POMT1

POMT1 stands for protein O-mannosyltransferase 1, a human gene encoding an enzyme that resides in the endoplasmic reticulum. It is a member of the protein O-mannosyltransferase family and, together with its partner POMT2, forms a functional complex that catalyzes the first step in the biosynthesis of O-mannosyl glycans.

Function and mechanism

POMT1 mediates the transfer of the first mannose residue from dolichol phosphate mannose to serine or threonine residues on the extracellular portion of alpha-dystroglycan, initiating O-mannosylation. This initial modification is then extended by other enzymes to produce mature O-mannosyl glycans, which are essential for the proper glycosylation of dystroglycan. Properly glycosylated dystroglycan binds extracellular matrix proteins such as laminin, helping to connect the cytoskeleton to the extracellular matrix and maintain muscle and brain tissue integrity.

Clinical significance

Mutations in POMT1 cause a spectrum of dystroglycanopathies, autosomal recessive disorders characterized by hypoglycosylation of alpha-dystroglycan. The resulting conditions range from severe congenital forms with brain and eye malformations (such as Walker-Warburg syndrome and related disorders) to milder congenital muscular dystrophies with varying degrees of cognitive involvement. The severity generally correlates with the residual activity of the POMT1-POMT2 complex.

Genetics and expression

POMT1 is expressed in tissues with muscle and brain involvement and operates in concert with POMT2. Disruption of the O-mannosylation pathway disrupts dystroglycan function and the structural integrity of muscle basement membranes and neural development.