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Kinase Fusion Gene:ENPP1_INSR |
Kinase Fusion Protein Summary |
Kinase Fusion gene summary |
Kinase Fusion partner gene information | Kinase Fusion gene name: ENPP1_INSR | KinaseFusionDB ID: KFG1973 | FusionGDB2.0 ID: KFG1973 | Hgene | Tgene | Gene symbol | ENPP1 | INSR | Gene ID | 5167 | 3643 | |
Gene name | ectonucleotide pyrophosphatase/phosphodiesterase 1 | insulin receptor | ||||||||||
Synonyms | ARHR2|COLED|M6S1|NPP1|NPPS|PC-1|PCA1|PDNP1 | CD220|HHF5 | ||||||||||
Cytomap | 6q23.2 | 19p13.2 | ||||||||||
Type of gene | protein-coding | protein-coding | ||||||||||
Description | ectonucleotide pyrophosphatase/phosphodiesterase family member 1E-NPP 1Ly-41 antigenalkaline phosphodiesterase 1membrane component, chromosome 6, surface marker 1phosphodiesterase I/nucleotide pyrophosphatase 1plasma-cell membrane glycoprotein 1pla | insulin receptorIR | ||||||||||
Modification date | 20240413 | 20240413 | ||||||||||
UniProtAcc | P22413 | P14616 | ||||||||||
Ensembl transtripts involved in fusion gene | ENST ids | ENST00000360971, | ENST00000302850, ENST00000341500, | |||||||||
Context (manual curation of fusion genes in KinaseFusionDB) | PubMed: ENPP1 [Title/Abstract] AND INSR [Title/Abstract] AND fusion [Title/Abstract] | |||||||||||
Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0) | ENPP1(132129415)-INSR(7152938), # samples:1 |
Gene ontology of each fusion partner gene with evidence of Inferred from Direct Assay (IDA) from Entrez |
Partner | Gene | GO ID | GO term | PubMed ID |
Hgene | ENPP1 | GO:0006091 | generation of precursor metabolites and energy | 12746903 |
Hgene | ENPP1 | GO:0006796 | phosphate-containing compound metabolic process | 10513816|11159191 |
Hgene | ENPP1 | GO:0009143 | nucleoside triphosphate catabolic process | 10513816 |
Hgene | ENPP1 | GO:0010035 | response to inorganic substance | 25644539 |
Hgene | ENPP1 | GO:0010467 | gene expression | 28592560 |
Hgene | ENPP1 | GO:0030282 | bone mineralization | 28652107 |
Hgene | ENPP1 | GO:0030308 | negative regulation of cell growth | 17849011 |
Hgene | ENPP1 | GO:0030505 | inorganic diphosphate transport | 10513816 |
Hgene | ENPP1 | GO:0030643 | intracellular phosphate ion homeostasis | 11159191 |
Hgene | ENPP1 | GO:0030730 | sequestering of triglyceride | 17849011 |
Hgene | ENPP1 | GO:0031953 | negative regulation of protein autophosphorylation | 11289049 |
Hgene | ENPP1 | GO:0032869 | cellular response to insulin stimulus | 7830796|17849011 |
Hgene | ENPP1 | GO:0033198 | response to ATP | 25644539 |
Hgene | ENPP1 | GO:0045599 | negative regulation of fat cell differentiation | 17849011 |
Hgene | ENPP1 | GO:0045719 | negative regulation of glycogen biosynthetic process | 11289049 |
Hgene | ENPP1 | GO:0046034 | ATP metabolic process | 25644539 |
Hgene | ENPP1 | GO:0046325 | negative regulation of glucose import | 17849011 |
Hgene | ENPP1 | GO:0046627 | negative regulation of insulin receptor signaling pathway | 7830796|17849011 |
Hgene | ENPP1 | GO:0050427 | 3'-phosphoadenosine 5'-phosphosulfate metabolic process | 7830796 |
Hgene | ENPP1 | GO:0055062 | phosphate ion homeostasis | 28652107 |
Hgene | ENPP1 | GO:0090304 | nucleic acid metabolic process | 22285541 |
Tgene | INSR | GO:0001934 | positive regulation of protein phosphorylation | 7556070 |
Tgene | INSR | GO:0002092 | positive regulation of receptor internalization | 25401701 |
Tgene | INSR | GO:0007186 | G protein-coupled receptor signaling pathway | 9092559 |
Tgene | INSR | GO:0008284 | positive regulation of cell population proliferation | 17925406 |
Tgene | INSR | GO:0008286 | insulin receptor signaling pathway | 6849137|8440175|20455999|38056462 |
Tgene | INSR | GO:0018108 | peptidyl-tyrosine phosphorylation | 8496180 |
Tgene | INSR | GO:0032148 | activation of protein kinase B activity | 7556070 |
Tgene | INSR | GO:0032869 | cellular response to insulin stimulus | 8440175 |
Tgene | INSR | GO:0043410 | positive regulation of MAPK cascade | 20455999 |
Tgene | INSR | GO:0045725 | positive regulation of glycogen biosynthetic process | 17925406 |
Tgene | INSR | GO:0046326 | positive regulation of glucose import | 3518947 |
Tgene | INSR | GO:0046777 | protein autophosphorylation | 6849137|8496180 |
Tgene | INSR | GO:0060267 | positive regulation of respiratory burst | 9092559 |
Kinase Fusion gene breakpoints across ENPP1 (5'-gene) * Click on the image to open the UCSC genome browser with custom track showing this image in a new window. |
Kinase Fusion gene breakpoints across INSR (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 |
Kinase Fusion gene information. |
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. |
Source | Sample | Hgene | Hchr | Hbp | Tgene | Tchr | Tbp |
ChimerDB4 | TCGA-3B-A9HS-01A | ENPP1 | chr6 | 132129415 | INSR | chr19 | 7152938 |
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Kinase Fusion ORF Analysis |
Kinase Fusion information from ORFfinder translation from full-length transcript sequence from KinaseFusionDB. |
Henst | Tenst | Hgene | Hchr | Hbp | Tgene | Tchr | Tbp | Seq length (transcript) | Seq length (amino acids) |
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Kinase Fusion Amino Acid Sequences |
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 |
Four levels of functional features of fusion genes Go to FGviewer search page for the most frequent breakpoint (https://ccsmweb.uth.edu/FGviewer/:132129415/:7152938) - 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. |
Main function of each fusion partner protein. (from UniProt) |
Hgene | Tgene |
ENPP1 | INSR |
FUNCTION: Nucleotide pyrophosphatase that generates diphosphate (PPi) and functions in bone mineralization and soft tissue calcification by regulating pyrophosphate levels (By similarity). PPi inhibits bone mineralization and soft tissue calcification by binding to nascent hydroxyapatite crystals, thereby preventing further growth of these crystals (PubMed:11004006). Preferentially hydrolyzes ATP, but can also hydrolyze other nucleoside 5' triphosphates such as GTP, CTP and UTP to their corresponding monophosphates with release of pyrophosphate, as well as diadenosine polyphosphates, and also 3',5'-cAMP to AMP (PubMed:27467858, PubMed:8001561, PubMed:25344812, PubMed:28011303, PubMed:35147247). May also be involved in the regulation of the availability of nucleotide sugars in the endoplasmic reticulum and Golgi, and the regulation of purinergic signaling (PubMed:27467858, PubMed:8001561). Inhibits ectopic joint calcification and maintains articular chondrocytes by repressing hedgehog signaling; it is however unclear whether hedgehog inhibition is direct or indirect (By similarity). Appears to modulate insulin sensitivity and function (PubMed:10615944). Also involved in melanogenesis (PubMed:28964717). Also able to hydrolyze 2',3'-cGAMP (cyclic GMP-AMP), a second messenger that activates TMEM173/STING and triggers type-I interferon production (PubMed:25344812). 2',3'-cGAMP degradation takes place in the lumen or extracellular space, and not in the cytosol where it is produced; the role of 2',3'-cGAMP hydrolysis is therefore unclear (PubMed:25344812). Not able to hydrolyze the 2',3'-cGAMP linkage isomer 3'-3'-cGAMP (PubMed:25344812). {ECO:0000250|UniProtKB:P06802, ECO:0000269|PubMed:10615944, ECO:0000269|PubMed:25344812, ECO:0000269|PubMed:27467858, ECO:0000269|PubMed:28011303, ECO:0000269|PubMed:28964717, ECO:0000269|PubMed:35147247, ECO:0000269|PubMed:8001561, ECO:0000305|PubMed:11004006}. | FUNCTION: Receptor with tyrosine-protein kinase activity. Functions as a pH sensing receptor which is activated by increased extracellular pH. Activates an intracellular signaling pathway that involves IRS1 and AKT1/PKB. {ECO:0000269|PubMed:21641549}. |
Retention 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 * Minus value of BPloci means that the break pointn is located before the CDS. |
- Retained domain in the 5'-partner of fusion protein (protein functional feature from UniProt). |
Partner | Hgeneene | Hbp | Tgeneene | Tbp | ENST | BPexon | TotalExon | Protein feature loci | BPloci | TotalLen | Feature | Note |
- Retained domain in the 3'-partner of fusion protein (protein functional feature from UniProt). |
Partner | Hgeneene | Hbp | Tgeneene | Tbp | ENST | BPexon | TotalExon | Protein feature loci | BPloci | TotalLen | Feature | Note |
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Kinase-Substrate Information of ENPP1_INSR |
Phosphorylation target of the kinase (phosphosite, 03-17-2024) |
Kinase | Kinase UniProt Acc | Kinase species | Substrate | Substrate UniProt Acc | Substrate phosphorylated residues | Substrate phosphorylated sites (+/-7AA) | Domain |
INSR | P06213 | human | IRS1 | P35568 | Y989 | VPssRGDyMTMQMSC | |
INSR | P06213 | human | INSR | P06213-2 | Y1173 | FGMTRDIyETDyyRK | PK_Tyr_Ser-Thr |
INSR | P06213 | human | INSR | P06213-2 | S1302 | EENKAPEsEELEMEF | |
INSR | P06213 | human | GAB1 | Q13480 | Y242 | FFQQQMIyDsPPSRA | |
INSR | P06213 | human | BLVRA | P53004 | Y291 | LAEEIQkyCCSRK__ | |
INSR | P06213 | human | PTEN | P60484 | Y174 | TIPSQRRyVyyysyL | |
INSR | P06213 | human | PIK3R3 | Q92569 | Y341 | NEDADENyFINEEDE | |
INSR | P06213 | human | INSR | P06213 | S1348 | GGRDGGSsLGFkRsy | |
INSR | P06213 | human | INSR | P06213-2 | Y1343 | sLGFKRSyEEHIPyT | |
INSR | P06213 | human | IRS1 | P35568 | Y896 | EPKsPGEyVNIEFGS | |
INSR | P06213 | human | DOK1 | Q99704 | Y362 | DPKEDPIyDEPEGLA | |
INSR | P06213 | human | PTEN | P60484 | Y27 | GFDLDLTyIYPNIIA | |
INSR | P06213 | human | GAB1 | Q13480 | Y659 | VADERVDyVVVDQQK | |
INSR | P06213 | human | GAB1 | Q13480 | Y373 | AsDtDssyCIPTAGM | |
INSR | P06213 | human | INSR | P06213 | Y999 | yASSNPEyLSASDVF | |
INSR | P06213 | human | IRS1 | P35568 | Y1179 | GLENGLNyIDLDLVk | |
INSR | P06213 | human | INSR | P06213 | S1314 | EENKAPEsEELEMEF | |
INSR | P06213 | human | GAB1 | Q13480 | Y589 | SHDSEENyVPMNPNL | |
INSR | P06213 | human | PPP2CA | P67775 | Y307 | VTRRtPDyFl_____ | |
INSR | P06213 | human | INSR | P06213 | Y1355 | sLGFkRsyEEHIPyt | |
INSR | P06213 | human | INSR | P06213 | Y1189 | RDIyEtDyyRkGGkG | PK_Tyr_Ser-Thr |
INSR | P06213 | human | BLVRA | P53004 | Y198 | EERKEDQyMKMtVCL | Biliv-reduc_cat |
INSR | P06213 | human | BLVRA | P53004 | Y228 | PGLKRNRyLsFHFks | Biliv-reduc_cat |
INSR | P06213 | human | PIK3R1 | P27986 | Y607 | NENtEDQysLVEDDE | |
INSR | P06213 | human | ARHGAP5 | Q13017 | Y306 | NHPDYEEyINLEGTR | RhoGAP-FF1 |
INSR | P06213 | human | DOK1 | Q99704 | Y398 | ARVkEEGyELPyNPA | |
INSR | P06213 | human | INSR | P06213-2 | Y1177 | RDIyETDyyRKGGKG | PK_Tyr_Ser-Thr |
INSR | P06213 | human | GAB1 | Q13480 | Y447 | SEELDENyVPMNPNs | |
INSR | P06213 | human | GAB1 | Q13480 | Y472 | EPIQEANyVPMtPGT | |
INSR | P06213 | human | INSR | P06213 | Y992 | DGPLGPLyASSNPEy | |
INSR | P06213 | human | INSR | P06213-2 | Y1349 | SyEEHIPyTHMNGGK | |
INSR | P06213 | human | INSR | P06213-2 | Y1178 | DIyETDyyRKGGKGL | PK_Tyr_Ser-Thr |
INSR | P06213 | human | PTPN6 | P29350 | Y536 | QkGQEsEyGNItyPP | |
INSR | P06213 | human | PHB1 | P35232 | Y114 | FtsIGEDyDERVLPs | Band_7 |
INSR | P06213 | human | PIK3R1 | P27986 | Y368 | STKMHGDytLTLRKG | SH2 |
INSR | P06213 | human | CCDC88C | Q9P219 | Y2025 | PQTVWyEyGCV____ | |
INSR | P06213 | human | NFKBIA | P25963 | Y42 | DsMkDEEyEQMVkEL | |
INSR | P06213 | human | GAB1 | Q13480 | Y285 | TEADGELyVFNTPSG | |
INSR | P06213 | human | INSR | P06213-2 | S1336 | GGRDGGSsLGFKRSy | |
INSR | P06213 | human | INSR | P06213 | Y1011 | DVFPCSVyVPDEWEV | |
INSR | P06213 | human | INSR | P06213 | Y1361 | syEEHIPytHMNGGK | |
INSR | P06213 | human | PIK3R1 | P27986 | Y580 | LRKtRDQyLMWLTQK | PI3K_P85_iSH2 |
INSR | P06213 | human | INSR | P06213 | Y1185 | FGMTRDIyEtDyyRk | PK_Tyr_Ser-Thr |
INSR | P06213 | human | GAB1 | Q13480 | Y627 | KGDKQVEyLDLDLDs | |
INSR | P06213 | human | INSR | P06213 | Y1190 | DIyEtDyyRkGGkGL | PK_Tyr_Ser-Thr |
Biological Network Integration of This Kinase and Substrates (GeneMANIA website) |
Enriched GO biological processes of the phosphorylation target genes of the kinase |
Kinase | GOID | GO term | P.adjust |
INSR | ID | Description | 0.00e+00 |
INSR | GO:0043491 | phosphatidylinositol 3-kinase/protein kinase B signal transduction | 7.50e-09 |
INSR | GO:0008286 | insulin receptor signaling pathway | 1.07e-05 |
INSR | GO:0032869 | cellular response to insulin stimulus | 8.71e-05 |
INSR | GO:0051896 | regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction | 1.64e-04 |
INSR | GO:0032868 | response to insulin | 1.96e-04 |
INSR | GO:0071375 | cellular response to peptide hormone stimulus | 3.28e-04 |
INSR | GO:0046326 | positive regulation of glucose import | 3.40e-04 |
INSR | GO:0043550 | regulation of lipid kinase activity | 3.50e-04 |
INSR | GO:0010828 | positive regulation of glucose transmembrane transport | 4.50e-04 |
INSR | GO:1901653 | cellular response to peptide | 4.92e-04 |
INSR | GO:0051347 | positive regulation of transferase activity | 7.34e-04 |
INSR | GO:0045088 | regulation of innate immune response | 7.42e-04 |
INSR | GO:0043434 | response to peptide hormone | 7.42e-04 |
INSR | GO:0046324 | regulation of glucose import | 7.42e-04 |
INSR | GO:0002757 | immune response-activating signaling pathway | 1.03e-03 |
INSR | GO:0002764 | immune response-regulating signaling pathway | 1.21e-03 |
INSR | GO:0002221 | pattern recognition receptor signaling pathway | 1.21e-03 |
INSR | GO:0046323 | glucose import | 1.21e-03 |
INSR | GO:0010827 | regulation of glucose transmembrane transport | 1.21e-03 |
INSR | GO:0002758 | innate immune response-activating signaling pathway | 1.40e-03 |
INSR | GO:0002218 | activation of innate immune response | 1.79e-03 |
INSR | GO:0042113 | B cell activation | 1.79e-03 |
INSR | GO:0045725 | positive regulation of glycogen biosynthetic process | 2.22e-03 |
INSR | GO:0070875 | positive regulation of glycogen metabolic process | 2.75e-03 |
INSR | GO:0031647 | regulation of protein stability | 2.89e-03 |
INSR | GO:1904659 | glucose transmembrane transport | 2.96e-03 |
INSR | GO:0008645 | hexose transmembrane transport | 2.97e-03 |
INSR | GO:0033674 | positive regulation of kinase activity | 2.97e-03 |
INSR | GO:0045089 | positive regulation of innate immune response | 2.98e-03 |
INSR | GO:0015749 | monosaccharide transmembrane transport | 2.98e-03 |
INSR | GO:0006661 | phosphatidylinositol biosynthetic process | 3.47e-03 |
INSR | GO:0002833 | positive regulation of response to biotic stimulus | 3.65e-03 |
INSR | GO:0034219 | carbohydrate transmembrane transport | 3.65e-03 |
INSR | GO:0043467 | regulation of generation of precursor metabolites and energy | 3.78e-03 |
INSR | GO:0002753 | cytosolic pattern recognition receptor signaling pathway | 4.24e-03 |
INSR | GO:0030183 | B cell differentiation | 4.74e-03 |
INSR | GO:0046488 | phosphatidylinositol metabolic process | 4.79e-03 |
INSR | GO:0008643 | carbohydrate transport | 5.03e-03 |
INSR | GO:0005979 | regulation of glycogen biosynthetic process | 5.62e-03 |
INSR | GO:0010962 | regulation of glucan biosynthetic process | 5.62e-03 |
INSR | GO:0051897 | positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction | 5.77e-03 |
INSR | GO:0043409 | negative regulation of MAPK cascade | 6.13e-03 |
INSR | GO:2000045 | regulation of G1/S transition of mitotic cell cycle | 6.72e-03 |
INSR | GO:0006109 | regulation of carbohydrate metabolic process | 7.11e-03 |
INSR | GO:0031349 | positive regulation of defense response | 7.19e-03 |
INSR | GO:0070873 | regulation of glycogen metabolic process | 7.36e-03 |
INSR | GO:0032885 | regulation of polysaccharide biosynthetic process | 7.59e-03 |
INSR | GO:0001953 | negative regulation of cell-matrix adhesion | 7.82e-03 |
INSR | GO:0006470 | protein dephosphorylation | 7.99e-03 |
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Related Drugs to ENPP1_INSR |
Drugs used for this fusion-positive patient. (Manual curation of PubMed, 04-30-2022 + MyCancerGenome) |
Hgene | Tgene | Drug | Source | PMID |
Distribution of the number of studies mentioning ENPP1-INSR and kinase inhibitors the PubMed Abstract (04-01-2024) |
Fusion gene - drug pair 1 | Fusion gene - drug pair 2 | PMID | Publication date | DOI | Study title |
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Related Diseases to ENPP1_INSR |
Diseases that have this fusion gene. (Manual curation of PubMed, 04-30-2022 + MyCancerGenome) |
Hgene | Tgene | Disease | Source | PMID |
Related diseases from the literature mentioned this fusion gene and drug. (PubMed, 04-01-2024) |
MeSH ID | MeSH term |
Diseases associated with fusion partners. (DisGeNet 4.0) |
Partner | Gene | Disease ID | Disease name | # pubmeds | Source |
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Clinical Trials of the Found Drugs/Small Molecules |
Statistics of the Clinical Trials of the Found Kinase Inibitors from clinicaltrials.gov (06-17-2024) |
Clinical Trials from clinicaltrials.gov (06-17-2024) |
Fusion Gene | Kinase Inhibitor | NCT ID | Study Status | Phases | Disease | # Enrolment | Date |