DMGDH Gene - Dimethylglycine Dehydrogenase | Function, Mutations & Diseases

DMGDH encodes dimethylglycine dehydrogenase, a mitochondrial flavoprotein that catalyzes the oxidative demethylation of dimethylglycine to sarcosine, with concomitant production of formaldehyde and hydrogen peroxide. This enzyme is involved in choline and one-carbon metabolism, linking betaine metabolism to the folate cycle. Mutations in DMGDH cause dimethylglycine dehydrogenase deficiency, a rare autosomal recessive disorder characterized by elevated dimethylglycine in body fluids.

Tissue Expression

Cell Line Expression

Hotspot Mutations

Mutation functional classification

• Glycine

• serine and threonine metabolism (KEGG: hsa00260)

• One carbon pool by folate (KEGG: hsa00670)

• Choline metabolism (Reactome: R-HSA-6798695)

Dimethylglycine dehydrogenase (DMGDH) is a 96 kDa mitochondrial matrix enzyme that functions as a homodimer. It contains a flavin adenine dinucleotide (FAD) cofactor and catalyzes the oxidative demethylation of dimethylglycine to sarcosine. The enzyme is critical for choline degradation and one-carbon metabolism, providing methyl groups for homocysteine remethylation. Deficiency leads to accumulation of dimethylglycine, with clinical features including muscle fatigue, elevated creatine kinase, and sometimes neurological symptoms.