Homo sapiens pyruvate kinase, liver and RBC

(PKLR), RefSeqGene on chromosome 1

Disease: Hereditary nonspherocytic hemolytic anemia

Mechanism leading to disease

● Several types of mutations at chromosomal location 1q22 can lead to the

disease.
● In the most severe example of alteration, unequal crossing over during
meiosis results in one product lacking exon 11 and the other one having
two copies of it.
● The resulting defective protein (pyruvate kinase) is either eliminated by
proteolysis or survives with very impaired activity.
● The protein is thus unable to contribute to glycolysis, which results in the
premature death of red blood cells.
The mutation affects only the last step of glycolysis - conversion of
phosphoenolpyruvate to pyruvate.
Homology in a model organism
Model organism: Mus musculus
Gene: Pklr pyruvate kinase liver and red blood cell

● Pklr deficiency was found in mutant mice, in association with hereditary nonspherocytic
hemolytic anemia, just like in humans.
● In response, bone marrow transplantation was attempted on mice. The experiment did cure the
anemia and provided a possible treatment approach for the disease in humans.

References:

M. Morimoto, H. Kanno, H. Asai, et al. Pyruvate kinase deficiency of mice associated with nonspherocytic hemolytic anemia and cure of the
anemia by marrow transplantation without host irradiation Blood, 86 (1995), pp. 4323–4330

http://omim.org/entry/266200?search=PKLR&highlight=pklr
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC295683/pdf/jcinvest00025-0286.pdf
https://www.ncbi.nlm.nih.gov/gene/18770