LARGE2
protein-codingLARGE xylosyl- and glucuronyltransferase 2, the group of Glycosyltransferase family 8
Gene summary
Predicted to enable dystroglycan binding activity; glucuronosyltransferase activity; and xylosyltransferase activity. Involved in protein O-linked glycosylation via mannose. Predicted to be located in Golgi membrane. Predicted to be active in Golgi apparatus. [provided by Alliance of Genome Resources, Jun 2026]
- GYLTL1B
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~7.5 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
No GenCC data available for this gene.
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to LARGE2 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_001300721.2. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 1 | 1 | ||||
| missense | 16 | 1 | 17 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 17 | 1 | 0 | 18 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_001287650.1 | 13 | MANE Select | |
| Ensembl | ENSP00000385235.1 | 13 | MANE Select | |
| RefSeq | NP_001287651.1 | 14 | Standard | |
| RefSeq | NP_689525.3 | 13 | Standard |
Model Organisms & Knockout Phenotypes
Observed phenotypic effects in mouse and zebrafish models
| Gene / Model | Organism | Observed Phenotype |
|---|---|---|
| large2 | Danio rerio | Structure: trunk Quality: deformed abnormal |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Mannose type O-glycan biosynthesis - Homo sapiens (human)
- Post-translational protein modification
- Metabolism of proteins
- O-linked glycosylation
Biological Process
- protein O-linked glycosylation
- protein O-linked mannosylation
- muscle cell cellular homeostasis
Molecular Function
- protein binding
- glucuronosyltransferase activity
- transferase activity, transferring glycosyl groups
- manganese ion binding
- UDP-xylosyltransferase activity
Cellular Component
- Golgi membrane
- Golgi apparatus
- integral component of membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000531526
- Coding exons
- 13
- Length
- 7476
- Individuals with no LoFs
- 125669
- Homozygous LoFs
- 1
- Heterozygous LoFs
- 78
- Defined
- 125748
- p
- 0.000314
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | -0.0646 | 409 | 405 | 1.01 | 0.0000267 | 4594 |
| Missense (PolyPhen) | 137 | 137.56 | 0.99592 | 1535 | ||
| Synonymous | -0.312 | 177 | 172 | 1.03 | 0.0000110 | 1539 |
| Loss of Function | 1.46 | 23 | 31.9 | 0.721 | 0.00000161 | 343 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00055 | 0.00055 | rare |
| Latino/Admixed American | 0.00041 | 0.00040 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.00016 | 0.00016 | rare |
| Finnish | 0.00014 | 0.00014 | rare |
| European (Non-Finnish) | 0.00028 | 0.00028 | rare |
| South Asian | 0.00046 | 0.00042 | rare |
| Other | 0.00082 | 0.00081 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Bifunctional glycosyltransferase with both xylosyltransferase and beta-1,3-glucuronyltransferase activities involved in the biosynthesis of the phosphorylated O-mannosyl trisaccharide (N-acetylgalactosamine-beta-3-N-acetylglucosamine- beta-4-(phosphate-6-)mannose), a carbohydrate structure present in alpha-dystroglycan (DAG1). Phosphorylated O-mannosyl trisaccharid is required for binding laminin G-like domain-containing extracellular proteins with high affinity. Elongates the glucuronyl-beta-1,4-xylose-beta disaccharide primer structure by adding repeating units [-3-Xylose-alpha-1,3-GlcA-beta-1-] to produce a heteropolysaccharide. Has a higher activity toward alpha-dystroglycan than LARGE. {ECO:0000269|PubMed:15661757, ECO:0000269|PubMed:15752776, ECO:0000269|PubMed:25138275}.;
Recessive Scores
- pRec
- 0.139
Intolerance Scores
- RVIS EVS
- -1.24
- RVIS percentile EVS
- 5.52
Essentials
- Essential (gene trap)
- N