GPD1 Gene - Glycerol-3-Phosphate Dehydrogenase 1 | Function, Mutations & Disease

The GPD1 gene encodes the cytosolic isoform of glycerol-3-phosphate dehydrogenase, a key enzyme that catalyzes the reversible conversion of dihydroxyacetone phosphate (DHAP) to glycerol-3-phosphate (G3P) using NADH as a cofactor. This reaction is essential for glycerol metabolism, triglyceride synthesis, and the glycerol-3-phosphate shuttle that transfers reducing equivalents from the cytosol to mitochondria. GPD1 is highly expressed in liver, adipose tissue, and skeletal muscle, and its deficiency leads to elevated serum triglycerides and glycerol levels.

Tissue Expression

Cell Line Expression

Hotspot Mutations

Mutation functional classification

• Glycerolipid metabolism (Reactome: R-HSA-8978868)

• Glycerol-3-phosphate shuttle (Reactome: R-HSA-1483191)

• Triglyceride biosynthesis (Reactome: R-HSA-75105)

• Metabolism of lipids (Reactome: R-HSA-556833)

GPD1 encodes a 349-amino acid cytosolic protein that functions as a homodimer. It catalyzes the NADH-dependent reduction of dihydroxyacetone phosphate to glycerol-3-phosphate, a critical step in triglyceride synthesis and the glycerol-3-phosphate shuttle. The enzyme is highly expressed in metabolically active tissues such as liver, adipose, and muscle. Deficiency due to biallelic loss-of-function mutations causes transient infantile hypertriglyceridemia and elevated serum glycerol. The protein structure includes a Rossmann fold for NADH binding and a catalytic domain.