Propionic acidemia (PA) is a recessive disorder caused by a deficiency of 
propionyl-CoA carboxylase (PCC), a dodecameric enzyme composed of two different 
proteins alpha-PCC and beta-PCC, nuclear encoded by the PCCA and PCCB genes, 
respectively. Mutations in either gene cause PA and to date, up to 47 different 
allelic variations in the PCCB gene have been identified in different 
populations. In this work, we describe the expression studies of 18 PCCB 
sequence changes in order to elucidate their functional consequences. We have 
used a PCCB-deficient transformed fibroblast cell line to target the wild-type 
and mutant proteins to their physiological situation, analysing the effect of 
the mutations on PCC activity and protein stability. Of the 18 mutant proteins 
tested for activity, those carrying the L17M and A497V substitutions showed an 
activity similar to the wild-type one, which proves that these changes do not 
have any effect on protein activity. The other 16 mutant proteins exhibited two 
different functional behaviours, 3 retained substantial activity (K218R, R410W 
and N536D), and the remaining 13 proteins showed null or very low activity. 
Western blot analysis demonstrated instability only for the L519P, R512C and 
G112D mutant proteins. We have proved the pathogenicity of R67S, R165Q and G112D 
mutation in PCCB gene, expressed for the first time in this work. The 
information derived from the expression analysis is discussed in the phenotype 
and genotype context in order to improve the knowledge of this complex disease.