SHMT1 Gene - Serine Hydroxymethyltransferase 1 | Function, Mutations & Disease

SHMT1 encodes the cytosolic form of serine hydroxymethyltransferase, a pyridoxal phosphate-dependent enzyme that catalyzes the reversible conversion of serine and tetrahydrofolate to glycine and 5,10-methylenetetrahydrofolate. This reaction is central to one-carbon metabolism, providing precursors for nucleotide biosynthesis, methylation, and redox homeostasis. SHMT1 is essential for cell proliferation and is implicated in cancer and developmental disorders.

Tissue Expression

Cell Line Expression

Hotspot Mutations

Mutation functional classification

• Folate metabolism (Reactome: R-HSA-196757)

• One-carbon metabolism (KEGG: hsa00670)

• Glycine

• serine and threonine metabolism (KEGG: hsa00260)

SHMT1 is a 483-amino acid cytosolic enzyme that forms homodimers and uses pyridoxal phosphate as a cofactor. It catalyzes the interconversion of serine and glycine while generating 5,10-methylenetetrahydrofolate, a key one-carbon donor for thymidylate and purine synthesis. The protein is highly expressed in proliferating tissues and is regulated by cellular folate status. Structural studies reveal a conserved fold with a large domain and a small domain that closes upon substrate binding.