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Fusion gene ID: 11636 |
FusionGeneSummary for ENPP1_INSR |
 Fusion gene summary |
| Fusion gene information | Fusion gene name: ENPP1_INSR | Fusion gene ID: 11636 | 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 | 20180519 | 20180523 | |
| UniProtAcc | P22413 | P06213 | |
| Ensembl transtripts involved in fusion gene | ENST00000360971, | ENST00000341500, ENST00000302850, | |
| Fusion gene scores | * DoF score | 4 X 3 X 3=36 | 13 X 10 X 6=780 |
| # samples | 4 | 15 | |
| ** MAII score | log2(4/36*10)=0.15200309344505 effective Gene in Pan-Cancer Fusion Genes (eGinPCFGs). DoF>8 and MAII>0 | log2(15/780*10)=-2.37851162325373 possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs). DoF>8 and MAII<0 | |
| Context | PubMed: ENPP1 [Title/Abstract] AND INSR [Title/Abstract] AND fusion [Title/Abstract] | ||
| Functional or gene categories assigned by FusionGDB annotation | |||
| * DoF score (Degree of Frequency) = # partners X # break points X # cancer types ** MAII score (Major Active Isofusion Index) = log2(# samples/DoF score*10) |
| 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:0030308 | negative regulation of cell growth | 17849011 |
| Hgene | ENPP1 | GO:0030505 | inorganic diphosphate transport | 10513816 |
| Hgene | ENPP1 | GO:0030643 | cellular 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:0045599 | negative regulation of fat cell differentiation | 17849011 |
| Hgene | ENPP1 | GO:0045719 | negative regulation of glycogen biosynthetic process | 11289049 |
| 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:0090305 | nucleic acid phosphodiester bond hydrolysis | 22285541 |
| Tgene | INSR | GO:0001934 | positive regulation of protein phosphorylation | 7556070 |
| Tgene | INSR | GO:0007186 | G-protein coupled receptor signaling pathway | 9092559 |
| Tgene | INSR | GO:0008284 | positive regulation of cell proliferation | 17925406 |
| Tgene | INSR | GO:0008286 | insulin receptor signaling pathway | 6849137|8440175|20455999 |
| 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:0051290 | protein heterotetramerization | 1898103 |
| Tgene | INSR | GO:0060267 | positive regulation of respiratory burst | 9092559 |
| Fusion gene information from three resources (ChiTars (NAR, 2018), tumorfusions (NAR, 2018), Gao et al. (Cell, 2018)) * 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. |
| Data type | Source | Cancer type | Sample | Hgene | Hchr | Hbp | Hstrand | Tgene | Tchr | Tbp | Tstrand |
| TCGA | RV | SARC | TCGA-3B-A9HS-01A | ENPP1 | chr6 | 132129415 | + | INSR | chr19 | 7152938 | - |
| * LD: Li Ding group's fusion gene list RV: Roel Verhaak group's fusion gene list ChiTaRs fusion database |
| Open reading frame (ORF) analsis of fusion genes based on Ensembl gene isoform structure. * Click on the break point to see the gene structure around the break point region using the UCSC Genome Browser. |
| ORF | Henst | Tenst | Hgene | Hchr | Hbp | Hstrand | Tgene | Tchr | Tbp | Tstrand |
| Frame-shift | ENST00000360971 | ENST00000341500 | ENPP1 | chr6 | 132129415 | + | INSR | chr19 | 7152938 | - |
| Frame-shift | ENST00000360971 | ENST00000302850 | ENPP1 | chr6 | 132129415 | + | INSR | chr19 | 7152938 | - |
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FusionProtFeatures for ENPP1_INSR |
| Main function of each fusion partner protein. (from UniProt) |
| Hgene | Tgene |
| ENPP1 | INSR |
| By generating PPi, plays a role in regulatingpyrophosphate levels, and functions in bone mineralization andsoft tissue calcification. PPi inhibits mineralization by bindingto nascent hydroxyapatite (HA) crystals, thereby preventingfurther growth of these crystals. Preferentially hydrolyzes ATP,but can also hydrolyze other nucleoside 5' triphosphates such asGTP, CTP, TTP and UTP to their corresponding monophosphates withrelease of pyrophosphate and diadenosine polyphosphates, and also3',5'-cAMP to AMP. May also be involved in the regulation of theavailability of nucleotide sugars in the endoplasmic reticulum andGolgi, and the regulation of purinergic signaling. Appears tomodulate insulin sensitivity and function.{ECO:0000269|PubMed:10615944, ECO:0000269|PubMed:27467858,ECO:0000269|PubMed:8001561}. | Receptor tyrosine kinase which mediates the pleiotropicactions of insulin. Binding of insulin leads to phosphorylation ofseveral intracellular substrates, including, insulin receptorsubstrates (IRS1, 2, 3, 4), SHC, GAB1, CBL and other signalingintermediates. Each of these phosphorylated proteins serve asdocking proteins for other signaling proteins that contain Src-homology-2 domains (SH2 domain) that specifically recognizedifferent phosphotyrosine residues, including the p85 regulatorysubunit of PI3K and SHP2. Phosphorylation of IRSs proteins lead tothe activation of two main signaling pathways: the PI3K-AKT/PKBpathway, which is responsible for most of the metabolic actions ofinsulin, and the Ras-MAPK pathway, which regulates expression ofsome genes and cooperates with the PI3K pathway to control cellgrowth and differentiation. Binding of the SH2 domains of PI3K tophosphotyrosines on IRS1 leads to the activation of PI3K and thegeneration of phosphatidylinositol-(3, 4, 5)-triphosphate (PIP3),a lipid second messenger, which activates several PIP3-dependentserine/threonine kinases, such as PDPK1 and subsequently AKT/PKB.The net effect of this pathway is to produce a translocation ofthe glucose transporter SLC2A4/GLUT4 from cytoplasmic vesicles tothe cell membrane to facilitate glucose transport. Moreover, uponinsulin stimulation, activated AKT/PKB is responsible for: anti-apoptotic effect of insulin by inducing phosphorylation of BAD;regulates the expression of gluconeogenic and lipogenic enzymes bycontrolling the activity of the winged helix or forkhead (FOX)class of transcription factors. Another pathway regulated by PI3K-AKT/PKB activation is mTORC1 signaling pathway which regulatescell growth and metabolism and integrates signals from insulin.AKT mediates insulin-stimulated protein synthesis byphosphorylating TSC2 thereby activating mTORC1 pathway. TheRas/RAF/MAP2K/MAPK pathway is mainly involved in mediating cellgrowth, survival and cellular differentiation of insulin.Phosphorylated IRS1 recruits GRB2/SOS complex, which triggers theactivation of the Ras/RAF/MAP2K/MAPK pathway. In addition tobinding insulin, the insulin receptor can bind insulin-like growthfactors (IGFI and IGFII). Isoform Short has a higher affinity forIGFII binding. When present in a hybrid receptor with IGF1R, bindsIGF1. PubMed:12138094 shows that hybrid receptors composed ofIGF1R and INSR isoform Long are activated with a high affinity byIGF1, with low affinity by IGF2 and not significantly activated byinsulin, and that hybrid receptors composed of IGF1R and INSRisoform Short are activated by IGF1, IGF2 and insulin. Incontrast, PubMed:16831875 shows that hybrid receptors composed ofIGF1R and INSR isoform Long and hybrid receptors composed of IGF1Rand INSR isoform Short have similar binding characteristics, bothbind IGF1 and have a low affinity for insulin.{ECO:0000269|PubMed:12138094, ECO:0000269|PubMed:16314505,ECO:0000269|PubMed:16831875, ECO:0000269|PubMed:8257688,ECO:0000269|PubMed:8276809, ECO:0000269|PubMed:8452530,ECO:0000269|PubMed:9428692}. |
| 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. |
| - In-frame and retained protein feature among the 13 regional features. |
| Partner | Gene | Hbp | Tbp | ENST | Strand | BPexon | TotalExon | Protein feature loci | *BPloci | TotalLen | Protein feature | Protein feature note |
| - In-frame and not-retained protein feature among the 13 regional features. |
| Partner | Gene | Hbp | Tbp | ENST | Strand | BPexon | TotalExon | Protein feature loci | *BPloci | TotalLen | Protein feature | Protein feature note |
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FusionGeneSequence for ENPP1_INSR |
| For in-frame fusion transcripts, we provide the fusion transcript sequences and fusion amino acid sequences. (nt: nucleotides, aa: amino acids) |
| * Fusion amino acid sequences. |
| * Fusion transcript sequences (only coding sequence (CDS) region). |
| * Fusion transcript sequences (Full-length transcript). |
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FusionGenePPI for ENPP1_INSR |
| Go to ChiPPI (Chimeric Protein-Protein interactions) to see the chimeric PPI interaction in . |
| Protein-protein interactors with each fusion partner protein in wild-type (BIOGRID-3.4.160) |
| Hgene | Hgene's interactors | Tgene | Tgene's interactors |
| ENPP1 | INSR, SQSTM1, PTCH1, BZW1, FNTB, PON2, HERC2, PSMD12, PSMA1, PSMB1, USP2, FANCE, ATP6V0D1, EIF2B2 | INSR | CSK, IRS1, FRS2, SOCS3, IRS2, GRB10, MAPK1, MAPK3, AHSG, KHDRBS1, PTPN11, PTPN6, ENPP1, HRAS, CAV1, GRB2, SMAD2, PRKCD, VAV3, INSRR, SH2B1, INPPL1, SNX6, SNX1, SNX2, SNX4, RASA1, JAK2, VAV1, GRB7, SHC1, SYNCRIP, GRB14, PTPN1, SORBS1, SH2B2, HGS, SOCS1, SOCS6, PLCG1, STAT5A, STAT5B, JAK1, DOK1, IRF7, TEAD1, MOK, ARRB2, KRT31, SNX17, SNX27, SQSTM1, ATIC, PTPLAD1, PRKAA1, PRKAA2, KIF5A, PTPRK, PON2, NTRK1, TMEM17, MARCH1, PPM1A, PPM1F, PTPRR, DUSP18, MPZL2, SSH1, UNC5CL, FAM19A4, SCGB1D1, CLEC3A, FAM19A3, INSL5, DNASE1L2, DUSP19, STYX, TRIM25, INSR, ACP1 |
| - Retained PPIs in in-frame fusion. |
| Partner | Gene | Hbp | Tbp | ENST | Strand | BPexon | TotalExon | Protein feature loci | *BPloci | TotalLen | Still interaction with |
| - Lost PPIs in in-frame fusion. |
| Partner | Gene | Hbp | Tbp | ENST | Strand | BPexon | TotalExon | Protein feature loci | *BPloci | TotalLen | Interaction lost with |
| - Retained PPIs, but lost function due to frame-shift fusion. |
| Partner | Gene | Hbp | Tbp | ENST | Strand | BPexon | TotalExon | Protein feature loci | *BPloci | TotalLen | Interaction lost with |
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RelatedDrugs for ENPP1_INSR |
| Drugs targeting genes involved in this fusion gene. (DrugBank Version 5.1.0 2018-04-02) |
| Partner | Gene | UniProtAcc | DrugBank ID | Drug name | Drug activity | Drug type | Drug status |
| Hgene | ENPP1 | P22413 | DB00811 | Ribavirin | Ectonucleotide pyrophosphatase/phosphodiesterase family member 1 | small molecule | approved |
| Hgene | ENPP1 | P22413 | DB01143 | Amifostine | Ectonucleotide pyrophosphatase/phosphodiesterase family member 1 | small molecule | approved|investigational |
| Tgene | INSR | P06213 | DB00046 | Insulin Lispro | Insulin receptor | biotech | approved |
| Tgene | INSR | P06213 | DB00047 | Insulin Glargine | Insulin receptor | biotech | approved |
| Tgene | INSR | P06213 | DB00071 | Insulin Pork | Insulin receptor | biotech | approved |
| Tgene | INSR | P06213 | DB01306 | Insulin Aspart | Insulin receptor | biotech | approved |
| Tgene | INSR | P06213 | DB01307 | Insulin Detemir | Insulin receptor | biotech | approved |
| Tgene | INSR | P06213 | DB01309 | Insulin Glulisine | Insulin receptor | biotech | approved |
| Tgene | INSR | P06213 | DB09564 | Insulin Degludec | Insulin receptor | biotech | approved |
| Tgene | INSR | P06213 | DB00030 | Insulin Human | Insulin receptor | biotech | approved|investigational |
| Tgene | INSR | P06213 | DB01277 | Mecasermin | Insulin receptor | biotech | approved|investigational |
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RelatedDiseases for ENPP1_INSR |
| Diseases associated with fusion partners. (DisGeNet 4.0) |
| Partner | Gene | Disease ID | Disease name | # pubmeds | Source |
| Hgene | ENPP1 | C1859727 | Arterial calcification of infancy | 6 | CTD_human;ORPHANET;UNIPROT |
| Hgene | ENPP1 | C2750078 | Hypophosphatemic Rickets, Autosomal Recessive, 2 | 4 | CTD_human;UNIPROT |
| Hgene | ENPP1 | C3809781 | Cole disease | 2 | ORPHANET;UNIPROT |
| Hgene | ENPP1 | C0014175 | Endometriosis | 1 | CTD_human |
| Hgene | ENPP1 | C1865343 | OSSIFICATION OF THE POSTERIOR LONGITUDINAL LIGAMENT OF SPINE | 1 | CTD_human;UNIPROT |
| Tgene | INSR | C0342278 | Diabetes Mellitus, Insulin-Resistant, with Acanthosis Nigricans | 18 | CTD_human;UNIPROT |
| Tgene | INSR | C0265344 | Donohue Syndrome | 14 | CTD_human;ORPHANET;UNIPROT |
| Tgene | INSR | C0271695 | Rabson-Mendenhall Syndrome | 7 | ORPHANET;UNIPROT |
| Tgene | INSR | C0011860 | Diabetes Mellitus, Non-Insulin-Dependent | 3 | HPO;UNIPROT |
| Tgene | INSR | C1864952 | Hyperinsulinemic Hypoglycemia, Familial, 5 | 3 | CTD_human;ORPHANET;UNIPROT |
| Tgene | INSR | C0011853 | Diabetes Mellitus, Experimental | 2 | CTD_human |
| Tgene | INSR | C0020459 | Hyperinsulinism | 2 | CTD_human;HPO |
| Tgene | INSR | C0021655 | Insulin Resistance | 2 | CTD_human |
| Tgene | INSR | C0024115 | Lung diseases | 2 | CTD_human |
| Tgene | INSR | C0002395 | Alzheimer's Disease | 1 | CTD_human |
| Tgene | INSR | C0011882 | Diabetic Neuropathies | 1 | CTD_human |
| Tgene | INSR | C0020429 | Hyperalgesia | 1 | CTD_human |
| Tgene | INSR | C0020456 | Hyperglycemia | 1 | CTD_human;HPO |
| Tgene | INSR | C0030567 | Parkinson Disease | 1 | CTD_human |
| Tgene | INSR | C0235833 | Congenital diaphragmatic hernia | 1 | CTD_human |
| Tgene | INSR | C0236969 | Substance-Related Disorders | 1 | CTD_human |
| Tgene | INSR | C0271650 | Impaired glucose tolerance | 1 | CTD_human |
| Tgene | INSR | C0752347 | Lewy Body Disease | 1 | CTD_human |
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