Overview
POMT2 works together with POMT1 in the O-mannosylation of alpha-dystroglycan. As the catalytic subunit of the POMT1/POMT2 complex, it transfers mannose residues to serine and threonine residues in proteins. Mutations in POMT2 cause muscular dystrophy-dystroglycanopathies with a spectrum of mild to severe phenotypes.
14q24.3 (Chromosome 14)
Hereditary Diseases
Autosomal recessive
Very rare
Function & Significance
POMT2 is the catalytic subunit of the POMT1/POMT2 enzyme complex. Both proteins must work together to perform the O-mannosylation of alpha-dystroglycan. This post-translational modification is essential for the binding of dystroglycan to laminin in the extracellular matrix.
Defects in POMT2 lead to similar phenotypes as POMT1 mutations, as both genes act in the same metabolic pathway. The severity of the disease depends on the type and position of the mutation.
🔬 POMT1/POMT2 Complex
The POMT1/POMT2 complex is the first step in the O-mannosylation cascade. Following the initial mannose addition by POMT1/POMT2, further glycosylation steps follow by other enzymes (POMGNT1, FKTN, FKRP, LARGE). Disruptions in any of these steps can lead to dystroglycanopathies.
Associated Diseases
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🧠 Walker-Warburg Syndrome
Severe congenital muscular dystrophy with lissencephaly, eye anomalies, and hydrocephalus
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💪 Limb-Girdle Muscular Dystrophy Type 2N (LGMD2N)
Milder form with proximal muscle weakness, elevated CK, normal intelligence
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🧬 Muscular Dystrophy-Dystroglycanopathy Type B
Intermediate form with congenital muscular dystrophy and mild brain anomalies
🧬 Relevant SNPs
Over 100 different mutations in POMT2 have been described. Most are private mutations (found only in individual families). Common mutation types include missense, nonsense, frameshift, and splice-site mutations.
⚕️ Clinical Significance
Diagnosis: Muscle biopsy shows reduced dystroglycan glycosylation. Brain MRI may show lissencephaly or other structural anomalies. Genetic sequencing of POMT2 and other dystroglycanopathy genes confirms the diagnosis.
Management: Supportive therapy with physiotherapy, orthotics, respiratory support if needed. Regular cardiological monitoring. Genetic counseling for families.
Research: Gene therapy approaches for dystroglycanopathies are being explored, including AAV-based gene replacement therapy and exon-skipping strategies.
📚 Data Sources
The information on this page is based on the following scientific sources:
- OMIM: #607439 (POMT2), #613158 (LGMD2N)
- ClinVar: Pathogenic POMT2 variants
- PubMed: Literature on POMT2 and dystroglycanopathies
- Orphanet: ORPHA370968 (Autosomal recessive limb-girdle muscular dystrophy type 2N)
Last Update: February 2026