PSPH Gene (Phosphoserine Phosphatase): Function, Expression & Disease Associations

The PSPH gene encodes phosphoserine phosphatase (PSP), a key enzyme in the L-serine biosynthesis pathway. This enzyme catalyzes the final step of serine biosynthesis, converting L-phosphoserine to L-serine and inorganic phosphate. PSP is a homodimeric enzyme that requires magnesium ions for its activity. The protein is primarily localized in the cytoplasm. Mutations in PSPH are associated with phosphoserine phosphatase deficiency, a rare autosomal recessive metabolic disorder characterized by congenital microcephaly, psychomotor retardation, and seizures. PSPH expression is particularly high in the brain, especially in the cerebellum, and is also detected in other tissues. Recent studies have also implicated PSPH in cancer biology, where its overexpression may contribute to tumor growth and progression.

Tissue Expression

Cell Line Expression

Hotspot Mutations

Mutation functional classification

• L-serine biosynthesis

• Glycine

• serine and threonine metabolism

• Metabolic pathways

• Amino acid metabolism

Phosphoserine phosphatase (PSP) is a homodimeric enzyme that catalyzes the hydrolysis of L-phosphoserine to L-serine, the final and rate-limiting step in the L-serine biosynthesis pathway. The protein consists of two identical subunits, each with a catalytic domain. It requires magnesium ions (Mg2+) as a cofactor for its activity. PSP is highly expressed in the brain, particularly in the cerebellum, where L-serine is essential for neuronal development and function. L-serine serves as a precursor for the synthesis of other amino acids, phospholipids, and neurotransmitters. Defects in PSP lead to phosphoserine phosphatase deficiency, a severe neurological disorder. The protein is localized in the cytoplasm.