LARGE1
LARGE xylosyl- and glucuronyltransferase 1
Gene Information Card
| Symbol | LARGE1 |
|---|---|
| Full Name | LARGE xylosyl- and glucuronyltransferase 1 |
| Gene Type | protein-coding |
| Chromosomal Location | 22q12.3 |
| NCBI Gene ID | 9215 ncbi.nlm.nih.gov/gene/9215 |
| Ensembl ID | ENSG00000133424 |
| UniProt ID | O95427 |
| OMIM ID | 603590 |
| HGNC ID | 6511 |
| Aliases | LARGE, MDC1D, MDDGA6, MDDGB6, MDDGC6 |
Description
LARGE1 encodes a bifunctional glycosyltransferase that adds alternating xylose and glucuronic acid residues to alpha-dystroglycan, essential for its function as a receptor for extracellular matrix proteins. Mutations in LARGE1 cause congenital muscular dystrophy type 1D (MDC1D) and other dystroglycanopathies.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Congenital muscular dystrophy type 1D (MDC1D) | Loss-of-function mutations impair alpha-dystroglycan glycosylation, disrupting basement membrane binding | OMIM #608840 |
| Muscular dystrophy-dystroglycanopathy type A6 (MDDGA6) | Biallelic LARGE1 mutations cause severe brain and eye malformations | OMIM #613154 |
| Muscular dystrophy-dystroglycanopathy type B6 (MDDGB6) | Milder limb-girdle phenotype with reduced glycosylation | OMIM #608840 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Heart | 8.2 | Medium |
| Skeletal muscle | 6.5 | Medium |
| Brain | 5.1 | Low |
| Placenta | 4.8 | Low |
| Lung | 3.9 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HeLa | 7.1 | Cervical adenocarcinoma |
| HepG2 | 5.3 | Hepatocellular carcinoma |
| K562 | 4.2 | Chronic myelogenous leukemia |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1987C>T (p.Arg663Ter) | Nonsense | Rare | Loss of function; truncates protein before catalytic domain |
| c.428G>A (p.Trp143Ter) | Nonsense | Rare | Loss of function; early truncation |
| c.1039G>A (p.Gly347Arg) | Missense | Rare | Likely loss of function; disrupts enzymatic activity |
Mutation functional classification
Loss of Function (LOF)
Most LARGE1 mutations are loss-of-function, leading to reduced or absent glycosylation of alpha-dystroglycan.
Gain of Function (GOF)
No gain-of-function mutations reported.
Dominant Negative (DN)
No dominant-negative mutations reported.
View complete mutation data：
Gene Ontology (GO)
| • xylosyltransferase activity (GO:0042285) | • glucuronosyltransferase activity (GO:0015020) |
| • protein glycosylation (GO:0006486) | • endoplasmic reticulum membrane (GO:0005789) |
Pathways
• O-mannosyl glycan biosynthesis (Reactome R-HSA-5173105)
• Dystroglycan-related disorders (KEGG hsa05310)
Protein Summary
LARGE1 is a bifunctional glycosyltransferase localized to the Golgi apparatus. It catalyzes the addition of alternating xylose and glucuronic acid residues to alpha-dystroglycan, a process critical for extracellular matrix binding. The protein contains two catalytic domains: a xylosyltransferase domain and a glucuronyltransferase domain.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| LARGE1 Knockout HEK293 Cell Line | EDJ-KQ6508 | Human | 9215 | Details Get a Quote |
| LARGE1 Knockout A-549 Cell Line | EDJ-KQ30653 | Human | 9215 | Details Get a Quote |
Displaying Records 1 To 2 Of 2 Records
