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INPPL1 (inositol polyphosphate phosphatase-like 1)

Written2009-06Nagendra K Prasad
Purdue Cancer Center, Purdue Oncological Sciences Center, Department of Basic Medical Sciences, Purdue University, West Lafayette, Indiana 47907, USA

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Identity

Alias_symbol (synonym)SHIP2
HGNC (Hugo) INPPL1
LocusID (NCBI) 3636
Atlas_Id 40984
Location 11q13.4  [Link to chromosome band 11q13]
Location_base_pair Starts at 71935882 and ends at 71950188 bp from pter ( according to hg19-Feb_2009)  [Mapping INPPL1.png]
Local_order 71578250 FOLR1-FOLR2-INPPL1-PHOX2A 71669874 (Entrez data).
Fusion genes
(updated 2016)
INPPL1 (11q13.4) / CD2BP2 (16p11.2)INPPL1 (11q13.4) / COIL (17q22)INPPL1 (11q13.4) / INPPL1 (11q13.4)
INPPL1 (11q13.4) / NPM1 (5q35.1)

DNA/RNA

Description The cDNA sequence for human SHIP2 is 3777 nucleotide long (full processed mRNA is 4733 ntd long) (Hejna et al., 1995; Pesesse et al., 1997). The coding region comprises 28 exons. There is evidence for the existence of a shorter transcript (372 ntd long of unknown significance coding for 123 amino acids. The C-terminus 74 codons (including the SAM-domain) are common for both the transcripts.
Transcription SHIP2 promoter is regulated by Sp1 transcription factors (Ishida et al., 2005). Mechanisms of transcriptional regulations are unknown and perhaps not present. SHIP2 mRNA is expressed ubiquitously at high levels (Pesesse et al., 1997; Habib et al., 1998) and the protein levels are regulated post-transcriptionally by microRNA-205 (inhibitory) or microRNA-184 (which is a suppressor of mir-205) (Yu et al., 2008).

Protein

 
  Structural features of SHIP2 protein: The positions of the SHIP2 catalytic domain and the protein interaction motifs are shown. Currently known SHIP2-interacting proteins are listed under the respective interaction domain/motifs. SH2 (src homology-2 domain), IPPc (inositol polyphosphate phosphatase catalytic domain), Pro-rich (proline rich region), SAM (sterile alpha-motif).
Description SHIP2 protein (1258 amino acids long) contains an inositol polyphosphate phosphatase domain (IPPc; aa 422-735). In addition, SHIP2 has an amino-terminal SH2-domain (aa 21-117) and a carboxyl-terminal proline-rich region (Pro-rich; aa 935-1105). Also, SHIP2 contains a NPXY motif (aa 983-986) and a SAM (sterile alpha-motif) domain (aa 1201-1258). These structural elements provide sites for protein-protein interactions which seem to play a major role in SHIP2 function. Several cellular proteins associate with SHIP2 via phosphotyrosine-dependent (SH2 or NPXY mediated) or proline-rich region (SH3 mediated) interactions (for a comprehensive list of interacting proteins and citations please see Prasad, 2009a).
Expression Ubiquitously expressed with higher levels of mRNA in skeletal muscle, liver, adipose tissue, placenta and brain (Pesesse et al., 1997; Habib et al., 1998; Muraille et al., 2001). Also expressed in B-cells, T-cells, platelets, mast cells and macrophages (Muraille et al., 1999; Dyson et al., 2003; Giuriato et al., 2003; Ai et al., 2006; Leung and Bolland, 2007). Protein levels are very low in normal tissues and cells. Higher levels of protein expression is noted in many types of cancer cells (Wisniewski et al., 1999; Prasad et al., 2001; Prasad and Decker 2005) and in human breast cancer tissues (Prasad et al., 2008). SHIP2 protein levels in skeletal muscle and fat are higher in obese db/db mice as compared to normal heterozygous (db/+) mice and SHIP2 protein levels are moderately increased in response to a high-fat diet in normal mice (Hori et al., 2002). SHIP2 genetic sequence in diabetic rats and humans contain mutations that may lead to increased levels of SHIP2 (Marion et al., 2002).
Localisation SHIP2 is diffusely cytoplasmic but membrane enrichment of SHIP2 occurs during cell attachment (Prasad et al., 2001), membrane ruffling (Dyson et al., 2001) or in response to m-CSF in macrophages (Wang et al., 2004). Mutation in the SH2-domain (R47G) causes punctate distribution pattern in the cytoplasm of HeLa cells (Prasad et al., 2001). SHIP2 has also been reported to localize to the nuclear speckles in vascular smooth muscle cells (Deleris et al., 2003).
Function Overview. Phosphoinositide (PI) lipids are important second messengers in the intracellular signaling pathways. PI lipids interact with the pleckstrin homology domain (PH-domain) containing cellular enzymes causing their membrane recruitment and/or allosteric activation. Phosphoinositide 3-kinase (PI3-kinase) is central to the signal-induced generation of new phosphoinositides and its activation is a key intermediate step in the signaling initiated by various external signals including many hormones (insulin and leptin), growth factors (EGF, IGF-1 and PDGF) as well as integrin ligation. SHIP2 dephosphorylates the 5-position of phosphatidylinositol-3,4,5-trisphosphate (PIP3) generated by the PI3-kinase, producing a new second messenger PI-3,4-bisphosphate (PI-3,4-P2). As PI3-kinase pathway aberrations play a major role in the development of cancer, diabetes and inflammation, SHIP2 function is expected to be critically important for the molecular pathogenesis of these diseases. SHIP2 also dephosphorylates PI-3,4-bisphosphate (Taylor et al., 2000). In vitro, a soluble inositol molecule, inositol-1,3,4,5-tetrakisphosphate (IP4) also serves as a high affinity substrate for SHIP2 (Pesesse et al., 1998; Chi et al., 2004; Batty et al., 2007).

Negative Regulator of insulin signaling. In cell culture overexpression studies, SHIP2 acts a mild suppressor of insulin signaling (Sasaoka et al., 2001; Wada et al., 2001). RNA interference studies, however, contradict these observations (Zhou et al., 2004; Huard et al., 2007). SHIP2 null-mice are viable but resistant to high-fat-diet-induced obesity (Sleeman et al., 2005). Insulin signaling was enhanced only modestly in these mice. However, liver-specific suppression of SHIP2 function in mice improves insulin function (Fukui et al., 2005; Grempler et al., 2007). Mechanisms by which SHIP2 achieves the energy homeostasis therefore remain unclear at present.

Negative Regulator of IGF-1 signaling. Exogenous SHIP2 in C2C12 skeletal muscle cells is shown to suppress IGF-1 signaling and to interfere with IGF-1-induced muscle hypertrophy (Rommel et al., 2001). Similarly SHIP2 blocks compensatory hypertrophy upon its exogenous expression in rat skeletal muscle myocytes (Bodine et al., 2001).

Positive Regulator of cytoskeleton remodeling, cell adhesion, lamellipodia formation/cell spreading. Transient exogenous expression of the wild type-SHIP2 increases cellular adhesion in SH2-domain dependent manner in HeLa cells (Prasad et al., 2001). Furthermore, catalytic activity of SHIP2 is important for efficient lamellipodia formation and cell spreading (Prasad et al., 2001). Interaction with c-Met is important for this function of SHIP2 in MDCK cells (Koch et al., 2005). Also, C-terminus proline-rich region of SHIP2 is shown to be important for membrane ruffling process through its interaction with Filamin (Dyson et al., 2003). Src kinase-induced tyrosine phosphorylation of SHIP2 and consequent SHIP2-Shc association are important for HeLa cell spreading on type I collagen (Prasad et al., 2002). In MDA-231 breast cancer cells, SHIP2 promotes cell migration and this effect is associated to sustained EGFR-Akt signaling and increased expression of chemokine receptor CXCR4 (Prasad, 2009b).

Negative Regulator of endocytosis (EGFR, Transferrin receptor, EphA2). Suppression of endogenous SHIP2 in cancer cells (HeLa cervical cancer cells and MDA-231 breast cancer cells) decreases ligand-induced endocytosis of the EGFR and EphA2 (Prasad and Decker, 2005; Zhuang et al., 2007). SHIP2 function in the endocytosis of EGFR is characterized by a direct and constitutive association between SHIP2 and c-Cbl ubiquitin ligase and changes in EGFR-Cbl association. Whereas SHIP2 directly interacts with EphA2 via SAM-domain and this interaction may be important for EphA2 endocytosis (Zhuang et al., 2007). SHIP2 associates with intersectin 1, a major regulator of EGFR endocytosis, and recruits it to the plasma membrane in response to EGF treatment (Xie et al., 2008).

Regulator of Cell Cycle progression and apoptosis. Early studies indicated a positive association between SHIP2 expression and cell proliferation where EGF increases the SHIP2 mRNA expression in thyrocytes (Pesesse et al., 1997). In addition, SHIP2 protein expression correlates with the EGFR expression in proliferating neurospheres (Muraille et al., 2001). Exogenous overexpression (using adenovirus vectors) of wild-type SHIP2 inhibits cell cycle progression in U87-MG glioblastoma cells (Taylor et al., 2000) and K562 leukemia cells (Giuriato et al., 2002) and of a dominant-negative SHIP2 (phosphatase-defective) increases proliferation of pancreatic beta-cells (Grempler et al., 2007). Whereas retroviral-mediated expression of SHIP2 does not inhibit cell cycle progression of Myeloma cells (Choi et al., 2002). Furthermore, RNAi-mediated suppression of endogenous SHIP2 in MDA-231 cells inhibits cell proliferation with G1 accumulation and decreased S-phase and delays in vivo tumorigenesis (Prasad et al., 2008). Retroviral-mediated expression of a catalytically inactive SHIP2 inhibits PDGF-induced proliferation of 3T3-L1 preadipocytes (Artemenko et al., 2009). Thus, this aspect of SHIP2 function appears to be influenced greatly by the experimental approach and/or the cell types employed.

Negative regulator of immune cell function. SHIP2 inhibits Fcgamma Receptor IIa signaling including Akt activation and NF-kb-dependent gene trasncription (Pengal et al., 2003), downregulates Fcgamma Receptor-mediated phagocytosis (Ai et al., 2006) and decreases mast cell degranulation (Leung and Bolland, 2007; Saini et al., 2009).

Homology SHIP2 is structurally related to SHIP1, another phosphoinositol 5-phosphatase expressed exclusively in hematopoietic tissues. SHIP1 is an important negative regulator of immune receptor and cytokine signaling. SHIP1 and SHIP2 show 64% identity in their inositol phosphatase domains and 54% identity in their SH2-domains. The C-terminus proline-rich region carries the least similarity (also the SAM-domain is present only in SHIP2 and not in SHIP1) and appears to be the key for functional divergence between these two enzymes. In addition to the human gene, SHIP2 gene has been cloned from mouse, rat, cattle, dog, monkey, chimpanzee and zebra fish genomes.

Mutations

Germinal There is R1142C mutation within the Proline-rich region of SHIP2 in Goto-Kakizaki (GK rats; a model for type 2 diabetes) and spontaneously hypertensive (SH-) rats. This mutation slightly impairs insulin signaling in cell culture (Marion et al., 2002).
Somatic In humans, a deletion in the SHIP2 3' untranslated region (UTR) has been identified in type 2 diabetic patients. In cell culture, this deletion enhances SHIP2 promoter activity in reporter assays and SHIP2 over-expression. This deletion is reported to be significantly associated with the presence of type 2 diabetes (Marion et al., 2002).

Implicated in

Note
  
Entity Chronic myelogenous leukemia (CML)
Note SHIP2 is expressed at high levels in Bcr-Abl transformed K562 CML cells where it is highly tyrosine phosphorylated and constitutively associated with the adapter protein Shc in K562 leukemia cells (Wisniewski et al., 1999). Adenoviral-mediated exogenous overexpression of SHIP2 in K562 cells inhibits cell cycle progression (see 'Function - Cell cycle regulation' above).
  
  
Entity Breast cancer
Note SHIP2 is overexpressed in many breast cancer cells when compared to non-transformed mammary epithelial cells (Prasad et al., 2008). Stable SHIP2 RNA interference in MDA-231 and MDA-468 breast cancer cells decreases cell proliferation (Prasad et al., 2008; Prasad, 2009b). SHIP2 suppression also causes delayed tumorigenesis in nude mouse mammary fatpad xenograft studies (Prasad et al., 2008). SHIP2 overexpression is reported in clinical specimens of human breast cancers [n=65 (Prasad et al., 2008); and n=285 (Prasad et al., 2008)]. In invasive breast cancers (n=145), SHIP2 expression is positively correlated with reduced disease-free survival and estrogen receptor-negative (ER-) and EGF receptor-positive (EGFR+) status (Prasad et al., 2008).
  
  
Entity Hepatocellular carcinoma
Note SHIP2 expression in the cancer cells is decreased as compared to the adjacent normal cells of the same cancer specimens (n = 20) (Sumie et al., 2007). Any possible association between the SHIP2 levels and glucose intolerance or the aggressiveness of the disease remains to be examined.
  
  
Entity Type 2 diabetes
Note Single nucleotide polymorphisms (SNPs) in the SHIP2 gene promoter and the 5' untranlated region correlates with the impaired fasting glycemia in Japanese population (Ishida et al., 2006). The haplotypes found more frequently in glucose intolerant people increase transcription from SHIP2 promoter in reporter gene assays.
Evidence from transgenic animal studies in mouse showed that SHIP2 function in liver is important for insulin-dependent glucose homeostasis (Fukui et al., 2005; Buettner et al., 2007; Grempler et al., 2007; Kagawa et al., 2008).
Metabolic syndrome. Single nucleotide polymorphisms (SNPs) and haplotypes of SHIP2 are significantly correlated with symptoms of the metabolic syndrome including hypertension in British and French people from type 2 Diabetes families (Kaisaki et al., 2004). This association was not found with essential hypertension (not linked to metabolic syndrome) (Marcano et al., 2007).
Obesity. Evidence from gene knockout studies in mouse showed that SHIP2 deletion caused resistance to high-fat diet induced obesity (Sleeman et al., 2005) although insulin signaling was only mildly enhanced. These studies raised the possibility that global inhibition of SHIP2 will be tolerated (not lethal) without significant side-effects.
  

Bibliography

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PMID 19082482
 
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PMID 19477690
 
SH2-containing inositol phosphatase 2 negatively regulates insulin-induced glycogen synthesis in L6 myotubes.
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Sasaoka T, Wada T, Tsuneki H.
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PMID 16842857
 
Absence of the lipid phosphatase SHIP2 confers resistance to dietary obesity.
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Significance of glucose intolerance and SHIP2 expression in hepatocellular carcinoma patients with HCV infection.
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PMID 17671700
 
5' phospholipid phosphatase SHIP-2 causes protein kinase B inactivation and cell cycle arrest in glioblastoma cells.
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PMID 10958682
 
Overexpression of SH2-containing inositol phosphatase 2 results in negative regulation of insulin-induced metabolic actions in 3T3-L1 adipocytes via its 5'-phosphatase catalytic activity.
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PMID 11238900
 
SHIP2 is recruited to the cell membrane upon macrophage colony-stimulating factor (M-CSF) stimulation and regulates M-CSF-induced signaling.
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PMID 15557176
 
A novel SH2-containing phosphatidylinositol 3,4,5-trisphosphate 5-phosphatase (SHIP2) is constitutively tyrosine phosphorylated and associated with src homologous and collagen gene (SHC) in chronic myelogenous leukemia progenitor cells.
Wisniewski D, Strife A, Swendeman S, Erdjument-Bromage H, Geromanos S, Kavanaugh WM, Tempst P, Clarkson B.
Blood. 1999 Apr 15;93(8):2707-20.
PMID 10194451
 
SHIP2 associates with intersectin and recruits it to the plasma membrane in response to EGF.
Xie J, Vandenbroere I, Pirson I.
FEBS Lett. 2008 Sep 3;582(20):3011-7. Epub 2008 Aug 8.
PMID 18692052
 
MicroRNA-184 antagonizes microRNA-205 to maintain SHIP2 levels in epithelia.
Yu J, Ryan DG, Getsios S, Oliveira-Fernandes M, Fatima A, Lavker RM.
Proc Natl Acad Sci U S A. 2008 Dec 9;105(49):19300-5. Epub 2008 Nov 25.
PMID 19033458
 
Analysis of insulin signalling by RNAi-based gene silencing.
Zhou QL, Park JG, Jiang ZY, Holik JJ, Mitra P, Semiz S, Guilherme A, Powelka AM, Tang X, Virbasius J, Czech MP.
Biochem Soc Trans. 2004 Nov;32(Pt 5):817-21. (REVIEW)
PMID 15494023
 
Regulation of EphA2 receptor endocytosis by SHIP2 lipid phosphatase via phosphatidylinositol 3-Kinase-dependent Rac1 activation.
Zhuang G, Hunter S, Hwang Y, Chen J.
J Biol Chem. 2007 Jan 26;282(4):2683-94. Epub 2006 Nov 29.
PMID 17135240
 

Citation

This paper should be referenced as such :
Prasad, NK
INPPL1 (inositol polyphosphate phosphatase-like 1)
Atlas Genet Cytogenet Oncol Haematol. 2010;14(5):454-459.
Free journal version : [ pdf ]   [ DOI ]
On line version : http://AtlasGeneticsOncology.org/Genes/INPPL1ID40984ch11q13.html


External links

Nomenclature
HGNC (Hugo)INPPL1   6080
Cards
AtlasINPPL1ID40984ch11q13
Entrez_Gene (NCBI)INPPL1  3636  inositol polyphosphate phosphatase like 1
AliasesOPSMD; SHIP2
GeneCards (Weizmann)INPPL1
Ensembl hg19 (Hinxton)ENSG00000165458 [Gene_View]  chr11:71935882-71950188 [Contig_View]  INPPL1 [Vega]
Ensembl hg38 (Hinxton)ENSG00000165458 [Gene_View]  chr11:71935882-71950188 [Contig_View]  INPPL1 [Vega]
ICGC DataPortalENSG00000165458
TCGA cBioPortalINPPL1
AceView (NCBI)INPPL1
Genatlas (Paris)INPPL1
WikiGenes3636
SOURCE (Princeton)INPPL1
Genetics Home Reference (NIH)INPPL1
Genomic and cartography
GoldenPath hg19 (UCSC)INPPL1  -     chr11:71935882-71950188 +  11q23   [Description]    (hg19-Feb_2009)
GoldenPath hg38 (UCSC)INPPL1  -     11q23   [Description]    (hg38-Dec_2013)
EnsemblINPPL1 - 11q23 [CytoView hg19]  INPPL1 - 11q23 [CytoView hg38]
Mapping of homologs : NCBIINPPL1 [Mapview hg19]  INPPL1 [Mapview hg38]
OMIM258480   600829   
Gene and transcription
Genbank (Entrez)BC140853 BG236320 L24444 L36818 Y14385
RefSeq transcript (Entrez)NM_001567
RefSeq genomic (Entrez)NC_000011 NC_018922 NG_023253 NT_167190 NW_004929380
Consensus coding sequences : CCDS (NCBI)INPPL1
Cluster EST : UnigeneHs.523875 [ NCBI ]
CGAP (NCI)Hs.523875
Alternative Splicing GalleryENSG00000165458
Gene ExpressionINPPL1 [ NCBI-GEO ]   INPPL1 [ EBI - ARRAY_EXPRESS ]   INPPL1 [ SEEK ]   INPPL1 [ MEM ]
Gene Expression Viewer (FireBrowse)INPPL1 [ Firebrowse - Broad ]
SOURCE (Princeton)Expression in : [Datasets]   [Normal Tissue Atlas]  [carcinoma Classsification]  [NCI60]
GenevisibleExpression in : [tissues]  [cell-lines]  [cancer]  [perturbations]  
BioGPS (Tissue expression)3636
GTEX Portal (Tissue expression)INPPL1
Protein : pattern, domain, 3D structure
UniProt/SwissProtO15357   [function]  [subcellular_location]  [family_and_domains]  [pathology_and_biotech]  [ptm_processing]  [expression]  [interaction]
NextProtO15357  [Sequence]  [Exons]  [Medical]  [Publications]
With graphics : InterProO15357
Splice isoforms : SwissVarO15357
Catalytic activity : Enzyme3.1.3.86 [ Enzyme-Expasy ]   3.1.3.863.1.3.86 [ IntEnz-EBI ]   3.1.3.86 [ BRENDA ]   3.1.3.86 [ KEGG ]   
PhosPhoSitePlusO15357
Domaine pattern : Prosite (Expaxy)SAM_DOMAIN (PS50105)    SH2 (PS50001)   
Domains : Interpro (EBI)Endo/exonuclease/phosphatase    IPPc    SAM    SAM/pointed    SH2   
Domain families : Pfam (Sanger)Exo_endo_phos (PF03372)    SAM_1 (PF00536)    SH2 (PF00017)   
Domain families : Pfam (NCBI)pfam03372    pfam00536    pfam00017   
Domain families : Smart (EMBL)IPPc (SM00128)  SAM (SM00454)  SH2 (SM00252)  
Conserved Domain (NCBI)INPPL1
DMDM Disease mutations3636
Blocks (Seattle)INPPL1
PDB (SRS)2K4P    2KSO    2MK2    3NR8    4A9C   
PDB (PDBSum)2K4P    2KSO    2MK2    3NR8    4A9C   
PDB (IMB)2K4P    2KSO    2MK2    3NR8    4A9C   
PDB (RSDB)2K4P    2KSO    2MK2    3NR8    4A9C   
Structural Biology KnowledgeBase2K4P    2KSO    2MK2    3NR8    4A9C   
SCOP (Structural Classification of Proteins)2K4P    2KSO    2MK2    3NR8    4A9C   
CATH (Classification of proteins structures)2K4P    2KSO    2MK2    3NR8    4A9C   
SuperfamilyO15357
Human Protein AtlasENSG00000165458
Peptide AtlasO15357
HPRD02900
IPIIPI00016932   IPI00795687   IPI01012176   IPI01011735   IPI01009446   IPI01009881   IPI01015539   IPI01015761   IPI01012922   IPI01013380   
Protein Interaction databases
DIP (DOE-UCLA)O15357
IntAct (EBI)O15357
FunCoupENSG00000165458
BioGRIDINPPL1
STRING (EMBL)INPPL1
ZODIACINPPL1
Ontologies - Pathways
QuickGOO15357
Ontology : AmiGOendochondral ossification  immune system process  actin binding  protein binding  cytoplasm  Golgi apparatus  cytosol  cytoskeleton  plasma membrane  glucose metabolic process  phosphatidylinositol biosynthetic process  endocytosis  actin filament organization  cell adhesion  negative regulation of cell proliferation  post-embryonic development  negative regulation of gene expression  SH3 domain binding  lamellipodium  filopodium  response to insulin  phosphatidylinositol-3,4,5-trisphosphate 5-phosphatase activity  SH2 domain binding  inositol phosphate metabolic process  phosphatidylinositol dephosphorylation  inositol-1,3,4,5-tetrakisphosphate 5-phosphatase activity  ruffle assembly  
Ontology : EGO-EBIendochondral ossification  immune system process  actin binding  protein binding  cytoplasm  Golgi apparatus  cytosol  cytoskeleton  plasma membrane  glucose metabolic process  phosphatidylinositol biosynthetic process  endocytosis  actin filament organization  cell adhesion  negative regulation of cell proliferation  post-embryonic development  negative regulation of gene expression  SH3 domain binding  lamellipodium  filopodium  response to insulin  phosphatidylinositol-3,4,5-trisphosphate 5-phosphatase activity  SH2 domain binding  inositol phosphate metabolic process  phosphatidylinositol dephosphorylation  inositol-1,3,4,5-tetrakisphosphate 5-phosphatase activity  ruffle assembly  
Pathways : BIOCARTASkeletal muscle hypertrophy is regulated via AKT/mTOR pathway [Genes]   
Pathways : KEGGInositol phosphate metabolism    Phosphatidylinositol signaling system    B cell receptor signaling pathway    Fc gamma R-mediated phagocytosis    Insulin signaling pathway   
REACTOMEO15357 [protein]
REACTOME Pathways1660499 [pathway]   1855204 [pathway]   912526 [pathway]   
NDEx NetworkINPPL1
Atlas of Cancer Signalling NetworkINPPL1
Wikipedia pathwaysINPPL1
Orthology - Evolution
OrthoDB3636
GeneTree (enSembl)ENSG00000165458
Phylogenetic Trees/Animal Genes : TreeFamINPPL1
HOVERGENO15357
HOGENOMO15357
Homologs : HomoloGeneINPPL1
Homology/Alignments : Family Browser (UCSC)INPPL1
Gene fusions - Rearrangements
Polymorphisms : SNP and Copy number variants
NCBI Variation ViewerINPPL1 [hg38]
dbSNP Single Nucleotide Polymorphism (NCBI)INPPL1
dbVarINPPL1
ClinVarINPPL1
1000_GenomesINPPL1 
Exome Variant ServerINPPL1
ExAC (Exome Aggregation Consortium)INPPL1 (select the gene name)
Genetic variants : HAPMAP3636
Genomic Variants (DGV)INPPL1 [DGVbeta]
DECIPHER (Syndromes)11:71935882-71950188  ENSG00000165458
CONAN: Copy Number AnalysisINPPL1 
Mutations
ICGC Data PortalINPPL1 
TCGA Data PortalINPPL1 
Broad Tumor PortalINPPL1
OASIS PortalINPPL1 [ Somatic mutations - Copy number]
Somatic Mutations in Cancer : COSMICINPPL1  [overview]  [genome browser]  [tissue]  [distribution]  
Mutations and Diseases : HGMDINPPL1
intOGen PortalINPPL1
LOVD (Leiden Open Variation Database)Whole genome datasets
LOVD (Leiden Open Variation Database)LOVD 3.0 shared installation
BioMutasearch INPPL1
DgiDB (Drug Gene Interaction Database)INPPL1
DoCM (Curated mutations)INPPL1 (select the gene name)
CIViC (Clinical Interpretations of Variants in Cancer)INPPL1 (select a term)
intoGenINPPL1
NCG5 (London)INPPL1
Cancer3DINPPL1(select the gene name)
Impact of mutations[PolyPhen2] [SIFT Human Coding SNP] [Buck Institute : MutDB] [Mutation Assessor] [Mutanalyser]
Diseases
OMIM258480    600829   
Orphanet553    2813   
MedgenINPPL1
Genetic Testing Registry INPPL1
NextProtO15357 [Medical]
TSGene3636
GENETestsINPPL1
Huge Navigator INPPL1 [HugePedia]
snp3D : Map Gene to Disease3636
BioCentury BCIQINPPL1
ClinGenINPPL1
Clinical trials, drugs, therapy
Chemical/Protein Interactions : CTD3636
Chemical/Pharm GKB GenePA29888
Clinical trialINPPL1
Miscellaneous
canSAR (ICR)INPPL1 (select the gene name)
Other databasehttp://cancergenome.broadinstitute.org/index.php?tgene=INPPL1
Probes
Litterature
PubMed100 Pubmed reference(s) in Entrez
GeneRIFsGene References Into Functions (Entrez)
CoreMineINPPL1
EVEXINPPL1
GoPubMedINPPL1
iHOPINPPL1
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

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