B4GAT1
protein-codingbeta-1,4-glucuronyltransferase 1
Gene summary
This gene encodes a member of the beta-1,3-N-acetylglucosaminyltransferase family. This enzyme is a type II transmembrane protein. It is essential for the synthesis of poly-N-acetyllactosamine, a determinant for the blood group i antigen. [provided by RefSeq, Jul 2008]
- B3GNT6
- B3GNT1
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~2.3 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AR
Disease ID:MONDO:0014120
Submitter: ClinGen
B4GAT1 was first reported in relation to Autosomal Recessive Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 13 (OMIM # 615287) in 2013 (Buysse et al., PMID: 23359570). This is a severe dystroglycanopathy that includes the clinical designations of Walker-Warburg syndrome (WWS) and muscle-eye-brain disease (MEB). Two variants (one complex missense allele, one frameshift) that have been reported in three probands in three publications (PMIDs: 23359570, 23877401, 34587870) are included in this curation. The mechanism of pathogenicity remains unclear. This gene-disease relationship is supported by experimental evidence including a mouse model with neuronal migration defects (PMID 23217742), a morpholino zebrafish knock out model recapitulating the muscular defects (PMID 23359570) and a drosophila model with CNS elongation (PMID 38996053). In summary, there is MODERATE evidence to support this gene-disease relationship. While more evidence is needed to establish this relationship definitively, no convincing contradictory evidence has emerged. This gene-disease pair was originally evaluated by the Brain Malformations GCEP on March 28, 2023. It was reevaluated on July 8, 2025 (SOP v 11). Although one additional case (PMID 34587870) and two new animal models (PMIDs 23217742, 38996053) were added to the evidence, previously curated evidence was rescored and the classification did not change.
Inheritance Pattern: AR
Disease ID:MONDO:0014120
Submitter: Labcorp Genetics (formerly Invitae)
Inheritance Pattern: AR
Disease ID:MONDO:0014120
Submitter: PanelApp Australia
Inheritance Pattern: AR
Disease ID:MONDO:0000171
Submitter: Orphanet
Clinical Genomic Database (CGD)
Manifestation: Musculoskeletal; Neurologic; Ophthalmologic
Intervention: General
Rationale: Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to B4GAT1 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_006876.3. 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 | 100 | 100 | ||||
| missense | 2 | 108 | 8 | 118 | ||
| nonsense | 2 | 1 | 3 | |||
| start loss | 1 | 1 | ||||
| frameshift | 2 | 3 | 5 | |||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 2 | 4 | 113 | 108 | 0 | 227 |
Highest pathogenic variant AF is 0.0000047883677
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_006867.1 | 2 | MANE Select | |
| Ensembl | ENSP00000309096.4 | 2 | MANE Select | |
| Ensembl | ENSP00000535285.1 | 2 | Standard | |
| Ensembl | ENSP00000535285.1 | 2 | Standard |
Model Organisms & Knockout Phenotypes
Observed phenotypic effects in mouse and zebrafish models
| Gene / Model | Organism | Observed Phenotype |
|---|---|---|
| b4gat1 | Danio rerio | Structure: muscle Quality: disorganized abnormal |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Mannose type O-glycan biosynthesis - Homo sapiens (human)
- Metabolism of carbohydrates
- Keratan sulfate biosynthesis
- Keratan sulfate/keratin metabolism
- Glycosphingolipid biosynthesis - neolactoseries
Biological Process
- protein O-linked glycosylation
- axon guidance
- keratan sulfate biosynthetic process
- poly-N-acetyllactosamine biosynthetic process
- protein O-linked mannosylation
Molecular Function
- protein binding
- N-acetyllactosaminide beta-1,3-N-acetylglucosaminyltransferase activity
- glucuronosyltransferase activity
- metal ion binding
Cellular Component
- Golgi membrane
- Golgi apparatus
- integral component of Golgi membrane
- extracellular exosome
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000311181
- Coding exons
- 2
- Length
- 2321
- Individuals with no LoFs
- 125717
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 13
- Defined
- 125730
- p
- 0.0000517
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 1.90 | 161 | 245 | 0.658 | 0.0000142 | 2633 |
| Missense (PolyPhen) | 49 | 83.127 | 0.58946 | 855 | ||
| Synonymous | 2.22 | 84 | 114 | 0.736 | 0.00000668 | 877 |
| Loss of Function | 2.12 | 6 | 14.8 | 0.406 | 8.06e-7 | 142 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0.000029 | 0.000029 | rare |
| Ashkenazi Jewish | 0.000099 | 0.000099 | rare |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0.000057 | 0.000046 | rare |
| European (Non-Finnish) | 0.000079 | 0.000070 | rare |
| South Asian | 0.000039 | 0.000033 | rare |
| Other | 0.00016 | 0.00016 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Beta-1,4-glucuronyltransferase involved in O- mannosylation of alpha-dystroglycan (DAG1). Transfers a glucuronic acid (GlcA) residue onto a xylose (Xyl) acceptor to produce the glucuronyl-beta-1,4-xylose-beta disaccharide primer, which is further elongated by LARGE1, during synthesis of phosphorylated O- mannosyl glycan (PubMed:25279699, PubMed:25279697). Phosphorylated O-mannosyl glycan is a carbohydrate is a carbohydrate structure present in alpha-dystroglycan (DAG1), which is required for binding laminin G-like domain-containing extracellular proteins with high affinity (PubMed:25279699, PubMed:25279697). Required for axon guidance; via its function in O-mannosylation of alpha- dystroglycan (DAG1) (By similarity). {ECO:0000250|UniProtKB:Q8BWP8, ECO:0000269|PubMed:19587235, ECO:0000269|PubMed:23359570, ECO:0000269|PubMed:25279697, ECO:0000269|PubMed:25279699}.;
Recessive Scores
- pRec
- 0.123
Essentials
- Essential (gene trap)
- N