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PNP (Purine Nucleoside Phosphorylase)

Written2018-03Rafig Gurbanov, Sinem Tunçer
Department of Molecular Biology and Genetics Bilecik SE University, 11230 Bilecik, rafig.gurbanov@bilecik.edu.tr (RG); Vocational School of Health Services, Department of Medical Laboratory Techniques, Bilecik S.E. University, Ankara, situncer@metu.edu.tr (ST), Turkey

Abstract The purine nucleoside phosphorylase gene (PNP) encodes an enzyme which reversibly catalyzes the phosphorolysis of purine nucleosides. PNP is ubiquitously expressed in mammalian cells and tissues. PNP mutations cause nucleoside phosphorylase deficiency which result in defective T cell mediated immunity but can also affect B cell immunity and antibody responses.

Keywords Purine nucleotide phosphorylase (PNP), purine metabolism, PNP deficiency, Immunodeficiency, cancer.

(Note : for Links provided by Atlas : click)

Identity

Alias_namesNP
nucleoside phosphorylase
Alias_symbol (synonym)PUNP
Other aliasNP (Nucleoside Phosphorylase)
PRO1837
HGNC (Hugo) PNP
LocusID (NCBI) 4860
Atlas_Id 46893
Location 14q11.2  [Link to chromosome band 14q11]
Location_base_pair Starts at 20469379 and ends at 20478006 bp from pter ( according to hg19-Feb_2009)  [Mapping PNP.png]
 
  Figure 1. Genomic location of PNP (Chromosome 14 - NC_000014.9 Reference GRCh38.p7 Primary Assembly)
Fusion genes
(updated 2017)
Data from Atlas, Mitelman, Cosmic Fusion, Fusion Cancer, TCGA fusion databases with official HUGO symbols (see references in chromosomal bands)

DNA/RNA

Note The PNP gene is 7,716 bp long (according to UCSC, GRCh38/hg38), located on the plus strandand spans 6 exons (NCBI Homo sapiens Annotation Release 108).
Transcription The gene has 8 transcripts (Table 1)
Table 1. Transcripts of human PNP gene (Ensemble, GRCh38.p10).
Name  Transcript IDbp  Protein (aa) Biotype
PNP-201  ENST00000361505.9 1509289 Protein coding
PNP-203  ENST00000553591.1 770221 Protein coding
PNP-202  ENST00000553418.555793 Protein coding
PNP-205  ENST00000554065.155461 Protein coding
PNP-207  ENST00000556754.1 2573 Retained intron
PNP-204  ENST00000554056.51635 Retained intron
PNP-206  ENST00000556293.5 1023 Retained intron
PNP-208  ENST00000557229.5 992 Retained intron
Pseudogene A pseudogene has been identified on chromosome 2 (NCBI Homo sapiens Annotation Release 108).

Protein

Note PNP encodes purine nucleoside phosphorylase (EC 2.4.2.1) (NCBI Homo sapiens Annotation Release 108). Mammalian PNPs are homotrimers with a monomeric molecular mass of about 31 kDa, each with a substrate-binding site (Figure 2) (Ting et al., 2004; Aust et al., 1992).
 
  Figure 2. Structure of human purine nucleoside phosphorylase. Structure of human PNP determined using X-ray diffraction (PDB ID: 3BGS) (Rinaldo-Matthis et al., 2008).
Expression PNP is ubiquitously expressed in human cells and tissues, but the highest activity is found in the peripheral red blood cells, blood granulocytes and lymphoid tissue (Roberts et al., 2004).
Localisation PNP is present in both the cytosol and the mitochondria (Roberts et al., 2004).
 
  Figure 3. Enzymatic pathways involved in the degradation of purine nucleosides. Thermodynamically, the equilibrium of the reaction is shifted in favor of nucleoside synthesis. However, phosphorolysis is highly favored over nucleoside synthesis, due to coupling with two additional enzymatic reactions: (1) oxidation and (2) phosphoribosylation of the liberated purine bases by xanthine oxidase (Xox) and hypoxanthine-guanine phosphoribosyltransferase (HGPRT), respectively (modified from Giuliani et al., 2016).
Function The PNP catalyzes the reversible phosphorolysis of purine nucleosides (primarily inosine and guanosine in humans) to generate the corresponding purine base and ribose 1-phosphate inosine in the presence of inorganic orthophosphate (Pi) (Jonsson et al., 1992; Furihata et al., 2014). PNP is a ubiquitous enzyme of purine metabolism that functions in the salvage pathway, thus enabling the cells to synthesize purine nucleotides from purine bases by avoiding the ex-novo synthesis which is energetically expensive (Figure 3). Under normal conditions, phosphorolysis is favored due to the coupling of the PNP reaction with either purine base oxidation by xanthine oxidase or purine base phosphoribosylation by hypoxanthine-guanine phosphoribosyl transferase (HGPRT). On the other hand, nucleoside synthesis is thermodynamically favored over phosphorolysis (Erion et al., 1997; Bzowska et al., 2000).
PNP activity is crucial for cell survival and function. PNP deficiency results in the accumulation of its substrates: inosine, deoxyinosine, guanosine, and deoxyguanosine. Increased phosphorylation of deoxyguanosine leads to dGTP accumulation, a potent feedback inhibitor of human ribonucleotide reductase. dGTP accumulation can also interfere with DNA synthesis or repair directly (Arpaia et al., 2000; Ghodke-Puranik et al., 2017) (Figure 4). Abnormal activity of the enzyme is associated with different pathologies (Giuliani et al., 2016).
 
  Figure 4. PNP in the degradation and salvage pathways of purine nucleosides. Phosphorolysis of the products of the ADA reaction, inosine and deoxyinosine, is catalyzed by PNP to yield hypoxanthine and ribose-1-phosphate. Of the four PNP substrates, only deoxyguanosine is phosphorylated by the mitochondrial deoxyguanosine kinase (dGK). Further phosphorylation of dGMP results in the accumulation of dGTP, which interferes with DNA synthesis or DNA repair directly or inhibits ribonucleotide reductase activity. The PNP product guanine is salvaged back to the guanine nucleotide pools by HGPRT activity (modified from Arpaia et al., 2000).
Homology PNP enzyme has been isolated isolated from different species, including bacteria, protozoa, rodents, and mammals. A high degree of homology is found between these PNP enzymes, with human and bovine and murine PNPs demonstrating more than 87% and 84% homology, respectively (Ochs et al., 2013) (Figure 5).
 
  Figure 5. Pairwise alignment of PNP gene and PNP protein sequences (in distance from human) (HomoloGene, NCBI).

Mutations

Note PNP deficiency is caused by PNP gene mutations. As mentioned before, PNP contains six exons. Exon skipping, missense, and frameshift mutations in these six exons have been found to cause PNP deficiency, and the most frequent mutations are the substitution of A to C or A to G at cDNA position 58 or 234, respectively (Brodszki et al., 2015). Up-to-date and comprehensive list of PNP associated mutations was given in Table 2. Furthermore, it should be also considered that PNP polymorphisms might be associated with variability in the clinical presentation and course of affected patients (Moallem et al., 2002).
Table 2. Purine nucleoside phosphorylase (PNP) deficiency related mutations.
#Location MutationProteinReference
[1]  Exon 2c.59A>C p.20H>P Yeates et al., 2017
[2]  Exon 2c.70C>Tp.Arg24XWalker et al., 2011
[3]  Exon 2c.172C>Tp.Arg57XWalker et al., 2011
[4]  Exon 2c.181G>Tp.Tyr5AlafsX28Walker et al., 2011
[5]  Exon 3c.199C>Tp.Arg67XWalker et al., 2011
[6]  Exon 3c.212G>Ap.71Gly>GluWalker et al., 2011
[7]  Exon 3c.257A>Gp.86His>ArgWalker et al., 2011
[8]  Exon 3c.265G>Ap.89Glu>LysWalker et al., 2011
[9]  Exon 4c.349G>Ap.117Ala>ThrGrunebaum et al., 2004
[10]  Exon 4c.383A>Gp.128Asp>GlyWalker et al., 2011
[11]  Exon 4c.385 387delATC p.Ile129delWalker et al., 2011
[12]  Exon 4c.437C>Tp.146Pro>LeuAlangari et al., 2009
[13]  Exon 5c.467G>C p.156Gly>AlaMoallem et al., 2002
[14]  Exon 5c.475T>G p.159Phe>ValWalker et al., 2011
[15]  Exon 5c.487T>C p.163Ser>ProAl-Saud et al., 2009
[16]  Exon 5c.520G>C p.174Ala>ProWalker et al., 2011
[17]  Exon 5c.569G>T p.190Gly>ValWalker et al., 2011
[18]  Exon 5c.575A>G p.192Tyr>CysWalker et al., 2011
[19]  Exon 6c.700C>G p.Arg234XWalker et al., 2011
[20]  Exon 6c.701G>Cp.234Arg>ProWalker et al., 2011
[21]  Exon 6c.729C>Gp.Asn243LysBrodszki et al., 2015
[22]  Exon 6c.730delA p.Lys244ArgfsX17 Walker et al., 2011
[23]  Exon 6.746A>Cp.Tyr249CysBrodszki et al., 2015
[25]  Exon 6c.770A>G p.257His>ArgWalker et al., 2011
[26]  Intron 3c.285+1G>Ap.Val61GlyfsX30Walker et al., 2011

Implicated in

Note Associated Pathologies
When PNP is defective, dGTP accumulation inhibits DNA replication and mitochondrial DNA repair which cause increased sensitivity of T lymphocytes to DNA damage and apoptosis during thymus selection. In addition, the lack of DNA replication is critical especially in the immune system: PNP deficiency leads to S-phase block in 7-11% of circulating lymphocytes. Mutations leading to PNP deficiency result in an autosomal recessive disorder known as severe combined immune deficiency (SCID) characterized by a profound deficiency in T cell function with variable B cell involvement. PNP deficiency is a very rare autosomal recessive condition, accounting for approximately 4% of all SCID cases (Madkaikar et al., 2011; Ghodke-Puranik et al., 2017). Small hypoplastic thymus, reduced T lymphocytes in peripheral blood, abnormal response of T lymphocytes to stimulation, and enlarged spleen are found in most PNP-deficient patients (Toro and Grunebaum, 2006). Lymphopenia, reduced serum uric acid, and abnormal PNP enzymatic activity assist in the diagnosis of PNP deficiency. Patients with SCID lack virtually all immune protection from foreign invaders such as bacteria, viruses, and fungi, therefore they are prone to repeated and persistent infections that can be very detrimental and life threatening. About two-thirds of individuals with PNP deficiency have neurological problems, including hypertonia, spasticity, tremors, ataxia, retarded motor development, behavioral difficulties, and varying degrees of mental retardation. People with PNP deficiency are also at increased risk of developing autoimmune disorders (autoimmune hemolytic anemia, idiopathic thrombocytopenic purpura-ITP, autoimmune neutropenia, thyroiditis, and lupus). Infants with SCID typically grow much more slowly than healthy children and experience pneumonia, chronic diarrhea, and widespread skin rashes. Without successful treatment to restore immune function, children with SCID usually live only into early childhood. Lymphoma and lymphosarcoma have also been reported in children with PNP immunodeficiency (Ghodke-Puranik et al., 2017; Arpaia et al., 2000).
On the other hand, PNP levels are significantly upregulated in several tumor cells (Figure 6). In comparison with healthy individuals, PNP activity was shown to be higher in lymphocytes of patients suffering from bronchogenic carcinoma (Gierek et al., 1987; Rendeková et al., 1983). Sanfilippo et al. claimed a relationship between tissue PNP and tumor invasiveness in human colon carcinoma (Sanfilippo et al., 1994). Furthermore, Roberts et al. showed that plasma PNP activity was higher also in patients with breast, gastric, colon, lung and ovarian cancers and lymphoma (Roberts et al., 2004). From the biomarker perspective, Vareed et al. found that PNP levels were higher in sera from pancreatic adenocarcinoma patients and levels of PNP-regulated metabolites in serum, guanosine and adenosine, were suitable to determine pancreatic adenocarcinoma and distinguish pancreatic adenocarcinoma from benign tumors (Vareed et al., 2011). Plasma PNP activity was also higher in patients with asthma than in either healthy subjects or patients with gout (Yamamoto et al., 1995). However, a low level of PNP activity was found in mononuclear cells from patients with acute myeloid and lymphoblastic leukemia and with chronic lymphocytic leukemia (Morisaki et al., 1986).
Treatment
Bone marrow transplantation in PNP deficiency has been attempted with variable degree of success. However, HLA-matched donors are not readily available, and transplants using HLA incompatible donors are frequently result in procedure-related morbidity, graft-versus-host disease or graft loss (Liao et al., 2008). Myers et al. suggested umbilical cord blood, a readily available and pathogen-free source of stem cells, transplantation as a treatment option for patients with PNP deficiency who do not have a HLA-matched donor (Myers et al., 2004).
Gene therapy with autologous cells, either total bone marrow (BM) or hematopoietic stem cells (HSCs) isolated from the BM, transduced with the normal gene sequence that can express the missing protein represents an attractive option for inherited hematological and immunological defects, including PNP deficiency (Liao et al., 2008). In in vitro, Foresman et al. showed that retroviral-mediated PNP gene transfer and expression correct the metabolic defects caused by PNP deficiency in murine lymphoid cells (Foresman et al., 1992). In PNP -/- mouse model, PNP deficiency was corrected by transplanting BM cells which have been transduced with lentiviral vectors containing the human PNP gene (lentiPNP) (Liao et al., 2008). However, 12 weeks after transplant, benefit of lentiPNP transduced cells decreased, which indicates that an improved gene expression strategy is required to afford a successful gene therapy for PNP deficiency (Liao et al., 2008). Indeed, PNP enzyme replacement therapy has been evaluated in PNP -/- mice by administration of PNP fused trans-activator of transcription (TAT) protein (TAT-PNP). TAT induced rapid and efficient delivery of active PNP into many tissues, including the brain, and TAT-PNP remained effective over 24 weeks post-treatment, and corrected metabolic abnormalities and immunodeficiency, and extended survival (Toro and Grunebaum, 2006). Similarly, PNP fused with protein transduction domain (PTD) from TAT protein was found to rapidly enter PNP deficient lymphocytes and increase intracellular enzyme activity for 96 h, and correct abnormal functions of PNP deficient lymphocytes including their response to stimulation and IL-2 secretion, in vitro (Toro et al., 2006). These results show that fusion protein approach for PNP deficiency is an attractive and promising method for intracellular delivery of PNP.
Since PNP deficiency results in selective cellular immunodeficiency, PNP inhibitors are considered to be potentially effective suppressors of T cell proliferative diseases, such as T cell lymphoma and T cell related autoimmune diseases, and may also be useful for the suppression of the graft-versus-host reaction (Ting et al., 2004). In addition, PNP inhibitors have shown to be promising based on their ability to potentiate the in vivo activity of antiviral and anticancer drugs (Erion et al., 1997). As an enzyme prodrug model, Krais et al. generated a fusion protein called as PNP-AV which is composed of E. coli PNP and human annexin V (AV). AV binds to phosphatidylserine (PS) expressed externally on tumor cells and endothelial cells of tumor vasculature, but not normal vascular endothelial cells. In in vitro, the recombinant fusion protein of PNP-AV was shown to bind and kill breast cancer and endothelial cells when used in the enzyme prodrug therapy with fludarabine. Krais et al. proposed that this approach allows for systemic administration of the fusion protein, with targeted accumulation of PNP in the tumor. After clearance of PNP-AV from the bloodstream, fludarabine, the substrate of E. coli PNP, can be administered systemically, so that 2-fluoroadenine is generated at the surface of the endothelial cells lining the tumor vasculature. This freely diffusible molecule is able to enter the cell and inhibit protein, RNA, and DNA synthesis in endothelial cell of tumor blood vessel. Since fludarabine is not a substrate of human PNP, the conversion of fludarabine to 2-fluoroadenine will not occur in normal tissue. Therefore, authors suggested that this strategy can be successful as a targeted therapy for breast cancer (Krais et al., 2013). More recently, phase I dose-escalating trial of E. coli PNP-fludarabine treatment was demonstrated to be safe and effective in head and neck squamous cell carcinoma, adenoid cystic carcinoma and melanoma. Successful regression of tumors without significant toxicity was shown in this first-in-human study of an effective prodrug activation strategy using E. coli PNP (Rosenthal et al., 2015).
  
Entity Lymphoma, Bronchogenic carcinoma, Colon carcinoma, Breast cancer, Gastric cancer, Lung cancer, Ovarian cancer, Pancreatic adenocarcinoma
Note PNP activity was found higher in patients with indicated cancer types compared to control groups (Roberts et al., 2004; Rendeková et al., 1983; Sanfilippo et al., 1994; Vareed et al., 2011).
  
  
Entity Acute myeloid leukemia, Lymphoblastic leukemia, Chronic lymphocytic leukemia
Note A low level of PNP activity was found in mononuclear cells from patients with acute myeloid and lymphoblastic leukemia and with chronic lymphocytic leukemia (Morisaki et al., 1986).
  
  
Entity Severe Combined Immune Deficiency (SCID)
Note PNP deficiency is an autosomal recessive enzyme disorder, engaged in four percent of SCID cases in humans (Pannicke et al., 1996).
  
  
Entity Asthma
Note PNP activity was higher in patients with asthma than in either healthy subjects or patients with gout (Yamamoto et al., 1995).
  

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Citation

This paper should be referenced as such :
Rafig Gurbanov, Sinem Tunçer
PNP (Purine Nucleoside Phosphorylase)
Atlas Genet Cytogenet Oncol Haematol. 2018;22(11):431-438.
Free journal version : [ pdf ]   [ DOI ]
On line version : http://AtlasGeneticsOncology.org/Genes/PNPID46893ch14q11.html


External links

Nomenclature
HGNC (Hugo)PNP   7892
LRG (Locus Reference Genomic)LRG_91
Cards
AtlasPNPID46893ch14q11
Entrez_Gene (NCBI)PNP  4860  purine nucleoside phosphorylase
AliasesNP; PRO1837; PUNP
GeneCards (Weizmann)PNP
Ensembl hg19 (Hinxton)ENSG00000198805 [Gene_View]
Ensembl hg38 (Hinxton)ENSG00000198805 [Gene_View]  ENSG00000198805 [Sequence]  chr14:20469379-20478006 [Contig_View]  PNP [Vega]
ICGC DataPortalENSG00000198805
TCGA cBioPortalPNP
AceView (NCBI)PNP
Genatlas (Paris)PNP
WikiGenes4860
SOURCE (Princeton)PNP
Genetics Home Reference (NIH)PNP
Genomic and cartography
GoldenPath hg38 (UCSC)PNP  -     chr14:20469379-20478006 +  14q11.2   [Description]    (hg38-Dec_2013)
GoldenPath hg19 (UCSC)PNP  -     14q11.2   [Description]    (hg19-Feb_2009)
EnsemblPNP - 14q11.2 [CytoView hg19]  PNP - 14q11.2 [CytoView hg38]
Mapping of homologs : NCBIPNP [Mapview hg19]  PNP [Mapview hg38]
OMIM164050   613179   
Gene and transcription
Genbank (Entrez)AK098544 AK126154 AK307340 AK307364 AK313490
RefSeq transcript (Entrez)NM_000270
RefSeq genomic (Entrez)
Consensus coding sequences : CCDS (NCBI)PNP
Cluster EST : UnigeneHs.75514 [ NCBI ]
CGAP (NCI)Hs.75514
Alternative Splicing GalleryENSG00000198805
Gene ExpressionPNP [ NCBI-GEO ]   PNP [ EBI - ARRAY_EXPRESS ]   PNP [ SEEK ]   PNP [ MEM ]
Gene Expression Viewer (FireBrowse)PNP [ Firebrowse - Broad ]
SOURCE (Princeton)Expression in : [Datasets]   [Normal Tissue Atlas]  [carcinoma Classsification]  [NCI60]
GenevestigatorExpression in : [tissues]  [cell-lines]  [cancer]  [perturbations]  
BioGPS (Tissue expression)4860
GTEX Portal (Tissue expression)PNP
Human Protein AtlasENSG00000198805-PNP [pathology]   [cell]   [tissue]
Protein : pattern, domain, 3D structure
UniProt/SwissProtP00491   [function]  [subcellular_location]  [family_and_domains]  [pathology_and_biotech]  [ptm_processing]  [expression]  [interaction]
NextProtP00491  [Sequence]  [Exons]  [Medical]  [Publications]
With graphics : InterProP00491
Splice isoforms : SwissVarP00491
Catalytic activity : Enzyme2.4.2.1 [ Enzyme-Expasy ]   2.4.2.12.4.2.1 [ IntEnz-EBI ]   2.4.2.1 [ BRENDA ]   2.4.2.1 [ KEGG ]   
PhosPhoSitePlusP00491
Domaine pattern : Prosite (Expaxy)PNP_MTAP_2 (PS01240)   
Domains : Interpro (EBI)Nucleoside_phosphorylase_d    Nucleoside_phosphorylase_sf    Pur_Nuc_Pase_Ino/Guo-sp    Purine_phosphorylase    Purine_phosphorylase-2_CS   
Domain families : Pfam (Sanger)PNP_UDP_1 (PF01048)   
Domain families : Pfam (NCBI)pfam01048   
Conserved Domain (NCBI)PNP
DMDM Disease mutations4860
Blocks (Seattle)PNP
PDB (SRS)1M73    1PF7    1PWY    1RCT    1RFG    1RR6    1RSZ    1RT9    1ULA    1ULB    1V2H    1V3Q    1V41    1V45    1YRY    2A0W    2A0X    2A0Y    2OC4    2OC9    2ON6    2Q7O    3BGS    3D1V    3GB9    3GGS    3INY    3K8O    3K8Q    3PHB    4EAR    4EB8    4ECE    4GKA    5ETJ    5UGF   
PDB (PDBSum)1M73    1PF7    1PWY    1RCT    1RFG    1RR6    1RSZ    1RT9    1ULA    1ULB    1V2H    1V3Q    1V41    1V45    1YRY    2A0W    2A0X    2A0Y    2OC4    2OC9    2ON6    2Q7O    3BGS    3D1V    3GB9    3GGS    3INY    3K8O    3K8Q    3PHB    4EAR    4EB8    4ECE    4GKA    5ETJ    5UGF   
PDB (IMB)1M73    1PF7    1PWY    1RCT    1RFG    1RR6    1RSZ    1RT9    1ULA    1ULB    1V2H    1V3Q    1V41    1V45    1YRY    2A0W    2A0X    2A0Y    2OC4    2OC9    2ON6    2Q7O    3BGS    3D1V    3GB9    3GGS    3INY    3K8O    3K8Q    3PHB    4EAR    4EB8    4ECE    4GKA    5ETJ    5UGF   
PDB (RSDB)1M73    1PF7    1PWY    1RCT    1RFG    1RR6    1RSZ    1RT9    1ULA    1ULB    1V2H    1V3Q    1V41    1V45    1YRY    2A0W    2A0X    2A0Y    2OC4    2OC9    2ON6    2Q7O    3BGS    3D1V    3GB9    3GGS    3INY    3K8O    3K8Q    3PHB    4EAR    4EB8    4ECE    4GKA    5ETJ    5UGF   
Structural Biology KnowledgeBase1M73    1PF7    1PWY    1RCT    1RFG    1RR6    1RSZ    1RT9    1ULA    1ULB    1V2H    1V3Q    1V41    1V45    1YRY    2A0W    2A0X    2A0Y    2OC4    2OC9    2ON6    2Q7O    3BGS    3D1V    3GB9    3GGS    3INY    3K8O    3K8Q    3PHB    4EAR    4EB8    4ECE    4GKA    5ETJ    5UGF   
SCOP (Structural Classification of Proteins)1M73    1PF7    1PWY    1RCT    1RFG    1RR6    1RSZ    1RT9    1ULA    1ULB    1V2H    1V3Q    1V41    1V45    1YRY    2A0W    2A0X    2A0Y    2OC4    2OC9    2ON6    2Q7O    3BGS    3D1V    3GB9    3GGS    3INY    3K8O    3K8Q    3PHB    4EAR    4EB8    4ECE    4GKA    5ETJ    5UGF   
CATH (Classification of proteins structures)1M73    1PF7    1PWY    1RCT    1RFG    1RR6    1RSZ    1RT9    1ULA    1ULB    1V2H    1V3Q    1V41    1V45    1YRY    2A0W    2A0X    2A0Y    2OC4    2OC9    2ON6    2Q7O    3BGS    3D1V    3GB9    3GGS    3INY    3K8O    3K8Q    3PHB    4EAR    4EB8    4ECE    4GKA    5ETJ    5UGF   
SuperfamilyP00491
Human Protein Atlas [tissue]ENSG00000198805-PNP [tissue]
Peptide AtlasP00491
HPRD01247
IPIIPI00017672   IPI01024886   IPI01024768   IPI01025075   IPI01025985   
Protein Interaction databases
DIP (DOE-UCLA)P00491
IntAct (EBI)P00491
FunCoupENSG00000198805
BioGRIDPNP
STRING (EMBL)PNP
ZODIACPNP
Ontologies - Pathways
QuickGOP00491
Ontology : AmiGOnucleoside binding  purine nucleobase binding  purine-nucleoside phosphorylase activity  purine-nucleoside phosphorylase activity  purine-nucleoside phosphorylase activity  extracellular region  intracellular  nucleus  cytoplasm  cytoplasm  cytosol  cytosol  cytoskeleton  nucleobase-containing compound metabolic process  inosine catabolic process  purine nucleotide catabolic process  nicotinamide riboside catabolic process  immune response  drug binding  NAD biosynthesis via nicotinamide riboside salvage pathway  urate biosynthetic process  secretory granule lumen  positive regulation of T cell proliferation  phosphate ion binding  response to drug  response to drug  purine-containing compound salvage  neutrophil degranulation  positive regulation of alpha-beta T cell differentiation  extracellular exosome  interleukin-2 secretion  ficolin-1-rich granule lumen  
Ontology : EGO-EBInucleoside binding  purine nucleobase binding  purine-nucleoside phosphorylase activity  purine-nucleoside phosphorylase activity  purine-nucleoside phosphorylase activity  extracellular region  intracellular  nucleus  cytoplasm  cytoplasm  cytosol  cytosol  cytoskeleton  nucleobase-containing compound metabolic process  inosine catabolic process  purine nucleotide catabolic process  nicotinamide riboside catabolic process  immune response  drug binding  NAD biosynthesis via nicotinamide riboside salvage pathway  urate biosynthetic process  secretory granule lumen  positive regulation of T cell proliferation  phosphate ion binding  response to drug  response to drug  purine-containing compound salvage  neutrophil degranulation  positive regulation of alpha-beta T cell differentiation  extracellular exosome  interleukin-2 secretion  ficolin-1-rich granule lumen  
Pathways : KEGGPurine metabolism    Pyrimidine metabolism    Nicotinate and nicotinamide metabolism   
REACTOMEP00491 [protein]
REACTOME PathwaysR-HSA-74259 [pathway]   
NDEx NetworkPNP
Atlas of Cancer Signalling NetworkPNP
Wikipedia pathwaysPNP
Orthology - Evolution
OrthoDB4860
GeneTree (enSembl)ENSG00000198805
Phylogenetic Trees/Animal Genes : TreeFamPNP
HOVERGENP00491
HOGENOMP00491
Homologs : HomoloGenePNP
Homology/Alignments : Family Browser (UCSC)PNP
Gene fusions - Rearrangements
Fusion : QuiverPNP
Polymorphisms : SNP and Copy number variants
NCBI Variation ViewerPNP [hg38]
dbSNP Single Nucleotide Polymorphism (NCBI)PNP
dbVarPNP
ClinVarPNP
1000_GenomesPNP 
Exome Variant ServerPNP
ExAC (Exome Aggregation Consortium)ENSG00000198805
GNOMAD BrowserENSG00000198805
Varsome BrowserPNP
Genetic variants : HAPMAP4860
Genomic Variants (DGV)PNP [DGVbeta]
DECIPHERPNP [patients]   [syndromes]   [variants]   [genes]  
CONAN: Copy Number AnalysisPNP 
Mutations
ICGC Data PortalPNP 
TCGA Data PortalPNP 
Broad Tumor PortalPNP
OASIS PortalPNP [ Somatic mutations - Copy number]
Somatic Mutations in Cancer : COSMICPNP  [overview]  [genome browser]  [tissue]  [distribution]  
Mutations and Diseases : HGMDPNP
LOVD (Leiden Open Variation Database)Whole genome datasets
LOVD (Leiden Open Variation Database)LOVD - Leiden Open Variation Database
LOVD (Leiden Open Variation Database)LOVD 3.0 shared installation
LOVD (Leiden Open Variation Database)**PUBLIC** CCHMC Molecular Genetics Laboratory Mutation Database
BioMutasearch PNP
DgiDB (Drug Gene Interaction Database)PNP
DoCM (Curated mutations)PNP (select the gene name)
CIViC (Clinical Interpretations of Variants in Cancer)PNP (select a term)
intoGenPNP
NCG5 (London)PNP
Cancer3DPNP(select the gene name)
Impact of mutations[PolyPhen2] [Provean] [Buck Institute : MutDB] [Mutation Assessor] [Mutanalyser]
Diseases
OMIM164050    613179   
Orphanet671   
DisGeNETPNP
MedgenPNP
Genetic Testing Registry PNP
NextProtP00491 [Medical]
TSGene4860
GENETestsPNP
Target ValidationPNP
Huge Navigator PNP [HugePedia]
snp3D : Map Gene to Disease4860
BioCentury BCIQPNP
ClinGenPNP
Clinical trials, drugs, therapy
Chemical/Protein Interactions : CTD4860
Chemical/Pharm GKB GenePA31694
Clinical trialPNP
Miscellaneous
canSAR (ICR)PNP (select the gene name)
Probes
Litterature
PubMed81 Pubmed reference(s) in Entrez
GeneRIFsGene References Into Functions (Entrez)
CoreMinePNP
EVEXPNP
GoPubMedPNP
iHOPPNP
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

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