LARGE1
Chr 22LARGE xylosyl- and glucuronyltransferase 1
Also known as: LARGE, MDC1D, MDDGA6, MDDGB6
LARGE1 encodes a glycosyltransferase that adds xylose and glucuronic acid to alpha-dystroglycan, enabling alpha-dystroglycan to bind laminin 211 and neurexin. Autosomal recessive mutations cause muscular dystrophy-dystroglycanopathy with brain and eye anomalies (type A6) or intellectual disability (type B6) due to abnormal glycosylation of alpha-dystroglycan. Loss-of-function mutations disrupt the critical glycosylation pathway required for proper dystroglycan function in muscle and brain development.
Definitive — sufficient evidence for diagnostic panels
Some data sources returned errors (1)
omim: Error: OMIM fetch failed: 429
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Highly LoF-intolerant (top ~10% of genes)
Mild missense constraint
ClinVar Variant Classifications
500 submitted variants in ClinVar
Classification Summary
Curated Variants Distribution
Classified variants from ClinVar · 5 ACMG categories
| Classification | LoF | Missense + Inframe | Non-coding | Synonymous | Total |
|---|---|---|---|---|---|
Pathogenic | 14 | 0 | 15 | 0 | 29 |
Likely Pathogenic | 8 | 0 | 2 | 0 | 10 |
VUS | 1 | 99 | 13 | 0 | 113 |
Likely Benign | 0 | 1 | 154 | 180 | 335 |
Benign | 0 | 0 | 0 | 0 | 0 |
| Total | 23 | 100 | 184 | 180 | 487 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
LARGE1 · 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
No active trials found for this gene.
Search ClinicalTrials.gov →External Resources
Links to major genomics databases and tools