PCCB Gene: Propionyl-CoA Carboxylase Subunit Beta – Function, Mutations, and Disease

The PCCB gene encodes the beta subunit of propionyl-CoA carboxylase, a biotin-dependent mitochondrial enzyme that catalyzes the carboxylation of propionyl-CoA to D-methylmalonyl-CoA. This reaction is a critical step in the catabolism of branched-chain amino acids, odd-chain fatty acids, and cholesterol side chains. Mutations in PCCB cause propionic acidemia (PA), an autosomal recessive metabolic disorder characterized by accumulation of propionic acid and its derivatives, leading to metabolic acidosis, neurological impairment, and multi-organ dysfunction.

Tissue Expression

Cell Line Expression

Hotspot Mutations

Mutation functional classification

• Propanoate metabolism

• Valine

• leucine and isoleucine degradation

• Metabolic pathways

The PCCB protein is the beta subunit of propionyl-CoA carboxylase (PCC), a heterododecameric enzyme composed of six alpha (PCCA) and six beta (PCCB) subunits. The beta subunit catalyzes the carboxyl transfer reaction using biotin as a cofactor. The enzyme is localized in the mitochondrial matrix and is essential for the metabolism of propionyl-CoA derived from catabolism of several amino acids, odd-chain fatty acids, and cholesterol. Deficiency leads to propionic acidemia.