MAG
Chr 19ARmyelin associated glycoprotein
Also known as: GMA, S-MAG, SIGLEC-4A, SIGLEC4, SIGLEC4A, SPG75
The myelin-associated glycoprotein (MAG) is an adhesion molecule that mediates interactions between myelinating cells and neurons, maintains normal axon myelination, and protects motor neurons against apoptosis. Mutations cause spastic paraplegia 75, an autosomal recessive disorder affecting the corticospinal tracts. The gene is highly constrained against loss-of-function variants (LOEUF 0.424), indicating that MAG function is essential for normal neurological development and maintenance.
Definitive — sufficient evidence for diagnostic panels
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
More LoF-intolerant than ~75% of genes
Mild missense constraint
This gene has evidence for multiple mechanisms of pathogenicity (gain-of-function and dominant-negative). Both the Badonyi & Marsh prediction and the broader genomic evidence point to gain-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.
Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.
ClinVar Variant Classifications
0 submitted variants in ClinVar
Protein Context — Lollipop Plot
MAG · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
3D Protein StructureAlphaFold
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
External Resources
Links to major genomics databases and tools