CBS Gene: Cystathionine Beta-Synthase – Function, Mutations, and Associated Diseases

The CBS gene encodes cystathionine beta-synthase, a heme-containing enzyme that catalyzes the condensation of homocysteine and serine to form cystathionine, the first step in the transsulfuration pathway. This enzyme is critical for homocysteine metabolism and the biosynthesis of cysteine. Mutations in CBS cause classic homocystinuria (OMIM #236200), an autosomal recessive disorder characterized by elevated homocysteine levels, thromboembolism, ectopia lentis, intellectual disability, and skeletal abnormalities. The gene is located on chromosome 21q22.3 and is expressed in multiple tissues, with highest levels in liver and kidney.

Tissue Expression

Cell Line Expression

Hotspot Mutations

Mutation functional classification

• Cysteine and methionine metabolism (KEGG:00270)

• Transsulfuration pathway (Reactome:R-HSA-1614558)

Cystathionine beta-synthase (UniProt P35520) is a 551-amino acid homotetrameric enzyme that uses pyridoxal phosphate (PLP) and heme as cofactors. It catalyzes the condensation of homocysteine and serine to form cystathionine. The protein is primarily expressed in liver and kidney, with lower levels in brain and other tissues. Mutations that reduce CBS activity cause homocystinuria, a metabolic disorder treatable with vitamin B6 in some cases.