Property Summary

NCBI Gene PubMed Count 87
PubMed Score 217.25
PubTator Score 237.65

Knowledge Summary

Patent (92,775)

Expression

  Differential Expression (5)

Disease log2 FC p
malignant mesothelioma 1.600 2.0e-07
psoriasis -4.000 4.5e-06
osteosarcoma -4.173 4.2e-13
glioblastoma 1.100 2.0e-04
medulloblastoma, large-cell 1.400 1.9e-05

Protein-protein Interaction (3)

MLP Assay (12)

AID Type Active / Inconclusive / Inactive Description
1541 confirmatory 7 / 87 / 26 Secondary assay for Activators of Human Liver Pyruvate Kinase
1543 confirmatory 8 / 79 / 21 Secondary assay for Activators of Human Reticulocyte Pyruvate Kinase
1781 confirmatory 0 / 32 / 81 Confirmation Concentration-Response Assay for Activators of Human Liver Pyruvate Kinase
1782 confirmatory 1 / 43 / 69 Confirmation Concentration-Response Assay for Activators of Human Reticulocyte Pyruvate Kinase
2534 confirmatory 0 / 3 / 95 Secondary Concentration-Response Assay for Activators of Human Reticulocyte Pyruvate Kinase: for Probe SAR
2535 confirmatory 0 / 2 / 189 Secondary Concentration-Response Assay for Activators of Human Liver Pyruvate Kinase: for Probe SAR
2562 confirmatory 1 / 24 / 138 Secondary LDH Assay for Activators of Human Reticulocyte Pyruvate Kinase: for Probe SAR
2625 confirmatory 0 / 19 / 174 Secondary LDH Assay for Activators of Human Liver Pyruvate Kinase: for Probe SAR
602379 confirmatory 0 / 0 / 6 qHTS for Activators of Human Muscle Isoform Pyruvate Kinase: Extended Characterization against Liver Pyruvate Kinase
602381 confirmatory 0 / 0 / 6 qHTS for Activators of Human Muscle Isoform 2 Pyruvate Kinase (PK): Extended Characterization using Reticulocyte PK
More...

Gene RIF (49)

PMID Text
26832193 An update of PKLR gene mutation database has been presented. (Review)
26829734 661G>A and 1528C>T mutations of PKLR gene are associated with pyruvate kinase deficiency.
26784545 PKLR promotes colorectal cancer liver colonization through induction of glutathione synthesis.
26728349 Two Novel Missense Mutations and a 5bp Deletion in the Erythroid-Specific Promoter of the PKLR Gene in Two Unrelated Patients With Pyruvate Kinase Deficient Transfusion-Dependent Chronic Nonspherocytic Hemolytic Anemia.
26658699 Pyruvate kinase variants modulate malaria phenotypes in a Thai population.
25629396 This study determined which interactions in the fructose 1,6-bisphosphate binding site of human liver pyruvate kinase contribute to allostery.
25388786 Partial pyruvate kinase deficiency aggravates the phenotypic expression of band 3 deficiency in a family with hereditary spherocytosis.
24969675 Case Report: unknown mutation in the pyruvate kinase gene (PKLR) identified from a neonate with severe jaundice.
24533562 11 patients from 10 unrelated pyruvate kinse deficiency families had 9 different disease-causing PKLR mutations, including 2 new ones: the point mutation c.878A>T (p.Asp293Val) and the frameshift deletion c.1553delG (p.(Arg518Leufs*12).
24375447 A new type of inherited PK hyperactivity having solely increased expression of a kinetically normal PK-R had no mutations or copy number variants. An upregulatory mutation at an unlinked site is proposed.
24330591 Hemolytic anemia associated with a novel heterozygous mutation 1183A in the pyruvate kinase gene has been found in two unrelated Jordanian patients.
23773021 Herpes simplex virus type 1 virion-derived US11 inhibits type 1 interferon-induced protein kinase R phosphorylation.
23270483 investigation of structure-function relationship of the N-terminus of liver pyruvate kinase and its regulation by oxidation/oxidative coupling and post-translational phosphorylation
23082140 A global geographical co-distribution between malaria and high frequency of PK deficiency seems to occur suggesting that malaria may be a selective force raising the frequency of this 277Lys variant.
22222284 These results suggest that SARS coronavirus could reduce pyruvate kinase activity via its nucleocapsid protein, and this may in turn cause disease.
21833022 Rich genetic diversity was detected in PKLR, including 59 single-nucleotide polymorphisms and several loss-of-function variants (frequency 1.5%).
21784452 We identified the pyruvate kinase liver/red cell enzyme gene mutation of 8 children previously diagnosed with pyruvate kinase deficiency who were living in a remote town in the western United States
21700219 The results reveal an acetylation regulation of pyruvate kinase and the link between lysine acetylation and chaperone-mediated autophagy.
20978194 Studies indicate that switching from pyruvate kinase spliced isoform PKM1 to PKM2 promotes aerobic glycolysis and provides a selective advantage for tumor formation, and the alternative splicing is controlled by hnRNP family members.
20682687 Observational study of gene-disease association and gene-environment interaction. (HuGE Navigator)
20602615 Observational study of gene-disease association. (HuGE Navigator)
19743919 These data suggest that reduced erythrocyte ATP levels may contribute to the malaria protection displayed by pyruvate kinase deficient erythrocytes in vitro.
19655166 Expression of pAkt, GLUT1 and TKTL1 were higher in breast cancer and DCIS than in normal tissue. Surprisingly, M2PK expression was highest in normal breast tissue.
19372549 Decreased pyruvate kinase M2 expression to oxaliplatin resistance in patients with colorectal cancer.
19320443 Results are consistent with a mechanism by which phosphorylation at L-PYK Ser12 interrupts an activating interaction of N-terminal residues (including those at positions 7-10) with the main body of the protein, as a means of inhibiting substrate affinity
19111066 We failed to provide evidence of an association between PKLR rs3020781 and type 2 diabetes, overweight, obesity or related quantitative metabolic phenotypes in large-scale studies of Danes
19111066 Observational study of gene-disease association. (HuGE Navigator)
19085939 Results provided a rationale for the observed enzyme deficiency and contribute to both a better understanding of the genotype-to-phenotype correlation in PK deficiency as well as the enzyme's structure and function.
18996102 Observational study of gene-disease association, gene-environment interaction, and pharmacogenomic / toxicogenomic. (HuGE Navigator)
18976975 Knockdown of pyruvate kinase, liver and RBC (PKLR) by siRNA has both activating and inhibiting activities on HIV-1 replication in HeLa P4/R5 cells, suggesting a regulatory role in HIV replication
18840520 Data report novel alterations of enzymescinvolved in glucose metabolism, including pyruvate kinase, that may be associated with the pathophysiology of insulin resistance and of renal damage in patients with type 1 diabetes mellitus with nephropathy.
18759866 This is the first study to correlate the clinical profile with the molecular defects causing PK deficiency from India where 10 novel mutations that produce non-spherocytic haemolytic anaemia were identified.
18726918 pyruvate kinase gene mutations are associated with anemia in pyruvate kinase deficient patients.
18698090 identified the -148C>T mutation in the erythroidspecific promoter of PKLR in 3 unrelated patients with low PK activity
18683378 The investigators identified a patient with pyruvate kinase deficiency caused by a mutation in the PK-LR gene.
18460648 Pyruvate kinase deficiency protects against malaria in humans
18420493 pyruvate kinase deficiency provides protection against infection and replication of P. falciparum in human erythrocytes, raising the possibility that mutant pyruvate kinase alleles may confer a protective advantage against malaria in human populations
18269685 Observational study of gene-disease association and gene-gene interaction. (HuGE Navigator)
17977029 14 different mutations in the coding sequence of the R-PK gene in 74 Iranian individuals with low enzyme activity were identified; the most common were the G1168A and G1529A mutations at exon 11 occurring in 54% of the cases
17574881 Northern Ireland has uncovered 4 new cases of pyruvate kinase deficiency. Molecular investigation revealed a total of six different mutations
17360088 genotype-phenotype association in pyruvate kinase deficiency [review]
16540430 The current work exploits a 'natural screen'- the 122 point mutations identified in the human gene encoding the erythrocyte PYK isozyme and associated with nonspherocytic hemolytic anemia.
15727904 regulatory element is a necessary transcriptional regulatory element in the erythroid-specific promoter of the human pyruvate kinase gene
12196482 Liver pyruvate kinase polymorphisms are associated with type 2 diabetes in northern European Caucasians.
12107439 PKLR- GBA region shows almost complete linkage disequilibrium over 70 kb in a set of worldwide populations.
11960989 first crystal structure of recombinant erythrocyte pyruvate kinase and the biochemical characterization of eight mutants found in nonspherocytic hemolytic anemia patients
11916152 Erythrocyte pyruvate kinase was modified with bromopyruvate and the kinetic behavior of the modified enzyme was investigated as model for the mutant enzyme associated with nonspherocytic hemolytic anemia.
11668614 congenital insensitivity to pain with anhidrosis (CIPA): novel mutations of the TRKA (NTRK1) gene, a putative uniparental disomy, and a linkage of the mutant TRKA and PKLR genes in a family with CIPA and pyruvate kinase deficiency
11459427 Observational study of genotype prevalence. (HuGE Navigator)

AA Sequence

MSIQENISSLQLRSWVSKSQRDLAKSILIGAPGGPAGYLRRASVAQLTQELGTAFFQQQQLPAAMADTFL      1 - 70
EHLCLLDIDSEPVAARSTSIIATIGPASRSVERLKEMIKAGMNIARLNFSHGSHEYHAESIANVREAVES     71 - 140
FAGSPLSYRPVAIALDTKGPEIRTGILQGGPESEVELVKGSQVLVTVDPAFRTRGNANTVWVDYPNIVRV    141 - 210
VPVGGRIYIDDGLISLVVQKIGPEGLVTQVENGGVLGSRKGVNLPGAQVDLPGLSEQDVRDLRFGVEHGV    211 - 280
DIVFASFVRKASDVAAVRAALGPEGHGIKIISKIENHEGVKRFDEILEVSDGIMVARGDLGIEIPAEKVF    281 - 350
LAQKMMIGRCNLAGKPVVCATQMLESMITKPRPTRAETSDVANAVLDGADCIMLSGETAKGNFPVEAVKM    351 - 420
QHAIAREAEAAVYHRQLFEELRRAAPLSRDPTEVTAIGAVEAAFKCCAAAIIVLTTTGRSAQLLSRYRPR    421 - 490
AAVIAVTRSAQAARQVHLCRGVFPLLYREPPEAIWADDVDRRVQFGIESGKLRGFLRVGDLVIVVTGWRP    491 - 560
GSGYTNIMRVLSIS                                                            561 - 574
//

Text Mined References (90)

PMID Year Title
26832193 2016 Red blood cell PK deficiency: An update of PK-LR gene mutation database.
26829734 2016 [Analysis and prenatal diagnosis of PKLR gene mutations in a family with pyruvate kinase deficiency].
26784545 2016 PKLR promotes colorectal cancer liver colonization through induction of glutathione synthesis.
26728349 2016 Two Novel Missense Mutations and a 5bp Deletion in the Erythroid-Specific Promoter of the PKLR Gene in Two Unrelated Patients With Pyruvate Kinase Deficient Transfusion-Dependent Chronic Nonspherocytic Hemolytic Anemia.
26658699 2015 Modulation of Malaria Phenotypes by Pyruvate Kinase (PKLR) Variants in a Thai Population.
25629396 2015 Distinguishing the interactions in the fructose 1,6-bisphosphate binding site of human liver pyruvate kinase that contribute to allostery.
25388786 2015 Partial pyruvate kinase deficiency aggravates the phenotypic expression of band 3 deficiency in a family with hereditary spherocytosis.
24969675 2014 A previously unknown mutation in the pyruvate kinase gene (PKLR) identified from a neonate with severe jaundice.
24533562 2014 Iron status in patients with pyruvate kinase deficiency: neonatal hyperferritinaemia associated with a novel frameshift deletion in the PKLR gene (p.Arg518fs), and low hepcidin to ferritin ratios.
24375447 2014 Novel type of red blood cell pyruvate kinase hyperactivity predicts a remote regulatory locus involved in PKLR gene expression.
24330591 2014 Hemolytic anemia associated with a novel heterozygote mutation 1183A in the PK-LR gene (PK- Jordan).
24275569 2014 An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome.
23773021 2013 Herpes simplex virus type 1 virion-derived US11 inhibits type 1 interferon-induced protein kinase R phosphorylation.
23270483 2013 Energetic coupling between an oxidizable cysteine and the phosphorylatable N-terminus of human liver pyruvate kinase.
23263486 2013 Genome-wide association analyses identify 18 new loci associated with serum urate concentrations.
23186163 2013 Toward a comprehensive characterization of a human cancer cell phosphoproteome.
23082140 2012 Pyruvate kinase deficiency in sub-Saharan Africa: identification of a highly frequent missense mutation (G829A;Glu277Lys) and association with malaria.
22222284 2012 SARS-CoV nucleocapsid protein interacts with cellular pyruvate kinase protein and inhibits its activity.
22001757 2011 Genome-wide association study identifies loci influencing concentrations of liver enzymes in plasma.
21833022 2012 Genetic diversity in human erythrocyte pyruvate kinase.
21794208 2011 Exome sequencing and unrelated findings in the context of complex disease research: ethical and clinical implications.
21784452 2011 Six children with pyruvate kinase deficiency from one small town: molecular characterization of the PK-LR gene.
21700219 2011 Acetylation targets the M2 isoform of pyruvate kinase for degradation through chaperone-mediated autophagy and promotes tumor growth.
20978194 2010 Turning on a fuel switch of cancer: hnRNP proteins regulate alternative splicing of pyruvate kinase mRNA.
20682687 2010 Common variants in 40 genes assessed for diabetes incidence and response to metformin and lifestyle intervention in the diabetes prevention program.
20602615 2010 Physiogenomic analysis of statin-treated patients: domain-specific counter effects within the ACACB gene on low-density lipoprotein cholesterol?
19743919 2009 Adenosine triphosphate depletion of erythrocytes simulates the phenotype associated with pyruvate kinase deficiency and confers protection against Plasmodium falciparum in vitro.
19655166 2010 Glycolytic phenotype in breast cancer: activation of Akt, up-regulation of GLUT1, TKTL1 and down-regulation of M2PK.
19372549 2009 A proteomic approach links decreased pyruvate kinase M2 expression to oxaliplatin resistance in patients with colorectal cancer and in human cell lines.
19320443 2009 An activating interaction between the unphosphorylated n-terminus of human liver pyruvate kinase and the main body of the protein is interrupted by phosphorylation.
19111066 2008 Lack of association between PKLR rs3020781 and NOS1AP rs7538490 and type 2 diabetes, overweight, obesity and related metabolic phenotypes in a Danish large-scale study: case-control studies and analyses of quantitative traits.
19085939 2009 Fifteen novel mutations in PKLR associated with pyruvate kinase (PK) deficiency: structural implications of amino acid substitutions in PK.
19056867 2009 Large-scale proteomics and phosphoproteomics of urinary exosomes.
18996102 2009 Physiogenomic comparison of edema and BMI in patients receiving rosiglitazone or pioglitazone.
18840520 2008 Glycolytic enzyme expression and pyruvate kinase activity in cultured fibroblasts from type 1 diabetic patients with and without nephropathy.
18759866 2009 Spectrum of novel mutations in the human PKLR gene in pyruvate kinase-deficient Indian patients with heterogeneous clinical phenotypes.
18726918 2008 Relative red blood cell enzyme levels as a clue to the diagnosis of pyruvate kinase deficiency.
18698090 2008 Characterization of the -148C>T promoter polymorphism in PKLR.
18683378 2008 Pyruvate kinase deficiency in a South African kindred caused by a 1529A mutation in the PK-LR gene.
18460648 2008 Pyruvate kinase deficiency protects against malaria in humans.
18420493 2008 Pyruvate kinase deficiency and malaria.
18269685 2008 Type 2 diabetes susceptibility genes on chromosome 1q21-24.
17977029 Prevalence of pyruvate kinase deficiency among the south Iranian population: quantitative assay and molecular analysis.
17574881 Pyruvate kinase deficient hemolytic anemia in the Northern Irish population.
17360088 2007 Pyruvate kinase deficiency: the genotype-phenotype association.
17192395 2007 Comparative gene expression profiling of in vitro differentiated megakaryocytes and erythroblasts identifies novel activatory and inhibitory platelet membrane proteins.
17081983 2006 Global, in vivo, and site-specific phosphorylation dynamics in signaling networks.
16540430 2006 Mining for allosteric information: natural mutations and positional sequence conservation in pyruvate kinase.
16289162 2006 The identification of myocilin-associated proteins in the human trabecular meshwork.
15996096 2005 Structural basis for tumor pyruvate kinase M2 allosteric regulation and catalysis.
15727904 Pyruvate kinase regulatory element 1 (PKR-RE1) mediates hexokinase gene expression in K562 cells.
15491302 2004 PK Aarau: first homozygous nonsense mutation causing pyruvate kinase deficiency.
15489334 2004 The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).
12477932 2002 Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences.
12393511 2003 Disruption of a novel regulatory element in the erythroid-specific promoter of the human PKLR gene causes severe pyruvate kinase deficiency.
12196482 2002 Liver pyruvate kinase polymorphisms are associated with type 2 diabetes in northern European Caucasians.
12107439 2002 PKLR- GBA region shows almost complete linkage disequilibrium over 70 kb in a set of worldwide populations.
12006652 2002 Paxillin-dependent paxillin kinase linker and p21-activated kinase localization to focal adhesions involves a multistep activation pathway.
11960989 2002 Structure and function of human erythrocyte pyruvate kinase. Molecular basis of nonspherocytic hemolytic anemia.
11916152 2001 Modification of human erythrocyte pyruvate kinase by an active site-directed reagent: bromopyruvate.
11698298 2001 Human erythrocyte pyruvate kinase: characterization of the recombinant enzyme and a mutant form (R510Q) causing nonspherocytic hemolytic anemia.
11668614 2001 Congenital insensitivity to pain with anhidrosis (CIPA): novel mutations of the TRKA (NTRK1) gene, a putative uniparental disomy, and a linkage of the mutant TRKA and PKLR genes in a family with CIPA and pyruvate kinase deficiency.
11459427 2001 Population genetics of four PKLR intragenic polymorphisms in Portugal and São Tomé e Príncipe (Gulf of Guinea).
11328279 2001 Molecular characterization of the PK-LR gene in sixteen pyruvate kinase-deficient patients.
10772876 2000 Hematologically important mutations: red cell pyruvate kinase (Third update).
10087985 1998 Hematologically important mutations: red cell pyruvate kinase (2nd update).
9886305 1998 A new sickle cell disease phenotype associating Hb S trait, severe pyruvate kinase deficiency (PK Conakry), and an alpha2 globin gene variant (Hb Conakry).
9827908 1998 Molecular characterization of the PK-LR gene in pyruvate kinase deficient Spanish patients. Red Cell Pathology Group of the Spanish Society of Haematology (AEHH).
9522120 1997 Complete genomic sequence of the human PK-L/R-gene includes four intragenic polymorphisms defining different haplotype backgrounds of normal and mutant PK-genes.
9482576 1998 Novel mutations and structural implications in R-type pyruvate kinase-deficient patients from Southern Italy.
9090535 1997 G-->T transition at cDNA nt 110 (K37Q) in the PKLR (pyruvate kinase) gene is the molecular basis of a case of hereditary increase of red blood cell ATP.
9075576 1996 Hematologically important mutations: red cell pyruvate kinase (1st update).
9057665 1997 Molecular analysis of 29 pyruvate kinase-deficient patients from central Europe with hereditary hemolytic anemia.
8807089 1996 Hematologically important mutations: red cell pyruvate kinase.
8664896 1996 Mutations in pyruvate kinase.
8483951 1993 Analysis of pyruvate kinase-deficiency mutations that produce nonspherocytic hemolytic anemia.
8481523 1993 Low substrate affinity of pyruvate kinase variant (PK Sapporo) caused by a single amino acid substitution (426 Arg-->Gln) associated with hereditary hemolytic anemia.
8476433 1993 Molecular basis of impaired pyruvate kinase isozyme conversion in erythroid cells: a single amino acid substitution near the active site and decreased mRNA content of the R-type PK.
8180378 1994 Mutations in the pyruvate kinase L gene in patients with hereditary hemolytic anemia.
8161798 1994 Molecular abnormality of erythrocyte pyruvate kinase deficiency in the Amish.
8125298 1994 Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides.
7706479 1995 Molecular study of pyruvate kinase deficient patients with hereditary nonspherocytic hemolytic anemia.
3566732 1987 Human liver type pyruvate kinase: cDNA cloning and chromosomal assignment.
3378452 1988 The human liver-type pyruvate kinase (PKL) gene is on chromosome 1 at band q21.
3126495 1988 Human liver type pyruvate kinase: complete amino acid sequence and the expression in mammalian cells.
2018831 1991 Point mutations in the L-type pyruvate kinase gene of two children with hemolytic anemia caused by pyruvate kinase deficiency.
1896471 1991 cDNA cloning of human R-type pyruvate kinase and identification of a single amino acid substitution (Thr384----Met) affecting enzymatic stability in a pyruvate kinase variant (PK Tokyo) associated with hereditary hemolytic anemia.
1602151 1992 Treatment of Haemophilus aphrophilus endocarditis with ciprofloxacin.
1536957 1992 Identical point mutations of the R-type pyruvate kinase (PK) cDNA found in unrelated PK variants associated with hereditary hemolytic anemia.
1445295 1992 Structural analysis of human pyruvate kinase L-gene and identification of the promoter activity in erythroid cells.