PKLR Gene (Pyruvate Kinase L/R): Function, Mutations, and Associated Diseases
Comprehensive biomedical resource on PKLR, including gene structure, expression, pathogenic variants, and clinical significance.
Gene Information Card
| Symbol | PKLR |
|---|---|
| Full Name | Pyruvate Kinase L/R |
| Gene Type | Protein coding |
| Chromosomal Location | 1q22 |
| NCBI Gene ID | 5313 ncbi.nlm.nih.gov/gene/5313 |
| Ensembl ID | ENSG00000143627 |
| UniProt ID | P30613 |
| OMIM ID | 609712 |
| HGNC ID | 9021 |
| Aliases | PK1, PKL, PKR, RPK, PyK, PK3 |
Description
The PKLR gene encodes pyruvate kinase, a key glycolytic enzyme that catalyzes the conversion of phosphoenolpyruvate to pyruvate, generating ATP. It has two tissue-specific isoforms: L-type (liver) and R-type (red blood cells), produced by alternative promoters. Mutations in PKLR cause pyruvate kinase deficiency, the most common hereditary non-spherocytic hemolytic anemia. The gene is also implicated in other metabolic and hematological conditions.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Pyruvate kinase deficiency (PKD) | Loss-of-function mutations reduce enzyme activity in red blood cells, impairing glycolysis and ATP production, leading to hemolytic anemia. | ClinVar, OMIM |
| Chronic hemolytic anemia | Same mechanism as PKD; severity varies with residual enzyme activity. | ClinVar, OMIM |
| Neonatal hyperbilirubinemia | Secondary to hemolysis in PKD patients, causing elevated bilirubin. | ClinVar |
| Gallstones (cholelithiasis) | Chronic hemolysis increases bilirubin load, predisposing to pigment gallstones. | ClinVar |
| Iron overload | Chronic hemolysis and transfusions can lead to iron accumulation. | ClinVar |
| Aplastic crisis | Parvovirus B19 infection suppresses erythropoiesis, worsening anemia in PKD. | ClinVar |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Liver | 30.1 | High |
| Bone Marrow | 20.5 | Medium |
| Spleen | 15.2 | Medium |
| Whole Blood | 12.8 | Medium |
| Small Intestine | 8.4 | Low |
| Kidney | 5.1 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| K-562 (leukemia) | 25.3 | High expression |
| HepG2 (liver cancer) | 22.7 | High expression |
| HL-60 (promyeloblast) | 18.9 | Medium |
| MCF7 (breast cancer) | 3.2 | Low |
| A549 (lung cancer) | 2.1 | Low |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1529G>A (p.Arg510Gln) | Missense | ~20% of PKD alleles | Reduced enzyme activity, causes hemolytic anemia |
| c.1456C>T (p.Arg486Trp) | Missense | ~10% of PKD alleles | Severe enzyme deficiency, common in Northern European |
| c.994G>A (p.Gly332Ser) | Missense | ~5% of PKD alleles | Moderate enzyme deficiency |
| c.1261A>G (p.Ile421Val) | Missense | ~3% of PKD alleles | Mild phenotype, often asymptomatic |
| c.721G>T (p.Glu241Ter) | Nonsense | Rare | Truncated protein, complete loss of function |
| c.1468C>T (p.Arg490Ter) | Nonsense | Rare | Premature stop, severe deficiency |
| c.1174A>G (p.Thr392Ala) | Missense | Rare | Reduced stability, associated with PKD |
| c.1493C>T (p.Pro498Leu) | Missense | Rare | Impaired catalytic activity |
Mutation functional classification
Loss of Function (LOF)
Most PKLR mutations are loss-of-function, reducing or abolishing pyruvate kinase activity in red blood cells. This leads to ATP depletion, oxidative stress, and premature red cell destruction, causing hemolytic anemia.
Gain of Function (GOF)
No gain-of-function mutations have been reported for PKLR. The enzyme's activity is tightly regulated; increased activity is not associated with disease.
Dominant Negative (DN)
Some missense mutations may exert a dominant-negative effect by producing subunits that interfere with the tetrameric enzyme complex, but this is rare. Most PKD cases are autosomal recessive, requiring biallelic mutations.
View complete mutation data：
Gene Ontology (GO)
| • ATP binding | • Kinase activity |
| • Magnesium ion binding | • Pyruvate kinase activity |
| • Phosphoenolpyruvate binding | • Glycolysis |
| • Cytoplasm | • Cytosol |
Pathways
• Glycolysis / Gluconeogenesis
• Pyruvate metabolism
• Metabolic pathways
• Carbon metabolism
• HIF-1 signaling pathway (indirect)
Protein Summary
The PKLR gene encodes two isoforms: the L-type (liver) and R-type (red blood cell) pyruvate kinase, both generated by alternative promoters. The protein is a tetramer of 4 identical subunits, each containing a catalytic domain. It catalyzes the final step of glycolysis, converting phosphoenolpyruvate to pyruvate with ATP production. In red blood cells, this enzyme is essential for maintaining ATP levels and cell integrity. Deficiency leads to hemolytic anemia. The protein is allosterically regulated by fructose-1,6-bisphosphate (activator) and ATP (inhibitor).
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| PKLR Knockout HEK293 Cell Line | EDJ-KQ5470 | Human | 5313 | Details Get a Quote |
| PKLR Knockout HeLa Cell Line | EDJ-KQ54147 | Human | 5313 | Details Get a Quote |
| PKLR Knockout A-549 Cell Line | EDJ-KQ62639 | Human | 5313 | Details Get a Quote |
| PKLR Knockout HCT 116 Cell Line | EDJ-KQ71107 | Human | 5313 | Details Get a Quote |
Displaying Records 1 To 4 Of 4 Records
