1. Gene Aliases

Pklr, Pyruvate Kinase L/R, Pyruvate Kinase, Liver And RBC, Red Cell/Liver Pyruvate Kinase, R-Type/L-Type Pyruvate Kinase, Pyruvate Kinase Isozymes L/R, Pyruvate Kinase PKLR, Pyruvate Kinase 1, EC 2.7.1.40, PK1, PKL, Pyruvate Kinase, Liver And Blood Cell, Pyruvate Kinase Isozymes R/L, Pyruvate Kinase Isozyme R/L, Pyruvate Kinase Type L, PKRL, RPK

[https://www.genecards.org/cgi-bin/carddisp.pl?gene=PKLR&keywords=Pklr].

2. Association with Toxicity and/or Disease at a Transcriptional Level

3. Summary of Protein Family and Structure

4. Proteins Known to Interact with Gene Product

Interactions with experimental support

Interactions with text mining support

5. Links to Gene Databases

6. GO Terms, MSigDB Signatures, Pathways Containing Gene with Descriptions of Gene Sets

Pathways:

GO terms:

cellular response to epinephrine stimulus [Any process that results in a change in state or activity of a cell (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of an epinephrine stimulus. Epinephrine is a catecholamine that has the formula C9H13NO3; it is secreted by the adrenal medulla to act as a hormone, and released by certain neurons to act as a neurotransmitter active in the central nervous system.|Note that epinephrine and norepinephrine are ligands for the same receptors, and there are multiple adrenergic receptors. GO:0071872]

cellular response to insulin stimulus [Any process that results in a change in state or activity of a cell (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of an insulin stimulus. Insulin is a polypeptide hormone produced by the islets of Langerhans of the pancreas in mammals, and by the homologous organs of other organisms. GO:0032869]

glycolytic process [The chemical reactions and pathways resulting in the breakdown of a carbohydrate into pyruvate, with the concomitant production of a small amount of ATP and the reduction of NAD(P) to NAD(P)H. Glycolysis begins with the metabolism of a carbohydrate to generate products that can enter the pathway and ends with the production of pyruvate. Pyruvate may be converted to acetyl-coenzyme A, ethanol, lactate, or other small molecules. GO:0006096]

phosphorylation [The process of introducing a phosphate group into a molecule, usually with the formation of a phosphoric ester, a phosphoric anhydride or a phosphoric amide. GO:0016310]

pyruvate biosynthetic process [The chemical reactions and pathways resulting in the formation of pyruvate, 2-oxopropanoate. GO:0042866]

response to ATP [Any process that results in a change in state or activity of a cell or an organism (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of an ATP (adenosine 5'-triphosphate) stimulus. GO:0033198]

response to cAMP [Any process that results in a change in state or activity of a cell or an organism (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a cAMP (cyclic AMP, adenosine 3',5'-cyclophosphate) stimulus. GO:0051591]

response to glucose [Any process that results in a change in state or activity of a cell or an organism (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a glucose stimulus. GO:0009749]

response to hypoxia [Any process that results in a change in state or activity of a cell or an organism (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a stimulus indicating lowered oxygen tension. Hypoxia, defined as a decline in O2 levels below normoxic levels of 20.8 - 20.95%, results in metabolic adaptation at both the cellular and organismal level.|Note that this term should not be confused with 'response to anoxia ; GO:0034059'. Note that in laboratory studies, hypoxia is typically studied at O2 concentrations ranging from 0.1 - 5%. GO:0001666]

response to metal ion [Any process that results in a change in state or activity of a cell or an organism (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a metal ion stimulus. GO:0010038]

response to nutrient [Any process that results in a change in state or activity of a cell or an organism (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a nutrient stimulus. GO:0007584]

response to other organism [Any process that results in a change in state or activity of a cell or an organism (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a stimulus from another living organism. GO:0051707]

MSigDB Signatures:

WP_NONALCOHOLIC_FATTY_LIVER_DISEASE: Nonalcoholic fatty liver disease [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/WP_NONALCOHOLIC_FATTY_LIVER_DISEASE.html]

KEGG_GLYCOLYSIS_GLUCONEOGENESIS: Glycolysis / Gluconeogenesis [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/KEGG_GLYCOLYSIS_GLUCONEOGENESIS.html]

REACTOME_GLUCOSE_METABOLISM: Glucose metabolism [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/REACTOME_GLUCOSE_METABOLISM.html]

REACTOME_INFECTIOUS_DISEASE: Infectious disease [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/REACTOME_INFECTIOUS_DISEASE.html]

REACTOME_GLYCOLYSIS: Glycolysis [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/REACTOME_GLYCOLYSIS.html]

KEGG_PYRUVATE_METABOLISM: Pyruvate metabolism [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/KEGG_PYRUVATE_METABOLISM.html]

KEGG_MEDICUS_REFERENCE_GLYCOLYSIS: Pathway Definition from KEGG: Glc-6P -- GPI >> PFK >> ALDO >> GAPDH >> PGK1/2 >> (PGAM,BPGM) >> ENO1/2/3/4 >> (PKLR,PKM) >> (LDH,LDHAL6) -> Lactate [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/KEGG_MEDICUS_REFERENCE_GLYCOLYSIS.html]

WP_GLYCOLYSIS_AND_GLUCONEOGENESIS: Glycolysis and gluconeogenesis [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/WP_GLYCOLYSIS_AND_GLUCONEOGENESIS.html]

REACTOME_METABOLISM_OF_CARBOHYDRATES: Metabolism of carbohydrates [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/REACTOME_METABOLISM_OF_CARBOHYDRATES.html]

REACTOME_INTEGRATION_OF_ENERGY_METABOLISM: Integration of energy metabolism [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/REACTOME_INTEGRATION_OF_ENERGY_METABOLISM.html]

KEGG_PURINE_METABOLISM: Purine metabolism [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/KEGG_PURINE_METABOLISM.html]

REACTOME_VIRAL_INFECTION_PATHWAYS: Viral Infection Pathways [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/REACTOME_VIRAL_INFECTION_PATHWAYS.html]

KEGG_INSULIN_SIGNALING_PATHWAY: Insulin signaling pathway [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/KEGG_INSULIN_SIGNALING_PATHWAY.html]

REACTOME_CHREBP_ACTIVATES_METABOLIC_GENE_EXPRESSION: ChREBP activates metabolic gene expression [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/REACTOME_CHREBP_ACTIVATES_METABOLIC_GENE_EXPRESSION.html]

KEGG_TYPE_II_DIABETES_MELLITUS: Type II diabetes mellitus [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/KEGG_TYPE_II_DIABETES_MELLITUS.html]

WP_METABOLIC_EPILEPTIC_DISORDERS: Metabolic Epileptic Disorders [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/WP_METABOLIC_EPILEPTIC_DISORDERS.html]

REACTOME_SARS_COV_1_INFECTION: SARS-CoV-1 Infection [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/REACTOME_SARS_COV_1_INFECTION.html]

REACTOME_SARS_COV_INFECTIONS: SARS-CoV Infections [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/REACTOME_SARS_COV_INFECTIONS.html]

REACTOME_DEVELOPMENTAL_BIOLOGY: Developmental Biology [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/REACTOME_DEVELOPMENTAL_BIOLOGY.html]

WP_CLEAR_CELL_RENAL_CELL_CARCINOMA_PATHWAYS: Clear cell renal cell carcinoma pathways [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/WP_CLEAR_CELL_RENAL_CELL_CARCINOMA_PATHWAYS.html]

KEGG_MATURITY_ONSET_DIABETES_OF_THE_YOUNG: Maturity onset diabetes of the young [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/KEGG_MATURITY_ONSET_DIABETES_OF_THE_YOUNG.html]

7. Gene Descriptions

NCBI Gene Summary: The protein encoded by this gene is a pyruvate kinase that catalyzes the transphosphorylation of phohsphoenolpyruvate into pyruvate and ATP, which is the rate-limiting step of glycolysis. Defects in this enzyme, due to gene mutations or genetic variations, are the common cause of chronic hereditary nonspherocytic hemolytic anemia (CNSHA or HNSHA). Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

GeneCards Summary: PKLR (Pyruvate Kinase L/R) is a Protein Coding gene. Diseases associated with PKLR include Pyruvate Kinase Deficiency Of Red Cells and Adenosine Triphosphate, Elevated, Of Erythrocytes. Among its related pathways are glycolysis (BioCyc) and Infectious disease. Gene Ontology (GO) annotations related to this gene include magnesium ion binding and pyruvate kinase activity. An important paralog of this gene is PKM.

UniProtKB/Swiss-Prot Summary: Pyruvate kinase that catalyzes the conversion of phosphoenolpyruvate to pyruvate with the synthesis of ATP, and which plays a key role in glycolysis.

8. Cellular Location of Gene Product

Cytoplasmic expression mainly in hepatocytes, hematopoietic cells, intestines and cells in renal tubules. Localized to the cytosol. Predicted location: Intracellular [https://www.proteinatlas.org/ENSG00000143627/subcellular]

9. Mechanistic Information

Summary

The PKLR gene encodes pyruvate kinase L/R, which is crucial for glycolysis, converting phosphoenolpyruvate to pyruvate and generating ATP. [CS: 10] In liver diseases and toxicities, the dysregulation of PKLR often manifests as an adaptive response to altered metabolic demands or damage. [CS: 8] For instance, in nonalcoholic fatty liver disease (NAFLD) and hepatocellular carcinoma (HCC), increased PKLR expression enhances glycolysis to meet the high energy demands of proliferating cells and tumor growth. [CS: 7] This upregulation likely helps the liver cells to adapt to the increased metabolic requirements of these disease states. [CS: 6]

In conditions like toxicant-associated steatotic liver disease, PKLR expression may decrease as seen in response to chlordane exposure. [CS: 5] This reduction could be a response to altered hepatic energy metabolism, where the liver shifts its metabolic focus away from glycolysis, possibly to reduce energy expenditure or adapt to a toxin-altered environment. [CS: 4] Similarly, under conditions like vitamin A deficiency, the downregulation of PKLR in Zucker rats indicates a metabolic shift, potentially reducing glycolytic flux in response to altered nutritional states. [CS: 5] These changes in PKLR expression represent a cellular attempt to maintain homeostasis and adapt to the metabolic challenges presented by liver diseases and toxic exposures. [CS: 6]

10. Upstream Regulators

11. Tissues/Cell Type Where Genes are Overexpressed

Tissue type enchanced: bone marrow, kidney, liver (tissue enhanced) [https://www.proteinatlas.org/ENSG00000143627/tissue]

Cell type enchanced: erythroid cells, hepatocytes, late spermatids, proximal enterocytes, proximal tubular cells (group enriched) [https://www.proteinatlas.org/ENSG00000143627/single+cell+type]

12. Role of Gene in Other Tissues

13. Chemicals Known to Elicit Transcriptional Response of Biomarker in Tissue of Interest

Compounds that increase expression of the gene:

Compounds that decrease expression of the gene:

14. DisGeNet Biomarker Associations to Disease in Organ of Interest

Most relevant biomarkers with lower score or lower probability of association with disease or organ of interest: