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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:HIPK2_KLRG2

Kinase Fusion Protein Summary

check button Kinase Fusion gene summary
Kinase Fusion partner gene informationKinase Fusion gene name: HIPK2_KLRG2
KinaseFusionDB ID: KFG2694
FusionGDB2.0 ID: KFG2694
HgeneTgene
Gene symbol

HIPK2

KLRG2

Gene ID

28996

346689

Gene namehomeodomain interacting protein kinase 2killer cell lectin like receptor G2
SynonymsPRO0593CLEC15B
Cytomap

7q34

7q34

Type of geneprotein-codingprotein-coding
Descriptionhomeodomain-interacting protein kinase 2hHIPk2killer cell lectin-like receptor subfamily G member 2C-type lectin domain family 15 member Bkiller cell lectin-like receptor subfamily G, member 2
Modification date2024031720240305
UniProtAcc

Q9H2X6

A4D1S0

Ensembl transtripts involved in fusion geneENST idsENST00000342645, ENST00000406875, 
ENST00000428878, 		ENST00000393039, 
ENST00000340940, 
Context (manual curation of fusion genes in KinaseFusionDB)

PubMed: HIPK2 [Title/Abstract] AND KLRG2 [Title/Abstract] AND fusion [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)HIPK2(139415731)-KLRG2(139164518), # 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
HgeneHIPK2

GO:0006468

protein phosphorylation

19448668

HgeneHIPK2

GO:0018105

peptidyl-serine phosphorylation

33591310

HgeneHIPK2

GO:0030330

DNA damage response, signal transduction by p53 class mediator

14647468

HgeneHIPK2

GO:0045766

positive regulation of angiogenesis

19046997

HgeneHIPK2

GO:0060395

SMAD protein signal transduction

12874272


check buttonKinase Fusion gene breakpoints across HIPK2 (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 KLRG2 (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-BC-4072-01BHIPK2chr7

139415731

KLRG2chr7

139164518



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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/:139415731/:139164518)
- 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
HIPK2

Q9H2X6

KLRG2

A4D1S0

FUNCTION: Serine/threonine-protein kinase involved in transcription regulation, p53/TP53-mediated cellular apoptosis and regulation of the cell cycle. Acts as a corepressor of several transcription factors, including SMAD1 and POU4F1/Brn3a and probably NK homeodomain transcription factors. Phosphorylates PDX1, ATF1, PML, p53/TP53, CREB1, CTBP1, CBX4, RUNX1, EP300, CTNNB1, HMGA1, ZBTB4 and DAZAP2. Inhibits cell growth and promotes apoptosis through the activation of p53/TP53 both at the transcription level and at the protein level (by phosphorylation and indirect acetylation). The phosphorylation of p53/TP53 may be mediated by a p53/TP53-HIPK2-AXIN1 complex. Involved in the response to hypoxia by acting as a transcriptional co-suppressor of HIF1A. Mediates transcriptional activation of TP73. In response to TGFB, cooperates with DAXX to activate JNK. Negative regulator through phosphorylation and subsequent proteasomal degradation of CTNNB1 and the antiapoptotic factor CTBP1. In the Wnt/beta-catenin signaling pathway acts as an intermediate kinase between MAP3K7/TAK1 and NLK to promote the proteasomal degradation of MYB. Phosphorylates CBX4 upon DNA damage and promotes its E3 SUMO-protein ligase activity. Activates CREB1 and ATF1 transcription factors by phosphorylation in response to genotoxic stress. In response to DNA damage, stabilizes PML by phosphorylation. PML, HIPK2 and FBXO3 may act synergically to activate p53/TP53-dependent transactivation. Promotes angiogenesis, and is involved in erythroid differentiation, especially during fetal liver erythropoiesis. Phosphorylation of RUNX1 and EP300 stimulates EP300 transcription regulation activity. Triggers ZBTB4 protein degradation in response to DNA damage. In response to DNA damage, phosphorylates DAZAP2 which localizes DAZAP2 to the nucleus, reduces interaction of DAZAP2 with HIPK2 and prevents DAZAP2-dependent ubiquitination of HIPK2 by E3 ubiquitin-protein ligase SIAH1 and subsequent proteasomal degradation (PubMed:33591310). Modulates HMGA1 DNA-binding affinity. In response to high glucose, triggers phosphorylation-mediated subnuclear localization shifting of PDX1. Involved in the regulation of eye size, lens formation and retinal lamination during late embryogenesis. {ECO:0000269|PubMed:11740489, ECO:0000269|PubMed:11925430, ECO:0000269|PubMed:12851404, ECO:0000269|PubMed:12874272, ECO:0000269|PubMed:14678985, ECO:0000269|PubMed:17018294, ECO:0000269|PubMed:17960875, ECO:0000269|PubMed:18695000, ECO:0000269|PubMed:18809579, ECO:0000269|PubMed:19015637, ECO:0000269|PubMed:19046997, ECO:0000269|PubMed:19448668, ECO:0000269|PubMed:20307497, ECO:0000269|PubMed:20573984, ECO:0000269|PubMed:20637728, ECO:0000269|PubMed:20980392, ECO:0000269|PubMed:21192925, ECO:0000269|PubMed:22825850, ECO:0000269|PubMed:33591310}.

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 HIPK2_KLRG2


check button Phosphorylation target of the kinase
(phosphosite, 03-17-2024)
KinaseKinase UniProt AccKinase speciesSubstrateSubstrate UniProt AccSubstrate phosphorylated residuesSubstrate phosphorylated sites (+/-7AA)Domain
HIPK2Q9H2X6humanHIPK2Q9H2X6T838SKRVKENtPPRCAMV
HIPK2Q9H2X6humanZBTB4Q9P1Z0T797ERPGGtPtPVIAYsK
HIPK2Q9H2X6humanKLF3P57682S78sPPsAGNsPSSLKFP
HIPK2Q9H2X6humanSIAH2O43255S68GGGAGPVsPQHHELT
HIPK2Q9H2X6humanHMGA1P17096T78ktrkttttPGrkPrG
HIPK2Q9H2X6humanHIPK2Q9H2X6S827SSSQAIssPQRSKRV
HIPK2Q9H2X6humanCTBP1Q13363S422AHPPHAPsPGQTVkP
HIPK2Q9H2X6humanPMLP29590S36PSEGRQPsPsPsPtE
HIPK2Q9H2X6humanTLE1Q04724S289DAsssPAstAsSASS
HIPK2Q9H2X6humanSIAH2O43255T119PTCRGALtPSIRNLA
HIPK2Q9H2X6humanMECP2P51608S216VkRVLEKsPGkLLVk
HIPK2Q9H2X6humanMECP2P51608S80AVPEAsAsPKQRRsI
HIPK2Q9H2X6humanTP53P04637S46AMDDLMLsPDDIEQWTAD2
HIPK2Q9H2X6humanSIRT1Q96EB6S682SDSGTCQsPSLEEPM
HIPK2Q9H2X6humanRUNX1Q01196S276VHPAtPIsPGRASGM
HIPK2Q9H2X6humanPMLP29590S8MEPAPARsPRPQQDP
HIPK2Q9H2X6humanEP300Q09472S2279PVQPNPMsPQQHMLP
HIPK2Q9H2X6humanHIPK2Q9H2X6T880QTIVIPDtPsPTVSV
HIPK2Q9H2X6humanCBX4O00257T497SLQVkPEtPASAAVA
HIPK2Q9H2X6humanHIPK2Q9H2X6Y361SkAVCstyLQsRYyRPkinase
HIPK2Q9H2X6humanKLF3P57682S108sPPIKKysPPsPGVQ
HIPK2Q9H2X6humanKLF3P57682S101GLsMPsssPPIKKys
HIPK2Q9H2X6humanTLE1Q04724S286LKkDAsssPAstAsS
HIPK2Q9H2X6humanCEBPBP17676S76HERAIDFsPyLEPLG
HIPK2Q9H2X6humanZBTB4Q9P1Z0T983AAPPAPPtPPPPTLP
HIPK2Q9H2X6humanHMGA1P17096S36PRkQPPVsPGtALVG
HIPK2Q9H2X6humanSIRT1Q96EB6S27ADREAAssPAGEPLR
HIPK2Q9H2X6humanHIPK2Q9H2X6S364VCstyLQsRYyRAPEPkinase
HIPK2Q9H2X6humanHDAC3O15379S374KMLNHAPsVQIHDVP
HIPK2Q9H2X6humanTP63Q9H3D4T491PQQRNALtPTTIPDG
HIPK2Q9H2X6humanHIPK2Q9H2X6S924SCVTVHDsPYSDSSS
HIPK2Q9H2X6humanRUNX1Q01196S249DTRQIQPsPPWsyDQ
HIPK2Q9H2X6humanTLE1Q04724S239KDSsHYDsDGDKsDD
HIPK2Q9H2X6humanKLF3P57682S250KRPLPVEsPDtQRKR
HIPK2Q9H2X6humanNOTCH1P46531T2511VPEHPFLtPsPEsPD
HIPK2Q9H2X6humanSIAH2O43255T26PPPQPQHtPsPAAPP
HIPK2Q9H2X6humanCTBP2P56545S428AHPSQAPsPNQPTKH
HIPK2Q9H2X6humanHMGA1P17096-2T67kTRkTTTtPGRkPrG
HIPK2Q9H2X6humanHIPK2Q9H2X6S848RCAMVHSsPACSTSV
HIPK2Q9H2X6humanPPM1DO15297S85PLPDAGAsPAPsRCCPP2C
HIPK2Q9H2X6humanRUNX1Q01196T273sPsVHPAtPIsPGRA
HIPK2Q9H2X6humanHIPK2Q9H2X6S934SDSSSNTsPYSVQQR
HIPK2Q9H2X6humanKLF3P57682S224PPLMNsVsPPQALLQ
HIPK2Q9H2X6humanKLF3P57682S111IKKysPPsPGVQPFG
HIPK2Q9H2X6humanHMGA1P17096T53kEPsEVPtPkRPrGr
HIPK2Q9H2X6humanKLF3P57682S71LTVNKRSsPPsAGNs
HIPK2Q9H2X6humanPPM1DO15297S54QPLPPRPsPAALPGG
HIPK2Q9H2X6humanHIPK2Q9H2X6S668GFQGLQAsPSkHAGY
HIPK2Q9H2X6humanCDKN1BP46527S10NVRVSNGsPsLErMD
HIPK2Q9H2X6humanHIPK2Q9H2X6S882IVIPDtPsPTVSVIT
HIPK2Q9H2X6humanZBTB4Q9P1Z0T795AAERPGGtPtPVIAY
HIPK2Q9H2X6humanELF4Q99607S369ASLELGPsLDEEIPT
HIPK2Q9H2X6humanCREB1P16220S257PGVVMAssPALPTQP
HIPK2Q9H2X6humanKLF3P57682S92PSSHRRAsPGLsMPs
HIPK2Q9H2X6humanPMLP29590S38EGRQPsPsPsPtERA
HIPK2Q9H2X6humanHMGA1P17096-2T42kEPsEVPtPkrPrGr
HIPK2Q9H2X6humanSIAH2O43255S28PQPQHtPsPAAPPAA
HIPK2Q9H2X6humanCEBPBP17676T235SsssPPGtPSPADAK
HIPK2Q9H2X6humanKLF3P57682S216DYYPEEMsPPLMNsV
HIPK2Q9H2X6humanSPASTQ9UBP0S268sGHHRAPsySGLSMV


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
HIPK2IDDescription0.00e+00
HIPK2GO:0042771intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator2.63e-08
HIPK2GO:0072331signal transduction by p53 class mediator2.70e-08
HIPK2GO:0030330DNA damage respons3.46e-10
HIPK2GO:0048511rhythmic process6.19e-07
HIPK2GO:0001666response to hypoxia6.19e-07
HIPK2GO:0008630intrinsic apoptotic signaling pathway in response to DNA damage6.82e-07
HIPK2GO:0036293response to decreased oxygen levels7.18e-07
HIPK2GO:0090398cellular senescence8.24e-07
HIPK2GO:0007623circadian rhythm8.24e-07
HIPK2GO:0070482response to oxygen levels1.02e-06
HIPK2GO:0097193intrinsic apoptotic signaling pathway1.48e-05
HIPK2GO:0042770signal transduction in response to DNA damage1.48e-05
HIPK2GO:1901796regulation of signal transduction by p53 class mediator2.66e-05
HIPK2GO:0040029epigenetic regulation of gene expression3.99e-05
HIPK2GO:0045444fat cell differentiation5.98e-05
HIPK2GO:0030099myeloid cell differentiation7.90e-05
HIPK2GO:0048732gland development9.11e-05
HIPK2GO:0071456cellular response to hypoxia9.32e-05
HIPK2GO:0051402neuron apoptotic process9.32e-05
HIPK2GO:0050872white fat cell differentiation1.03e-04
HIPK2GO:0070059intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress1.05e-04
HIPK2GO:0036294cellular response to decreased oxygen levels1.08e-04
HIPK2GO:0006977DNA damage respons1.46e-06
HIPK2GO:0051170import into nucleus1.26e-04
HIPK2GO:0071453cellular response to oxygen levels1.54e-04
HIPK2GO:0048638regulation of developmental growth1.68e-04
HIPK2GO:0006913nucleocytoplasmic transport1.68e-04
HIPK2GO:0051169nuclear transport1.68e-04
HIPK2GO:0030324lung development1.95e-04
HIPK2GO:0030323respiratory tube development2.10e-04
HIPK2GO:0060541respiratory system development3.30e-04
HIPK2GO:0031571mitotic G1 DNA damage checkpoint signaling3.30e-04
HIPK2GO:0044819mitotic G1/S transition checkpoint signaling3.30e-04
HIPK2GO:0018205peptidyl-lysine modification3.54e-04
HIPK2GO:1990830cellular response to leukemia inhibitory factor4.10e-04
HIPK2GO:0007179transforming growth factor beta receptor signaling pathway4.17e-04
HIPK2GO:1990823response to leukemia inhibitory factor4.20e-04
HIPK2GO:0043523regulation of neuron apoptotic process4.22e-04
HIPK2GO:0007178transmembrane receptor protein serine/threonine kinase signaling pathway4.27e-04
HIPK2GO:0042752regulation of circadian rhythm5.10e-04
HIPK2GO:0009314response to radiation5.10e-04
HIPK2GO:0031112positive regulation of microtubule polymerization or depolymerization5.10e-04
HIPK2GO:0016570histone modification5.82e-04
HIPK2GO:0046660female sex differentiation5.82e-04
HIPK2GO:0022612gland morphogenesis6.08e-04
HIPK2GO:0072089stem cell proliferation6.55e-04
HIPK2GO:0060251regulation of glial cell proliferation6.80e-04
HIPK2GO:0044772mitotic cell cycle phase transition7.59e-04
HIPK2GO:0014014negative regulation of gliogenesis8.67e-04

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Related Drugs to HIPK2_KLRG2


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 HIPK2-KLRG2 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 HIPK2_KLRG2


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