RGD Reference Report - Molecular abnormality of erythrocyte pyruvate kinase deficiency in the Amish. - Rat Genome Database

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Molecular abnormality of erythrocyte pyruvate kinase deficiency in the Amish.

Authors: Kanno, H  Ballas, SK  Miwa, S  Fujii, H  Bowman, HS 
Citation: Kanno H, etal., Blood. 1994 Apr 15;83(8):2311-6.
RGD ID: 11535983
Pubmed: PMID:8161798   (View Abstract at PubMed)

We describe the cellular and molecular biologic studies of the erythrocyte pyruvate kinase (PK) deficiency of the Amish deme in Pennsylvania. Nucleotide sequencing of the patient's PK gene showed a point mutation, CGC to CAC, corresponding to no. 1436 from the translational initiation site of the R-type PK (R-PK) mRNA, and it caused a single amino acid substitution from Arg to His at the 479th amino acid residue of the R-PK. The substituted Arg residue is located in the C domain of PK subunit, that is essential for both the intersubunit contact and the allosteric regulation. Because this enzyme shows the catalytic activity only as a dimer or tetramer, it is rational that the structural alteration would result in severe PK deficiency. To elucidate the effect of the PK deficiency on red blood cell (RBC) membrane, we performed the cellular studies of the patients' RBCs. Ouabain-insensitive K+ efflux was increased to 142% to 145% of normal controls and not inhibited by furosemide, as previously observed in HbSC disease RBCs.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
congenital nonspherocytic hemolytic anemia  IAGP 11535983DNA:missense mutation:cds:p.R479H (human)RGD 
congenital nonspherocytic hemolytic anemia  ISOPKLR (Homo sapiens)11535983; 11535983DNA:missense mutation:cds:p.R479H (human)RGD 

Phenotype Annotations    Click to see Annotation Detail View

Manual Human Phenotype Annotations - RGD

TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
Reduced red cell pyruvate kinase level  IAGP 11535983DNA:missense mutation:cds:p.R479HRGD 
Objects Annotated

Genes (Rattus norvegicus)
Pklr  (pyruvate kinase L/R)

Genes (Mus musculus)
Pklr  (pyruvate kinase liver and red blood cell)

Genes (Homo sapiens)
PKLR  (pyruvate kinase L/R)


Additional Information