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Genetics Home Reference: your guide to understanding genetic conditions
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PKLR

Reviewed April 2012

What is the official name of the PKLR gene?

The official name of this gene is “pyruvate kinase, liver and RBC.”

PKLR is the gene's official symbol. The PKLR gene is also known by other names, listed below.

What is the normal function of the PKLR gene?

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.

How are changes in the PKLR gene related to health conditions?

pyruvate kinase deficiency - caused by mutations in the PKLR gene

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).

other disorders - associated with the PKLR gene

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.

Where is the PKLR gene located?

Cytogenetic Location: 1q21

Molecular Location on chromosome 1: base pairs 155,289,292 to 155,308,722

The PKLR gene is located on the long (q) arm of chromosome 1 at position 21.

The PKLR gene is located on the long (q) arm of chromosome 1 at position 21.

More precisely, the PKLR gene is located from base pair 155,289,292 to base pair 155,308,722 on chromosome 1.

See How do geneticists indicate the location of a gene? (http://ghr.nlm.nih.gov/handbook/howgeneswork/genelocation) in the Handbook.

Where can I find additional information about PKLR?

You and your healthcare professional may find the following resources about PKLR helpful.

You may also be interested in these resources, which are designed for genetics professionals and researchers.

What other names do people use for the PKLR gene or gene products?

  • KPYR_HUMAN
  • PK1
  • PKL
  • PKR
  • PKRL
  • pyruvate kinase 1
  • pyruvate kinase isozyme R/L
  • pyruvate kinase, liver and blood cell
  • pyruvate kinase type L
  • red cell/liver pyruvate kinase
  • RPK
  • R-type/L-type pyruvate kinase

See How are genetic conditions and genes named? (http://ghr.nlm.nih.gov/handbook/mutationsanddisorders/naming) in the Handbook.

What glossary definitions help with understanding PKLR?

acids ; adenosine diphosphate ; adenosine triphosphate ; ADP ; anemia ; ATP ; bile ; bilirubin ; cell ; deficiency ; enzyme ; expressed ; gallbladder ; gene ; glucose ; iron ; isozyme ; jaundice ; kinase ; malaria ; molecule ; mutation ; oxygen ; pallor ; phosphate ; phosphorus ; protein ; RBC ; simple sugar

You may find definitions for these and many other terms in the Genetics Home Reference Glossary (http://www.ghr.nlm.nih.gov/glossary).

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. (http://www.ncbi.nlm.nih.gov/pubmed/18420493?dopt=Abstract)
  • 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. (http://www.ncbi.nlm.nih.gov/pubmed/10828047?dopt=Abstract)
  • Climent F, Roset F, Repiso A, Pérez 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. Review. (http://www.ncbi.nlm.nih.gov/pubmed/19519368?dopt=Abstract)
  • 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. (http://www.ncbi.nlm.nih.gov/pubmed/18460648?dopt=Abstract)
  • NCBI Gene (http://www.ncbi.nlm.nih.gov/gene/5313)
  • OMIM: PYRUVATE KINASE, LIVER AND RED BLOOD CELL (http://omim.org/entry/609712)
  • 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. (http://www.ncbi.nlm.nih.gov/pubmed/21815188?dopt=Abstract)
  • 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. (http://www.ncbi.nlm.nih.gov/pubmed/19085939?dopt=Abstract)
  • 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. Epub 2005 Jul 28. Review. (http://www.ncbi.nlm.nih.gov/pubmed/16051738?dopt=Abstract)
  • 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. Epub 2007 Mar 13. Review. (http://www.ncbi.nlm.nih.gov/pubmed/17360088?dopt=Abstract)
  • 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. Review. (http://www.ncbi.nlm.nih.gov/pubmed/15982340?dopt=Abstract)

 

The resources on this site should not be used as a substitute for professional medical care or advice. Users seeking information about a personal genetic disease, syndrome, or condition should consult with a qualified healthcare professional. See How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.

 
Reviewed: April 2012
Published: October 20, 2014