POMGNT2

POMGNT2, also known as POMGnT2, is a human gene encoding a Golgi-resident glycosyltransferase that participates in the maturation of O-mannosyl glycans on α-dystroglycan (α-DG). The enzyme is categorized as a beta-1,4-N-acetylglucosaminyltransferase and functions in the extension of the O-mannose glycan that is essential for proper α-DG glycosylation.

Biological function of POMGNT2 lies in adding N-acetylglucosamine (GlcNAc) in a beta-1,4 linkage to core O-mannose on α-DG. This modification contributes to the formation of the laminin-binding glycoepitope that enables α-DG to interact with extracellular matrix proteins such as laminin, agrin, and perlecan. The process is part of a broader O-mannosylation pathway that is critical for the structural integrity of muscle, brain, and other tissues.

Clinical significance of POMGNT2 mutations is primarily recognized in the spectrum of dystroglycanopathies, disorders arising from defective glycosylation of α-DG. Pathogenic variants can lead to reduced laminin-binding and abnormal α-DG glycosylation, with clinical presentations ranging from congenital muscular dystrophy with brain involvement to milder muscular phenotypes. Inheritance is typically autosomal recessive.

Expression of POMGNT2 has been reported in skeletal muscle, brain, and other tissues, reflecting its role in widespread glycosylation processes. It functions alongside other glycosyltransferases in the O-mannosylation pathway, including POMGNT1, within the Golgi apparatus. Model organisms with disrupted POMGNT2 show impaired α-DG glycosylation and associated muscular or neurological abnormalities, underscoring its physiological importance.