POMT2

POMT2 (protein O-mannosyltransferase 2) is a human gene that encodes a membrane-associated O-mannosyltransferase involved in the initial step of O-mannosyl glycosylation. The enzyme is an integral endoplasmic reticulum protein with multiple transmembrane domains that functions together with POMT1 to transfer mannose from dolichol-phosphate-mannose to serine or threonine residues on target proteins.

A principal substrate of POMT2-dependent glycosylation is alpha-dystroglycan, a cell-surface receptor required for binding extracellular matrix proteins such as laminins. Proper O-mannosylation of alpha-dystroglycan is essential for muscle integrity, neuronal migration, and eye development. Pathogenic biallelic variants in POMT2 disrupt this glycosylation and underlie a spectrum of recessive congenital disorders known as dystroglycanopathies. Clinical presentations range from severe phenotypes like Walker–Warburg syndrome and muscle–eye–brain disease, which include profound muscle weakness, structural brain malformations, and eye abnormalities, to milder limb-girdle muscular dystrophy–type presentations.

Diagnosis is made by genetic testing and biochemical assays of alpha-dystroglycan glycosylation. Management is supportive and multidisciplinary, addressing respiratory, neuromuscular, and ophthalmologic complications. Ongoing research aims to clarify POMT2 structure and mechanism, genotype–phenotype correlations, and potential therapeutic strategies targeting defective glycosylation.