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Normal Function
The PKLR gene is active (expressed) in the liver and in red blood cells, where it provides instructions for producing an enzyme called pyruvate kinase. This enzyme is involved in a critical energy-producing process known as glycolysis. During glycolysis, the simple sugar glucose is broken down to produce energy. Specifically, pyruvate kinase is involved in the last step of the glycolytic pathway. In this step, a cluster of oxygen and phosphorus atoms (a phosphate group) is moved from a molecule called phosphoenolpyruvate to another molecule called adenosine diphosphate (ADP), resulting in molecules called pyruvate and adenosine triphosphate (ATP). ATP is the cell's main energy source.
Health Conditions Related to Genetic Changes
Pyruvate kinase deficiency
More than 200 mutations in the PKLR gene have been identified in people with pyruvate kinase deficiency. People with this disorder have two PKLR gene mutations in each cell. Most of the mutations that cause pyruvate kinase deficiency replace single protein building blocks (amino acids) in the pyruvate kinase enzyme or result in an enzyme that is abnormally short. The mutations lead to reduced pyruvate kinase enzyme function, causing a shortage of ATP in red blood cells and increased levels of other molecules produced earlier in the glycolysis process. The abnormal red blood cells are gathered up by the spleen and destroyed.
The resulting shortage of oxygen-carrying red blood cells (anemia) leads to extreme tiredness (fatigue), unusually pale skin (pallor), and shortness of breath. Iron and a molecule called bilirubin are released when red blood cells are destroyed, resulting in an excess of these substances circulating in the blood. Excess bilirubin in the blood causes yellowing of the eyes and skin (jaundice) and increases the risk of developing small pebble-like deposits in the gallbladder or bile ducts (gallstones).
More About This Health ConditionOther disorders
Researchers believe that people who have one copy of a PKLR gene mutation in each cell may be partially protected against malaria, an infectious disease carried by a certain type of mosquito. Mutations that lead to a reduction in the amount of functional pyruvate kinase appear to make it more difficult for this parasite to invade red blood cells. Studies indicate that individuals from populations in Africa, where malaria is a frequent cause of death in children, carry one copy of a mutated PKLR gene in each cell more than twice as often as individuals of European descent. The increased frequency of PKLR gene mutations may contribute to resistance against malaria in these African populations.
Other Names for This Gene
- KPYR_HUMAN
- PK1
- PKL
- PKR
- PKRL
- pyruvate kinase 1
- pyruvate kinase isozyme R/L
- pyruvate kinase type L
- pyruvate kinase, liver and blood cell
- pyruvate kinase, liver and RBC
- R-type/L-type pyruvate kinase
- red cell/liver pyruvate kinase
- RPK
Additional Information & Resources
Tests Listed in the Genetic Testing Registry
Scientific Articles on PubMed
Catalog of Genes and Diseases from OMIM
References
- Ayi K, Min-Oo G, Serghides L, Crockett M, Kirby-Allen M, Quirt I, Gros P, Kain KC. Pyruvate kinase deficiency and malaria. N Engl J Med. 2008 Apr 24;358(17):1805-10. doi: 10.1056/NEJMoa072464. Epub 2008 Apr 16. Citation on PubMed
- Beutler E, Gelbart T. Estimating the prevalence of pyruvate kinase deficiency from the gene frequency in the general white population. Blood. 2000 Jun 1;95(11):3585-8. Citation on PubMed
- Climent F, Roset F, Repiso A, Perez de la Ossa P. Red cell glycolytic enzyme disorders caused by mutations: an update. Cardiovasc Hematol Disord Drug Targets. 2009 Jun;9(2):95-106. doi: 10.2174/187152909788488636. Citation on PubMed
- Durand PM, Coetzer TL. Pyruvate kinase deficiency protects against malaria in humans. Haematologica. 2008 Jun;93(6):939-40. doi: 10.3324/haematol.12450. Epub 2008 May 6. No abstract available. Citation on PubMed
- Rider NL, Strauss KA, Brown K, Finkenstedt A, Puffenberger EG, Hendrickson CL, Robinson DL, Muenke N, Tselepis C, Saunders L, Zoller H, Morton DH. Erythrocyte pyruvate kinase deficiency in an old-order Amish cohort: longitudinal risk and disease management. Am J Hematol. 2011 Oct;86(10):827-34. doi: 10.1002/ajh.22118. Epub 2011 Aug 3. Citation on PubMed
- van Wijk R, Huizinga EG, van Wesel AC, van Oirschot BA, Hadders MA, van Solinge WW. Fifteen novel mutations in PKLR associated with pyruvate kinase (PK) deficiency: structural implications of amino acid substitutions in PK. Hum Mutat. 2009 Mar;30(3):446-53. doi: 10.1002/humu.20915. Citation on PubMed
- van Wijk R, van Solinge WW. The energy-less red blood cell is lost: erythrocyte enzyme abnormalities of glycolysis. Blood. 2005 Dec 15;106(13):4034-42. doi: 10.1182/blood-2005-04-1622. Epub 2005 Jul 28. Citation on PubMed
- Zanella A, Fermo E, Bianchi P, Chiarelli LR, Valentini G. Pyruvate kinase deficiency: the genotype-phenotype association. Blood Rev. 2007 Jul;21(4):217-31. doi: 10.1016/j.blre.2007.01.001. Epub 2007 Mar 13. Citation on PubMed
- Zanella A, Fermo E, Bianchi P, Valentini G. Red cell pyruvate kinase deficiency: molecular and clinical aspects. Br J Haematol. 2005 Jul;130(1):11-25. doi: 10.1111/j.1365-2141.2005.05527.x. Citation on PubMed
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