B4GALT1
protein-codingbeta-1,4-galactosyltransferase 1, the group of Beta 4-glycosyltransferases
Gene summary
This gene is one of seven beta-1,4-galactosyltransferase (beta4GalT) genes. They encode type II membrane-bound glycoproteins that appear to have exclusive specificity for the donor substrate UDP-galactose; all transfer galactose in a beta1,4 linkage to similar acceptor sugars: GlcNAc, Glc, and Xyl. Each beta4GalT has a distinct function in the biosynthesis of different glycoconjugates and saccharide structures. As type II membrane proteins, they have an N-terminal hydrophobic signal sequence that directs the protein to the Golgi apparatus and which then remains uncleaved to function as a transmembrane anchor. By sequence similarity, the beta4GalTs form four groups: beta4GalT1 and beta4GalT2, beta4GalT3 and beta4GalT4, beta4GalT5 and beta4GalT6, and beta4GalT7. This gene is unique among the beta4GalT genes because it encodes an enzyme that participates both in glycoconjugate and lactose biosynthesis. For the first activity, the enzyme adds galactose to N-acetylglucosamine residues that are either monosaccharides or the nonreducing ends of glycoprotein carbohydrate chains. The second activity is restricted to lactating mammary tissues where the enzyme forms a heterodimer with alpha-lactalbumin to catalyze UDP-galactose + D-glucose <=> UDP + lactose. The two enzymatic forms result from alternate transcription initiation sites and post-translational processing. Two transcripts, which differ only at the 5' end, with approximate lengths of 4.1 kb and 3.9 kb encode the same protein. The longer transcript encodes the type II membrane-bound, trans-Golgi resident protein involved in glycoconjugate biosynthesis. The shorter transcript encodes a protein which is cleaved to form the soluble lactose synthase. [provided by RefSeq, Jul 2008]
- GGTB2
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~66.8 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AR
Disease ID:MONDO:0011772
Submitter: Ambry Genetics
Inheritance Pattern: AR
Disease ID:MONDO:0011772
Submitter: Orphanet
Inheritance Pattern: AR
Disease ID:MONDO:0011772
Submitter: PanelApp Australia
Inheritance Pattern: AR
Disease ID:MONDO:0011772
Submitter: G2P
Inheritance Pattern: AR
Disease ID:MONDO:0011772
Submitter: Labcorp Genetics (formerly Invitae)
Inheritance Pattern: AR
Disease ID:MONDO:0011772
Submitter: ClinGen
B4GALT1 was first reported in relation to autosomal recessive B4GALT1-congenital disorder of glycosylation in 2002 (Hansske et al. PMID:11901181). Five variants (missense, nonsense, frameshift) that have been reported in 5 probands in 5 publications (PMIDs: 11901181, 30653653, 32157688, 21920538, 33258288) are included in this curation. More evidence is available in the literature, but the maximum score for genetic evidence (12 pts) has been reached. B4GALT1-congenital disorder of glycosylation is characterized by severe psychomotor and developmental delay, as well as blood coagulation abnormalities. The disease mechanism appears to be biallelic loss of function. Heterozygous carriers are reportedly unaffected. This gene-disease relationship is also supported by in vitro and in vivo assays showing a defect in glycosylation (PMIDs 11901181, 31800099) as well as animal models (PMIDs 11463354, 9155011). In summary, there is definitive evidence supporting the relationship between B4GALT1 and autosomal recessive B4GALT1-congenital disorder of glycosylation. This has been repeatedly demonstrated in both the research and clinical diagnostic settings, and has been upheld over time. This classification was approved by the ClinGen Congenital Disorders of Glycosylation GCEP on the meeting date May 18, 2026 (SOP Version 12).
Clinical Genomic Database (CGD)
Manifestation: Biochemical; Cardiovascular; Hematologic; Gastrointestinal; Musculoskeletal; Neurologic; Renal
Intervention: Hematologic; Gastrointestinal
Rationale: Awareness of coagulopathies may be beneficial in terms of medical management, especially in situations such as surgery; Individuals have been described with hepatosplenomegaly and transient cholestatic jaundice, which was treated with ursodeoxycholic acid
Comments: Hepatic-metabolized agents should be avoided
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to B4GALT1 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_001497.4. 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 | 4 | 20 | 1 | 25 | ||
| missense | 1 | 68 | 7 | 76 | ||
| nonsense | 1 | 1 | ||||
| start loss | 0 | |||||
| frameshift | 1 | 1 | ||||
| splice donor/acceptor (+/-2bp) | 1 | 1 | ||||
| Total | 3 | 0 | 73 | 27 | 1 | 104 |
Highest pathogenic variant AF is 0.00005576367
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_001488.2 | 6 | MANE Select | |
| Ensembl | ENSP00000369055.4 | 6 | MANE Select | |
| RefSeq | NP_001365424.1 | 6 | Standard | |
| RefSeq | NP_001365425.1 | 5 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- N-Glycan biosynthesis - Homo sapiens (human)
- Other types of O-glycan biosynthesis - Homo sapiens (human)
- Mannose type O-glycan biosynthesis - Homo sapiens (human)
- Glycosphingolipid biosynthesis - lacto and neolacto series - Homo sapiens (human)
- Galactose metabolism - Homo sapiens (human)
Biological Process
- epithelial cell development
- acute inflammatory response
- lactose biosynthetic process
- galactose metabolic process
- protein N-linked glycosylation
Molecular Function
- beta-N-acetylglucosaminylglycopeptide beta-1,4-galactosyltransferase activity
- N-acetyllactosamine synthase activity
- lactose synthase activity
- galactosyltransferase activity
- manganese ion binding
Cellular Component
- Golgi trans cisterna
- Golgi membrane
- extracellular space
- Golgi apparatus
- plasma membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000379731
- Coding exons
- 6
- Length
- 63275
- Individuals with no LoFs
- 125739
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 9
- Defined
- 125748
- p
- 0.0000358
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.976 | 184 | 225 | 0.817 | 0.0000128 | 2549 |
| Missense (PolyPhen) | 69 | 98.431 | 0.701 | 1137 | ||
| Synonymous | -0.472 | 100 | 94.2 | 1.06 | 0.00000499 | 833 |
| Loss of Function | 2.38 | 5 | 14.9 | 0.335 | 7.31e-7 | 171 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0 | 0.0 | absent |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.000054 | 0.000054 | rare |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.000071 | 0.000070 | rare |
| South Asian | 0 | 0.0 | absent |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: The Golgi complex form catalyzes the production of lactose in the lactating mammary gland and could also be responsible for the synthesis of complex-type N-linked oligosaccharides in many glycoproteins as well as the carbohydrate moieties of glycolipids.;
- Disease
- DISEASE: Congenital disorder of glycosylation 2D (CDG2D) [MIM:607091]: A multisystem disorder caused by a defect in glycoprotein biosynthesis and characterized by under-glycosylated serum glycoproteins. Congenital disorders of glycosylation result in a wide variety of clinical features, such as defects in the nervous system development, psychomotor retardation, dysmorphic features, hypotonia, coagulation disorders, and immunodeficiency. The broad spectrum of features reflects the critical role of N- glycoproteins during embryonic development, differentiation, and maintenance of cell functions. {ECO:0000269|PubMed:11901181}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
Recessive Scores
- pRec
- 0.210
Intolerance Scores
- LoFtool
- 0.203
- RVIS EVS
- -0.52
- RVIS percentile EVS
- 21.2
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.994
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |