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Center for Computational Systems Medicine
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Fusion Gene Summary

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Fusion Gene ORF analysis

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Fusion Genomic Features

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Fusion Protein Features

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Fusion Gene Sequence

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Fusion Gene PPI analysis

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Related Drugs

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Related Diseases

Fusion gene:ENPP1-INSR (FusionGDB2 ID:HG5167TG3643)

Fusion Gene Summary for ENPP1-INSR

check button Fusion gene summary
Fusion gene informationFusion gene name: ENPP1-INSR
Fusion gene ID: hg5167tg3643
HgeneTgene
Gene symbol

ENPP1

INSR

Gene ID

5167

3643

Gene nameectonucleotide pyrophosphatase/phosphodiesterase 1insulin receptor
SynonymsARHR2|COLED|M6S1|NPP1|NPPS|PC-1|PCA1|PDNP1CD220|HHF5
Cytomap('ENPP1')('INSR')

6q23.2

19p13.2

Type of geneprotein-codingprotein-coding
Descriptionectonucleotide pyrophosphatase/phosphodiesterase family member 1E-NPP 1Ly-41 antigenalkaline phosphodiesterase 1membrane component, chromosome 6, surface marker 1phosphodiesterase I/nucleotide pyrophosphatase 1plasma-cell membrane glycoprotein 1plainsulin receptorIR
Modification date2020031320200313
UniProtAcc.

P06213

Ensembl transtripts involved in fusion geneENST00000360971, 
Fusion gene scores* DoF score6 X 6 X 4=14420 X 13 X 8=2080
# samples 620
** MAII scorelog2(6/144*10)=-1.26303440583379
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0		log2(20/2080*10)=-3.37851162325373
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]

Most frequent breakpointENPP1(132129415)-INSR(7152938), # samples:1
Anticipated loss of major functional domain due to fusion event.ENPP1-INSR seems lost the major protein functional domain in Hgene partner, which is a cell metabolism gene due to the frame-shifted ORF.
ENPP1-INSR seems lost the major protein functional domain in Tgene partner, which is a IUPHAR drug target due to the frame-shifted ORF.
ENPP1-INSR seems lost the major protein functional domain in Tgene partner, which is a kinase due to the frame-shifted ORF.
* DoF score (Degree of Frequency) = # partners X # break points X # cancer types
** MAII score (Major Active Isofusion Index) = log2(# samples/DoF score*10)

check button Gene ontology of each fusion partner gene with evidence of Inferred from Direct Assay (IDA) from Entrez
PartnerGeneGO IDGO termPubMed ID
HgeneENPP1

GO:0006091

generation of precursor metabolites and energy

12746903

HgeneENPP1

GO:0006796

phosphate-containing compound metabolic process

10513816|11159191

HgeneENPP1

GO:0009143

nucleoside triphosphate catabolic process

10513816

HgeneENPP1

GO:0030308

negative regulation of cell growth

17849011

HgeneENPP1

GO:0030505

inorganic diphosphate transport

10513816

HgeneENPP1

GO:0030643

cellular phosphate ion homeostasis

11159191

HgeneENPP1

GO:0030730

sequestering of triglyceride

17849011

HgeneENPP1

GO:0031953

negative regulation of protein autophosphorylation

11289049

HgeneENPP1

GO:0032869

cellular response to insulin stimulus

7830796|17849011

HgeneENPP1

GO:0045599

negative regulation of fat cell differentiation

17849011

HgeneENPP1

GO:0045719

negative regulation of glycogen biosynthetic process

11289049

HgeneENPP1

GO:0046325

negative regulation of glucose import

17849011

HgeneENPP1

GO:0046627

negative regulation of insulin receptor signaling pathway

7830796|17849011

HgeneENPP1

GO:0050427

3'-phosphoadenosine 5'-phosphosulfate metabolic process

7830796

HgeneENPP1

GO:0090305

nucleic acid phosphodiester bond hydrolysis

22285541

TgeneINSR

GO:0001934

positive regulation of protein phosphorylation

7556070

TgeneINSR

GO:0002092

positive regulation of receptor internalization

25401701

TgeneINSR

GO:0007186

G protein-coupled receptor signaling pathway

9092559

TgeneINSR

GO:0008284

positive regulation of cell proliferation

17925406

TgeneINSR

GO:0008286

insulin receptor signaling pathway

6849137|8440175|20455999

TgeneINSR

GO:0018108

peptidyl-tyrosine phosphorylation

8496180

TgeneINSR

GO:0032148

activation of protein kinase B activity

7556070

TgeneINSR

GO:0032869

cellular response to insulin stimulus

8440175

TgeneINSR

GO:0043410

positive regulation of MAPK cascade

20455999

TgeneINSR

GO:0045725

positive regulation of glycogen biosynthetic process

17925406

TgeneINSR

GO:0046326

positive regulation of glucose import

3518947

TgeneINSR

GO:0046777

protein autophosphorylation

6849137|8496180

TgeneINSR

GO:0060267

positive regulation of respiratory burst

9092559



check button Fusion gene information
* 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.
SourceDiseaseSampleHgeneHchrHbpHstrandTgeneTchrTbpTstrand
ChimerDB4SARCTCGA-3B-A9HS-01AENPP1chr6

132129415

-INSRchr19

7152938

-


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Fusion Gene ORF analysis for ENPP1-INSR

check button 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.
ORFHenstTenstHgeneHchrHbpHstrandTgeneTchrTbpTstrand
Frame-shiftENST00000360971ENST00000302850ENPP1chr6

132129415

-INSRchr19

7152938

-
Frame-shiftENST00000360971ENST00000341500ENPP1chr6

132129415

-INSRchr19

7152938

-

check buttonORFfinder result based on the fusion transcript sequence of in-frame fusion genes.
HenstTenstHgeneHchrHbpHstrandTgeneTchrTbpTstrandSeq length
(transcript)		BP loci
(transcript)		Predicted start
(transcript)		Predicted stop
(transcript)		Seq length
(amino acids)

check buttonDeepORF prediction of the coding potential based on the fusion transcript sequence of in-frame fusion genes. DeepORF is a coding potential classifier based on convolutional neural network by comparing the real Ribo-seq data. If the no-coding score < 0.5 and coding score > 0.5, then the in-frame fusion transcript is predicted as being likely translated.
HenstTenstHgeneHchrHbpHstrandTgeneTchrTbpTstrandNo-coding scoreCoding score

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Fusion Genomic Features for ENPP1-INSR


check buttonFusionAI prediction of the potential fusion gene breakpoint based on the pre-mature RNA sequence context (+/- 5kb of individual partner genes, total 20kb length sequence). FusionAI is a fusion gene breakpoint classifier based on convolutional neural network by comparing the fusion positive and negative sequence context of ~ 20K fusion gene data. From here, we can have the relative potentency of the 20K genomic sequence how individual sequnce will be likely used as the gene fusion breakpoints.
HgeneHchrHbpHstrandTgeneTchrTbpTstrand1-pp (fusion gene breakpoint)


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Fusion Protein Features for ENPP1-INSR


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/: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.
FGviewer

check buttonMain function of each fusion partner protein. (from UniProt)
HgeneTgene
.INSR

P06213

FUNCTION: Transcriptional activator which is required for calcium-dependent dendritic growth and branching in cortical neurons. Recruits CREB-binding protein (CREBBP) to nuclear bodies. Component of the CREST-BRG1 complex, a multiprotein complex that regulates promoter activation by orchestrating a calcium-dependent release of a repressor complex and a recruitment of an activator complex. In resting neurons, transcription of the c-FOS promoter is inhibited by BRG1-dependent recruitment of a phospho-RB1-HDAC1 repressor complex. Upon calcium influx, RB1 is dephosphorylated by calcineurin, which leads to release of the repressor complex. At the same time, there is increased recruitment of CREBBP to the promoter by a CREST-dependent mechanism, which leads to transcriptional activation. The CREST-BRG1 complex also binds to the NR2B promoter, and activity-dependent induction of NR2B expression involves a release of HDAC1 and recruitment of CREBBP (By similarity). {ECO:0000250}.FUNCTION: Receptor tyrosine kinase which mediates the pleiotropic actions of insulin. Binding of insulin leads to phosphorylation of several intracellular substrates, including, insulin receptor substrates (IRS1, 2, 3, 4), SHC, GAB1, CBL and other signaling intermediates. Each of these phosphorylated proteins serve as docking proteins for other signaling proteins that contain Src-homology-2 domains (SH2 domain) that specifically recognize different phosphotyrosine residues, including the p85 regulatory subunit of PI3K and SHP2. Phosphorylation of IRSs proteins lead to the activation of two main signaling pathways: the PI3K-AKT/PKB pathway, which is responsible for most of the metabolic actions of insulin, and the Ras-MAPK pathway, which regulates expression of some genes and cooperates with the PI3K pathway to control cell growth and differentiation. Binding of the SH2 domains of PI3K to phosphotyrosines on IRS1 leads to the activation of PI3K and the generation of phosphatidylinositol-(3, 4, 5)-triphosphate (PIP3), a lipid second messenger, which activates several PIP3-dependent serine/threonine kinases, such as PDPK1 and subsequently AKT/PKB. The net effect of this pathway is to produce a translocation of the glucose transporter SLC2A4/GLUT4 from cytoplasmic vesicles to the cell membrane to facilitate glucose transport. Moreover, upon insulin 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 by controlling 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 regulates cell growth and metabolism and integrates signals from insulin. AKT mediates insulin-stimulated protein synthesis by phosphorylating TSC2 thereby activating mTORC1 pathway. The Ras/RAF/MAP2K/MAPK pathway is mainly involved in mediating cell growth, survival and cellular differentiation of insulin. Phosphorylated IRS1 recruits GRB2/SOS complex, which triggers the activation of the Ras/RAF/MAP2K/MAPK pathway. In addition to binding insulin, the insulin receptor can bind insulin-like growth factors (IGFI and IGFII). Isoform Short has a higher affinity for IGFII binding. When present in a hybrid receptor with IGF1R, binds IGF1. PubMed:12138094 shows that hybrid receptors composed of IGF1R and INSR isoform Long are activated with a high affinity by IGF1, with low affinity by IGF2 and not significantly activated by insulin, and that hybrid receptors composed of IGF1R and INSR isoform Short are activated by IGF1, IGF2 and insulin. In contrast, PubMed:16831875 shows that hybrid receptors composed of IGF1R and INSR isoform Long and hybrid receptors composed of IGF1R and INSR isoform Short have similar binding characteristics, both bind IGF1 and have a low affinity for insulin. In adipocytes, inhibits lipolysis (By similarity). {ECO:0000250|UniProtKB:P15208, 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}.

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.
- In-frame and retained protein feature among the 13 regional features.
PartnerGeneHbpTbpENSTStrandBPexonTotalExonProtein feature loci*BPlociTotalLenProtein featureProtein feature note

- In-frame and not-retained protein feature among the 13 regional features.
PartnerGeneHbpTbpENSTStrandBPexonTotalExonProtein feature loci*BPlociTotalLenProtein featureProtein feature note


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Fusion Gene Sequence for ENPP1-INSR


check button For in-frame fusion transcripts, we provide the fusion transcript sequences and fusion amino acid sequences. To have fusion amino acid sequence, we ran ORFfinder and chose the longest ORF among the all predicted ones.

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Fusion Gene PPI Analysis for ENPP1-INSR


check button Go to ChiPPI (Chimeric Protein-Protein interactions) to see the chimeric PPI interaction in

ChiPPI page.


check button Protein-protein interactors with each fusion partner protein in wild-type (BIOGRID-3.4.160)
HgeneHgene's interactorsTgeneTgene's interactors


check button - Retained PPIs in in-frame fusion.
PartnerGeneHbpTbpENSTStrandBPexonTotalExonProtein feature loci*BPlociTotalLenStill interaction with


check button - Lost PPIs in in-frame fusion.
PartnerGeneHbpTbpENSTStrandBPexonTotalExonProtein feature loci*BPlociTotalLenInteraction lost with


check button - Retained PPIs, but lost function due to frame-shift fusion.
PartnerGeneHbpTbpENSTStrandBPexonTotalExonProtein feature loci*BPlociTotalLenInteraction lost with


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Related Drugs for ENPP1-INSR


check button Drugs targeting genes involved in this fusion gene.
(DrugBank Version 5.1.8 2021-05-08)
PartnerGeneUniProtAccDrugBank IDDrug nameDrug activityDrug typeDrug status
TgeneINSRP06213DB00046Insulin lisproAgonistBiotechApproved
TgeneINSRP06213DB00047Insulin glargineAgonistBiotechApproved
TgeneINSRP06213DB00071Insulin porkBinderBiotechApproved
TgeneINSRP06213DB01306Insulin aspartAgonistBiotechApproved
TgeneINSRP06213DB01307Insulin detemirAgonistBiotechApproved
TgeneINSRP06213DB01309Insulin glulisineAgonistBiotechApproved
TgeneINSRP06213DB09129Chromic chlorideActivatorSmall moleculeApproved
TgeneINSRP06213DB09564Insulin degludecLigandBiotechApproved
TgeneINSRP06213DB14751Mecasermin rinfabateBiotechApproved
TgeneINSRP06213DB00030Insulin humanAgonistBiotechApproved|Investigational
TgeneINSRP06213DB01277MecaserminBiotechApproved|Investigational
TgeneINSRP06213DB12010FostamatinibInhibitorSmall moleculeApproved|Investigational
TgeneINSRP06213DB12267BrigatinibBindingSmall moleculeApproved|Investigational

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Related Diseases for ENPP1-INSR


check button Diseases associated with fusion partners.
(DisGeNet 4.0)
PartnerGeneDisease IDDisease name# pubmedsSource
HgeneENPP1C4551985ARTERIAL CALCIFICATION, GENERALIZED, OF INFANCY, 17GENOMICS_ENGLAND;UNIPROT
HgeneENPP1C2750078Hypophosphatemic Rickets, Autosomal Recessive, 24CTD_human;GENOMICS_ENGLAND;UNIPROT
HgeneENPP1C3809781Cole disease4CTD_human;GENOMICS_ENGLAND;ORPHANET;UNIPROT
HgeneENPP1C0014175Endometriosis1CTD_human
HgeneENPP1C0033847Pseudoxanthoma Elasticum1ORPHANET
HgeneENPP1C0269102Endometrioma1CTD_human
HgeneENPP1C1865343OSSIFICATION OF THE POSTERIOR LONGITUDINAL LIGAMENT OF SPINE1GENOMICS_ENGLAND;UNIPROT
TgeneC0265344Donohue Syndrome23CTD_human;GENOMICS_ENGLAND;ORPHANET;UNIPROT
TgeneC0342278Diabetes Mellitus, Insulin-Resistant, with Acanthosis Nigricans18CTD_human;GENOMICS_ENGLAND;ORPHANET;UNIPROT
TgeneC0271695Rabson-Mendenhall Syndrome10CTD_human;GENOMICS_ENGLAND;ORPHANET;UNIPROT
TgeneC0011860Diabetes Mellitus, Non-Insulin-Dependent3UNIPROT
TgeneC0002152Alloxan Diabetes2CTD_human
TgeneC0011853Diabetes Mellitus, Experimental2CTD_human
TgeneC0020459Hyperinsulinism2CTD_human
TgeneC0021655Insulin Resistance2CTD_human
TgeneC0024115Lung diseases2CTD_human
TgeneC0038433Streptozotocin Diabetes2CTD_human
TgeneC0342336Insulin resistance - type A2ORPHANET
TgeneC0920563Insulin Sensitivity2CTD_human
TgeneC1257963Endogenous Hyperinsulinism2CTD_human
TgeneC1257964Exogenous Hyperinsulinism2CTD_human
TgeneC1257965Compensatory Hyperinsulinemia2CTD_human
TgeneC1864952Hyperinsulinemic Hypoglycemia, Familial, 52CTD_human;GENOMICS_ENGLAND;ORPHANET;UNIPROT
TgeneC0002395Alzheimer's Disease1CTD_human
TgeneC0011265Presenile dementia1CTD_human
TgeneC0011882Diabetic Neuropathies1CTD_human
TgeneC0013146Drug abuse1CTD_human
TgeneC0013170Drug habituation1CTD_human
TgeneC0013222Drug Use Disorders1CTD_human
TgeneC0020429Hyperalgesia1CTD_human
TgeneC0020456Hyperglycemia1CTD_human
TgeneC0029231Organic Mental Disorders, Substance-Induced1CTD_human
TgeneC0030567Parkinson Disease1CTD_human
TgeneC0038580Substance Dependence1CTD_human
TgeneC0038586Substance Use Disorders1CTD_human
TgeneC0235833Congenital diaphragmatic hernia1CTD_human
TgeneC0236969Substance-Related Disorders1CTD_human
TgeneC0265699Congenital hernia of foramen of Morgagni1CTD_human
TgeneC0265700Congenital hernia of foramen of Bochdalek1CTD_human
TgeneC0271650Impaired glucose tolerance1CTD_human
TgeneC0271673Symmetric Diabetic Proximal Motor Neuropathy1CTD_human
TgeneC0271674Asymmetric Diabetic Proximal Motor Neuropathy1CTD_human
TgeneC0271678Diabetic Mononeuropathy1CTD_human
TgeneC0271680Diabetic Polyneuropathies1CTD_human
TgeneC0271685Diabetic Amyotrophy1CTD_human
TgeneC0271686Diabetic Autonomic Neuropathy1CTD_human
TgeneC0276496Familial Alzheimer Disease (FAD)1CTD_human
TgeneC0393835Diabetic Asymmetric Polyneuropathy1CTD_human
TgeneC0458247Allodynia1CTD_human
TgeneC0494463Alzheimer Disease, Late Onset1CTD_human
TgeneC0546126Acute Confusional Senile Dementia1CTD_human
TgeneC0740858Substance abuse problem1CTD_human
TgeneC0750900Alzheimer's Disease, Focal Onset1CTD_human
TgeneC0750901Alzheimer Disease, Early Onset1CTD_human
TgeneC0751074Diabetic Neuralgia1CTD_human
TgeneC0751211Hyperalgesia, Primary1CTD_human
TgeneC0751212Hyperalgesia, Secondary1CTD_human
TgeneC0751213Tactile Allodynia1CTD_human
TgeneC0751214Hyperalgesia, Thermal1CTD_human
TgeneC0752347Lewy Body Disease1CTD_human
TgeneC1510472Drug Dependence1CTD_human
TgeneC1855520Hyperglycemia, Postprandial1CTD_human
TgeneC2936719Mechanical Allodynia1CTD_human
TgeneC4316881Prescription Drug Abuse1CTD_human