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Center for Computational Systems Medicine
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FusionGeneSummary

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FusionProtFeature

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FusionGeneSequence

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FusionGenePPI

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RelatedDrugs

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RelatedDiseases

Fusion gene ID: 11439

FusionGeneSummary for ELL_INSR

check button Fusion gene summary
Fusion gene informationFusion gene name: ELL_INSR
Fusion gene ID: 11439
HgeneTgene
Gene symbol

ELL

INSR

Gene ID

8178

3643

Gene nameelongation factor for RNA polymerase IIinsulin receptor
SynonymsC19orf17|ELL1|MEN|PPP1R68CD220|HHF5
Cytomap

19p13.11

19p13.2

Type of geneprotein-codingprotein-coding
DescriptionRNA polymerase II elongation factor ELLELL gene (11-19 lysine-rich leukemia gene)eleven-nineteen lysine-rich leukemia proteinelongation factor RNA polymerase IIprotein phosphatase 1, regulatory subunit 68insulin receptorIR
Modification date2018051920180523
UniProtAcc

P55199

P06213

Ensembl transtripts involved in fusion geneENST00000262809, ENST00000596124, 
ENST00000341500, ENST00000302850, 
Fusion gene scores* DoF score14 X 8 X 11=123213 X 10 X 6=780
# samples 1615
** MAII scorelog2(16/1232*10)=-2.94485844580754
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
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: ELL [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)

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

GO:0010923

negative regulation of phosphatase activity

19389623

TgeneINSR

GO:0001934

positive regulation of protein phosphorylation

7556070

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:0051290

protein heterotetramerization

1898103

TgeneINSR

GO:0060267

positive regulation of respiratory burst

9092559


check button 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 typeSourceCancer typeSampleHgeneHchrHbpHstrandTgeneTchrTbpTstrand
TCGARVBRCATCGA-AC-A7VB-01AELLchr19

18632731

-INSRchr19

7267907

-
* LD: Li Ding group's fusion gene list
  RV: Roel Verhaak group's fusion gene list
  ChiTaRs fusion database

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-shitENST00000262809ENST00000341500ELLchr19

18632731

-INSRchr19

7267907

-
Frame-shitENST00000262809ENST00000302850ELLchr19

18632731

-INSRchr19

7267907

-
intron-3CDSENST00000596124ENST00000341500ELLchr19

18632731

-INSRchr19

7267907

-
intron-3CDSENST00000596124ENST00000302850ELLchr19

18632731

-INSRchr19

7267907

-

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FusionProtFeatures for ELL_INSR


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

P55199

INSR

P06213

Elongation factor component of the super elongationcomplex (SEC), a complex required to increase the catalytic rateof RNA polymerase II transcription by suppressing transientpausing by the polymerase at multiple sites along the DNA.Elongation factor component of the little elongation complex(LEC), a complex required to regulate small nuclear RNA (snRNA)gene transcription by RNA polymerase II and III (PubMed:22195968,PubMed:23932780). Specifically required for stimulating theelongation step of RNA polymerase II- and III-dependent snRNA genetranscription (PubMed:23932780). ELL also plays an early rolebefore its assembly into in the SEC complex by stabilizing RNApolymerase II recruitment/initiation and entry into the pausesite. Required to stabilize the pre-initiation complex and earlyelongation. {ECO:0000269|PubMed:16006523,ECO:0000269|PubMed:20159561, ECO:0000269|PubMed:20471948,ECO:0000269|PubMed:22195968, ECO:0000269|PubMed:22252557,ECO:0000269|PubMed:23932780, ECO:0000269|PubMed:8596958}. 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}.

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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FusionGeneSequence for ELL_INSR


check button 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 ELL_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
ELLSIRT2, ZHX1, TP53, EAF1, EAF2, SNF8, USPL1, MLLT3, MLLT1, KMT2A, TFPT, UBC, MED26, ICE2, ICE1, AFF4, CDK9, MCM2, SNRPA1, ELL3, DENND2D, OFD1, DYNLL1, CTR9, HUWE1, NCBP2, FGFR1OP2, SIKE1, VWA9, ASPM, CAMKV, PIP4K2A, TRIM25INSRCSK, 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


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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RelatedDrugs for ELL_INSR


check button Drugs targeting genes involved in this fusion gene.
(DrugBank Version 5.1.0 2018-04-02)
PartnerGeneUniProtAccDrugBank IDDrug nameDrug activityDrug typeDrug status
TgeneINSRP06213DB00046Insulin LisproInsulin receptorbiotechapproved
TgeneINSRP06213DB00047Insulin GlargineInsulin receptorbiotechapproved
TgeneINSRP06213DB00071Insulin PorkInsulin receptorbiotechapproved
TgeneINSRP06213DB01306Insulin AspartInsulin receptorbiotechapproved
TgeneINSRP06213DB01307Insulin DetemirInsulin receptorbiotechapproved
TgeneINSRP06213DB01309Insulin GlulisineInsulin receptorbiotechapproved
TgeneINSRP06213DB09564Insulin DegludecInsulin receptorbiotechapproved
TgeneINSRP06213DB00030Insulin HumanInsulin receptorbiotechapproved|investigational
TgeneINSRP06213DB01277MecaserminInsulin receptorbiotechapproved|investigational

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RelatedDiseases for ELL_INSR


check button Diseases associated with fusion partners.
(DisGeNet 4.0)
PartnerGeneDisease IDDisease name# pubmedsSource
TgeneINSRC0342278Diabetes Mellitus, Insulin-Resistant, with Acanthosis Nigricans18CTD_human;UNIPROT
TgeneINSRC0265344Donohue Syndrome14CTD_human;ORPHANET;UNIPROT
TgeneINSRC0271695Rabson-Mendenhall Syndrome7ORPHANET;UNIPROT
TgeneINSRC0011860Diabetes Mellitus, Non-Insulin-Dependent3HPO;UNIPROT
TgeneINSRC1864952Hyperinsulinemic Hypoglycemia, Familial, 53CTD_human;ORPHANET;UNIPROT
TgeneINSRC0011853Diabetes Mellitus, Experimental2CTD_human
TgeneINSRC0020459Hyperinsulinism2CTD_human;HPO
TgeneINSRC0021655Insulin Resistance2CTD_human
TgeneINSRC0024115Lung diseases2CTD_human
TgeneINSRC0002395Alzheimer's Disease1CTD_human
TgeneINSRC0011882Diabetic Neuropathies1CTD_human
TgeneINSRC0020429Hyperalgesia1CTD_human
TgeneINSRC0020456Hyperglycemia1CTD_human;HPO
TgeneINSRC0030567Parkinson Disease1CTD_human
TgeneINSRC0235833Congenital diaphragmatic hernia1CTD_human
TgeneINSRC0236969Substance-Related Disorders1CTD_human
TgeneINSRC0271650Impaired glucose tolerance1CTD_human
TgeneINSRC0752347Lewy Body Disease1CTD_human