-02
RAF1GO:0071453cellular response to oxygen levels2.03e-02
RAF1GO:1902107positive regulation of leukocyte differentiation2.10e-02
RAF1GO:1903708positive regulation of hemopoiesis2.10e-02
RAF1GO:0032872regulation of stress-activated MAPK cascade2.10e-02
RAF1GO:0070302regulation of stress-activated protein kinase signaling cascade2.10e-02
RAF1GO:2001242regulation of intrinsic apoptotic signaling pathway2.10e-02
RAF1GO:0071466cellular response to xenobiotic stimulus2.10e-02
RAF1GO:0009749response to glucose2.10e-02
RAF1GO:0009746response to hexose2.10e-02
RAF1GO:0002520immune system development2.10e-02
RAF1GO:0030073insulin secretion2.10e-02
RAF1GO:0034284response to monosaccharide2.20e-02

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Related Drugs to RAF1_PPARG


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 RAF1-PPARG 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 RAF1_PPARG


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
HgeneRAF1C0028326Noonan Syndrome10CLINGEN;CTD_human;GENOMICS_ENGLAND;ORPHANET
HgeneRAF1C0175704LEOPARD Syndrome7CLINGEN;CTD_human;GENOMICS_ENGLAND
HgeneRAF1C1969057Noonan Syndrome 54CTD_human;GENOMICS_ENGLAND;UNIPROT
HgeneRAF1C1969056LEOPARD SYNDROME 23CTD_human;GENOMICS_ENGLAND;UNIPROT
HgeneRAF1C0007194Hypertrophic Cardiomyopathy2CTD_human
HgeneRAF1C0041409Turner Syndrome, Male2CTD_human
HgeneRAF1C1519086Pilomyxoid astrocytoma2ORPHANET
HgeneRAF1C1527404Female Pseudo-Turner Syndrome2CTD_human
HgeneRAF1C4551472Hypertrophic obstructive cardiomyopathy2CTD_human
HgeneRAF1C4551602Noonan Syndrome 12CTD_human
TgenePPARGC0011860Diabetes Mellitus, Non-Insulin-Dependent6CTD_human;GENOMICS_ENGLAND
TgenePPARGC0238463Papillary thyroid carcinoma4ORPHANET
TgenePPARGC0002152Alloxan Diabetes3CTD_human
TgenePPARGC0002395Alzheimer's Disease3CTD_human
TgenePPARGC0011265Presenile dementia3CTD_human
TgenePPARGC0011853Diabetes Mellitus, Experimental3CTD_human
TgenePPARGC0020538Hypertensive disease3CTD_human
TgenePPARGC0021655Insulin Resistance3CTD_human
TgenePPARGC0022660Kidney Failure, Acute3CTD_human
TgenePPARGC0028754Obesity3CTD_human;GENOMICS_ENGLAND;UNIPROT
TgenePPARGC0035126Reperfusion Injury3CTD_human
TgenePPARGC0038433Streptozotocin Diabetes3CTD_human
TgenePPARGC0276496Familial Alzheimer Disease (FAD)3CTD_human
TgenePPARGC0494463Alzheimer Disease, Late Onset3CTD_human
TgenePPARGC0546126Acute Confusional Senile Dementia3CTD_human
TgenePPARGC0750900Alzheimer's Disease, Focal Onset3CTD_human
TgenePPARGC0750901Alzheimer Disease, Early Onset3CTD_human
TgenePPARGC0920563Insulin Sensitivity3CTD_human
TgenePPARGC1565662Acute Kidney Insufficiency3CTD_human
TgenePPARGC1720861Familial Partial Lipodystrophy, Type 33CTD_human;GENOMICS_ENGLAND;ORPHANET;UNIPROT
TgenePPARGC2609414Acute kidney injury3CTD_human
TgenePPARGC0021368Inflammation2CTD_human
TgenePPARGC0022116Ischemia2CTD_human
TgenePPARGC0024623Malignant neoplasm of stomach2CTD_human
TgenePPARGC0025202melanoma2CTD_human
TgenePPARGC0030297Pancreatic Neoplasm2CTD_human
TgenePPARGC0038356Stomach Neoplasms2CTD_human
TgenePPARGC0346647Malignant neoplasm of pancreas2CTD_human
TgenePPARGC1708349Hereditary Diffuse Gastric Cancer2CTD_human


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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