LARGE2
LARGE xylosyl- and glucuronyltransferase 2
Gene Information Card
| Symbol | LARGE2 |
|---|---|
| Full Name | LARGE xylosyl- and glucuronyltransferase 2 |
| Gene Type | protein-coding |
| Chromosomal Location | 11p11.2 |
| NCBI Gene ID | 120071 ncbi.nlm.nih.gov/gene/120071 |
| Ensembl ID | ENSG00000149257 |
| UniProt ID | Q8N6F7 |
| OMIM ID | 611599 |
| HGNC ID | 18742 |
| Aliases | GYLT1B, LARGE2, LARGE-like |
Description
LARGE2 encodes a bifunctional glycosyltransferase that adds xylose and glucuronic acid to O-mannosyl glycans, primarily modifying alpha-dystroglycan. This post-translational modification is essential for the high-affinity binding of alpha-dystroglycan to extracellular matrix proteins such as laminin. LARGE2 is closely related to LARGE1 and can partially compensate for its function. Mutations in LARGE2 are associated with congenital muscular dystrophy and other glycosylation disorders.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Congenital muscular dystrophy-dystroglycanopathy with brain and eye anomalies type A14 | Loss-of-function mutations impair O-mannosyl glycosylation of alpha-dystroglycan, reducing laminin binding | ClinVar, OMIM 615350 |
| Walker-Warburg syndrome (overlap) | Defective glycosylation of alpha-dystroglycan leads to severe neuronal migration defects | OMIM 236670 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Heart | 12.5 | Medium |
| Skeletal muscle | 8.3 | Low |
| Brain | 6.7 | Low |
| Placenta | 15.2 | Medium |
| Lung | 9.1 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK 293 | 18.4 | Moderate expression |
| HeLa | 7.2 | Low expression |
| K562 | 3.5 | Very low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1234C>T (p.Arg412*) | Nonsense | Rare | Loss of function; truncation of catalytic domain |
| c.789_790del (p.Glu264Glyfs*12) | Frameshift | Rare | Loss of function; premature stop codon |
| c.1567G>A (p.Gly523Arg) | Missense | Rare | Likely loss of function; disrupts enzyme activity |
Mutation functional classification
Loss of Function (LOF)
Nonsense and frameshift mutations lead to truncated, non-functional protein; missense mutations may impair catalytic activity.
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)
| • glycosyltransferase activity | • xylosyltransferase activity |
| • glucuronyltransferase activity | • protein O-linked mannosylation |
| • endoplasmic reticulum lumen | • Golgi apparatus |
Pathways
• O-mannosyl glycan biosynthesis
• Dystroglycan glycosylation
• Laminin binding pathway
Protein Summary
LARGE2 is a 720-amino acid type II transmembrane protein localized to the Golgi apparatus. It possesses two glycosyltransferase domains: a xylosyltransferase domain and a glucuronyltransferase domain. The enzyme catalyzes the addition of alternating xylose and glucuronic acid residues to O-mannosyl glycans on alpha-dystroglycan. This modification is critical for the structural integrity of the dystrophin-glycoprotein complex and for cell-matrix adhesion. LARGE2 shares 60% sequence identity with LARGE1 and can functionally compensate for LARGE1 deficiency in some tissues.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| LARGE2 Knockout HEK293 Cell Line | EDJ-KQ7655 | Human | 120071 | Details Get a Quote |
| LARGE2 Knockout A-549 Cell Line | EDJ-KQ33011 | Human | 120071 | Details Get a Quote |
| LARGE2 Knockout HCT 116 Cell Line | EDJ-KQ33012 | Human | 120071 | Details Get a Quote |
| LARGE2 Knockout HeLa Cell Line | EDJ-KQ31680 | Human | 120071 | Details Get a Quote |
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