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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_NXPH1

Kinase Fusion Protein Summary

check button Kinase Fusion gene summary
Kinase Fusion partner gene informationKinase Fusion gene name: RAF1_NXPH1
KinaseFusionDB ID: KFG5255
FusionGDB2.0 ID: KFG5255
HgeneTgene
Gene symbol

RAF1

NXPH1

Gene ID

6037

30010

Gene nameneurexophilin 1
SynonymsNPH1|Nbla00697
Cytomap

7p21.3

Type of geneprotein-coding
Descriptionneurexophilin-1
Modification date20240305
UniProtAcc

P04049

P58417

Ensembl transtripts involved in fusion geneENST idsENST00000251849, ENST00000442415, 
ENST00000542177, ENST00000534997, 
ENST00000405863, ENST00000497400, 
ENST00000602349, 
Context (manual curation of fusion genes in KinaseFusionDB)

PubMed: RAF1 [Title/Abstract] AND NXPH1 [Title/Abstract] AND fusion [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)RAF1(12705312)-NXPH1(8790638), # samples:3
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 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 NXPH1 (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-DK-A6B5-01ARAF1chr3

12705312

NXPH1chr7

8790638



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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/:8790638)
- 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

NXPH1

P58417

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: May be signaling molecules that resemble neuropeptides and that act by binding to alpha-neurexins and possibly other receptors. {ECO:0000305}.

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_NXPH1


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_NXPH1


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-NXPH1 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_NXPH1


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


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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